JP6213266B2 - Amide compounds and their use for controlling harmful arthropods - Google Patents

Description

  The present invention relates to an amide compound and its use for controlling harmful arthropods.

  Conventionally, many harmful arthropod control agents have been developed and put into practical use for controlling harmful arthropods. Patent Document 1 describes certain types of amide compounds.

JP-A-57-75961

  An object of the present invention is to provide a compound having an excellent control effect against harmful arthropods.

〔式中、
Ａは、酸素原子及び−Ｓ（Ｏ）_ｔ−からなる群より選ばれる１個以上の原子または基を環構成成分として含む３−７員飽和へテロ環を表し、該飽和へテロ環は、群Ｄより選ばれる１〜３個の原子または基を有していてもよく、
ｔは０、１、または２を表し、
Ｒ^１及びＲ^２は、同一または相異なり、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、または水素原子を表し、
ｎは、０、１、または２を表し、
下式（ＩＩ）

は、５員芳香環を表し、
Ｚは窒素原子または炭素原子を表し、
Ｚが窒素原子を表す場合、Ｘ^１、Ｘ^２、及びＸ^３は各々同一または相異なり、窒素原子、ＣＲ^５、酸素原子、硫黄原子又はＮＲ^６を表し、該Ｘ^１、Ｘ^２、及びＸ^３の少なくとも１つは窒素原子、酸素原子、硫黄原子又はＮＲ^６であり、
Ｚが炭素原子を表す場合、Ｘ^１、Ｘ^２、及びＸ^３は各々同一または相異なり、窒素原子、ＣＲ^５、酸素原子、硫黄原子又はＮＲ^６を表し、該Ｘ^１、Ｘ^２、及びＸ^３の少なくとも２つは窒素原子、酸素原子、硫黄原子又はＮＲ^６であり、該Ｘ^１、Ｘ^２、及びＸ^３の少なくとも１つは窒素原子またはＮＲ^６であり、
Ｒ^５は各々同一または相異なり、ハロゲン原子、シアノ基、ホルミル基、カルボキシル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシカルボニル基、カルバモイル基、−ＯＲ^７およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ３炭化水素基、又は水素原子を表し、
Ｒ^６はメチル基又は水素原子を表し、Ｒ^７は−Ｃ（＝Ｓ）ＳＲ^８又は水素原子を表し、Ｒ^８は１個以上のハロゲン原子を有していてもよいＣ１−Ｃ３炭化水素基を表し、
Ｒ^３及びＲ^４は、同一または相異なり、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、ハロゲン原子、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基または水素原子を表し、
Ｙは、単結合、酸素原子、または−Ｓ（Ｏ）_ｕ−を表し
Ｙが単結合の場合は、ｍは０を表し、
Ｙが酸素原子、または−Ｓ（Ｏ）_ｕ−である場合は、ｍは０、１、２、３、４、５、６または７を表し、
Ｙが単結合の場合は、Ｑは群Ｆより選ばれる１個以上の原子または基を有しているＣ１−Ｃ８鎖式炭化水素基、または
Ｃ３−Ｃ８鎖式炭化水素基を表し、
Ｙが酸素原子、または−Ｓ（Ｏ）_ｕ−である場合は、Ｑは群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基、
または群Ａより選ばれる１個の基を表し、
ｕは０、１、または２を表す。
群Ａ：群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいＣ３−Ｃ８シクロアルキル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいインダニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，２，３，４−テトラヒドロナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいピリジル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいキノリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいチエニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾフラニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾチエニル基、及び群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，３−ベンゾジオキソリル基からなる群。
群Ｂ：１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、１個以上のベンジルオキシ基を有しているＣ１−Ｃ４アルキル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシ基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキルチオ基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキルスルフィニル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキルスルホニル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシカルボニル基、群Ｅより選ばれる１個以上の原子若しくは基を有していてもよいビニル基、群Ｅより選ばれる原子若しくは基を有していてもよいエチニル基、フェニル基、フェノキシ基、シアノ基、ニトロ基、カルボキシル基、ヒドロキシル基、−ＣＯＮＲ^１２Ｒ^１３基、メトキシメチル基及びハロゲン原子からなる群。
Ｒ^１２及びＲ^１３は、同一または相異なり、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、または水素原子を表す。
群Ｄ：１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシ基、及びハロゲン原子からなる群。
群Ｅ：１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基及びハロゲン原子からなる群。
群Ｆ：群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいＣ３−Ｃ８シクロアルキル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいインダニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，２，３，４−テトラヒドロナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいピリジル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいキノリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいチエニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾフラニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾチエニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，３−ベンゾジオキソリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，４−ベンゾジオキサニル基、ハロゲン原子、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシカルボニル基、シアノ基、ニトロ基、カルボキシル基、ヒドロキシル基、および−ＣＯＮＲ^１２Ｒ^１３基からなる群。
群Ｇ：群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいＣ３−Ｃ８シクロアルキル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいインダニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，２，３，４−テトラヒドロナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェノキシ基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいピリジル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいキノリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいチエニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾフラニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾチエニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，３−ベンゾジオキソリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，４−ベンゾジオキサニル基、ハロゲン原子、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシカルボニル基、シアノ基、ニトロ基、カルボキシル基、ヒドロキシル基、および−ＣＯＮＲ^１２Ｒ^１３基からなる群。〕
で示されるアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［２］式（Ｉ）において、Ｒ^５が各々同一または相異なり、ハロゲン原子、シアノ基、メチル基又は水素原子であり、Ｒ^３及びＲ^４が、同一または相異なり、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、ハロゲン原子、または水素原子であり、
群Ｂが１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシ基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキルチオ基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキルスルフィニル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキルスルホニル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシカルボニル基、群Ｅより選ばれる１個以上の原子若しくは基を有していてもよいビニル基、群Ｅより選ばれる原子若しくは基を有していてもよいエチニル基、シアノ基、ニトロ基、カルボキシル基、ヒドロキシル基、−ＣＯＮＲ^１２Ｒ^１３基、メトキシメチル基及びハロゲン原子からなる群であり、
Ｙが、単結合、酸素原子、または−Ｓ（Ｏ）_ｕ−であり、
Ｙが酸素原子、または−Ｓ（Ｏ）_ｕ−である場合は、ｍが０、１、２、３または４であり、Ｙが酸素原子、または−Ｓ（Ｏ）_ｕ−である場合は、Ｑが群Ｆより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基、または群Ａより選ばれる１個の基である［１］記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［３］式（Ｉ）において
Ｒ^５が各々同一または相異なり、ハロゲン原子、シアノ基、ハロゲン原子を有していてもよいメチル基又は水素原子であり、
ｍが０〜２であり、
Ｑが、群Ａより選ばれる１個の基又は群Ａより選ばれる１個の基を有してもよいＣ１−Ｃ８鎖式炭化水素基であり、
Ｙが、−ＣＲ^８Ｒ^９−、−ＣＲ^９＝ＣＲ^９−、酸素原子、または−Ｓ（Ｏ）_ｕ−であり、
Ｒ^８が１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、ハロゲン原子、または水素原子を表すか、Ｒ^３とＲ^８とが一緒になって、−（ＣＲ^１０Ｒ^１１）_ｖ−、酸素原子、または硫黄原子であり、
Ｒ^９が１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、ハロゲン原子、または水素原子であり、
Ｒ^１０及びＲ^１１が、同一または相異なり、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、ハロゲン原子、または水素原子であり、
ｖが１、２、３、または４であり、
群Ｂが、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシ基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキルチオ基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキルスルフィニル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキルスルホニル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシカルボニル基、群Ｅより選ばれる１個以上の原子若しくは基を有していてもよいビニル基、群Ｅより選ばれる原子若しくは基を有していてもよいエチニル基、シアノ基、ニトロ基、カルボキシル基、ヒドロキシル基、−ＣＯＮＲ^１２Ｒ^１３基、及びハロゲン原子からなる群である［１］記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［４］Ａが、下式（ＩＩＩ−ａ）または（ＩＩＩ−ｂ）

〔式中、Ａ^１は酸素原子または硫黄原子を表し、Ｄ^１は群Ｄより選ばれる原子若しくは基を表し、ｒは０または１を表し、ｐは０、１、または２を表し、ｑは０または１を表す。〕で示される基である［１］〜［３］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［５］式（Ｉ）において、Ａが、下式（ＩＩＩ−ｄ）

〔式中、Ｄ^１は群Ｄより選ばれる原子若しくは基を表し、ｒは０または１を表す。〕で示される基である［１］〜［３］記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［６］Ａが、下式（ＩＩＩ−ｃ）

〔式中、ｐは０、１、または２を表す。〕
で示される基である［１］〜［３］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［７］式（Ｉ−ａ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表し、Ｘ^１及びＸ^２は各々同一または相異なり、窒素原子またはＣＲ^５を表し、Ｘ^１及びＸ^２の１〜２個は窒素原子を表し、Ｘ^３は酸素原子、硫黄原子又はＮＲ^６を表し、Ｒ^５及びＲ^６は［１］における定義と同じ意味を表す。〕
で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［８］式（Ｉ−ｂ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表し、Ｘ^１及びＸ^３は各々同一または相異なり、窒素原子またはＣＲ^５を表し、Ｘ^１及びＸ^３の１〜２個は窒素原子を表し、Ｘ^２は酸素原子、硫黄原子又はＮＲ^６を表し、Ｒ^５及びＲ^６は［１］における定義と同じ意味を表す。〕
で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［９］式（Ｉ−ｃ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表し、Ｘ^２及びＸ^３は各々同一または相異なり、窒素原子またはＣＲ^５を表し、Ｘ^２及びＸ^３の１〜２個は窒素原子を表し、Ｘ^１は酸素原子、硫黄原子又はＮＲ^６を表し、Ｒ^５及びＲ^６は［１］における定義と同じ意味を表す。〕
で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［１０］式（Ｉ−ｄ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表し、Ｘ^１、Ｘ^２及びＸ^３は各々同一または相異なり、窒素原子またはＣＲ^５を表し、Ｘ^１、Ｘ^２及びＸ^３の１〜３個は窒素原子を表し、Ｒ^５は［１］における定義と同じ意味を表す。〕で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［１１］式（Ｉ−ｅ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表し、Ｘ^１及びＸ^２は各々同一または相異なり、窒素原子またはＣＲ^５を表し、Ｘ^１及びＸ^２の１〜２個は窒素原子を表し、Ｒ^５は［１］における定義と同じ意味を表す。〕で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［１２］式（Ｉ−ｆ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表し、Ｘ^１及びＸ^２は各々同一または相異なり、窒素原子またはＣＲ^５を表し、Ｘ^１及びＸ^２の１〜２個は窒素原子を表し、Ｒ^５は［１］における定義と同じ意味を表す。〕で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［１３］式（Ｉ−ｇ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表し、Ｘ^１及びＸ^２は各々同一または相異なり、窒素原子またはＣＲ^５を表し、Ｘ^１及びＸ^２の１〜２個は窒素原子を表し、Ｒ^５及びＲ^６は［１］における定義と同じ意味を表す。〕で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［１４］式（Ｉ−ｈ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表し、Ｘ^１及びＸ^３は各々同一または相異なり、窒素原子またはＣＲ^５を表し、Ｘ^１及びＸ^３の１〜２個は窒素原子を表し、Ｒ^５は［１］における定義と同じ意味を表す。〕で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［１５］式（Ｉ−ｉ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表し、Ｘ^１及びＸ^３は各々同一または相異なり、窒素原子またはＣＲ^５を表し、Ｘ^１及びＸ^３の１〜２個は窒素原子を表し、Ｒ^５は［１］における定義と同じ意味を表す。〕で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［１６］式（Ｉ−ｊ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表し、Ｘ^１及びＸ^３は各々同一または相異なり、窒素原子またはＣＲ^５を表し、Ｘ^１及びＸ^３の１〜２個は窒素原子を表し、Ｒ^５及びＲ^６は［１］における定義と同じ意味を表す。〕で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［１７］式（Ｉ−ｋ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表し、Ｘ^２及びＸ^３は各々同一または相異なり、窒素原子またはＣＲ^５を表し、Ｘ^２及びＸ^３の１〜２個は窒素原子を表し、Ｒ^５は［１］における定義と同じ意味を表す。〕で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［１８］式（Ｉ−ｌ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表し、Ｘ^２及びＸ^３は各々同一または相異なり、窒素原子またはＣＲ^５を表し、Ｘ^２及びＸ^３の１〜２個は窒素原子を表し、Ｒ^５は［１］における定義と同じ意味を表す。〕で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［１９］式（Ｉ−ｋ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表し、Ｘ^２及びＸ^３は各々同一または相異なり、窒素原子またはＣＲ^５を表し、Ｘ^２及びＸ^３の１〜２個は窒素原子を表し、Ｒ^５及びＲ^６は［１］における定義と同じ意味を表す。〕で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［２０］式（Ｉ−ｍ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表し、Ｘ^１は窒素原子またはＣＲ^５を表し、Ｘ^３は酸素原子、硫黄原子又はＮＲ^６を表し、Ｒ^５及びＲ^６は［１］における定義と同じ意味を表す。〕で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［２１］式（Ｉ−ｎ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表し、Ｘ^１は窒素原子またはＣＲ^５を表し、Ｘ^２は酸素原子、硫黄原子又はＮＲ^６を表し、Ｒ^５及びＲ^６は［１］における定義と同じ意味を表す。〕で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［２２］式（Ｉ−ｏ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ｒ^５、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表し、Ｘ^２およびＸ^３の一方は窒素原子であり、もう一方は酸素原子、硫黄原子又はＮＲ^６を表し、Ｒ^６は［１］における定義と同じ意味を表す。〕で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［２３］式（Ｉ−ｐ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表し、Ｘ^１は窒素原子またはＣＲ^５を表し、Ｒ^５は［１］における定義と同じ意味を表す。〕
で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［２４］式（Ｉ−ｑ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表し、Ｘ^１は窒素原子またはＣＲ^５を表し、Ｒ^５は［１］における定義と同じ意味を表す。〕で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［２５］式（Ｉ−ｒ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表し、Ｘ^３は窒素原子またはＣＲ^５を表し、Ｒ^５は［１］における定義と同じ意味を表す。〕で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［２６］式（Ｉ−ｓ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ｒ^５、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表す。〕
で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［２７］式（Ｉ−ｔ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ｒ^５、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表す。〕
で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［２８］式（Ｉ−ｕ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ｒ^５、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表す。〕で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［２９］式（Ｉ−ｖ）

〔式中、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ａ、Ｑ、Ｙ、ｍ及びｎは［１］における定義と同じ意味を表す。〕で示される［１］〜［６］いずれか一項に記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［３０］式（Ｉ）において、ｎが１である［１］〜［２９］いずれか一項記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［３１］式（Ｉ）において、ｍが１である［１］〜［３０］いずれか一項記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［３２］式（Ｉ）においてＹが酸素原子である［１］〜［３１］いずれか一項記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［３３］式（Ｉ）においてＹが−ＣＲ^８Ｒ^９−である［３］〜［３１］いずれか一項記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［３４］式（Ｉ）においてＹが−ＣＲ^８Ｒ^９−であり、Ｒ^８及びＲ^９が水素原子である［３］〜［３１］いずれか一項記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［３５］式（Ｉ）においてＱが群Ａより選ばれる基である［１］〜［３４］いずれか一項記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［３６］式（Ｉ）においてＱがＣ１−Ｃ８鎖式炭化水素基である［２］〜［３４］いずれか一項記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［３７］式（Ｉ）においてＹが単結合である［１］、［２］および［４］〜［２９］いずれか一項記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［３８］式（Ｉ）においてＱが群Ａより選ばれる１個の基を有しているＣ１−Ｃ８鎖式炭化水素基である［３］〜［３４］いずれか一項記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［３９］式（Ｉ）においてＱが群Ａより選ばれる１個の基を有するメチル基である［３］〜［３４］いずれか一項記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［４０］式（Ｉ）においてＱがＣ３−Ｃ８鎖式炭化水素基である［１］、［２］および［４］〜［３４］いずれか一項記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［４１］式（Ｉ）においてＱが群Ｆより選ばれる１個以上の原子または基を有してもよいＣ１−Ｃ８鎖式炭化水素基である［２］〜［３４］いずれか一項記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［４２］式（Ｉ）においてＱが群Gより選ばれる１個以上の原子または基を有しているＣ１−Ｃ８鎖式炭化水素基である［１］および［４］〜［３４］いずれか一項記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［４３］式（Ｉ）においてＱが群Ｆより選ばれる１個以上の原子または基を有しているＣ１−Ｃ８鎖式炭化水素基である［１］、［２］および［４］〜［３４］いずれか一項記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［４４］式（Ｉ）においてＱが群Ｆより選ばれる１個の基を有するＣ１−Ｃ８鎖式炭化水素基である［１］、［２］および［４］〜［３４］いずれか一項記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［４５］式（Ｉ）においてＱが群Ｆより選ばれる１個の基を有するメチル基である［２］〜［３４］いずれか一項記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［４６］式（Ｉ）においてＲ^５がヒドロキシル基およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ２アルキル基または水素原子である［２６］および［３０］〜［４５］いずれか一項記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［４７］［１］〜［４６］いずれか一項記載の式（Ｉ）で示されるアミド化合物の有効量を有害節足動物または有害節足動物の生育場所に施用する有害節足動物の防除方法。
［４８］式（Ｉ−ｓ）

〔式中、
Ａは、酸素原子及び−Ｓ（Ｏ）_ｔ−からなる群より選ばれる１個以上の原子または基を環構成成分として含む３−７員飽和へテロ環を表し、該飽和へテロ環は、群Ｄより選ばれる１〜３個の原子または基を有していてもよく、
ｔは０、１、または２を表し、
Ｒ^１及びＲ^２は、同一または相異なり、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、または水素原子を表し、
ｎは、０、１、または２を表し、
Ｒ^５は、ハロゲン原子、シアノ基、ホルミル基、カルボキシル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシカルボニル基、カルバモイル基、−ＯＲ^７およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ３炭化水素基、又は水素原子を表し、
Ｒ^７は−Ｃ（＝Ｓ）ＳＲ^８又は水素原子を表し、Ｒ^８は１個以上のハロゲン原子を有していてもよいＣ１−Ｃ３炭化水素基を表し、
Ｒ^３及びＲ^４は、同一または相異なり、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、ハロゲン原子、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基または水素原子を表し、
Ｙは、単結合、酸素原子、または−Ｓ（Ｏ）_ｕ−を表し
Ｙが単結合の場合は、ｍは０を表し、
Ｙが酸素原子、または−Ｓ（Ｏ）_ｕ−である場合は、ｍは０、１、２、３、４、５、６または７を表し、
Ｙが単結合の場合は、Ｑは群Ｆより選ばれる１個以上の原子または基を有しているＣ１−Ｃ８鎖式炭化水素基を表し、
Ｙが酸素原子であり、ｍが０、２、３、４、５、６または７である場合、またはＹが−Ｓ（Ｏ）_ｕ−である場合は、Ｑは群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基、または群Ａより選ばれる１個の基を表し、
Ｙが酸素原子であり、ｍが１である場合は、Ｑは群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基、または群Ｈより選ばれる１個の基を表し、
ｕは０、１、または２を表す。
群Ａ：群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいＣ３−Ｃ８シクロアルキル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいインダニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，２，３，４−テトラヒドロナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいピリジル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいキノリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいチエニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾフラニル基、及び群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾチエニル基からなる群。
群Ｂ：１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、１個以上のベンジルオキシ基を有しているＣ１−Ｃ４アルキル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシ基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキルチオ基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキルスルフィニル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキルスルホニル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシカルボニル基、群Ｅより選ばれる１個以上の原子若しくは基を有していてもよいビニル基、群Ｅより選ばれる原子若しくは基を有していてもよいエチニル基、フェニル基、フェノキシ基、シアノ基、ニトロ基、カルボキシル基、ヒドロキシル基、−ＣＯＮＲ^１２Ｒ^１３基、メトキシメチル基及びハロゲン原子からなる群。
Ｒ^１２及びＲ^１３は、同一または相異なり、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、または水素原子を表す。
群Ｄ：１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシ基、及びハロゲン原子からなる群。
群Ｅ：１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基及びハロゲン原子からなる群。
群Ｆ：群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいＣ３−Ｃ８シクロアルキル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいインダニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，２，３，４−テトラヒドロナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいピリジル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいキノリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいチエニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾフラニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾチエニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，３−ベンゾジオキソリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，４−ベンゾジオキサニル基、ハロゲン原子、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシカルボニル基、シアノ基、ニトロ基、カルボキシル基、ヒドロキシル基、および−ＣＯＮＲ^１２Ｒ^１３基からなる群。
群Ｇ：群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいＣ３−Ｃ８シクロアルキル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいインダニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，２，３，４−テトラヒドロナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェノキシ基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいピリジル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいキノリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいチエニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾフラニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾチエニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，３−ベンゾジオキソリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，４−ベンゾジオキサニル基、ハロゲン原子、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシカルボニル基、シアノ基、ニトロ基、カルボキシル基、ヒドロキシル基、および−ＣＯＮＲ^１２Ｒ^１３基からなる群。
群Ｈ：群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいＣ３−Ｃ８シクロアルキル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいインダニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいチエニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾフラニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾチエニル基、及び群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，３−ベンゾジオキソリル基からなる群。〕で示されるアミド化合物。
［４９］式（Ｉ−ｓ）で示されるアミド化合物であって、Ｒ^５が、ハロゲン原子、シアノ基、メチル基又は水素原子であり、
Ｒ^３及びＲ^４が、同一または相異なり、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、ハロゲン原子、または水素原子であり、
群Ｂが１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシ基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキルチオ基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキルスルフィニル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキルスルホニル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシカルボニル基、群Ｅより選ばれる１個以上の原子若しくは基を有していてもよいビニル基、群Ｅより選ばれる原子若しくは基を有していてもよいエチニル基、シアノ基、ニトロ基、カルボキシル基、ヒドロキシル基、−ＣＯＮＲ^１２Ｒ^１３基、メトキシメチル基及びハロゲン原子からなる群であり、
Ｙが酸素原子、または−Ｓ（Ｏ）_ｕ−である場合は、ｍが０、１、２、３または４であり、Ｙが酸素原子、または−Ｓ（Ｏ）_ｕ−である場合は、Ｑが群Ｆより選ばれる１個以上の原子または基を有してもよいＣ１−Ｃ８鎖式炭化水素基である［４８］記載のアミド化合物。
［５０］式（Ｉ−ｓ）で示されるアミド化合物であって、Ａが、下式（ＩＩＩ−ａ）または（ＩＩＩ−ｂ）

〔式中、Ａ^１は酸素原子または硫黄原子を表し、Ｄ^１は群Ｄより選ばれる原子若しくは基を表し、ｒは０または１を表し、ｐは０、１、または２を表し、ｑは０または１を表す。〕
で示される基である［４８］または［４９］記載のアミド化合物。
［５１］式（Ｉ−ｓ）で示されるアミド化合物であって、Ａが、下式（ＩＩＩ−ｄ）

〔式中、Ｄ^１は群Ｄより選ばれる原子若しくは基を表し、ｒは０または１を表す。〕で示される基である［４８］または［４９］記載のアミド化合物。
［５２］式（Ｉ−ｓ）で示されるアミド化合物であって、Ａが、下式（ＩＩＩ−ｃ）

〔式中、ｐは０、１、または２を表す。〕
で示される基である［４８］または［４９］記載のアミド化合物。
［５３］式（Ｉ−ｓ）で示されるアミド化合物であって、ｎが１である［４８］〜［５２］いずれか一項記載のアミド化合物。
［５４］式（Ｉ−ｓ）で示されるアミド化合物であって、ｍが１である［４８］〜［５３］いずれか一項記載のアミド化合物。
［５５］式（Ｉ−ｓ）で示されるアミド化合物であって、Ｙが酸素原子である［４８］〜［５４］いずれか一項記載のアミド化合物。
［５６］式（Ｉ−ｓ）で示されるアミド化合物であって、Ｙが単結合である［４８］〜［５４］いずれか一項記載のアミド化合物。
［５７］式（Ｉ−ｓ）で示されるアミド化合物であって、Ｑが群Ａより選ばれる基である［４８］〜［５６］いずれか一項記載のアミド化合物。
［５８］式（Ｉ−ｓ）で示されるアミド化合物であって、Ｑが群Ｈより選ばれる１個の基である［４８］〜［５５］いずれか一項記載のアミド化合物。
［５９］式（Ｉ−ｓ）で示されるアミド化合物であって、Ｑが群Ｇより選ばれる１個以上の原子または基を有してもよいＣ１−Ｃ８鎖式炭化水素基である［４８］〜［５５］いずれか一項記載のアミド化合物。
［６０］式（Ｉ−ｓ）で示されるアミド化合物であって、Ｑが群Ｆより選ばれる１個以上原子または基を有しているＣ１−Ｃ８鎖式炭化水素基である［４８］〜［５４］および［５６］いずれか一項記載のアミド化合物。
［６１］式（Ｉ−ｓ）で示されるアミド化合物であって、Ｑが群Ｆより選ばれる１個の基を有するＣ１−Ｃ８鎖式炭化水素基である［４８］〜［５６］いずれか一項記載のアミド化合物。
［６２］式（Ｉ−ｓ）で示されるアミド化合物であって、Ｑが群Ｆより選ばれる１個の基を有するメチル基である［４８］〜［５６］いずれか一項記載のアミド化合物。
［６３］式（Ｉ−ｓ）で示されるアミド化合物であって、Ｒ^５がヒドロキシル基およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ２アルキル基または水素原子である［４８］〜［６２］いずれか一項記載のアミド化合物。
［６４］式（Ｉ−ｓ）で示されるアミド化合物であって、
Ａが、下式（ＩＩＩ−ａ）、（ＩＩＩ−ｂ）又は（ＩＩＩ−ｄ）

〔式中、Ａ^１は酸素原子または硫黄原子を表し、Ｄ^１は１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基を表し、ｒは０または１を表し、ｐは０、１、または２を表し、ｑは０または１を表す。〕で示される基であり、
Ｒ^１及びＲ^２が、水素原子であり、
ｎが、０、１、または２であり、
Ｒ^５が、水素原子、ハロゲン原子、ホルミル基、またはヒドロキシル基およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ２アルキル基であり、
Ｒ^３及びＲ^４が、同一または相異なり、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、または水素原子であり、
群Ｂが、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、１個以上のベンジルオキシ基を有しているＣ１−Ｃ４アルキル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシ基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキルチオ基、フェニル基、フェノキシ基、シアノ基及びハロゲン原子からなる群であり、
群Ｆが、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいキノリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾチエニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，３−ベンゾジオキソリル基、ハロゲン原子からなる群であり、
群Ｇが、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいＣ３−Ｃ８シクロアルキル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，２，３，４−テトラヒドロナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェノキシ基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいキノリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいチエニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾフラニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾチエニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，３−ベンゾジオキソリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，４−ベンゾジオキサニル基からなる群であり、
群Ｈが、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいＣ３−Ｃ８シクロアルキル基、及び群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，３−ベンゾジオキソリル基からなる群であり、
Ｙが、単結合、酸素原子、または硫黄原子であり、
Ｙが単結合の場合は、ｍが０であり、
Ｙが酸素原子、または硫黄原子である場合は、ｍが１、２、３、４、５、６または７であり、
Ｙが単結合の場合は、Ｑが群Ｆより選ばれる１個以上の原子または基を有しているＣ１−Ｃ８鎖式炭化水素基であり、
Ｙが酸素原子であり、ｍが２、３、４、５、６または７である場合、またはＹが硫黄原子である場合は、Ｑが群Ｇより選ばれる１個以上の基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であり、
Ｙが酸素原子であり、ｍが１である場合は、Ｑが群Ｇより選ばれる１個以上の基を有していてもよいＣ１−Ｃ８鎖式炭化水素基、または群Ｈより選ばれる１個の基である［４８］記載のアミド化合物。
［６５］式（Ｉ−ｓ）において
Ａが、下式（ＩＩＩ−ａ）、（ＩＩＩ−ｂ）又は（ＩＩＩ−ｄ）

〔式中、Ａ^１は酸素原子または硫黄原子を表し、Ｄ^１は１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基を表し、ｒは０または１を表し、ｐは０、１、または２を表し、ｑは０または１を表す。〕で示される基であり、
Ｒ^１及びＲ^２が、水素原子であり、
ｎが、０、１、または２であり、
Ｒ^５が、水素原子、ハロゲン原子、ホルミル基、またはヒドロキシル基およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ２アルキル基であり、
Ｒ^３及びＲ^４が、同一または相異なり、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、または水素原子であり、
群Ａが、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいＣ３−Ｃ８シクロアルキル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，２，３，４−テトラヒドロナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいキノリル基、及び群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，３−ベンゾジオキソリル基からなる群であり、
群Ｂが、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキル基、１個以上のベンジルオキシ基を有しているＣ１−Ｃ４アルキル基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシ基、１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルキルチオ基、フェニル基、フェノキシ基、シアノ基及びハロゲン原子からなる群であり、
群Ｆが、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいキノリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾチエニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，３−ベンゾジオキソリル基、ハロゲン原子からなる群であり、
群Ｇが、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいＣ３−Ｃ８シクロアルキル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，２，３，４−テトラヒドロナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェノキシ基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいキノリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいチエニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾフラニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾチエニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，３−ベンゾジオキソリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，４−ベンゾジオキサニル基からなる群であり、
Ｙが、単結合、酸素原子、または硫黄原子であり、
Ｙが単結合の場合は、ｍが０であり、
Ｙが酸素原子、または−Ｓ（Ｏ）_ｕ−である場合は、ｍが０、１、２、３、４、５、６または７であり、
Ｙが単結合の場合は、Ｑが群Ｆより選ばれる１個以上の原子または基を有しているＣ１−Ｃ８鎖式炭化水素基、またはＣ３−Ｃ８鎖式炭化水素基であり、
Ｙが酸素原子、または硫黄原子である場合は、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基、または群Ａより選ばれる１個の基である［２６］記載のアミド化合物と不活性担体とを含有する有害節足動物防除剤。
［６６］［６５］記載の式（Ｉ−ｓ）で示されるアミド化合物の有効量を有害節足動物または有害節足動物の生育場所に施用する有害節足動物の防除方法。 As a result of intensive studies to find a compound having an excellent control effect against harmful arthropods, the present inventors have found an amide compound represented by the following formula (I) (hereinafter sometimes referred to as the present compound). Was found to have an excellent control effect on harmful arthropods, and the present invention was completed.
That is, the present invention is as follows.
[1] Formula (I)

[Where,
A is an oxygen atom and -S (O) _t -Represents a 3-7 membered saturated hetero ring containing at least one atom or group selected from the group consisting of-as a ring constituent, wherein the saturated hetero ring is 1 to 3 atoms selected from group D or May have a group,
t represents 0, 1, or 2;
R ¹ And R ² Are the same or different and each represents a C1-C4 alkyl group optionally having one or more halogen atoms, or a hydrogen atom,
n represents 0, 1, or 2;
Formula (II)

Represents a 5-membered aromatic ring,
Z represents a nitrogen atom or a carbon atom,
When Z represents a nitrogen atom, X ¹ , X ² And X ³ Are the same or different, nitrogen atom, CR ⁵ , Oxygen atom, sulfur atom or NR ⁶ X ¹ , X ² And X ³ At least one of nitrogen atom, oxygen atom, sulfur atom or NR ⁶ And
When Z represents a carbon atom, X ¹ , X ² And X ³ Are the same or different, nitrogen atom, CR ⁵ , Oxygen atom, sulfur atom or NR ⁶ X ¹ , X ² And X ³ At least two of the nitrogen atom, oxygen atom, sulfur atom or NR ⁶ And the X ¹ , X ² And X ³ At least one of nitrogen atom or NR ⁶ And
R ⁵ Are the same or different and each is a halogen atom, cyano group, formyl group, carboxyl group, C1-C4 alkoxycarbonyl group optionally having one or more halogen atoms, carbamoyl group, -OR ⁷ And a C1-C3 hydrocarbon group optionally having one or more atoms or groups selected from the group consisting of halogen atoms, or a hydrogen atom,
R ⁶ Represents a methyl group or a hydrogen atom, R ⁷ Is -C (= S) SR ⁸ Or a hydrogen atom, R ⁸ Represents a C1-C3 hydrocarbon group optionally having one or more halogen atoms,
R ³ And R ⁴ Are the same or different, a C1-C4 alkyl group optionally having one or more halogen atoms, a halogen atom, a phenyl group optionally having one or more atoms or groups selected from group B Or a hydrogen atom,
Y is a single bond, an oxygen atom, or -S (O) _u -Represents
When Y is a single bond, m represents 0;
Y is an oxygen atom or -S (O) _u When-, m represents 0, 1, 2, 3, 4, 5, 6 or 7;
When Y is a single bond, Q is a C1-C8 chain hydrocarbon group having one or more atoms or groups selected from group F, or
Represents a C3-C8 chain hydrocarbon group,
Y is an oxygen atom or -S (O) _u When-is, C is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G;
Or one group selected from group A,
u represents 0, 1, or 2.
Group A: C3-C8 cycloalkyl group optionally having one or more atoms or groups selected from Group B, Indanyl group optionally having one or more atoms or groups selected from Group B A 1,2,3,4-tetrahydronaphthyl group which may have one or more atoms or groups selected from group B, or one or more atoms or groups selected from group B. A good phenyl group, a naphthyl group optionally having one or more atoms or groups selected from group B, a pyridyl group optionally having one or more atoms or groups selected from group B, group B A quinolyl group optionally having one or more atoms or groups selected from the group, a furyl group optionally having one or more atoms or groups selected from the group B, one or more selected from group B May have any atom or group A thienyl group, a benzofuranyl group optionally having one or more atoms or groups selected from group B, a benzothienyl group optionally having one or more atoms or groups selected from group B, and a group A group consisting of a 1,3-benzodioxolyl group optionally having one or more atoms or groups selected from B.
Group B: C1-C4 alkyl group optionally having one or more halogen atoms, C1-C4 alkyl group having one or more benzyloxy groups, having one or more halogen atoms C1-C4 alkoxy group which may have one, C1-C4 alkylthio group which may have one or more halogen atoms, C1-C4 alkylsulfinyl group which may have one or more halogen atoms, one C1-C4 alkylsulfonyl group optionally having one or more halogen atoms, C1-C4 alkoxycarbonyl group optionally having one or more halogen atoms, one or more atoms or groups selected from group E A vinyl group which may have, an ethynyl group which may have an atom or group selected from group E, a phenyl group, a phenoxy group, a cyano group, a nitro group, a carboxyl group A hydroxyl group, -CONR ¹² R ¹³ A group consisting of a group, a methoxymethyl group and a halogen atom.
R ¹² And R ¹³ Are the same or different and each represents a C1-C4 alkyl group optionally having one or more halogen atoms, or a hydrogen atom.
Group D: a group consisting of a C1-C4 alkyl group optionally having one or more halogen atoms, a C1-C4 alkoxy group optionally having one or more halogen atoms, and a halogen atom.
Group E: A group consisting of a C1-C4 alkyl group optionally having one or more halogen atoms and a halogen atom.
Group F: a C3-C8 cycloalkyl group optionally having one or more atoms or groups selected from Group B, an indanyl group optionally having one or more atoms or groups selected from Group B A 1,2,3,4-tetrahydronaphthyl group which may have one or more atoms or groups selected from group B, or one or more atoms or groups selected from group B. A good phenyl group, a naphthyl group optionally having one or more atoms or groups selected from group B, a pyridyl group optionally having one or more atoms or groups selected from group B, group B A quinolyl group optionally having one or more atoms or groups selected from the group, a furyl group optionally having one or more atoms or groups selected from the group B, one or more selected from group B May have any atom or group A thienyl group, a benzofuranyl group optionally having one or more atoms or groups selected from group B, a benzothienyl group optionally having one or more atoms or groups selected from group B, group B 1,3-benzodioxolyl group optionally having one or more atoms or groups selected from 1,4, optionally having one or more atoms or groups selected from group B Benzodioxanyl group, halogen atom, C1-C4 alkoxycarbonyl group optionally having one or more halogen atoms, cyano group, nitro group, carboxyl group, hydroxyl group, and -CONR ¹² R ¹³ A group of groups.
Group G: a C3-C8 cycloalkyl group optionally having one or more atoms or groups selected from Group B, an indanyl group optionally having one or more atoms or groups selected from Group B A 1,2,3,4-tetrahydronaphthyl group which may have one or more atoms or groups selected from group B, or one or more atoms or groups selected from group B. A good phenyl group, a phenoxy group optionally having one or more atoms or groups selected from group B, a naphthyl group optionally having one or more atoms or groups selected from group B, group B A pyridyl group optionally having one or more atoms or groups selected from the group, a quinolyl group optionally having one or more atoms or groups selected from the group B, one or more selected from group B Having an atom or group of A good furyl group, a thienyl group optionally having one or more atoms or groups selected from group B, a benzofuranyl group optionally having one or more atoms or groups selected from group B, group B A benzothienyl group optionally having one or more atoms or groups selected from 1, a 1,3-benzodioxolyl group optionally having one or more atoms or groups selected from group B; 1,4-benzodioxanyl group optionally having one or more atoms or groups selected from group B, halogen atom, C1-C4 alkoxycarbonyl optionally having one or more halogen atoms Group, cyano group, nitro group, carboxyl group, hydroxyl group, and -CONR ¹² R ¹³ A group of groups. ]
A harmful arthropod control agent comprising the amide compound represented by the above and an inert carrier.
[2] In the formula (I), R ⁵ Are the same or different and are each a halogen atom, a cyano group, a methyl group or a hydrogen atom, and R ³ And R ⁴ Are the same or different, a C1-C4 alkyl group which may have one or more halogen atoms, a halogen atom, or a hydrogen atom,
Group B has a C1-C4 alkyl group which may have one or more halogen atoms, a C1-C4 alkoxy group which may have one or more halogen atoms, and one or more halogen atoms A C1-C4 alkylthio group optionally having one or more halogen atoms, a C1-C4 alkylsulfinyl group optionally having one or more halogen atoms, a C1-C4 alkylsulfonyl group optionally having one or more halogen atoms, A C1-C4 alkoxycarbonyl group optionally having one or more halogen atoms, a vinyl group optionally having one or more atoms or groups selected from group E, an atom or group selected from group E Ethynyl group, cyano group, nitro group, carboxyl group, hydroxyl group, -CONR ¹² R ¹³ A group consisting of a group, a methoxymethyl group and a halogen atom,
Y is a single bond, an oxygen atom, or -S (O) _u −
Y is an oxygen atom or -S (O) _u When-, m is 0, 1, 2, 3, or 4, Y is an oxygen atom, or -S (O) _u In the case of-, Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group F, or one group selected from group A [1. ] A harmful arthropod control agent comprising the amide compound described above and an inert carrier.
[3] In the formula (I)
R ⁵ Are the same or different and each is a halogen atom, a cyano group, a methyl group optionally having a halogen atom or a hydrogen atom,
m is 0-2,
Q is a C1-C8 chain hydrocarbon group which may have one group selected from group A or one group selected from group A;
Y is -CR ⁸ R ⁹ -, -CR ⁹ = CR ⁹ -, Oxygen atom, or -S (O) _u −
R ⁸ Represents a C1-C4 alkyl group optionally having one or more halogen atoms, a halogen atom, or a hydrogen atom, or R ³ And R ⁸ Together with-(CR ¹⁰ R ¹¹ ) _v -, An oxygen atom or a sulfur atom,
R ⁹ Is a C1-C4 alkyl group optionally having one or more halogen atoms, a halogen atom, or a hydrogen atom,
R ¹⁰ And R ¹¹ Are the same or different, a C1-C4 alkyl group which may have one or more halogen atoms, a halogen atom, or a hydrogen atom,
v is 1, 2, 3, or 4;
Group B has a C1-C4 alkyl group which may have one or more halogen atoms, a C1-C4 alkoxy group which may have one or more halogen atoms, and one or more halogen atoms. C1-C4 alkylthio group which may have one, C1-C4 alkylsulfinyl group which may have one or more halogen atoms, C1-C4 alkylsulfonyl group which may have one or more halogen atoms A C1-C4 alkoxycarbonyl group optionally having one or more halogen atoms, a vinyl group optionally having one or more atoms or groups selected from group E, an atom selected from group E, or Ethynyl group, cyano group, nitro group, carboxyl group, hydroxyl group, -CONR which may have a group ¹² R ¹³ A harmful arthropod control agent comprising an amide compound according to [1], which is a group consisting of a group and a halogen atom, and an inert carrier.
[4] A is represented by the following formula (III-a) or (III-b)

[Where A ¹ Represents an oxygen atom or a sulfur atom, and D ¹ Represents an atom or group selected from the group D, r represents 0 or 1, p represents 0, 1, or 2, and q represents 0 or 1. A harmful arthropod control agent comprising the amide compound according to any one of [1] to [3], which is a group represented by the formula:
[5] In the formula (I), A represents the following formula (III-d)

[Where D ¹ Represents an atom or group selected from group D, and r represents 0 or 1. A harmful arthropod control agent comprising the amide compound according to [1] to [3], which is a group represented by the formula:
[6] A represents the following formula (III-c)

[Wherein, p represents 0, 1, or 2. ]
A harmful arthropod control agent comprising the amide compound according to any one of [1] to [3], which is a group represented by
[7] Formula (Ia)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , A, Q, Y, m and n have the same meaning as defined in [1], and X ¹ And X ² Are the same or different and are each a nitrogen atom or CR ⁵ X ¹ And X ² 1 to 2 of X represents a nitrogen atom, and X ³ Is an oxygen atom, sulfur atom or NR ⁶ Represents R ⁵ And R ⁶ Represents the same meaning as defined in [1]. ]
A harmful arthropod control agent comprising the amide compound according to any one of [1] to [6] and an inert carrier.
[8] Formula (Ib)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , A, Q, Y, m and n have the same meaning as defined in [1], and X ¹ And X ³ Are the same or different and are each a nitrogen atom or CR ⁵ X ¹ And X ³ 1 to 2 of X represents a nitrogen atom, and X ² Is an oxygen atom, sulfur atom or NR ⁶ Represents R ⁵ And R ⁶ Represents the same meaning as defined in [1]. ]
A harmful arthropod control agent comprising the amide compound according to any one of [1] to [6] and an inert carrier.
[9] Formula (Ic)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , A, Q, Y, m and n have the same meaning as defined in [1], and X ² And X ³ Are the same or different and are each a nitrogen atom or CR ⁵ X ² And X ³ 1 to 2 of X represents a nitrogen atom, and X ¹ Is an oxygen atom, sulfur atom or NR ⁶ Represents R ⁵ And R ⁶ Represents the same meaning as defined in [1]. ]
A harmful arthropod control agent comprising the amide compound according to any one of [1] to [6] and an inert carrier.
[10] Formula (Id)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , A, Q, Y, m and n have the same meaning as defined in [1], and X ¹ , X ² And X ³ Are the same or different and are each a nitrogen atom or CR ⁵ X ¹ , X ² And X ³ 1-3 represent a nitrogen atom, R ⁵ Represents the same meaning as defined in [1]. ] The harmful arthropod control agent containing the amide compound as described in any one of [1] to [6] and an inert carrier.
[11] Formula (Ie)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , A, Q, Y, m and n have the same meaning as defined in [1], and X ¹ And X ² Are the same or different and are each a nitrogen atom or CR ⁵ X ¹ And X ² 1 to 2 of these represent a nitrogen atom, R ⁵ Represents the same meaning as defined in [1]. ] The harmful arthropod control agent containing the amide compound as described in any one of [1] to [6] and an inert carrier.
[12] Formula (If)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , A, Q, Y, m and n have the same meaning as defined in [1], and X ¹ And X ² Are the same or different and are each a nitrogen atom or CR ⁵ X ¹ And X ² 1 to 2 of these represent a nitrogen atom, R ⁵ Represents the same meaning as defined in [1]. ] The harmful arthropod control agent containing the amide compound as described in any one of [1] to [6] and an inert carrier.
[13] Formula (Ig)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , A, Q, Y, m and n have the same meaning as defined in [1], and X ¹ And X ² Are the same or different and are each a nitrogen atom or CR ⁵ X ¹ And X ² 1 to 2 of these represent a nitrogen atom, R ⁵ And R ⁶ Represents the same meaning as defined in [1]. ] The harmful arthropod control agent containing the amide compound as described in any one of [1] to [6] and an inert carrier.
[14] Formula (Ih)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , A, Q, Y, m and n have the same meaning as defined in [1], and X ¹ And X ³ Are the same or different and are each a nitrogen atom or CR ⁵ X ¹ And X ³ 1 to 2 of these represent a nitrogen atom, R ⁵ Represents the same meaning as defined in [1]. ] The harmful arthropod control agent containing the amide compound as described in any one of [1] to [6] and an inert carrier.
[15] Formula (Ii)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , A, Q, Y, m and n have the same meaning as defined in [1], and X ¹ And X ³ Are the same or different and are each a nitrogen atom or CR ⁵ X ¹ And X ³ 1 to 2 of these represent a nitrogen atom, R ⁵ Represents the same meaning as defined in [1]. ] The harmful arthropod control agent containing the amide compound as described in any one of [1] to [6] and an inert carrier.
[16] Formula (Ij)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , A, Q, Y, m and n have the same meaning as defined in [1], and X ¹ And X ³ Are the same or different and are each a nitrogen atom or CR ⁵ X ¹ And X ³ 1 to 2 of these represent a nitrogen atom, R ⁵ And R ⁶ Represents the same meaning as defined in [1]. ] The harmful arthropod control agent containing the amide compound as described in any one of [1] to [6] and an inert carrier.
[17] Formula (Ik)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , A, Q, Y, m and n have the same meaning as defined in [1], and X ² And X ³ Are the same or different and are each a nitrogen atom or CR ⁵ X ² And X ³ 1 to 2 of these represent a nitrogen atom, R ⁵ Represents the same meaning as defined in [1]. ] The harmful arthropod control agent containing the amide compound as described in any one of [1] to [6] and an inert carrier.
[18] Formula (I-1)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , A, Q, Y, m and n have the same meaning as defined in [1], and X ² And X ³ Are the same or different and are each a nitrogen atom or CR ⁵ X ² And X ³ 1 to 2 of these represent a nitrogen atom, R ⁵ Represents the same meaning as defined in [1]. ] The harmful arthropod control agent containing the amide compound as described in any one of [1] to [6] and an inert carrier.
[19] Formula (Ik)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , A, Q, Y, m and n have the same meaning as defined in [1], and X ² And X ³ Are the same or different and are each a nitrogen atom or CR ⁵ X ² And X ³ 1 to 2 of these represent a nitrogen atom, R ⁵ And R ⁶ Represents the same meaning as defined in [1]. ] The harmful arthropod control agent containing the amide compound as described in any one of [1] to [6] and an inert carrier.
[20] Formula (Im)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , A, Q, Y, m and n have the same meaning as defined in [1], and X ¹ Is a nitrogen atom or CR ⁵ X ³ Is an oxygen atom, sulfur atom or NR ⁶ Represents R ⁵ And R ⁶ Represents the same meaning as defined in [1]. ] The harmful arthropod control agent containing the amide compound as described in any one of [1] to [6] and an inert carrier.
[21] Formula (In)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , A, Q, Y, m and n have the same meaning as defined in [1], and X ¹ Is a nitrogen atom or CR ⁵ X ² Is an oxygen atom, sulfur atom or NR ⁶ Represents R ⁵ And R ⁶ Represents the same meaning as defined in [1]. ] The harmful arthropod control agent containing the amide compound as described in any one of [1] to [6] and an inert carrier.
[22] Formula (Io)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , A, Q, Y, m and n have the same meaning as defined in [1], and X ² And X ³ One is a nitrogen atom and the other is an oxygen atom, a sulfur atom or NR ⁶ Represents R ⁶ Represents the same meaning as defined in [1]. ] The harmful arthropod control agent containing the amide compound as described in any one of [1] to [6] and an inert carrier.
[23] Formula (Ip)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , A, Q, Y, m and n have the same meaning as defined in [1], and X ¹ Is a nitrogen atom or CR ⁵ Represents R ⁵ Represents the same meaning as defined in [1]. ]
A harmful arthropod control agent comprising the amide compound according to any one of [1] to [6] and an inert carrier.
[24] Formula (Iq)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , A, Q, Y, m and n have the same meaning as defined in [1], and X ¹ Is a nitrogen atom or CR ⁵ Represents R ⁵ Represents the same meaning as defined in [1]. ] The harmful arthropod control agent containing the amide compound as described in any one of [1] to [6] and an inert carrier.
[25] Formula (Ir)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , A, Q, Y, m and n have the same meaning as defined in [1], and X ³ Is a nitrogen atom or CR ⁵ Represents R ⁵ Represents the same meaning as defined in [1]. ] The harmful arthropod control agent containing the amide compound as described in any one of [1] to [6] and an inert carrier.
[26] Formula (I-s)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , A, Q, Y, m, and n have the same meaning as defined in [1]. ]
A harmful arthropod control agent comprising the amide compound according to any one of [1] to [6] and an inert carrier.
[27] Formula (It)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , A, Q, Y, m, and n have the same meaning as defined in [1]. ]
A harmful arthropod control agent comprising the amide compound according to any one of [1] to [6] and an inert carrier.
[28] Formula (Iu)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , A, Q, Y, m, and n have the same meaning as defined in [1]. ] The harmful arthropod control agent containing the amide compound as described in any one of [1] to [6] and an inert carrier.
[29] Formula (Iv)

[In the formula, R ¹ , R ² , R ³ , R ⁴ , A, Q, Y, m, and n have the same meaning as defined in [1]. ] The harmful arthropod control agent containing the amide compound as described in any one of [1] to [6] and an inert carrier.
[30] A harmful arthropod control agent comprising the amide compound according to any one of [1] to [29] wherein n is 1 in the formula (I) and an inert carrier.
[31] A harmful arthropod control agent comprising the amide compound according to any one of [1] to [30], wherein m is 1 in formula (I), and an inert carrier.
[32] A harmful arthropod control agent comprising the amide compound according to any one of [1] to [31], wherein Y is an oxygen atom in the formula (I), and an inert carrier.
[33] In formula (I), Y is —CR ⁸ R ⁹ A harmful arthropod control agent comprising the amide compound according to any one of [3] to [31] and an inert carrier.
[34] In formula (I), Y is —CR ⁸ R ⁹ -And R ⁸ And R ⁹ A harmful arthropod control agent comprising the amide compound according to any one of [3] to [31], wherein is a hydrogen atom, and an inert carrier.
[35] A harmful arthropod control agent comprising the amide compound according to any one of [1] to [34], wherein Q is a group selected from group A in formula (I) and an inert carrier.
[36] A harmful arthropod control agent comprising the amide compound according to any one of [2] to [34], wherein Q is a C1-C8 chain hydrocarbon group in the formula (I) and an inert carrier.
[37] Control of harmful arthropods comprising the amide compound according to any one of [1], [2] and [4] to [29], wherein Y is a single bond in formula (I) and an inert carrier Agent.
[38] The amide compound according to any one of [3] to [34], wherein in formula (I), Q is a C1-C8 chain hydrocarbon group having one group selected from group A; A harmful arthropod control agent comprising an inert carrier.
[39] A noxious node comprising the amide compound according to any one of [3] to [34], wherein Q in the formula (I) is a methyl group having one group selected from group A and an inert carrier Foot animal control agent.
[40] The amide compound according to any one of [1], [2] and [4] to [34], wherein Q is a C3-C8 chain hydrocarbon group in the formula (I) and an inert carrier A harmful arthropod control agent.
[41] Any one of [2] to [34], wherein in formula (I), Q is a C1-C8 chain hydrocarbon group which may have one or more atoms or groups selected from group F. A harmful arthropod control agent comprising the amide compound of claim 1 and an inert carrier.
[42] Any of [1] and [4] to [34], wherein in formula (I), Q is a C1-C8 chain hydrocarbon group having one or more atoms or groups selected from group G A harmful arthropod control agent comprising the amide compound according to claim 1 and an inert carrier.
[43] [1], [2] and [4] to [4], wherein Q is a C1-C8 chain hydrocarbon group having one or more atoms or groups selected from group F in formula (I) 34] A harmful arthropod control agent comprising the amide compound according to any one of the above and an inert carrier.
[44] Any one of [1], [2] and [4] to [34], wherein Q is a C1-C8 chain hydrocarbon group having one group selected from group F in formula (I) A harmful arthropod control agent comprising the amide compound described above and an inert carrier.
[45] A noxious node comprising the amide compound according to any one of [2] to [34], wherein Q in the formula (I) is a methyl group having one group selected from group F, and an inert carrier Foot animal control agent.
[46] R in formula (I) ⁵ Any one of [26] and [30] to [45], in which is a C1-C2 alkyl group or a hydrogen atom optionally having one or more atoms or groups selected from the group consisting of a hydroxyl group and a halogen atom A harmful arthropod control agent comprising the amide compound according to Item and an inert carrier.
[47] Control of harmful arthropods, wherein an effective amount of the amide compound represented by formula (I) according to any one of [1] to [46] is applied to the harmful arthropods or the place where the harmful arthropods grow. Method.
[48] Formula (I-s)

[Where,
A is an oxygen atom and -S (O) _t -Represents a 3-7 membered saturated hetero ring containing at least one atom or group selected from the group consisting of-as a ring constituent, wherein the saturated hetero ring is 1 to 3 atoms selected from group D or May have a group,
t represents 0, 1, or 2;
R ¹ And R ² Are the same or different and each represents a C1-C4 alkyl group optionally having one or more halogen atoms, or a hydrogen atom,
n represents 0, 1, or 2;
R ⁵ Is a halogen atom, cyano group, formyl group, carboxyl group, C1-C4 alkoxycarbonyl group optionally having one or more halogen atoms, carbamoyl group, -OR ⁷ And a C1-C3 hydrocarbon group optionally having one or more atoms or groups selected from the group consisting of halogen atoms, or a hydrogen atom,
R ⁷ Is -C (= S) SR ⁸ Or a hydrogen atom, R ⁸ Represents a C1-C3 hydrocarbon group optionally having one or more halogen atoms,
R ³ And R ⁴ Are the same or different, a C1-C4 alkyl group optionally having one or more halogen atoms, a halogen atom, a phenyl group optionally having one or more atoms or groups selected from group B Or a hydrogen atom,
Y is a single bond, an oxygen atom, or -S (O) _u -Represents
When Y is a single bond, m represents 0;
Y is an oxygen atom or -S (O) _u When-, m represents 0, 1, 2, 3, 4, 5, 6 or 7;
When Y is a single bond, Q represents a C1-C8 chain hydrocarbon group having one or more atoms or groups selected from group F;
Y is an oxygen atom and m is 0, 2, 3, 4, 5, 6 or 7, or Y is -S (O) _u In the case of-, Q represents a C1-C8 chain hydrocarbon group which may have one or more atoms or groups selected from group G, or one group selected from group A;
When Y is an oxygen atom and m is 1, Q is a C1-C8 chain hydrocarbon group which may have one or more atoms or groups selected from Group G, or Group H Represents one group
u represents 0, 1, or 2.
Group A: C3-C8 cycloalkyl group optionally having one or more atoms or groups selected from Group B, Indanyl group optionally having one or more atoms or groups selected from Group B A 1,2,3,4-tetrahydronaphthyl group which may have one or more atoms or groups selected from group B, or one or more atoms or groups selected from group B. A good phenyl group, a naphthyl group optionally having one or more atoms or groups selected from group B, a pyridyl group optionally having one or more atoms or groups selected from group B, group B A quinolyl group optionally having one or more atoms or groups selected from the group, a furyl group optionally having one or more atoms or groups selected from the group B, one or more selected from group B May have any atom or group It consists of a thienyl group, a benzofuranyl group optionally having one or more atoms or groups selected from group B, and a benzothienyl group optionally having one or more atoms or groups selected from group B. group.
Group B: C1-C4 alkyl group optionally having one or more halogen atoms, C1-C4 alkyl group having one or more benzyloxy groups, having one or more halogen atoms C1-C4 alkoxy group which may have one, C1-C4 alkylthio group which may have one or more halogen atoms, C1-C4 alkylsulfinyl group which may have one or more halogen atoms, one C1-C4 alkylsulfonyl group optionally having one or more halogen atoms, C1-C4 alkoxycarbonyl group optionally having one or more halogen atoms, one or more atoms or groups selected from group E A vinyl group which may have, an ethynyl group which may have an atom or group selected from group E, a phenyl group, a phenoxy group, a cyano group, a nitro group, a carboxyl group A hydroxyl group, -CONR ¹² R ¹³ A group consisting of a group, a methoxymethyl group and a halogen atom.
R ¹² And R ¹³ Are the same or different and each represents a C1-C4 alkyl group optionally having one or more halogen atoms, or a hydrogen atom.
Group D: a group consisting of a C1-C4 alkyl group optionally having one or more halogen atoms, a C1-C4 alkoxy group optionally having one or more halogen atoms, and a halogen atom.
Group E: A group consisting of a C1-C4 alkyl group optionally having one or more halogen atoms and a halogen atom.
Group F: a C3-C8 cycloalkyl group optionally having one or more atoms or groups selected from Group B, an indanyl group optionally having one or more atoms or groups selected from Group B A 1,2,3,4-tetrahydronaphthyl group which may have one or more atoms or groups selected from group B, or one or more atoms or groups selected from group B. A good phenyl group, a naphthyl group optionally having one or more atoms or groups selected from group B, a pyridyl group optionally having one or more atoms or groups selected from group B, group B A quinolyl group optionally having one or more atoms or groups selected from the group, a furyl group optionally having one or more atoms or groups selected from the group B, one or more selected from group B May have any atom or group A thienyl group, a benzofuranyl group optionally having one or more atoms or groups selected from group B, a benzothienyl group optionally having one or more atoms or groups selected from group B, group B 1,3-benzodioxolyl group optionally having one or more atoms or groups selected from 1,4, optionally having one or more atoms or groups selected from group B Benzodioxanyl group, halogen atom, C1-C4 alkoxycarbonyl group optionally having one or more halogen atoms, cyano group, nitro group, carboxyl group, hydroxyl group, and -CONR ¹² R ¹³ A group of groups.
Group G: a C3-C8 cycloalkyl group optionally having one or more atoms or groups selected from Group B, an indanyl group optionally having one or more atoms or groups selected from Group B A 1,2,3,4-tetrahydronaphthyl group which may have one or more atoms or groups selected from group B, or one or more atoms or groups selected from group B. A good phenyl group, a phenoxy group optionally having one or more atoms or groups selected from group B, a naphthyl group optionally having one or more atoms or groups selected from group B, group B A pyridyl group optionally having one or more atoms or groups selected from the group, a quinolyl group optionally having one or more atoms or groups selected from the group B, one or more selected from group B Having an atom or group of A good furyl group, a thienyl group optionally having one or more atoms or groups selected from group B, a benzofuranyl group optionally having one or more atoms or groups selected from group B, group B A benzothienyl group optionally having one or more atoms or groups selected from 1, a 1,3-benzodioxolyl group optionally having one or more atoms or groups selected from group B; 1,4-benzodioxanyl group optionally having one or more atoms or groups selected from group B, halogen atom, C1-C4 alkoxycarbonyl optionally having one or more halogen atoms Group, cyano group, nitro group, carboxyl group, hydroxyl group, and -CONR ¹² R ¹³ A group of groups.
Group H: a C3-C8 cycloalkyl group optionally having one or more atoms or groups selected from Group B, an indanyl group optionally having one or more atoms or groups selected from Group B A furyl group optionally having one or more atoms or groups selected from group B; a thienyl group optionally having one or more atoms or groups selected from group B; A benzofuranyl group optionally having one or more atoms or groups, a benzothienyl group optionally having one or more atoms or groups selected from group B, and one or more selected from group B A group consisting of 1,3-benzodioxolyl group which may have an atom or a group. ] The amide compound shown by this.
[49] An amide compound represented by the formula (Is), wherein R ⁵ Is a halogen atom, a cyano group, a methyl group or a hydrogen atom,
R ³ And R ⁴ Are the same or different, a C1-C4 alkyl group which may have one or more halogen atoms, a halogen atom, or a hydrogen atom,
Group B has a C1-C4 alkyl group which may have one or more halogen atoms, a C1-C4 alkoxy group which may have one or more halogen atoms, and one or more halogen atoms A C1-C4 alkylthio group optionally having one or more halogen atoms, a C1-C4 alkylsulfinyl group optionally having one or more halogen atoms, a C1-C4 alkylsulfonyl group optionally having one or more halogen atoms, A C1-C4 alkoxycarbonyl group optionally having one or more halogen atoms, a vinyl group optionally having one or more atoms or groups selected from group E, an atom or group selected from group E Ethynyl group, cyano group, nitro group, carboxyl group, hydroxyl group, -CONR ¹² R ¹³ A group consisting of a group, a methoxymethyl group and a halogen atom,
Y is an oxygen atom or -S (O) _u When-, m is 0, 1, 2, 3, or 4, Y is an oxygen atom, or -S (O) _u When it is-, the amide compound according to [48], wherein Q is a C1-C8 chain hydrocarbon group which may have one or more atoms or groups selected from group F.
[50] An amide compound represented by the formula (Is), wherein A represents the following formula (III-a) or (III-b)

[Where A ¹ Represents an oxygen atom or a sulfur atom, and D ¹ Represents an atom or group selected from the group D, r represents 0 or 1, p represents 0, 1, or 2, and q represents 0 or 1. ]
The amide compound according to [48] or [49], which is a group represented by:
[51] An amide compound represented by the formula (Is), wherein A represents the following formula (III-d)

[Where D ¹ Represents an atom or group selected from group D, and r represents 0 or 1. The amide compound according to [48] or [49], which is a group represented by the formula:
[52] An amide compound represented by the formula (Is), wherein A represents the following formula (III-c)

[Wherein, p represents 0, 1, or 2. ]
The amide compound according to [48] or [49], which is a group represented by:
[53] The amide compound according to any one of [48] to [52], which is an amide compound represented by the formula (I-s), wherein n is 1.
[54] The amide compound according to any one of [48] to [53], which is an amide compound represented by the formula (I-s), wherein m is 1.
[55] The amide compound according to any one of [48] to [54], which is an amide compound represented by the formula (I-s), wherein Y is an oxygen atom.
[56] The amide compound according to any one of [48] to [54], which is an amide compound represented by the formula (I-s), wherein Y is a single bond.
[57] The amide compound according to any one of [48] to [56], which is an amide compound represented by the formula (I-s), wherein Q is a group selected from group A.
[58] The amide compound according to any one of [48] to [55], which is an amide compound represented by the formula (I-s), wherein Q is one group selected from Group H.
[59] An amide compound represented by the formula (I-s), wherein Q is a C1-C8 chain hydrocarbon group which may have one or more atoms or groups selected from group G [48] ] The amide compound as described in any one of [55].
[60] An amide compound represented by the formula (Is), wherein Q is a C1-C8 chain hydrocarbon group having one or more atoms or groups selected from group F [48] to [48] [54] The amide compound according to any one of [56].
[61] Any of [48] to [56], which is an amide compound represented by the formula (Is), wherein Q is a C1-C8 chain hydrocarbon group having one group selected from group F The amide compound according to one item.
[62] The amide compound represented by the formula (Is), wherein Q is a methyl group having one group selected from group F [48] to [56] .
[63] An amide compound represented by the formula (Is), wherein R ⁵ The amide according to any one of [48] to [62], wherein is a C1-C2 alkyl group or a hydrogen atom which may have one or more atoms or groups selected from the group consisting of a hydroxyl group and a halogen atom Compound.
[64] An amide compound represented by the formula (Is),
A is represented by the following formula (III-a), (III-b) or (III-d)

[Where A ¹ Represents an oxygen atom or a sulfur atom, and D ¹ Represents a C1-C4 alkyl group which may have one or more halogen atoms, r represents 0 or 1, p represents 0, 1, or 2, and q represents 0 or 1. Is a group represented by
R ¹ And R ² Is a hydrogen atom,
n is 0, 1, or 2;
R ⁵ Is a C1-C2 alkyl group optionally having one or more atoms or groups selected from the group consisting of a hydrogen atom, a halogen atom, a formyl group, or a hydroxyl group and a halogen atom,
R ³ And R ⁴ Are the same or different, a C1-C4 alkyl group which may have one or more halogen atoms, or a hydrogen atom,
Group B has a C1-C4 alkyl group optionally having one or more halogen atoms, a C1-C4 alkyl group having one or more benzyloxy groups, and one or more halogen atoms A C1-C4 alkoxy group which may have one, a C1-C4 alkylthio group which may have one or more halogen atoms, a phenyl group, a phenoxy group, a cyano group and a halogen atom,
Group F, a phenyl group optionally having one or more atoms or groups selected from Group B, a naphthyl group optionally having one or more atoms or groups selected from Group B, Group B A quinolyl group optionally having one or more atoms or groups selected from the group, a benzothienyl group optionally having one or more atoms or groups selected from the group B, and one selected from group B A group consisting of a 1,3-benzodioxolyl group optionally having the above atoms or groups, a halogen atom,
Group G may have one or more atoms or groups selected from group B and may have one or more atoms or groups selected from group B. , 2,3,4-tetrahydronaphthyl group, a phenyl group optionally having one or more atoms or groups selected from group B, and one or more atoms or groups selected from group B A phenoxy group, a naphthyl group optionally having one or more atoms or groups selected from group B, a quinolyl group optionally having one or more atoms or groups selected from group B, a group A furyl group optionally having one or more atoms or groups selected from B, a thienyl group optionally having one or more atoms or groups selected from Group B, one selected from Group B Even if it has more atoms or groups A benzofuranyl group, a benzothienyl group optionally having one or more atoms or groups selected from group B, and a one or more atoms or groups selected from group B A group consisting of a benzodioxolyl group, a 1,4-benzodioxanyl group optionally having one or more atoms or groups selected from group B;
Group H may have a C3-C8 cycloalkyl group optionally having one or more atoms or groups selected from Group B, and one or more atoms or groups selected from Group B. A group consisting of 1,3-benzodioxolyl groups,
Y is a single bond, an oxygen atom, or a sulfur atom;
When Y is a single bond, m is 0;
When Y is an oxygen atom or a sulfur atom, m is 1, 2, 3, 4, 5, 6 or 7,
When Y is a single bond, Q is a C1-C8 chain hydrocarbon group having one or more atoms or groups selected from group F;
When Y is an oxygen atom and m is 2, 3, 4, 5, 6 or 7, or when Y is a sulfur atom, Q has one or more groups selected from group G A C1-C8 chain hydrocarbon group,
When Y is an oxygen atom and m is 1, C is a C1-C8 chain hydrocarbon group which may have one or more groups selected from group G, or 1 selected from group H. The amide compound according to [48], which is a group.
[65] In the formula (I-s)
A is represented by the following formula (III-a), (III-b) or (III-d)

[Where A ¹ Represents an oxygen atom or a sulfur atom, and D ¹ Represents a C1-C4 alkyl group which may have one or more halogen atoms, r represents 0 or 1, p represents 0, 1, or 2, and q represents 0 or 1. Is a group represented by
R ¹ And R ² Is a hydrogen atom,
n is 0, 1, or 2;
R ⁵ Is a C1-C2 alkyl group optionally having one or more atoms or groups selected from the group consisting of a hydrogen atom, a halogen atom, a formyl group, or a hydroxyl group and a halogen atom,
R ³ And R ⁴ Are the same or different, a C1-C4 alkyl group which may have one or more halogen atoms, or a hydrogen atom,
Group A may have one or more atoms or groups selected from Group B and may have one or more atoms or groups selected from Group B. , 2,3,4-tetrahydronaphthyl group, a phenyl group optionally having one or more atoms or groups selected from group B, and one or more atoms or groups selected from group B A quinolyl group, and a 1,3-benzodioxolyl group optionally having one or more atoms or groups selected from group B;
Group B has a C1-C4 alkyl group optionally having one or more halogen atoms, a C1-C4 alkyl group having one or more benzyloxy groups, and one or more halogen atoms A C1-C4 alkoxy group which may have one, a C1-C4 alkylthio group which may have one or more halogen atoms, a phenyl group, a phenoxy group, a cyano group and a halogen atom,
Group F, a phenyl group optionally having one or more atoms or groups selected from Group B, a naphthyl group optionally having one or more atoms or groups selected from Group B, Group B A quinolyl group optionally having one or more atoms or groups selected from the group, a benzothienyl group optionally having one or more atoms or groups selected from the group B, and one selected from group B A group consisting of a 1,3-benzodioxolyl group optionally having the above atoms or groups, a halogen atom,
Group G may have one or more atoms or groups selected from group B and may have one or more atoms or groups selected from group B. , 2,3,4-tetrahydronaphthyl group, a phenyl group optionally having one or more atoms or groups selected from group B, and one or more atoms or groups selected from group B A phenoxy group, a naphthyl group optionally having one or more atoms or groups selected from group B, a quinolyl group optionally having one or more atoms or groups selected from group B, a group A furyl group optionally having one or more atoms or groups selected from B, a thienyl group optionally having one or more atoms or groups selected from Group B, one selected from Group B Even if it has more atoms or groups A benzofuranyl group, a benzothienyl group optionally having one or more atoms or groups selected from group B, and a one or more atoms or groups selected from group B A group consisting of a benzodioxolyl group, a 1,4-benzodioxanyl group optionally having one or more atoms or groups selected from group B;
Y is a single bond, an oxygen atom, or a sulfur atom;
When Y is a single bond, m is 0;
Y is an oxygen atom or -S (O) _u -Is m is 0, 1, 2, 3, 4, 5, 6 or 7,
When Y is a single bond, Q is a C1-C8 chain hydrocarbon group having one or more atoms or groups selected from group F, or a C3-C8 chain hydrocarbon group,
When Y is an oxygen atom or a sulfur atom, Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G, or 1 selected from group A A harmful arthropod control agent comprising the amide compound according to [26], which is a group, and an inert carrier.
[66] A method for controlling harmful arthropods, which comprises applying an effective amount of the amide compound represented by the formula (Is) according to [65] to harmful arthropods or a place where the harmful arthropods grow.

  Since the compound of the present invention has an excellent control effect against harmful arthropods, it is useful as an active ingredient of a harmful arthropod control agent.

  The compound of the present invention may have an isomer derived from an asymmetric carbon atom and an isomer derived from a double bond. A ratio of isomer mixtures is included.

In the present invention, “a 3-7-membered saturated heterocyclic ring containing at least one atom or group selected from the group consisting of an oxygen atom and —S (O) _t — as a ring component (wherein the saturated heterocyclic ring May have 1 to 3 atoms or groups selected from group D.) "
Oxetane-2-yl group, oxetane-3-yl group,
Tetrahydrofuran-2-yl group, tetrahydrofuran-3-yl group, 1,3-dioxolan-2-yl group, 1,3-dioxolan-4-yl group,
Tetrahydropyran-2-yl group, tetrahydropyran-3-yl group, tetrahydropyran-4-yl group,
1,3-dioxane-4-yl group, 1,3-dioxane-5-yl group, 1,4-dioxane-2-yl group,
Oxepan-2-yl group, oxepan-3-yl group, oxepan-4-yl group, 1,3-dioxepan-4-yl group, 1,3-dioxepan-5-yl group, 1,4-dioxepan-2 1 to 3 atoms or groups selected from group D, such as -yl group, 1,4-dioxepan-5-yl group and 1,4-dioxepan-6-yl group, A 3-7 membered saturated heterocycle containing one or more oxygen atoms as ring constituents;
Thietan-2-yl group, thietan-3-yl group,
Tetrahydrothiophen-2-yl group, tetrahydrothiophen-3-yl group, 1,3-dithiolan-4-yl group,
Tetrahydrothiopyran-2-yl group, tetrahydrothiopyran-3-yl group, tetrahydrothiopyran-4-yl group,
1,3-dithian-4-yl group, 1,3-dithian-5-yl group, 1,4-dithian-2-yl group,
Thiepan-2-yl group, thiepan-3-yl group, thiepan-4-yl group, 1,3-dithiepan-4-yl group, 1,3-dithiepan-5-yl group, 1,4-dithiepan-2 1 to 3 atoms or groups selected from group D, such as -yl group, 1,4-dithiepan-5-yl group and 1,4-dithiepan-6-yl group, A 3-7 membered saturated heterocycle containing one or more sulfur atoms as ring constituents;
1-oxo-thietan-2-yl group, 1-oxo-thietan-3-yl group,
1-oxo-tetrahydrothiophen-2-yl group, 1-oxo-tetrahydrothiophen-3-yl group,
1-oxo-tetrahydrothiopyran-2-yl group, 1-oxo-tetrahydrothiopyran-3-yl group, 1-oxo-tetrahydrothiopyran-4-yl group,
Having 1 to 3 atoms or groups selected from group D such as 1-oxo-thiepan-2-yl group, 1-oxo-thiepan-3-yl group, 1-oxo-thiepan-4-yl group, etc. A 3-7 membered saturated heterocycle containing one or more —SO— as a ring component, which may be
1,1-dioxo-thietan-2-yl group, 1,1-dioxo-thietan-3-yl group,
1,1-dioxo-tetrahydrothiophen-2-yl group, 1,1-dioxo-tetrahydrothiophen-3-yl group,
1,1-dioxo-tetrahydrothiopyran-2-yl group, 1,1-dioxo-tetrahydrothiopyran-3-yl group, 1,1-dioxo-tetrahydrothiopyran-4-yl group, 1,1-dioxo 1 to 3 atoms or groups selected from group D, such as -thiepan-2-yl group, 1,1-dioxo-thiepan-3-yl group, 1,1-dioxo-thiepan-4-yl group; A 3-7 membered saturated heterocycle containing one or more —SO ₂ — as a ring constituent, which may be present;
1,3-oxathietan-2-yl group,
1,3-oxathiolan-2-yl group, 1,3-oxathiolan-4-yl group, 1,3-oxathiolan-5-yl group,
1,3-oxathian-2-yl group, 1,3-oxathiolan-4-yl group, 1,3-oxathiolan-5-yl group,
One or more oxygens optionally having 1 to 3 atoms or groups selected from group D, such as a 1,4-oxathian-2-yl group, a 1,4-oxathian-3-yl group, etc. 3-7 membered saturated heterocycle containing an atom and one or more -S (O) _t- as a ring component.

In the present invention, examples of the “halogen atom” include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.

In the present invention, examples of the “C1-C4 alkyl group optionally having one or more halogen atoms” include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, and a sec-butyl group. Tert-butyl group, iodomethyl group, bromomethyl group, chloromethyl group, fluoromethyl group, difluoromethyl group, chlorodifluoromethyl group, bromodifluoromethyl group, dichlorofluoromethyl group, trichloromethyl group, trifluoromethyl group, 2, Examples include 2,2-trifluoroethyl group, 1,1,2,2-tetrafluoroethyl group, and 1,1,2,2,2-pentafluoroethyl group.

における○は、環構造が芳香族性を有することを意味する。
下式（ＩＩ）で示される５員芳香環としては、例えば、イミダゾール、オキサゾール、チアゾール、ピラゾール、イソキサゾール、イソチアゾール、１，２，３−トリアゾール、１，２，４−トリアゾール、１，２，４−オキサジアゾール、１，３，４−オキサジアゾール、１，２，４−チアジアゾール、１，３，４−チアジアゾール、１，２，４−トリアゾール、１，３，４−トリアゾール、テトラゾールが挙げられる。該５員芳香環を有する本発明化合物として、例えば以下の式（Ｉ−ｓ）、（Ｉ−ｔ）、（Ｉ−ｖ）および(Ｉ−１)〜（Ｉ〜３１）で示される化合物が挙げられる（式中、Ｙ、A、Ｑ、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ｒ^５、Ｒ^６、ｍ及びｎは［１］と同じ意味を表す。）。 In the present invention,
Formula (II)

○ in means that the ring structure has aromaticity.
Examples of the 5-membered aromatic ring represented by the following formula (II) include imidazole, oxazole, thiazole, pyrazole, isoxazole, isothiazole, 1,2,3-triazole, 1,2,4-triazole, 1,2, 4-oxadiazole, 1,3,4-oxadiazole, 1,2,4-thiadiazole, 1,3,4-thiadiazole, 1,2,4-triazole, 1,3,4-triazole, tetrazole Can be mentioned. Examples of the compound of the present invention having the 5-membered aromatic ring include compounds represented by the following formulas (Is), (It), (Iv) and (I-1) to (I-31). (Wherein, Y, A, Q, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , m and n have the same meaning as [1]).

In the present invention, the “methyl group optionally having a halogen atom” includes, for example,
Examples thereof include a methyl group, iodomethyl group, bromomethyl group, chloromethyl group, fluoromethyl group, difluoromethyl group, chlorodifluoromethyl group, bromodifluoromethyl group, dichlorofluoromethyl group, trichloromethyl group, and trifluoromethyl group.

In the present invention, examples of the “C1-C3 hydrocarbon group optionally having one or more atoms or groups selected from the group consisting of —OR ⁷ and a halogen atom” include a methyl group, an ethyl group, and a propyl group. , Isopropyl group, iodomethyl group, bromomethyl group, chloromethyl group, fluoromethyl group, difluoromethyl group, chlorodifluoromethyl group, bromodifluoromethyl group, dichlorofluoromethyl group, trichloromethyl group, trifluoromethyl group, 1-fluoroethyl Group, 2-fluoroethyl group, 1-fluoropropyl group, 2-fluoropropyl group, 3-fluoropropyl group, 1-fluoro-1-methylethyl group, 1-chloroethyl group, 2-chloroethyl group, 1-chloropropyl Group, 2-chloropropyl group, 3-chloropropyl group, 1-chloro- 1-methylethyl group, 1-bromoethyl group, 2-bromoethyl group, 1-bromopropyl group, 2-bromopropyl group, 3-bromopropyl group, 1-bromo-1-methylethyl group, 2,2,2- Trifluoroethyl group, 1,1,2,2-tetrafluoroethyl group, 1,1,2,2,2-pentafluoroethyl group, hydroxymethyl group, 1-hydroxyethyl group, 2-hydroxyethyl group, 1 -Hydroxypropyl group, 2-hydroxypropyl group, 3-hydroxypropyl group, 1-hydroxy-1-methylethyl group, 1- (S-methyldithiocarbonyloxy) methyl group, 1- (S-methyldithiocarbonyloxy) Ethyl, 2- (S-methyldithiocarbonyloxy) ethyl, 1- (S-methyldithiocarbonyloxy) propyl, 2- (S-methyldithio) Ocarbonyloxy) propyl group, 3- (S-methyldithiocarbonyloxy) propyl group, 1- (S-methyldithiocarbonyloxy) -1-methylethyl group, 1- (S-ethyldithiocarbonyloxy) methyl group, 1- (S-ethyldithiocarbonyloxy) ethyl group, 2- (S-ethyldithiocarbonyloxy) ethyl group, 1- (S-ethyldithiocarbonyloxy) propyl group, 2- (S-ethyldithiocarbonyloxy) propyl Group, 3- (S-ethyldithiocarbonyloxy) propyl group, 1- (S-ethyldithiocarbonyloxy) -1-methylethyl group, 1- (S-propyldithiocarbonyloxy) methyl group, 1- (S- Propyldithiocarbonyloxy) ethyl group, 2- (S-propyldithiocarbonyloxy) ethyl group, 1- (S-propyldithiocarbo) Ruoxy) propyl group, 2- (S-propyldithiocarbonyloxy) propyl group, 3- (S-propyldithiocarbonyloxy) propyl group, 1- (S-propyldithiocarbonyloxy) -1-methylethyl group, 1- (S-isopropyldithiocarbonyloxy) methyl group, 1- (S-isopropyldithiocarbonyloxy) ethyl group, 2- (S-isopropyldithiocarbonyloxy) ethyl group, 1- (S-isopropyldithiocarbonyloxy) propyl group, 2- (S-isopropyldithiocarbonyloxy) propyl group, 3- (S-isopropyldithiocarbonyloxy) propyl group, 1- (S-isopropyldithiocarbonyloxy) -1-methylethyl group,
Is mentioned.

In the present invention, examples of the “C1-C3 hydrocarbon group optionally having one or more halogen atoms” include a methyl group, an ethyl group, a propyl group, an isopropyl group, an iodomethyl group, a bromomethyl group, and a chloromethyl group. , Fluoromethyl group, difluoromethyl group, chlorodifluoromethyl group, bromodifluoromethyl group, dichlorofluoromethyl group, trichloromethyl group, trifluoromethyl group, 1-fluoroethyl group, 2-fluoroethyl group, 1-fluoropropyl group 2-fluoropropyl group, 3-fluoropropyl group, 1-fluoro-1-methylethyl group, 1-chloroethyl group, 2-chloroethyl group, 1-chloropropyl group, 2-chloropropyl group, 3-chloropropyl group 1-chloro-1-methylethyl group, 1-bromoethyl group, 2-bromine Ethyl group, 1-bromopropyl group, 2-bromopropyl group, 3-bromopropyl group, 1-bromo-1-methylethyl group, 2,2,2-trifluoroethyl group, 1,1,2,2- Examples include a tetrafluoroethyl group and a 1,1,2,2,2-pentafluoroethyl group.

In the present invention, examples of the “C3-C8 cycloalkyl group optionally having one or more atoms or groups selected from group B” include cyclopropyl group, 1-methylcyclopropyl group, 2,2 -Dichlorocyclopropyl group, 2,2-difluorocyclopropyl group, cyclopentyl group, 1-methylcyclopentyl group, 2-methylcyclopentyl group, 3-methylcyclopentyl group, 2-chlorocyclopentyl group, 3-chlorocyclopentyl group, 2- Fluorocyclopentyl group, 3-fluorocyclopentyl group, 2,2-difluorocyclopentyl group, 3,3-difluorocyclopentyl group, 2-cyanocyclopentyl group, 3-cyanocyclopentyl group, cyclohexyl group, 1-methylcyclohexyl group, 2-methyl Cyclohexyl group, 3-methyl Cyclohexyl group, 4-methylcyclohexyl group, 2-chlorocyclohexyl group, 3-chlorocyclohexyl group, 4-chlorocyclohexyl group, 4,4-dichlorocyclohexyl group, 4,4-difluorocyclohexyl group, 4-cyanocyclohexyl group, cyclo Heptyl group, cyclooctyl group,
Is mentioned.

In the present invention, the “indanyl group optionally having one or more atoms or groups selected from group B” includes, for example,
1-indanyl group,
4-methyl-1-indanyl group, 5-methyl-1-indanyl group,
4-cyano-1-indanyl group, 5-cyano-1-indanyl group,
4-carboxyl-1-indanyl group, 5-carboxyl-1-indanyl group,
4-hydroxyl-1-indanyl group, 5-hydroxyl-1-indanyl group,
4-trifluoromethyl-1-indanyl group, 5-trifluoromethyl-1-indanyl group,
4-trifluoromethoxy-1-indanyl group, 5-trifluoromethoxy-1-indanyl group,
4-trifluoromethylthio-1-indanyl group, 5-trifluoromethylthio-1-indanyl group,
4-trifluoromethanesulfinyl-1-indanyl group, 5-trifluoromethanesulfinyl-1-indanyl group,
4-trifluoromethanesulfonyl-1-indanyl group, 5-trifluoromethanesulfonyl-1-indanyl group,
4-fluoro-1-indanyl group, 5-fluoro-1-indanyl group,
4-chloro-1-indanyl group, 5-chloro-1-indanyl group,
4-bromo-1-indanyl group, 5-bromo-1-indanyl group,
"1-indanyl group optionally having one or more atoms or groups selected from group B";
2-indanyl group,
4-methyl-2-indanyl group, 5-methyl-2-indanyl group, 6-methyl-2-indanyl group, 7-methyl-2-indanyl group,
4-cyano-2-indanyl group, 5-cyano-2-indanyl group, 6-cyano-2-indanyl group, 7-cyano-2-indanyl group,
4-carboxyl-2-indanyl group, 5-carboxyl-2-indanyl group, 6-carboxyl-2-indanyl group, 7-carboxyl-2-indanyl group,
4-hydroxyl-2-indanyl group, 5-hydroxyl-2-indanyl group, 6-hydroxyl-2-indanyl group, 7-hydroxyl-2-indanyl group,
4-trifluoromethyl-2-indanyl group, 5-trifluoromethyl-2-indanyl group, 6-trifluoromethyl-2-indanyl group, 7-trifluoromethyl-2-indanyl group,
4-trifluoromethoxy-2-indanyl group, 5-trifluoromethoxy-2-indanyl group, 6-trifluoromethoxy-2-indanyl group, 7-trifluoromethoxy-2-indanyl group,
4-trifluoromethylthio-2-indanyl group, 5-trifluoromethylthio-2-indanyl group, 6-trifluoromethylthio-2-indanyl group, 7-trifluoromethylthio-2-indanyl group,
4-trifluoromethanesulfinyl-2-indanyl group, 5-trifluoromethanesulfinyl-2-indanyl group, 6-trifluoromethanesulfinyl-2-indanyl group, 7-trifluoromethanesulfinyl-2-indanyl group,
4-trifluoromethanesulfonyl-2-indanyl group, 5-trifluoromethanesulfonyl-2-indanyl group, 6-trifluoromethanesulfonyl-2-indanyl group, 7-trifluoromethanesulfonyl-2-indanyl group,
4-fluoro-2-indanyl group, 5-fluoro-2-indanyl group, 6-fluoro-2-indanyl group, 7-fluoro-2-indanyl group,
4-chloro-2-indanyl group, 5-chloro-2-indanyl group, 6-chloro-2-indanyl group, 7-chloro-2-indanyl group,
4-bromo-2-indanyl group, 5-bromo-2-indanyl group, 6-bromo-2-indanyl group, 7-bromo-2-indanyl group,
"2-indanyl group optionally having one or more atoms or groups selected from group B";
Is mentioned.

In the present invention, the “1,2,3,4-tetrahydronaphthyl group optionally having one or more atoms or groups selected from group B” includes, for example,
1- (1,2,3,4-tetrahydronaphthyl) group, 1- (5-methyl-1,2,3,4-tetrahydronaphthyl) group, 1- (6-methyl-1,2,3,4) -Tetrahydronaphthyl) group, 1- (7-methyl-1,2,3,4-tetrahydronaphthyl) group, 1- (8-methyl-1,2,3,4-tetrahydronaphthyl) group,
1- (5-cyano-1,2,3,4-tetrahydronaphthyl) group, 1- (6-cyano-1,2,3,4-tetrahydronaphthyl) group, 1- (7-cyano-1,2 , 3,4-tetrahydronaphthyl) group, 1- (8-cyano-1,2,3,4-tetrahydronaphthyl) group,
1- (5-carboxyl-1,2,3,4-tetrahydronaphthyl) group, 1- (6-carboxyl-1,2,3,4-tetrahydronaphthyl) group, 1- (7-carboxyl-1,2) , 3,4-tetrahydronaphthyl) group, 1- (8-carboxyl-1,2,3,4-tetrahydronaphthyl) group,
1- (5-hydroxyl-1,2,3,4-tetrahydronaphthyl) group, 1- (6-hydroxyl-1,2,3,4-tetrahydronaphthyl) group, 1- (7-hydroxyl-1,2 , 3,4-tetrahydronaphthyl) group, 1- (8-hydroxyl-1,2,3,4-tetrahydronaphthyl) group,
1- (5-trifluoromethyl-1,2,3,4-tetrahydronaphthyl) group, 1- (6-trifluoromethyl-1,2,3,4-tetrahydronaphthyl) group, 1- (7-trimethyl) Fluoromethyl-1,2,3,4-tetrahydronaphthyl) group, 1- (8-trifluoromethyl-1,2,3,4-tetrahydronaphthyl) group,
1- (5-trifluoromethylthio-1,2,3,4-tetrahydronaphthyl) group, 1- (6-trifluoromethylthio-1,2,3,4-tetrahydronaphthyl) group, 1- (7-trimethyl) Fluoromethylthio-1,2,3,4-tetrahydronaphthyl) group, 1- (8-trifluoromethylthio-1,2,3,4-tetrahydronaphthyl) group,
1- (5-trifluoromethoxy-1,2,3,4-tetrahydronaphthyl) group, 1- (6-trifluoromethoxy-1,2,3,4-tetrahydronaphthyl) group, 1- (7-trimethyl) Fluoromethoxy-1,2,3,4-tetrahydronaphthyl) group, 1- (8-trifluoromethoxy-1,2,3,4-tetrahydronaphthyl) group,
1- (5-trifluoromethanesulfinyl-1,2,3,4-tetrahydronaphthyl) group, 1- (6-trifluoromethanesulfinyl-1,2,3,4-tetrahydronaphthyl) group, 1- (7-trifluoro) Lomethanesulfinyl-1,2,3,4-tetrahydronaphthyl) group, 1- (8-trifluoromethanesulfinyl-1,2,3,4-tetrahydronaphthyl) group,
1- (5-trifluoromethanesulfonyl-1,2,3,4-tetrahydronaphthyl) group, 1- (6-trifluoromethanesulfonyl-1,2,3,4-tetrahydronaphthyl) group, 1- (7-trifluoro) Lomethanesulfonyl-1,2,3,4-tetrahydronaphthyl) group, 1- (8-trifluoromethanesulfonyl-1,2,3,4-tetrahydronaphthyl) group,
"1- (1,2,3,4-tetrahydronaphthyl) group optionally having one or more atoms or groups selected from group B";
2- (1,2,3,4-tetrahydronaphthyl) group, 2- (5-methyl-1,2,3,4-tetrahydronaphthyl) group, 2- (6-methyl-1,2,3,4) -Tetrahydronaphthyl) group, 2- (7-methyl-1,2,3,4-tetrahydronaphthyl) group, 2- (8-methyl-1,2,3,4-tetrahydronaphthyl) group,
2- (5-cyano-1,2,3,4-tetrahydronaphthyl) group, 2- (6-cyano-1,2,3,4-tetrahydronaphthyl) group, 2- (7-cyano-1,2 , 3,4-tetrahydronaphthyl) group, 2- (8-cyano-1,2,3,4-tetrahydronaphthyl) group,
2- (5-carboxyl-1,2,3,4-tetrahydronaphthyl) group, 2- (6-carboxyl-1,2,3,4-tetrahydronaphthyl) group, 2- (7-carboxyl-1,2) , 3,4-tetrahydronaphthyl) group, 2- (8-carboxyl-1,2,3,4-tetrahydronaphthyl) group,
2- (5-hydroxyl-1,2,3,4-tetrahydronaphthyl) group, 2- (6-hydroxyl-1,2,3,4-tetrahydronaphthyl) group, 2- (7-hydroxyl-1,2) , 3,4-tetrahydronaphthyl) group, 2- (8-hydroxyl-1,2,3,4-tetrahydronaphthyl) group,
2- (5-trifluoromethyl-1,2,3,4-tetrahydronaphthyl) group, 2- (6-trifluoromethyl-1,2,3,4-tetrahydronaphthyl) group, 2- (7-trimethyl) Fluoromethyl-1,2,3,4-tetrahydronaphthyl) group, 2- (8-trifluoromethyl-1,2,3,4-tetrahydronaphthyl) group,
2- (5-trifluoromethylthio-1,2,3,4-tetrahydronaphthyl) group, 2- (6-trifluoromethylthio-1,2,3,4-tetrahydronaphthyl) group, 2- (7-trimethyl) Fluoromethylthio-1,2,3,4-tetrahydronaphthyl) group, 2- (8-trifluoromethylthio-1,2,3,4-tetrahydronaphthyl) group,
2- (5-trifluoromethoxy-1,2,3,4-tetrahydronaphthyl) group, 2- (6-trifluoromethoxy-1,2,3,4-tetrahydronaphthyl) group, 2- (7-trimethyl) Fluoromethoxy-1,2,3,4-tetrahydronaphthyl) group, 2- (8-trifluoromethoxy-1,2,3,4-tetrahydronaphthyl) group,
2- (5-trifluoromethanesulfinyl-1,2,3,4-tetrahydronaphthyl) group, 2- (6-trifluoromethanesulfinyl-1,2,3,4-tetrahydronaphthyl) group, 2- (7-trifluoro) Lomethanesulfinyl-1,2,3,4-tetrahydronaphthyl) group, 2- (8-trifluoromethanesulfinyl-1,2,3,4-tetrahydronaphthyl) group,
2- (5-trifluoromethanesulfonyl-1,2,3,4-tetrahydronaphthyl) group, 2- (6-trifluoromethanesulfonyl-1,2,3,4-tetrahydronaphthyl) group, 2- (7-trifluoro) Lomethanesulfonyl-1,2,3,4-tetrahydronaphthyl) group, 2- (8-trifluoromethanesulfonyl-1,2,3,4-tetrahydronaphthyl) group,
"2- (1,2,3,4-tetrahydronaphthyl) group optionally having one or more atoms or groups selected from group B";
Is mentioned.

In the present invention, examples of the “phenyl group optionally having one or more atoms or groups selected from group B” include a phenyl group, a 2-cyanophenyl group, a 3-cyanophenyl group, and 4-cyano. Phenyl group, 2-nitrophenyl group, 3-nitrophenyl group, 4-nitrophenyl group, 2-carboxylphenyl group, 3-carboxylphenyl group, 4-carboxylphenyl group, 2-hydroxylphenyl group, 3-hydroxylphenyl group 4-hydroxyphenyl group, 2- (N-methylcarboamido) phenyl group, 3- (N-methylcarboamido) phenyl group, 4- (N-methylcarboamido) phenyl group, 2- (N, N- Dimethylcarboamido) phenyl group, 3- (N, N-dimethylcarboamido) phenyl group, 4- (N, N-dimethylcarbohydrate) Amido) phenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 3,4-dimethylphenyl group, 2-ethylphenyl group, 3-ethylphenyl group, 4-ethylphenyl group, 2 -Trifluoromethylphenyl group, 3-trifluoromethylphenyl group, 4-trifluoromethylphenyl group, 3,4-ditrifluoromethylphenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group 2-trifluoromethoxyphenyl group, 3-trifluoromethoxyphenyl group, 4-trifluoromethoxyphenyl group, 2-methylthiophenyl group, 3-methylthiophenyl group, 4-methylthiophenyl group, 2-methylsulfinylphenyl group, 3-methylsulfinylphenyl group, 4-methylsulfur Nylphenyl group, 2-methylsulfonylphenyl group, 3-methylsulfonylphenyl group, 4-methylsulfonylphenyl group, 2-trifluoromethylthiophenyl group, 3-trifluoromethylthiophenyl group, 4-trifluoromethylthiophenyl group, 2- Trifluoromethylsulfinylphenyl group, 3-trifluoromethylsulfinylphenyl group, 4-trifluoromethylsulfinylphenyl group, 2-trifluoromethylsulfonylphenyl group, 3-trifluoromethylsulfonylphenyl group, 4-trifluoromethylsulfonylphenyl Group, 2-methoxycarbonylphenyl group, 3-methoxycarbonylphenyl group, 4-methoxycarbonylphenyl group, 2-vinylphenyl group, 3-vinylphenyl group, 4-vinylphenyl group, 2 -(2 ', 2'-difluorovinyl) phenyl group, 3- (2', 2'-difluorovinyl) phenyl group, 4- (2 ', 2'-difluorovinyl) phenyl group, 2-ethynylphenyl group, 3-ethynylphenyl group, 4-ethynylphenyl group, 2- (2′-fluoroethynyl) phenyl group, 3- (2′-fluoroethynyl) phenyl group, 4- (2′-fluoroethynyl) phenyl group, 2- Fluorophenyl group, 3-fluorophenyl group, 4-fluorophenyl group, 3,4-difluorophenyl group, pentafluorophenyl group, 2-chlorophenyl group, 3-chlorophenyl group, 4-chlorophenyl group, 3,4-dichlorophenyl group ,
Is mentioned.

In the present invention, examples of the phenoxy group which may have one or more atoms or groups selected from group B include, for example, phenoxy group, 2-cyanophenoxy group, 3-cyanophenoxy group, 4-cyanophenoxy group. 2-nitrophenoxy group, 3-nitrophenoxy group, 4-nitrophenoxy group, 2-carboxylphenoxy group, 3-carboxylphenoxy group, 4-carboxylphenoxy group, 2-hydroxylphenoxy group, 3-hydroxylphenoxy group, 4 -Hydroxyphenoxy group, 2- (N-methylcarboamido) phenoxy group, 3- (N-methylcarboamido) phenoxy group, 4- (N-methylcarboamido) phenoxy group, 2- (N, N-dimethylcarbohydrate) Amido) phenoxy group, 3- (N, N-dimethylcarboamido) pheno Si group, 4- (N, N-dimethylcarboamido) phenoxy group, 2-methylphenoxy group, 3-methylphenoxy group, 4-methylphenoxy group, 3,4-dimethylphenoxy group, 2-ethylphenoxy group, 3 -Ethylphenoxy group, 4-ethylphenoxy group, 2-trifluoromethylphenoxy group, 3-trifluoromethylphenoxy group, 4-trifluoromethylphenoxy group, 3,4-ditrifluoromethylphenoxy group, 2-methoxyphenoxy group 3-methoxyphenoxy group, 4-methoxyphenoxy group, 2-trifluoromethoxyphenoxy group, 3-trifluoromethoxyphenoxy group, 4-trifluoromethoxyphenoxy group, 2-methylthiophenoxy group, 3-methylthiophenoxy group, 4 -Methylthiophenoxy group, 2-methyl Sulfinylphenoxy group, 3-methylsulfinylphenoxy group, 4-methylsulfinylphenoxy group, 2-methylsulfonylphenoxy group, 3-methylsulfonylphenoxy group, 4-methylsulfonylphenoxy group, 2-trifluoromethylthiophenoxy group, 3-triphenyl Fluoromethylthiophenoxy group, 4-trifluoromethylthiophenoxy group, 2-trifluoromethylsulfinylphenoxy group, 3-trifluoromethylsulfinylphenoxy group, 4-trifluoromethylsulfinylphenoxy group, 2-trifluoromethylsulfonylphenoxy group, 3 -Trifluoromethylsulfonylphenoxy group, 4-trifluoromethylsulfonylphenoxy group, 2-methoxycarbonylphenoxy group, 3-methoxycarbonylpheno group Xyl group, 4-methoxycarbonylphenoxy group, 2-vinylphenoxy group, 3-vinylphenoxy group, 4-vinylphenoxy group, 2- (2 ′, 2′-difluorovinyl) phenoxy group, 3- (2 ′, 2 '-Difluorovinyl) phenoxy group, 4- (2', 2'-difluorovinyl) phenoxy group, 2-ethynylphenoxy group, 3-ethynylphenoxy group, 4-ethynylphenoxy group, 2- (2'-fluoroethynyl) Phenoxy group, 3- (2′-fluoroethynyl) phenoxy group, 4- (2′-fluoroethynyl) phenoxy group, 2-fluorophenoxy group, 3-fluorophenoxy group, 4-fluorophenoxy group, 3,4-difluoro Phenoxy group, pentafluorophenoxy group, 2-chlorophenoxy group, 3-chlorophenoxy group, 4- Rorofenokishi groups include 3,4-dichlorophenoxy group.

In the present invention, examples of the “naphthyl group optionally having one or more atoms or groups selected from group B” include 1-naphthyl group,
2-cyano-1-naphthyl group, 3-cyano-1-naphthyl group, 4-cyano-1-naphthyl group,
2-nitro-1-naphthyl group, 3-nitro-1-naphthyl group, 4-nitro-1-naphthyl group,
2-carboxyl-1-naphthyl group, 3-carboxyl-1-naphthyl group, 4-carboxyl-1-naphthyl group,
2-hydroxyl-1-naphthyl group, 3-hydroxyl-1-naphthyl group, 4-hydroxyl-1-naphthyl group,
2-methyl-1-naphthyl group, 3-methyl-1-naphthyl group, 4-methyl-1-naphthyl group,
2-trifluoromethyl-1-naphthyl group, 3-trifluoromethyl-1-naphthyl group, 4-trifluoromethyl-1-naphthyl group,
2-methoxy-1-naphthyl group, 3-methoxy-1-naphthyl group, 4-methoxy-1-naphthyl group,
2-trifluoromethoxy-1-naphthyl group, 3-trifluoromethoxy-1-naphthyl group, 4-trifluoromethoxy-1-naphthyl group,
2-trifluoromethylthio-1-naphthyl group, 3-trifluoromethylthio-1-naphthyl group, 4-trifluoromethylthio-1-naphthyl group,
2-trifluoromethylsulfinyl-1-naphthyl group, 3-trifluoromethylsulfinyl-1-naphthyl group, 4-trifluoromethylsulfinyl-1-naphthyl group,
2-trifluoromethylsulfonyl-1-naphthyl group, 3-trifluoromethylsulfonyl-1-naphthyl group, 4-trifluoromethylsulfonyl-1-naphthyl group,
2-methoxycarbonyl-1-naphthyl group, 3-methoxycarbonyl-1-naphthyl group, 4-methoxycarbonyl-1-naphthyl group,
2-vinyl-1-naphthyl group, 3-vinyl-1-naphthyl group, 4-vinyl-1-naphthyl group,
2- (2 ′, 2′-difluorovinyl) -1-naphthyl group, 3- (2 ′, 2′-difluorovinyl) -1-naphthyl group, 4- (2 ′, 2′-difluorovinyl) -1 A naphthyl group,
2-ethynyl-1-naphthyl group, 3-ethynyl-1-naphthyl group, 4-ethynyl-1-naphthyl group,
2- (2′-fluoroethynyl) -1-naphthyl group, 3- (2′-fluoroethynyl) -1-naphthyl group, 4- (2′-fluoroethynyl) -1-naphthyl group,
2-fluoro-1-naphthyl group, 3-fluoro-1-naphthyl group, 4-fluoro-1-naphthyl group,
“1 or more atoms or groups selected from group B may be included 1 such as 2-chloro-1-naphthyl group, 3-chloro-1-naphthyl group, 4-chloro-1-naphthyl group, etc. -Naphthyl group ";
2-naphthyl group,
1-cyano-2-naphthyl group, 3-cyano-2-naphthyl group, 4-cyano-2-naphthyl group,
1-nitro-2-naphthyl group, 3-nitro-2-naphthyl group, 4-nitro-2-naphthyl group,
1-carboxyl-2-naphthyl group, 3-carboxyl-2-naphthyl group, 4-carboxyl-2-naphthyl group,
1-hydroxyl-2-naphthyl group, 3-hydroxyl-2-naphthyl group, 4-hydroxyl-2-naphthyl group,
1-methyl-2-naphthyl group, 3-methyl-2-naphthyl group, 4-methyl-2-naphthyl group,
1-trifluoromethyl-2-naphthyl group, 3-trifluoromethyl-2-naphthyl group, 4-trifluoromethyl-2-naphthyl group,
1-methoxy-2-naphthyl group, 3-methoxy-2-naphthyl group, 4-methoxy-2-naphthyl group,
1-trifluoromethoxy-2-naphthyl group, 3-trifluoromethoxy-2-naphthyl group, 4-trifluoromethoxy-2-naphthyl group,
1-trifluoromethylthio-2-naphthyl group, 3-trifluoromethylthio-2-naphthyl group, 4-trifluoromethylthio-2-naphthyl group,
1-trifluoromethylsulfinyl-2-naphthyl group, 3-trifluoromethylsulfinyl-2-naphthyl group, 4-trifluoromethylsulfinyl-2-naphthyl group,
1-trifluoromethylsulfonyl-2-naphthyl group, 3-trifluoromethylsulfonyl-2-naphthyl group, 4-trifluoromethylsulfonyl-2-naphthyl group,
1-methoxycarbonyl-2-naphthyl group, 3-methoxycarbonyl-2-naphthyl group, 4-methoxycarbonyl-2-naphthyl group,
1-vinyl-2-naphthyl group, 3-vinyl-2-naphthyl group, 4-vinyl-2-naphthyl group,
1- (2 ′, 2′-difluorovinyl) -2-naphthyl group, 3- (2 ′, 2′-difluorovinyl) -2-naphthyl group, 4- (2 ′, 2′-difluorovinyl) -2 A naphthyl group,
1-ethynyl-2-naphthyl group, 3-ethynyl-2-naphthyl group, 4-ethynyl-2-naphthyl group,
1- (2′-fluoroethynyl) -2-naphthyl group, 3- (2′-fluoroethynyl) -2-naphthyl group, 4- (2′-fluoroethynyl) -2-naphthyl group,
1-fluoro-2-naphthyl group, 3-fluoro-2-naphthyl group, 4-fluoro-2-naphthyl group,
1-chloro-2-naphthyl group, 3-chloro-2-naphthyl group, 4-chloro-2-naphthyl group, etc., “may have one or more atoms or groups selected from group B 2 -Naphthyl group ";

In the present invention, examples of the “pyridyl group optionally having one or more atoms or groups selected from group B” include 2-pyridyl group, 3-cyano-2-pyridyl group, 4-cyano- 2-pyridyl group, 5-cyano-2-pyridyl group, 6-cyano-2-pyridyl group,
3-nitro-2-pyridyl group, 4-nitro-2-pyridyl group, 5-nitro-2-pyridyl group, 6-nitro-2-pyridyl group,
3-carboxyl-2-pyridyl group, 4-carboxyl-2-pyridyl group, 5-carboxyl-2-pyridyl group, 6-carboxyl-2-pyridyl group,
3-hydroxyl-2-pyridyl group, 4-hydroxyl-2-pyridyl group, 5-hydroxyl-2-pyridyl group, 6-hydroxyl-2-pyridyl group,
3-methyl-2-pyridyl group, 4-methyl-2-pyridyl group, 5-methyl-2-pyridyl group, 6-methyl-2-pyridyl group,
3-trifluoromethyl-2-pyridyl group, 4-trifluoromethyl-2-pyridyl group, 5-trifluoromethyl-2-pyridyl group, 6-trifluoromethyl-2-pyridyl group,
3-methoxy-2-pyridyl group, 4-methoxy-2-pyridyl group, 5-methoxy-2-pyridyl group, 6-methoxy-2-pyridyl group,
3-trifluoromethoxy-2-pyridyl group, 4-trifluoromethoxy-2-pyridyl group, 5-trifluoromethoxy-2-pyridyl group, 6-trifluoromethoxy-2-pyridyl group,
3-methoxycarbonyl-2-pyridyl group, 4-methoxycarbonyl-2-pyridyl group, 5-methoxycarbonyl-2-pyridyl group, 6-methoxycarbonyl-2-pyridyl group,
3-vinyl-2-pyridyl group, 4-vinyl-2-pyridyl group, 5-vinyl-2-pyridyl group, 6-vinyl-2-pyridyl group,
3- (2 ′, 2′-difluorovinyl) -2-pyridyl group, 4- (2 ′, 2′-difluorovinyl) -2-pyridyl group, 5- (2 ′, 2′-difluorovinyl) -2 -Pyridyl group, 6- (2 ', 2'-difluorovinyl) -2-pyridyl group,
3-ethynyl-2-pyridyl group, 4-ethynyl-2-pyridyl group, 5-ethynyl-2-pyridyl group, 6-ethynyl-2-pyridyl group,
3- (2′-fluoroethynyl) -2-pyridyl group, 4- (2′-fluoroethynyl) -2-pyridyl group, 5- (2′-fluoroethynyl) -2-pyridyl group, 6- (2 ′ -Fluoroethynyl) -2-pyridyl group,
3-fluoro-2-pyridyl group, 4-fluoro-2-pyridyl group, 5-fluoro-2-pyridyl group, 6-fluoro-2-pyridyl group,
One or more atoms or groups selected from group B such as 3-chloro-2-pyridyl group, 4-chloro-2-pyridyl group, 5-chloro-2-pyridyl group, 6-chloro-2-pyridyl group 2-pyridyl group which may have
3-pyridyl group, 2-cyano-3-pyridyl group, 4-cyano-3-pyridyl group, 5-cyano-3-pyridyl group, 6-cyano-3-pyridyl group,
2-nitro-3-pyridyl group, 4-nitro-3-pyridyl group, 5-nitro-3-pyridyl group, 6-nitro-3-pyridyl group,
2-carboxyl-3-pyridyl group, 4-carboxyl-3-pyridyl group, 5-carboxyl-3-pyridyl group, 6-carboxyl-3-pyridyl group,
2-hydroxyl-3-pyridyl group, 4-hydroxyl-3-pyridyl group, 5-hydroxyl-3-pyridyl group, 6-hydroxyl-3-pyridyl group,
2-methyl-3-pyridyl group, 4-methyl-3-pyridyl group, 5-methyl-3-pyridyl group, 6-methyl-3-pyridyl group,
2-trifluoromethyl-3-pyridyl group, 4-trifluoromethyl-3-pyridyl group, 5-trifluoromethyl-3-pyridyl group, 6-trifluoromethyl-3-pyridyl group,
2-methoxy-3-pyridyl group, 4-methoxy-3-pyridyl group, 5-methoxy-3-pyridyl group, 6-methoxy-3-pyridyl group,
2-trifluoromethoxy-3-pyridyl group, 4-trifluoromethoxy-3-pyridyl group, 5-trifluoromethoxy-3-pyridyl group, 6-trifluoromethoxy-3-pyridyl group,
2-methoxycarbonyl-3-pyridyl group, 4-methoxycarbonyl-3-pyridyl group, 5-methoxycarbonyl-3-pyridyl group, 6-methoxycarbonyl-3-pyridyl group,
2-vinyl-3-pyridyl group, 4-vinyl-3-pyridyl group, 5-vinyl-3-pyridyl group, 6-vinyl-3-pyridyl group,
2- (2 ′, 2′-difluorovinyl) -3-pyridyl group, 4- (2 ′, 2′-difluorovinyl) -3-pyridyl group, 5- (2 ′, 2′-difluorovinyl) -3 -Pyridyl group, 6- (2 ', 2'-difluorovinyl) -3-pyridyl group,
2-ethynyl-3-pyridyl group, 4-ethynyl-3-pyridyl group, 5-ethynyl-3-pyridyl group, 6-ethynyl-3-pyridyl group,
2- (2′-fluoroethynyl) -3-pyridyl group, 4- (2′-fluoroethynyl) -3-pyridyl group, 5- (2′-fluoroethynyl) -3-pyridyl group, 6- (2 ′ -Fluoroethynyl) -3-pyridyl group,
2-fluoro-3-pyridyl group, 4-fluoro-3-pyridyl group, 5-fluoro-3-pyridyl group, 6-fluoro-3-pyridyl group,
One or more atoms or groups selected from group B, such as 2-chloro-3-pyridyl group, 4-chloro-3-pyridyl group, 5-chloro-3-pyridyl group, 6-chloro-3-pyridyl group, etc. Optionally having a 3-pyridyl group;
4-pyridyl group, 2-cyano-4-pyridyl group, 3-cyano-4-pyridyl group 2-nitro-4-pyridyl group, 3-nitro-4-pyridyl group,
2-carboxyl-4-pyridyl group, 3-carboxyl-4-pyridyl group,
2-hydroxyl-4-pyridyl group, 3-hydroxyl-4-pyridyl group,
2-methyl-4-pyridyl group, 3-methyl-4-pyridyl group,
2-trifluoromethyl-4-pyridyl group, 3-trifluoromethyl-4-pyridyl group,
2-methoxy-4-pyridyl group, 3-methoxy-4-pyridyl group,
2-trifluoromethoxy-4-pyridyl group, 3-trifluoromethoxy-4-pyridyl group,
2-methoxycarbonyl-4-pyridyl group, 3-methoxycarbonyl-4-pyridyl group,
2-vinyl-4-pyridyl group, 3-vinyl-4-pyridyl group,
2- (2 ′, 2′-difluorovinyl) -4-pyridyl group, 3- (2 ′, 2′-difluorovinyl) -4-pyridyl group,
2-ethynyl-4-pyridyl group, 3-ethynyl-4-pyridyl group,
2- (2′-fluoroethynyl) -4-pyridyl group, 3- (2′-fluoroethynyl) -4-pyridyl group,
2-fluoro-4-pyridyl group, 3-fluoro-4-pyridyl group,
"4-pyridyl group optionally having one or more atoms or groups selected from group B" such as 2-chloro-4-pyridyl group, 3-chloro-4-pyridyl group;
Is mentioned.

In the present invention, examples of the “quinolyl group optionally having one or more atoms or groups selected from group B” include a 2-quinolyl group,
5-cyano-2-quinolyl group, 6-cyano-2-quinolyl group, 7-cyano-2-quinolyl group, 8-cyano-2-quinolyl group,
5-nitro-2-quinolyl group, 6-nitro-2-quinolyl group, 7-nitro-2-quinolyl group, 7-nitro-2-quinolyl group,
5-carboxyl-2-quinolyl group, 6-carboxyl-2-quinolyl group, 7-carboxyl-2-quinolyl group, 8-carboxyl-2-quinolyl group,
5-hydroxyl-2-quinolyl group, 6-hydroxyl-2-quinolyl group, 7-hydroxyl-2-quinolyl group, 8-hydroxyl-2-quinolyl group,
5-methyl-2-quinolyl group, 6-methyl-2-quinolyl group, 7-methyl-2-quinolyl group, 8-methyl-2-quinolyl group,
5-trifluoromethyl-2-quinolyl group, 6-trifluoromethyl-2-quinolyl group, 7-trifluoromethyl-2-quinolyl group, 8-trifluoromethyl-2-quinolyl group,
5-methoxy-2-quinolyl group, 6-methoxy-2-quinolyl group, 7-methoxy-2-quinolyl group, 8-methoxy-2-quinolyl group,
5-trifluoromethoxy-2-quinolyl group, 6-trifluoromethoxy-2-quinolyl group, 7-trifluoromethoxy-2-quinolyl group, 8-trifluoromethoxy-2-quinolyl group,
5-methoxycarbonyl-2-quinolyl group, 6-methoxycarbonyl-2-quinolyl group, 7-methoxycarbonyl-2-quinolyl group, 8-methoxycarbonyl-2-quinolyl group,
5-vinyl-2-quinolyl group, 6-vinyl-2-quinolyl group, 7-vinyl-2-quinolyl group, 8-vinyl-2-quinolyl group,
5- (2 ′, 2′-difluorovinyl) -2-quinolyl group, 6- (2 ′, 2′-difluorovinyl) -2-quinolyl group, 7- (2 ′, 2′-difluorovinyl) -2 -Quinolyl group, 8- (2 ', 2'-difluorovinyl) -2-quinolyl group,
5-ethynyl-2-quinolyl group, 6-ethynyl-2-quinolyl group, 7-ethynyl-2-quinolyl group, 8-ethynyl-2-quinolyl group,
5- (2′-fluoroethynyl) -2-quinolyl group, 6- (2′-fluoroethynyl) -2-quinolyl group, 7- (2′-fluoroethynyl) -2-quinolyl group, 8- (2 ′ -Fluoroethynyl) -2-quinolyl group,
5-fluoro-2-quinolyl group, 6-fluoro-2-quinolyl group, 7-fluoro-2-quinolyl group, 8-fluoro-2-quinolyl group, 5,6,7,8-tetrafluoro-2-quinolyl Group,
“One or more atoms selected from group B, such as a 5-chloro-2-quinolyl group, a 6-chloro-2-quinolyl group, a 7-chloro-2-quinolyl group, and an 8-chloro-2-quinolyl group; A 2-quinolyl group optionally having a group ";
3-quinolyl group,
5-cyano-3-quinolyl group, 6-cyano-3-quinolyl group, 7-cyano-3-quinolyl group, 8-cyano-3-quinolyl group,
5-nitro-3-quinolyl group, 6-nitro-3-quinolyl group, 7-nitro-3-quinolyl group, 7-nitro-3-quinolyl group,
5-carboxyl-3-quinolyl group, 6-carboxyl-3-quinolyl group, 7-carboxyl-3-quinolyl group, 8-carboxyl-3-quinolyl group,
5-hydroxyl-3-quinolyl group, 6-hydroxyl-3-quinolyl group, 7-hydroxyl-3-quinolyl group, 8-hydroxyl-3-quinolyl group,
5-methyl-3-quinolyl group, 6-methyl-3-quinolyl group, 7-methyl-3-quinolyl group, 8-methyl-3-quinolyl group,
5-trifluoromethyl-3-quinolyl group, 6-trifluoromethyl-3-quinolyl group, 7-trifluoromethyl-3-quinolyl group, 8-trifluoromethyl-3-quinolyl group,
5-methoxy-3-quinolyl group, 6-methoxy-3-quinolyl group, 7-methoxy-3-quinolyl group, 8-methoxy-3-quinolyl group,
5-trifluoromethoxy-3-quinolyl group, 6-trifluoromethoxy-3-quinolyl group, 7-trifluoromethoxy-3-quinolyl group, 8-trifluoromethoxy-3-quinolyl group,
5-methoxycarbonyl-3-quinolyl group, 6-methoxycarbonyl-3-quinolyl group, 7-methoxycarbonyl-3-quinolyl group, 8-methoxycarbonyl-3-quinolyl group,
5-vinyl-3-quinolyl group, 6-vinyl-3-quinolyl group, 7-vinyl-3-quinolyl group, 8-vinyl-3-quinolyl group,
5- (2 ′, 2′-difluorovinyl) -3-quinolyl group, 6- (2 ′, 2′-difluorovinyl) -3-quinolyl group, 7- (2 ′, 2′-difluorovinyl) -3 -Quinolyl group, 8- (2 ', 2'-difluorovinyl) -3-quinolyl group,
5-ethynyl-3-quinolyl group, 6-ethynyl-3-quinolyl group, 7-ethynyl-3-quinolyl group, 8-ethynyl-3-quinolyl group,
5- (2′-fluoroethynyl) -3-quinolyl group, 6- (2′-fluoroethynyl) -3-quinolyl group, 7- (2′-fluoroethynyl) -3-quinolyl group, 8- (2 ′ -Fluoroethynyl) -3-quinolyl group,
5-fluoro-3-quinolyl group, 6-fluoro-3-quinolyl group, 7-fluoro-3-quinolyl group, 8-fluoro-3-quinolyl group, 5,6,7,8-tetrafluoro-3-quinolyl Group,
“One or more atoms selected from group B, such as a 5-chloro-3-quinolyl group, a 6-chloro-3-quinolyl group, a 7-chloro-3-quinolyl group, and an 8-chloro-3-quinolyl group; A 3-quinolyl group optionally having a group ";
4-quinolyl group, 2-cyano-4-quinolyl group, 3-cyano-4-quinolyl group,
2-nitro-4-quinolyl group, 3-nitro-4-quinolyl group,
2-carboxyl-4-quinolyl group, 3-carboxyl-4-quinolyl group,
2-hydroxyl-4-quinolyl group, 3-hydroxyl-4-quinolyl group,
2-methyl-4-quinolyl group, 3-methyl-4-quinolyl group,
2-trifluoromethyl-4-quinolyl group, 3-trifluoromethyl-4-quinolyl group,
2-methoxy-4-quinolyl group, 3-methoxy-4-quinolyl group,
2-trifluoromethoxy-4-quinolyl group, 3-trifluoromethoxy-4-quinolyl group,
2-methoxycarbonyl-4-quinolyl group, 3-methoxycarbonyl-4-quinolyl group,
2-vinyl-4-quinolyl group, 3-vinyl-4-quinolyl group,
2- (2 ′, 2′-difluorovinyl) -4-quinolyl group, 3- (2 ′, 2′-difluorovinyl) -4-quinolyl group,
2-ethynyl-4-quinolyl group, 3-ethynyl-4-quinolyl group,
2- (2′-fluoroethynyl) -4-quinolyl group, 3- (2′-fluoroethynyl) -4-quinolyl group,
2-fluoro-4-quinolyl group, 3-fluoro-4-quinolyl group,
“4-quinolyl group optionally having one or more atoms or groups selected from group B” such as 2-chloro-4-quinolyl group and 3-chloro-4-quinolyl group;

In the present invention, examples of the “furyl group optionally having one or more atoms or groups selected from group B” include 2-furyl group, 3-cyano-2-furyl group, 4-cyano- 2-furyl group, 5-cyano-2-furyl group,
3-nitro-2-furyl group, 4-nitro-2-furyl group, 5-nitro-2-furyl group,
3-carboxyl-2-furyl group, 4-carboxyl-2-furyl group, 5-carboxyl-2-furyl group,
3-hydroxyl-2-furyl group, 4-hydroxyl-2-furyl group, 5-hydroxyl-2-furyl group,
3-methyl-2-furyl group, 4-methyl-2-furyl group, 5-methyl-2-furyl group,
3-trifluoromethyl-2-furyl group, 4-trifluoromethyl-2-furyl group, 5-trifluoromethyl-2-furyl group,
3-methoxy-2-furyl group, 4-methoxy-2-furyl group, 5-methoxy-2-furyl group,
3-trifluoromethoxy-2-furyl group, 4-trifluoromethoxy-2-furyl group, 5-trifluoromethoxy-2-furyl group,
3-methoxycarbonyl-2-furyl group, 4-methoxycarbonyl-2-furyl group, 5-methoxycarbonyl-2-furyl group,
3-vinyl-2-furyl group, 4-vinyl-2-furyl group, 5-vinyl-2-furyl group,
3- (2 ′, 2′-difluorovinyl) -2-furyl group, 4- (2 ′, 2′-difluorovinyl) -2-furyl group, 5- (2 ′, 2′-difluorovinyl) -2 -Furyl group,
3-ethynyl-2-furyl group, 4-ethynyl-2-furyl group, 5-ethynyl-2-furyl group,
3- (2′-fluoroethynyl) -2-furyl group, 4- (2′-fluoroethynyl) -2-furyl group, 5- (2′-fluoroethynyl) -2-furyl group,
3-fluoro-2-furyl group, 4-fluoro-2-furyl group, 5-fluoro-2-furyl group,
“May have one or more atoms or groups selected from group B, such as 3-chloro-2-furyl group, 4-chloro-2-furyl group, 5-chloro-2-furyl group, etc. -Furyl group ";
3-furyl group, 2-cyano-3-furyl group, 4-cyano-3-furyl group, 5-cyano-3-furyl group,
2-nitro-3-furyl group, 4-nitro-3-furyl group, 5-nitro-3-furyl group,
2-carboxyl-3-furyl group, 4-carboxyl-3-furyl group, 5-carboxyl-3-furyl group,
2-hydroxyl-3-furyl group, 4-hydroxyl-3-furyl group, 5-hydroxyl-3-furyl group,
2-methyl-3-furyl group, 4-methyl-3-furyl group, 5-methyl-3-furyl group,
2-trifluoromethyl-3-furyl group, 4-trifluoromethyl-3-furyl group, 5-trifluoromethyl-3-furyl group,
2-methoxy-3-furyl group, 4-methoxy-3-furyl group, 5-methoxy-3-furyl group,
2-trifluoromethoxy-3-furyl group, 4-trifluoromethoxy-3-furyl group, 5-trifluoromethoxy-3-furyl group,
2-methoxycarbonyl-3-furyl group, 4-methoxycarbonyl-3-furyl group, 5-methoxycarbonyl-3-furyl group,
2-vinyl-3-furyl group, 4-vinyl-3-furyl group, 5-vinyl-3-furyl group,
2- (2 ′, 2′-difluorovinyl) -3-furyl group, 4- (2 ′, 2′-difluorovinyl) -3-furyl group, 5- (2 ′, 2′-difluorovinyl) -3 -Furyl group,
2-ethynyl-3-furyl group, 4-ethynyl-3-furyl group, 5-ethynyl-3-furyl group,
2- (2′-fluoroethynyl) -3-furyl group, 4- (2′-fluoroethynyl) -3-furyl group, 5- (2′-fluoroethynyl) -3-furyl group,
2-fluoro-3-furyl group, 4-fluoro-3-furyl group, 5-fluoro-3-furyl group,
“May have one or more atoms or groups selected from group B, such as 2-chloro-3-furyl group, 4-chloro-3-furyl group, 5-chloro-3-furyl group, etc. -Furyl group ";

In the present invention, examples of the “thienyl group optionally having one or more atoms or groups selected from group B” include 2-thienyl group, 3-cyano-2-thienyl group, 4-cyano- 2-thienyl group, 5-cyano-2-thienyl group,
3-nitro-2-thienyl group, 4-nitro-2-thienyl group, 5-nitro-2-thienyl group,
3-carboxyl-2-thienyl group, 4-carboxyl-2-thienyl group, 5-carboxyl-2-thienyl group,
3-hydroxyl-2-thienyl group, 4-hydroxyl-2-thienyl group, 5-hydroxyl-2-thienyl group,
3-methyl-2-thienyl group, 4-methyl-2-thienyl group, 5-methyl-2-thienyl group,
3-trifluoromethyl-2-thienyl group, 4-trifluoromethyl-2-thienyl group, 5-trifluoromethyl-2-thienyl group,
3-methoxy-2-thienyl group, 4-methoxy-2-thienyl group, 5-methoxy-2-thienyl group,
3-trifluoromethoxy-2-thienyl group, 4-trifluoromethoxy-2-thienyl group, 5-trifluoromethoxy-2-thienyl group,
3-methoxycarbonyl-2-thienyl group, 4-methoxycarbonyl-2-thienyl group, 5-methoxycarbonyl-2-thienyl group,
3-vinyl-2-thienyl group, 4-vinyl-2-thienyl group, 5-vinyl-2-thienyl group,
3- (2 ′, 2′-difluorovinyl) -2-thienyl group, 4- (2 ′, 2′-difluorovinyl) -2-thienyl group, 5- (2 ′, 2′-difluorovinyl) -2 A thienyl group,
3-ethynyl-2-thienyl group, 4-ethynyl-2-thienyl group, 5-ethynyl-2-thienyl group,
3- (2′-fluoroethynyl) -2-thienyl group, 4- (2′-fluoroethynyl) -2-thienyl group, 5- (2′-fluoroethynyl) -2-thienyl group,
3-fluoro-2-thienyl group, 4-fluoro-2-thienyl group, 5-fluoro-2-thienyl group,
Such as 3-chloro-2-thienyl group, 4-chloro-2-thienyl group, 5-chloro-2-thienyl group, etc., which may have “one or more atoms or groups selected from group B 2 -Thienyl group ";
3-thienyl group, 2-cyano-3-thienyl group, 4-cyano-3-thienyl group, 5-cyano-3-thienyl group,
2-nitro-3-thienyl group, 4-nitro-3-thienyl group, 5-nitro-3-thienyl group,
2-carboxyl-3-thienyl group, 4-carboxyl-3-thienyl group, 5-carboxyl-3-thienyl group,
2-hydroxyl-3-thienyl group, 4-hydroxyl-3-thienyl group, 5-hydroxyl-3-thienyl group,
2-methyl-3-thienyl group, 4-methyl-3-thienyl group, 5-methyl-3-thienyl group,
2-trifluoromethyl-3-thienyl group, 4-trifluoromethyl-3-thienyl group, 5-trifluoromethyl-3-thienyl group,
2-methoxy-3-thienyl group, 4-methoxy-3-thienyl group, 5-methoxy-3-thienyl group,
2-trifluoromethoxy-3-thienyl group, 4-trifluoromethoxy-3-thienyl group, 5-trifluoromethoxy-3-thienyl group,
2-methoxycarbonyl-3-thienyl group, 4-methoxycarbonyl-3-thienyl group, 5-methoxycarbonyl-3-thienyl group,
2-vinyl-3-thienyl group, 4-vinyl-3-thienyl group, 5-vinyl-3-thienyl group,
2- (2 ′, 2′-difluorovinyl) -3-thienyl group, 4- (2 ′, 2′-difluorovinyl) -3-thienyl group, 5- (2 ′, 2′-difluorovinyl) -3 A thienyl group,
2-ethynyl-3-thienyl group, 4-ethynyl-3-thienyl group, 5-ethynyl-3-thienyl group,
2- (2′-fluoroethynyl) -3-thienyl group, 4- (2′-fluoroethynyl) -3-thienyl group, 5- (2′-fluoroethynyl) -3-thienyl group,
2-fluoro-3-thienyl group, 4-fluoro-3-thienyl group, 5-fluoro-3-thienyl group,
“May have one or more atoms or groups selected from group B, such as 2-chloro-3-thienyl group, 4-chloro-3-thienyl group, 5-chloro-3-thienyl group, etc. -Thienyl group ".

In the present invention, examples of the “benzofuranyl group optionally having one or more atoms or groups selected from group B” include a 2- (1-benzofuranyl) group,
4-cyano-2- (1-benzofuranyl) group, 5-cyano-2- (1-benzofuranyl) group, 6-cyano-2- (1-benzofuranyl) group, 7-cyano-2- (1-benzofuranyl) group Group,
4-nitro-2- (1-benzofuranyl) group, 5-nitro-2- (1-benzofuranyl) group, 6-nitro-2- (1-benzofuranyl) group, 7-nitro-2- (1-benzofuranyl) group Group,
4-carboxyl-2- (1-benzofuranyl) group, 5-carboxyl-2- (1-benzofuranyl) group, 6-carboxyl-2- (1-benzofuranyl) group, 7-carboxyl-2- (1-benzofuranyl) group Group,
4-hydroxyl-2- (1-benzofuranyl) group, 5-hydroxyl-2- (1-benzofuranyl) group, 6-hydroxyl-2- (1-benzofuranyl) group, 7-hydroxyl-2- (1-benzofuranyl) group Group,
4-methyl-2- (1-benzofuranyl) group, 5-methyl-2- (1-benzofuranyl) group, 6-methyl-2- (1-benzofuranyl) group, 7-methyl-2- (1-benzofuranyl) group Group,
4-trifluoromethyl-2- (1-benzofuranyl) group, 5-trifluoromethyl-2- (1-benzofuranyl) group, 6-trifluoromethyl-2- (1-benzofuranyl) group, 7-trifluoromethyl A 2- (1-benzofuranyl) group,
4-methoxy-2- (1-benzofuranyl) group, 5-methoxy-2- (1-benzofuranyl) group, 6-methoxy-2- (1-benzofuranyl) group, 7-methoxy-2- (1-benzofuranyl) group Group,
4-trifluoromethoxy-2- (1-benzofuranyl) group, 5-trifluoromethoxy-2- (1-benzofuranyl) group, 6-trifluoromethoxy-2- (1-benzofuranyl) group, 7-trifluoromethoxy A 2- (1-benzofuranyl) group,
4-methoxycarbonyl-2- (1-benzofuranyl) group, 5-methoxycarbonyl-2- (1-benzofuranyl) group, 6-methoxycarbonyl-2- (1-benzofuranyl) group, 7-methoxycarbonyl-2- ( 1-benzofuranyl) group,
4-vinyl-2- (1-benzofuranyl) group, 5-vinyl-2- (1-benzofuranyl) group, 6-vinyl-2- (1-benzofuranyl) group, 7-vinyl-2- (1-benzofuranyl) Group,
4- (2 ′, 2′-difluorovinyl) -2- (1-benzofuranyl) group, 5- (2 ′, 2′-difluorovinyl) -2- (1-benzofuranyl) group, 6- (2 ′, 2′-difluorovinyl) -2- (1-benzofuranyl) group, 7- (2 ′, 2′-difluorovinyl) -2- (1-benzofuranyl) group,
4-ethynyl-2- (1-benzofuranyl) group, 5-ethynyl-2- (1-benzofuranyl) group, 6-ethynyl-2- (1-benzofuranyl) group, 7-ethynyl-2- (1-benzofuranyl) group Group,
4- (2'-fluoroethynyl) -2- (1-benzofuranyl) group, 5- (2'-fluoroethynyl) -2- (1-benzofuranyl) group, 6- (2'-fluoroethynyl) -2- (1-benzofuranyl) group, 7- (2′-fluoroethynyl) -2- (1-benzofuranyl) group,
4-fluoro-2- (1-benzofuranyl) group, 5-fluoro-2- (1-benzofuranyl) group, 6-fluoro-2- (1-benzofuranyl) group, 7-fluoro-2- (1-benzofuranyl) group A group, 4,5,6,7-tetrafluoro-2- (1-benzofuranyl) group,
4-chloro-2- (1-benzofuranyl) group, 5-chloro-2- (1-benzofuranyl) group, 6-chloro-2- (1-benzofuranyl) group, 7-chloro-2- (1-benzofuranyl) group "2- (1-benzofuranyl) group optionally having one or more atoms or groups selected from group B", such as a group;
A 3- (1-benzofuranyl) group,
4-cyano-3- (1-benzofuranyl) group, 5-cyano-3- (1-benzofuranyl) group, 6-cyano-3- (1-benzofuranyl) group, 7-cyano-3- (1-benzofuranyl) group Group,
4-nitro-3- (1-benzofuranyl) group, 5-nitro-3- (1-benzofuranyl) group, 6-nitro-3- (1-benzofuranyl) group, 7-nitro-3- (1-benzofuranyl) group Group,
4-carboxyl-3- (1-benzofuranyl) group, 5-carboxyl-3- (1-benzofuranyl) group, 6-carboxyl-3- (1-benzofuranyl) group, 7-carboxyl-3- (1-benzofuranyl) Group,
4-hydroxyl-3- (1-benzofuranyl) group, 5-hydroxyl-3- (1-benzofuranyl) group, 6-hydroxyl-3- (1-benzofuranyl) group, 7-hydroxyl-3- (1-benzofuranyl) group Group,
4-methyl-3- (1-benzofuranyl) group, 5-methyl-3- (1-benzofuranyl) group, 6-methyl-3- (1-benzofuranyl) group, 7-methyl-3- (1-benzofuranyl) group Group,
4-trifluoromethyl-3- (1-benzofuranyl) group, 5-trifluoromethyl-3- (1-benzofuranyl) group, 6-trifluoromethyl-3- (1-benzofuranyl) group, 7-trifluoromethyl A 3- (1-benzofuranyl) group,
4-methoxy-3- (1-benzofuranyl) group, 5-methoxy-3- (1-benzofuranyl) group, 6-methoxy-3- (1-benzofuranyl) group, 7-methoxy-3- (1-benzofuranyl) group Group,
4-trifluoromethoxy-3- (1-benzofuranyl) group, 5-trifluoromethoxy-3- (1-benzofuranyl) group, 6-trifluoromethoxy-3- (1-benzofuranyl) group, 7-trifluoromethoxy A 3- (1-benzofuranyl) group,
4-methoxycarbonyl-3- (1-benzofuranyl) group, 5-methoxycarbonyl-3- (1-benzofuranyl) group, 6-methoxycarbonyl-3- (1-benzofuranyl) group, 7-methoxycarbonyl-3- ( 1-benzofuranyl) group,
4-vinyl-3- (1-benzofuranyl) group, 5-vinyl-3- (1-benzofuranyl) group, 6-vinyl-3- (1-benzofuranyl) group, 7-vinyl-3- (1-benzofuranyl) group Group,
4- (2 ′, 2′-difluorovinyl) -3- (1-benzofuranyl) group, 5- (2 ′, 2′-difluorovinyl) -3- (1-benzofuranyl) group, 6- (2 ′, 2′-difluorovinyl) -3- (1-benzofuranyl) group, 7- (2 ′, 2′-difluorovinyl) -3- (1-benzofuranyl) group,
4-ethynyl-3- (1-benzofuranyl) group, 5-ethynyl-3- (1-benzofuranyl) group, 6-ethynyl-3- (1-benzofuranyl) group, 7-ethynyl-3- (1-benzofuranyl) group Group,
4- (2′-fluoroethynyl) -3- (1-benzofuranyl) group, 5- (2′-fluoroethynyl) -3- (1-benzofuranyl) group, 6- (2′-fluoroethynyl) -3- (1-benzofuranyl) group, 7- (2′-fluoroethynyl) -3- (1-benzofuranyl) group,
4-fluoro-3- (1-benzofuranyl) group, 5-fluoro-3- (1-benzofuranyl) group, 6-fluoro-3- (1-benzofuranyl) group, 7-fluoro-3- (1-benzofuranyl) Group, 4,5,6,7-tetrafluoro-3- (1-benzofuranyl) group,
4-chloro-3- (1-benzofuranyl) group, 5-chloro-3- (1-benzofuranyl) group, 6-chloro-3- (1-benzofuranyl) group, 7-chloro-3- (1-benzofuranyl) group “3- (1-benzofuranyl) group optionally having one or more atoms or groups selected from group B”, such as a group;

In the present invention, examples of the “benzothienyl group optionally having one or more atoms or groups selected from group B” include a 2- (1-benzothienyl) group,
4-cyano-2- (1-benzothienyl) group, 5-cyano-2- (1-benzothienyl) group, 6-cyano-2- (1-benzothienyl) group, 7-cyano-2- (1 -Benzothienyl) group,
4-nitro-2- (1-benzothienyl) group, 5-nitro-2- (1-benzothienyl) group, 6-nitro-2- (1-benzothienyl) group, 7-nitro-2- (1 -Benzothienyl) group,
4-carboxyl-2- (1-benzothienyl) group, 5-carboxyl-2- (1-benzothienyl) group, 6-carboxyl-2- (1-benzothienyl) group, 7-carboxyl-2- (1 -Benzothienyl) group,
4-hydroxyl-2- (1-benzothienyl) group, 5-hydroxyl-2- (1-benzothienyl) group, 6-hydroxyl-2- (1-benzothienyl) group, 7-hydroxyl-2- (1 -Benzothienyl) group,
4-methyl-2- (1-benzothienyl) group, 5-methyl-2- (1-benzothienyl) group, 6-methyl-2- (1-benzothienyl) group, 7-methyl-2- (1 -Benzothienyl) group,
4-trifluoromethyl-2- (1-benzothienyl) group, 5-trifluoromethyl-2- (1-benzothienyl) group, 6-trifluoromethyl-2- (1-benzothienyl) group, 7- A trifluoromethyl-2- (1-benzothienyl) group,
4-methoxy-2- (1-benzothienyl) group, 5-methoxy-2- (1-benzothienyl) group, 6-methoxy-2- (1-benzothienyl) group, 7-methoxy-2- (1 -Benzothienyl) group,
4-trifluoromethoxy-2- (1-benzothienyl) group, 5-trifluoromethoxy-2- (1-benzothienyl) group, 6-trifluoromethoxy-2- (1-benzothienyl) group, 7- Trifluoromethoxy-2- (1-benzothienyl) group,
4-methoxycarbonyl-2- (1-benzothienyl) group, 5-methoxycarbonyl-2- (1-benzothienyl) group, 6-methoxycarbonyl-2- (1-benzothienyl) group, 7-methoxycarbonyl- A 2- (1-benzothienyl) group,
4-vinyl-2- (1-benzothienyl) group, 5-vinyl-2- (1-benzothienyl) group, 6-vinyl-2- (1-benzothienyl) group, 7-vinyl-2- (1 -Benzothienyl) group,
4- (2 ′, 2′-difluorovinyl) -2- (1-benzothienyl) group, 5- (2 ′, 2′-difluorovinyl) -2- (1-benzothienyl) group, 6- (2 ', 2'-difluorovinyl) -2- (1-benzothienyl) group, 7- (2', 2'-difluorovinyl) -2- (1-benzothienyl) group,
4-ethynyl-2- (1-benzothienyl) group, 5-ethynyl-2- (1-benzothienyl) group, 6-ethynyl-2- (1-benzothienyl) group, 7-ethynyl-2- (1 -Benzothienyl) group,
4- (2'-fluoroethynyl) -2- (1-benzothienyl) group, 5- (2'-fluoroethynyl) -2- (1-benzothienyl) group, 6- (2'-fluoroethynyl)- 2- (1-benzothienyl) group, 7- (2′-fluoroethynyl) -2- (1-benzothienyl) group,
4-fluoro-2- (1-benzothienyl) group, 5-fluoro-2- (1-benzothienyl) group, 6-fluoro-2- (1-benzothienyl) group, 7-fluoro-2- (1 -Benzothienyl) group, 4,5,6,7-tetrafluoro-2- (1-benzothienyl) group,
4-chloro-2- (1-benzothienyl) group, 5-chloro-2- (1-benzothienyl) group, 6-chloro-2- (1-benzothienyl) group, 7-chloro-2- (1 A “2- (1-benzothienyl) group optionally having one or more atoms or groups selected from group B”, such as a —benzothienyl) group;
A 3- (1-benzothienyl) group,
4-cyano-3- (1-benzothienyl) group, 5-cyano-3- (1-benzothienyl) group, 6-cyano-3- (1-benzothienyl) group, 7-cyano-3- (1 -Benzothienyl) group,
4-nitro-3- (1-benzothienyl) group, 5-nitro-3- (1-benzothienyl) group, 6-nitro-3- (1-benzothienyl) group, 7-nitro-3- (1 -Benzothienyl) group,
4-carboxyl-3- (1-benzothienyl) group, 5-carboxyl-3- (1-benzothienyl) group, 6-carboxyl-3- (1-benzothienyl) group, 7-carboxyl-3- (1 -Benzothienyl) group,
4-hydroxyl-3- (1-benzothienyl) group, 5-hydroxyl-3- (1-benzothienyl) group, 6-hydroxyl-3- (1-benzothienyl) group, 7-hydroxyl-3- (1 -Benzothienyl) group,
4-methyl-3- (1-benzothienyl) group, 5-methyl-3- (1-benzothienyl) group, 6-methyl-3- (1-benzothienyl) group, 7-methyl-3- (1 -Benzothienyl) group,
4-trifluoromethyl-3- (1-benzothienyl) group, 5-trifluoromethyl-3- (1-benzothienyl) group, 6-trifluoromethyl-3- (1-benzothienyl) group, 7- A trifluoromethyl-3- (1-benzothienyl) group,
4-methoxy-3- (1-benzothienyl) group, 5-methoxy-3- (1-benzothienyl) group, 6-methoxy-3- (1-benzothienyl) group, 7-methoxy-3- (1 -Benzothienyl) group,
4-trifluoromethoxy-3- (1-benzothienyl) group, 5-trifluoromethoxy-3- (1-benzothienyl) group, 6-trifluoromethoxy-3- (1-benzothienyl) group, 7- Trifluoromethoxy-3- (1-benzothienyl) group,
4-methoxycarbonyl-3- (1-benzothienyl) group, 5-methoxycarbonyl-3- (1-benzothienyl) group, 6-methoxycarbonyl-3- (1-benzothienyl) group, 7-methoxycarbonyl- A 3- (1-benzothienyl) group,
4-vinyl-3- (1-benzothienyl) group, 5-vinyl-3- (1-benzothienyl) group, 6-vinyl-3- (1-benzothienyl) group, 7-vinyl-3- (1 -Benzothienyl) group,
4- (2 ′, 2′-difluorovinyl) -3- (1-benzothienyl) group, 5- (2 ′, 2′-difluorovinyl) -3- (1-benzothienyl) group, 6- (2 ', 2'-difluorovinyl) -3- (1-benzothienyl) group, 7- (2', 2'-difluorovinyl) -3- (1-benzothienyl) group,
4-ethynyl-3- (1-benzothienyl) group, 5-ethynyl-3- (1-benzothienyl) group, 6-ethynyl-3- (1-benzothienyl) group, 7-ethynyl-3- (1 -Benzothienyl) group,
4- (2′-fluoroethynyl) -3- (1-benzothienyl) group, 5- (2′-fluoroethynyl) -3- (1-benzothienyl) group, 6- (2′-fluoroethynyl)- 3- (1-benzothienyl) group, 7- (2′-fluoroethynyl) -3- (1-benzothienyl) group,
4-fluoro-3- (1-benzothienyl) group, 5-fluoro-3- (1-benzothienyl) group, 6-fluoro-3- (1-benzothienyl) group, 7-fluoro-3- (1 -Benzothienyl) group, 4,5,6,7-tetrafluoro-3- (1-benzothienyl) group,
4-chloro-3- (1-benzothienyl) group, 5-chloro-3- (1-benzothienyl) group, 6-chloro-3- (1-benzothienyl) group, 7-chloro-3- (1 A “3- (1-benzothienyl) group optionally having one or more atoms or groups selected from group B”, such as a —benzothienyl) group;
Is mentioned.

In the present invention, the “1,3-benzodioxolanyl group optionally having one or more atoms or groups selected from group B” includes, for example,
A 2- (1,3-benzodioxolanyl) group,
4-cyano-2- (1,3-benzodioxolanyl) group, 5-cyano-2- (1,3-benzodioxolanyl) group,
4-nitro-2- (1,3-benzodioxolanyl) group, 5-nitro-2- (1,3-benzodioxolanyl) group,
4-carboxyl-2- (1,3-benzodioxolanyl) group, 5-carboxyl-2- (1,3-benzodioxolanyl) group,
4-hydroxyl-2- (1,3-benzodioxolanyl) group, 5-hydroxyl-2- (1,3-benzodioxolanyl) group,
4-methyl-2- (1,3-benzodioxolanyl) group, 5-methyl-2- (1,3-benzodioxolanyl) group,
4-trifluoromethyl-2- (1,3-benzodioxolanyl) group, 5-trifluoromethyl-2- (1,3-benzodioxolanyl) group,
4-methoxy-2- (1,3-benzodioxolanyl) group, 5-methoxy-2- (1,3-benzodioxolanyl) group,
4-trifluoromethoxy-2- (1,3-benzodioxolanyl) group, 5-trifluoromethoxy-2- (1,3-benzodioxolanyl) group,
4-methoxycarbonyl-2- (1,3-benzodioxolanyl) group, 5-methoxycarbonyl-2- (1,3-benzodioxolanyl) group,
4-vinyl-2- (1,3-benzodioxolanyl) group, 5-vinyl-2- (1,3-benzodioxolanyl) group,
4-ethynyl-2- (1,3-benzodioxolanyl) group, 5-ethynyl-2- (1,3-benzodioxolanyl) group,
4-fluoro-2- (1,3-benzodioxolanyl) group, 5-fluoro-2- (1,3-benzodioxolanyl) group, 4,5,6,7-tetrafluoro-2- ( 1,3-benzodioxolanyl) group,
4-chloro-2- (1,3-benzodioxolanyl) group, 5-chloro-2- (1,3-benzodioxolanyl) group,
"2- (1,3-benzodioxolanyl) group optionally having one or more atoms or groups selected from group B";
A 4- (1,3-benzodioxolanyl) group,
4- (1,3-benzodioxolanyl) group, 5-cyano-4- (1,3-benzodioxolanyl) group, 6-cyano-4- (1,3-benzodioxolanyl) group, A 7-cyano-4- (1,3-benzodioxolanyl) group,
5-nitro-4- (1,3-benzodioxolanyl) group, 6-nitro-4- (1,3-benzodioxolanyl) group, 7-nitro-4- (1,3-benzodioxolanyl) group Nyl) group,
5-carboxyl-4- (1,3-benzodioxolanyl) group, 6-carboxyl-4- (1,3-benzodioxolanyl) group, 7-carboxyl-4- (1,3-benzodioxolanyl) group Nyl) group,
5-hydroxyl-4- (1,3-benzodioxolanyl) group, 6-hydroxyl-4- (1,3-benzodioxolanyl) group, 7-hydroxyl-4- (1,3-benzodioxolanyl) group Nyl) group,
5-methyl-4- (1,3-benzodioxolanyl) group, 6-methyl-4- (1,3-benzodioxolanyl) group, 7-methyl-4- (1,3-benzodioxolan) Nyl) group,
5-trifluoromethyl-4- (1,3-benzodioxolanyl) group, 6-trifluoromethyl-4- (1,3-benzodioxolanyl) group, 7-trifluoromethyl-4- (1 , 3-benzodioxolanyl) group,
5-methoxy-4- (1,3-benzodioxolanyl) group, 6-methoxy-4- (1,3-benzodioxolanyl) group, 7-methoxy-4- (1,3-benzodioxolan) Nyl) group,
5-trifluoromethoxy-4- (1,3-benzodioxolanyl) group, 6-trifluoromethoxy-4- (1,3-benzodioxolanyl) group, 7-trifluoromethoxy-4- (1 , 3-benzodioxolanyl) group,
5-methoxycarbonyl-4- (1,3-benzodioxolanyl) group, 6-methoxycarbonyl-4- (1,3-benzodioxolanyl) group, 7-methoxycarbonyl-4- (1,3- Benzodioxolanyl) group,
5-vinyl-4- (1,3-benzodioxolanyl) group, 6-vinyl-4- (1,3-benzodioxolanyl) group, 7-vinyl-4- (1,3-benzodioxolanyl) group Nyl) group,
5-ethynyl-4- (1,3-benzodioxolanyl) group, 6-ethynyl-4- (1,3-benzodioxolanyl) group, 7-ethynyl-4- (1,3-benzodioxolan) Nyl) group,
5-fluoro-4- (1,3-benzodioxolanyl) group, 6-fluoro-4- (1,3-benzodioxolanyl) group, 7-fluoro-4- (1,3-benzodioxolanyl) group Nyl) group, 4,5,6,7-tetrafluoro-4- (1,3-benzodioxolanyl) group,
4-chloro-4- (1,3-benzodioxolanyl) group, 5-chloro-4- (1,3-benzodioxolanyl) group, 6-chloro-4- (1,3-benzodioxolanyl) group Nyl) group, 7-chloro-4- (1,3-benzodioxolanyl) group, 4- (2,2-difluoro-1,3-benzodioxolanyl) group, etc. A 4- (1,3-benzodioxolanyl) group optionally having one or more atoms or groups ";
A 5- (1,3-benzodioxolanyl) group,
5- (1,3-benzodioxolanyl) group, 4-cyano-5- (1,3-benzodioxolanyl) group, 6-cyano-5- (1,3-benzodioxolanyl) group, A 7-cyano-5- (1,3-benzodioxolanyl) group,
4-nitro-5- (1,3-benzodioxolanyl) group, 6-nitro-5- (1,3-benzodioxolanyl) group, 7-nitro-5- (1,3-benzodioxolanyl) group Nyl) group,
4-carboxyl-5- (1,3-benzodioxolanyl) group, 6-carboxyl-5- (1,3-benzodioxolanyl) group, 7-carboxyl-5- (1,3-benzodioxolanyl) group Nyl) group,
4-hydroxyl-5- (1,3-benzodioxolanyl) group, 6-hydroxyl-5- (1,3-benzodioxolanyl) group, 7-hydroxyl-5- (1,3-benzodioxolanyl) group Nyl) group,
4-methyl-5- (1,3-benzodioxolanyl) group, 6-methyl-5- (1,3-benzodioxolanyl) group, 7-methyl-5- (1,3-benzodioxolanyl) group Nyl) group,
4-trifluoromethyl-5- (1,3-benzodioxolanyl) group, 6-trifluoromethyl-5- (1,3-benzodioxolanyl) group, 7-trifluoromethyl-5- (1 , 3-benzodioxolanyl) group,
4-methoxy-5- (1,3-benzodioxolanyl) group, 6-methoxy-5- (1,3-benzodioxolanyl) group, 7-methoxy-5- (1,3-benzodioxolanyl) group Nyl) group,
4-trifluoromethoxy-5- (1,3-benzodioxolanyl) group, 6-trifluoromethoxy-5- (1,3-benzodioxolanyl) group, 7-trifluoromethoxy-5- (1 , 3-benzodioxolanyl) group,
4-methoxycarbonyl-5- (1,3-benzodioxolanyl) group, 6-methoxycarbonyl-5- (1,3-benzodioxolanyl) group, 7-methoxycarbonyl-4- (1,3- Benzodioxolanyl) group,
4-vinyl-5- (1,3-benzodioxolanyl) group, 6-vinyl-5- (1,3-benzodioxolanyl) group, 7-vinyl-5- (1,3-benzodioxolanyl) group Nyl) group,
4-ethynyl-5- (1,3-benzodioxolanyl) group, 6-ethynyl-5- (1,3-benzodioxolanyl) group, 7-ethynyl-5- (1,3-benzodioxolan) Nyl) group,
4-fluoro-5- (1,3-benzodioxolanyl) group, 6-fluoro-5- (1,3-benzodioxolanyl) group, 7-fluoro-5- (1,3-benzodioxolanyl) group Nyl) group, 4,5,6,7-tetrafluoro-5- (1,3-benzodioxolanyl) group,
4-chloro-5- (1,3-benzodioxolanyl) group, 6-chloro-5- (1,3-benzodioxolanyl) group, 7-chloro-5- (1,3-benzodioxolanyl) group Nyl) group, 5- (2,2-difluoro-1,3-benzodioxolanyl) group and the like “may have one or more atoms or groups selected from group B 5- (1 , 3-benzodioxolyl) group ";
Is mentioned.

In the present invention, examples of the “1,4-benzodioxanyl group optionally having one or more atoms or groups selected from group B” include 2- (1,4-benzodioxanyl). ) Group,
5-cyano-2- (1,4-benzodioxanyl) group, 6-cyano-2- (1,4-benzodioxanyl) group,
5-nitro-2- (1,4-benzodioxanyl) group, 6-nitro-2- (1,4-benzodioxanyl) group,
5-carboxyl-2- (1,4-benzodioxanyl) group, 6-carboxyl-2- (1,4-benzodioxanyl) group,
5-hydroxyl-2- (1,4-benzodioxanyl) group, 6-hydroxyl-2- (1,4-benzodioxanyl) group,
5-methyl-2- (1,4-benzodioxanyl) group, 6-methyl-2- (1,4-benzodioxanyl) group,
5-trifluoromethyl-2- (1,4-benzodioxanyl) group, 6-trifluoromethyl-2- (1,4-benzodioxanyl) group,
5-methoxy-2- (1,4-benzodioxanyl) group, 6-methoxy-2- (1,4-benzodioxanyl) group,
5-trifluoromethoxy-2- (1,4-benzodioxanyl) group, 6-trifluoromethoxy-2- (1,4-benzodioxanyl) group,
5-methoxycarbonyl-2- (1,4-benzodioxanyl) group, 6-methoxycarbonyl-2- (1,4-benzodioxanyl) group,
5-vinyl-2- (1,4-benzodioxanyl) group, 6-vinyl-2- (1,4-benzodioxanyl) group,
5-ethynyl-2- (1,4-benzodioxanyl) group, 6-ethynyl-2- (1,4-benzodioxanyl) group,
5-fluoro-2- (1,4-benzodioxanyl) group, 6-fluoro-2- (1,4-benzodioxanyl) group, 4,5,6,7-tetrafluoro-2- ( 1,4-benzodioxanyl) group,
5-chloro-2- (1,4-benzodioxanyl) group, 6-chloro-2- (1,4-benzodioxanyl) group,
"2- (1,4-benzodioxanyl) group optionally having one or more atoms or groups selected from group B";
5- (1,4-benzodioxanyl) group, 4-cyano-5- (1,4-benzodioxanyl) group, 6-cyano-5- (1,4-benzodioxanyl) group, A 7-cyano-5- (1,4-benzodioxanyl) group,
4-nitro-5- (1,4-benzodioxanyl) group, 6-nitro-5- (1,4-benzodioxanyl) group, 7-nitro-5- (1,4-benzodioxan) Nyl) group,
4-carboxyl-5- (1,4-benzodioxanyl) group, 6-carboxyl-5- (1,4-benzodioxanyl) group, 7-carboxyl-5- (1,4-benzodioxa) Nyl) group,
4-hydroxyl-5- (1,4-benzodioxanyl) group, 6-hydroxyl-5- (1,4-benzodioxanyl) group, 7-hydroxyl-5- (1,4-benzodioxan) group Nyl) group,
4-methyl-5- (1,4-benzodioxanyl) group, 6-methyl-5- (1,4-benzodioxanyl) group, 7-methyl-5- (1,4-benzodioxa) Nyl) group,
4-trifluoromethyl-5- (1,4-benzodioxanyl) group, 6-trifluoromethyl-5- (1,4-benzodioxanyl) group, 7-trifluoromethyl-5- (1 , 4-benzodioxanyl) group,
4-methoxy-5- (1,4-benzodioxanyl) group, 6-methoxy-5- (1,4-benzodioxanyl) group, 7-methoxy-5- (1,4-benzodioxa) Nyl) group,
4-trifluoromethoxy-5- (1,4-benzodioxanyl) group, 6-trifluoromethoxy-5- (1,4-benzodioxanyl) group, 7-trifluoromethoxy-5- (1 , 4-benzodioxanyl) group,
4-methoxycarbonyl-5- (1,4-benzodioxanyl) group, 6-methoxycarbonyl-5- (1,4-benzodioxanyl) group, 7-methoxycarbonyl-4- (1,4- Benzodioxanyl) group,
4-vinyl-5- (1,4-benzodioxanyl) group, 6-vinyl-5- (1,4-benzodioxanyl) group, 7-vinyl-5- (1,4-benzodioxan) Nyl) group,
4-ethynyl-5- (1,4-benzodioxanyl) group, 6-ethynyl-5- (1,4-benzodioxanyl) group, 7-ethynyl-5- (1,4-benzodioxa) Nyl) group,
4-fluoro-5- (1,4-benzodioxanyl) group, 6-fluoro-5- (1,4-benzodioxanyl) group, 7-fluoro-5- (1,4-benzodioxan) group Nyl) group, 4,5,6,7-tetrafluoro-5- (1,4-benzodioxanyl) group,
4-chloro-5- (1,4-benzodioxanyl) group, 6-chloro-5- (1,4-benzodioxanyl) group, 7-chloro-5- (1,4-benzodioxa) group Nyl) group, such as “5- (1,4-benzodioxanyl) group optionally having one or more atoms or groups selected from group B”;
Is mentioned.

In the present invention, “a C1-C8 chain hydrocarbon group which may have one or more atoms or groups selected from group F” and “one or more atoms or groups selected from group G” Examples of the “C1-C8 chain hydrocarbon group” in “C1-C8 chain hydrocarbon group” may include, for example, methyl group, ethyl group, isopropyl group, tert-butyl group, propyl group, sec-butyl group, isobutyl. Group, 1,1-dimethylpropyl group, 2,2-dimethylpropyl group, 1,2-dimethylpropyl group, 1-ethylpropyl group, butyl group, 1-methylbutyl group, 2-methylbutyl group, 3-methylbutyl group, 1,1-dimethylbutyl group, 2,2-dimethylbutyl group, 3,3-dimethylbutyl group, 1,2,3-trimethylbutyl group, 1-ethylbutyl group, 2-ethylbutyl group, pliers Group, 1-methylpentyl group, 2-methylpentyl group, 3-methylpentyl group, 4-methylpentyl group, 1,1-dimethylpentyl group, 2,2-dimethylpentyl group, 3,3-dimethylpentyl group 4,4-dimethylpentyl group, 1-ethylpentyl group, 2-ethylpentyl group, 3-ethylpentyl group, 1-propylpentyl group, 2-propylpentyl group, hexyl group, 1-methylhexyl group, 2- Methylhexyl group, 3-methylhexyl group, 4-methylhexyl group, 5-methylhexyl group, 1,1-dimethylhexyl group, 2,2-dimethylhexyl group, 3,3-dimethylhexyl group, 4,4- Dimethylhexyl group, 5,5-dimethylhexyl group, 1-ethylhexyl group, 2-ethylhexyl group, 3-ethylhexyl group, 4-ethylhexyl C1-C8 alkyl such as heptyl group, 1-methylheptyl group, 2-methylheptyl group, 3-methylheptyl group, 4-methylheptyl group, 5-methylheptyl group, 6-methylheptyl group, octyl group, etc. Group ";

Vinyl group, 1-propenyl group, 2-propenyl group, 1-methyl-1-propenyl group, 1-methyl-2-propenyl group, 1,2-dimethyl-1-propenyl group, 1,1-dimethyl-2- Propenyl group, 1-ethyl-1-propenyl group, 1-ethyl-2-propenyl group, 1-butenyl group, 2-butenyl group, 3-butenyl group, 1-methyl-1-butenyl group, 2-methyl-1 -Butenyl group, 2-methyl-2-butenyl group, 2-methyl-3-butenyl group, 3-methyl-3-butenyl group, 1,1-dimethyl-3-butenyl group, 1,1-dimethyl-2- Butenyl group, 1-ethyl-1-butenyl group, 1-ethyl-2-butenyl group, 1-ethyl-3-butenyl group, 1-pentenyl group, 2-pentenyl group, 3-pentenyl group, 4-pentenyl group, 1-methyl-1- Nthenyl group, 1-methyl-2-pentenyl group, 1-methyl-3-pentenyl group, 1-methyl-4-pentenyl group, 2-methyl-1-pentenyl group, 2-methyl-2-pentenyl group, 3- Methyl-2-pentenyl group, 3-methyl-3-pentenyl group, 4-methyl-3-pentenyl group, 4-methyl-4-pentenyl group, 1,1-dimethyl-2-pentenyl group, 1,1-dimethyl -3-pentenyl group, 1,1-dimethyl-4-pentenyl group, 1-ethyl-1-pentenyl group, 1-ethyl-2-pentenyl group, 1-ethyl-3-pentenyl group, 1-ethyl-4- A pentenyl group,
1-hexenyl group, 2-hexenyl group, 3-hexenyl group, 4-hexenyl group, 5-hexenyl group, 1-methyl-1-hexenyl group, 1-methyl-2-hexenyl group, 1-methyl-3-hexenyl Group, 1-methyl-4-hexenyl group, 1-methyl-5-hexenyl group, 2-methyl-1-hexenyl group, 2-methyl-2-hexenyl group, 3-methyl-2-hexenyl group, 3-methyl -3-hexenyl group, 4-methyl-3-hexenyl group, 4-methyl-4-hexenyl group, 5-methyl-4-hexenyl group, 5-methyl-5-hexenyl group, 1,1-dimethyl-2- Hexenyl group, 1,1-dimethyl-3-hexenyl group, 1,1-dimethyl-4-hexenyl group, 1,1-dimethyl-5-hexenyl group, 1-ethyl-1-hexenyl group, 1-ethyl- - hexenyl group, 1-ethyl-3-hexenyl group, 1-ethyl-4-hexenyl group, 1-ethyl-5-hexenyl group,
1-heptenyl group, 2-heptenyl group, 3-heptenyl group, 4-heptenyl group, 5-heptenyl group, 6-heptenyl group, 1-methyl-1-heptenyl group, 1-methyl-2-heptenyl group, 1- Methyl-3-heptenyl group, 1-methyl-4-heptenyl group, 1-methyl-5-heptenyl group, 1-methyl-6-heptenyl group, 2-methyl-1-heptenyl group, 2-methyl-2-heptenyl group Group, 3-methyl-2-heptenyl group, 3-methyl-3-heptenyl group, 4-methyl-3-heptenyl group, 4-methyl-4-heptenyl group, 5-methyl-4-heptenyl group, 5-methyl -5-heptenyl group, 6-methyl-5-heptenyl group, 6-methyl-6-heptenyl group,
1-octenyl group, 2-octenyl group, 3-octenyl group, 4-octenyl group, 5-octenyl group, 6-octenyl group, 7-octenyl group,
A "C2-C8 alkenyl group" such as;

Ethynyl group, 1-propynyl group, 2-propynyl group, 1-methyl-2-propynyl group, 1,1-dimethyl-2-propynyl group, 1-ethyl-2-propynyl group, 1-butynyl group, 2-butynyl Group, 3-butynyl group, 1-methyl-2-butynyl group, 1-methyl-3-butynyl group, 1,1-dimethyl-2-butynyl group, 1,1-dimethyl-3-butynyl group, 1-ethyl 2-butynyl group, 1-ethyl-3-butynyl group, 1-pentynyl group, 2-pentynyl group, 3-pentynyl group, 4-pentynyl group, 1-methyl-2-pentynyl group, 1-methyl-3- Pentynyl group, 1-methyl-4-pentynyl group, 1,1-dimethyl-2-pentynyl group, 1,1-dimethyl-3-pentynyl group, 1,1-dimethyl-4-pentynyl group, 1-ethyl-2 -Pentini Group, 1-ethyl-3-pentynyl group, 1-ethyl-4-pentynyl group, 1-hexynyl group, 2-hexynyl group, 3-hexynyl group, 4-hexynyl group, 5-hexynyl group, 1-methyl-2 -Hexynyl group, 1-methyl-3-hexynyl group, 1-methyl-4-hexynyl group, 1-methyl-5-hexynyl group, 1,1-dimethyl-2-hexynyl group, 1,1-dimethyl-3- Hexynyl group, 1,1-dimethyl-4-hexynyl group, 1,1-dimethyl-5-hexynyl group, 1-ethyl-2-hexynyl group, 1-ethyl-3-hexynyl group, 1-ethyl-4-hexynyl Group, 1-ethyl-5-hexynyl group, 1-heptynyl group, 2-heptynyl group, 3-heptynyl group, 4-heptynyl group, 5-heptynyl group, 6-heptynyl group, 1-methyl-2-heptyl group Tinyl group, 1-methyl-3-heptynyl group, 1-methyl-4-heptynyl group, 1-methyl-5-heptynyl group, 1-methyl-6-heptynyl group, 1-octynyl group, 2-octynyl group, 3 -Octynyl group, 4-octynyl group, 5-octynyl group, 6-octynyl group, 7-octynyl group,
A “C 2 -C 8 alkynyl group”;
Is mentioned.

In the present invention, examples of the “C3-C8 chain hydrocarbon group” in the “C3-C8 chain hydrocarbon group” include isopropyl group, tert-butyl group, propyl group, sec-butyl group, isobutyl group, 1 , 1-dimethylpropyl group, 2,2-dimethylpropyl group, 1,2-dimethylpropyl group, 1-ethylpropyl group, butyl group, 1-methylbutyl group, 2-methylbutyl group, 3-methylbutyl group, 1,1 -Dimethylbutyl group, 2,2-dimethylbutyl group, 3,3-dimethylbutyl group, 1,2,3-trimethylbutyl group, 1-ethylbutyl group, 2-ethylbutyl group, pentyl group, 1-methylpentyl group, 2-methylpentyl group, 3-methylpentyl group, 4-methylpentyl group, 1,1-dimethylpentyl group, 2,2-dimethylpentyl group, 3,3 Dimethylpentyl group, 4,4-dimethylpentyl group, 1-ethylpentyl group, 2-ethylpentyl group, 3-ethylpentyl group, 1-propylpentyl group, 2-propylpentyl group, hexyl group, 1-methylhexyl group 2-methylhexyl group, 3-methylhexyl group, 4-methylhexyl group, 5-methylhexyl group, 1,1-dimethylhexyl group, 2,2-dimethylhexyl group, 3,3-dimethylhexyl group, 4 , 4-dimethylhexyl group, 5,5-dimethylhexyl group, 1-ethylhexyl group, 2-ethylhexyl group, 3-ethylhexyl group, 4-ethylhexyl group, heptyl group, 1-methylheptyl group, 2-methylheptyl group, 3-methylheptyl group, 4-methylheptyl group, 5-methylheptyl group, 6-methylheptyl group, octyl Etc., "C3-C8 alkyl group";

1-propenyl group, 2-propenyl group, 1-methyl-1-propenyl group, 1-methyl-2-propenyl group, 1,2-dimethyl-1-propenyl group, 1,1-dimethyl-2-propenyl group, 1-ethyl-1-propenyl group, 1-ethyl-2-propenyl group, 1-butenyl group, 2-butenyl group, 3-butenyl group, 1-methyl-1-butenyl group, 2-methyl-1-butenyl group 2-methyl-2-butenyl group, 2-methyl-3-butenyl group, 3-methyl-3-butenyl group, 1,1-dimethyl-3-butenyl group, 1,1-dimethyl-2-butenyl group, 1-ethyl-1-butenyl group, 1-ethyl-2-butenyl group, 1-ethyl-3-butenyl group, 1-pentenyl group, 2-pentenyl group, 3-pentenyl group, 4-pentenyl group, 1-methyl -1-pentenyl 1-methyl-2-pentenyl group, 1-methyl-3-pentenyl group, 1-methyl-4-pentenyl group, 2-methyl-1-pentenyl group, 2-methyl-2-pentenyl group, 3-methyl- 2-pentenyl group, 3-methyl-3-pentenyl group, 4-methyl-3-pentenyl group, 4-methyl-4-pentenyl group, 1,1-dimethyl-2-pentenyl group, 1,1-dimethyl-3 -Pentenyl group, 1,1-dimethyl-4-pentenyl group, 1-ethyl-1-pentenyl group, 1-ethyl-2-pentenyl group, 1-ethyl-3-pentenyl group, 1-ethyl-4-pentenyl group ,
1-hexenyl group, 2-hexenyl group, 3-hexenyl group, 4-hexenyl group, 5-hexenyl group, 1-methyl-1-hexenyl group, 1-methyl-2-hexenyl group, 1-methyl-3-hexenyl Group, 1-methyl-4-hexenyl group, 1-methyl-5-hexenyl group, 2-methyl-1-hexenyl group, 2-methyl-2-hexenyl group, 3-methyl-2-hexenyl group, 3-methyl -3-hexenyl group, 4-methyl-3-hexenyl group, 4-methyl-4-hexenyl group, 5-methyl-4-hexenyl group, 5-methyl-5-hexenyl group, 1,1-dimethyl-2- Hexenyl group, 1,1-dimethyl-3-hexenyl group, 1,1-dimethyl-4-hexenyl group, 1,1-dimethyl-5-hexenyl group, 1-ethyl-1-hexenyl group, 1-ethyl- - hexenyl group, 1-ethyl-3-hexenyl group, 1-ethyl-4-hexenyl group, 1-ethyl-5-hexenyl group,
1-heptenyl group, 2-heptenyl group, 3-heptenyl group, 4-heptenyl group, 5-heptenyl group, 6-heptenyl group, 1-methyl-1-heptenyl group, 1-methyl-2-heptenyl group, 1- Methyl-3-heptenyl group, 1-methyl-4-heptenyl group, 1-methyl-5-heptenyl group, 1-methyl-6-heptenyl group, 2-methyl-1-heptenyl group, 2-methyl-2-heptenyl group Group, 3-methyl-2-heptenyl group, 3-methyl-3-heptenyl group, 4-methyl-3-heptenyl group, 4-methyl-4-heptenyl group, 5-methyl-4-heptenyl group, 5-methyl -5-heptenyl group, 6-methyl-5-heptenyl group, 6-methyl-6-heptenyl group,
1-octenyl group, 2-octenyl group, 3-octenyl group, 4-octenyl group, 5-octenyl group, 6-octenyl group, 7-octenyl group,
A “C3-C8 alkenyl group” such as;

1-propynyl group, 2-propynyl group, 1-methyl-2-propynyl group, 1,1-dimethyl-2-propynyl group, 1-ethyl-2-propynyl group, 1-butynyl group, 2-butynyl group, 3 -Butynyl group, 1-methyl-2-butynyl group, 1-methyl-3-butynyl group, 1,1-dimethyl-2-butynyl group, 1,1-dimethyl-3-butynyl group, 1-ethyl-2- Butynyl group, 1-ethyl-3-butynyl group, 1-pentynyl group, 2-pentynyl group, 3-pentynyl group, 4-pentynyl group, 1-methyl-2-pentynyl group, 1-methyl-3-pentynyl group, 1-methyl-4-pentynyl group, 1,1-dimethyl-2-pentynyl group, 1,1-dimethyl-3-pentynyl group, 1,1-dimethyl-4-pentynyl group, 1-ethyl-2-pentynyl group , 1-D Ru-3-pentynyl group, 1-ethyl-4-pentynyl group, 1-hexynyl group, 2-hexynyl group, 3-hexynyl group, 4-hexynyl group, 5-hexynyl group, 1-methyl-2-hexynyl group, 1-methyl-3-hexynyl group, 1-methyl-4-hexynyl group, 1-methyl-5-hexynyl group, 1,1-dimethyl-2-hexynyl group, 1,1-dimethyl-3-hexynyl group, 1 , 1-dimethyl-4-hexynyl group, 1,1-dimethyl-5-hexynyl group, 1-ethyl-2-hexynyl group, 1-ethyl-3-hexynyl group, 1-ethyl-4-hexynyl group, 1- Ethyl-5-hexynyl group, 1-heptynyl group, 2-heptynyl group, 3-heptynyl group, 4-heptynyl group, 5-heptynyl group, 6-heptynyl group, 1-methyl-2-heptynyl group, -Methyl-3-heptynyl group, 1-methyl-4-heptynyl group, 1-methyl-5-heptynyl group, 1-methyl-6-heptynyl group, 1-octynyl group, 2-octynyl group, 3-octynyl group, 4-octynyl group, 5-octynyl group, 6-octynyl group, 7-octynyl group,
A “C3-C8 alkynyl group”, and the like;
Is mentioned.

In the present invention, the “C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group F” includes, for example,
Benzyl group, phenyldifluoromethyl group, 1-phenylethyl group, 1,1-difluoro-1-phenylethyl group, 2,2,2-trifluoro-1-phenylethyl group, 1,1,2,2,2 -Pentafluoro-1-phenylethyl group, 2-phenylethyl group, 1,1-difluoro-2-phenylethyl group, 2,2-difluoro-2-phenylethyl group, 1,1,2,2-tetrafluoro 2-phenylethyl group, 3-phenylpropyl group, 1,1-difluoro-3-phenylpropyl group, 2,2-difluoro-3-phenylpropyl group, 3,3-difluoro-3-phenylpropyl group, 1 1,2,2,3,3-hexafluoro-3-phenylpropyl group, 4-phenylbutyl group, 1,1-difluoro-4-phenylbutyl group, 2,2-diph Oro-4-phenylbutyl group, 3,3-difluoro-4-phenylbutyl group, 4,4-difluoro-4-phenylbutyl group, 1,1,2,2,3,3,4,4-octafluoro -3-4-phenylbutyl group, 5-phenylpentyl group, 1,1-difluoro-5-phenylpentyl group, 2,2-difluoro-5-phenylpentyl group, 3,3-difluoro-5-phenylpentyl group 4,4-difluoro-5-phenylpentyl group, 5,5-difluoro-5-phenylpentyl group, 6-phenylhexyl group, 1,1-difluoro-6-phenylhexyl group, 2,2-difluoro-6 -Phenylhexyl group, 3,3-difluoro-6-phenylhexyl group, 4,4-difluoro-6-phenylhexyl group, 5,5-difluoro-6-phenylhexyl group Sil group, 6,6-difluoro-6-phenylhexyl group, 7-phenylheptyl group, 1,1-difluoro-7-phenylheptyl group, 2,2-difluoro-7-phenylheptyl group, 3,3-difluoro -7-phenylheptyl group, 4,4-difluoro-7-phenylheptyl group, 5,5-difluoro-7-phenylheptyl group, 6,6-difluoro-7-phenylheptyl group, 7,7-difluoro-7 -Phenylheptyl group, 8-phenyloctyl group, 1,1-difluoro-8-phenyloctyl group, 2,2-difluoro-8-phenyloctyl group, 3,3-difluoro-8-phenyloctyl group, 4,4 -Difluoro-8-phenyloctyl group, 5,5-difluoro-8-phenyloctyl group, 6,6-difluoro-8-phenyloctyl group Group, 7,7-difluoro-8-phenyloctyl group, 8,8-difluoro-8-phenyloctyl group,

4-cyanobenzyl group, 4-nitrobenzyl group, 4-carboxylbenzyl group, 4-hydroxylbenzyl group, 4- (N-methylcarboamido) benzyl group, 4- (N, N-dimethylcarboamido) benzyl group, 4-methylbenzyl group, 4-trifluoromethylbenzyl group, 4-methoxybenzyl group, 4-trifluoromethoxybenzyl group, 4-methylthiobenzyl group, 4-methylsulfinylbenzyl group, 4-methylsulfonylbenzyl group, 4- Methoxycarbonylbenzyl group, 4-vinylbenzyl group, 4- (2 ′, 2′-difluorovinyl) benzyl group, 4-ethynylbenzyl group, 4- (2′-fluoroethynyl) benzyl group, 4-fluorobenzyl group, 4-chlorobenzyl group, 3,4-dichlorobenzyl group,
(4′-cyanophenyl) difluoromethyl group, (4′-nitrophenyl) difluoromethyl group, (4′-carboxylphenyl) difluoromethyl group, (4′-hydroxylphenyl) difluoromethyl group, (4 ′-(N -Methylcarboamido) phenyl) difluoromethyl group, (4 '-(N, N-dimethylcarboamido) phenyl) difluoromethyl group, (4'-methylphenyl) difluoromethyl group, (4'-trifluoromethylphenyl) Difluoromethyl group, (4′-methoxyphenyl) difluoromethyl group, (4′-trifluoromethoxyphenyl) difluoromethyl group, (4′-methylthiophenyl) difluoromethyl group, (4′-methylsulfinylphenyl) difluoromethyl group , (4′-methylsulfonylphenyl) difluoromethyl group, (4′-methoxycarbonylphenyl) difluoromethyl group, (4′-vinylphenyl) difluoromethyl group, (4 ′-(2 ′, 2′-difluorovinyl) phenyl) difluoromethyl group, (4′-ethynylphenyl) Difluoromethyl group, (4 ′-(2′-fluoroethynyl) phenyl) difluoromethyl group, (4′-fluorophenyl) difluoromethyl group, (4′-chlorophenyl) difluoromethyl group, 3, (4′-dichlorophenyl) Difluoromethyl group,

1-naphthylmethyl group, (1′-naphthyl) difluoromethyl group, 1- (1′-naphthyl) ethyl group, 1,1-difluoro-1- (1′-naphthyl) ethyl group, 2,2,2- Trifluoro-1- (1′-naphthyl) ethyl group, 1,1,2,2,2-pentafluoro-1- (1′-naphthyl) ethyl group, 2- (1′-naphthyl) ethyl group, 1 , 1-Difluoro-2- (1′-naphthyl) ethyl group, 2,2-difluoro-2- (1′-naphthyl) ethyl group, 1,1,2,2-tetrafluoro-2- (1′- Naphthyl) ethyl group, 3- (1′-naphthyl) propyl group, 1,1-difluoro-3- (1′-naphthyl) propyl group, 2,2-difluoro-3- (1′-naphthyl) propyl group, 3,3-difluoro-3- (1′-naphthyl) propyl group, , 1,2,2,3,3-hexafluoro-3- (1′-naphthyl) propyl group, 4- (1′-naphthyl) butyl group, 1,1-difluoro-4- (1′-naphthyl) Butyl group, 2,2-difluoro-4- (1′-naphthyl) butyl group, 3,3-difluoro-4- (1′-naphthyl) butyl group, 4,4-difluoro-4- (1′-naphthyl) ) Butyl group, 1,1,2,2,3,3,4,4-octafluoro-3--4- (1′-naphthyl) butyl group, 5- (1′-naphthyl) pentyl group, 1,1 -Difluoro-5- (1'-naphthyl) pentyl group, 2,2-difluoro-5- (1'-naphthyl) pentyl group, 3,3-difluoro-5- (1'-naphthyl) pentyl group, 4, 4-difluoro-5- (1′-naphthyl) pentyl group, 5,5-difluoro 5- (1′-naphthyl) pentyl group, 6- (1′-naphthyl) hexyl group, 1,1-difluoro-6- (1′-naphthyl) hexyl group, 2,2-difluoro-6- (1 ′ -Naphthyl) hexyl group, 3,3-difluoro-6- (1'-naphthyl) hexyl group, 4,4-difluoro-6- (1'-naphthyl) hexyl group, 5,5-difluoro-6- (1 '-Naphthyl) hexyl group, 6,6-difluoro-6- (1'-naphthyl) hexyl group, 7- (1'-naphthyl) heptyl group, 1,1-difluoro-7- (1'-naphthyl) heptyl Group, 2,2-difluoro-7- (1′-naphthyl) heptyl group, 3,3-difluoro-7- (1′-naphthyl) heptyl group, 4,4-difluoro-7- (1′-naphthyl) Heptyl group, 5,5-difluoro-7- (1′-naphthyl) heptyl group, 6,6-difluoro-7- (1′-naphthyl) heptyl group, 7,7-difluoro-7- (1′-naphthyl) heptyl group, 8- (1′-naphthyl) ) Octyl group, 1,1-difluoro-8- (1′-naphthyl) octyl group, 2,2-difluoro-8- (1′-naphthyl) octyl group, 3,3-difluoro-8- (1′-) Naphthyl) octyl group, 4,4-difluoro-8- (1′-naphthyl) octyl group, 5,5-difluoro-8- (1′-naphthyl) octyl group, 6,6-difluoro-8- (1 ′) -Naphthyl) octyl group, 7,7-difluoro-8- (1'-naphthyl) octyl group, 8,8-difluoro-8- (1'-naphthyl) octyl group,

6-cyano-1-naphthylmethyl group, 6-nitro-1-naphthylmethyl group, 6-carboxyl-1-naphthylmethyl group, 6-hydroxyl-1-naphthylmethyl group, 6- (N-methylcarboamido)- 1-naphthylmethyl group, 6- (N, N-dimethylcarboamido) -1-naphthylmethyl group, 6-methyl-1-naphthylmethyl group, 6-trifluoromethyl-1-naphthylmethyl group, 6-methoxy- 1-naphthylmethyl group, 6-trifluoromethoxy-1-naphthylmethyl group, 6-methylthio-1-naphthylmethyl group, 6-methylsulfinyl-1-naphthylmethyl group, 6-methylsulfonyl-1-naphthylmethyl group, 6-methoxycarbonyl-1-naphthylmethyl group, 6-vinyl-1-naphthylmethyl group, 6- (2 ′, 2′-difluorovinyl -1-naphthylmethyl group, 6-ethynyl-1-naphthylmethyl group, 6- (2′-fluoroethynyl) -1-naphthylmethyl group, 6-fluoro-1-naphthylmethyl group, 6-chloro-1-naphthyl Methyl group,
(6′-cyano-1-naphthyl) -difluoromethyl group, (6′-nitro-1-naphthyl) -difluoromethyl group, (6′-carboxyl-1-naphthyl) -difluoromethyl group, (6′-hydroxyl) -1-naphthyl) -difluoromethyl group, (6 ′-(N-methylcarboamido) -1-naphthyl) -difluoromethyl group, (6 ′-(N, N-dimethylcarboamido) -1-naphthyl)- Difluoromethyl group, (6′-methyl-1-naphthyl) -difluoromethyl group, (6′-trifluoromethyl-1-naphthyl) -difluoromethyl group, (6′-methoxy-1-naphthyl) -difluoromethyl group , (6′-trifluoromethoxy-1-naphthyl) -difluoromethyl group, (6′-methylthio-1-naphthyl) -difluoromethyl group, (6′-methylsulfuric acid) Nyl-1-naphthyl) -difluoromethyl group, (6′-methylsulfonyl-1-naphthyl) -difluoromethyl group, (6′-methoxycarbonyl-1-naphthyl) -difluoromethyl group, (6′-vinyl-1) -Naphthyl) -difluoromethyl group, (6 '-(2', 2'-difluorovinyl) -1-naphthyl) -difluoromethyl group, (6'-ethynyl-1-naphthyl) -difluoromethyl group, (6 '-(2'-fluoroethynyl) -1-naphthyl) -difluoromethyl group, (6'-fluoro-1-naphthyl) -difluoromethyl group, (6'-chloro-1-naphthyl) -difluoromethyl group,

2-naphthylmethyl group, (2′-naphthyl) difluoromethyl group, 1- (2′-naphthyl) ethyl group, 1,1-difluoro-1- (2′-naphthyl) ethyl group, 2,2,2- Trifluoro-1- (2′-naphthyl) ethyl group, 1,1,2,2,2-pentafluoro-1- (2′-naphthyl) ethyl group, 2- (2′-naphthyl) ethyl group, 1 , 1-Difluoro-2- (2′-naphthyl) ethyl group, 2,2-difluoro-2- (2′-naphthyl) ethyl group, 1,1,2,2-tetrafluoro-2- (2′- Naphthyl) ethyl group, 3- (2′-naphthyl) propyl group, 1,1-difluoro-3- (2′-naphthyl) propyl group, 2,2-difluoro-3- (2′-naphthyl) propyl group, 3,3-difluoro-3- (2′-naphthyl) propyl group, 1,2,2,3,3-hexafluoro-3- (2'-naphthyl) propyl group, 4- (2'-naphthyl) butyl group, 1,1-difluoro-4- (2'-naphthyl) Butyl group, 2,2-difluoro-4- (2′-naphthyl) butyl group, 3,3-difluoro-4- (2′-naphthyl) butyl group, 4,4-difluoro-4- (2′-naphthyl) ) Butyl group, 1,1,2,2,3,3,4,4-octafluoro-3--4- (2′-naphthyl) butyl group, 5- (2′-naphthyl) pentyl group, 1,1 -Difluoro-5- (2'-naphthyl) pentyl group, 2,2-difluoro-5- (2'-naphthyl) pentyl group, 3,3-difluoro-5- (2'-naphthyl) pentyl group, 4, 4-difluoro-5- (2′-naphthyl) pentyl group, 5,5-difluoro 5- (2′-naphthyl) pentyl group, 6- (2′-naphthyl) hexyl group, 1,1-difluoro-6- (2′-naphthyl) hexyl group, 2,2-difluoro-6- (2 ′ -Naphthyl) hexyl group, 3,3-difluoro-6- (2'-naphthyl) hexyl group, 4,4-difluoro-6- (2'-naphthyl) hexyl group, 5,5-difluoro-6- (2 '-Naphthyl) hexyl group, 6,6-difluoro-6- (2'-naphthyl) hexyl group, 7- (2'-naphthyl) heptyl group, 1,1-difluoro-7- (2'-naphthyl) heptyl Group, 2,2-difluoro-7- (2′-naphthyl) heptyl group, 3,3-difluoro-7- (2′-naphthyl) heptyl group, 4,4-difluoro-7- (2′-naphthyl) Heptyl group, 5,5-difluoro-7- (2′-naphthyl) heptyl group, 6,6-difluoro-7- (2′-naphthyl) heptyl group, 7,7-difluoro-7- (2′-naphthyl) heptyl group, 8- (2′-naphthyl) ) Octyl group, 1,1-difluoro-8- (2′-naphthyl) octyl group, 2,2-difluoro-8- (2′-naphthyl) octyl group, 3,3-difluoro-8- (2′-) Naphthyl) octyl group, 4,4-difluoro-8- (2′-naphthyl) octyl group, 5,5-difluoro-8- (2′-naphthyl) octyl group, 6,6-difluoro-8- (2 ′) -Naphthyl) octyl group, 7,7-difluoro-8- (2'-naphthyl) octyl group, 8,8-difluoro-8- (2'-naphthyl) octyl group,

6-cyano-2-naphthylmethyl group, 6-nitro-2-naphthylmethyl group, 6-carboxyl-2-naphthylmethyl group, 6-hydroxyl-2-naphthylmethyl group, 6- (N-methylcarboamido)- 2-naphthylmethyl group, 6- (N, N-dimethylcarboamido) -2-naphthylmethyl group, 6-methyl-2-naphthylmethyl group, 6-trifluoromethyl-2-naphthylmethyl group, 6-methoxy- 2-naphthylmethyl group, 6-trifluoromethoxy-2-naphthylmethyl group, 6-methylthio-2-naphthylmethyl group, 6-methylsulfinyl-2-naphthylmethyl group, 6-methylsulfonyl-2-naphthylmethyl group, 6-methoxycarbonyl-2-naphthylmethyl group, 6-vinyl-2-naphthylmethyl group, 6- (2 ′, 2′-difluorovinyl 2-naphthylmethyl group, 6-ethynyl-2-naphthylmethyl group, 6- (2′-fluoroethynyl) -2-naphthylmethyl group, 6-fluoro-2-naphthylmethyl group, 6-chloro-2-naphthyl group Methyl group,
(6′-cyano-1-naphthyl) -difluoromethyl group, (6′-nitro-2-naphthyl) -difluoromethyl group, (6′-carboxyl-2-naphthyl) -difluoromethyl group, (6′-hydroxyl) -2-naphthyl) -difluoromethyl group, (6 ′-(N-methylcarboamido) -2-naphthyl) -difluoromethyl group, (6 ′-(N, N-dimethylcarboamido) -2-naphthyl)- Difluoromethyl group, (6′-methyl-2-naphthyl) -difluoromethyl group, (6′-trifluoromethyl-2-naphthyl) -difluoromethyl group, (6′-methoxy-2-naphthyl) -difluoromethyl group , (6′-trifluoromethoxy-2-naphthyl) -difluoromethyl group, (6′-methylthio-2-naphthyl) -difluoromethyl group, (6′-methylsulfuric acid) Nyl-2-naphthyl) -difluoromethyl group, (6′-methylsulfonyl-2-naphthyl) -difluoromethyl group, (6′-methoxycarbonyl-2-naphthyl) -difluoromethyl group, (6′-vinyl-2) -Naphthyl) -difluoromethyl group, (6 '-(2', 2'-difluorovinyl) -2-naphthyl) -difluoromethyl group, (6'-ethynyl-2-naphthyl) -difluoromethyl group, (6 '-(2'-fluoroethynyl) -2-naphthyl) -difluoromethyl group, (6'-fluoro-1-naphthyl) -difluoromethyl group, (6'-chloro-2-naphthyl) -difluoromethyl group,

2-pyridylmethyl group, 1- (2′-pyridyl) ethyl group, 2- (2′-pyridyl) ethyl group, 3- (2′-pyridyl) propyl group, 4- (2′-pyridyl) butyl group, 5- (2′-pyridyl) pentyl group, 6- (2′-pyridyl) hexyl group, 7- (2′-pyridyl) heptyl group, 8- (2′-pyridyl) octyl group,

4-cyano-2-pyridylmethyl group, 4-nitro-2-pyridylmethyl group, 4-carboxyl-2-pyridylmethyl group, 4-hydroxyl-2-pyridylmethyl group, 4- (N-methylcarboamido)- 2-pyridylmethyl group, 4- (N, N-dimethylcarboamido) -2-pyridylmethyl group, 4-methyl-2-pyridylmethyl group, 4-trifluoromethyl-2-pyridylmethyl group, 4-methoxy- 2-pyridylmethyl group, 4-trifluoromethoxy-2-pyridylmethyl group, 4-methylthio-2-pyridylmethyl group, 4-methylsulfinyl-2-pyridylmethyl group, 4-methylsulfonyl-2-pyridylmethyl group, 4-methoxycarbonyl-2-pyridylmethyl group, 4-vinyl-2-pyridylmethyl group, 4- (2 ′, 2′-difluorovini ) -2-pyridylmethyl group, 4-ethynyl-2-pyridylmethyl group, 4- (2′-fluoroethynyl) -2-pyridylmethyl group, 4-fluoro-2-pyridylmethyl group, 4-chloro-2- A pyridylmethyl group,

5-cyano-2-pyridylmethyl group, 5-nitro-2-pyridylmethyl group, 5-carboxyl-2-pyridylmethyl group, 5-hydroxyl-2-pyridylmethyl group, 5- (N-methylcarboamido)- 2-pyridylmethyl group, 5- (N, N-dimethylcarboamido) -2-pyridylmethyl group, 5-methyl-2-pyridylmethyl group, 5-trifluoromethyl-2-pyridylmethyl group, 5-methoxy- 2-pyridylmethyl group, 5-trifluoromethoxy-2-pyridylmethyl group, 5-methylthio-2-pyridylmethyl group, 5-methylsulfinyl-2-pyridylmethyl group, 5-methylsulfonyl-2-pyridylmethyl group, 5-methoxycarbonyl-2-pyridylmethyl group, 5-vinyl-2-pyridylmethyl group, 5- (2 ′, 2′-difluorovini ) -2-pyridylmethyl group, 5-ethynyl-2-pyridylmethyl group, 5- (2′-fluoroethynyl) -2-pyridylmethyl group, 5-fluoro-2-pyridylmethyl group, 5-chloro-2- A pyridylmethyl group,

6-cyano-2-pyridylmethyl group, 6-nitro-2-pyridylmethyl group, 6-carboxyl-2-pyridylmethyl group, 6-hydroxyl-2-pyridylmethyl group, 6- (N-methylcarboamido)- 2-pyridylmethyl group, 6- (N, N-dimethylcarboamido) -2-pyridylmethyl group, 6-methyl-2-pyridylmethyl group, 6-trifluoromethyl-2-pyridylmethyl group, 6-methoxy- 2-pyridylmethyl group, 6-trifluoromethoxy-2-pyridylmethyl group, 6-methylthio-2-pyridylmethyl group, 6-methylsulfinyl-2-pyridylmethyl group, 6-methylsulfonyl-2-pyridylmethyl group, 6-methoxycarbonyl-2-pyridylmethyl group, 6-vinyl-2-pyridylmethyl group, 6- (2 ′, 2′-difluorovini ) -2-pyridylmethyl group, 6-ethynyl-2-pyridylmethyl group, 6- (2′-fluoroethynyl) -2-pyridylmethyl group, 6-fluoro-2-pyridylmethyl group, 6-chloro-2- Pyridylmethyl group, 6,6-dichloro-2-pyridylmethyl group,

3-pyridylmethyl group, 1- (3′-pyridyl) ethyl group, 2- (3′-pyridyl) ethyl group, 3- (3′-pyridyl) propyl group, 4- (3′-pyridyl) butyl group, 5- (3′-pyridyl) pentyl group, 6- (3′-pyridyl) hexyl group, 7- (3′-pyridyl) heptyl group, 8- (3′-pyridyl) octyl group,

5-cyano-3-pyridylmethyl group, 5-nitro-3-pyridylmethyl group, 5-carboxyl-3-pyridylmethyl group, 5-hydroxyl-3-pyridylmethyl group, 5- (N-methylcarboxamide)- 3-pyridylmethyl group, 5- (N, N-dimethylcarboamido) -3-pyridylmethyl group, 5-methyl-3-pyridylmethyl group, 5-trifluoromethyl-3-pyridylmethyl group, 5-methoxy- 3-pyridylmethyl group, 5-trifluoromethoxy-3-pyridylmethyl group, 5-methylthio-3-pyridylmethyl group, 5-methylsulfinyl-3-pyridylmethyl group, 5-methylsulfonyl-3-pyridylmethyl group, 5-methoxycarbonyl-3-pyridylmethyl group, 5-vinyl-3-pyridylmethyl group, 5- (2 ′, 2′-difluorovini ) -3-pyridylmethyl group, 5-ethynyl-3-pyridylmethyl group, 5- (2′-fluoroethynyl) -3-pyridylmethyl group, 5-fluoro-3-pyridylmethyl group, 5-chloro-3- A pyridylmethyl group,

6-cyano-3-pyridylmethyl group, 6-nitro-3-pyridylmethyl group, 6-carboxyl-3-pyridylmethyl group, 6-hydroxyl-3-pyridylmethyl group, 6- (N-methylcarboxamide)- 3-pyridylmethyl group, 6- (N, N-dimethylcarboamido) -3-pyridylmethyl group, 6-methyl-3-pyridylmethyl group, 6-trifluoromethyl-3-pyridylmethyl group, 6-methoxy- 3-pyridylmethyl group, 6-trifluoromethoxy-3-pyridylmethyl group, 6-methylthio-3-pyridylmethyl group, 6-methylsulfinyl-3-pyridylmethyl group, 6-methylsulfonyl-3-pyridylmethyl group, 6-methoxycarbonyl-3-pyridylmethyl group, 6-vinyl-3-pyridylmethyl group, 6- (2 ′, 2′-difluorovini ) -3-pyridylmethyl group, 6-ethynyl-3-pyridylmethyl group, 6- (2′-fluoroethynyl) -3-pyridylmethyl group, 6-fluoro-3-pyridylmethyl group, 6-chloro-3- A pyridylmethyl group,

4-pyridylmethyl group, 1- (4′-pyridyl) ethyl group, 2- (4′-pyridyl) ethyl group, 3- (4′-pyridyl) propyl group, 4- (4′-pyridyl) butyl group, 5- (4′-pyridyl) pentyl group, 6- (4′-pyridyl) hexyl group, 7- (4′-pyridyl) heptyl group, 8- (4′-pyridyl) octyl group,

2-cyano-4-pyridylmethyl group, 2-nitro-4-pyridylmethyl group, 2-carboxyl-4-pyridylmethyl group, 2-hydroxyl-4-pyridylmethyl group, 2- (N-methylcarboxamide)- 4-pyridylmethyl group, 2- (N, N-dimethylcarboamido) -4-pyridylmethyl group, 2-methyl-4-pyridylmethyl group, 2-trifluoromethyl-4-pyridylmethyl group, 2-methoxy- 4-pyridylmethyl group, 2-trifluoromethoxy-4-pyridylmethyl group, 2-methylthio-4-pyridylmethyl group, 2-methylsulfinyl-4-pyridylmethyl group, 2-methylsulfonyl-4-pyridylmethyl group, 2-methoxycarbonyl-4-pyridylmethyl group, 2-vinyl-4-pyridylmethyl group, 2- (2 ′, 2′-difluorovini ) -4-pyridylmethyl group, 2-ethynyl-4-pyridylmethyl group, 2- (2′-fluoroethynyl) -4-pyridylmethyl group, 2-fluoro-4-pyridylmethyl group, 2-chloro-4- A pyridylmethyl group,

6-cyano-4-pyridylmethyl group, 6-nitro-4-pyridylmethyl group, 6-carboxyl-4-pyridylmethyl group, 6-hydroxyl-4-pyridylmethyl group, 6- (N-methylcarboamido)- 4-pyridylmethyl group, 6- (N, N-dimethylcarboamido) -4-pyridylmethyl group, 6-methyl-4-pyridylmethyl group, 6-trifluoromethyl-4-pyridylmethyl group, 6-methoxy- 4-pyridylmethyl group, 6-trifluoromethoxy-4-pyridylmethyl group, 6-methylthio-4-pyridylmethyl group, 6-methylsulfinyl-4-pyridylmethyl group, 6-methylsulfonyl-4-pyridylmethyl group, 6-methoxycarbonyl-4-pyridylmethyl group, 6-vinyl-4-pyridylmethyl group, 6- (2 ′, 2′-difluorovini ) -4-pyridylmethyl group, 6-ethynyl-4-pyridylmethyl group, 6- (2′-fluoroethynyl) -4-pyridylmethyl group, 6-fluoro-4-pyridylmethyl group, 6-chloro-4- A pyridylmethyl group,

2-quinolylmethyl group, 1- (2′-quinolyl) ethyl group, 2- (2′-quinolyl) ethyl group, 3- (2′-quinolyl) propyl group, 4- (2′-quinolyl) butyl group, 5 -(2'-quinolyl) pentyl group, 6- (2'-quinolyl) hexyl group, 7- (2'-quinolyl) heptyl group, 8- (2'-quinolyl) octyl group,

6-cyano-2-quinolylmethyl group, 6-nitro-2-quinolylmethyl group, 6-carboxyl-2-quinolylmethyl group, 6-hydroxyl-2-quinolylmethyl group, 6- (N-methylcarboamido) -2-quinolylmethyl group 6- (N, N-dimethylcarboamido) -2-quinolylmethyl group, 6-methyl-2-quinolylmethyl group, 6-trifluoromethyl-2-quinolylmethyl group, 6-methoxy-2-quinolylmethyl group, 6-triol Fluoromethoxy-2-quinolylmethyl group, 6-methylthio-2-quinolylmethyl group, 6-methylsulfinyl-2-quinolylmethyl group, 6-methylsulfonyl-2-quinolylmethyl group, 6-methoxycarbonyl-2-quinolylmethyl group, 6-vinyl 2-quinolylmethyl group, 6- (2 ′, 2′-difluorovini ) -2-quinolylmethyl group, a 6-ethynyl-2-quinolylmethyl group, 6- (2'-fluoro-ethynyl) -2-quinolylmethyl group, 6-fluoro-2-quinolylmethyl group, 6-chloro-2-quinolylmethyl group,

3-quinolylmethyl group, 1- (3′-quinolyl) ethyl group, 2- (3′-quinolyl) ethyl group, 3- (3′-quinolyl) propyl group, 4- (3′-quinolyl) butyl group, 5 -(3'-quinolyl) pentyl group, 6- (3'-quinolyl) hexyl group, 7- (3'-quinolyl) heptyl group, 8- (3'-quinolyl) octyl group,

6-cyano-3-quinolylmethyl group, 6-nitro-3-quinolylmethyl group, 6-carboxyl-3-quinolylmethyl group, 6-hydroxyl-3-quinolylmethyl group, 6- (N-methylcarboamido) -3-quinolylmethyl group 6- (N, N-dimethylcarboamido) -3-quinolylmethyl group, 6-methyl-3-quinolylmethyl group, 6-trifluoromethyl-3-quinolylmethyl group, 6-methoxy-3-quinolylmethyl group, 6-triol Fluoromethoxy-3-quinolylmethyl group, 6-methylthio-3-quinolylmethyl group, 6-methylsulfinyl-3-quinolylmethyl group, 6-methylsulfonyl-3-quinolylmethyl group, 6-methoxycarbonyl-3-quinolylmethyl group, 6-vinyl -3-quinolylmethyl group, 6- (2 ′, 2′-difluorovini ) -3-quinolylmethyl group, a 6-ethynyl-3-quinolylmethyl group, 6- (2'-fluoro-ethynyl) -3-quinolylmethyl group, 6-fluoro-3-quinolylmethyl group, 6-chloro-3-quinolylmethyl group,

4-quinolylmethyl group, 1- (4′-quinolyl) ethyl group, 2- (4′-quinolyl) ethyl group, 3- (4′-quinolyl) propyl group, 4- (4′-quinolyl) butyl group, 5 -(3'-quinolyl) pentyl group, 6- (4'-quinolyl) hexyl group, 7- (4'-quinolyl) heptyl group, 8- (4'-quinolyl) octyl group,

6-cyano-4-quinolylmethyl group, 6-nitro-4-quinolylmethyl group, 6-carboxyl-4-quinolylmethyl group, 6-hydroxyl-4-quinolylmethyl group, 6- (N-methylcarboamido) -4-quinolylmethyl group 6- (N, N-dimethylcarboamido) -4-quinolylmethyl group, 6-methyl-4-quinolylmethyl group, 6-trifluoromethyl-4-quinolylmethyl group, 6-methoxy-4-quinolylmethyl group, 6-triol Fluoromethoxy-4-quinolylmethyl group, 6-methylthio-4-quinolylmethyl group, 6-methylsulfinyl-4-quinolylmethyl group, 6-methylsulfonyl-4-quinolylmethyl group, 6-methoxycarbonyl-4-quinolylmethyl group, 6-vinyl -4-quinolylmethyl group, 6- (2 ', 2'-difluorovini ) -4-quinolylmethyl group, 6-ethynyl-4-quinolylmethyl group, 6- (2'-fluoro ethynyl) -4-quinolylmethyl group, 6-fluoro-4-quinolylmethyl group, 6-chloro-4-quinolylmethyl group,

2-furylmethyl group, 1- (2′-furyl) ethyl group, 2- (2′-furyl) ethyl group, 3- (2′-furyl) propyl group, 4- (2′-furyl) butyl group, 5- (2′-furyl) pentyl group, 6- (2′-furyl) hexyl group, 7- (2′-furyl) heptyl group, 8- (2′-furyl) octyl group,

4-cyano-2-furylmethyl group, 4-nitro-2-furylmethyl group, 4-carboxyl-2-furylmethyl group, 4-hydroxyl-2-furylmethyl group, 4- (N-methylcarboamido)- 2-furylmethyl group, 4- (N, N-dimethylcarboamido) -2-furylmethyl group, 4-methyl-2-furylmethyl group, 4-trifluoromethyl-2-furylmethyl group, 4-methoxy- 2-furylmethyl group, 4-trifluoromethoxy-2-furylmethyl group, 4-methylthio-2-furylmethyl group, 4-methylsulfinyl-2-furylmethyl group, 4-methylsulfonyl-2-furylmethyl group, 4-methoxycarbonyl-2-furylmethyl group, 4-vinyl-2-furylmethyl group, 4- (2 ′, 2′-difluorovinyl) -2-furylmethyl group, 4- Ethynyl-2-furylmethyl group, 4- (2'-fluoro-ethynyl) -2-furylmethyl group, 4-fluoro-2-furylmethyl group, 4-chloro-2-furylmethyl group,

3-furylmethyl group, 1- (3′-furyl) ethyl group, 2- (3′-furyl) ethyl group, 3- (3′-furyl) propyl group, 4- (3′-furyl) butyl group, 5- (3′-furyl) pentyl group, 6- (3′-furyl) hexyl group, 7- (3′-furyl) heptyl group, 8- (3′-furyl) octyl group,

4-cyano-3-furylmethyl group, 4-nitro-3-furylmethyl group, 4-carboxyl-3-furylmethyl group, 4-hydroxyl-3-furylmethyl group, 4- (N-methylcarboxamide)- 3-furylmethyl group, 4- (N, N-dimethylcarboamido) -3-furylmethyl group, 4-methyl-3-furylmethyl group, 4-trifluoromethyl-3-furylmethyl group, 4-methoxy- 3-furylmethyl group, 4-trifluoromethoxy-3-furylmethyl group, 4-methylthio-3-furylmethyl group, 4-methylsulfinyl-3-furylmethyl group, 4-methylsulfonyl-3-furylmethyl group, 4-methoxycarbonyl-3-furylmethyl group, 4-vinyl-3-furylmethyl group, 4- (2 ′, 2′-difluorovinyl) -3-furylmethyl group, 4- Ethynyl-3-furylmethyl group, 4- (2'-fluoro-ethynyl) -3-furylmethyl group, 4-fluoro-3-furylmethyl group, 4-chloro-3-furylmethyl group,

2-thienylmethyl group, 1- (2′-thienyl) ethyl group, 2- (2′-thienyl) ethyl group, 3- (2′-thienyl) propyl group, 4- (2′-thienyl) butyl group, 5- (2′-thienyl) pentyl group, 6- (2′-thienyl) hexyl group, 7- (2′-thienyl) heptyl group, 8- (2′-thienyl) octyl group,

4-cyano-2-thienylmethyl group, 4-nitro-2-thienylmethyl group, 4-carboxyl-2-thienylmethyl group, 4-hydroxyl-2-thienylmethyl group, 4- (N-methylcarboamido)- 2-thienylmethyl group, 4- (N, N-dimethylcarboamido) -2-thienylmethyl group, 4-methyl-2-thienylmethyl group, 4-trifluoromethyl-2-thienylmethyl group, 4-methoxy- 2-thienylmethyl group, 4-trifluoromethoxy-2-thienylmethyl group, 4-methylthio-2-thienylmethyl group, 4-methylsulfinyl-2-thienylmethyl group, 4-methylsulfonyl-2-thienylmethyl group, 4-methoxycarbonyl-2-thienylmethyl group, 4-vinyl-2-thienylmethyl group, 4- (2 ′, 2′-difluorovini ) -2-thienylmethyl group, 4-ethynyl-2-thienylmethyl group, 4- (2'-fluoroethynyl) -2-thienylmethyl group, 4-fluoro-2-thienylmethyl group, 4-chloro-2- Thienylmethyl group,

3-thienylmethyl group, 1- (3′-thienyl) ethyl group, 2- (3′-thienyl) ethyl group, 3- (3′-thienyl) propyl group, 4- (3′-thienyl) butyl group, 5- (3′-thienyl) pentyl group, 6- (3′-thienyl) hexyl group, 7- (3′-thienyl) heptyl group, 8- (3′-thienyl) octyl group,

4-cyano-3-thienylmethyl group, 4-nitro-3-thienylmethyl group, 4-carboxyl-3-thienylmethyl group, 4-hydroxyl-3-thienylmethyl group, 4- (N-methylcarboamido)- 3-thienylmethyl group, 4- (N, N-dimethylcarboamido) -3-thienylmethyl group, 4-methyl-3-thienylmethyl group, 4-trifluoromethyl-3-thienylmethyl group, 4-methoxy- 3-thienylmethyl group, 4-trifluoromethoxy-3-thienylmethyl group, 4-methylthio-3-thienylmethyl group, 4-methylsulfinyl-3-thienylmethyl group, 4-methylsulfonyl-3-thienylmethyl group, 4-methoxycarbonyl-3-thienylmethyl group, 4-vinyl-3-thienylmethyl group, 4- (2 ′, 2′-difluorovini ) -3-thienylmethyl group, 4-ethynyl-3-thienylmethyl group, 4- (2'-fluoroethynyl) -3-thienylmethyl group, 4-fluoro-3-thienylmethyl group, 4-chloro-3- Thienylmethyl group,

2- (1-benzofuranyl) methyl group, 1- (2 ′-(1′-benzofuranyl)) ethyl group, 2- (2 ′-(1′-benzofuranyl)) ethyl group, 3- (2 ′-(1 '-Benzofuranyl)) propyl group, 4- (2'-(1'-benzofuranyl)) butyl group, 5- (2 '-(1'-benzofuranyl)) pentyl group, 6- (2'-(1'-) Benzofuranyl)) hexyl group, 7- (2 ′-(1′-benzofuranyl)) heptyl group, 8- (2 ′-(1′-benzofuranyl)) octyl group,

5-cyano-2- (1-benzofuranyl) methyl group, 5-nitro-2- (1-benzofuranyl) methyl group, 5-carboxyl-2- (1-benzofuranyl) methyl group, 5-hydroxyl-2- (1 -Benzofuranyl) methyl group, 5- (N-methylcarboamido) -2- (1-benzofuranyl) methyl group, 5- (N, N-dimethylcarboamido) -2- (1-benzofuranyl) methyl group, 5- Methyl-2- (1-benzofuranyl) methyl group, 5-trifluoromethyl-2- (1-benzofuranyl) methyl group, 5-methoxy-2- (1-benzofuranyl) methyl group, 5-trifluoromethoxy-2- (1-benzofuranyl) methyl group, 5-methylthio-2- (1-benzofuranyl) methyl group, 5-methylsulfinyl-2- (1-benzofuranyl) Methyl group, 5-methylsulfonyl-2- (1-benzofuranyl) methyl group, 5-methoxycarbonyl-2- (1-benzofuranyl) methyl group, 5-vinyl-2- (1-benzofuranyl) methyl group, 5- ( 2 ', 2'-difluorovinyl) -2- (1-benzofuranyl) methyl group, 5-ethynyl-2- (1-benzofuranyl) methyl group, 5- (2'-fluoroethynyl) -2- (1-benzofuranyl) ) Methyl group, 5-fluoro-2- (1-benzofuranyl) methyl group, 5-chloro-2- (1-benzofuranyl) methyl group,
3- (1-benzofuranyl) methyl group, 1- (3 ′-(1′-benzofuranyl)) ethyl group, 2- (3 ′-(1′-benzofuranyl)) ethyl group, 3- (3 ′-(1 '-Benzofuranyl)) propyl group, 4- (3'-(1'-benzofuranyl)) butyl group, 5- (3 '-(1'-benzofuranyl)) pentyl group, 6- (3'-(1'-) Benzofuranyl)) hexyl group, 7- (3 ′-(1′-benzofuranyl)) heptyl group, 8- (3 ′-(1′-benzofuranyl)) octyl group,

5-cyano-3- (1-benzofuranyl) methyl group, 5-nitro-3- (1-benzofuranyl) methyl group, 5-carboxyl-3- (1-benzofuranyl) methyl group, 5-hydroxyl-3- (1 -Benzofuranyl) methyl group, 5- (N-methylcarboamido) -3- (1-benzofuranyl) methyl group, 5- (N, N-dimethylcarbamido) -3- (1-benzofuranyl) methyl group, 5- Methyl-3- (1-benzofuranyl) methyl group, 5-trifluoromethyl-3- (1-benzofuranyl) methyl group, 5-methoxy-3- (1-benzofuranyl) methyl group, 5-trifluoromethoxy-3- (1-benzofuranyl) methyl group, 5-methylthio-3- (1-benzofuranyl) methyl group, 5-methylsulfinyl-3- (1-benzofuranyl) Methyl group, 5-methylsulfonyl-3- (1-benzofuranyl) methyl group, 5-methoxycarbonyl-3- (1-benzofuranyl) methyl group, 5-vinyl-3- (1-benzofuranyl) methyl group, 5- ( 2 ', 2'-difluorovinyl) -3- (1-benzofuranyl) methyl group, 5-ethynyl-3- (1-benzofuranyl) methyl group, 5- (2'-fluoroethynyl) -3- (1-benzofuranyl) ) Methyl group, 5-fluoro-3- (1-benzofuranyl) methyl group, 5-chloro-3- (1-benzofuranyl) methyl group,

2- (1-benzothienyl) methyl group, 1- (2 ′-(1′-benzothienyl)) ethyl group, 2- (2 ′-(1′-benzothienyl)) ethyl group, 3- (2 ′ -(1'-benzothienyl)) propyl group, 4- (2 '-(1'-benzothienyl)) butyl group, 5- (2'-(1'-benzothienyl)) pentyl group, 6- (2 '-(1'-benzothienyl)) hexyl group, 7- (2'-(1'-benzothienyl)) heptyl group, 8- (2 '-(1'-benzothienyl)) octyl group,

5-cyano-2- (1-benzothienyl) methyl group, 5-nitro-2- (1-benzothienyl) methyl group, 5-carboxyl-2- (1-benzothienyl) methyl group, 5-hydroxyl-2 -(1-benzothienyl) methyl group, 5- (N-methylcarboamido) -2- (1-benzothienyl) methyl group, 5- (N, N-dimethylcarboamido) -2- (1-benzothienyl) ) Methyl group, 5-methyl-2- (1-benzothienyl) methyl group, 5-trifluoromethyl-2- (1-benzothienyl) methyl group, 5-methoxy-2- (1-benzothienyl) methyl group , 5-trifluoromethoxy-2- (1-benzothienyl) methyl group, 5-methylthio-2- (1-benzothienyl) methyl group, 5-methylsulfinyl-2- (1-benzothienyl) Methyl group, 5-methylsulfonyl-2- (1-benzothienyl) methyl group, 5-methoxycarbonyl-2- (1-benzothienyl) methyl group, 5-vinyl-2- (1-benzothienyl) methyl group, 5- (2 ′, 2′-difluorovinyl) -2- (1-benzothienyl) methyl group, 5-ethynyl-2- (1-benzothienyl) methyl group, 5- (2′-fluoroethynyl) -2 -(1-benzothienyl) methyl group, 5-fluoro-2- (1-benzothienyl) methyl group, 5-chloro-2- (1-benzothienyl) methyl group,

3- (1-benzothienyl) methyl group, 1- (3 ′-(1′-benzothienyl)) ethyl group, 2- (3 ′-(1′-benzothienyl)) ethyl group, 3- (3 ′ -(1'-benzothienyl)) propyl group, 4- (3 '-(1'-benzothienyl)) butyl group, 5- (3'-(1'-benzothienyl)) pentyl group, 6- (3 '-(1'-benzothienyl)) hexyl group, 7- (3'-(1'-benzothienyl)) heptyl group, 8- (3 '-(1'-benzothienyl)) octyl group,

5-cyano-3- (1-benzothienyl) methyl group, 5-nitro-3- (1-benzothienyl) methyl group, 5-carboxyl-3- (1-benzothienyl) methyl group, 5-hydroxyl-3 -(1-benzothienyl) methyl group, 5- (N-methylcarboamido) -3- (1-benzothienyl) methyl group, 5- (N, N-dimethylcarboamido) -3- (1-benzothienyl) ) Methyl group, 5-methyl-3- (1-benzothienyl) methyl group, 5-trifluoromethyl-3- (1-benzothienyl) methyl group, 5-methoxy-3- (1-benzothienyl) methyl group 5-trifluoromethoxy-3- (1-benzothienyl) methyl group, 5-methylthio-3- (1-benzothienyl) methyl group, 5-methylsulfinyl-3- (1-benzothienyl) Methyl group, 5-methylsulfonyl-3- (1-benzothienyl) methyl group, 5-methoxycarbonyl-3- (1-benzothienyl) methyl group, 5-vinyl-3- (1-benzothienyl) methyl group, 5- (2 ′, 2′-difluorovinyl) -3- (1-benzothienyl) methyl group, 5-ethynyl-3- (1-benzothienyl) methyl group, 5- (2′-fluoroethynyl) -3 -(1-benzothienyl) methyl group, 5-fluoro-3- (1-benzothienyl) methyl group, 5-chloro-3- (1-benzothienyl) methyl group

Fluoromethyl group, 1-fluoroethyl group, 1,1-difluoroethyl, 2-fluoroethyl group, 2,2-difluoroethyl group, 2,2,2-trifluoroethyl group, 3-fluoropropyl group, 3, 3,3-trifluoropropyl, 4-fluorobutyl group, 4,4,4-trifluorobutyl group, 3,3,4,4,4-pentafluorobutyl group, 5-fluoropentyl group, 6-fluorohexyl Group, 7-fluoroheptyl group, 8-fluorooctyl group,

Chloromethyl group, 1-chloroethyl group, 2-chloroethyl group, 3-chloropropyl group, 4-chlorobutyl group, 5-chloropentyl group, 6-chlorohexyl group, 7-chloroheptyl group, 8-chlorooctyl group,

Bromomethyl group, 1-bromoethyl group, 2-bromoethyl group, 3-bromopropyl group, 4-bromobutyl group, 5-bromopentyl group, 6-bromohexyl group, 7-bromoheptyl group, 8-bromooctyl group,

(Methoxycarbonyl) methyl group, 1- (methoxycarbonyl) ethyl group, 2- (methoxycarbonyl) ethyl group, 3- (methoxycarbonyl) propyl group, 4- (methoxycarbonyl) butyl group, 5- (methoxycarbonyl) pentyl Group, 6- (methoxycarbonyl) hexyl group, 7- (methoxycarbonyl) heptyl group, 8- (methoxycarbonyl) octyl group,

Cyanomethyl group, 1-cyanoethyl group, 2-cyanoethyl group, 3-cyanopropyl group, 4-cyanobutyl group, 5-cyanopentyl group, 6-cyanohexyl group, 7-cyanoheptyl group, 8-cyanooctyl group,

Nitromethyl group, 1-nitroethyl group, 2-nitroethyl group, 3-nitropropyl group, 4-nitrobutyl group, 5-nitropentyl group, 6-nitrohexyl group, 7-nitroheptyl group, 8-nitrooctyl group,

(Carboxy) methyl group, 1- (carboxy) ethyl group, 2- (carboxy) ethyl group, 3- (carboxy) propyl group, 4- (carboxy) butyl group, 5- (carboxy) pentyl group, 6- (carboxy) ) Hexyl group, 7- (carboxy) heptyl group, 8- (carboxy) octyl group,

Hydroxymethyl group, 1-hydroxyethyl group, 2-hydroxyethyl group, 3-hydroxypropyl group, 4-hydroxybutyl group, 5-hydroxypentyl group, 6-hydroxyhexyl group, 7-hydroxyheptyl group, 8-hydroxyoctyl Group,
Etc.

In the present invention, the “C1-C8 chain hydrocarbon group having one or more atoms or groups selected from group F” includes, for example,
Benzyl group, phenyldifluoromethyl group, 1-phenylethyl group, 1,1-difluoro-1-phenylethyl group, 2,2,2-trifluoro-1-phenylethyl group, 1,1,2,2,2 -Pentafluoro-1-phenylethyl group, 2-phenylethyl group, 1,1-difluoro-2-phenylethyl group, 2,2-difluoro-2-phenylethyl group, 1,1,2,2-tetrafluoro 2-phenylethyl group, 3-phenylpropyl group, 1,1-difluoro-3-phenylpropyl group, 2,2-difluoro-3-phenylpropyl group, 3,3-difluoro-3-phenylpropyl group, 1 1,2,2,3,3-hexafluoro-3-phenylpropyl group, 4-phenylbutyl group, 1,1-difluoro-4-phenylbutyl group, 2,2-diph Oro-4-phenylbutyl group, 3,3-difluoro-4-phenylbutyl group, 4,4-difluoro-4-phenylbutyl group, 1,1,2,2,3,3,4,4-octafluoro -3-4-phenylbutyl group, 5-phenylpentyl group, 1,1-difluoro-5-phenylpentyl group, 2,2-difluoro-5-phenylpentyl group, 3,3-difluoro-5-phenylpentyl group 4,4-difluoro-5-phenylpentyl group, 5,5-difluoro-5-phenylpentyl group, 6-phenylhexyl group, 1,1-difluoro-6-phenylhexyl group, 2,2-difluoro-6 -Phenylhexyl group, 3,3-difluoro-6-phenylhexyl group, 4,4-difluoro-6-phenylhexyl group, 5,5-difluoro-6-phenylhexyl group Sil group, 6,6-difluoro-6-phenylhexyl group, 7-phenylheptyl group, 1,1-difluoro-7-phenylheptyl group, 2,2-difluoro-7-phenylheptyl group, 3,3-difluoro -7-phenylheptyl group, 4,4-difluoro-7-phenylheptyl group, 5,5-difluoro-7-phenylheptyl group, 6,6-difluoro-7-phenylheptyl group, 7,7-difluoro-7 -Phenylheptyl group, 8-phenyloctyl group, 1,1-difluoro-8-phenyloctyl group, 2,2-difluoro-8-phenyloctyl group, 3,3-difluoro-8-phenyloctyl group, 4,4 -Difluoro-8-phenyloctyl group, 5,5-difluoro-8-phenyloctyl group, 6,6-difluoro-8-phenyloctyl group Group, 7,7-difluoro-8-phenyloctyl group, 8,8-difluoro-8-phenyloctyl group,

4-cyanobenzyl group, 4-nitrobenzyl group, 4-carboxylbenzyl group, 4-hydroxylbenzyl group, 4- (N-methylcarboamido) benzyl group, 4- (N, N-dimethylcarboamido) benzyl group, 4-methylbenzyl group, 4-trifluoromethylbenzyl group, 4-methoxybenzyl group, 4-trifluoromethoxybenzyl group, 4-methylthiobenzyl group, 4-methylsulfinylbenzyl group, 4-methylsulfonylbenzyl group, 4- Methoxycarbonylbenzyl group, 4-vinylbenzyl group, 4- (2 ′, 2′-difluorovinyl) benzyl group, 4-ethynylbenzyl group, 4- (2′-fluoroethynyl) benzyl group, 4-fluorobenzyl group, 4-chlorobenzyl group, 3,4-dichlorobenzyl group,
(4′-cyanophenyl) difluoromethyl group, (4′-nitrophenyl) difluoromethyl group, (4′-carboxylphenyl) difluoromethyl group, (4′-hydroxylphenyl) difluoromethyl group, (4 ′-(N -Methylcarboamido) phenyl) difluoromethyl group, (4 '-(N, N-dimethylcarboamido) phenyl) difluoromethyl group, (4'-methylphenyl) difluoromethyl group, (4'-trifluoromethylphenyl) Difluoromethyl group, (4′-methoxyphenyl) difluoromethyl group, (4′-trifluoromethoxyphenyl) difluoromethyl group, (4′-methylthiophenyl) difluoromethyl group, (4′-methylsulfinylphenyl) difluoromethyl group , (4′-methylsulfonylphenyl) difluoromethyl group, (4′-methoxycarbonylphenyl) difluoromethyl group, (4′-vinylphenyl) difluoromethyl group, (4 ′-(2 ′, 2′-difluorovinyl) phenyl) difluoromethyl group, (4′-ethynylphenyl) Difluoromethyl group, (4 ′-(2′-fluoroethynyl) phenyl) difluoromethyl group, (4′-fluorophenyl) difluoromethyl group, (4′-chlorophenyl) difluoromethyl group, 3, (4′-dichlorophenyl) Difluoromethyl group,

1-naphthylmethyl group, (1′-naphthyl) difluoromethyl group, 1- (1′-naphthyl) ethyl group, 1,1-difluoro-1- (1′-naphthyl) ethyl group, 2,2,2- Trifluoro-1- (1′-naphthyl) ethyl group, 1,1,2,2,2-pentafluoro-1- (1′-naphthyl) ethyl group, 2- (1′-naphthyl) ethyl group, 1 , 1-Difluoro-2- (1′-naphthyl) ethyl group, 2,2-difluoro-2- (1′-naphthyl) ethyl group, 1,1,2,2-tetrafluoro-2- (1′- Naphthyl) ethyl group, 3- (1′-naphthyl) propyl group, 1,1-difluoro-3- (1′-naphthyl) propyl group, 2,2-difluoro-3- (1′-naphthyl) propyl group, 3,3-difluoro-3- (1′-naphthyl) propyl group, , 1,2,2,3,3-hexafluoro-3- (1′-naphthyl) propyl group, 4- (1′-naphthyl) butyl group, 1,1-difluoro-4- (1′-naphthyl) Butyl group, 2,2-difluoro-4- (1′-naphthyl) butyl group, 3,3-difluoro-4- (1′-naphthyl) butyl group, 4,4-difluoro-4- (1′-naphthyl) ) Butyl group, 1,1,2,2,3,3,4,4-octafluoro-3--4- (1′-naphthyl) butyl group, 5- (1′-naphthyl) pentyl group, 1,1 -Difluoro-5- (1'-naphthyl) pentyl group, 2,2-difluoro-5- (1'-naphthyl) pentyl group, 3,3-difluoro-5- (1'-naphthyl) pentyl group, 4, 4-difluoro-5- (1′-naphthyl) pentyl group, 5,5-difluoro 5- (1′-naphthyl) pentyl group, 6- (1′-naphthyl) hexyl group, 1,1-difluoro-6- (1′-naphthyl) hexyl group, 2,2-difluoro-6- (1 ′ -Naphthyl) hexyl group, 3,3-difluoro-6- (1'-naphthyl) hexyl group, 4,4-difluoro-6- (1'-naphthyl) hexyl group, 5,5-difluoro-6- (1 '-Naphthyl) hexyl group, 6,6-difluoro-6- (1'-naphthyl) hexyl group, 7- (1'-naphthyl) heptyl group, 1,1-difluoro-7- (1'-naphthyl) heptyl Group, 2,2-difluoro-7- (1′-naphthyl) heptyl group, 3,3-difluoro-7- (1′-naphthyl) heptyl group, 4,4-difluoro-7- (1′-naphthyl) Heptyl group, 5,5-difluoro-7- (1′-naphthyl) heptyl group, 6,6-difluoro-7- (1′-naphthyl) heptyl group, 7,7-difluoro-7- (1′-naphthyl) heptyl group, 8- (1′-naphthyl) ) Octyl group, 1,1-difluoro-8- (1′-naphthyl) octyl group, 2,2-difluoro-8- (1′-naphthyl) octyl group, 3,3-difluoro-8- (1′-) Naphthyl) octyl group, 4,4-difluoro-8- (1′-naphthyl) octyl group, 5,5-difluoro-8- (1′-naphthyl) octyl group, 6,6-difluoro-8- (1 ′) -Naphthyl) octyl group, 7,7-difluoro-8- (1'-naphthyl) octyl group, 8,8-difluoro-8- (1'-naphthyl) octyl group,

6-cyano-1-naphthylmethyl group, 6-nitro-1-naphthylmethyl group, 6-carboxyl-1-naphthylmethyl group, 6-hydroxyl-1-naphthylmethyl group, 6- (N-methylcarboamido)- 1-naphthylmethyl group, 6- (N, N-dimethylcarboamido) -1-naphthylmethyl group, 6-methyl-1-naphthylmethyl group, 6-trifluoromethyl-1-naphthylmethyl group, 6-methoxy- 1-naphthylmethyl group, 6-trifluoromethoxy-1-naphthylmethyl group, 6-methylthio-1-naphthylmethyl group, 6-methylsulfinyl-1-naphthylmethyl group, 6-methylsulfonyl-1-naphthylmethyl group, 6-methoxycarbonyl-1-naphthylmethyl group, 6-vinyl-1-naphthylmethyl group, 6- (2 ′, 2′-difluorovinyl -1-naphthylmethyl group, 6-ethynyl-1-naphthylmethyl group, 6- (2′-fluoroethynyl) -1-naphthylmethyl group, 6-fluoro-1-naphthylmethyl group, 6-chloro-1-naphthyl Methyl group,
(6′-cyano-1-naphthyl) -difluoromethyl group, (6′-nitro-1-naphthyl) -difluoromethyl group, (6′-carboxyl-1-naphthyl) -difluoromethyl group, (6′-hydroxyl) -1-naphthyl) -difluoromethyl group, (6 ′-(N-methylcarboamido) -1-naphthyl) -difluoromethyl group, (6 ′-(N, N-dimethylcarboamido) -1-naphthyl)- Difluoromethyl group, (6′-methyl-1-naphthyl) -difluoromethyl group, (6′-trifluoromethyl-1-naphthyl) -difluoromethyl group, (6′-methoxy-1-naphthyl) -difluoromethyl group , (6′-trifluoromethoxy-1-naphthyl) -difluoromethyl group, (6′-methylthio-1-naphthyl) -difluoromethyl group, (6′-methylsulfuric acid) Nyl-1-naphthyl) -difluoromethyl group, (6′-methylsulfonyl-1-naphthyl) -difluoromethyl group, (6′-methoxycarbonyl-1-naphthyl) -difluoromethyl group, (6′-vinyl-1) -Naphthyl) -difluoromethyl group, (6 '-(2', 2'-difluorovinyl) -1-naphthyl) -difluoromethyl group, (6'-ethynyl-1-naphthyl) -difluoromethyl group, (6 '-(2'-fluoroethynyl) -1-naphthyl) -difluoromethyl group, (6'-fluoro-1-naphthyl) -difluoromethyl group, (6'-chloro-1-naphthyl) -difluoromethyl group,

2-naphthylmethyl group, (2′-naphthyl) difluoromethyl group, 1- (2′-naphthyl) ethyl group, 1,1-difluoro-1- (2′-naphthyl) ethyl group, 2,2,2- Trifluoro-1- (2′-naphthyl) ethyl group, 1,1,2,2,2-pentafluoro-1- (2′-naphthyl) ethyl group, 2- (2′-naphthyl) ethyl group, 1 , 1-Difluoro-2- (2′-naphthyl) ethyl group, 2,2-difluoro-2- (2′-naphthyl) ethyl group, 1,1,2,2-tetrafluoro-2- (2′- Naphthyl) ethyl group, 3- (2′-naphthyl) propyl group, 1,1-difluoro-3- (2′-naphthyl) propyl group, 2,2-difluoro-3- (2′-naphthyl) propyl group, 3,3-difluoro-3- (2′-naphthyl) propyl group, 1,2,2,3,3-hexafluoro-3- (2'-naphthyl) propyl group, 4- (2'-naphthyl) butyl group, 1,1-difluoro-4- (2'-naphthyl) Butyl group, 2,2-difluoro-4- (2′-naphthyl) butyl group, 3,3-difluoro-4- (2′-naphthyl) butyl group, 4,4-difluoro-4- (2′-naphthyl) ) Butyl group, 1,1,2,2,3,3,4,4-octafluoro-3--4- (2′-naphthyl) butyl group, 5- (2′-naphthyl) pentyl group, 1,1 -Difluoro-5- (2'-naphthyl) pentyl group, 2,2-difluoro-5- (2'-naphthyl) pentyl group, 3,3-difluoro-5- (2'-naphthyl) pentyl group, 4, 4-difluoro-5- (2′-naphthyl) pentyl group, 5,5-difluoro 5- (2′-naphthyl) pentyl group, 6- (2′-naphthyl) hexyl group, 1,1-difluoro-6- (2′-naphthyl) hexyl group, 2,2-difluoro-6- (2 ′ -Naphthyl) hexyl group, 3,3-difluoro-6- (2'-naphthyl) hexyl group, 4,4-difluoro-6- (2'-naphthyl) hexyl group, 5,5-difluoro-6- (2 '-Naphthyl) hexyl group, 6,6-difluoro-6- (2'-naphthyl) hexyl group, 7- (2'-naphthyl) heptyl group, 1,1-difluoro-7- (2'-naphthyl) heptyl Group, 2,2-difluoro-7- (2′-naphthyl) heptyl group, 3,3-difluoro-7- (2′-naphthyl) heptyl group, 4,4-difluoro-7- (2′-naphthyl) Heptyl group, 5,5-difluoro-7- (2′-naphthyl) heptyl group, 6,6-difluoro-7- (2′-naphthyl) heptyl group, 7,7-difluoro-7- (2′-naphthyl) heptyl group, 8- (2′-naphthyl) ) Octyl group, 1,1-difluoro-8- (2′-naphthyl) octyl group, 2,2-difluoro-8- (2′-naphthyl) octyl group, 3,3-difluoro-8- (2′-) Naphthyl) octyl group, 4,4-difluoro-8- (2′-naphthyl) octyl group, 5,5-difluoro-8- (2′-naphthyl) octyl group, 6,6-difluoro-8- (2 ′) -Naphthyl) octyl group, 7,7-difluoro-8- (2'-naphthyl) octyl group, 8,8-difluoro-8- (2'-naphthyl) octyl group,

6-cyano-2-naphthylmethyl group, 6-nitro-2-naphthylmethyl group, 6-carboxyl-2-naphthylmethyl group, 6-hydroxyl-2-naphthylmethyl group, 6- (N-methylcarboamido)- 2-naphthylmethyl group, 6- (N, N-dimethylcarboamido) -2-naphthylmethyl group, 6-methyl-2-naphthylmethyl group, 6-trifluoromethyl-2-naphthylmethyl group, 6-methoxy- 2-naphthylmethyl group, 6-trifluoromethoxy-2-naphthylmethyl group, 6-methylthio-2-naphthylmethyl group, 6-methylsulfinyl-2-naphthylmethyl group, 6-methylsulfonyl-2-naphthylmethyl group, 6-methoxycarbonyl-2-naphthylmethyl group, 6-vinyl-2-naphthylmethyl group, 6- (2 ′, 2′-difluorovinyl 2-naphthylmethyl group, 6-ethynyl-2-naphthylmethyl group, 6- (2′-fluoroethynyl) -2-naphthylmethyl group, 6-fluoro-2-naphthylmethyl group, 6-chloro-2-naphthyl group Methyl group,
(6′-cyano-1-naphthyl) -difluoromethyl group, (6′-nitro-2-naphthyl) -difluoromethyl group, (6′-carboxyl-2-naphthyl) -difluoromethyl group, (6′-hydroxyl) -2-naphthyl) -difluoromethyl group, (6 ′-(N-methylcarboamido) -2-naphthyl) -difluoromethyl group, (6 ′-(N, N-dimethylcarboamido) -2-naphthyl)- Difluoromethyl group, (6′-methyl-2-naphthyl) -difluoromethyl group, (6′-trifluoromethyl-2-naphthyl) -difluoromethyl group, (6′-methoxy-2-naphthyl) -difluoromethyl group , (6′-trifluoromethoxy-2-naphthyl) -difluoromethyl group, (6′-methylthio-2-naphthyl) -difluoromethyl group, (6′-methylsulfuric acid) Nyl-2-naphthyl) -difluoromethyl group, (6′-methylsulfonyl-2-naphthyl) -difluoromethyl group, (6′-methoxycarbonyl-2-naphthyl) -difluoromethyl group, (6′-vinyl-2) -Naphthyl) -difluoromethyl group, (6 '-(2', 2'-difluorovinyl) -2-naphthyl) -difluoromethyl group, (6'-ethynyl-2-naphthyl) -difluoromethyl group, (6 '-(2'-fluoroethynyl) -2-naphthyl) -difluoromethyl group, (6'-fluoro-1-naphthyl) -difluoromethyl group, (6'-chloro-2-naphthyl) -difluoromethyl group,

2-pyridylmethyl group, 1- (2′-pyridyl) ethyl group, 2- (2′-pyridyl) ethyl group, 3- (2′-pyridyl) propyl group, 4- (2′-pyridyl) butyl group, 5- (2′-pyridyl) pentyl group, 6- (2′-pyridyl) hexyl group, 7- (2′-pyridyl) heptyl group, 8- (2′-pyridyl) octyl group,

4-cyano-2-pyridylmethyl group, 4-nitro-2-pyridylmethyl group, 4-carboxyl-2-pyridylmethyl group, 4-hydroxyl-2-pyridylmethyl group, 4- (N-methylcarboamido)- 2-pyridylmethyl group, 4- (N, N-dimethylcarboamido) -2-pyridylmethyl group, 4-methyl-2-pyridylmethyl group, 4-trifluoromethyl-2-pyridylmethyl group, 4-methoxy- 2-pyridylmethyl group, 4-trifluoromethoxy-2-pyridylmethyl group, 4-methylthio-2-pyridylmethyl group, 4-methylsulfinyl-2-pyridylmethyl group, 4-methylsulfonyl-2-pyridylmethyl group, 4-methoxycarbonyl-2-pyridylmethyl group, 4-vinyl-2-pyridylmethyl group, 4- (2 ′, 2′-difluorovini ) -2-pyridylmethyl group, 4-ethynyl-2-pyridylmethyl group, 4- (2′-fluoroethynyl) -2-pyridylmethyl group, 4-fluoro-2-pyridylmethyl group, 4-chloro-2- A pyridylmethyl group,

5-cyano-2-pyridylmethyl group, 5-nitro-2-pyridylmethyl group, 5-carboxyl-2-pyridylmethyl group, 5-hydroxyl-2-pyridylmethyl group, 5- (N-methylcarboamido)- 2-pyridylmethyl group, 5- (N, N-dimethylcarboamido) -2-pyridylmethyl group, 5-methyl-2-pyridylmethyl group, 5-trifluoromethyl-2-pyridylmethyl group, 5-methoxy- 2-pyridylmethyl group, 5-trifluoromethoxy-2-pyridylmethyl group, 5-methylthio-2-pyridylmethyl group, 5-methylsulfinyl-2-pyridylmethyl group, 5-methylsulfonyl-2-pyridylmethyl group, 5-methoxycarbonyl-2-pyridylmethyl group, 5-vinyl-2-pyridylmethyl group, 5- (2 ′, 2′-difluorovini ) -2-pyridylmethyl group, 5-ethynyl-2-pyridylmethyl group, 5- (2′-fluoroethynyl) -2-pyridylmethyl group, 5-fluoro-2-pyridylmethyl group, 5-chloro-2- A pyridylmethyl group,

6-cyano-2-pyridylmethyl group, 6-nitro-2-pyridylmethyl group, 6-carboxyl-2-pyridylmethyl group, 6-hydroxyl-2-pyridylmethyl group, 6- (N-methylcarboamido)- 2-pyridylmethyl group, 6- (N, N-dimethylcarboamido) -2-pyridylmethyl group, 6-methyl-2-pyridylmethyl group, 6-trifluoromethyl-2-pyridylmethyl group, 6-methoxy- 2-pyridylmethyl group, 6-trifluoromethoxy-2-pyridylmethyl group, 6-methylthio-2-pyridylmethyl group, 6-methylsulfinyl-2-pyridylmethyl group, 6-methylsulfonyl-2-pyridylmethyl group, 6-methoxycarbonyl-2-pyridylmethyl group, 6-vinyl-2-pyridylmethyl group, 6- (2 ′, 2′-difluorovini ) -2-pyridylmethyl group, 6-ethynyl-2-pyridylmethyl group, 6- (2′-fluoroethynyl) -2-pyridylmethyl group, 6-fluoro-2-pyridylmethyl group, 6-chloro-2- Pyridylmethyl group, 6,6-dichloro-2-pyridylmethyl group,

3-pyridylmethyl group, 1- (3′-pyridyl) ethyl group, 2- (3′-pyridyl) ethyl group, 3- (3′-pyridyl) propyl group, 4- (3′-pyridyl) butyl group, 5- (3′-pyridyl) pentyl group, 6- (3′-pyridyl) hexyl group, 7- (3′-pyridyl) heptyl group, 8- (3′-pyridyl) octyl group,

5-cyano-3-pyridylmethyl group, 5-nitro-3-pyridylmethyl group, 5-carboxyl-3-pyridylmethyl group, 5-hydroxyl-3-pyridylmethyl group, 5- (N-methylcarboxamide)- 3-pyridylmethyl group, 5- (N, N-dimethylcarboamido) -3-pyridylmethyl group, 5-methyl-3-pyridylmethyl group, 5-trifluoromethyl-3-pyridylmethyl group, 5-methoxy- 3-pyridylmethyl group, 5-trifluoromethoxy-3-pyridylmethyl group, 5-methylthio-3-pyridylmethyl group, 5-methylsulfinyl-3-pyridylmethyl group, 5-methylsulfonyl-3-pyridylmethyl group, 5-methoxycarbonyl-3-pyridylmethyl group, 5-vinyl-3-pyridylmethyl group, 5- (2 ′, 2′-difluorovini ) -3-pyridylmethyl group, 5-ethynyl-3-pyridylmethyl group, 5- (2′-fluoroethynyl) -3-pyridylmethyl group, 5-fluoro-3-pyridylmethyl group, 5-chloro-3- A pyridylmethyl group,

6-cyano-3-pyridylmethyl group, 6-nitro-3-pyridylmethyl group, 6-carboxyl-3-pyridylmethyl group, 6-hydroxyl-3-pyridylmethyl group, 6- (N-methylcarboxamide)- 3-pyridylmethyl group, 6- (N, N-dimethylcarboamido) -3-pyridylmethyl group, 6-methyl-3-pyridylmethyl group, 6-trifluoromethyl-3-pyridylmethyl group, 6-methoxy- 3-pyridylmethyl group, 6-trifluoromethoxy-3-pyridylmethyl group, 6-methylthio-3-pyridylmethyl group, 6-methylsulfinyl-3-pyridylmethyl group, 6-methylsulfonyl-3-pyridylmethyl group, 6-methoxycarbonyl-3-pyridylmethyl group, 6-vinyl-3-pyridylmethyl group, 6- (2 ′, 2′-difluorovini ) -3-pyridylmethyl group, 6-ethynyl-3-pyridylmethyl group, 6- (2′-fluoroethynyl) -3-pyridylmethyl group, 6-fluoro-3-pyridylmethyl group, 6-chloro-3- A pyridylmethyl group,

4-pyridylmethyl group, 1- (4′-pyridyl) ethyl group, 2- (4′-pyridyl) ethyl group, 3- (4′-pyridyl) propyl group, 4- (4′-pyridyl) butyl group, 5- (4′-pyridyl) pentyl group, 6- (4′-pyridyl) hexyl group, 7- (4′-pyridyl) heptyl group, 8- (4′-pyridyl) octyl group,

2-cyano-4-pyridylmethyl group, 2-nitro-4-pyridylmethyl group, 2-carboxyl-4-pyridylmethyl group, 2-hydroxyl-4-pyridylmethyl group, 2- (N-methylcarboxamide)- 4-pyridylmethyl group, 2- (N, N-dimethylcarboamido) -4-pyridylmethyl group, 2-methyl-4-pyridylmethyl group, 2-trifluoromethyl-4-pyridylmethyl group, 2-methoxy- 4-pyridylmethyl group, 2-trifluoromethoxy-4-pyridylmethyl group, 2-methylthio-4-pyridylmethyl group, 2-methylsulfinyl-4-pyridylmethyl group, 2-methylsulfonyl-4-pyridylmethyl group, 2-methoxycarbonyl-4-pyridylmethyl group, 2-vinyl-4-pyridylmethyl group, 2- (2 ′, 2′-difluorovini ) -4-pyridylmethyl group, 2-ethynyl-4-pyridylmethyl group, 2- (2′-fluoroethynyl) -4-pyridylmethyl group, 2-fluoro-4-pyridylmethyl group, 2-chloro-4- A pyridylmethyl group,

6-cyano-4-pyridylmethyl group, 6-nitro-4-pyridylmethyl group, 6-carboxyl-4-pyridylmethyl group, 6-hydroxyl-4-pyridylmethyl group, 6- (N-methylcarboamido)- 4-pyridylmethyl group, 6- (N, N-dimethylcarboamido) -4-pyridylmethyl group, 6-methyl-4-pyridylmethyl group, 6-trifluoromethyl-4-pyridylmethyl group, 6-methoxy- 4-pyridylmethyl group, 6-trifluoromethoxy-4-pyridylmethyl group, 6-methylthio-4-pyridylmethyl group, 6-methylsulfinyl-4-pyridylmethyl group, 6-methylsulfonyl-4-pyridylmethyl group, 6-methoxycarbonyl-4-pyridylmethyl group, 6-vinyl-4-pyridylmethyl group, 6- (2 ′, 2′-difluorovini ) -4-pyridylmethyl group, 6-ethynyl-4-pyridylmethyl group, 6- (2′-fluoroethynyl) -4-pyridylmethyl group, 6-fluoro-4-pyridylmethyl group, 6-chloro-4- A pyridylmethyl group,

2-quinolylmethyl group, 1- (2′-quinolyl) ethyl group, 2- (2′-quinolyl) ethyl group, 3- (2′-quinolyl) propyl group, 4- (2′-quinolyl) butyl group, 5 -(2'-quinolyl) pentyl group, 6- (2'-quinolyl) hexyl group, 7- (2'-quinolyl) heptyl group, 8- (2'-quinolyl) octyl group,

6-cyano-2-quinolylmethyl group, 6-nitro-2-quinolylmethyl group, 6-carboxyl-2-quinolylmethyl group, 6-hydroxyl-2-quinolylmethyl group, 6- (N-methylcarboamido) -2-quinolylmethyl group 6- (N, N-dimethylcarboamido) -2-quinolylmethyl group, 6-methyl-2-quinolylmethyl group, 6-trifluoromethyl-2-quinolylmethyl group, 6-methoxy-2-quinolylmethyl group, 6-triol Fluoromethoxy-2-quinolylmethyl group, 6-methylthio-2-quinolylmethyl group, 6-methylsulfinyl-2-quinolylmethyl group, 6-methylsulfonyl-2-quinolylmethyl group, 6-methoxycarbonyl-2-quinolylmethyl group, 6-vinyl 2-quinolylmethyl group, 6- (2 ′, 2′-difluorovini ) -2-quinolylmethyl group, a 6-ethynyl-2-quinolylmethyl group, 6- (2'-fluoro-ethynyl) -2-quinolylmethyl group, 6-fluoro-2-quinolylmethyl group, 6-chloro-2-quinolylmethyl group,

3-quinolylmethyl group, 1- (3′-quinolyl) ethyl group, 2- (3′-quinolyl) ethyl group, 3- (3′-quinolyl) propyl group, 4- (3′-quinolyl) butyl group, 5 -(3'-quinolyl) pentyl group, 6- (3'-quinolyl) hexyl group, 7- (3'-quinolyl) heptyl group, 8- (3'-quinolyl) octyl group,

6-cyano-3-quinolylmethyl group, 6-nitro-3-quinolylmethyl group, 6-carboxyl-3-quinolylmethyl group, 6-hydroxyl-3-quinolylmethyl group, 6- (N-methylcarboamido) -3-quinolylmethyl group 6- (N, N-dimethylcarboamido) -3-quinolylmethyl group, 6-methyl-3-quinolylmethyl group, 6-trifluoromethyl-3-quinolylmethyl group, 6-methoxy-3-quinolylmethyl group, 6-triol Fluoromethoxy-3-quinolylmethyl group, 6-methylthio-3-quinolylmethyl group, 6-methylsulfinyl-3-quinolylmethyl group, 6-methylsulfonyl-3-quinolylmethyl group, 6-methoxycarbonyl-3-quinolylmethyl group, 6-vinyl -3-quinolylmethyl group, 6- (2 ′, 2′-difluorovini ) -3-quinolylmethyl group, a 6-ethynyl-3-quinolylmethyl group, 6- (2'-fluoro-ethynyl) -3-quinolylmethyl group, 6-fluoro-3-quinolylmethyl group, 6-chloro-3-quinolylmethyl group,

4-quinolylmethyl group, 1- (4′-quinolyl) ethyl group, 2- (4′-quinolyl) ethyl group, 3- (4′-quinolyl) propyl group, 4- (4′-quinolyl) butyl group, 5 -(3'-quinolyl) pentyl group, 6- (4'-quinolyl) hexyl group, 7- (4'-quinolyl) heptyl group, 8- (4'-quinolyl) octyl group,

6-cyano-4-quinolylmethyl group, 6-nitro-4-quinolylmethyl group, 6-carboxyl-4-quinolylmethyl group, 6-hydroxyl-4-quinolylmethyl group, 6- (N-methylcarboamido) -4-quinolylmethyl group 6- (N, N-dimethylcarboamido) -4-quinolylmethyl group, 6-methyl-4-quinolylmethyl group, 6-trifluoromethyl-4-quinolylmethyl group, 6-methoxy-4-quinolylmethyl group, 6-triol Fluoromethoxy-4-quinolylmethyl group, 6-methylthio-4-quinolylmethyl group, 6-methylsulfinyl-4-quinolylmethyl group, 6-methylsulfonyl-4-quinolylmethyl group, 6-methoxycarbonyl-4-quinolylmethyl group, 6-vinyl -4-quinolylmethyl group, 6- (2 ', 2'-difluorovini ) -4-quinolylmethyl group, 6-ethynyl-4-quinolylmethyl group, 6- (2'-fluoro ethynyl) -4-quinolylmethyl group, 6-fluoro-4-quinolylmethyl group, 6-chloro-4-quinolylmethyl group,

2-furylmethyl group, 1- (2′-furyl) ethyl group, 2- (2′-furyl) ethyl group, 3- (2′-furyl) propyl group, 4- (2′-furyl) butyl group, 5- (2′-furyl) pentyl group, 6- (2′-furyl) hexyl group, 7- (2′-furyl) heptyl group, 8- (2′-furyl) octyl group,

4-cyano-2-furylmethyl group, 4-nitro-2-furylmethyl group, 4-carboxyl-2-furylmethyl group, 4-hydroxyl-2-furylmethyl group, 4- (N-methylcarboamido)- 2-furylmethyl group, 4- (N, N-dimethylcarboamido) -2-furylmethyl group, 4-methyl-2-furylmethyl group, 4-trifluoromethyl-2-furylmethyl group, 4-methoxy- 2-furylmethyl group, 4-trifluoromethoxy-2-furylmethyl group, 4-methylthio-2-furylmethyl group, 4-methylsulfinyl-2-furylmethyl group, 4-methylsulfonyl-2-furylmethyl group, 4-methoxycarbonyl-2-furylmethyl group, 4-vinyl-2-furylmethyl group, 4- (2 ′, 2′-difluorovinyl) -2-furylmethyl group, 4- Ethynyl-2-furylmethyl group, 4- (2'-fluoro-ethynyl) -2-furylmethyl group, 4-fluoro-2-furylmethyl group, 4-chloro-2-furylmethyl group,

3-furylmethyl group, 1- (3′-furyl) ethyl group, 2- (3′-furyl) ethyl group, 3- (3′-furyl) propyl group, 4- (3′-furyl) butyl group, 5- (3′-furyl) pentyl group, 6- (3′-furyl) hexyl group, 7- (3′-furyl) heptyl group, 8- (3′-furyl) octyl group,

4-cyano-3-furylmethyl group, 4-nitro-3-furylmethyl group, 4-carboxyl-3-furylmethyl group, 4-hydroxyl-3-furylmethyl group, 4- (N-methylcarboxamide)- 3-furylmethyl group, 4- (N, N-dimethylcarboamido) -3-furylmethyl group, 4-methyl-3-furylmethyl group, 4-trifluoromethyl-3-furylmethyl group, 4-methoxy- 3-furylmethyl group, 4-trifluoromethoxy-3-furylmethyl group, 4-methylthio-3-furylmethyl group, 4-methylsulfinyl-3-furylmethyl group, 4-methylsulfonyl-3-furylmethyl group, 4-methoxycarbonyl-3-furylmethyl group, 4-vinyl-3-furylmethyl group, 4- (2 ′, 2′-difluorovinyl) -3-furylmethyl group, 4- Ethynyl-3-furylmethyl group, 4- (2'-fluoro-ethynyl) -3-furylmethyl group, 4-fluoro-3-furylmethyl group, 4-chloro-3-furylmethyl group,

2-thienylmethyl group, 1- (2′-thienyl) ethyl group, 2- (2′-thienyl) ethyl group, 3- (2′-thienyl) propyl group, 4- (2′-thienyl) butyl group, 5- (2′-thienyl) pentyl group, 6- (2′-thienyl) hexyl group, 7- (2′-thienyl) heptyl group, 8- (2′-thienyl) octyl group,

4-cyano-2-thienylmethyl group, 4-nitro-2-thienylmethyl group, 4-carboxyl-2-thienylmethyl group, 4-hydroxyl-2-thienylmethyl group, 4- (N-methylcarboamido)- 2-thienylmethyl group, 4- (N, N-dimethylcarboamido) -2-thienylmethyl group, 4-methyl-2-thienylmethyl group, 4-trifluoromethyl-2-thienylmethyl group, 4-methoxy- 2-thienylmethyl group, 4-trifluoromethoxy-2-thienylmethyl group, 4-methylthio-2-thienylmethyl group, 4-methylsulfinyl-2-thienylmethyl group, 4-methylsulfonyl-2-thienylmethyl group, 4-methoxycarbonyl-2-thienylmethyl group, 4-vinyl-2-thienylmethyl group, 4- (2 ′, 2′-difluorovini ) -2-thienylmethyl group, 4-ethynyl-2-thienylmethyl group, 4- (2'-fluoroethynyl) -2-thienylmethyl group, 4-fluoro-2-thienylmethyl group, 4-chloro-2- Thienylmethyl group,

3-thienylmethyl group, 1- (3′-thienyl) ethyl group, 2- (3′-thienyl) ethyl group, 3- (3′-thienyl) propyl group, 4- (3′-thienyl) butyl group, 5- (3′-thienyl) pentyl group, 6- (3′-thienyl) hexyl group, 7- (3′-thienyl) heptyl group, 8- (3′-thienyl) octyl group,

4-cyano-3-thienylmethyl group, 4-nitro-3-thienylmethyl group, 4-carboxyl-3-thienylmethyl group, 4-hydroxyl-3-thienylmethyl group, 4- (N-methylcarboamido)- 3-thienylmethyl group, 4- (N, N-dimethylcarboamido) -3-thienylmethyl group, 4-methyl-3-thienylmethyl group, 4-trifluoromethyl-3-thienylmethyl group, 4-methoxy- 3-thienylmethyl group, 4-trifluoromethoxy-3-thienylmethyl group, 4-methylthio-3-thienylmethyl group, 4-methylsulfinyl-3-thienylmethyl group, 4-methylsulfonyl-3-thienylmethyl group, 4-methoxycarbonyl-3-thienylmethyl group, 4-vinyl-3-thienylmethyl group, 4- (2 ′, 2′-difluorovini ) -3-thienylmethyl group, 4-ethynyl-3-thienylmethyl group, 4- (2'-fluoroethynyl) -3-thienylmethyl group, 4-fluoro-3-thienylmethyl group, 4-chloro-3- Thienylmethyl group,

2- (1-benzofuranyl) methyl group, 1- (2 ′-(1′-benzofuranyl)) ethyl group, 2- (2 ′-(1′-benzofuranyl)) ethyl group, 3- (2 ′-(1 '-Benzofuranyl)) propyl group, 4- (2'-(1'-benzofuranyl)) butyl group, 5- (2 '-(1'-benzofuranyl)) pentyl group, 6- (2'-(1'-) Benzofuranyl)) hexyl group, 7- (2 ′-(1′-benzofuranyl)) heptyl group, 8- (2 ′-(1′-benzofuranyl)) octyl group,

5-cyano-2- (1-benzofuranyl) methyl group, 5-nitro-2- (1-benzofuranyl) methyl group, 5-carboxyl-2- (1-benzofuranyl) methyl group, 5-hydroxyl-2- (1 -Benzofuranyl) methyl group, 5- (N-methylcarboamido) -2- (1-benzofuranyl) methyl group, 5- (N, N-dimethylcarboamido) -2- (1-benzofuranyl) methyl group, 5- Methyl-2- (1-benzofuranyl) methyl group, 5-trifluoromethyl-2- (1-benzofuranyl) methyl group, 5-methoxy-2- (1-benzofuranyl) methyl group, 5-trifluoromethoxy-2- (1-benzofuranyl) methyl group, 5-methylthio-2- (1-benzofuranyl) methyl group, 5-methylsulfinyl-2- (1-benzofuranyl) Methyl group, 5-methylsulfonyl-2- (1-benzofuranyl) methyl group, 5-methoxycarbonyl-2- (1-benzofuranyl) methyl group, 5-vinyl-2- (1-benzofuranyl) methyl group, 5- ( 2 ', 2'-difluorovinyl) -2- (1-benzofuranyl) methyl group, 5-ethynyl-2- (1-benzofuranyl) methyl group, 5- (2'-fluoroethynyl) -2- (1-benzofuranyl) ) Methyl group, 5-fluoro-2- (1-benzofuranyl) methyl group, 5-chloro-2- (1-benzofuranyl) methyl group,
3- (1-benzofuranyl) methyl group, 1- (3 ′-(1′-benzofuranyl)) ethyl group, 2- (3 ′-(1′-benzofuranyl)) ethyl group, 3- (3 ′-(1 '-Benzofuranyl)) propyl group, 4- (3'-(1'-benzofuranyl)) butyl group, 5- (3 '-(1'-benzofuranyl)) pentyl group, 6- (3'-(1'-) Benzofuranyl)) hexyl group, 7- (3 ′-(1′-benzofuranyl)) heptyl group, 8- (3 ′-(1′-benzofuranyl)) octyl group,

5-cyano-3- (1-benzofuranyl) methyl group, 5-nitro-3- (1-benzofuranyl) methyl group, 5-carboxyl-3- (1-benzofuranyl) methyl group, 5-hydroxyl-3- (1 -Benzofuranyl) methyl group, 5- (N-methylcarboamido) -3- (1-benzofuranyl) methyl group, 5- (N, N-dimethylcarbamido) -3- (1-benzofuranyl) methyl group, 5- Methyl-3- (1-benzofuranyl) methyl group, 5-trifluoromethyl-3- (1-benzofuranyl) methyl group, 5-methoxy-3- (1-benzofuranyl) methyl group, 5-trifluoromethoxy-3- (1-benzofuranyl) methyl group, 5-methylthio-3- (1-benzofuranyl) methyl group, 5-methylsulfinyl-3- (1-benzofuranyl) Methyl group, 5-methylsulfonyl-3- (1-benzofuranyl) methyl group, 5-methoxycarbonyl-3- (1-benzofuranyl) methyl group, 5-vinyl-3- (1-benzofuranyl) methyl group, 5- ( 2 ', 2'-difluorovinyl) -3- (1-benzofuranyl) methyl group, 5-ethynyl-3- (1-benzofuranyl) methyl group, 5- (2'-fluoroethynyl) -3- (1-benzofuranyl) ) Methyl group, 5-fluoro-3- (1-benzofuranyl) methyl group, 5-chloro-3- (1-benzofuranyl) methyl group,

2- (1-benzothienyl) methyl group, 1- (2 ′-(1′-benzothienyl)) ethyl group, 2- (2 ′-(1′-benzothienyl)) ethyl group, 3- (2 ′ -(1'-benzothienyl)) propyl group, 4- (2 '-(1'-benzothienyl)) butyl group, 5- (2'-(1'-benzothienyl)) pentyl group, 6- (2 '-(1'-benzothienyl)) hexyl group, 7- (2'-(1'-benzothienyl)) heptyl group, 8- (2 '-(1'-benzothienyl)) octyl group,

5-cyano-2- (1-benzothienyl) methyl group, 5-nitro-2- (1-benzothienyl) methyl group, 5-carboxyl-2- (1-benzothienyl) methyl group, 5-hydroxyl-2 -(1-benzothienyl) methyl group, 5- (N-methylcarboamido) -2- (1-benzothienyl) methyl group, 5- (N, N-dimethylcarboamido) -2- (1-benzothienyl) ) Methyl group, 5-methyl-2- (1-benzothienyl) methyl group, 5-trifluoromethyl-2- (1-benzothienyl) methyl group, 5-methoxy-2- (1-benzothienyl) methyl group , 5-trifluoromethoxy-2- (1-benzothienyl) methyl group, 5-methylthio-2- (1-benzothienyl) methyl group, 5-methylsulfinyl-2- (1-benzothienyl) Methyl group, 5-methylsulfonyl-2- (1-benzothienyl) methyl group, 5-methoxycarbonyl-2- (1-benzothienyl) methyl group, 5-vinyl-2- (1-benzothienyl) methyl group, 5- (2 ′, 2′-difluorovinyl) -2- (1-benzothienyl) methyl group, 5-ethynyl-2- (1-benzothienyl) methyl group, 5- (2′-fluoroethynyl) -2 -(1-benzothienyl) methyl group, 5-fluoro-2- (1-benzothienyl) methyl group, 5-chloro-2- (1-benzothienyl) methyl group,

3- (1-benzothienyl) methyl group, 1- (3 ′-(1′-benzothienyl)) ethyl group, 2- (3 ′-(1′-benzothienyl)) ethyl group, 3- (3 ′ -(1'-benzothienyl)) propyl group, 4- (3 '-(1'-benzothienyl)) butyl group, 5- (3'-(1'-benzothienyl)) pentyl group, 6- (3 '-(1'-benzothienyl)) hexyl group, 7- (3'-(1'-benzothienyl)) heptyl group, 8- (3 '-(1'-benzothienyl)) octyl group,

5-cyano-3- (1-benzothienyl) methyl group, 5-nitro-3- (1-benzothienyl) methyl group, 5-carboxyl-3- (1-benzothienyl) methyl group, 5-hydroxyl-3 -(1-benzothienyl) methyl group, 5- (N-methylcarboamido) -3- (1-benzothienyl) methyl group, 5- (N, N-dimethylcarboamido) -3- (1-benzothienyl) ) Methyl group, 5-methyl-3- (1-benzothienyl) methyl group, 5-trifluoromethyl-3- (1-benzothienyl) methyl group, 5-methoxy-3- (1-benzothienyl) methyl group 5-trifluoromethoxy-3- (1-benzothienyl) methyl group, 5-methylthio-3- (1-benzothienyl) methyl group, 5-methylsulfinyl-3- (1-benzothienyl) Methyl group, 5-methylsulfonyl-3- (1-benzothienyl) methyl group, 5-methoxycarbonyl-3- (1-benzothienyl) methyl group, 5-vinyl-3- (1-benzothienyl) methyl group, 5- (2 ′, 2′-difluorovinyl) -3- (1-benzothienyl) methyl group, 5-ethynyl-3- (1-benzothienyl) methyl group, 5- (2′-fluoroethynyl) -3 -(1-benzothienyl) methyl group, 5-fluoro-3- (1-benzothienyl) methyl group, 5-chloro-3- (1-benzothienyl) methyl group

Fluoromethyl group, 1-fluoroethyl group, 1,1-difluoroethyl, 2-fluoroethyl group, 2,2-difluoroethyl group, 2,2,2-trifluoroethyl group, 3-fluoropropyl group, 3, 3,3-trifluoropropyl, 4-fluorobutyl group, 4,4,4-trifluorobutyl group, 3,3,4,4,4-pentafluorobutyl group, 5-fluoropentyl group, 6-fluorohexyl Group, 7-fluoroheptyl group, 8-fluorooctyl group,

Chloromethyl group, 1-chloroethyl group, 2-chloroethyl group, 3-chloropropyl group, 4-chlorobutyl group, 5-chloropentyl group, 6-chlorohexyl group, 7-chloroheptyl group, 8-chlorooctyl group,

Bromomethyl group, 1-bromoethyl group, 2-bromoethyl group, 3-bromopropyl group, 4-bromobutyl group, 5-bromopentyl group, 6-bromohexyl group, 7-bromoheptyl group, 8-bromooctyl group,

(Methoxycarbonyl) methyl group, 1- (methoxycarbonyl) ethyl group, 2- (methoxycarbonyl) ethyl group, 3- (methoxycarbonyl) propyl group, 4- (methoxycarbonyl) butyl group, 5- (methoxycarbonyl) pentyl Group, 6- (methoxycarbonyl) hexyl group, 7- (methoxycarbonyl) heptyl group, 8- (methoxycarbonyl) octyl group,

Cyanomethyl group, 1-cyanoethyl group, 2-cyanoethyl group, 3-cyanopropyl group, 4-cyanobutyl group, 5-cyanopentyl group, 6-cyanohexyl group, 7-cyanoheptyl group, 8-cyanooctyl group,

Nitromethyl group, 1-nitroethyl group, 2-nitroethyl group, 3-nitropropyl group, 4-nitrobutyl group, 5-nitropentyl group, 6-nitrohexyl group, 7-nitroheptyl group, 8-nitrooctyl group,

(Carboxy) methyl group, 1- (carboxy) ethyl group, 2- (carboxy) ethyl group, 3- (carboxy) propyl group, 4- (carboxy) butyl group, 5- (carboxy) pentyl group, 6- (carboxy) ) Hexyl group, 7- (carboxy) heptyl group, 8- (carboxy) octyl group,

Hydroxymethyl group, 1-hydroxyethyl group, 2-hydroxyethyl group, 3-hydroxypropyl group, 4-hydroxybutyl group, 5-hydroxypentyl group, 6-hydroxyhexyl group, 7-hydroxyheptyl group, 8-hydroxyoctyl Group,
Etc.

In the present invention, the “C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G” includes, for example,
Benzyl group, phenyldifluoromethyl group, 1-phenylethyl group, 1,1-difluoro-1-phenylethyl group, 2,2,2-trifluoro-1-phenylethyl group, 1,1,2,2,2 -Pentafluoro-1-phenylethyl group, 2-phenylethyl group, 1,1-difluoro-2-phenylethyl group, 2,2-difluoro-2-phenylethyl group, 1,1,2,2-tetrafluoro 2-phenylethyl group, 3-phenylpropyl group, 1,1-difluoro-3-phenylpropyl group, 2,2-difluoro-3-phenylpropyl group, 3,3-difluoro-3-phenylpropyl group, 1 1,2,2,3,3-hexafluoro-3-phenylpropyl group, 4-phenylbutyl group, 1,1-difluoro-4-phenylbutyl group, 2,2-diph Oro-4-phenylbutyl group, 3,3-difluoro-4-phenylbutyl group, 4,4-difluoro-4-phenylbutyl group, 1,1,2,2,3,3,4,4-octafluoro -3-4-phenylbutyl group, 5-phenylpentyl group, 1,1-difluoro-5-phenylpentyl group, 2,2-difluoro-5-phenylpentyl group, 3,3-difluoro-5-phenylpentyl group 4,4-difluoro-5-phenylpentyl group, 5,5-difluoro-5-phenylpentyl group, 6-phenylhexyl group, 1,1-difluoro-6-phenylhexyl group, 2,2-difluoro-6 -Phenylhexyl group, 3,3-difluoro-6-phenylhexyl group, 4,4-difluoro-6-phenylhexyl group, 5,5-difluoro-6-phenylhexyl group Sil group, 6,6-difluoro-6-phenylhexyl group, 7-phenylheptyl group, 1,1-difluoro-7-phenylheptyl group, 2,2-difluoro-7-phenylheptyl group, 3,3-difluoro -7-phenylheptyl group, 4,4-difluoro-7-phenylheptyl group, 5,5-difluoro-7-phenylheptyl group, 6,6-difluoro-7-phenylheptyl group, 7,7-difluoro-7 -Phenylheptyl group, 8-phenyloctyl group, 1,1-difluoro-8-phenyloctyl group, 2,2-difluoro-8-phenyloctyl group, 3,3-difluoro-8-phenyloctyl group, 4,4 -Difluoro-8-phenyloctyl group, 5,5-difluoro-8-phenyloctyl group, 6,6-difluoro-8-phenyloctyl group Group, 7,7-difluoro-8-phenyloctyl group, 8,8-difluoro-8-phenyloctyl group,

4-cyanobenzyl group, 4-nitrobenzyl group, 4-carboxylbenzyl group, 4-hydroxylbenzyl group, 4- (N-methylcarboamido) benzyl group, 4- (N, N-dimethylcarboamido) benzyl group, 4-methylbenzyl group, 4-trifluoromethylbenzyl group, 4-methoxybenzyl group, 4-trifluoromethoxybenzyl group, 4-methylthiobenzyl group, 4-methylsulfinylbenzyl group, 4-methylsulfonylbenzyl group, 4- Methoxycarbonylbenzyl group, 4-vinylbenzyl group, 4- (2 ′, 2′-difluorovinyl) benzyl group, 4-ethynylbenzyl group, 4- (2′-fluoroethynyl) benzyl group, 4-fluorobenzyl group, 4-chlorobenzyl group, 3,4-dichlorobenzyl group,
(4′-cyanophenyl) difluoromethyl group, (4′-nitrophenyl) difluoromethyl group, (4′-carboxylphenyl) difluoromethyl group, (4′-hydroxylphenyl) difluoromethyl group, (4 ′-(N -Methylcarboamido) phenyl) difluoromethyl group, (4 '-(N, N-dimethylcarboamido) phenyl) difluoromethyl group, (4'-methylphenyl) difluoromethyl group, (4'-trifluoromethylphenyl) Difluoromethyl group, (4′-methoxyphenyl) difluoromethyl group, (4′-trifluoromethoxyphenyl) difluoromethyl group, (4′-methylthiophenyl) difluoromethyl group, (4′-methylsulfinylphenyl) difluoromethyl group , (4′-methylsulfonylphenyl) difluoromethyl group, (4′-methoxycarbonylphenyl) difluoromethyl group, (4′-vinylphenyl) difluoromethyl group, (4 ′-(2 ′, 2′-difluorovinyl) phenyl) difluoromethyl group, (4′-ethynylphenyl) Difluoromethyl group, (4 ′-(2′-fluoroethynyl) phenyl) difluoromethyl group, (4′-fluorophenyl) difluoromethyl group, (4′-chlorophenyl) difluoromethyl group, 3, (4′-dichlorophenyl) Difluoromethyl group,

1-naphthylmethyl group, (1′-naphthyl) difluoromethyl group, 1- (1′-naphthyl) ethyl group, 1,1-difluoro-1- (1′-naphthyl) ethyl group, 2,2,2- Trifluoro-1- (1′-naphthyl) ethyl group, 1,1,2,2,2-pentafluoro-1- (1′-naphthyl) ethyl group, 2- (1′-naphthyl) ethyl group, 1 , 1-Difluoro-2- (1′-naphthyl) ethyl group, 2,2-difluoro-2- (1′-naphthyl) ethyl group, 1,1,2,2-tetrafluoro-2- (1′- Naphthyl) ethyl group, 3- (1′-naphthyl) propyl group, 1,1-difluoro-3- (1′-naphthyl) propyl group, 2,2-difluoro-3- (1′-naphthyl) propyl group, 3,3-difluoro-3- (1′-naphthyl) propyl group, , 1,2,2,3,3-hexafluoro-3- (1′-naphthyl) propyl group, 4- (1′-naphthyl) butyl group, 1,1-difluoro-4- (1′-naphthyl) Butyl group, 2,2-difluoro-4- (1′-naphthyl) butyl group, 3,3-difluoro-4- (1′-naphthyl) butyl group, 4,4-difluoro-4- (1′-naphthyl) ) Butyl group, 1,1,2,2,3,3,4,4-octafluoro-3--4- (1′-naphthyl) butyl group, 5- (1′-naphthyl) pentyl group, 1,1 -Difluoro-5- (1'-naphthyl) pentyl group, 2,2-difluoro-5- (1'-naphthyl) pentyl group, 3,3-difluoro-5- (1'-naphthyl) pentyl group, 4, 4-difluoro-5- (1′-naphthyl) pentyl group, 5,5-difluoro 5- (1′-naphthyl) pentyl group, 6- (1′-naphthyl) hexyl group, 1,1-difluoro-6- (1′-naphthyl) hexyl group, 2,2-difluoro-6- (1 ′ -Naphthyl) hexyl group, 3,3-difluoro-6- (1'-naphthyl) hexyl group, 4,4-difluoro-6- (1'-naphthyl) hexyl group, 5,5-difluoro-6- (1 '-Naphthyl) hexyl group, 6,6-difluoro-6- (1'-naphthyl) hexyl group, 7- (1'-naphthyl) heptyl group, 1,1-difluoro-7- (1'-naphthyl) heptyl Group, 2,2-difluoro-7- (1′-naphthyl) heptyl group, 3,3-difluoro-7- (1′-naphthyl) heptyl group, 4,4-difluoro-7- (1′-naphthyl) Heptyl group, 5,5-difluoro-7- (1′-naphthyl) heptyl group, 6,6-difluoro-7- (1′-naphthyl) heptyl group, 7,7-difluoro-7- (1′-naphthyl) heptyl group, 8- (1′-naphthyl) ) Octyl group, 1,1-difluoro-8- (1′-naphthyl) octyl group, 2,2-difluoro-8- (1′-naphthyl) octyl group, 3,3-difluoro-8- (1′-) Naphthyl) octyl group, 4,4-difluoro-8- (1′-naphthyl) octyl group, 5,5-difluoro-8- (1′-naphthyl) octyl group, 6,6-difluoro-8- (1 ′) -Naphthyl) octyl group, 7,7-difluoro-8- (1'-naphthyl) octyl group, 8,8-difluoro-8- (1'-naphthyl) octyl group,

6-cyano-1-naphthylmethyl group, 6-nitro-1-naphthylmethyl group, 6-carboxyl-1-naphthylmethyl group, 6-hydroxyl-1-naphthylmethyl group, 6- (N-methylcarboamido)- 1-naphthylmethyl group, 6- (N, N-dimethylcarboamido) -1-naphthylmethyl group, 6-methyl-1-naphthylmethyl group, 6-trifluoromethyl-1-naphthylmethyl group, 6-methoxy- 1-naphthylmethyl group, 6-trifluoromethoxy-1-naphthylmethyl group, 6-methylthio-1-naphthylmethyl group, 6-methylsulfinyl-1-naphthylmethyl group, 6-methylsulfonyl-1-naphthylmethyl group, 6-methoxycarbonyl-1-naphthylmethyl group, 6-vinyl-1-naphthylmethyl group, 6- (2 ′, 2′-difluorovinyl -1-naphthylmethyl group, 6-ethynyl-1-naphthylmethyl group, 6- (2′-fluoroethynyl) -1-naphthylmethyl group, 6-fluoro-1-naphthylmethyl group, 6-chloro-1-naphthyl Methyl group,
(6′-cyano-1-naphthyl) -difluoromethyl group, (6′-nitro-1-naphthyl) -difluoromethyl group, (6′-carboxyl-1-naphthyl) -difluoromethyl group, (6′-hydroxyl) -1-naphthyl) -difluoromethyl group, (6 ′-(N-methylcarboamido) -1-naphthyl) -difluoromethyl group, (6 ′-(N, N-dimethylcarboamido) -1-naphthyl)- Difluoromethyl group, (6′-methyl-1-naphthyl) -difluoromethyl group, (6′-trifluoromethyl-1-naphthyl) -difluoromethyl group, (6′-methoxy-1-naphthyl) -difluoromethyl group , (6′-trifluoromethoxy-1-naphthyl) -difluoromethyl group, (6′-methylthio-1-naphthyl) -difluoromethyl group, (6′-methylsulfuric acid) Nyl-1-naphthyl) -difluoromethyl group, (6′-methylsulfonyl-1-naphthyl) -difluoromethyl group, (6′-methoxycarbonyl-1-naphthyl) -difluoromethyl group, (6′-vinyl-1) -Naphthyl) -difluoromethyl group, (6 '-(2', 2'-difluorovinyl) -1-naphthyl) -difluoromethyl group, (6'-ethynyl-1-naphthyl) -difluoromethyl group, (6 '-(2'-fluoroethynyl) -1-naphthyl) -difluoromethyl group, (6'-fluoro-1-naphthyl) -difluoromethyl group, (6'-chloro-1-naphthyl) -difluoromethyl group,

2-naphthylmethyl group, (2′-naphthyl) difluoromethyl group, 1- (2′-naphthyl) ethyl group, 1,1-difluoro-1- (2′-naphthyl) ethyl group, 2,2,2- Trifluoro-1- (2′-naphthyl) ethyl group, 1,1,2,2,2-pentafluoro-1- (2′-naphthyl) ethyl group, 2- (2′-naphthyl) ethyl group, 1 , 1-Difluoro-2- (2′-naphthyl) ethyl group, 2,2-difluoro-2- (2′-naphthyl) ethyl group, 1,1,2,2-tetrafluoro-2- (2′- Naphthyl) ethyl group, 3- (2′-naphthyl) propyl group, 1,1-difluoro-3- (2′-naphthyl) propyl group, 2,2-difluoro-3- (2′-naphthyl) propyl group, 3,3-difluoro-3- (2′-naphthyl) propyl group, 1,2,2,3,3-hexafluoro-3- (2'-naphthyl) propyl group, 4- (2'-naphthyl) butyl group, 1,1-difluoro-4- (2'-naphthyl) Butyl group, 2,2-difluoro-4- (2′-naphthyl) butyl group, 3,3-difluoro-4- (2′-naphthyl) butyl group, 4,4-difluoro-4- (2′-naphthyl) ) Butyl group, 1,1,2,2,3,3,4,4-octafluoro-3--4- (2′-naphthyl) butyl group, 5- (2′-naphthyl) pentyl group, 1,1 -Difluoro-5- (2'-naphthyl) pentyl group, 2,2-difluoro-5- (2'-naphthyl) pentyl group, 3,3-difluoro-5- (2'-naphthyl) pentyl group, 4, 4-difluoro-5- (2′-naphthyl) pentyl group, 5,5-difluoro 5- (2′-naphthyl) pentyl group, 6- (2′-naphthyl) hexyl group, 1,1-difluoro-6- (2′-naphthyl) hexyl group, 2,2-difluoro-6- (2 ′ -Naphthyl) hexyl group, 3,3-difluoro-6- (2'-naphthyl) hexyl group, 4,4-difluoro-6- (2'-naphthyl) hexyl group, 5,5-difluoro-6- (2 '-Naphthyl) hexyl group, 6,6-difluoro-6- (2'-naphthyl) hexyl group, 7- (2'-naphthyl) heptyl group, 1,1-difluoro-7- (2'-naphthyl) heptyl Group, 2,2-difluoro-7- (2′-naphthyl) heptyl group, 3,3-difluoro-7- (2′-naphthyl) heptyl group, 4,4-difluoro-7- (2′-naphthyl) Heptyl group, 5,5-difluoro-7- (2′-naphthyl) heptyl group, 6,6-difluoro-7- (2′-naphthyl) heptyl group, 7,7-difluoro-7- (2′-naphthyl) heptyl group, 8- (2′-naphthyl) ) Octyl group, 1,1-difluoro-8- (2′-naphthyl) octyl group, 2,2-difluoro-8- (2′-naphthyl) octyl group, 3,3-difluoro-8- (2′-) Naphthyl) octyl group, 4,4-difluoro-8- (2′-naphthyl) octyl group, 5,5-difluoro-8- (2′-naphthyl) octyl group, 6,6-difluoro-8- (2 ′) -Naphthyl) octyl group, 7,7-difluoro-8- (2'-naphthyl) octyl group, 8,8-difluoro-8- (2'-naphthyl) octyl group,

6-cyano-2-naphthylmethyl group, 6-nitro-2-naphthylmethyl group, 6-carboxyl-2-naphthylmethyl group, 6-hydroxyl-2-naphthylmethyl group, 6- (N-methylcarboamido)- 2-naphthylmethyl group, 6- (N, N-dimethylcarboamido) -2-naphthylmethyl group, 6-methyl-2-naphthylmethyl group, 6-trifluoromethyl-2-naphthylmethyl group, 6-methoxy- 2-naphthylmethyl group, 6-trifluoromethoxy-2-naphthylmethyl group, 6-methylthio-2-naphthylmethyl group, 6-methylsulfinyl-2-naphthylmethyl group, 6-methylsulfonyl-2-naphthylmethyl group, 6-methoxycarbonyl-2-naphthylmethyl group, 6-vinyl-2-naphthylmethyl group, 6- (2 ′, 2′-difluorovinyl 2-naphthylmethyl group, 6-ethynyl-2-naphthylmethyl group, 6- (2′-fluoroethynyl) -2-naphthylmethyl group, 6-fluoro-2-naphthylmethyl group, 6-chloro-2-naphthyl group Methyl group,
(6′-cyano-1-naphthyl) -difluoromethyl group, (6′-nitro-2-naphthyl) -difluoromethyl group, (6′-carboxyl-2-naphthyl) -difluoromethyl group, (6′-hydroxyl) -2-naphthyl) -difluoromethyl group, (6 ′-(N-methylcarboamido) -2-naphthyl) -difluoromethyl group, (6 ′-(N, N-dimethylcarboamido) -2-naphthyl)- Difluoromethyl group, (6′-methyl-2-naphthyl) -difluoromethyl group, (6′-trifluoromethyl-2-naphthyl) -difluoromethyl group, (6′-methoxy-2-naphthyl) -difluoromethyl group , (6′-trifluoromethoxy-2-naphthyl) -difluoromethyl group, (6′-methylthio-2-naphthyl) -difluoromethyl group, (6′-methylsulfuric acid) Nyl-2-naphthyl) -difluoromethyl group, (6′-methylsulfonyl-2-naphthyl) -difluoromethyl group, (6′-methoxycarbonyl-2-naphthyl) -difluoromethyl group, (6′-vinyl-2) -Naphthyl) -difluoromethyl group, (6 '-(2', 2'-difluorovinyl) -2-naphthyl) -difluoromethyl group, (6'-ethynyl-2-naphthyl) -difluoromethyl group, (6 '-(2'-fluoroethynyl) -2-naphthyl) -difluoromethyl group, (6'-fluoro-1-naphthyl) -difluoromethyl group, (6'-chloro-2-naphthyl) -difluoromethyl group,

2-pyridylmethyl group, 1- (2′-pyridyl) ethyl group, 2- (2′-pyridyl) ethyl group, 3- (2′-pyridyl) propyl group, 4- (2′-pyridyl) butyl group, 5- (2′-pyridyl) pentyl group, 6- (2′-pyridyl) hexyl group, 7- (2′-pyridyl) heptyl group, 8- (2′-pyridyl) octyl group,

4-cyano-2-pyridylmethyl group, 4-nitro-2-pyridylmethyl group, 4-carboxyl-2-pyridylmethyl group, 4-hydroxyl-2-pyridylmethyl group, 4- (N-methylcarboamido)- 2-pyridylmethyl group, 4- (N, N-dimethylcarboamido) -2-pyridylmethyl group, 4-methyl-2-pyridylmethyl group, 4-trifluoromethyl-2-pyridylmethyl group, 4-methoxy- 2-pyridylmethyl group, 4-trifluoromethoxy-2-pyridylmethyl group, 4-methylthio-2-pyridylmethyl group, 4-methylsulfinyl-2-pyridylmethyl group, 4-methylsulfonyl-2-pyridylmethyl group, 4-methoxycarbonyl-2-pyridylmethyl group, 4-vinyl-2-pyridylmethyl group, 4- (2 ′, 2′-difluorovini ) -2-pyridylmethyl group, 4-ethynyl-2-pyridylmethyl group, 4- (2′-fluoroethynyl) -2-pyridylmethyl group, 4-fluoro-2-pyridylmethyl group, 4-chloro-2- A pyridylmethyl group,

5-cyano-2-pyridylmethyl group, 5-nitro-2-pyridylmethyl group, 5-carboxyl-2-pyridylmethyl group, 5-hydroxyl-2-pyridylmethyl group, 5- (N-methylcarboamido)- 2-pyridylmethyl group, 5- (N, N-dimethylcarboamido) -2-pyridylmethyl group, 5-methyl-2-pyridylmethyl group, 5-trifluoromethyl-2-pyridylmethyl group, 5-methoxy- 2-pyridylmethyl group, 5-trifluoromethoxy-2-pyridylmethyl group, 5-methylthio-2-pyridylmethyl group, 5-methylsulfinyl-2-pyridylmethyl group, 5-methylsulfonyl-2-pyridylmethyl group, 5-methoxycarbonyl-2-pyridylmethyl group, 5-vinyl-2-pyridylmethyl group, 5- (2 ′, 2′-difluorovini ) -2-pyridylmethyl group, 5-ethynyl-2-pyridylmethyl group, 5- (2′-fluoroethynyl) -2-pyridylmethyl group, 5-fluoro-2-pyridylmethyl group, 5-chloro-2- A pyridylmethyl group,

6-cyano-2-pyridylmethyl group, 6-nitro-2-pyridylmethyl group, 6-carboxyl-2-pyridylmethyl group, 6-hydroxyl-2-pyridylmethyl group, 6- (N-methylcarboamido)- 2-pyridylmethyl group, 6- (N, N-dimethylcarboamido) -2-pyridylmethyl group, 6-methyl-2-pyridylmethyl group, 6-trifluoromethyl-2-pyridylmethyl group, 6-methoxy- 2-pyridylmethyl group, 6-trifluoromethoxy-2-pyridylmethyl group, 6-methylthio-2-pyridylmethyl group, 6-methylsulfinyl-2-pyridylmethyl group, 6-methylsulfonyl-2-pyridylmethyl group, 6-methoxycarbonyl-2-pyridylmethyl group, 6-vinyl-2-pyridylmethyl group, 6- (2 ′, 2′-difluorovini ) -2-pyridylmethyl group, 6-ethynyl-2-pyridylmethyl group, 6- (2′-fluoroethynyl) -2-pyridylmethyl group, 6-fluoro-2-pyridylmethyl group, 6-chloro-2- Pyridylmethyl group, 6,6-dichloro-2-pyridylmethyl group,

3-pyridylmethyl group, 1- (3′-pyridyl) ethyl group, 2- (3′-pyridyl) ethyl group, 3- (3′-pyridyl) propyl group, 4- (3′-pyridyl) butyl group, 5- (3′-pyridyl) pentyl group, 6- (3′-pyridyl) hexyl group, 7- (3′-pyridyl) heptyl group, 8- (3′-pyridyl) octyl group,

5-cyano-3-pyridylmethyl group, 5-nitro-3-pyridylmethyl group, 5-carboxyl-3-pyridylmethyl group, 5-hydroxyl-3-pyridylmethyl group, 5- (N-methylcarboxamide)- 3-pyridylmethyl group, 5- (N, N-dimethylcarboamido) -3-pyridylmethyl group, 5-methyl-3-pyridylmethyl group, 5-trifluoromethyl-3-pyridylmethyl group, 5-methoxy- 3-pyridylmethyl group, 5-trifluoromethoxy-3-pyridylmethyl group, 5-methylthio-3-pyridylmethyl group, 5-methylsulfinyl-3-pyridylmethyl group, 5-methylsulfonyl-3-pyridylmethyl group, 5-methoxycarbonyl-3-pyridylmethyl group, 5-vinyl-3-pyridylmethyl group, 5- (2 ′, 2′-difluorovini ) -3-pyridylmethyl group, 5-ethynyl-3-pyridylmethyl group, 5- (2′-fluoroethynyl) -3-pyridylmethyl group, 5-fluoro-3-pyridylmethyl group, 5-chloro-3- A pyridylmethyl group,

6-cyano-3-pyridylmethyl group, 6-nitro-3-pyridylmethyl group, 6-carboxyl-3-pyridylmethyl group, 6-hydroxyl-3-pyridylmethyl group, 6- (N-methylcarboxamide)- 3-pyridylmethyl group, 6- (N, N-dimethylcarboamido) -3-pyridylmethyl group, 6-methyl-3-pyridylmethyl group, 6-trifluoromethyl-3-pyridylmethyl group, 6-methoxy- 3-pyridylmethyl group, 6-trifluoromethoxy-3-pyridylmethyl group, 6-methylthio-3-pyridylmethyl group, 6-methylsulfinyl-3-pyridylmethyl group, 6-methylsulfonyl-3-pyridylmethyl group, 6-methoxycarbonyl-3-pyridylmethyl group, 6-vinyl-3-pyridylmethyl group, 6- (2 ′, 2′-difluorovini ) -3-pyridylmethyl group, 6-ethynyl-3-pyridylmethyl group, 6- (2′-fluoroethynyl) -3-pyridylmethyl group, 6-fluoro-3-pyridylmethyl group, 6-chloro-3- A pyridylmethyl group,

4-pyridylmethyl group, 1- (4′-pyridyl) ethyl group, 2- (4′-pyridyl) ethyl group, 3- (4′-pyridyl) propyl group, 4- (4′-pyridyl) butyl group, 5- (4′-pyridyl) pentyl group, 6- (4′-pyridyl) hexyl group, 7- (4′-pyridyl) heptyl group, 8- (4′-pyridyl) octyl group,

2-cyano-4-pyridylmethyl group, 2-nitro-4-pyridylmethyl group, 2-carboxyl-4-pyridylmethyl group, 2-hydroxyl-4-pyridylmethyl group, 2- (N-methylcarboxamide)- 4-pyridylmethyl group, 2- (N, N-dimethylcarboamido) -4-pyridylmethyl group, 2-methyl-4-pyridylmethyl group, 2-trifluoromethyl-4-pyridylmethyl group, 2-methoxy- 4-pyridylmethyl group, 2-trifluoromethoxy-4-pyridylmethyl group, 2-methylthio-4-pyridylmethyl group, 2-methylsulfinyl-4-pyridylmethyl group, 2-methylsulfonyl-4-pyridylmethyl group, 2-methoxycarbonyl-4-pyridylmethyl group, 2-vinyl-4-pyridylmethyl group, 2- (2 ′, 2′-difluorovini ) -4-pyridylmethyl group, 2-ethynyl-4-pyridylmethyl group, 2- (2′-fluoroethynyl) -4-pyridylmethyl group, 2-fluoro-4-pyridylmethyl group, 2-chloro-4- A pyridylmethyl group,

6-cyano-4-pyridylmethyl group, 6-nitro-4-pyridylmethyl group, 6-carboxyl-4-pyridylmethyl group, 6-hydroxyl-4-pyridylmethyl group, 6- (N-methylcarboamido)- 4-pyridylmethyl group, 6- (N, N-dimethylcarboamido) -4-pyridylmethyl group, 6-methyl-4-pyridylmethyl group, 6-trifluoromethyl-4-pyridylmethyl group, 6-methoxy- 4-pyridylmethyl group, 6-trifluoromethoxy-4-pyridylmethyl group, 6-methylthio-4-pyridylmethyl group, 6-methylsulfinyl-4-pyridylmethyl group, 6-methylsulfonyl-4-pyridylmethyl group, 6-methoxycarbonyl-4-pyridylmethyl group, 6-vinyl-4-pyridylmethyl group, 6- (2 ′, 2′-difluorovini ) -4-pyridylmethyl group, 6-ethynyl-4-pyridylmethyl group, 6- (2′-fluoroethynyl) -4-pyridylmethyl group, 6-fluoro-4-pyridylmethyl group, 6-chloro-4- A pyridylmethyl group,

2-quinolylmethyl group, 1- (2′-quinolyl) ethyl group, 2- (2′-quinolyl) ethyl group, 3- (2′-quinolyl) propyl group, 4- (2′-quinolyl) butyl group, 5 -(2'-quinolyl) pentyl group, 6- (2'-quinolyl) hexyl group, 7- (2'-quinolyl) heptyl group, 8- (2'-quinolyl) octyl group,

6-cyano-2-quinolylmethyl group, 6-nitro-2-quinolylmethyl group, 6-carboxyl-2-quinolylmethyl group, 6-hydroxyl-2-quinolylmethyl group, 6- (N-methylcarboamido) -2-quinolylmethyl group 6- (N, N-dimethylcarboamido) -2-quinolylmethyl group, 6-methyl-2-quinolylmethyl group, 6-trifluoromethyl-2-quinolylmethyl group, 6-methoxy-2-quinolylmethyl group, 6-triol Fluoromethoxy-2-quinolylmethyl group, 6-methylthio-2-quinolylmethyl group, 6-methylsulfinyl-2-quinolylmethyl group, 6-methylsulfonyl-2-quinolylmethyl group, 6-methoxycarbonyl-2-quinolylmethyl group, 6-vinyl 2-quinolylmethyl group, 6- (2 ′, 2′-difluorovini ) -2-quinolylmethyl group, a 6-ethynyl-2-quinolylmethyl group, 6- (2'-fluoro-ethynyl) -2-quinolylmethyl group, 6-fluoro-2-quinolylmethyl group, 6-chloro-2-quinolylmethyl group,

3-quinolylmethyl group, 1- (3′-quinolyl) ethyl group, 2- (3′-quinolyl) ethyl group, 3- (3′-quinolyl) propyl group, 4- (3′-quinolyl) butyl group, 5 -(3'-quinolyl) pentyl group, 6- (3'-quinolyl) hexyl group, 7- (3'-quinolyl) heptyl group, 8- (3'-quinolyl) octyl group,

6-cyano-3-quinolylmethyl group, 6-nitro-3-quinolylmethyl group, 6-carboxyl-3-quinolylmethyl group, 6-hydroxyl-3-quinolylmethyl group, 6- (N-methylcarboamido) -3-quinolylmethyl group 6- (N, N-dimethylcarboamido) -3-quinolylmethyl group, 6-methyl-3-quinolylmethyl group, 6-trifluoromethyl-3-quinolylmethyl group, 6-methoxy-3-quinolylmethyl group, 6-triol Fluoromethoxy-3-quinolylmethyl group, 6-methylthio-3-quinolylmethyl group, 6-methylsulfinyl-3-quinolylmethyl group, 6-methylsulfonyl-3-quinolylmethyl group, 6-methoxycarbonyl-3-quinolylmethyl group, 6-vinyl -3-quinolylmethyl group, 6- (2 ′, 2′-difluorovini ) -3-quinolylmethyl group, a 6-ethynyl-3-quinolylmethyl group, 6- (2'-fluoro-ethynyl) -3-quinolylmethyl group, 6-fluoro-3-quinolylmethyl group, 6-chloro-3-quinolylmethyl group,

4-quinolylmethyl group, 1- (4′-quinolyl) ethyl group, 2- (4′-quinolyl) ethyl group, 3- (4′-quinolyl) propyl group, 4- (4′-quinolyl) butyl group, 5 -(3'-quinolyl) pentyl group, 6- (4'-quinolyl) hexyl group, 7- (4'-quinolyl) heptyl group, 8- (4'-quinolyl) octyl group,

6-cyano-4-quinolylmethyl group, 6-nitro-4-quinolylmethyl group, 6-carboxyl-4-quinolylmethyl group, 6-hydroxyl-4-quinolylmethyl group, 6- (N-methylcarboamido) -4-quinolylmethyl group 6- (N, N-dimethylcarboamido) -4-quinolylmethyl group, 6-methyl-4-quinolylmethyl group, 6-trifluoromethyl-4-quinolylmethyl group, 6-methoxy-4-quinolylmethyl group, 6-triol Fluoromethoxy-4-quinolylmethyl group, 6-methylthio-4-quinolylmethyl group, 6-methylsulfinyl-4-quinolylmethyl group, 6-methylsulfonyl-4-quinolylmethyl group, 6-methoxycarbonyl-4-quinolylmethyl group, 6-vinyl -4-quinolylmethyl group, 6- (2 ', 2'-difluorovini ) -4-quinolylmethyl group, 6-ethynyl-4-quinolylmethyl group, 6- (2'-fluoro ethynyl) -4-quinolylmethyl group, 6-fluoro-4-quinolylmethyl group, 6-chloro-4-quinolylmethyl group,

2-furylmethyl group, 1- (2′-furyl) ethyl group, 2- (2′-furyl) ethyl group, 3- (2′-furyl) propyl group, 4- (2′-furyl) butyl group, 5- (2′-furyl) pentyl group, 6- (2′-furyl) hexyl group, 7- (2′-furyl) heptyl group, 8- (2′-furyl) octyl group,

4-cyano-2-furylmethyl group, 4-nitro-2-furylmethyl group, 4-carboxyl-2-furylmethyl group, 4-hydroxyl-2-furylmethyl group, 4- (N-methylcarboamido)- 2-furylmethyl group, 4- (N, N-dimethylcarboamido) -2-furylmethyl group, 4-methyl-2-furylmethyl group, 4-trifluoromethyl-2-furylmethyl group, 4-methoxy- 2-furylmethyl group, 4-trifluoromethoxy-2-furylmethyl group, 4-methylthio-2-furylmethyl group, 4-methylsulfinyl-2-furylmethyl group, 4-methylsulfonyl-2-furylmethyl group, 4-methoxycarbonyl-2-furylmethyl group, 4-vinyl-2-furylmethyl group, 4- (2 ′, 2′-difluorovinyl) -2-furylmethyl group, 4- Ethynyl-2-furylmethyl group, 4- (2'-fluoro-ethynyl) -2-furylmethyl group, 4-fluoro-2-furylmethyl group, 4-chloro-2-furylmethyl group,

3-furylmethyl group, 1- (3′-furyl) ethyl group, 2- (3′-furyl) ethyl group, 3- (3′-furyl) propyl group, 4- (3′-furyl) butyl group, 5- (3′-furyl) pentyl group, 6- (3′-furyl) hexyl group, 7- (3′-furyl) heptyl group, 8- (3′-furyl) octyl group,

4-cyano-3-furylmethyl group, 4-nitro-3-furylmethyl group, 4-carboxyl-3-furylmethyl group, 4-hydroxyl-3-furylmethyl group, 4- (N-methylcarboxamide)- 3-furylmethyl group, 4- (N, N-dimethylcarboamido) -3-furylmethyl group, 4-methyl-3-furylmethyl group, 4-trifluoromethyl-3-furylmethyl group, 4-methoxy- 3-furylmethyl group, 4-trifluoromethoxy-3-furylmethyl group, 4-methylthio-3-furylmethyl group, 4-methylsulfinyl-3-furylmethyl group, 4-methylsulfonyl-3-furylmethyl group, 4-methoxycarbonyl-3-furylmethyl group, 4-vinyl-3-furylmethyl group, 4- (2 ′, 2′-difluorovinyl) -3-furylmethyl group, 4- Ethynyl-3-furylmethyl group, 4- (2'-fluoro-ethynyl) -3-furylmethyl group, 4-fluoro-3-furylmethyl group, 4-chloro-3-furylmethyl group,

2-thienylmethyl group, 1- (2′-thienyl) ethyl group, 2- (2′-thienyl) ethyl group, 3- (2′-thienyl) propyl group, 4- (2′-thienyl) butyl group, 5- (2′-thienyl) pentyl group, 6- (2′-thienyl) hexyl group, 7- (2′-thienyl) heptyl group, 8- (2′-thienyl) octyl group,

4-cyano-2-thienylmethyl group, 4-nitro-2-thienylmethyl group, 4-carboxyl-2-thienylmethyl group, 4-hydroxyl-2-thienylmethyl group, 4- (N-methylcarboamido)- 2-thienylmethyl group, 4- (N, N-dimethylcarboamido) -2-thienylmethyl group, 4-methyl-2-thienylmethyl group, 4-trifluoromethyl-2-thienylmethyl group, 4-methoxy- 2-thienylmethyl group, 4-trifluoromethoxy-2-thienylmethyl group, 4-methylthio-2-thienylmethyl group, 4-methylsulfinyl-2-thienylmethyl group, 4-methylsulfonyl-2-thienylmethyl group, 4-methoxycarbonyl-2-thienylmethyl group, 4-vinyl-2-thienylmethyl group, 4- (2 ′, 2′-difluorovini ) -2-thienylmethyl group, 4-ethynyl-2-thienylmethyl group, 4- (2'-fluoroethynyl) -2-thienylmethyl group, 4-fluoro-2-thienylmethyl group, 4-chloro-2- Thienylmethyl group,

3-thienylmethyl group, 1- (3′-thienyl) ethyl group, 2- (3′-thienyl) ethyl group, 3- (3′-thienyl) propyl group, 4- (3′-thienyl) butyl group, 5- (3′-thienyl) pentyl group, 6- (3′-thienyl) hexyl group, 7- (3′-thienyl) heptyl group, 8- (3′-thienyl) octyl group,

4-cyano-3-thienylmethyl group, 4-nitro-3-thienylmethyl group, 4-carboxyl-3-thienylmethyl group, 4-hydroxyl-3-thienylmethyl group, 4- (N-methylcarboamido)- 3-thienylmethyl group, 4- (N, N-dimethylcarboamido) -3-thienylmethyl group, 4-methyl-3-thienylmethyl group, 4-trifluoromethyl-3-thienylmethyl group, 4-methoxy- 3-thienylmethyl group, 4-trifluoromethoxy-3-thienylmethyl group, 4-methylthio-3-thienylmethyl group, 4-methylsulfinyl-3-thienylmethyl group, 4-methylsulfonyl-3-thienylmethyl group, 4-methoxycarbonyl-3-thienylmethyl group, 4-vinyl-3-thienylmethyl group, 4- (2 ′, 2′-difluorovini ) -3-thienylmethyl group, 4-ethynyl-3-thienylmethyl group, 4- (2'-fluoroethynyl) -3-thienylmethyl group, 4-fluoro-3-thienylmethyl group, 4-chloro-3- Thienylmethyl group,

2- (1-benzofuranyl) methyl group, 1- (2 ′-(1′-benzofuranyl)) ethyl group, 2- (2 ′-(1′-benzofuranyl)) ethyl group, 3- (2 ′-(1 '-Benzofuranyl)) propyl group, 4- (2'-(1'-benzofuranyl)) butyl group, 5- (2 '-(1'-benzofuranyl)) pentyl group, 6- (2'-(1'-) Benzofuranyl)) hexyl group, 7- (2 ′-(1′-benzofuranyl)) heptyl group, 8- (2 ′-(1′-benzofuranyl)) octyl group,

5-cyano-2- (1-benzofuranyl) methyl group, 5-nitro-2- (1-benzofuranyl) methyl group, 5-carboxyl-2- (1-benzofuranyl) methyl group, 5-hydroxyl-2- (1 -Benzofuranyl) methyl group, 5- (N-methylcarboamido) -2- (1-benzofuranyl) methyl group, 5- (N, N-dimethylcarboamido) -2- (1-benzofuranyl) methyl group, 5- Methyl-2- (1-benzofuranyl) methyl group, 5-trifluoromethyl-2- (1-benzofuranyl) methyl group, 5-methoxy-2- (1-benzofuranyl) methyl group, 5-trifluoromethoxy-2- (1-benzofuranyl) methyl group, 5-methylthio-2- (1-benzofuranyl) methyl group, 5-methylsulfinyl-2- (1-benzofuranyl) Methyl group, 5-methylsulfonyl-2- (1-benzofuranyl) methyl group, 5-methoxycarbonyl-2- (1-benzofuranyl) methyl group, 5-vinyl-2- (1-benzofuranyl) methyl group, 5- ( 2 ', 2'-difluorovinyl) -2- (1-benzofuranyl) methyl group, 5-ethynyl-2- (1-benzofuranyl) methyl group, 5- (2'-fluoroethynyl) -2- (1-benzofuranyl) ) Methyl group, 5-fluoro-2- (1-benzofuranyl) methyl group, 5-chloro-2- (1-benzofuranyl) methyl group,
3- (1-benzofuranyl) methyl group, 1- (3 ′-(1′-benzofuranyl)) ethyl group, 2- (3 ′-(1′-benzofuranyl)) ethyl group, 3- (3 ′-(1 '-Benzofuranyl)) propyl group, 4- (3'-(1'-benzofuranyl)) butyl group, 5- (3 '-(1'-benzofuranyl)) pentyl group, 6- (3'-(1'-) Benzofuranyl)) hexyl group, 7- (3 ′-(1′-benzofuranyl)) heptyl group, 8- (3 ′-(1′-benzofuranyl)) octyl group,

5-cyano-3- (1-benzofuranyl) methyl group, 5-nitro-3- (1-benzofuranyl) methyl group, 5-carboxyl-3- (1-benzofuranyl) methyl group, 5-hydroxyl-3- (1 -Benzofuranyl) methyl group, 5- (N-methylcarboamido) -3- (1-benzofuranyl) methyl group, 5- (N, N-dimethylcarbamido) -3- (1-benzofuranyl) methyl group, 5- Methyl-3- (1-benzofuranyl) methyl group, 5-trifluoromethyl-3- (1-benzofuranyl) methyl group, 5-methoxy-3- (1-benzofuranyl) methyl group, 5-trifluoromethoxy-3- (1-benzofuranyl) methyl group, 5-methylthio-3- (1-benzofuranyl) methyl group, 5-methylsulfinyl-3- (1-benzofuranyl) Methyl group, 5-methylsulfonyl-3- (1-benzofuranyl) methyl group, 5-methoxycarbonyl-3- (1-benzofuranyl) methyl group, 5-vinyl-3- (1-benzofuranyl) methyl group, 5- ( 2 ', 2'-difluorovinyl) -3- (1-benzofuranyl) methyl group, 5-ethynyl-3- (1-benzofuranyl) methyl group, 5- (2'-fluoroethynyl) -3- (1-benzofuranyl) ) Methyl group, 5-fluoro-3- (1-benzofuranyl) methyl group, 5-chloro-3- (1-benzofuranyl) methyl group,

2- (1-benzothienyl) methyl group, 1- (2 ′-(1′-benzothienyl)) ethyl group, 2- (2 ′-(1′-benzothienyl)) ethyl group, 3- (2 ′ -(1'-benzothienyl)) propyl group, 4- (2 '-(1'-benzothienyl)) butyl group, 5- (2'-(1'-benzothienyl)) pentyl group, 6- (2 '-(1'-benzothienyl)) hexyl group, 7- (2'-(1'-benzothienyl)) heptyl group, 8- (2 '-(1'-benzothienyl)) octyl group,

5-cyano-2- (1-benzothienyl) methyl group, 5-nitro-2- (1-benzothienyl) methyl group, 5-carboxyl-2- (1-benzothienyl) methyl group, 5-hydroxyl-2 -(1-benzothienyl) methyl group, 5- (N-methylcarboamido) -2- (1-benzothienyl) methyl group, 5- (N, N-dimethylcarboamido) -2- (1-benzothienyl) ) Methyl group, 5-methyl-2- (1-benzothienyl) methyl group, 5-trifluoromethyl-2- (1-benzothienyl) methyl group, 5-methoxy-2- (1-benzothienyl) methyl group , 5-trifluoromethoxy-2- (1-benzothienyl) methyl group, 5-methylthio-2- (1-benzothienyl) methyl group, 5-methylsulfinyl-2- (1-benzothienyl) Methyl group, 5-methylsulfonyl-2- (1-benzothienyl) methyl group, 5-methoxycarbonyl-2- (1-benzothienyl) methyl group, 5-vinyl-2- (1-benzothienyl) methyl group, 5- (2 ′, 2′-difluorovinyl) -2- (1-benzothienyl) methyl group, 5-ethynyl-2- (1-benzothienyl) methyl group, 5- (2′-fluoroethynyl) -2 -(1-benzothienyl) methyl group, 5-fluoro-2- (1-benzothienyl) methyl group, 5-chloro-2- (1-benzothienyl) methyl group,

3- (1-benzothienyl) methyl group, 1- (3 ′-(1′-benzothienyl)) ethyl group, 2- (3 ′-(1′-benzothienyl)) ethyl group, 3- (3 ′ -(1'-benzothienyl)) propyl group, 4- (3 '-(1'-benzothienyl)) butyl group, 5- (3'-(1'-benzothienyl)) pentyl group, 6- (3 '-(1'-benzothienyl)) hexyl group, 7- (3'-(1'-benzothienyl)) heptyl group, 8- (3 '-(1'-benzothienyl)) octyl group,

5-cyano-3- (1-benzothienyl) methyl group, 5-nitro-3- (1-benzothienyl) methyl group, 5-carboxyl-3- (1-benzothienyl) methyl group, 5-hydroxyl-3 -(1-benzothienyl) methyl group, 5- (N-methylcarboamido) -3- (1-benzothienyl) methyl group, 5- (N, N-dimethylcarboamido) -3- (1-benzothienyl) ) Methyl group, 5-methyl-3- (1-benzothienyl) methyl group, 5-trifluoromethyl-3- (1-benzothienyl) methyl group, 5-methoxy-3- (1-benzothienyl) methyl group 5-trifluoromethoxy-3- (1-benzothienyl) methyl group, 5-methylthio-3- (1-benzothienyl) methyl group, 5-methylsulfinyl-3- (1-benzothienyl) Methyl group, 5-methylsulfonyl-3- (1-benzothienyl) methyl group, 5-methoxycarbonyl-3- (1-benzothienyl) methyl group, 5-vinyl-3- (1-benzothienyl) methyl group, 5- (2 ′, 2′-difluorovinyl) -3- (1-benzothienyl) methyl group, 5-ethynyl-3- (1-benzothienyl) methyl group, 5- (2′-fluoroethynyl) -3 -(1-benzothienyl) methyl group, 5-fluoro-3- (1-benzothienyl) methyl group, 5-chloro-3- (1-benzothienyl) methyl group

Fluoromethyl group, 1-fluoroethyl group, 1,1-difluoroethyl, 2-fluoroethyl group, 2,2-difluoroethyl group, 2,2,2-trifluoroethyl group, 3-fluoropropyl group, 3, 3,3-trifluoropropyl, 4-fluorobutyl group, 4,4,4-trifluorobutyl group, 3,3,4,4,4-pentafluorobutyl group, 5-fluoropentyl group, 6-fluorohexyl Group, 7-fluoroheptyl group, 8-fluorooctyl group,

Chloromethyl group, 1-chloroethyl group, 2-chloroethyl group, 3-chloropropyl group, 4-chlorobutyl group, 5-chloropentyl group, 6-chlorohexyl group, 7-chloroheptyl group, 8-chlorooctyl group,

Bromomethyl group, 1-bromoethyl group, 2-bromoethyl group, 3-bromopropyl group, 4-bromobutyl group, 5-bromopentyl group, 6-bromohexyl group, 7-bromoheptyl group, 8-bromooctyl group,

(Methoxycarbonyl) methyl group, 1- (methoxycarbonyl) ethyl group, 2- (methoxycarbonyl) ethyl group, 3- (methoxycarbonyl) propyl group, 4- (methoxycarbonyl) butyl group, 5- (methoxycarbonyl) pentyl Group, 6- (methoxycarbonyl) hexyl group, 7- (methoxycarbonyl) heptyl group, 8- (methoxycarbonyl) octyl group,

Cyanomethyl group, 1-cyanoethyl group, 2-cyanoethyl group, 3-cyanopropyl group, 4-cyanobutyl group, 5-cyanopentyl group, 6-cyanohexyl group, 7-cyanoheptyl group, 8-cyanooctyl group,

Nitromethyl group, 1-nitroethyl group, 2-nitroethyl group, 3-nitropropyl group, 4-nitrobutyl group, 5-nitropentyl group, 6-nitrohexyl group, 7-nitroheptyl group, 8-nitrooctyl group,

(Carboxy) methyl group, 1- (carboxy) ethyl group, 2- (carboxy) ethyl group, 3- (carboxy) propyl group, 4- (carboxy) butyl group, 5- (carboxy) pentyl group, 6- (carboxy) ) Hexyl group, 7- (carboxy) heptyl group, 8- (carboxy) octyl group,

Hydroxymethyl group, 1-hydroxyethyl group, 2-hydroxyethyl group, 3-hydroxypropyl group, 4-hydroxybutyl group, 5-hydroxypentyl group, 6-hydroxyhexyl group, 7-hydroxyheptyl group, 8-hydroxyoctyl Group,
Etc.

In the present invention, the “C1-C4 alkyl group having one or more benzyloxy groups” includes, for example,
Benzyloxymethyl group, 1-benzyloxyethyl group, 2-benzyloxyethyl group, 1-benzyloxypropyl group, 2-benzyloxypropyl group, 3-benzyloxypropyl group, 1-benzyloxy-1-methylethyl group, 1-benzyloxybutyl group, 2-benzyloxybutyl group, 3-benzyloxybutyl group, 4-benzyloxybutyl group, 1-benzyloxy-1-methylpropyl group, 2-benzyloxy-1-methylpropyl group, 1- Benzyloxy-2-methylpropyl group, 2-benzyloxy-2-methylpropyl group,
Etc .;

In the present invention, the “C1-C4 alkoxy group optionally having one or more halogen atoms” includes, for example,
Methoxy group, ethoxy group, propoxy group, isopropoxy group, isobutoxy group, difluoromethoxy group, trifluoromethoxy group, trichloromethoxy group, 2,2,2-trifluoroethoxy group, 1,1,2,2-tetrafluoro Examples thereof include an ethoxy group and a 1,1,2,2,2-pentafluoroethoxy group.

In the present invention, the “C1-C4 alkylthio group optionally having one or more halogen atoms” includes, for example,
Methylthio group, ethylthio group, 1-propylthio group, 2-propylthio group, isobutylthio group, difluoromethylthio group, trifluoromethylthio group, trichloromethylthio group, 2,2,2-trifluoroethylthio group, 1,1,2, , 2-tetrafluoroethylthio group and 1,1,2,2,2-pentafluoroethylthio group.

In the present invention, the “C1-C4 alkylsulfinyl group optionally having one or more halogen atoms” includes, for example,
Methanesulfinyl group, ethanesulfinyl group, 1-propanesulfinyl group, 2-propanesulfinyl group, isobutanesulfinyl group, difluoromethanesulfinyl group, trifluoromethanesulfinyl group, trichloromethanesulfinyl group, 2,2,2-trifluoroethanesulfinyl group 1,1,2,2-tetrafluoroethanesulfinyl group and 1,1,2,2,2-pentafluoroethanesulfinyl group.

In the present invention, the “C1-C4 alkylsulfonyl group optionally having one or more halogen atoms” includes, for example,
Methanesulfonyl group, ethanesulfonyl group, 1-propanesulfonyl group, 2-propanesulfonyl group, isobutanesulfonyl group, difluoromethanesulfonyl group, trifluoromethanesulfonyl group, trichloromethanesulfonyl group, 2,2,2-trifluoroethanesulfonyl group 1,1,2,2-tetrafluoroethanesulfonyl group and 1,1,2,2,2-pentafluoroethanesulfonyl group.

In the present invention, examples of the “C1-C4 alkoxycarbonyl group optionally having one or more halogen atoms” include methoxycarbonyl group, ethoxycarbonyl group, propoxycarbonyl group, isopropoxycarbonyl group, butoxycarbonyl group, tert-butoxycarbonyl group, difluoromethoxycarbonyl group, trifluoromethoxycarbonyl group, trichloromethoxycarbonyl group, 2,2,2-trifluoroethoxycarbonyl group, 1,1,2,2-terolafluoroethoxycarbonyl group and 1, A 1,2,2,2-pentafluoroethoxycarbonyl group may be mentioned.

In the present invention, examples of the “vinyl group optionally having one or more atoms or groups selected from group E” include a vinyl group, a 2-fluorovinyl group, a 2,2-difluorovinyl group, 2, A 2-dichlorovinyl group is mentioned.

Examples of the “ethynyl group optionally having an atom or group selected from group E” in the present invention include ethynyl group and 2-fluoroethynyl group.

In the present invention, “a C1-C3 hydrocarbon group having one or more atoms or groups selected from the group consisting of a hydroxyl group and a halogen atom”
Hydroxymethyl group, fluoromethyl group, chloromethyl group, bromomethyl group, difluoromethyl group, trifluoromethyl group, 1-hydroxy-1-ethyl group, 1-fluoro-1-ethyl group, 2-hydroxyl-1-ethyl group 1,1-difluoro-1-ethyl group, 1-chloro-1-ethyl group, 2-chloro-1-ethyl group, 1-bromo-1-ethyl group, 1-hydroxy-1-propyl group, difluoromethyl 1-hydroxy-2,2,2-trifluoro-1-ethyl group, 1-hydroxy-2,2,3,3-pentafluoro-1-propyl group and 1-hydroxy-3,3,3- A trifluoro-1-propyl group may be mentioned.

In the present invention, “a C1-C3 hydrocarbon group optionally having one or more atoms or groups selected from the group consisting of a hydroxyl group and a halogen atom”
Methyl group, ethyl group, propyl group, hydroxymethyl group, fluoromethyl group, chloromethyl group, bromomethyl group, difluoromethyl group, trifluoromethyl group, 1-hydroxy-1-ethyl group, 1-fluoro-1-ethyl group 2-hydroxy-1-ethyl group, 1,1-difluoro-1-ethyl group, 1-chloro-1-ethyl group, 2-chloro-1-ethyl group, 1-bromo-1-ethyl group, 1- Hydroxy-1-propyl group, difluoromethyl group, 1-hydroxy-2,2,2-trifluoro-1-ethyl group, 1-hydroxy-2,2,3,3-pentafluoro-1-propyl group and 1 -Hydroxy-3,3,3-trifluoro-1-propyl group.

In the present invention, examples of the “C1-C2 hydrocarbon group optionally having one or more halogen atoms” include a methyl group, an ethyl group, an iodomethyl group, a bromomethyl group, a chloromethyl group, a fluoromethyl group, and a difluoro. Methyl group, chlorodifluoromethyl group, bromodifluoromethyl group, dichlorofluoromethyl group, trichloromethyl group, trifluoromethyl group, 1-fluoroethyl group, 2-fluoroethyl group, 1-fluoro-1-methylethyl group, 1 -Chloroethyl group, 2-chloroethyl group, 1-chloro-1-methylethyl group, 1-bromoethyl group, 2-bromoethyl group, 1-bromo-1-methylethyl group, 2,2,2-trifluoroethyl group, 1,1,2,2-tetrafluoroethyl group and 1,1,2,2,2-pentafluoroethyl group It is.

In the present invention, examples of the C1-C8 chain hydrocarbon group having one group selected from group F include benzyl group, 1-phenylethyl group, 3-phenylpropyl group, 4-phenylbutyl group, 5 -Phenylpentyl group, 6-phenylhexyl group, 7-phenylheptyl group, 8-phenyloctyl group, 4-cyanobenzyl group, 4-nitrobenzyl group, 4-carboxylbenzyl group, 4-hydroxylbenzyl group, 4- ( N-methylcarboamido) benzyl group, 4- (N, N-dimethylcarboamido) benzyl group, 4-methylbenzyl group, 4-trifluoromethylbenzyl group, 4-methoxybenzyl group, 4-trifluoromethoxybenzyl group 4-methylthiobenzyl group, 4-methylsulfinylbenzyl group, 4-methylsulfonylbenzyl group, 4 Methoxycarbonylbenzyl group, 4-vinylbenzyl group, 4- (2 ′, 2′-difluorovinyl) benzyl group, 4-ethynylbenzyl group, 4- (2′-fluoroethynyl) benzyl group, 4-fluorobenzyl group, 4-chlorobenzyl group, 3,4-dichlorobenzyl group, 1-naphthylmethyl group, 2-naphthylmethyl group, 1- (1′-naphthyl) ethyl group, 2- (1′-naphthyl) ethyl group, 3- (1'-naphthyl) propyl group, 4- (1'-naphthyl) butyl group, 5- (1'-naphthyl) pentyl group, 6- (1'-naphthyl) hexyl group, 7- (1'-naphthyl) Heptyl group, 8- (1′-naphthyl) octyl group, 6-cyano-1-naphthylmethyl group, 6-nitro-1-naphthylmethyl group, 6-carboxyl-1-naphthylmethyl group, 6-hydroxyl-1- Naphthylmethyl group, 6- (N-methylcarboamido) -1-naphthylmethyl group, 6- (N, N-dimethylcarboamido) -1-naphthylmethyl group, 6-methyl-1-naphthylmethyl group, 6- Trifluoromethyl-1-naphthylmethyl group, 6-methoxy-1-naphthylmethyl group, 6-trifluoromethoxy-1-naphthylmethyl group, 6-methylthio-1-naphthylmethyl group, 6-methylsulfinyl-1-naphthyl Methyl group, 6-methylsulfonyl-1-naphthylmethyl group, 6-methoxycarbonyl-1-naphthylmethyl group, 6-vinyl-1-naphthylmethyl group, 6- (2 ′, 2′-difluorovinyl) -1- Naphthylmethyl group, 6-ethynyl-1-naphthylmethyl group, 6- (2′-fluoroethynyl) -1-naphthylmethyl group, 6-fluoro-1 Naphthylmethyl group, 6-chloro-1-naphthylmethyl group, 1- (2′-naphthyl) ethyl group, 3- (2′-naphthyl) propyl group, 4- (2′-naphthyl) butyl group, 5- ( 2'-naphthyl) pentyl group, 6- (2'-naphthyl) hexyl group, 7- (2'-naphthyl) heptyl group, 8- (2'-naphthyl) octyl group, 6-cyano-2-naphthylmethyl group 6-nitro-2-naphthylmethyl group, 6-carboxyl-2-naphthylmethyl group, 6-hydroxyl-2-naphthylmethyl group, 6- (N-methylcarboamido) -2-naphthylmethyl group, 6- ( N, N-dimethylcarboamido) -2-naphthylmethyl group, 6-methyl-2-naphthylmethyl group, 6-trifluoromethyl-2-naphthylmethyl group, 6-methoxy-2-naphthylmethyl group, 6-trifluoro Olomethoxy-2-naphthylmethyl group, 6-methylthio-2-naphthylmethyl group, 6-methylsulfinyl-2-naphthylmethyl group, 6-methylsulfonyl-2-naphthylmethyl group, 6-methoxycarbonyl-2-naphthylmethyl group 6-vinyl-2-naphthylmethyl group, 6- (2 ′, 2′-difluorovinyl) -2-naphthylmethyl group, 6-ethynyl-2-naphthylmethyl group, 6- (2′-fluoroethynyl)- 2-naphthylmethyl group, 6-fluoro-2-naphthylmethyl group, 6-chloro-2-naphthylmethyl group, 2-pyridylmethyl group, 1- (2′-pyridyl) ethyl group, 2- (2′-pyridyl) ) Ethyl group, 3- (2′-pyridyl) propyl group, 4- (2′-pyridyl) butyl group, 5- (2′-pyridyl) pentyl group, 6- (2′-pyridyl) hexyl Group, 7- (2′-pyridyl) heptyl group, 8- (2′-pyridyl) octyl group, 4-cyano-2-pyridylmethyl group, 4-nitro-2-pyridylmethyl group, 4-carboxyl-2 -Pyridylmethyl group, 4-hydroxyl-2-pyridylmethyl group, 4- (N-methylcarboamido) -2-pyridylmethyl group, 4- (N, N-dimethylcarboamido) -2-pyridylmethyl group, 4 -Methyl-2-pyridylmethyl group, 4-trifluoromethyl-2-pyridylmethyl group, 4-methoxy-2-pyridylmethyl group, 4-trifluoromethoxy-2-pyridylmethyl group, 4-methylthio-2-pyridyl group Methyl group, 4-methylsulfinyl-2-pyridylmethyl group, 4-methylsulfonyl-2-pyridylmethyl group, 4-methoxycarbonyl-2-pyridylmethyl Group, 4-vinyl-2-pyridylmethyl group, 4- (2 ′, 2′-difluorovinyl) -2-pyridylmethyl group, 4-ethynyl-2-pyridylmethyl group, 4- (2′-fluoroethynyl) 2-pyridylmethyl group, 4-fluoro-2-pyridylmethyl group, 4-chloro-2-pyridylmethyl group, 5-cyano-2-pyridylmethyl group, 5-nitro-2-pyridylmethyl group, 5-carboxyl 2-pyridylmethyl group, 5-hydroxyl-2-pyridylmethyl group, 5- (N-methylcarboamido) -2-pyridylmethyl group, 5- (N, N-dimethylcarboamido) -2-pyridylmethyl group 5-methyl-2-pyridylmethyl group, 5-trifluoromethyl-2-pyridylmethyl group, 5-methoxy-2-pyridylmethyl group, 5-trifluoromethoxy-2-pi Dilmethyl group, 5-methylthio-2-pyridylmethyl group, 5-methylsulfinyl-2-pyridylmethyl group, 5-methylsulfonyl-2-pyridylmethyl group, 5-methoxycarbonyl-2-pyridylmethyl group, 5-vinyl- 2-pyridylmethyl group, 5- (2 ′, 2′-difluorovinyl) -2-pyridylmethyl group, 5-ethynyl-2-pyridylmethyl group, 5- (2′-fluoroethynyl) -2-pyridylmethyl group 5-fluoro-2-pyridylmethyl group, 5-chloro-2-pyridylmethyl group, 6-cyano-2-pyridylmethyl group, 6-nitro-2-pyridylmethyl group, 6-carboxyl-2-pyridylmethyl group 6-hydroxyl-2-pyridylmethyl group, 6- (N-methylcarboamido) -2-pyridylmethyl group, 6- (N, N-dimethylcarboxyl) Boamido) -2-pyridylmethyl group, 6-methyl-2-pyridylmethyl group, 6-trifluoromethyl-2-pyridylmethyl group, 6-methoxy-2-pyridylmethyl group, 6-trifluoromethoxy-2-pyridyl group Methyl group, 6-methylthio-2-pyridylmethyl group, 6-methylsulfinyl-2-pyridylmethyl group, 6-methylsulfonyl-2-pyridylmethyl group, 6-methoxycarbonyl-2-pyridylmethyl group, 6-vinyl- 2-pyridylmethyl group, 6- (2 ′, 2′-difluorovinyl) -2-pyridylmethyl group, 6-ethynyl-2-pyridylmethyl group, 6- (2′-fluoroethynyl) -2-pyridylmethyl group 6-fluoro-2-pyridylmethyl group, 6-chloro-2-pyridylmethyl group, 6,6-dichloro-2-pyridylmethyl group, 3- Lysylmethyl group, 1- (3′-pyridyl) ethyl group, 2- (3′-pyridyl) ethyl group, 3- (3′-pyridyl) propyl group, 4- (3′-pyridyl) butyl group, 5- ( 3'-pyridyl) pentyl group, 6- (3'-pyridyl) hexyl group, 7- (3'-pyridyl) heptyl group, 8- (3'-pyridyl) octyl group, 5-cyano-3-pyridylmethyl group 5-nitro-3-pyridylmethyl group, 5-carboxyl-3-pyridylmethyl group, 5-hydroxyl-3-pyridylmethyl group, 5- (N-methylcarboamido) -3-pyridylmethyl group, 5- ( N, N-dimethylcarboamido) -3-pyridylmethyl group, 5-methyl-3-pyridylmethyl group, 5-trifluoromethyl-3-pyridylmethyl group, 5-methoxy-3-pyridylmethyl group, 5-triidyl group Fluoro Methoxy-3-pyridylmethyl group, 5-methylthio-3-pyridylmethyl group, 5-methylsulfinyl-3-pyridylmethyl group, 5-methylsulfonyl-3-pyridylmethyl group, 5-methoxycarbonyl-3-pyridylmethyl group , 5-vinyl-3-pyridylmethyl group, 5- (2 ′, 2′-difluorovinyl) -3-pyridylmethyl group, 5-ethynyl-3-pyridylmethyl group, 5- (2′-fluoroethynyl)- 3-pyridylmethyl group, 5-fluoro-3-pyridylmethyl group, 5-chloro-3-pyridylmethyl group, 6-cyano-3-pyridylmethyl group, 6-nitro-3-pyridylmethyl group, 6-carboxyl- 3-pyridylmethyl group, 6-hydroxyl-3-pyridylmethyl group, 6- (N-methylcarboamido) -3-pyridylmethyl group, 6- (N N-dimethylcarboamido) -3-pyridylmethyl group, 6-methyl-3-pyridylmethyl group, 6-trifluoromethyl-3-pyridylmethyl group, 6-methoxy-3-pyridylmethyl group, 6-trifluoromethoxy -3-pyridylmethyl group, 6-methylthio-3-pyridylmethyl group, 6-methylsulfinyl-3-pyridylmethyl group, 6-methylsulfonyl-3-pyridylmethyl group, 6-methoxycarbonyl-3-pyridylmethyl group, 6-vinyl-3-pyridylmethyl group, 6- (2 ′, 2′-difluorovinyl) -3-pyridylmethyl group, 6-ethynyl-3-pyridylmethyl group, 6- (2′-fluoroethynyl) -3 -Pyridylmethyl group, 6-fluoro-3-pyridylmethyl group, 6-chloro-3-pyridylmethyl group, 4-pyridylmethyl group, 1- 4'-pyridyl) ethyl group, 2- (4'-pyridyl) ethyl group, 3- (4'-pyridyl) propyl group, 4- (4'-pyridyl) butyl group, 5- (4'-pyridyl) pentyl Group, 6- (4′-pyridyl) hexyl group, 7- (4′-pyridyl) heptyl group, 8- (4′-pyridyl) octyl group, 2-cyano-4-pyridylmethyl group, 2-nitro-4 -Pyridylmethyl group, 2-carboxyl-4-pyridylmethyl group, 2-hydroxyl-4-pyridylmethyl group, 2- (N-methylcarboamido) -4-pyridylmethyl group, 2- (N, N-dimethylcarbohydrate) Amide) -4-pyridylmethyl, 2-methyl-4-pyridylmethyl, 2-trifluoromethyl-4-pyridylmethyl, 2-methoxy-4-pyridylmethyl, 2-trifluoromethoxy-4-pyridyl Til group, 2-methylthio-4-pyridylmethyl group, 2-methylsulfinyl-4-pyridylmethyl group, 2-methylsulfonyl-4-pyridylmethyl group, 2-methoxycarbonyl-4-pyridylmethyl group, 2-vinyl- 4-pyridylmethyl group, 2- (2 ′, 2′-difluorovinyl) -4-pyridylmethyl group, 2-ethynyl-4-pyridylmethyl group, 2- (2′-fluoroethynyl) -4-pyridylmethyl group 2-fluoro-4-pyridylmethyl group, 2-chloro-4-pyridylmethyl group, 6-cyano-4-pyridylmethyl group, 6-nitro-4-pyridylmethyl group, 6-carboxyl-4-pyridylmethyl group 6-hydroxyl-4-pyridylmethyl group, 6- (N-methylcarboamido) -4-pyridylmethyl group, 6- (N, N-dimethylcarboa) D) -4-pyridylmethyl group, 6-methyl-4-pyridylmethyl group, 6-trifluoromethyl-4-pyridylmethyl group, 6-methoxy-4-pyridylmethyl group, 6-trifluoromethoxy-4-pyridyl Methyl group, 6-methylthio-4-pyridylmethyl group, 6-methylsulfinyl-4-pyridylmethyl group, 6-methylsulfonyl-4-pyridylmethyl group, 6-methoxycarbonyl-4-pyridylmethyl group, 6-vinyl- 4-pyridylmethyl group, 6- (2 ′, 2′-difluorovinyl) -4-pyridylmethyl group, 6-ethynyl-4-pyridylmethyl group, 6- (2′-fluoroethynyl) -4-pyridylmethyl group 6-fluoro-4-pyridylmethyl group, 6-chloro-4-pyridylmethyl group, 2-quinolylmethyl group, 1- (2′-quinolyl) ethyl 2- (2′-quinolyl) ethyl group, 3- (2′-quinolyl) propyl group, 4- (2′-quinolyl) butyl group, 5- (2′-quinolyl) pentyl group, 6- (2 ′) -Key
Noryl) hexyl group, 7- (2′-quinolyl) heptyl group, 8- (2′-quinolyl) octyl group, 6-cyano-2-quinolylmethyl group, 6-nitro-2-quinolylmethyl group, 6-carboxyl-2 -Quinolylmethyl group, 6-hydroxyl-2-quinolylmethyl group, 6- (N-methylcarboamido) -2-quinolylmethyl group, 6- (N, N-dimethylcarboamido) -2-quinolylmethyl group, 6-methyl-2 -Quinolylmethyl group, 6-trifluoromethyl-2-quinolylmethyl group, 6-methoxy-2-quinolylmethyl group, 6-trifluoromethoxy-2-quinolylmethyl group, 6-methylthio-2-quinolylmethyl group, 6-methylsulfinyl-2 -Quinolylmethyl group, 6-methylsulfonyl-2-quinolylmethyl group, 6-methoxycarbonyl-2 Quinolylmethyl group, 6-vinyl-2-quinolylmethyl group, 6- (2 ′, 2′-difluorovinyl) -2-quinolylmethyl group, 6-ethynyl-2-quinolylmethyl group, 6- (2′-fluoroethynyl) -2 -Quinolylmethyl group, 6-fluoro-2-quinolylmethyl group, 6-chloro-2-quinolylmethyl group, 3-quinolylmethyl group, 1- (3'-quinolyl) ethyl group, 2- (3'-quinolyl) ethyl group, 3 -(3'-quinolyl) propyl group, 4- (3'-quinolyl) butyl group, 5- (3'-quinolyl) pentyl group, 6- (3'-quinolyl) hexyl group, 7- (3'-quinolyl) ) Heptyl group, 8- (3′-quinolyl) octyl group, 6-cyano-3-quinolylmethyl group, 6-nitro-3-quinolylmethyl group, 6-carboxyl-3-quinolylmethyl group, 6-hydroxyl Ru-3-quinolylmethyl group, 6- (N-methylcarboamido) -3-quinolylmethyl group, 6- (N, N-dimethylcarboamido) -3-quinolylmethyl group, 6-methyl-3-quinolylmethyl group, 6- Trifluoromethyl-3-quinolylmethyl group, 6-methoxy-3-quinolylmethyl group, 6-trifluoromethoxy-3-quinolylmethyl group, 6-methylthio-3-quinolylmethyl group, 6-methylsulfinyl-3-quinolylmethyl group, 6- Methylsulfonyl-3-quinolylmethyl group, 6-methoxycarbonyl-3-quinolylmethyl group, 6-vinyl-3-quinolylmethyl group, 6- (2 ′, 2′-difluorovinyl) -3-quinolylmethyl group, 6-ethynyl-3 -Quinolylmethyl group, 6- (2'-fluoroethynyl) -3-quinolylmethyl group, 6-phenyl Oro-3-quinolylmethyl group, 6-chloro-3-quinolylmethyl group, 4-quinolylmethyl group, 1- (4′-quinolyl) ethyl group, 2- (4′-quinolyl) ethyl group, 3- (4′-quinolyl) ) Propyl group, 4- (4′-quinolyl) butyl group, 5- (3′-quinolyl) pentyl group, 6- (4′-quinolyl) hexyl group, 7- (4′-quinolyl) heptyl group, 8- (4′-quinolyl) octyl group, 6-cyano-4-quinolylmethyl group, 6-nitro-4-quinolylmethyl group, 6-carboxyl-4-quinolylmethyl group, 6-hydroxyl-4-quinolylmethyl group, 6- (N— Methylcarboamido) -4-quinolylmethyl group, 6- (N, N-dimethylcarboamido) -4-quinolylmethyl group, 6-methyl-4-quinolylmethyl group, 6-trifluoromethyl-4-ki Rylmethyl group, 6-methoxy-4-quinolylmethyl group, 6-trifluoromethoxy-4-quinolylmethyl group, 6-methylthio-4-quinolylmethyl group, 6-methylsulfinyl-4-quinolylmethyl group, 6-methylsulfonyl-4-quinolylmethyl Group, 6-methoxycarbonyl-4-quinolylmethyl group, 6-vinyl-4-quinolylmethyl group, 6- (2 ′, 2′-difluorovinyl) -4-quinolylmethyl group, 6-ethynyl-4-quinolylmethyl group, 6- (2′-fluoroethynyl) -4-quinolylmethyl group, 6-fluoro-4-quinolylmethyl group, 6-chloro-4-quinolylmethyl group, 2-furylmethyl group, 1- (2′-furyl) ethyl group, 2- (2′-furyl) ethyl group, 3- (2′-furyl) propyl group, 4- (2′-furyl) butyl group, 5- ( '-Furyl) pentyl group, 6- (2'-furyl) hexyl group, 7- (2'-furyl) heptyl group, 8- (2'-furyl) octyl group, 4-cyano-2-furylmethyl group, 4-nitro-2-furylmethyl group, 4-carboxyl-2-furylmethyl group, 4-hydroxyl-2-furylmethyl group, 4- (N-methylcarboamido) -2-furylmethyl group, 4- (N , N-dimethylcarboamido) -2-furylmethyl group, 4-methyl-2-furylmethyl group, 4-trifluoromethyl-2-furylmethyl group, 4-methoxy-2-furylmethyl group, 4-trifluoro Methoxy-2-furylmethyl group, 4-methylthio-2-furylmethyl group, 4-methylsulfinyl-2-furylmethyl group, 4-methylsulfonyl-2-furylmethyl group, 4-methoxycarbonyl 2-furylmethyl group, 4-vinyl-2-furylmethyl group, 4- (2 ′, 2′-difluorovinyl) -2-furylmethyl group, 4-ethynyl-2-furylmethyl group, 4- (2 ′ -Fluoroethynyl) -2-furylmethyl group, 4-fluoro-2-furylmethyl group, 4-chloro-2-furylmethyl group, 3-furylmethyl group, 1- (3'-furyl) ethyl group, 2- (3'-furyl) ethyl group, 3- (3'-furyl) propyl group, 4- (3'-furyl) butyl group, 5- (3'-furyl) pentyl group, 6- (3'-furyl) Hexyl group, 7- (3′-furyl) heptyl group, 8- (3′-furyl) octyl group, 4-cyano-3-furylmethyl group, 4-nitro-3-furylmethyl group, 4-carboxyl-3 -Furylmethyl group, 4-hydroxyl-3-furylmethyl group, 4- (N -Methylcarboamido) -3-furylmethyl group, 4- (N, N-dimethylcarboamido) -3-furylmethyl group, 4-methyl-3-furylmethyl group, 4-trifluoromethyl-3-furylmethyl Group, 4-methoxy-3-furylmethyl group, 4-trifluoromethoxy-3-furylmethyl group, 4-methylthio-3-furylmethyl group, 4-methylsulfinyl-3-furylmethyl group, 4-methylsulfonyl- 3-furylmethyl group, 4-methoxycarbonyl-3-furylmethyl group, 4-vinyl-3-furylmethyl group, 4- (2 ′, 2′-difluorovinyl) -3-furylmethyl group, 4-ethynyl- 3-furylmethyl group, 4- (2′-fluoroethynyl) -3-furylmethyl group, 4-fluoro-3-furylmethyl group, 4-chloro-3-furylmethyl group, 2- Enylmethyl group, 1- (2′-thienyl) ethyl group, 2- (2′-thienyl) ethyl group, 3- (2′-thienyl) propyl group, 4- (2′-thienyl) butyl group, 5- ( 2'-thienyl) pentyl group, 6- (2'-thienyl) hexyl group, 7- (2'-thienyl) heptyl group, 8- (2'-thienyl) octyl group, 4-cyano-2-thienylmethyl group 4-nitro-2-thienylmethyl group, 4-carboxyl-2-thienylmethyl group, 4-hydroxyl-2-thienylmethyl group, 4- (N-methylcarboamido) -2-thienylmethyl group, 4- ( N, N-dimethylcarboamido) -2-thienylmethyl group, 4-methyl-2-thienylmethyl group, 4-trifluoromethyl-2-thienylmethyl group, 4-methoxy-2-thienylmethyl group, 4-triethyl Fluoro Methoxy-2-thienylmethyl group, 4-methylthio-2-thienylmethyl group, 4-methylsulfinyl-2-thienylmethyl group, 4-methylsulfonyl-2-thienylmethyl group, 4-methoxycarbonyl-2-thienylmethyl group 4-vinyl-2-thienylmethyl group, 4- (2 ′, 2′-difluorovinyl) -2-thienylmethyl group, 4-ethynyl-2-thienylmethyl group, 4- (2′-fluoroethynyl)- 2-thienylmethyl group, 4-fluoro-2-thienylmethyl group, 4-chloro-2-thienylmethyl group, 3-thienylmethyl group, 1- (3′-thienyl) ethyl group, 2- (3′-thienyl) ) Ethyl group, 3- (3′-thienyl) propyl group, 4- (3′-thienyl) butyl group, 5- (3′-thienyl) pentyl group, 6- (3′-thienyl) hexyl group 7- (3′-thienyl) heptyl group, 8- (3′-thienyl) octyl group, 4-cyano-3-thienylmethyl group, 4-nitro-3-thienylmethyl group, 4-carboxyl-3-thienylmethyl Group, 4-hydroxyl-3-thienylmethyl group, 4- (N-methylcarboamido) -3-thienylmethyl group, 4- (N, N-dimethylcarboamido) -3-thienylmethyl group, 4-methyl- 3-thienylmethyl group, 4-trifluoromethyl-3-thienylmethyl group, 4-methoxy-3-thienylmethyl group, 4-trifluoromethoxy-3-thienylmethyl group, 4-methylthio-3-thienylmethyl group, 4-methylsulfinyl-3-thienylmethyl group, 4-methylsulfonyl-3-thienylmethyl group, 4-methoxycarbonyl-3-thienylmethyl group, 4-vinyl-3-thienylmethyl group, 4- (2 ′, 2′-difluorovinyl) -3-thienylmethyl group, 4-ethynyl-3-thienylmethyl group, 4- (2′-fluoroethynyl) -3 -Thienylmethyl group, 4-fluoro-3-thienylmethyl group, 4-chloro-3-thienylmethyl group, 2- (1-benzofuranyl) methyl group, 1- (2 '-(1'-benzofuranyl)) ethyl group 2- (2 ′-(1′-benzofuranyl)) ethyl group, 3- (2 ′-(1′-benzofuranyl)) propyl group, 4- (2 ′-(1′-benzofuranyl)) butyl group, 5 -(2 '-(1'-benzofuranyl)) pentyl group, 6- (2'-(1'-benzofuranyl)) hexyl group, 7- (2 '-(1'-benzofuranyl)) heptyl group, 8- ( 2 ′-(1′-benzofuranyl)) octyl group, 5-sia No-2- (1-benzofuranyl) methyl group, 5-nitro-2- (1-benzofuranyl) methyl group, 5-carboxyl-2- (1-benzofuranyl) methyl group, 5-hydroxyl-2- (1-benzofuranyl) ) Methyl group, 5- (N-methylcarboamido) -2- (1-benzofuranyl) methyl group, 5- (N, N-dimethylcarboamido) -2- (1-benzofuranyl) methyl group, 5-methyl- 2- (1-benzofuranyl) methyl group, 5-trifluoromethyl-2- (1-benzofuranyl) methyl group, 5-methoxy-2- (1-benzofuranyl) methyl group, 5-trifluoromethoxy-2- (1 -Benzofuranyl) methyl group, 5-methylthio-2- (1-benzofuranyl) methyl group, 5-methylsulfinyl-2- (1-benzofuranyl) methyl 5-methylsulfonyl-2- (1-benzofuranyl) methyl group, 5-methoxycarbonyl-2- (1-benzofuranyl) methyl group, 5-vinyl-2- (1-benzofuranyl) methyl group, 5- (2 ′ , 2′-difluorovinyl) -2- (1-benzofuranyl) methyl group, 5-ethynyl-2- (1-benzofuranyl) methyl group, 5- (2′-fluoroethynyl) -2- (1-benzofuranyl) methyl Group, 5-fluoro-2- (1-benzofuranyl) methyl group, 5-chloro-2- (1-benzofuranyl) methyl group, 3- (1-benzofuranyl) methyl group, 1- (3 ′-(1′-) Benzofuranyl)) ethyl group, 2- (3 ′-(1′-benzofuranyl)) ethyl group, 3- (3 ′-(1′-benzofuranyl)) propyl group, 4- (3 ′-(1′-benzofuranyl) ) Til, 5- (3 '-(1'-benzofuranyl)) pentyl, 6- (3'-(1'-benzofuranyl)) hexyl, 7- (3 '-(1'-benzofuranyl)) heptyl 8- (3 ′-(1′-benzofuranyl)) octyl group, 5-cyano-3- (1-benzofuranyl) methyl group, 5-nitro-3- (1-benzofuranyl) methyl group, 5-carboxyl-3 -(1-benzofuranyl) methyl group, 5-hydroxyl-3- (1-benzofuranyl) methyl group, 5- (N-methylcarbamido) -3- (1-benzofuranyl) methyl group, 5- (N, N- Dimethylcarboamido) -3- (1-benzofuranyl) methyl group, 5-methyl-3- (1-benzofuranyl) methyl group, 5-trifluoromethyl-3- (1-benzofuranyl) methyl group, 5-methoxy- - (1-benzofuranyl) methyl, 5-trifluoro-methoxy-3- (1-benzofuranyl) methyl, 5-
Methylthio-3- (1-benzofuranyl) methyl group, 5-methylsulfinyl-3- (1-benzofuranyl) methyl group, 5-methylsulfonyl-3- (1-benzofuranyl) methyl group, 5-methoxycarbonyl-3- ( 1-benzofuranyl) methyl group, 5-vinyl-3- (1-benzofuranyl) methyl group, 5- (2 ′, 2′-difluorovinyl) -3- (1-benzofuranyl) methyl group, 5-ethynyl-3- (1-benzofuranyl) methyl group, 5- (2′-fluoroethynyl) -3- (1-benzofuranyl) methyl group, 5-fluoro-3- (1-benzofuranyl) methyl group, 5-chloro-3- (1 -Benzofuranyl) methyl group, 2- (1-benzothienyl) methyl group, 1- (2 '-(1'-benzothienyl)) ethyl group, 2- (2'-(1'-benzothi) Enyl)) ethyl group, 3- (2 ′-(1′-benzothienyl)) propyl group, 4- (2 ′-(1′-benzothienyl)) butyl group, 5- (2 ′-(1′-) Benzothienyl)) pentyl group, 6- (2 ′-(1′-benzothienyl)) hexyl group, 7- (2 ′-(1′-benzothienyl)) heptyl group, 8- (2 ′-(1 ′) -Benzothienyl)) octyl group, 5-cyano-2- (1-benzothienyl) methyl group, 5-nitro-2- (1-benzothienyl) methyl group, 5-carboxyl-2- (1-benzothienyl) Methyl group, 5-hydroxyl-2- (1-benzothienyl) methyl group, 5- (N-methylcarboamido) -2- (1-benzothienyl) methyl group, 5- (N, N-dimethylcarboamido) -2- (1-benzothienyl) methyl group, 5-methyl-2- ( -Benzothienyl) methyl group, 5-trifluoromethyl-2- (1-benzothienyl) methyl group, 5-methoxy-2- (1-benzothienyl) methyl group, 5-trifluoromethoxy-2- (1- Benzothienyl) methyl group, 5-methylthio-2- (1-benzothienyl) methyl group, 5-methylsulfinyl-2- (1-benzothienyl) methyl group, 5-methylsulfonyl-2- (1-benzothienyl) Methyl group, 5-methoxycarbonyl-2- (1-benzothienyl) methyl group, 5-vinyl-2- (1-benzothienyl) methyl group, 5- (2 ′, 2′-difluorovinyl) -2- ( 1-benzothienyl) methyl group, 5-ethynyl-2- (1-benzothienyl) methyl group, 5- (2′-fluoroethynyl) -2- (1-benzothienyl) methyl group 5-fluoro-2- (1-benzothienyl) methyl group, 5-chloro-2- (1-benzothienyl) methyl group, 3- (1-benzothienyl) methyl group, 1- (3 ′-(1 ′) -Benzothienyl)) ethyl group, 2- (3 '-(1'-benzothienyl)) ethyl group, 3- (3'-(1'-benzothienyl)) propyl group, 4- (3 '-(1 '-Benzothienyl)) butyl group, 5- (3'-(1'-benzothienyl)) pentyl group, 6- (3 '-(1'-benzothienyl)) hexyl group, 7- (3'-( 1'-benzothienyl)) heptyl group, 8- (3 '-(1'-benzothienyl)) octyl group, 5-cyano-3- (1-benzothienyl) methyl group, 5-nitro-3- (1 -Benzothienyl) methyl group, 5-carboxyl-3- (1-benzothienyl) methyl group, 5-hydride Xyl-3- (1-benzothienyl) methyl group, 5- (N-methylcarboamido) -3- (1-benzothienyl) methyl group, 5- (N, N-dimethylcarboamido) -3- (1 -Benzothienyl) methyl group, 5-methyl-3- (1-benzothienyl) methyl group, 5-trifluoromethyl-3- (1-benzothienyl) methyl group, 5-methoxy-3- (1-benzothienyl) ) Methyl group, 5-trifluoromethoxy-3- (1-benzothienyl) methyl group, 5-methylthio-3- (1-benzothienyl) methyl group, 5-methylsulfinyl-3- (1-benzothienyl) methyl Group, 5-methylsulfonyl-3- (1-benzothienyl) methyl group, 5-methoxycarbonyl-3- (1-benzothienyl) methyl group, 5-vinyl-3- (1-benzothi Enyl) methyl group, 5- (2 ′, 2′-difluorovinyl) -3- (1-benzothienyl) methyl group, 5-ethynyl-3- (1-benzothienyl) methyl group, 5- (2′- Fluoroethynyl) -3- (1-benzothienyl) methyl group, 5-fluoro-3- (1-benzothienyl) methyl group, 5-chloro-3- (1-benzothienyl) methyl group, (methoxycarbonyl) methyl Group, 1- (methoxycarbonyl) ethyl group, 2- (methoxycarbonyl) ethyl group, 3- (methoxycarbonyl) propyl group, 4- (methoxycarbonyl) butyl group, 5- (methoxycarbonyl) pentyl group, 6- ( Methoxycarbonyl) hexyl group, 7- (methoxycarbonyl) heptyl group, 8- (methoxycarbonyl) octyl group, cyanomethyl group, 1-cyanoethyl 2-cyanoethyl group, 3-cyanopropyl group, 4-cyanobutyl group, 5-cyanopentyl group, 6-cyanohexyl group, 7-cyanoheptyl group, 8-cyanooctyl group, nitromethyl group, 1-nitroethyl group, 2 -Nitroethyl group, 3-nitropropyl group, 4-nitrobutyl group, 5-nitropentyl group, 6-nitrohexyl group, 7-nitroheptyl group, 8-nitrooctyl group, (carboxy) methyl group, 1- (carboxy) Ethyl group, 2- (carboxy) ethyl group, 3- (carboxy) propyl group, 4- (carboxy) butyl group, 5- (carboxy) pentyl group, 6- (carboxy) hexyl group, 7- (carboxy) heptyl group 8- (carboxy) octyl group, hydroxymethyl group, 1-hydroxyethyl group, 2-hydroxyethyl group, - hydroxypropyl, 4-hydroxybutyl group, 5-hydroxypentyl group, 6-hydroxyhexyl group, and 7-hydroxy-heptyl group and 8-hydroxy octyl groups.

In the present invention, examples of the methyl group having one group selected from group F include a benzyl group, 4-cyanobenzyl group, 4-nitrobenzyl group, 4-carboxylbenzyl group, 4-hydroxylbenzyl group, 4 -(N-methylcarboamido) benzyl group, 4- (N, N-dimethylcarboamido) benzyl group, 4-methylbenzyl group, 4-trifluoromethylbenzyl group, 4-methoxybenzyl group, 4-trifluoromethoxy Benzyl group, 4-methylthiobenzyl group, 4-methylsulfinylbenzyl group, 4-methylsulfonylbenzyl group, 4-methoxycarbonylbenzyl group, 4-vinylbenzyl group, 4- (2 ′, 2′-difluorovinyl) benzyl group 4-ethynylbenzyl group, 4- (2′-fluoroethynyl) benzyl group, 4-fluoroben Group, 4-chlorobenzyl group, 3,4-dichlorobenzyl group, 1-naphthylmethyl group, 2-naphthylmethyl group, 6-cyano-1-naphthylmethyl group, 6-nitro-1-naphthylmethyl group, 6 -Carboxyl-1-naphthylmethyl group, 6-hydroxyl-1-naphthylmethyl group, 6- (N-methylcarboamido) -1-naphthylmethyl group, 6- (N, N-dimethylcarboamido) -1-naphthyl Methyl group, 6-methyl-1-naphthylmethyl group, 6-trifluoromethyl-1-naphthylmethyl group, 6-methoxy-1-naphthylmethyl group, 6-trifluoromethoxy-1-naphthylmethyl group, 6-methylthio -1-naphthylmethyl group, 6-methylsulfinyl-1-naphthylmethyl group, 6-methylsulfonyl-1-naphthylmethyl group, 6-methoxy Carbonyl-1-naphthylmethyl group, 6-vinyl-1-naphthylmethyl group, 6- (2 ′, 2′-difluorovinyl) -1-naphthylmethyl group, 6-ethynyl-1-naphthylmethyl group, 6- ( 2'-fluoroethynyl) -1-naphthylmethyl group, 6-fluoro-1-naphthylmethyl group, 6-chloro-1-naphthylmethyl group, 6-cyano-2-naphthylmethyl group, 6-nitro-2-naphthyl group Methyl group, 6-carboxyl-2-naphthylmethyl group, 6-hydroxyl-2-naphthylmethyl group, 6- (N-methylcarboamido) -2-naphthylmethyl group, 6- (N, N-dimethylcarboamido) 2-naphthylmethyl group, 6-methyl-2-naphthylmethyl group, 6-trifluoromethyl-2-naphthylmethyl group, 6-methoxy-2-naphthylmethyl group, 6- Trifluoromethoxy-2-naphthylmethyl group, 6-methylthio-2-naphthylmethyl group, 6-methylsulfinyl-2-naphthylmethyl group, 6-methylsulfonyl-2-naphthylmethyl group, 6-methoxycarbonyl-2-naphthyl group Methyl group, 6-vinyl-2-naphthylmethyl group, 6- (2 ′, 2′-difluorovinyl) -2-naphthylmethyl group, 6-ethynyl-2-naphthylmethyl group, 6- (2′-fluoroethynyl) ) -2-Naphtylmethyl group, 6-fluoro-2-naphthylmethyl group, 6-chloro-2-naphthylmethyl group, 2-pyridylmethyl group, 4-cyano-2-pyridylmethyl group, 4-nitro-2- Pyridylmethyl group, 4-carboxyl-2-pyridylmethyl group, 4-hydroxyl-2-pyridylmethyl group, 4- (N-methylcarboxamide) 2-pyridylmethyl group, 4- (N, N-dimethylcarboamido) -2-pyridylmethyl group, 4-methyl-2-pyridylmethyl group, 4-trifluoromethyl-2-pyridylmethyl group, 4-methoxy 2-pyridylmethyl group, 4-trifluoromethoxy-2-pyridylmethyl group, 4-methylthio-2-pyridylmethyl group, 4-methylsulfinyl-2-pyridylmethyl group, 4-methylsulfonyl-2-pyridylmethyl group 4-methoxycarbonyl-2-pyridylmethyl group, 4-vinyl-2-pyridylmethyl group, 4- (2 ′, 2′-difluorovinyl) -2-pyridylmethyl group, 4-ethynyl-2-pyridylmethyl group 4- (2′-fluoroethynyl) -2-pyridylmethyl group, 4-fluoro-2-pyridylmethyl group, 4-chloro-2-pyridylmethyl group Group, 5-cyano-2-pyridylmethyl group, 5-nitro-2-pyridylmethyl group, 5-carboxyl-2-pyridylmethyl group, 5-hydroxyl-2-pyridylmethyl group, 5- (N-methylcarbo Amide) -2-pyridylmethyl group, 5- (N, N-dimethylcarboamido) -2-pyridylmethyl group, 5-methyl-2-pyridylmethyl group, 5-trifluoromethyl-2-pyridylmethyl group, 5 -Methoxy-2-pyridylmethyl group, 5-trifluoromethoxy-2-pyridylmethyl group, 5-methylthio-2-pyridylmethyl group, 5-methylsulfinyl-2-pyridylmethyl group, 5-methylsulfonyl-2-pyridyl Methyl group, 5-methoxycarbonyl-2-pyridylmethyl group, 5-vinyl-2-pyridylmethyl group, 5- (2 ′, 2′-difluoro) Nyl) -2-pyridylmethyl group, 5-ethynyl-2-pyridylmethyl group, 5- (2′-fluoroethynyl) -2-pyridylmethyl group, 5-fluoro-2-pyridylmethyl group, 5-chloro-2 -Pyridylmethyl group, 6-cyano-2-pyridylmethyl group, 6-nitro-2-pyridylmethyl group, 6-carboxyl-2-pyridylmethyl group, 6-hydroxyl-2-pyridylmethyl group, 6- (N- Methylcarboamido) -2-pyridylmethyl group, 6- (N, N-dimethylcarboamido) -2-pyridylmethyl group, 6-methyl-2-pyridylmethyl group, 6-trifluoromethyl-2-pyridylmethyl group 6-methoxy-2-pyridylmethyl group, 6-trifluoromethoxy-2-pyridylmethyl group, 6-methylthio-2-pyridylmethyl group, 6-methyls Finyl-2-pyridylmethyl group, 6-methylsulfonyl-2-pyridylmethyl group, 6-methoxycarbonyl-2-pyridylmethyl group, 6-vinyl-2-pyridylmethyl group, 6- (2 ′, 2′-difluoro Vinyl) -2-pyridylmethyl group, 6-ethynyl-2-pyridylmethyl group, 6- (2′-fluoroethynyl) -2-pyridylmethyl group, 6-fluoro-2-pyridylmethyl group, 6-chloro-2 -Pyridylmethyl group, 6,6-dichloro-2-pyridylmethyl group, 3-pyridylmethyl group, 5-cyano-3-pyridylmethyl group, 5-nitro-3-pyridylmethyl group, 5-carboxyl-3-pyridyl Methyl group, 5-hydroxyl-3-pyridylmethyl group, 5- (N-methylcarboamido) -3-pyridylmethyl group, 5- (N, N-dimethylcarbohydrate) Mido) -3-pyridylmethyl group, 5-methyl-3-pyridylmethyl group, 5-trifluoromethyl-3-pyridylmethyl group, 5-methoxy-3-pyridylmethyl group, 5-trifluoromethoxy-3-pyridyl Methyl group, 5-methylthio-3-pyridylmethyl group, 5-methylsulfinyl-3-pyridylmethyl group, 5-methylsulfonyl-3-pyridylmethyl group, 5-methoxycarbonyl-3-pyridylmethyl group, 5-vinyl- 3-pyridylmethyl group, 5- (2 ′, 2′-difluorovinyl) -3-pyridylmethyl group, 5-ethynyl-3-pyridylmethyl group, 5- (2′-fluoroethynyl) -3-pyridylmethyl group 5-fluoro-3-pyridylmethyl group, 5-chloro-3-pyridylmethyl group, 6-cyano-3-pyridylmethyl group, 6-nitro-3 -Pyridylmethyl group, 6-carboxyl-3-pyridylmethyl group, 6-hydroxyl-3-pyridylmethyl group, 6- (N-methylcarboamido) -3-pyridylmethyl group, 6- (N, N-dimethylcarbohydrate) Amide) -3-pyridylmethyl group, 6-methyl-3-pyridylmethyl group, 6-trifluoromethyl-3-pyridylmethyl group, 6-methoxy-3-pyridylmethyl group, 6-trifluoromethoxy-3-pyridyl group Methyl group, 6-methylthio-3-pyridylmethyl group, 6-methylsulfinyl-3-pyridylmethyl group, 6-methylsulfonyl-3-pyridylmethyl group, 6-methoxycarbonyl-3-pyridylmethyl group, 6-vinyl- 3-pyridylmethyl group, 6- (2 ′, 2′-difluorovinyl) -3-pyridylmethyl group, 6-ethynyl-3-pyri Rumethyl group, 6- (2′-fluoroethynyl) -3-pyridylmethyl group, 6-fluoro-3-pyridylmethyl group, 6-chloro-3-pyridylmethyl group, 4-pyridylmethyl group, 2-cyano-4 -Pyridylmethyl group, 2-nitro-4-pyridylmethyl group, 2-carboxyl-4-pyridylmethyl group, 2-hydroxyl-4-pyridylmethyl group, 2- (N-methylcarboamido) -4-pyridylmethyl group 2- (N, N-dimethylcarboamido) -4-pyridylmethyl group, 2-methyl-4-pyridylmethyl group, 2-trifluoromethyl-4-pyridylmethyl group, 2-methoxy-4-pyridylmethyl group 2-trifluoromethoxy-4-pyridylmethyl group, 2-methylthio-4-pyridylmethyl group, 2-methylsulfinyl-4-pyridylmethyl group 2-methylsulfonyl-4-pyridylmethyl group, 2-methoxycarbonyl-4-pyridylmethyl group, 2-vinyl-4-pyridylmethyl group, 2- (2 ′, 2′-difluorovinyl) -4-pyridylmethyl group 2-ethynyl-4-pyridylmethyl group, 2- (2′-fluoroethynyl) -4-pyridylmethyl group, 2-fluoro-4-pyridylmethyl group, 2-chloro-4-pyridylmethyl group, 6-cyano -4-pyridylmethyl group, 6-nitro-4-pyridylmethyl group, 6-carboxyl-4-pyridylmethyl group, 6-hydroxyl-4-pyridylmethyl group, 6- (N-methylcarboamido) -4-pyridyl Methyl group, 6- (N, N-dimethylcarboamido) -4-pyridylmethyl group, 6-methyl-4-pyridylmethyl group, 6-trifluoromethyl-4-pi Lysylmethyl group, 6-methoxy-4-pyridylmethyl group, 6-trifluoromethoxy-4-pyridylmethyl group, 6-methylthio-4-pyridylmethyl group, 6-methylsulfinyl-4-pyridylmethyl group, 6-methylsulfonyl -4-pyridylmethyl group, 6-methoxycarbonyl-4-pyridylmethyl group, 6-vinyl-4-pyridylmethyl group, 6- (2 ', 2'-difluorovinyl) -4-pyridylmethyl group, 6-ethynyl -4-pyridylmethyl group, 6- (2'-fluoroethynyl) -4-pyridylmethyl group, 6-fluoro-4-pyridylmethyl group, 6-chloro-4-pyridylmethyl group, 2-quinolylmethyl group, 6- Cyano-2-quinolylmethyl group, 6-nitro-2-quinolylmethyl group, 6-carboxyl-2-quinolylmethyl group, 6-hydroxyl Ru-2-quinolylmethyl group, 6- (N-methylcarboamido) -2-quinolylmethyl group, 6- (N, N-dimethylcarboamido) -2-quinolylmethyl group, 6-methyl-2-quinolylmethyl group, 6- Trifluoromethyl-2-quinolylmethyl group, 6-methoxy-2-quinolylmethyl group, 6-trifluoromethoxy-2-quinolylmethyl group, 6-methylthio-2-quinolylmethyl group, 6-methylsulfinyl-2-quinolylmethyl group, 6- Methylsulfonyl-2-quinolylmethyl group, 6-methoxycarbonyl-2-quinolylmethyl group, 6-vinyl-2-quinolylmethyl group, 6- (2 ′, 2′-difluorovinyl) -2-quinolylmethyl group, 6-ethynyl-2 -Quinolylmethyl group, 6- (2'-fluoroethynyl) -2-quinolylmethyl group, 6-phenyl Oro-2-quinolylmethyl group, 6-chloro-2-quinolylmethyl group, 3-quinolylmethyl group, 6-cyano-3-quinolylmethyl group, 6-nitro-3-quinolylmethyl group, 6-carboxyl-3-quinolylmethyl group, 6- Hydroxyl-3-quinolylmethyl group, 6- (N-methylcarboamido) -3-quinolylmethyl group, 6- (N, N-dimethylcarboamido) -3-quinolylmethyl group, 6-methyl-3-quinolylmethyl group, 6- Trifluoromethyl-3-quinolylmethyl group, 6-methoxy-3-quinolylmethyl group, 6-trifluoromethoxy-3-quinolylmethyl group, 6-methylthio-3-quinolylmethyl group, 6-methylsulfinyl-3-quinolylmethyl group, 6- Methylsulfonyl-3-quinolylmethyl group, 6-methoxycarbonyl-3- Quinolylmethyl group, 6-vinyl-3-quinolylmethyl group, 6- (2 ′, 2′-difluorovinyl) -3-quinolylmethyl group, 6-ethynyl-3-quinolylmethyl group, 6- (2′-fluoroethynyl) -3 -Quinolylmethyl group, 6-fluoro-3-quinolylmethyl group, 6-chloro-3-quinolylmethyl group, 4-quinolylmethyl group, 6-cyano-4-quinolylmethyl group, 6-nitro-4-quinolylmethyl group, 6-carboxyl-4 -Quinolylmethyl group, 6-hydroxyl-4-quinolylmethyl group, 6- (N-methylcarboamido) -4-quinolylmethyl group, 6- (N, N-dimethylcarboamido) -4-quinolylmethyl group, 6-methyl-4 -Quinolylmethyl group, 6-trifluoromethyl-4-quinolylmethyl group, 6-methoxy-4-quinolylmethyl group 6-trifluoromethoxy-4-quinolylmethyl group, 6-methylthio-4-quinolylmethyl group, 6-methylsulfinyl-4-quinolylmethyl group, 6-methylsulfonyl-4-quinolylmethyl group, 6-methoxycarbonyl-4-quinolylmethyl group, 6-vinyl-4-quinolylmethyl group, 6- (2 ′, 2′-difluorovinyl) -4-quinolylmethyl group, 6-ethynyl-4-quinolylmethyl group, 6- (2′-fluoroethynyl) -4-quinolylmethyl group 6-fluoro-4-quinolylmethyl group, 6-chloro-4-quinolylmethyl group, 2-furylmethyl group, 4-cyano-2-furylmethyl group, 4-nitro-2-furylmethyl group, 4-carboxyl-2 -Furylmethyl group, 4-hydroxyl-2-furylmethyl group, 4- (N-methylcarboxamide)- -Furylmethyl group, 4- (N, N-dimethylcarboamido) -2-furylmethyl group, 4-methyl-2-furylmethyl group, 4-trifluoromethyl-2-furylmethyl group, 4-methoxy-2 -Furylmethyl group, 4-trifluoromethoxy-2-furylmethyl group, 4-methylthio-2-furylmethyl group, 4-methylsulfinyl-2-furylmethyl group, 4-methylsulfonyl-2-furylmethyl group, 4 -Methoxycarbonyl-2-furylmethyl group, 4-vinyl-2-furylmethyl group, 4- (2 ', 2'-difluorovinyl) -2-furylmethyl group, 4-ethynyl-2-furylmethyl group, 4 -(2'-fluoroethynyl) -2-furylmethyl group, 4-fluoro-2-furylmethyl group, 4-chloro-2-furylmethyl group, 3-furylmethyl group, 4-cyano -3-furylmethyl group, 4-nitro-3-furylmethyl group, 4-carboxyl-3-furylmethyl group, 4-hydroxyl-3-furylmethyl group, 4- (N-methylcarboamido) -3-furyl Methyl group, 4- (N, N-dimethylcarboamido) -3-furylmethyl group, 4-methyl-3-furylmethyl group, 4-trifluoromethyl-3-furylmethyl group, 4-methoxy-3-furyl Methyl group, 4-trifluoromethoxy-3-furylmethyl group, 4-methylthio-3-furylmethyl group, 4-methylsulfinyl-3-furylmethyl group, 4-methylsulfonyl-3-furylmethyl group, 4-methoxy Carbonyl-3-furylmethyl group, 4-vinyl-3-furylmethyl group, 4- (2 ′, 2′-difluorovinyl) -3-furylmethyl group, 4-ethynyl-3 Furylmethyl group, 4- (2′-fluoroethynyl) -3-furylmethyl group, 4-fluoro-3-furylmethyl group, 4-chloro-3-furylmethyl group, 2-thienylmethyl group, 4-cyano- 2-thienylmethyl group, 4-nitro-2-thienylmethyl group, 4-carboxyl-2-thienylmethyl group, 4-hydroxyl-2-thienylmethyl group, 4- (N-methylcarboamido) -2-thienylmethyl Group, 4- (N, N-dimethylcarboamido) -2-thienylmethyl group, 4-methyl-2-thienylmethyl group, 4-trifluoromethyl-2-thienylmethyl group, 4-methoxy-2-thienylmethyl group Group, 4-trifluoromethoxy-2-thienylmethyl group, 4-methylthio-2-thienylmethyl group, 4-methylsulfinyl-2-thienylmethyl group, -Methylsulfonyl-2-thienylmethyl group, 4-methoxycarbonyl-2-thienylmethyl group, 4-vinyl-2-thienylmethyl group, 4- (2 ', 2'-difluorovinyl) -2-thienylmethyl group, 4-ethynyl-2-thienylmethyl group, 4- (2′-fluoroethynyl) -2-thienylmethyl group, 4-fluoro-2-thienylmethyl group, 4-chloro-2-thienylmethyl group, 3-thienylmethyl Group, 4-cyano-3-thienylmethyl group, 4-nitro-3-thienylmethyl group, 4-carboxyl-3-thienylmethyl group, 4-hydroxyl-3-thienylmethyl group, 4- (N-methylcarboxamide) ) -3-thienylmethyl group, 4- (N, N-dimethylcarboamido) -3-thienylmethyl group, 4-methyl-3-thienylmethyl group, 4-trif Fluoromethyl-3-thienylmethyl group, 4-methoxy-3-thienylmethyl group, 4-trifluoromethoxy-3-thienylmethyl group, 4-methylthio-3-thienylmethyl group, 4-methylsulfinyl-3-thienylmethyl group 4-methylsulfonyl-3-thienylmethyl group, 4-methoxycarbonyl-3-thienylmethyl group, 4-vinyl-3-thienylmethyl group, 4- (2 ′, 2′-difluorovinyl) -3-thienylmethyl Group, 4-ethynyl-3-thienylmethyl group, 4- (2′-fluoroethynyl) -3-thienylmethyl group, 4-fluoro-3-thienylmethyl group, 4-chloro-3-thienylmethyl group, 2- (1-benzofuranyl) methyl group, 5-cyano-2- (1-benzofuranyl) methyl group, 5-nitro-2- (1-benzofuranyl) Til group, 5-carboxyl-2- (1-benzofuranyl) methyl group, 5-hydroxyl-2- (1-benzofuranyl) methyl group, 5- (N-methylcarboamido) -2- (1-benzofuranyl) methyl group 5- (N, N-dimethylcarboamido) -2- (1-benzofuranyl) methyl group, 5-methyl-2- (1-benzofuranyl) methyl group, 5-trifluoromethyl-2- (1-benzofuranyl) Methyl group, 5-methoxy-2- (1-benzofuranyl) methyl group, 5-trifluoromethoxy-2- (1-benzofuranyl) methyl group, 5-methylthio-2- (1-benzofuranyl) methyl group, 5-methyl Sulfinyl-2- (1-benzofuranyl) methyl group, 5-methylsulfonyl-2- (1-benzofuranyl) methyl group, 5-methoxycal Nyl-2- (1-benzofuranyl) methyl group, 5-vinyl-2- (1-benzofuranyl) methyl group, 5- (2 ′, 2′-difluorovinyl) -2- (1-benzofuranyl) methyl group, 5 -Ethynyl-2- (1-benzofuranyl) methyl group, 5- (2'-fluoroethynyl) -2- (1-benzofuranyl) methyl group, 5-fluoro-2- (1-benzofuranyl) methyl group, 5-chloro 2- (1-benzofuranyl) methyl group, 3- (1-benzofuranyl) methyl group, 5-cyano-3- (1-benzofuranyl) methyl group, 5-nitro-3- (1-benzofuranyl) methyl group, 5 -Carboxyl-3- (1-benzofuranyl) methyl group, 5-hydroxyl-3- (1-benzofuranyl) methyl group, 5- (N-methylcarbamido) -3- (1-benzofur Ranyl) methyl group, 5- (N, N-dimethylcarboamido) -3- (1-benzofuranyl) methyl group, 5-methyl-3- (1-benzofuranyl) methyl group, 5-trifluoromethyl-3- ( 1-benzofuranyl) methyl group, 5-methoxy-3- (1-benzofuranyl) methyl group, 5-trifluoromethoxy-3- (1-benzofuranyl) methyl group, 5-methylthio-3- (1-benzofuranyl) methyl group 5-methylsulfinyl-3- (1-benzofuranyl) methyl group, 5-methylsulfonyl-3- (1-benzofuranyl) methyl group, 5-methoxycarbonyl-3- (1-benzofuranyl) methyl group, 5-vinyl- 3- (1-benzofuranyl) methyl group, 5- (2 ′, 2′-difluorovinyl) -3- (1-benzofuranyl) methyl group, 5- Tinyl-3- (1-benzofuranyl) methyl group, 5- (2′-fluoroethynyl) -3- (1-benzofuranyl) methyl group, 5-fluoro-3- (1-benzofuranyl) methyl group, 5-chloro- 3- (1-benzofuranyl) methyl group, 2- (1-benzothienyl) methyl group, 5-cyano-2- (1-benzothienyl) methyl group, 5-nitro-2- (1-benzothienyl) methyl group , 5-carboxyl-2- (1-benzothienyl) methyl group, 5-hydroxyl-2- (1-benzothienyl) methyl group, 5- (N-methylcarboamido) -2- (1-benzothienyl) methyl Group, 5- (N, N-dimethylcarboamido) -2- (1-benzothienyl) methyl group, 5-methyl-2- (1-benzothienyl) methyl group, 5-trifluoromethyl-2 (1-benzothienyl) methyl group, 5-methoxy-2- (1-benzothienyl) methyl group, 5-trifluoromethoxy-2- (1-benzothienyl) methyl group, 5-methylthio-2- (1- Benzothienyl) methyl group, 5-methylsulfinyl-2- (1-benzothienyl) methyl group, 5-methylsulfonyl-2- (1-benzothienyl) methyl group, 5-methoxycarbonyl-2- (1-benzothienyl) ) Methyl group, 5-vinyl-2- (1-benzothienyl) methyl group, 5- (2 ′, 2′-difluorovinyl) -2- (1-benzothienyl) methyl group, 5-ethynyl-2- ( 1-benzothienyl) methyl group, 5- (2′-fluoroethynyl) -2- (1-benzothienyl) methyl group, 5-fluoro-2- (1-benzothienyl) methyl group, Loro-2- (1-benzothienyl) methyl group, 3- (1-benzothienyl) methyl group, 5-cyano-3- (1-benzothienyl) methyl group, 5-nitro-3- (1-benzothienyl) ) Methyl group, 5-carboxyl-3- (1-benzothienyl) methyl group, 5-hydroxyl-3- (1-benzothienyl) methyl group, 5- (N-methylcarboamido) -3- (1-benzo Thienyl) methyl group, 5- (N, N-dimethylcarboamido) -3- (1-benzothienyl) methyl group, 5-methyl-3- (1-benzothienyl) methyl group, 5-trifluoromethyl-3 -(1-benzothienyl) methyl group, 5-methoxy-3- (1-benzothienyl) methyl group, 5-trifluoromethoxy-3- (1-benzothienyl) methyl group, 5-methylthio-3- ( -Benzothienyl) methyl group, 5-methylsulfinyl-3- (1-benzothienyl) methyl group, 5-methylsulfonyl-3- (1-benzothienyl) methyl group, 5-methoxycarbonyl-3- (1-benzo Thienyl) methyl group, 5-vinyl-3- (1-benzothienyl) methyl group, 5- (2 ′, 2′-difluorovinyl) -3- (1-benzothienyl) methyl group, 5-ethynyl-3- (1-benzothienyl) methyl group, 5- (2′-fluoroethynyl) -3- (1-benzothienyl) methyl group, 5-fluoro-3- (1-benzothienyl) methyl group, 5-chloro-3 Examples include-(1-benzothienyl) methyl group, (methoxycarbonyl) methyl group, cyanomethyl group, nitromethyl group, (carboxy) methyl group, and hydroxymethyl group.

In the present invention, examples of the C1-C2 alkyl group optionally having one or more atoms or groups selected from the group consisting of a hydroxyl group and a halogen atom include a methyl group, a hydroxylmethyl group, a fluoromethyl group, Difluoromethyl group, trifluoromethyl group, chloromethyl group, bromomethyl group, ethyl group, 1-hydroxyl-1-ethyl group, 2-hydroxyl-1-ethyl group, 1-fluoro-1-ethyl group, 1,1- Examples include a difluoro-1-ethyl group, a 1-chloro-1-ethyl group, a 2-chloro-1-ethyl group, and a 1-bromo-1-ethyl group.

で示される基であり、Ａ^１が酸素原子または硫黄原子であり、ｒが０または１であり、ｐが０、１または２である化合物、即ち、式（Ｉ−Ｓ）

で示されるアミド化合物；
式（Ｉ−Ｓ）において、ｎが１であり、Ｒ^１およびＲ^２が水素原子であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３およびＲ^４が水素原子であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３およびＲ^４が水素原子であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３およびＲ^４が水素原子であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｎが１であり、Ｒ^１およびＲ^２が水素原子であり、Ｒ^５が水素原子であるアミド化合物；
式（Ｉ−Ｓ）において、ｎが１であり、Ｒ^１およびＲ^２が水素原子であり、Ｒ^５が−ＯＲ^７およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ３炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｎが１であり、Ｒ^１およびＲ^２が水素原子であり、Ｒ^５がヒドロキシル基およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ２アルキル基であるアミド化合物；
式（Ｉ−Ｓ）において、ｎが１であり、Ｒ^１およびＲ^２が水素原子であり、Ｒ^５がメチル基であるアミド化合物；
式（Ｉ−Ｓ）において、ｎが１であり、Ｒ^１およびＲ^２が水素原子であり、Ｒ^５がヒドロキシメチル基であるアミド化合物；
式（Ｉ−Ｓ）において、ｎが１であり、Ｒ^１およびＲ^２が水素原子であり、Ｒ^５がフルオロメチル基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^５が水素原子であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^５が水素原子であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^５が水素原子であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３、Ｒ^４およびＲ^５が水素原子であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３、Ｒ^４およびＲ^５が水素原子であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３、Ｒ^４およびＲ^５が水素原子であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^５が−ＯＲ^７およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ３炭化水素基であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^５が−ＯＲ^７およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ３炭化水素基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^５が−ＯＲ^７およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ３炭化水素基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５が−ＯＲ^７およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ３炭化水素基であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５が−ＯＲ^７およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ３炭化水素基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５が−ＯＲ^７およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ３炭化水素基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^５がヒドロキシル基およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ２アルキル基であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^５がヒドロキシル基およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ２アルキル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^５がヒドロキシル基およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ２アルキル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がヒドロキシル基およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ２アルキル基であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がヒドロキシル基およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ２アルキル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がヒドロキシル基およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ２アルキル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^５がメチル基であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^５がメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^５がメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がメチル基であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^５がヒドロキシメチル基であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^５がヒドロキシメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^５がヒドロキシメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がヒドロキシメチル基であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がヒドロキシメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がヒドロキシメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^５がフルオロメチル基であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^５がフルオロメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^５がフルオロメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がフルオロメチル基であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がフルオロメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、Ｙが酸素原子であり、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がフルオロメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２およびＲ^５が水素原子であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２およびＲ^５が水素原子であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２およびＲ^５が水素原子であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４およびＲ^５が水素原子であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４およびＲ^５が水素原子であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４およびＲ^５が水素原子であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２およびＲ^５が−ＯＲ^７およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ３炭化水素基であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２およびＲ^５が−ＯＲ^７およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ３炭化水素基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２およびＲ^５が−ＯＲ^７およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ３炭化水素基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５が−ＯＲ^７およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ３炭化水素基であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５が−ＯＲ^７およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ３炭化水素基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５が−ＯＲ^７およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ３炭化水素基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２およびＲ^５がヒドロキシル基およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ２アルキル基であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２およびＲ^５がヒドロキシル基およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ２アルキル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２およびＲ^５がヒドロキシル基およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ２アルキル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がヒドロキシル基およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ２アルキル基であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がヒドロキシル基およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ２アルキル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がヒドロキシル基およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ２アルキル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２およびＲ^５がメチル基であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２およびＲ^５がメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２およびＲ^５がメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がメチル基であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２およびＲ^５がヒドロキシメチル基であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２およびＲ^５がヒドロキシメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２およびＲ^５がヒドロキシメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がヒドロキシメチル基であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がヒドロキシメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がヒドロキシメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２およびＲ^５がフルオロメチル基であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２およびＲ^５がフルオロメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２およびＲ^５がフルオロメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がフルオロメチル基であり、Ｑが群Ｇより選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がフルオロメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物；
式（Ｉ−Ｓ）において、ｍが１であり、ｎが１であり、Ｙが酸素原子であり、Ｒ^１、Ｒ^２、Ｒ^３およびＲ^４が水素原子であり、Ｒ^５がフルオロメチル基であり、Ｑが群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基を有していてもよいＣ１−Ｃ８鎖式炭化水素基であるアミド化合物； As an aspect of this invention compound, the following amide compounds are mentioned, for example.
In the formula (I-s), A represents the formula (III-a)

A group represented by ¹ Is an oxygen atom or a sulfur atom, r is 0 or 1, and p is 0, 1 or 2, that is, the compound of formula (IS)

An amide compound represented by:
In formula (IS), n is 1 and R ¹ And R ² An amide compound in which is a hydrogen atom;
A C1-C8 chain hydrocarbon group in which m is 1, Y is an oxygen atom and Q may have one or more atoms or groups selected from group G in formula (IS) An amide compound;
In the formula (IS), m is 1, Y is an oxygen atom, and Q may have a phenyl group which may have one or more atoms or groups selected from group B. An amide compound which is a good C1-C8 chain hydrocarbon group;
In the formula (IS), m is 1, Y is an oxygen atom, and Q has a naphthyl group which may have one or more atoms or groups selected from group B. An amide compound which is a good C1-C8 chain hydrocarbon group;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ And R ⁴ An amide compound wherein is a hydrogen atom and Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ And R ⁴ An amide compound in which is a hydrogen atom and Q is a C1-C8 chain hydrocarbon group optionally having a phenyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ And R ⁴ An amide compound wherein is a hydrogen atom and Q is a C1-C8 chain hydrocarbon group optionally having a naphthyl group optionally having one or more atoms or groups selected from group B;
In formula (IS), n is 1 and R ¹ And R ² Is a hydrogen atom and R ⁵ An amide compound in which is a hydrogen atom;
In formula (IS), n is 1 and R ¹ And R ² Is a hydrogen atom and R ⁵ Is -OR ⁷ And an amide compound which is a C1-C3 hydrocarbon group optionally having one or more atoms or groups selected from the group consisting of halogen atoms;
In formula (IS), n is 1 and R ¹ And R ² Is a hydrogen atom and R ⁵ An amide compound in which is a C1-C2 alkyl group optionally having one or more atoms or groups selected from the group consisting of a hydroxyl group and a halogen atom;
In formula (IS), n is 1 and R ¹ And R ² Is a hydrogen atom and R ⁵ An amide compound in which is a methyl group;
In formula (IS), n is 1 and R ¹ And R ² Is a hydrogen atom and R ⁵ An amide compound in which is a hydroxymethyl group;
In formula (IS), n is 1 and R ¹ And R ² Is a hydrogen atom and R ⁵ An amide compound in which is a fluoromethyl group;
In the formula (IS), m is 1, Y is an oxygen atom, R ⁵ An amide compound wherein is a hydrogen atom and Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G;
In the formula (IS), m is 1, Y is an oxygen atom, R ⁵ An amide compound in which is a hydrogen atom and Q is a C1-C8 chain hydrocarbon group optionally having a phenyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, Y is an oxygen atom, R ⁵ An amide compound wherein is a hydrogen atom and Q is a C1-C8 chain hydrocarbon group optionally having a naphthyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ , R ⁴ And R ⁵ An amide compound wherein is a hydrogen atom and Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ , R ⁴ And R ⁵ An amide compound in which is a hydrogen atom and Q is a C1-C8 chain hydrocarbon group optionally having a phenyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ , R ⁴ And R ⁵ An amide compound wherein is a hydrogen atom and Q is a C1-C8 chain hydrocarbon group optionally having a naphthyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, Y is an oxygen atom, R ⁵ Is -OR ⁷ And a C1-C3 hydrocarbon group which may have one or more atoms or groups selected from the group consisting of halogen atoms, and Q has one or more atoms or groups selected from group G An amide compound which may be a C1-C8 chain hydrocarbon group;
In the formula (IS), m is 1, Y is an oxygen atom, R ⁵ Is -OR ⁷ And a C1-C3 hydrocarbon group which may have one or more atoms or groups selected from the group consisting of halogen atoms, and Q has one or more atoms or groups selected from group B An amide compound which is a C1-C8 chain hydrocarbon group optionally having a phenyl group;
In the formula (IS), m is 1, Y is an oxygen atom, R ⁵ Is -OR ⁷ And a C1-C3 hydrocarbon group which may have one or more atoms or groups selected from the group consisting of halogen atoms, and Q has one or more atoms or groups selected from group B An amide compound which is a C1-C8 chain hydrocarbon group optionally having a naphthyl group;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ And R ⁴ Is a hydrogen atom and R ⁵ Is -OR ⁷ And a C1-C3 hydrocarbon group which may have one or more atoms or groups selected from the group consisting of halogen atoms, and Q has one or more atoms or groups selected from group G An amide compound which may be a C1-C8 chain hydrocarbon group;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ And R ⁴ Is a hydrogen atom and R ⁵ Is -OR ⁷ And a C1-C3 hydrocarbon group which may have one or more atoms or groups selected from the group consisting of halogen atoms, and Q has one or more atoms or groups selected from group B An amide compound which is a C1-C8 chain hydrocarbon group optionally having a phenyl group;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ And R ⁴ Is a hydrogen atom and R ⁵ Is -OR ⁷ And a C1-C3 hydrocarbon group which may have one or more atoms or groups selected from the group consisting of halogen atoms, and Q has one or more atoms or groups selected from group B An amide compound which is a C1-C8 chain hydrocarbon group optionally having a naphthyl group;
In the formula (IS), m is 1, Y is an oxygen atom, R ⁵ Is a C1-C2 alkyl group optionally having one or more atoms or groups selected from the group consisting of a hydroxyl group and a halogen atom, and Q has one or more atoms or groups selected from the group G. An amide compound which may be a C1-C8 chain hydrocarbon group;
In the formula (IS), m is 1, Y is an oxygen atom, R ⁵ Is a C1-C2 alkyl group optionally having one or more atoms or groups selected from the group consisting of a hydroxyl group and a halogen atom, and Q has one or more atoms or groups selected from group B. An amide compound which is a C1-C8 chain hydrocarbon group optionally having a phenyl group;
In the formula (IS), m is 1, Y is an oxygen atom, R ⁵ Is a C1-C2 alkyl group optionally having one or more atoms or groups selected from the group consisting of a hydroxyl group and a halogen atom, and Q has one or more atoms or groups selected from group B. An amide compound which is a C1-C8 chain hydrocarbon group optionally having a naphthyl group;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ And R ⁴ Is a hydrogen atom and R ⁵ Is a C1-C2 alkyl group optionally having one or more atoms or groups selected from the group consisting of a hydroxyl group and a halogen atom, and Q has one or more atoms or groups selected from the group G. An amide compound which may be a C1-C8 chain hydrocarbon group;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ And R ⁴ Is a hydrogen atom and R ⁵ Is a C1-C2 alkyl group optionally having one or more atoms or groups selected from the group consisting of a hydroxyl group and a halogen atom, and Q has one or more atoms or groups selected from group B. An amide compound which is a C1-C8 chain hydrocarbon group optionally having a phenyl group;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ And R ⁴ Is a hydrogen atom and R ⁵ Is a C1-C2 alkyl group optionally having one or more atoms or groups selected from the group consisting of a hydroxyl group and a halogen atom, and Q has one or more atoms or groups selected from group B. An amide compound which is a C1-C8 chain hydrocarbon group optionally having a naphthyl group;
In the formula (IS), m is 1, Y is an oxygen atom, R ⁵ An amide compound wherein is a methyl group and Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G;
In the formula (IS), m is 1, Y is an oxygen atom, R ⁵ An amide compound in which is a methyl group and Q is a C1-C8 chain hydrocarbon group optionally having a phenyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, Y is an oxygen atom, R ⁵ An amide compound in which is a methyl group and Q is a C1-C8 chain hydrocarbon group optionally having a naphthyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ And R ⁴ Is a hydrogen atom and R ⁵ An amide compound wherein is a methyl group and Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ And R ⁴ Is a hydrogen atom and R ⁵ An amide compound in which is a methyl group and Q is a C1-C8 chain hydrocarbon group optionally having a phenyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ And R ⁴ Is a hydrogen atom and R ⁵ An amide compound in which is a methyl group and Q is a C1-C8 chain hydrocarbon group optionally having a naphthyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, Y is an oxygen atom, R ⁵ An amide compound wherein is a hydroxymethyl group and Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G;
In the formula (IS), m is 1, Y is an oxygen atom, R ⁵ An amide compound in which is a hydroxymethyl group and Q is a C1-C8 chain hydrocarbon group optionally having a phenyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, Y is an oxygen atom, R ⁵ An amide compound in which is a hydroxymethyl group and Q is a C1-C8 chain hydrocarbon group optionally having a naphthyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ And R ⁴ Is a hydrogen atom and R ⁵ An amide compound wherein is a hydroxymethyl group and Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ And R ⁴ Is a hydrogen atom and R ⁵ An amide compound in which is a hydroxymethyl group and Q is a C1-C8 chain hydrocarbon group optionally having a phenyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ And R ⁴ Is a hydrogen atom and R ⁵ An amide compound in which is a hydroxymethyl group and Q is a C1-C8 chain hydrocarbon group optionally having a naphthyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, Y is an oxygen atom, R ⁵ An amide compound in which is a fluoromethyl group and Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G;
In the formula (IS), m is 1, Y is an oxygen atom, R ⁵ An amide compound in which is a fluoromethyl group and Q is a C1-C8 chain hydrocarbon group optionally having a phenyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, Y is an oxygen atom, R ⁵ An amide compound in which is a fluoromethyl group and Q is a C1-C8 chain hydrocarbon group optionally having a naphthyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ And R ⁴ Is a hydrogen atom and R ⁵ An amide compound in which is a fluoromethyl group and Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ And R ⁴ Is a hydrogen atom and R ⁵ An amide compound in which is a fluoromethyl group and Q is a C1-C8 chain hydrocarbon group optionally having a phenyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, Y is an oxygen atom, R ³ And R ⁴ Is a hydrogen atom and R ⁵ An amide compound in which is a fluoromethyl group and Q is a C1-C8 chain hydrocarbon group optionally having a naphthyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² And R ⁵ An amide compound wherein is a hydrogen atom and Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² And R ⁵ An amide compound in which is a hydrogen atom and Q is a C1-C8 chain hydrocarbon group optionally having a phenyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² And R ⁵ An amide compound wherein is a hydrogen atom and Q is a C1-C8 chain hydrocarbon group optionally having a naphthyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² , R ³ , R ⁴ And R ⁵ An amide compound wherein is a hydrogen atom and Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² , R ³ , R ⁴ And R ⁵ An amide compound in which is a hydrogen atom and Q is a C1-C8 chain hydrocarbon group optionally having a phenyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² , R ³ , R ⁴ And R ⁵ An amide compound wherein is a hydrogen atom and Q is a C1-C8 chain hydrocarbon group optionally having a naphthyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² And R ⁵ Is -OR ⁷ And a C1-C3 hydrocarbon group which may have one or more atoms or groups selected from the group consisting of halogen atoms, and Q has one or more atoms or groups selected from group G An amide compound which may be a C1-C8 chain hydrocarbon group;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² And R ⁵ Is -OR ⁷ And a C1-C3 hydrocarbon group which may have one or more atoms or groups selected from the group consisting of halogen atoms, and Q has one or more atoms or groups selected from group B An amide compound which is a C1-C8 chain hydrocarbon group optionally having a phenyl group;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² And R ⁵ Is -OR ⁷ And a C1-C3 hydrocarbon group which may have one or more atoms or groups selected from the group consisting of halogen atoms, and Q has one or more atoms or groups selected from group B An amide compound which is a C1-C8 chain hydrocarbon group optionally having a naphthyl group;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² , R ³ And R ⁴ Is a hydrogen atom and R ⁵ Is -OR ⁷ And a C1-C3 hydrocarbon group which may have one or more atoms or groups selected from the group consisting of halogen atoms, and Q has one or more atoms or groups selected from group G An amide compound which may be a C1-C8 chain hydrocarbon group;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² , R ³ And R ⁴ Is a hydrogen atom and R ⁵ Is -OR ⁷ And a C1-C3 hydrocarbon group which may have one or more atoms or groups selected from the group consisting of halogen atoms, and Q has one or more atoms or groups selected from group B An amide compound which is a C1-C8 chain hydrocarbon group optionally having a phenyl group;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² , R ³ And R ⁴ Is a hydrogen atom and R ⁵ Is -OR ⁷ And a C1-C3 hydrocarbon group which may have one or more atoms or groups selected from the group consisting of halogen atoms, and Q has one or more atoms or groups selected from group B An amide compound which is a C1-C8 chain hydrocarbon group optionally having a naphthyl group;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² And R ⁵ Is a C1-C2 alkyl group optionally having one or more atoms or groups selected from the group consisting of a hydroxyl group and a halogen atom, and Q has one or more atoms or groups selected from the group G. An amide compound which may be a C1-C8 chain hydrocarbon group;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² And R ⁵ Is a C1-C2 alkyl group optionally having one or more atoms or groups selected from the group consisting of a hydroxyl group and a halogen atom, and Q has one or more atoms or groups selected from group B. An amide compound which is a C1-C8 chain hydrocarbon group optionally having a phenyl group;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² And R ⁵ Is a C1-C2 alkyl group optionally having one or more atoms or groups selected from the group consisting of a hydroxyl group and a halogen atom, and Q has one or more atoms or groups selected from group B. An amide compound which is a C1-C8 chain hydrocarbon group optionally having a naphthyl group;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² , R ³ And R ⁴ Is a hydrogen atom and R ⁵ Is a C1-C2 alkyl group optionally having one or more atoms or groups selected from the group consisting of a hydroxyl group and a halogen atom, and Q has one or more atoms or groups selected from the group G. An amide compound which may be a C1-C8 chain hydrocarbon group;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² , R ³ And R ⁴ Is a hydrogen atom and R ⁵ Is a C1-C2 alkyl group optionally having one or more atoms or groups selected from the group consisting of a hydroxyl group and a halogen atom, and Q has one or more atoms or groups selected from group B. An amide compound which is a C1-C8 chain hydrocarbon group optionally having a phenyl group;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² , R ³ And R ⁴ Is a hydrogen atom and R ⁵ Is a C1-C2 alkyl group optionally having one or more atoms or groups selected from the group consisting of a hydroxyl group and a halogen atom, and Q has one or more atoms or groups selected from group B. An amide compound which is a C1-C8 chain hydrocarbon group optionally having a naphthyl group;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² And R ⁵ An amide compound wherein is a methyl group and Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² And R ⁵ An amide compound in which is a methyl group and Q is a C1-C8 chain hydrocarbon group optionally having a phenyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² And R ⁵ An amide compound in which is a methyl group and Q is a C1-C8 chain hydrocarbon group optionally having a naphthyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² , R ³ And R ⁴ Is a hydrogen atom and R ⁵ An amide compound wherein is a methyl group and Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² , R ³ And R ⁴ Is a hydrogen atom and R ⁵ An amide compound in which is a methyl group and Q is a C1-C8 chain hydrocarbon group optionally having a phenyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² , R ³ And R ⁴ Is a hydrogen atom and R ⁵ An amide compound in which is a methyl group and Q is a C1-C8 chain hydrocarbon group optionally having a naphthyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² And R ⁵ An amide compound wherein is a hydroxymethyl group and Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² And R ⁵ An amide compound in which is a hydroxymethyl group and Q is a C1-C8 chain hydrocarbon group optionally having a phenyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² And R ⁵ An amide compound in which is a hydroxymethyl group and Q is a C1-C8 chain hydrocarbon group optionally having a naphthyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² , R ³ And R ⁴ Is a hydrogen atom and R ⁵ An amide compound wherein is a hydroxymethyl group and Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² , R ³ And R ⁴ Is a hydrogen atom and R ⁵ An amide compound in which is a hydroxymethyl group and Q is a C1-C8 chain hydrocarbon group optionally having a phenyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² , R ³ And R ⁴ Is a hydrogen atom and R ⁵ An amide compound in which is a hydroxymethyl group and Q is a C1-C8 chain hydrocarbon group optionally having a naphthyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² And R ⁵ An amide compound in which is a fluoromethyl group and Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² And R ⁵ An amide compound in which is a fluoromethyl group and Q is a C1-C8 chain hydrocarbon group optionally having a phenyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² And R ⁵ An amide compound in which is a fluoromethyl group and Q is a C1-C8 chain hydrocarbon group optionally having a naphthyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² , R ³ And R ⁴ Is a hydrogen atom and R ⁵ An amide compound in which is a fluoromethyl group and Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² , R ³ And R ⁴ Is a hydrogen atom and R ⁵ An amide compound in which is a fluoromethyl group and Q is a C1-C8 chain hydrocarbon group optionally having a phenyl group optionally having one or more atoms or groups selected from group B;
In the formula (IS), m is 1, n is 1, Y is an oxygen atom, R ¹ , R ² , R ³ And R ⁴ Is a hydrogen atom and R ⁵ An amide compound in which is a fluoromethyl group and Q is a C1-C8 chain hydrocarbon group optionally having a naphthyl group optionally having one or more atoms or groups selected from group B;

Next, the manufacturing method of this invention compound is demonstrated.
The compound of the present invention can be produced, for example, according to the following (Production Method 1) to (Production Method 13).

［式中、Ｘ^１、Ｘ^２、Ｘ^３、Ｙ、A、Ｚ、Ｑ、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、ｍ及びｎは前記と同じ意味を表す。］
該反応は、通常縮合剤の存在下、必要に応じて塩基の存在下、溶媒中で行なわれる。
該反応に用いられる縮合剤としては、例えば、ジシクロヘキシルカルボジイミド及び１−エチル−３−（３−ジメチルアミノプロピル）カルボジイミド塩酸塩、ベンゾトリアゾール−１−イルオキシトリス（ジメチルアミノ）ホスホニウムヘキサフルオロホスフェート及びヘキサフルオロリン酸（ベンゾトリアゾール-1-イルオキシ）トリピロリジノホスホニウムが挙げられる。
該反応に用いられる塩基としては、例えば炭酸ナトリウム、炭酸カリウム等の炭酸塩類、トリエチルアミン、ジイソプロピルエチルアミン、１，８−ジアザビシクロ［５．４．０］ウンデカ−７−エン、１，５−ジアザビシクロ［４．３．０］ノン−５−エン等の第３級アミン類及びピリジン、４−ジメチルアミノピリジン等の含窒素芳香族化合物が挙げられる。
該反応に用いられる溶媒としては、例えば、ベンゼン、トルエン等の芳香族炭化水素類、ヘキサン等の炭化水素類、ジエチルエーテル、テトラヒドロフラン等のエーテル類、ジクロロメタン、クロロホルム、１，２−ジクロロエタン、クロロベンゼン等のハロゲン化炭化水素類、Ｎ，Ｎ−ジメチルホルムアミド等の酸アミド類、及び酢酸エチル、酢酸ブチル等のエステル類等が挙げられる。
該反応は、さらに必要に応じて式（１）で示される化合物１モルに対して、通常は０．０１モル〜１モルまで任意の割合で、好ましくは０．０５モル〜０．２モルの割合で１−ヒドロキシベンゾトリアゾール、１−ヒドロキシ−７−アザベンゾトリアゾール、Ｎ−ヒドロキシコハク酸イミド等を加えて行うこともできる。
該反応の反応時間は、通常、５分間〜７２時間の範囲である。
該反応の反応温度は、通常、−２０℃〜１００℃（但し、使用する溶媒の沸点が１００℃未満の場合には、−２０℃〜溶媒の沸点）の範囲である。
該反応において、式（１）で示される化合物と、式（２）で示される化合物との使用モル比は任意に設定できるが、好ましくは、等モル又はそれに近い比、例えば式（１）で示される化合物１モルに対して式（２）で示される化合物が１モル〜３モルの割合である。
該反応に用いられる縮合剤の量は、式（１）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合で使用することができ、好ましくは１モル〜３モルである。
該反応に用いられる塩基の量は、式（１）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合で使用することができ、好ましくは１モル〜３モルである。
反応終了後は、反応混合物を水に注加した後に有機溶媒抽出、濃縮等の通常の後処理操作を施すことにより、本発明合物を単離することができる。また単離された本発明化合物はクロマトグラフィ−、再結晶、蒸留等の操作によって精製することもできる。 (Production method 1)
The compound of the present invention can be produced by reacting the compound represented by the formula (1) with the compound represented by the formula (2) in the presence of a condensing agent.

[Wherein, X ¹ , X ² , X ³ , Y, A, Z, Q, R ¹ , R ² , R ³ , R ⁴ , m, and n represent the same meaning as described above. ]
The reaction is usually carried out in a solvent in the presence of a condensing agent and optionally in the presence of a base.
Examples of the condensing agent used in the reaction include dicyclohexylcarbodiimide and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride, benzotriazol-1-yloxytris (dimethylamino) phosphonium hexafluorophosphate, and hexa Fluorophosphoric acid (benzotriazol-1-yloxy) tripyrrolidinophosphonium.
Examples of the base used in the reaction include carbonates such as sodium carbonate and potassium carbonate, triethylamine, diisopropylethylamine, 1,8-diazabicyclo [5.4.0] undec-7-ene, 1,5-diazabicyclo [4]. .3.0] Tertiary amines such as non-5-ene and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine.
Examples of the solvent used in the reaction include aromatic hydrocarbons such as benzene and toluene, hydrocarbons such as hexane, ethers such as diethyl ether and tetrahydrofuran, dichloromethane, chloroform, 1,2-dichloroethane, chlorobenzene and the like. And halogenated hydrocarbons, acid amides such as N, N-dimethylformamide, and esters such as ethyl acetate and butyl acetate.
The reaction is usually carried out at an arbitrary ratio of 0.01 mol to 1 mol, preferably 0.05 mol to 0.2 mol, per 1 mol of the compound represented by the formula (1), if necessary. It can also be carried out by adding 1-hydroxybenzotriazole, 1-hydroxy-7-azabenzotriazole, N-hydroxysuccinimide and the like in proportion.
The reaction time is usually in the range of 5 minutes to 72 hours.
The reaction temperature of the reaction is usually in the range of −20 ° C. to 100 ° C. (however, when the boiling point of the solvent used is less than 100 ° C., it is −20 ° C. to the boiling point of the solvent).
In the reaction, the molar ratio of the compound represented by the formula (1) and the compound represented by the formula (2) can be arbitrarily set, but is preferably equimolar or a ratio close thereto, for example, the formula (1) The compound shown by Formula (2) is a ratio of 1 mol-3 mol with respect to 1 mol of shown compounds.
The amount of the condensing agent used in the reaction is usually 1 mol to an excess amount, and preferably 1 mol to 3 mol with respect to 1 mol of the compound represented by the formula (1). It is.
The amount of the base used in the reaction can be usually used in an arbitrary ratio from 1 mol to an excess amount with respect to 1 mol of the compound represented by the formula (1), preferably 1 mol to 3 mol. is there.
After completion of the reaction, the compound of the present invention can be isolated by pouring the reaction mixture into water and subjecting it to usual post-treatment operations such as organic solvent extraction and concentration. The isolated compound of the present invention can also be purified by operations such as chromatography, recrystallization and distillation.

［式中、Ｇ^１は脱離基（例えば塩素原子、臭素原子等）を表し、Ｘ^１、Ｘ^２、Ｘ^３、A、Ｙ、Ｚ、Ｑ、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、ｍ及びｎは前記と同じ意味を表す。］
該反応は、塩基の存在下、通常溶媒中で行われる。
該反応に用いられる塩基としては、例えば、炭酸ナトリウム、炭酸カリウム等の炭酸塩類、トリエチルアミン、ジイソプロピルエチルアミン、１，８−ジアザビシクロ［５．４．０］ウンデカ−７−エン、１，５−ジアザビシクロ［４．３．０］ノン−５−エン等の第３級アミン類及びピリジン、４−ジメチルアミノピリジン等の含窒素芳香族化合物が挙げられる。
該反応に用いられる溶媒としては、例えば、１，４−ジオキサン、テトラヒドロフラン、エチレングリコールジメチルエーテル、ｔｅｒｔ−ブチルメチルエーテル等のエーテル類、ヘキサン、ヘプタン、オクタン等の脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン等のハロゲン化炭化水素類、酢酸エチル、酢酸ブチル等のエステル類、アセトニトリル、ブチロニトリル等のニトリル類、Ｎ，Ｎ−ジメチルホルムアミド等の酸アミド類、ジメチルスルホキシド等のスルホキシド類及びこれらの混合物が挙げられる。
該反応の反応時間は、通常、５分間〜７２時間の範囲である。
該反応の反応温度は、通常、−２０〜１００℃の範囲である。
該反応において、式（３）で示される化合物と、式（２）で示される化合物の使用モル比は任意に設定できるが、好ましくは、等モル又はそれに近い比、具体的には式（５）で示される化合物１モルに対して、式（２）で示される化合物が０．５〜３モルである。
該反応に用いられる塩基の量は、式（３）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合で使用することができ、好ましくは１〜３モルである。
反応終了後は、反応混合物を水に注加した後に有機溶媒抽出、濃縮等の通常の後処理操作を施すことにより、本発明化合物を単離することができる。また単離された本発明化合物はクロマトグラフィー、再結晶、蒸留等の操作によって精製することもできる。 (Production method 2)
The compound of the present invention can be produced by reacting the compound represented by the formula (3) with the compound represented by the formula (2) in the presence of a base.

[Wherein, G ¹ represents a leaving group (for example, chlorine atom, bromine atom, etc.), and X ¹ , X ² , X ³ , A, Y, Z, Q, R ¹ , R ² , R ³ , R ⁴ , M, and n represent the same meaning as described above. ]
The reaction is usually performed in a solvent in the presence of a base.
Examples of the base used in the reaction include carbonates such as sodium carbonate and potassium carbonate, triethylamine, diisopropylethylamine, 1,8-diazabicyclo [5.4.0] undec-7-ene, 1,5-diazabicyclo [ 4.3.0] tertiary amines such as non-5-ene and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine.
Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, and tert-butyl methyl ether, aliphatic hydrocarbons such as hexane, heptane, and octane, toluene, xylene, and the like. Aromatic hydrocarbons, halogenated hydrocarbons such as chlorobenzene, esters such as ethyl acetate and butyl acetate, nitriles such as acetonitrile and butyronitrile, acid amides such as N, N-dimethylformamide, dimethyl sulfoxide and the like Examples include sulfoxides and mixtures thereof.
The reaction time is usually in the range of 5 minutes to 72 hours.
The reaction temperature of the reaction is usually in the range of -20 to 100 ° C.
In the reaction, the molar ratio of the compound represented by the formula (3) and the compound represented by the formula (2) can be arbitrarily set, but is preferably equimolar or a ratio close thereto, specifically, the formula (5 The compound represented by the formula (2) is 0.5 to 3 mol per 1 mol of the compound represented by
The amount of the base used in the reaction can be usually used in an arbitrary ratio from 1 mol to an excess amount with respect to 1 mol of the compound represented by the formula (3), preferably 1 to 3 mol. .
After completion of the reaction, the compound of the present invention can be isolated by pouring the reaction mixture into water and subjecting it to usual post-treatment operations such as organic solvent extraction and concentration. The isolated compound of the present invention can also be purified by operations such as chromatography, recrystallization and distillation.

［式中、Ｇ^２は脱離基（例えば塩素原子、臭素原子、ヨウ素原子、メタンスルホニルオキシ基、トリフルオロメタンスルホニルオキシ基又は４−トルエンスルホニルオキシ基等）を表し、Ｙ^１は酸素原子、または硫黄原子を表し、Ｘ^１、Ｘ^２、Ｘ^３、Ｑ、A、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、ｍ及びｎは前記と同じ意味を表す。］
該反応は、塩基の存在下、通常溶媒中で行われる。
該反応に用いられる塩基としては、例えば、ナトリウム、カリウム等のアルカリ金属類、ｎ−ブチルリチウム等のアルキルリチウム類、水素化ナトリウム、水素化カリウム等の金属水素化合物、炭酸ナトリウム、炭酸カリウム等の炭酸塩類、カリウム−ｔ−ブトキシド等のアルカリ金属アルコキシド、トリエチルアミン、ジイソプロピルエチルアミン、１，８−ジアザビシクロ［５．４．０］ウンデカ−７−エン、１，５−ジアザビシクロ［４．３．０］ノン−５−エン等の第３級アミン類及びピリジン、４−ジメチルアミノピリジン等の含窒素芳香族化合物が挙げられる。
該反応に用いられる溶媒としては、例えば、１，４−ジオキサン、テトラヒドロフラン、エチレングリコールジメチルエーテル、ｔｅｒｔ−ブチルメチルエーテル等のエーテル類、ヘキサン、ヘプタン、オクタン等の脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン等のハロゲン化炭化水素類、酢酸エチル、酢酸ブチル等のエステル類、アセトニトリル、ブチロニトリル等のニトリル類、Ｎ，Ｎ−ジメチルホルムアミド等の酸アミド類、ジメチルスルホキシド等のスルホキシド類及びこれらの混合物が挙げられる。
該反応の反応時間は、通常、５分間〜７２時間の範囲である。
該反応の反応温度は、通常、−２０〜１００℃の範囲である。
該反応において、式（４）で示される化合物と、式（５）で示される化合物の使用モル比は任意に設定できるが、好ましくは、等モル又はそれに近い比、具体的には式（４）で示される化合物１モルに対して、式（５）で示される化合物が０．５〜３モルである。
該反応に用いられる塩基の量は、式（５）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合で使用することができ、好ましくは１〜３モルである。
反応終了後は、反応混合物を水に注加した後に有機溶媒抽出、濃縮等の通常の後処理操作を施すことにより、本発明化合物を単離することができる。また単離された本発明化合物はクロマトグラフィー、再結晶、蒸留等の操作によって精製することもできる。
（製造法４）
式（Ｉ−ｓ）で示される化合物は、例えば，Ｅｕｒｏｐｅａｎ Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ，４８５２−４８６０，（２００６）記載の方法に準じて下記スキームで示されるルートにより製造することができる。

［式中、Ｙ、A、Ｑ、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ｒ^５、ｍ及びｎは前記と同じ意味を表す。］
（製造法５）
式（Ｉ−ｔ）で示される化合物は、例えば，Ｅｕｒｏｐｅａｎ Ｊｏｕｒｎａｌ ｏｆ Ｏｒｇａｎｉｃ Ｃｈｅｍｉｓｔｒｙ，４８５２−４８６０，（２００６）記載の方法に準じて下記スキームで示されるルートにより製造することができる。

［式中、Ｙ、A、Ｑ、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ｒ^５、ｍ及びｎは前記と同じ意味を表す。］
（製造法６）
式（Ｉ−ｘ）で示される化合物は、例えば， 例えば、Ｐｈｏｓｐｈｏｒｕｓ ａｎｄ Ｓｕｌｆｕｒ ａｎｄ ｔｈｅ Ｒｅｌａｔｅｄ Ｅｌｅｍｅｎｔｓ，１５（２），１３７−４２（１９８３）記載の方法に準じて下記スキームで示されるルートにより製造することができる。

［式中、Ｙ、A、Ｑ、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、Ｒ^５、ｍ及びｎは前記と同じ意味を表す。］ (Production method 3)
The compound represented by the formula (Iw) can be produced by reacting the compound represented by the formula (4) with the compound represented by the formula (5) in the presence of a base.

[Wherein G ² represents a leaving group (for example, a chlorine atom, a bromine atom, an iodine atom, a methanesulfonyloxy group, a trifluoromethanesulfonyloxy group, a 4-toluenesulfonyloxy group, etc.), and Y ¹ represents an oxygen atom, or Represents a sulfur atom, and X ¹ , X ² , X ³ , Q, A, R ¹ , R ² , R ³ , R ⁴ , m, and n represent the same meaning as described above. ]
The reaction is usually performed in a solvent in the presence of a base.
Examples of the base used in the reaction include alkali metals such as sodium and potassium, alkyllithiums such as n-butyllithium, metal hydride compounds such as sodium hydride and potassium hydride, sodium carbonate, potassium carbonate and the like. Carbonates, alkali metal alkoxides such as potassium t-butoxide, triethylamine, diisopropylethylamine, 1,8-diazabicyclo [5.4.0] undec-7-ene, 1,5-diazabicyclo [4.3.0] non Examples include tertiary amines such as -5-ene and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine.
Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, and tert-butyl methyl ether, aliphatic hydrocarbons such as hexane, heptane, and octane, toluene, xylene, and the like. Aromatic hydrocarbons, halogenated hydrocarbons such as chlorobenzene, esters such as ethyl acetate and butyl acetate, nitriles such as acetonitrile and butyronitrile, acid amides such as N, N-dimethylformamide, dimethyl sulfoxide and the like Examples include sulfoxides and mixtures thereof.
The reaction time is usually in the range of 5 minutes to 72 hours.
The reaction temperature of the reaction is usually in the range of -20 to 100 ° C.
In the reaction, the molar ratio of the compound represented by the formula (4) and the compound represented by the formula (5) can be arbitrarily set, but is preferably equimolar or a ratio close thereto, specifically, the formula (4 The compound represented by the formula (5) is 0.5 to 3 mol per 1 mol of the compound represented by
The amount of the base used in the reaction can be generally used in an arbitrary ratio from 1 mol to an excess amount, preferably 1 to 3 mol, with respect to 1 mol of the compound represented by the formula (5). .
After completion of the reaction, the compound of the present invention can be isolated by pouring the reaction mixture into water and subjecting it to usual post-treatment operations such as organic solvent extraction and concentration. The isolated compound of the present invention can also be purified by operations such as chromatography, recrystallization and distillation.
(Production Method 4)
The compound represented by the formula (I-s) can be produced, for example, by the route shown in the following scheme according to the method described in European Journal of Organic Chemistry, 4852-4860, (2006).

[Wherein, Y, A, Q, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , m, and n represent the same meaning as described above. ]
(Production method 5)
The compound represented by the formula (It) can be produced, for example, by the route shown in the following scheme according to the method described in European Journal of Organic Chemistry, 4852-4860, (2006).

[Wherein, Y, A, Q, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , m, and n represent the same meaning as described above. ]
(Production method 6)
The compound represented by the formula (Ix) is produced by, for example, the route shown in the following scheme according to the method described in Phosphorus and Sulfur and the Related Elements, 15 (2), 137-42 (1983). be able to.

[Wherein, Y, A, Q, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , m, and n represent the same meaning as described above. ]

［式中、Ｇ^２は脱離基（例えば塩素、臭素、ヨウ素、メタンスルホニルオキシ基、トリフルオロメタンスルホニルオキシ基又はトルエンスルホニルオキシ基等）を表し、Ｘ^１、Ｘ^２、Ｘ^３、Ｑ、Ｙ、A、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、ｍ及びｎは前記と同じ意味を表す。］
該カップリング反応としては例えば、
（１）Ｎｅｇｉｓｈｉカップリング反応
（２）Ｓｔｉｌｌｅカップリング反応
（３）Ｓｕｚｕｋｉカップリング反応
（４）グリニャール試薬（Ｇｒｉｇｎａｒｄ Ｒｅａｇｅｎｔ）、有機銅試薬、有機リチウム試薬等の有機金属試薬を用いる方法
等が挙げられる。
一例として（１）Ｎｅｇｉｓｈｉカップリング反応による方法を具体的に挙げる。
該反応は、通常窒素等の不活性気体雰囲気下、通常遷移金属触媒、無機亜鉛塩類及び有機金属試薬の存在下、必要に応じてリガンドの存在下、溶媒中で行なわれる。
該反応に用いられる遷移金属触媒としては、例えば酢酸パラジウム、パラジウムジクロリド、ジクロロビス（トリフェニルホスフィン）パラジウム、テトラキス（トリフェニルホスフィン）パラジウム等のパラジウム触媒等が挙げられる。
該反応に用いられるリガンドとしては、トリメチルホスフィン、トリシクロヘキシルホスフィン、トリフェニルホスフィン等のホスフィン類、１，３−ビス（２，４，６−トリメチルフェニル）イミダゾリウムクロリド等のイミダゾリウム塩類、アセチルアセトン、オクタフルオロアセチルアセトンなどのジケトン類、１，１’−ビス（ジフェニルホスフィノ）フェロセン、２−ジシクロヘキシルホスフィノ−２’，６’−ジメトキシビフェニル等が挙げられる。
該反応に用いられる無機亜鉛塩類としては、塩化亜鉛等が挙げられる。
該反応に用いられる有機金属試薬としては、メチルマグネシウムクロリド、エチルマグネシウムクロリド、プロピルマグネシウムクロリド、ブチルマグネシウムクロリド、ペンチルマグネシウムブロミド、へキシルマグネシウムクロリド等の有機マグネシウムハロゲン化物、メチルリチウム、エチルリチウム等の有機リチウム化合物等が挙げられる。
該反応に用いられる溶媒としては、例えば、ベンゼン、トルエン等の芳香族炭化水素類、ヘキサン等の炭化水素類、ジエチルエーテル、テトラヒドロフラン等のエーテル類等が挙げられる。
該反応の反応時間は、通常、５分間〜７２時間の範囲である。
該反応の反応温度は、通常、−２０℃〜１００℃（但し、使用する溶媒の沸点が１００℃未満の場合には、−２０℃〜溶媒の沸点）の範囲である。
該反応に用いられる遷移金属触媒の量は、式（１２）で示される化合物１モルに対して通常０．００１〜０．５モルの割合である。
該反応に用いられるリガンドの量は、式（１２）で示される化合物１モルに対して、通常０．００１〜０．５モルの割合である。
該反応に用いられる無機亜鉛塩類の量は、式（１２）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合で使用することができ、好ましくは１モル〜３モルである。
該反応に用いられる有機金属試薬の量は、式（１２）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合で使用することができ、好ましくは１モル〜３モルである。
反応終了後は、反応混合物を水に注加した後に有機溶媒抽出、濃縮等の通常の後処理操作を施すことにより、本発明合物を単離することができる。また単離された本発明化合物はクロマトグラフィ−、再結晶、蒸留等の操作によって精製することもできる。 (Production method 7)
The compound represented by the formula (Iw) can be produced by subjecting the compound represented by the formula (12) to a coupling reaction.

[Wherein G ² represents a leaving group (for example, chlorine, bromine, iodine, methanesulfonyloxy group, trifluoromethanesulfonyloxy group, toluenesulfonyloxy group, etc.), and X ¹ , X ² , X ³ , Q, Y , A, R ¹ , R ² , R ³ , R ⁴ , m and n represent the same meaning as described above. ]
Examples of the coupling reaction include
(1) Negishi coupling reaction (2) Stille coupling reaction (3) Suzuki coupling reaction (4) Grignard reagent, organic copper reagent, method using organolithium reagent, etc. .
As an example, (1) a method based on Negishi coupling reaction is specifically mentioned.
The reaction is usually carried out in a solvent in an inert gas atmosphere such as nitrogen, usually in the presence of a transition metal catalyst, an inorganic zinc salt and an organometallic reagent, and optionally in the presence of a ligand.
Examples of the transition metal catalyst used in the reaction include palladium catalysts such as palladium acetate, palladium dichloride, dichlorobis (triphenylphosphine) palladium, and tetrakis (triphenylphosphine) palladium.
Examples of the ligand used in the reaction include phosphines such as trimethylphosphine, tricyclohexylphosphine, and triphenylphosphine, imidazolium salts such as 1,3-bis (2,4,6-trimethylphenyl) imidazolium chloride, acetylacetone, Examples include diketones such as octafluoroacetylacetone, 1,1′-bis (diphenylphosphino) ferrocene, and 2-dicyclohexylphosphino-2 ′, 6′-dimethoxybiphenyl.
Examples of inorganic zinc salts used in the reaction include zinc chloride.
Examples of organometallic reagents used in the reaction include methylmagnesium chloride, ethylmagnesium chloride, propylmagnesium chloride, butylmagnesium chloride, pentylmagnesium bromide, hexylmagnesium chloride and other organomagnesium halides, and organic compounds such as methyllithium and ethyllithium. A lithium compound etc. are mentioned.
Examples of the solvent used in the reaction include aromatic hydrocarbons such as benzene and toluene, hydrocarbons such as hexane, ethers such as diethyl ether and tetrahydrofuran, and the like.
The reaction time is usually in the range of 5 minutes to 72 hours.
The reaction temperature of the reaction is usually in the range of −20 ° C. to 100 ° C. (however, when the boiling point of the solvent used is less than 100 ° C., it is −20 ° C. to the boiling point of the solvent).
The amount of the transition metal catalyst used in the reaction is usually 0.001 to 0.5 mol with respect to 1 mol of the compound represented by the formula (12).
The amount of the ligand used in the reaction is usually 0.001 to 0.5 mol with respect to 1 mol of the compound represented by the formula (12).
The amount of the inorganic zinc salt used in the reaction can be generally used in an arbitrary ratio from 1 mol to an excess amount with respect to 1 mol of the compound represented by the formula (12), preferably 1 mol to 3 mol. Is a mole.
The amount of the organometallic reagent used in the reaction can be usually used in an arbitrary ratio from 1 mol to an excess amount with respect to 1 mol of the compound represented by the formula (12), preferably 1 to 3 mol. Is a mole.
After completion of the reaction, the compound of the present invention can be isolated by pouring the reaction mixture into water and subjecting it to usual post-treatment operations such as organic solvent extraction and concentration. The isolated compound of the present invention can also be purified by operations such as chromatography, recrystallization and distillation.

［式中、Ｒ^ｘはハロゲン原子、ホルミル基、カルボキシル基、またはヒドロキシル基およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有していてもよいＣ１−Ｃ３炭化水素基を表し、Ｘ^２、Ｘ^３、Ｙ、A、Ｚ、Ｑ、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、ｍ及びｎは前記と同じ意味を表す。］
該反応は、通常窒素等の不活性気体雰囲気下、塩基の存在下、溶媒中で行なわれる。
該反応に用いられる塩基としては、ナトリウムアミド、リチウムジイソプロピルアミド、ナトリウムビス（トリメチルシリル）アミド等の金属アミド、カリウム−ｔｅｒｔ−ブトキシド等のアルカリ金属アルコキシド、メチルリチウム、エチルリチウム、ｎ−ブチルリチウム、ｓｅｃ−ブチルリチウム、ｔｅｒｔ−ブチルリチウム、２，４，６−トリメチルフェニルリチウム等の有機リチウム化合物、メチルマグネシウムクロリド、エチルマグネシウムクロリド、プロピルマグネシウムクロリド、ブチルマグネシウムクロリド、ペンチルマグネシウムブロミド、へキシルマグネシウムクロリド等の有機マグネシウムハロゲン化物、２，２，６，６−テトラメチルピペリジニルマグネシウムクロリド・リチウムクロリド錯体が挙げられる。
該反応に用いられる求電子剤としては、Ｎ，Ｎ−ジメチルホルムアミド、ホルムアルデヒド、パラホルムアルデヒド、アセトアルデヒド、プロピオンアルデヒド、ヨードメタン、ヨードエタン、１，２−ジブロモエタン、１−ブロモ−２−クロロエタン、１−クロロプロパン、１−ブロモプロパン、１−ヨードプロパン、硫酸ジメチル、硫酸ジエチル、メチルトシラート、臭素、ヨウ素、Ｎ−ブロモスクシンイミド、Ｎ−クロロスクシンイミド、Ｎ−ヨードスクシンイミド、二酸化炭素、Ｎ−フルオロ−２，４，６−トリメチルピリジニウムトリフラート等のＮ−フルオロピリジニウム塩、Ｎ−フルオロ−Ｎ’−（クロロメチル）トリエチレンジアミンビス（テトラフルオロボラート）、Ｎ−フルオロベンゼンスルホンイミド等の求電子的フッ素化剤が挙げられる。
該反応に用いられる溶媒としては、例えば、ヘキサン等の炭化水素類、ベンゼン、トルエン、キシレン等の芳香族炭化水素類、ジエチルエーテル、テトラヒドロフラン等のエーテル類及びこれらの混合物が挙げられる。
該反応の反応時間は、通常、５分間〜７２時間の範囲である。
該反応の反応温度は、通常、−１００℃〜４０℃（但し、使用する溶媒の沸点が４０℃未満の場合には、−１００℃〜溶媒の沸点）の範囲である。
該反応に用いられる塩基の量は、式（Ｉ−ｙ）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合で使用することができ、好ましくは２モル〜３モルである。
該反応に用いられる求電子剤の量は、式（Ｉ−ｙ）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合で使用することができ、好ましくは１モル〜３モルである。
反応終了後は、反応混合物を水に注加した後に有機溶媒抽出、濃縮等の通常の後処理操作を施すことにより、本発明合物を単離することができる。また単離された本発明化合物はクロマトグラフィー、再結晶、蒸留等の操作によって精製することもできる。 (Production method 8)
The compound represented by the formula (I-y) can be produced by reacting the compound represented by the formula (1-x) with a base and then reacting with an electrophile.

[Wherein, R ^x represents a C1-C3 hydrocarbon group optionally having one or more atoms or groups selected from the group consisting of a halogen atom, a formyl group, a carboxyl group, or a hydroxyl group and a halogen atom. , X ² , X ³ , Y, A, Z, Q, R ¹ , R ² , R ³ , R ⁴ , m and n represent the same meaning as described above. ]
The reaction is usually carried out in a solvent in the presence of a base under an inert gas atmosphere such as nitrogen.
Examples of the base used in the reaction include metal amides such as sodium amide, lithium diisopropylamide, sodium bis (trimethylsilyl) amide, alkali metal alkoxides such as potassium tert-butoxide, methyl lithium, ethyl lithium, n-butyl lithium, sec -Organic lithium compounds such as butyllithium, tert-butyllithium, 2,4,6-trimethylphenyllithium, methylmagnesium chloride, ethylmagnesium chloride, propylmagnesium chloride, butylmagnesium chloride, pentylmagnesium bromide, hexylmagnesium chloride, etc. Examples thereof include organic magnesium halides and 2,2,6,6-tetramethylpiperidinyl magnesium chloride / lithium chloride complexes.
The electrophile used in the reaction includes N, N-dimethylformamide, formaldehyde, paraformaldehyde, acetaldehyde, propionaldehyde, iodomethane, iodoethane, 1,2-dibromoethane, 1-bromo-2-chloroethane, 1-chloropropane. 1-bromopropane, 1-iodopropane, dimethyl sulfate, diethyl sulfate, methyl tosylate, bromine, iodine, N-bromosuccinimide, N-chlorosuccinimide, N-iodosuccinimide, carbon dioxide, N-fluoro-2,4 Electrophilic fluorides such as N-fluoropyridinium salts such as 1,6-trimethylpyridinium triflate, N-fluoro-N ′-(chloromethyl) triethylenediaminebis (tetrafluoroborate), N-fluorobenzenesulfonimide and the like. Examples thereof include an elemental agent.
Examples of the solvent used in the reaction include hydrocarbons such as hexane, aromatic hydrocarbons such as benzene, toluene and xylene, ethers such as diethyl ether and tetrahydrofuran, and mixtures thereof.
The reaction time is usually in the range of 5 minutes to 72 hours.
The reaction temperature of the reaction is usually in the range of −100 ° C. to 40 ° C. (however, when the boiling point of the solvent used is less than 40 ° C., it is −100 ° C. to the boiling point of the solvent).
The amount of the base used in the reaction can be usually used in an arbitrary ratio from 1 mol to an excess amount with respect to 1 mol of the compound represented by the formula (Iy), preferably 2 to 3 mol. Is a mole.
The amount of the electrophile used in the reaction can be usually used in an arbitrary ratio from 1 mol to an excess amount with respect to 1 mol of the compound represented by the formula (Iy), preferably 1 mol. ~ 3 moles.
After completion of the reaction, the compound of the present invention can be isolated by pouring the reaction mixture into water and subjecting it to usual post-treatment operations such as organic solvent extraction and concentration. The isolated compound of the present invention can also be purified by operations such as chromatography, recrystallization and distillation.

［式中、Ｒ^ｙは１個以上のハロゲン原子を有していてもよいＣ１−Ｃ４アルコキシカルボニル基またはカルバモイル基を表し、Ｘ^２、Ｘ^３、Ｙ、A、Ｚ、Ｑ、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、ｍ及びｎは前記と同じ意味を表す。］
該反応は、通常窒素等の不活性気体雰囲気下、ハロゲン化剤の存在下、必要に応じてＮ，Ｎ−ジメチルホルミアミドの存在下、溶媒中で行なわれる。
該反応に用いられるハロゲン化剤としては、例えば、塩化チオニル、塩化オキサリル及びオキシ塩化リンが挙げられる。
該反応に用いられる求核剤としては、例えば、メチルアルコール、エチルアルコール、プロピルアルコール、ブチルアルコール等のＣ１−Ｃ４アルコール、アンモニア、水酸化アンモニウムが挙げられる。
該反応に用いられる溶媒としては、例えば、酢酸エチル、酢酸ブチル等のエステル類、１，４−ジオキサン、テトラヒドロフラン、エチレングリコールジメチルエーテル、ｔｅｒｔ−ブチルメチルエーテル等のエーテル類、ヘキサン、ヘプタン等の脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン等のハロゲン化炭化水素類及びこれらの混合物が挙げられる。
該反応の反応時間は、通常、５分間〜２４時間の範囲である。
該反応の反応温度は、通常、０〜１００℃（但し、使用する溶媒の沸点が１００℃未満の場合には、０℃〜溶媒の沸点）の範囲である。
該反応に用いられるハロゲン化剤の量は、式（１−ｔ）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合で使用することができ、好ましくは１〜５モルである。
必要に応じて用いられるＮ，Ｎ−ジメチルホルミアミドは、式（１−ｔ）で示される化合物１モルに対して、通常は０．０１モルから過剰量まで任意の割合、好ましくは０．０１〜０．１モルの割合で使用される。
該反応に用いられる求核剤の量は、式（Ｉ−ｔ）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合で使用することができ、好ましくは１モル〜５モルである。
反応終了後は、反応混合物を水に注加した後に有機溶媒抽出、濃縮等の通常の後処理操作を施すことにより、本発明合物を単離することができる。また単離された本発明化合物はクロマトグラフィー、再結晶、蒸留等の操作によって精製することもできる。 (Production method 9)
The compound represented by the formula (Iu) can be produced by reacting the compound represented by the formula (1-t) with a halogenating agent and then reacting with a nucleophile.

[Wherein, R ^y represents a C1-C4 alkoxycarbonyl group or carbamoyl group optionally having one or more halogen atoms, and X ² , X ³ , Y, A, Z, Q, R ¹ , R ² , R ³ , R ⁴ , m and n represent the same meaning as described above. ]
The reaction is usually carried out in a solvent in an inert gas atmosphere such as nitrogen, in the presence of a halogenating agent, and optionally in the presence of N, N-dimethylformamide.
Examples of the halogenating agent used in the reaction include thionyl chloride, oxalyl chloride, and phosphorus oxychloride.
Examples of the nucleophile used in the reaction include C1-C4 alcohols such as methyl alcohol, ethyl alcohol, propyl alcohol, and butyl alcohol, ammonia, and ammonium hydroxide.
Examples of the solvent used in the reaction include esters such as ethyl acetate and butyl acetate, ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and tert-butyl methyl ether, and aliphatic such as hexane and heptane. Examples include hydrocarbons, aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as chlorobenzene, and mixtures thereof.
The reaction time is usually in the range of 5 minutes to 24 hours.
The reaction temperature of the reaction is usually in the range of 0 to 100 ° C (provided that the boiling point of the solvent used is less than 100 ° C, 0 ° C to the boiling point of the solvent).
The amount of the halogenating agent used in the reaction can be usually used in an arbitrary ratio from 1 mol to an excess amount with respect to 1 mol of the compound represented by the formula (1-t). 5 moles.
The N, N-dimethylformamide used as necessary is usually in an arbitrary ratio from 0.01 mol to an excess amount relative to 1 mol of the compound represented by the formula (1-t), preferably 0.8. Used in a proportion of 01 to 0.1 mol.
The amount of the nucleophile used in the reaction can be usually used in an arbitrary ratio from 1 mol to an excess amount with respect to 1 mol of the compound represented by the formula (It), preferably 1 mol. ~ 5 moles.
After completion of the reaction, the compound of the present invention can be isolated by pouring the reaction mixture into water and subjecting it to usual post-treatment operations such as organic solvent extraction and concentration. The isolated compound of the present invention can also be purified by operations such as chromatography, recrystallization and distillation.

［式中、Ｒ^ｚはヒドロキシル基およびハロゲン原子からなる群より選ばれる１個以上の原子または基を有するＣ１−Ｃ３炭化水素基を表し、Ｘ^２、Ｘ^３、Ｙ、A、Ｚ、Ｑ、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、ｍ及びｎは前記と同じ意味を表す。］
該反応は、通常溶媒中で行われる。
該反応に用いられる求核剤としては、例えば、メチルマグネシウムクロリド、エチルマグネシウムクロリド、プロピルマグネシウムクロリド等の有機マグネシウムハロゲン化物、メチルリチウム、エチルリチウム、プロピルリチウム等の有機リチウム化合物、
水素化ホウ素ナトリウム等の金属水素化物、ジメチル亜鉛、ジエチル亜鉛等の有機亜鉛試薬、（ジエチルアミノ）サルファートリフルオリド、ビス（２−メトキシエチル）アミノサルファートリフルオリド等の求核的フッ素化剤が挙げられる。
該反応に用いられる溶媒としては、例えば、１，４−ジオキサン、テトラヒドロフラン、エチレングリコールジメチルエーテル、ｔｅｒｔ−ブチルメチルエーテル等のエーテル類、ヘキサン、ヘプタン、オクタン等の脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン等のハロゲン化炭化水素類、メチルアルコール、エチルアルコール等のアルコール類及びこれらの混合物が挙げられる。
該反応の反応時間は、通常、５分間〜７２時間の範囲である。
該反応の反応温度は、通常、−４０〜６０℃（但し、使用する溶媒の沸点が６０℃未満の場合には、−４０℃〜溶媒の沸点）の範囲である。
該反応に用いられる求核剤の量は、式（１−ｌ）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合で使用することができ、好ましくは１〜５モルである。
反応終了後は、反応混合物を水に注加した後に有機溶媒抽出、濃縮等の通常の後処理操作を施すことにより、本発明化合物を単離することができる。また単離された本発明化合物はクロマトグラフィー、再結晶、蒸留等の操作によって精製することもできる。 (Production method 10)
The compound represented by the formula (Im) can be produced by reacting the compound represented by the formula (1-1) with a nucleophile.

[Wherein R ^z represents a C1-C3 hydrocarbon group having one or more atoms or groups selected from the group consisting of a hydroxyl group and a halogen atom, and X ² , X ³ , Y, A, Z, Q, R ¹ , R ² , R ³ , R ⁴ , m and n represent the same meaning as described above. ]
The reaction is usually performed in a solvent.
Examples of the nucleophile used in the reaction include organic magnesium halides such as methylmagnesium chloride, ethylmagnesium chloride, and propylmagnesium chloride, organolithium compounds such as methyllithium, ethyllithium, and propyllithium,
Metal hydrides such as sodium borohydride, organozinc reagents such as dimethyl zinc and diethyl zinc, and nucleophilic fluorinating agents such as (diethylamino) sulfur trifluoride and bis (2-methoxyethyl) aminosulfur trifluoride .
Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, and tert-butyl methyl ether, aliphatic hydrocarbons such as hexane, heptane, and octane, toluene, xylene, and the like. Aromatic hydrocarbons, halogenated hydrocarbons such as chlorobenzene, alcohols such as methyl alcohol and ethyl alcohol, and mixtures thereof.
The reaction time is usually in the range of 5 minutes to 72 hours.
The reaction temperature of the reaction is usually in the range of −40 to 60 ° C. (provided that the boiling point of the solvent used is less than 60 ° C., −40 ° C. to the boiling point of the solvent).
The amount of the nucleophile used in the reaction can be generally used in an arbitrary ratio from 1 mol to an excess amount with respect to 1 mol of the compound represented by the formula (1-1). 5 moles.
After completion of the reaction, the compound of the present invention can be isolated by pouring the reaction mixture into water and subjecting it to usual post-treatment operations such as organic solvent extraction and concentration. The isolated compound of the present invention can also be purified by operations such as chromatography, recrystallization and distillation.

［式中、Ｒ^ｉは１個以上のハロゲン原子を有していてもよいＣ１−Ｃ２炭化水素基または水素原子を表し、Ｘ^２、Ｘ^３、Ｙ、A、Ｚ、Ｑ、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、ｍ及びｎは前記と同じ意味を表す。］
該反応は、フッ素化剤の存在下、通常溶媒中で行われる。
該反応に用いられるフッ素化剤としては、例えば、４−ｔｅｒｔ−ブチル−２，６−ジメチルフェニルサルファートリフルオリド（Ｆｌｕｏｌｅａｄ）、ビス（２−メトキシエチル）アミノサルファートリフルオリド（Ｄｅｏｘｏ−Ｆｌｕｏｒ）、（ジエチルアミノ）サルファートリフルオリド（ＤＡＳＴ）、（ジエチルアミノ）ジフルオロスルホニウムテトラフルオロボラート（ＸｔａｌＦｌｕｏｒ−Ｅ）、ジフルオロ（モルホリノ）スルホニウムテトラフルオロボラート（ＸｔａｌＦｌｕｏｒ−Ｍ）が挙げられる。
反応に用いられる溶媒としては、例えば、１，４−ジオキサン、テトラヒドロフラン、エチレングリコールジメチルエーテル、ｔｅｒｔ−ブチルメチルエーテル等のエーテル類、ヘキサン、ヘプタン、オクタン等の脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、ジクロロメタン、クロロホルム、クロロベンゼン等のハロゲン化炭化水素類、酢酸エチル、酢酸ブチル等のエステル類、アセトニトリル、ブチロニトリル等のニトリル類、Ｎ，Ｎ−ジメチルホルムアミド等の酸アミド類、ジメチルスルホキシド等のスルホキシド類及びこれらの混合物が挙げられる。
該反応の反応時間は、通常、５分間〜７２時間の範囲である。
該反応の反応温度は、通常、−７８〜１００℃（但し、使用する溶媒の沸点が１００℃未満の場合には、−７８℃〜溶媒の沸点）の範囲である。
該反応に用いられる還元剤の量は、式（Ｉ−ｎ）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合で使用することができ、好ましくは１〜５モルである。
反応終了後は、反応混合物を希塩酸または水に注加した後に有機溶媒抽出、濃縮等の通常の後処理操作を施すことにより、本発明化合物を単離することができる。また単離された本発明化合物はクロマトグラフィー、再結晶、蒸留等の操作によって精製することもできる。 (Production method 11)
The compound represented by the formula (Io) can be produced by reacting the compound represented by the formula (In) with a fluorinating agent.

[Wherein R ⁱ represents a C1-C2 hydrocarbon group or a hydrogen atom optionally having one or more halogen atoms, and X ² , X ³ , Y, A, Z, Q, R ¹ , R ² , R ³ , R ⁴ , m and n represent the same meaning as described above. ]
The reaction is usually performed in a solvent in the presence of a fluorinating agent.
Examples of the fluorinating agent used in the reaction include 4-tert-butyl-2,6-dimethylphenylsulfur trifluoride (Fluolead), bis (2-methoxyethyl) aminosulfur trifluoride (Deoxo-Fluor), ( Examples include diethylamino) sulfur trifluoride (DAST), (diethylamino) difluorosulfonium tetrafluoroborate (XtalFluor-E), and difluoro (morpholino) sulfonium tetrafluoroborate (XtalFluor-M).
Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, and tert-butyl methyl ether, aliphatic hydrocarbons such as hexane, heptane, and octane, toluene, xylene, and the like. Aromatic hydrocarbons, halogenated hydrocarbons such as dichloromethane, chloroform and chlorobenzene, esters such as ethyl acetate and butyl acetate, nitriles such as acetonitrile and butyronitrile, acid amides such as N, N-dimethylformamide, dimethyl Examples thereof include sulfoxides such as sulfoxide and mixtures thereof.
The reaction time is usually in the range of 5 minutes to 72 hours.
The reaction temperature of the reaction is usually in the range of −78 to 100 ° C. (however, when the boiling point of the solvent used is less than 100 ° C., it is −78 ° C. to the boiling point of the solvent).
The amount of the reducing agent used in the reaction can be generally used in an arbitrary ratio from 1 mol to an excess amount with respect to 1 mol of the compound represented by the formula (In), preferably 1 to 5 Is a mole.
After completion of the reaction, the compound of the present invention can be isolated by pouring the reaction mixture into dilute hydrochloric acid or water and subjecting it to usual post-treatment operations such as organic solvent extraction and concentration. The isolated compound of the present invention can also be purified by operations such as chromatography, recrystallization and distillation.

［式中、Ｒ^ｉは１個以上のハロゲン原子を有していてもよいＣ１−Ｃ２炭化水素基または水素原子を表し、Ｘ^２、Ｘ^３、Ｙ、A、Ｚ、Ｑ、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、ｍ及びｎは前記と同じ意味を表す。］
（工程１）
該反応は、通常窒素等の不活性気体雰囲気下、塩基及び二硫化炭素の存在下、溶媒中で行われ、さらにメチル化剤による後処理が行われる。
該反応に用いられる塩基としては、ｎ−ブチルリチウム、ｓｅｃ−ブチルリチウム、ｔｅｒｔ−ブチルリチウム、２，４，６−トリメチルフェニルリチウム等の有機リチウム化合物、リチウムジイソプロピルアミド、リチウムヘキサメチルジシラジド、水素化ナトリウム等が挙げられる。
該反応に用いられるメチル化剤としては、ヨウ化メチル、ジメチル硫酸、メチルトシラート等が挙げられる。
該反応に用いられる溶媒としては、例えば、ベンゼン、トルエン等の芳香族炭化水素類、ヘキサン等の炭化水素類、ジエチルエーテル、テトラヒドロフラン等のエーテル類等が挙げられる。
該反応の反応時間は、通常、１分間〜７２時間の範囲である。
該反応の反応温度は、通常、−７８℃〜１００℃（但し、使用する溶媒の沸点が１００℃未満の場合には、−７８℃〜溶媒の沸点）の範囲である。
該反応に用いられる塩基の量は、式（Ｉ−ｎ）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合で使用することができ、好ましくは１モル〜３モルである。
該反応に用いられる二硫化炭素の量は、式（Ｉ−ｎ）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合で使用することができ、好ましくは１モル〜５モルである。
該反応に用いられるメチル化剤の量は、式（Ｉ−ｎ）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合、好ましくは１〜５モルの割合で使用される。
反応終了後は、反応混合物を希塩酸または水に注加した後に有機溶媒抽出、濃縮等の通常の後処理操作を施すことにより、式（Ｉ−ｐ）で示される化合物を単離することができる。また単離された式（Ｉ−ｐ）で示される化合物はクロマトグラフィー、再結晶、蒸留等の操作によって精製することもできる。
（工程２）
該反応は、通常窒素等の不活性気体雰囲気下、トリブチルスズヒドリド及びラジカル開始剤の存在下、溶媒中で行われる。
該反応に用いられるラジカル開始剤としては、アゾビスイソブチロニトリル（ＡＩＢＮ）、１，１’−アゾビス（シクロヘキサンカルボニトリル）（ＡＢＣＮ）等のアゾ化合物、ジ−ｔｅｒｔ−ブチルペルオキシド、過酸化ベンゾイル（ＢＰＯ）等の有機過酸化物、トリエチルボラン及びジエチル亜鉛等が挙げられる。
該反応に用いられる溶媒としては、例えば、ベンゼン、トルエン等の芳香族炭化水素類、クロロホルム、クロロベンゼン等のハロゲン炭化水素類、ヘキサン等の炭化水素類、ジエチルエーテル、テトラヒドロフラン等のエーテル類等が挙げられる。
該反応の反応時間は、通常、１分間〜７２時間の範囲である。
該反応の反応温度は、通常、０℃〜１００℃の範囲である。
該反応に用いられるトリブチルスズヒドリドの量は、式（Ｉ−ｐ）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合で使用することができ、好ましくは１モル〜３モルである。
該反応に用いられるラジカル開始剤の量は、式（Ｉ−ｐ）で示される化合物１モルに対して、通常は０．０１モルから過剰量まで任意の割合で使用することができ、好ましくは０．１モル〜１モルである。
反応終了後は、濃縮等の通常の後処理操作を施すことにより、式（Ｉ−ｐ）で示される化合物を単離することができる。また単離された式（Ｉ−ｐ）で示される化合物はクロマトグラフィー、再結晶、蒸留等の操作によって精製することもできる。 (Production method 12)
The compounds represented by the formula (Ip) and the formula (Iq) can be produced, for example, by the route shown in the following scheme according to the method described in Journal of Organic Chemistry, 63, 4011-4017 (1998). .

[Wherein R ⁱ represents a C1-C2 hydrocarbon group or a hydrogen atom optionally having one or more halogen atoms, and X ² , X ³ , Y, A, Z, Q, R ¹ , R ² , R ³ , R ⁴ , m and n represent the same meaning as described above. ]
(Process 1)
The reaction is usually performed in a solvent in the presence of a base and carbon disulfide in an inert gas atmosphere such as nitrogen, and further post-treatment with a methylating agent is performed.
Examples of the base used in the reaction include n-butyllithium, sec-butyllithium, tert-butyllithium, organolithium compounds such as 2,4,6-trimethylphenyllithium, lithium diisopropylamide, lithium hexamethyldisilazide, Sodium hydride etc. are mentioned.
Examples of the methylating agent used in the reaction include methyl iodide, dimethyl sulfate, methyl tosylate and the like.
Examples of the solvent used in the reaction include aromatic hydrocarbons such as benzene and toluene, hydrocarbons such as hexane, ethers such as diethyl ether and tetrahydrofuran, and the like.
The reaction time of the reaction is usually in the range of 1 minute to 72 hours.
The reaction temperature of the reaction is usually in the range of −78 ° C. to 100 ° C. (however, when the boiling point of the solvent used is less than 100 ° C., it is −78 ° C. to the boiling point of the solvent).
The amount of the base used in the reaction can be usually used in an arbitrary ratio from 1 mol to an excess amount with respect to 1 mol of the compound represented by the formula (In), preferably 1 mol to 3 Is a mole.
The amount of carbon disulfide used in the reaction is usually 1 mol to an excess amount, and preferably 1 mol, per 1 mol of the compound represented by the formula (In). ~ 5 moles.
The amount of the methylating agent used in the reaction is usually 1 mol to an excess amount, preferably 1 to 5 mol, with respect to 1 mol of the compound represented by the formula (In). Is done.
After completion of the reaction, the compound represented by the formula (Ip) can be isolated by pouring the reaction mixture into dilute hydrochloric acid or water and subjecting it to usual post-treatment operations such as organic solvent extraction and concentration. . The isolated compound represented by the formula (Ip) can also be purified by operations such as chromatography, recrystallization and distillation.
(Process 2)
The reaction is usually carried out in a solvent in the presence of tributyltin hydride and a radical initiator under an inert gas atmosphere such as nitrogen.
Examples of the radical initiator used in the reaction include azo compounds such as azobisisobutyronitrile (AIBN) and 1,1′-azobis (cyclohexanecarbonitrile) (ABCN), di-tert-butyl peroxide, and benzoyl peroxide. Examples thereof include organic peroxides such as (BPO), triethylborane, and diethylzinc.
Examples of the solvent used in the reaction include aromatic hydrocarbons such as benzene and toluene, halogen hydrocarbons such as chloroform and chlorobenzene, hydrocarbons such as hexane, ethers such as diethyl ether and tetrahydrofuran, and the like. It is done.
The reaction time of the reaction is usually in the range of 1 minute to 72 hours.
The reaction temperature of the reaction is usually in the range of 0 ° C to 100 ° C.
The amount of tributyltin hydride used in the reaction can be generally used in an arbitrary ratio from 1 mol to an excess amount with respect to 1 mol of the compound represented by the formula (Ip), preferably from 1 mol to 3 moles.
The amount of the radical initiator used in the reaction can be generally used in an arbitrary ratio from 0.01 mol to an excess amount with respect to 1 mol of the compound represented by the formula (Ip), preferably 0.1 mol to 1 mol.
After completion of the reaction, the compound represented by the formula (Ip) can be isolated by subjecting to usual post-treatment operations such as concentration. The isolated compound represented by the formula (Ip) can also be purified by operations such as chromatography, recrystallization and distillation.

［式中、Ｊは群Ｉより選ばれる１個の基、Ｇ^ｂは脱離基（例えば塩素原子、臭素原子およびヨウ素原子等）表し、Ｘ^１、Ｘ^２、Ｘ^３、Ｙ、A、Ｚ、Ｒ^１、Ｒ^２、Ｒ^３、Ｒ^４、ｍ及びｎは前記と同じ意味を表す。
群Ｉ：群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいインダニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよい１，２，３，４−テトラヒドロナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフェニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいナフチル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいピリジル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいキノリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいフリル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいチエニル基、群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾフラニル基、及び群Ｂより選ばれる１個以上の原子若しくは基を有していてもよいベンゾチエニル基からなる群。］
該反応は、通常窒素等の不活性気体雰囲気下、通常遷移金属触媒、無機銅塩類、アルキン及び塩基の存在下、溶媒中で行なわれる。
該反応に用いられる遷移金属触媒としては、例えば酢酸パラジウム、パラジウムジクロリド、ジクロロビス（トリフェニルホスフィン）パラジウム、テトラキス（トリフェニルホスフィン）パラジウム等のパラジウム触媒等が挙げられる。
該反応に用いられる無機銅塩類としては、臭化銅（Ｉ）、沃化銅（Ｉ）等が挙げられる。
該反応に用いられる塩基としては、例えば炭酸ナトリウム、炭酸カリウム等の炭酸塩類、トリエチルアミン、ジイソプロピルエチルアミン、１，８−ジアザビシクロ［５．４．０］ウンデカ−７−エン、１，５−ジアザビシクロ［４．３．０］ノン−５−エン等の第３級アミン類及びピリジン、４−ジメチルアミノピリジン等の含窒素芳香族化合物が挙げられる。
該反応に用いられる溶媒としては、例えば、ベンゼン、トルエン等の芳香族炭化水素類、ヘキサン等の炭化水素類、ジエチルエーテル、テトラヒドロフラン等のエーテル類、ジクロロメタン、１，２−ジクロロエタン、クロロベンゼン等のハロゲン化炭化水素類、Ｎ，Ｎ−ジメチルホルムアミド等の酸アミド類、及び酢酸エチル、酢酸ブチル等のエステル類等が挙げられる。
該反応の反応時間は、通常、５分間〜７２時間の範囲である。
該反応の反応温度は、通常、−２０℃〜１００℃（但し、使用する溶媒の沸点が１００℃未満の場合には、−２０℃〜溶媒の沸点）の範囲である。
該反応に用いられる遷移金属触媒の量は、式（Ｉ−ｅ）で示される化合物１モルに対して通常０．００１〜０．５モルの割合である。
該反応に用いられる無機銅塩類の量は、式（Ｉ−ｅ）で示される化合物１モルに対して通常０．００１〜０．５モルの割合である。
該反応に用いられるアルキンの量は、式（Ｉ−ｅ）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合で使用することができ、好ましくは１モル〜５モルである。
該反応に用いられる塩基の量は、式（Ｉ−ｅ）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合で使用することができ、好ましくは１モル〜３モルである。
反応終了後は、反応混合物を水に注加した後、有機溶媒抽出、濃縮等の通常の後処理操作を施すことにより、式（Ｉ−ｆ）で示される化合物を得ることができる。また得られた式（Ｉ−ｆ）で示される化合物はクロマトグラフィー、再結晶、蒸留等の操作によって精製することもできる。 (Production method 13)
The compound represented by the formula (If) can be produced by subjecting the compound represented by the formula (Ie) and an aryl halide to a Sonogashira reaction.

[Wherein J represents one group selected from group I, G ^b represents a leaving group (for example, a chlorine atom, a bromine atom, an iodine atom, etc.), and X ¹ , X ² , X ³ , Y, A, Z , R ¹ , R ² , R ³ , R ⁴ , m and n represent the same meaning as described above.
Group I: an indanyl group which may have one or more atoms or groups selected from Group B, and one, two, three, which may have one or more atoms or groups selected from Group B A 4-tetrahydronaphthyl group, a phenyl group optionally having one or more atoms or groups selected from group B, a naphthyl group optionally having one or more atoms or groups selected from group B, A pyridyl group optionally having one or more atoms or groups selected from group B, a quinolyl group optionally having one or more atoms or groups selected from group B, 1 selected from group B Furyl group optionally having one or more atoms or groups, thienyl group optionally having one or more atoms or groups selected from group B, one or more atoms or groups selected from group B Benzofuranyl which may have And the group consisting of one or more atoms or optionally benzothienyl group which may have a group selected from the group B. ]
The reaction is usually carried out in a solvent in an inert gas atmosphere such as nitrogen, usually in the presence of a transition metal catalyst, inorganic copper salts, alkyne and base.
Examples of the transition metal catalyst used in the reaction include palladium catalysts such as palladium acetate, palladium dichloride, dichlorobis (triphenylphosphine) palladium, and tetrakis (triphenylphosphine) palladium.
Examples of inorganic copper salts used in the reaction include copper (I) bromide and copper (I) iodide.
Examples of the base used in the reaction include carbonates such as sodium carbonate and potassium carbonate, triethylamine, diisopropylethylamine, 1,8-diazabicyclo [5.4.0] undec-7-ene, 1,5-diazabicyclo [4]. .3.0] Tertiary amines such as non-5-ene and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine.
Examples of the solvent used in the reaction include aromatic hydrocarbons such as benzene and toluene, hydrocarbons such as hexane, ethers such as diethyl ether and tetrahydrofuran, halogen such as dichloromethane, 1,2-dichloroethane, and chlorobenzene. Hydrocarbons, acid amides such as N, N-dimethylformamide, and esters such as ethyl acetate and butyl acetate.
The reaction time is usually in the range of 5 minutes to 72 hours.
The reaction temperature of the reaction is usually in the range of −20 ° C. to 100 ° C. (however, when the boiling point of the solvent used is less than 100 ° C., it is −20 ° C. to the boiling point of the solvent).
The amount of the transition metal catalyst used in the reaction is usually 0.001 to 0.5 mol with respect to 1 mol of the compound represented by the formula (Ie).
The amount of the inorganic copper salt used in the reaction is usually 0.001 to 0.5 mol with respect to 1 mol of the compound represented by the formula (Ie).
The amount of the alkyne used in the reaction can be usually used in an arbitrary ratio from 1 mol to an excess amount with respect to 1 mol of the compound represented by the formula (Ie), preferably 1 mol to 5 mol. Is a mole.
The amount of the base used in the reaction can be usually used in an arbitrary ratio from 1 mol to an excess amount with respect to 1 mol of the compound represented by the formula (Ie), and preferably 1 mol to 3 mol. Is a mole.
After completion of the reaction, the compound represented by the formula (If) can be obtained by pouring the reaction mixture into water and subjecting it to usual post-treatment operations such as organic solvent extraction and concentration. The obtained compound represented by the formula (If) can also be purified by operations such as chromatography, recrystallization, distillation and the like.

  Next, the manufacturing method of the manufacturing intermediate of this invention compound is demonstrated.

［式中、Ｒ^ａはメチル基又はエチル基を表し、Ｘ^１、Ｘ^２、Ｘ^３、Ｙ、Ｚ、Ｑ、Ｒ^３、Ｒ^４、及びｍは前記と同じ意味を表す。］
該反応は、塩基の存在下、水及び有機溶媒の存在下で行われる。
該反応に用いられる塩基としては例えば、水酸化リチウム、水酸化ナトリウム、水酸化カリウム等のアルカリ金属水酸化物が挙げられる。
該反応に用いられる溶媒としては例えば、１，４−ジオキサン、テトラヒドロフラン、エチレングリコールジメチルエーテル、ｔｅｒｔ−ブチルメチルエーテル等のエーテル類、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン等ののハロゲン化炭化水素類、アセトニトリル、ブチロニトリル等のニトリル類、メタノール、エタノール、プロパノール等のアルコール類及びこれらの混合物が挙げられる。
該反応の反応時間は、通常、５分間〜７２時間の範囲である。
該反応の反応温度は、通常、０℃〜１００℃（但し、使用する溶媒の沸点が１００℃未満の場合には、０℃〜溶媒の沸点）の範囲である。
該反応に用いられる塩基の量は、式（１３）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合で使用することができ、好ましくは１モル〜５モルである。
反応終了後は、反応混合物を水に注加し、有機溶媒洗浄後、水層を酸性水（塩酸等）により中和し、有機溶媒抽出、濃縮等の通常の後処理操作を施すことにより、式（１）で示される化合物を得ることができる。また得られた式（１）で示される化合物は、通常精製することなく次の工程の反応に用いられるが、必要によりクロマトグラフィ−、再結晶等の操作によって精製することもできる。 (Reference production method 1)
The compound represented by the formula (1) can be produced by subjecting the compound represented by the formula (13) to a hydrolysis reaction in the presence of a base.

[Wherein, R ^a represents a methyl group or an ethyl group, and X ¹ , X ² , X ³ , Y, Z, Q, R ³ , R ⁴ , and m represent the same meaning as described above. ]
The reaction is performed in the presence of a base and water and an organic solvent.
Examples of the base used in the reaction include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide.
Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and tert-butyl methyl ether, aromatic hydrocarbons such as toluene and xylene, and halogenated carbonization such as chlorobenzene. Examples thereof include hydrogen, nitriles such as acetonitrile and butyronitrile, alcohols such as methanol, ethanol and propanol, and mixtures thereof.
The reaction time is usually in the range of 5 minutes to 72 hours.
The reaction temperature of the reaction is usually in the range of 0 ° C to 100 ° C (provided that the boiling point of the solvent used is less than 100 ° C, 0 ° C to the boiling point of the solvent).
The amount of the base used in the reaction can be usually used in an arbitrary ratio from 1 mol to an excess amount with respect to 1 mol of the compound represented by the formula (13), preferably 1 mol to 5 mol. is there.
After completion of the reaction, the reaction mixture is poured into water, washed with an organic solvent, the aqueous layer is neutralized with acidic water (hydrochloric acid, etc.), and subjected to usual post-treatment operations such as organic solvent extraction and concentration, A compound represented by the formula (1) can be obtained. The obtained compound represented by the formula (1) is usually used for the reaction in the next step without purification, but can be purified by operations such as chromatography and recrystallization as necessary.

［式中、Ｇは塩素原子、臭素原子を表し、Ｙ^２は−ＣＲ^８Ｒ^９−、酸素原子、または−Ｓ（Ｏ）_２−を表し、Ｘ^１、Ｘ^２、Ｘ^３、Ｑ、Ｚ、Ｒ^３、Ｒ^４、及びｍは前記と同じ意味を表す。］
該反応は、必要に応じて溶媒中で行われる。
該反応に用いられるハロゲン化剤としては、例えば、塩化チオニル、塩化オキサリル及びオキシ塩化リンが挙げられる。
該反応に用いられる溶媒としては、例えば、１，４−ジオキサン、テトラヒドロフラン、エチレングリコールジメチルエーテル、ｔｅｒｔ−ブチルメチルエーテル等のエーテル類、ヘキサン、ヘプタン等の脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン等のハロゲン化炭化水素類及びこれらの混合物が挙げられる。
該反応の反応時間は、通常、５分間〜２４時間の範囲である。
該反応の反応温度は、通常、０〜１００℃の範囲である。
該反応に用いられるハロゲン化剤の量は、式（１）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合で使用することができ、好ましくは１〜５モルである。
反応終了後は、反応混合物をそのまま濃縮する等の後処理操作を行うことにより、式（３）で示される化合物を単離することができる。単離された式（３）で示される化合物は、通常精製することなく次の工程の反応に用いられるが、必要により蒸留等により精製することができる。 (Reference production method 2)
The compound represented by the formula (3) can be produced, for example, by reacting the compound represented by the formula (1) with a halogenating agent.

[In the formula, G represents a chlorine atom or a bromine atom, Y ² represents —CR ⁸ R ⁹ —, an oxygen atom, or —S (O) ₂ —, and X ¹ , X ² , X ³ , Q, Z , R ³ , R ⁴ , and m represent the same meaning as described above. ]
The reaction is performed in a solvent as necessary.
Examples of the halogenating agent used in the reaction include thionyl chloride, oxalyl chloride, and phosphorus oxychloride.
Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and tert-butyl methyl ether, aliphatic hydrocarbons such as hexane and heptane, and aromatics such as toluene and xylene. Group hydrocarbons, halogenated hydrocarbons such as chlorobenzene, and mixtures thereof.
The reaction time is usually in the range of 5 minutes to 24 hours.
The reaction temperature of the reaction is usually in the range of 0 to 100 ° C.
The amount of the halogenating agent used in the reaction is usually 1 mol to an excess amount, and preferably 1 to 5 mol with respect to 1 mol of the compound represented by the formula (1). It is.
After completion of the reaction, the compound represented by the formula (3) can be isolated by performing post-treatment operations such as concentrating the reaction mixture as it is. The isolated compound represented by the formula (3) is usually used for the next step without purification, but can be purified by distillation or the like as necessary.

〔式中、Ｒ^ａはメチル基又はエチル基を表し、Ｙ、Ｑ、Ｒ^３、Ｒ^４、Ｒ^５及びｍは前記と同じ意味を表す。〕 (Reference production method 3)
Among the compounds (13), the compound (13-a) is prepared according to, for example, Journal of Chemical Society, Perkin Trans. , 14, 1716, (2001) according to the method described in the following scheme.

[Wherein, R ^a represents a methyl group or an ethyl group, and Y, Q, R ³ , R ⁴ , R ⁵ and m represent the same meaning as described above. ]

〔式中、Ｒ^ａはメチル基又はエチル基を表し、Ｙ、Ｑ、Ｒ^３、Ｒ^４、及びｍは前記と同じ意味を表す。〕 (Reference production method 4)
Among the compounds (13), the compound (13-b) is prepared according to, for example, Journal of Chemical Society, Perkin Trans. , 14, 1716, (2001) according to the method described in the following scheme.

[Wherein, R ^a represents a methyl group or an ethyl group, and Y, Q, R ³ , R ⁴ , and m represent the same meaning as described above. ]

〔式中、Ｒ^ａはメチル基又はエチル基を表し、Ｙ、Ｑ、Ｒ^３、Ｒ^４、Ｒ^５及びｍは前記と同じ意味を表す。〕 (Reference production method 5)
Among compounds (13), compound (13-a) can be produced, for example, by the route shown in the following scheme according to the method described in European Journal of Organic Chemistry, 4852-4860, (2006).

[Wherein, R ^a represents a methyl group or an ethyl group, and Y, Q, R ³ , R ⁴ , R ⁵ and m represent the same meaning as described above. ]

〔式中、Ｒ^ａはメチル基又はエチル基を表し、Ｙ、Ｑ、Ｒ^３、Ｒ^４、Ｒ^５及びｍは前記と同じ意味を表す。〕 (Reference production method 6)
Among compounds (13), compound (13-c) can be produced, for example, by the route shown in the following scheme according to the method described in European Journal of Organic Chemistry, 4852-4860, (2006).

[Wherein, R ^a represents a methyl group or an ethyl group, and Y, Q, R ³ , R ⁴ , R ⁵ and m represent the same meaning as described above. ]

〔式中、Ｒ^ａはメチル基又はエチル基を表し、Ｙ、Ｑ、Ｒ^３、Ｒ^４、Ｒ^５及びｍは前記と同じ意味を表す。〕 (Reference production method 7)
Among compounds (13), compound (13-e) is produced by the route shown in the following scheme according to the method described in Phosphorus and Sulfur and the Related Elements, 15 (2), 137-42 (1983), for example. can do.

[Wherein, R ^a represents a methyl group or an ethyl group, and Y, Q, R ³ , R ⁴ , R ⁵ and m represent the same meaning as described above. ]

〔式中、Ｒ^ａはメチル基又はエチル基を表し、Ｙ、Ｑ、Ｒ^３、Ｒ^４、及びｍは前記と同じ意味を表す。〕
（参考製造法９）
化合物（１３）のうち、化合物（１３−ｆ）は、例えば、Ｐｈｏｓｐｈｏｒｕｓ ａｎｄ Ｓｕｌｆｕｒ ａｎｄ ｔｈｅ Ｒｅｌａｔｅｄ Ｅｌｅｍｅｎｔｓ，１５（２），１３７−４２（１９８３）記載の方法に準じて下記スキームで示されるルートにより製造することができる。

〔式中、Ｒ^ａはメチル基又はエチル基を表し、Ｙ、Ｑ、Ｒ^３、Ｒ^４、Ｒ^５及びｍは前記と同じ意味を表す。〕
（参考製造法１０）
化合物（１３）のうち、化合物（１３−ｈ）は、例えば下記スキームで示されるルートに従って、例えばＴｅｔｒａｈｅｄｒｏｎ，６９，８５６４−８５７１（２０１３）に記載の方法に準じて製造することができる。

〔式中、Ｇ^３は、メトキシ基、エトキシ基等を表し、Ｒ^ａはメチル基又はエチル基を表し、Ｇ^２、Ｙ、Ｑ、Ｒ^３、Ｒ^４、Ｒ^５、及びｍは前記と同じ意味を表す。〕 (Reference production method 8)
Of compound (13), compound (13-f) can be produced, for example, by the route shown in the following scheme according to the method described in Journal of Organic Chemistry, 39, 962-964, (1974).

[Wherein, R ^a represents a methyl group or an ethyl group, and Y, Q, R ³ , R ⁴ , and m represent the same meaning as described above. ]
(Reference production method 9)
Among compounds (13), compound (13-f) is produced by the route shown in the following scheme according to the method described in Phosphorus and Sulfur and the Related Elements, 15 (2), 137-42 (1983), for example. can do.

[Wherein, R ^a represents a methyl group or an ethyl group, and Y, Q, R ³ , R ⁴ , R ⁵ and m represent the same meaning as described above. ]
(Reference production method 10)
Among compounds (13), compound (13-h) can be produced, for example, according to the method described in Tetrahedron, 69, 8564-8571 (2013), for example, according to the route shown in the following scheme.

Wherein, ^{G 3} is methoxy group, an ethoxy group, etc., ^{R a} represents a methyl group or an ethyl ^{group, G 2, Y, Q,} R 3, R 4, R 5, and m are as defined above Represents meaning. ]

〔式中、Ｅは保護基（例えばテトラヒドロピラン−２−イル基、ｔ−ブチルジメチルシリル基等）を表し、X^ａは酸素原子、窒素原子またはＮＲ^６を表し、Ｒ^ａ、Ｘ^２、Ｙ、Ｑ、Ｒ^３、Ｒ^４、Ｒ^５、及びｍは前記と同じ意味を表す。〕 (Reference production method 11)
Among the compounds (1), the compound (1-a) is produced, for example, according to the route shown in the following scheme, for example, after preparing the compound (27) according to the method described in WO2005068432, Advanced organic chemistry, fourth edition, part B , 747-809 (2001, Kluwer Academic / Plenum Publishers).

[In the formula, E represents a protecting group (for example, tetrahydropyran-2-yl group, t-butyldimethylsilyl group, etc.), X ^a represents an oxygen atom, a nitrogen atom or NR ⁶ , and R ^a , X ² , Y , Q, R ³ , R ⁴ , R ⁵ , and m represent the same meaning as described above. ]

〔式中、X^ｂは酸素原子、またはＮＲ^６を表し、Ｒ^ａ、Ｙ、Ｑ、Ｒ^３、Ｒ^４、Ｒ^５、Ｒ^６、及びｍは前記と同じ意味を表す。〕 (Reference production method 12)
Of compound (13), compound (13-i) can be produced, for example, according to the route shown in the following scheme, for example, according to the method described in Bioorganic & Medicinal Chemistry Letters, 23, 273-280 (2013). it can.

[Wherein, X ^b represents an oxygen atom or NR ⁶ , and R ^a , Y, Q, R ³ , R ⁴ , R ⁵ , R ⁶ , and m represent the same meaning as described above. ]

〔式中、Ｇ^１、Ｒ^ａ、Ｙ、Ｑ、Ｒ^３、Ｒ^４、Ｒ^５、Ｒ^６、及びｍは前記と同じ意味を表す。〕 (Reference production method 13)
Of compound (13), compound (13-j) can be produced, for example, according to the route described in the following scheme, for example, according to the method described in Heterocycles, 23, 1759, (1985).

[Wherein, G ¹ , R ^a , Y, Q, R ³ , R ⁴ , R ⁵ , R ⁶ , and m represent the same meaning as described above. ]

〔式中、Ｇ^１、Ｒ^ａ、X^ａ、Ｙ、Ｑ、Ｒ^３、Ｒ^４、Ｒ^５、Ｒ^６、及びｍは前記と同じ意味を表す。〕 (Reference production method 14)
Of compound (13), compound (13-k) can be produced, for example, according to the method described in JP-A No. 2001-58979, for example, according to the route shown in the following scheme.

[Wherein, G ¹ , R ^a , X ^a , Y, Q, R ³ , R ⁴ , R ⁵ , R ⁶ , and m represent the same meaning as described above. ]

［式中、Ｘ^１、Ｘ^２、Ｘ^３、Ｙ^１、Ｚ、Ｇ^２、Ｑ、Ｒ^ａ、Ｒ^３、Ｒ^ａ及びｍは前記と同じ意味を表す。］
該反応は、塩基の存在下、通常溶媒中で行われる。
該反応に用いられる塩基としては、例えば、ナトリウム、カリウム等のアルカリ金属類、ｎ−ブチルリチウム等のアルキルリチウム類、水素化ナトリウム、水素化カリウム等の金属水素化合物、炭酸ナトリウム、炭酸カリウム等の炭酸塩類、カリウム−ｔ−ブトキシド等のアルカリ金属アルコキシド、トリエチルアミン、ジイソプロピルエチルアミン、１，８−ジアザビシクロ［５．４．０］ウンデカ−７−エン、１，５−ジアザビシクロ［４．３．０］ノン−５−エン等の第３級アミン類及びピリジン、４−ジメチルアミノピリジン等の含窒素芳香族化合物が挙げられる。
該反応に用いられる溶媒としては、例えば、１，４−ジオキサン、テトラヒドロフラン、エチレングリコールジメチルエーテル、ｔｅｒｔ−ブチルメチルエーテル等のエーテル類、ヘキサン、ヘプタン、オクタン等の脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン等のハロゲン化炭化水素類、酢酸エチル、酢酸ブチル等のエステル類、アセトニトリル、ブチロニトリル等のニトリル類、Ｎ，Ｎ−ジメチルホルムアミド等の酸アミド類、ジメチルスルホキシド等のスルホキシド類及びこれらの混合物が挙げられる。
該反応の反応時間は、通常、５分間〜７２時間の範囲である。
該反応の反応温度は、通常、−２０〜１００℃の範囲である。
該反応において、式（３５）で示される化合物と、式（５）で示される化合物の使用モル比は任意に設定できるが、好ましくは、等モル又はそれに近い比、具体的には式（３５）で示される化合物１モルに対して、式（５）で示される化合物が０．５〜３モルである。
該反応に用いられる塩基の量は、式（３５）で示される化合物１モルに対して、通常は１モルから過剰量まで任意の割合で使用することができ、好ましくは１〜３モルである。
反応終了後は、反応混合物を水に注加した後に有機溶媒抽出、濃縮等の通常の後処理操作を施すことにより、本発明化合物を単離することができる。また単離された本発明化合物はクロマトグラフィー、再結晶、蒸留等の操作によって精製することもできる。 (Reference production method 15)
The compound represented by the formula (13) can be produced by reacting the compound represented by the formula (35) with the compound represented by the formula (5) in the presence of a base.

[Wherein, X ¹ , X ² , X ³ , Y ¹ , Z, G ² , Q, R ^a , R ³ , R ^a and m represent the same meaning as described above. ]
The reaction is usually performed in a solvent in the presence of a base.
Examples of the base used in the reaction include alkali metals such as sodium and potassium, alkyllithiums such as n-butyllithium, metal hydride compounds such as sodium hydride and potassium hydride, sodium carbonate, potassium carbonate and the like. Carbonates, alkali metal alkoxides such as potassium t-butoxide, triethylamine, diisopropylethylamine, 1,8-diazabicyclo [5.4.0] undec-7-ene, 1,5-diazabicyclo [4.3.0] non Examples include tertiary amines such as -5-ene and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine.
Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, and tert-butyl methyl ether, aliphatic hydrocarbons such as hexane, heptane, and octane, toluene, xylene, and the like. Aromatic hydrocarbons, halogenated hydrocarbons such as chlorobenzene, esters such as ethyl acetate and butyl acetate, nitriles such as acetonitrile and butyronitrile, acid amides such as N, N-dimethylformamide, dimethyl sulfoxide and the like Examples include sulfoxides and mixtures thereof.
The reaction time is usually in the range of 5 minutes to 72 hours.
The reaction temperature of the reaction is usually in the range of -20 to 100 ° C.
In the reaction, the molar ratio of the compound represented by the formula (35) and the compound represented by the formula (5) can be arbitrarily set, but is preferably equimolar or a ratio close thereto, specifically, the formula (35 The compound represented by the formula (5) is 0.5 to 3 mol per 1 mol of the compound represented by
The amount of the base used in the reaction can be usually used in an arbitrary ratio from 1 mol to an excess amount with respect to 1 mol of the compound represented by the formula (35), preferably 1 to 3 mol. .
After completion of the reaction, the compound of the present invention can be isolated by pouring the reaction mixture into water and subjecting it to usual post-treatment operations such as organic solvent extraction and concentration. The isolated compound of the present invention can also be purified by operations such as chromatography, recrystallization and distillation.

［式中、Ｇ^ａは脱離基（例えば、メタンスルホニルオキシ基、トリフルオロメタンスルホニルオキシ基または４−トルエンスルホニルオキシ基等）を表し、Ｘ^１、Ｘ^２、Ｘ^３、Ｚ、Ｒ^ａ、Ｒ^３、Ｒ^４及びｍは前記と同じ意味を表す。］ (Reference production method 16)
Among compounds (35), compound (35-a) can be produced, for example, by the route shown in the following scheme according to the method described in Journal of Chemical Society, Parkin Trans1, 206-215 (2001).

[Wherein, G ^a represents a leaving group (eg, methanesulfonyloxy group, trifluoromethanesulfonyloxy group, 4-toluenesulfonyloxy group, etc.), and X ¹ , X ² , X ³ , Z, R ^a , R ³ , R ⁴ and m represent the same meaning as described above. ]

［式中、Ｘ^１、Ｘ^２、Ｘ^３、Ｚ、Ｇ^ｂ、Ｒ^ａ、Ｒ^３、Ｒ^４及びｍは前記と同じ意味を表す。］ (Reference production method 17)
Among compounds (35), compound (35-b) can be produced, for example, by the route shown in the following scheme according to the method described in Chemistry-A European Journal, 993-1005 (2001).

[Wherein, X ¹ , X ² , X ³ , Z, G ^b , R ^a , R ³ , R ⁴ and m represent the same meaning as described above. ]

［式中、Ｘ^１、Ｘ^２、Ｘ^３、Ｚ、Ｊ、Ｒ^ａ、Ｒ^３、Ｒ^４及びｍは前記と同じ意味を表す。］ (Reference production method 18)
Compound (36) can be produced by, for example, a Mitsunobu reaction represented by the following scheme according to the method described in Strategic applications of named reactions in organic synthesis, 294-295 (2005, Elsevier Academic Press).

[Wherein, X ¹ , X ² , X ³ , Z, J, R ^a , R ³ , R ⁴ and m represent the same meaning as described above. ]

［式中、Ｘ^１、Ｘ^２、Ｘ^３、Ｙ^１、Ｚ、Ｇ^２、Ｑ、Ｒ^ａ、Ｒ^３、Ｒ^ａ及びｍは前記と同じ意味を表す。］ (Reference production method 19)
The compound represented by the formula (1) is obtained by converting the compound represented by the formula (35) into (13) according to the method described in the reference production method 15, and then purifying it without purification. It can manufacture by attaching | subjecting to a hydrolysis reaction according to a method.

[Wherein, X ¹ , X ² , X ³ , Y ¹ , Z, G ² , Q, R ^a , R ³ , R ^a and m represent the same meaning as described above. ]

Examples of harmful arthropods to which the compound of the present invention exhibits a controlling effect include harmful insects and harmful mites. More specifically, the following are mentioned.
Hemiptera: small brown planthopper (Laodelphax striatellus), brown planthopper (Nilaparvata lugens), Sejirounka (Sogatella furcifera) planthoppers such as, green rice leafhopper (Nephotettix cincticeps), Taiwan green rice leafhopper (Nephotettix virescens) leafhoppers such as, cotton aphid (Aphis gossypii) Aphids such as peach mosquito aphids (Myzus persicae), Nezoa antennata, Riptortus clavetus, Eysarcoris larvae ris parvus), Plautia crossota green bug (Plautia stali), brown marmorated stink bug (Halyomorpha mista) red streaks Miridae (Stenotus rubrovittatus), stink bugs such as Trigonotylus caelestialium (Trigonotylus ruficornis), greenhouse whitefly (Trialeurodes vaporariorum), silverleaf whitefly (Bemisia whiteflies such as argentifolii, Aonidiella aurantii, Santocho scale insect (Comstockcaspis perniciosa), Citrus snow scale (Unaspis citri), Ruby worm (Ceroplaste) s rubens), scale insects such as Icerya purchasi, bedbugs, bed bugs such as bed bugs (Cimex electrarius), lice, etc .;

Lepidoptera: rice stem borer (Chilo suppressalis), leaf roller (Cnaphalocrocis medinalis), Watanomeiga (Notarcha derogata), Pyralidae such as Indian meal moth (Plodia interpunctella), common cutworm (Spodoptera litura), armyworm (Pseudaletia separata), Trichoplusia spp., Heliotis genus, Helicobelpa genus moths, white butterflies (Pieris rapae), white butterflies, Adoxofies genus, Nashihime shinsukii (Grapholita molesta), codling moth (Cydia pomonella), etc., peach sinc ensis), mosquito moths such as Lionettia genus, Limantria genus, Euproctinis genus moths, moths such as Plutella xylostella, cotton moths such as Pectinophora gossypiella, cunea), tigers such as tiger (Tinea bissellella), and so on.

Diptera: Culex pipiens pallens, Culex tritaenor hyeschus, Culex quasius es, etc. Houseflies such as Anopheles, Chironomid, Housefly (Musca domestica), Muscina stabulans, etc. Lirio Hyzaglyflies such as myza trifolii), fruit flies, Drosophila, flies such as Drosophila flies (Megella spiracularis), flies such as Drosophila such as Drosophila such as Clogmia albipuncta;

Coleoptera: Western corn root worms (Diabrotica virgifera virgifera), Southern corn root worms (Diabrotica undecimuccita wiard), etc. Weevil such as Sitophilus zeamais, Rice weevil (Lissohoptrus oryzophilus), Azuki beetle (Callosobrchuchus chiensis), Chilobole moss, Tenebrio molit aneum, etc., Olema oryzae, Auracophora femaris, Phyllotreta stomata, etc. , Epilacunas such as Epilachna vigintioctopuncta, Oysterworm, Nagashimushimushi, Leopard beetle, Longicorn beetle, Paederus fuscipes, etc .;

Cockroach pests: German cockroaches (Blatella germanica), Black cockroaches (Periplaneta furiginosa), American cockroaches (Periplaneta americana), Japanese cockroaches (Peripraneta brunet)

Thrips of the order Thrips palmi, Tripas tabaci, Franklinella occidentalis, Franklin, etc.
Hymenoptera: Monomorium phalaosis, Formica fusca japonica, Ochellelus glaben, Phytomidae, Phitomae (Phitomidae) japonica) and the like;

Straight-eyed pests: keratoids, grasshoppers, crickets, etc .;
Lepidoptera: Cat fleas (Ctenocephalides felis), Dog fleas (Ctenocephalides canis), Human fleas (Pulex irritans), Xenopsilla cheopes, etc.
Lice insect pests: Pediculus humanus corporis, phethyrus pubis, cattle lice (Haematopinus eurysternus), sheep lice (Dalmalinia ovis), pig lice
Termite pests: Yamato termites (Reticulites spertermus), Western termites (Cantopterites teremite) (Reticulitermes tibias), Subteranian termites such as dessert Subteranian termite (Heterotermes aureus), Dora such as American termite minor (Incitermes minor) Wood terpolymers mites such, Nevada dump wood coater termite (Zootermopsis nevadensis) Dump Wood terpolymers mitogen such as such;

Mite order pests: Tetanychus urticae, Kanzawa spider mite (Tetranychus kanzawai), citrus spider mite (Panonychus citri), mite spider mite (Panonychus ulmi), spider mite (Aponicus mite) Mites (Aculus schleechtendali), mites (Polyphagotaronemusus latus), mites, terrestrial mites, mites (Haemaphysalis longis), Mites Merikan dog ticks (Dermacentor varis), Tick ticks (Haemphysalis flava), Tick ticks (Dermacetor taiusicus), Tick ticks (Ixodes ovasus) Tick such as Amblyomma americanum, Rhipicephalus sanguineus, Mite, Tyrophagus putrescentiae, Mite, Dermatode mite hagoides farinae), D. pteronyssinus (Dermatophagoides ptrenyssnus) house dust mite such as, Hosotsumedani (Cheyletus eruditus), Stag Tsumedani (Cheyletus malaccensis), Tsumedani such as Minami Tsumedani (Cheyletus moorei), house dust mite (Ornithonyssus bacoti), Torisashidani (Ornithonyssus sylvairum), Cucumbers such as Dermanyssus gallinae, tsutsugamushi such as Leptotrophidium akamushi;
Spiders: Chiracanthium japonicum, Latroectus hasseltii, etc .;

Lip and leg class: Geeu (Thereunema hilgendorfi), Tobismadede (Scolopendra subspinepes), etc .;
Double leg class: Oxidus gracilis, Nedyopus tambanus, etc .;
Isopods: Armadillium vulgare, etc .;

  The harmful arthropod control agent of the present invention contains the compound of the present invention and an inert carrier. In the present invention, the inert carrier represents a bulking agent, a diluent and the like used in the field of prevention and agriculture. The harmful arthropod control agent of the present invention is usually a mixture of the compound of the present invention and an inert carrier such as a solid carrier, liquid carrier, gaseous carrier, etc. Adjuvants are added and formulated into emulsions, oils, powders, granules, wettable powders, flowables, microcapsules, aerosols, smokers, poison baits, resin formulations and the like. These preparations usually contain 0.01 to 95% by weight of the compound of the present invention.

  Examples of the solid carrier used for formulation include clays (kaolin clay, diatomaceous earth, bentonite, fusami clay, acidic clay), synthetic hydrous silicon oxide, talc, ceramic, and other inorganic minerals (sericite, quartz, Sulfur, activated carbon, calcium carbonate, hydrated silica, etc.), chemical fertilizers (ammonium sulfate, phosphorous acid, ammonium nitrate, urea, ammonium chloride, etc.), etc.

  Examples of the liquid carrier include water, alcohols (methanol, ethanol, isopropyl alcohol, butanol, hexanol, benzyl alcohol, ethylene glycol, propylene glycol, phenoxyethanol, etc.), ketones (acetone, methyl ethyl ketone, cyclohexanone, etc.), and aromatic carbonization. Hydrogen (toluene, xylene, ethylbenzene, dodecylbenzene, phenylxylylethane, methylnaphthalene, etc.), aliphatic hydrocarbons (hexane, cyclohexane, kerosene, light oil, etc.), esters (ethyl acetate, butyl acetate, isopropyl myristate) , Ethyl oleate, diisopropyl adipate, diisobutyl adipate, propylene glycol monomethyl ether acetate, etc.), nitriles (acetonitrile, isobutyrate) Nitriles), ethers (diisopropyl ether, 1,4-dioxane, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, diethylene glycol monomethyl ether, propylene glycol monomethyl ether, dipropylene glycol monomethyl ether, 3-methoxy-3-methyl-1-butanol, etc. ), Acid amides (N, N-dimethylformamide, N, N-dimethylacetamide, etc.), halogenated hydrocarbons (dichloromethane, trichloroethane, carbon tetrachloride, etc.), sulfoxides (dimethylsulfoxide, etc.), propylene carbonate and vegetable oil (Soybean oil, cottonseed oil, etc.).

  Examples of the gaseous carrier include fluorocarbon, butane gas, LPG (liquefied petroleum gas), dimethyl ether, and carbon dioxide gas.

  Examples of the surfactant include nonionic surfactants such as polyoxyethylene alkyl ether, polyoxyethylene alkyl aryl ether, and polyethylene glycol fatty acid ester, and alkyl sulfonates, alkyl benzene sulfonates, alkyl sulfates, and the like. Anionic surfactants may be mentioned.

  Other adjuvants for preparation include sticking agents, dispersants, colorants and stabilizers, such as casein, gelatin, saccharides (starch, gum arabic, cellulose derivatives, alginic acid, etc.), lignin derivatives, bentonite. , Synthetic water-soluble polymers (polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acids, etc.), PAP (isopropyl acid phosphate), BHT (2,6-di-tert-butyl-4-methylphenol), BHA (2-tert -Mixture of butyl-4-methoxyphenol and 3-tert-butyl-4-methoxyphenol).

  The harmful arthropod can be controlled by applying the harmful arthropod control agent of the present invention, for example, directly to the harmful arthropod and / or the habitat of the harmful arthropod.

  The method for controlling harmful arthropods is not particularly limited as long as the compound of the present invention can be practically applied. For example, the effective amount of the compound of the present invention is reduced to the amount of harmful arthropods or harmful arthropod inhabitants. It is done by applying to the place. In the harmful arthropod control method of the present invention, the compound of the present invention is usually used in the form of the harmful arthropod control agent of the present invention.

Examples of habitats for harmful arthropods include paddy fields, fields, orchards, non-agricultural land, and houses.
The above application can be carried out by the same application method as before as long as the compound of the present invention can be brought into contact with or ingested by a harmful arthropod.
Examples of such application methods include spraying treatment, soil treatment, seed treatment, and hydroponic liquid treatment.

When the harmful arthropod control agent of the present invention is used for controlling harmful arthropods in the agricultural field, the application amount is the amount of the compound of the present invention per 10,000 m ² and is usually 1 to 10,000 g. When the harmful arthropod control agent of the present invention is formulated into an emulsion, a wettable powder, a flowable agent, etc., it is usually diluted with water so that the active ingredient concentration becomes 0.01 to 10,000 ppm. Granules, powders and the like are usually applied as they are.

  These preparations and water dilutions of these preparations may be sprayed directly on harmful arthropods or plants such as crops to be protected from harmful arthropods, and harmful arthropods that inhabit the soil of cultivated land. You may treat to this soil in order to control.

  Moreover, it can also process by the method of wrapping the resin formulation processed into the sheet form or the string form around the crop, stretching over the crop vicinity, and laying on the stock soil.

When the harmful arthropod control agent of the present invention is used for controlling harmful arthropods that live in the house, the amount applied is usually the amount of the compound of the present invention per 1 m ² when treated on the surface. , 0.01 to 1000 mg, and when processing in a space, the amount of the compound of the present invention per 1 m ³ of the processing space is usually 0.01 to 500 mg. When the harmful arthropod control agent of the present invention is formulated into an emulsion, a wettable powder, a flowable agent, etc., it is usually diluted with water so that the active ingredient concentration is 0.1 to 1000 ppm, and applied. Apply oils, aerosols, smoke, poison baits, etc. as they are.

The compound of the present invention can be used in farmland where the following crops are cultivated.
Agricultural crops: corn, rice, wheat, barley, rye, oat, sorghum, cotton, soybean, peanut, buckwheat, sugar beet, rapeseed, sunflower, sugarcane, tobacco, etc.
Vegetables: Solanum vegetables (eggplants, tomatoes, peppers, peppers, potatoes, etc.), Cucurbitaceae vegetables (cucumbers, pumpkins, zucchini, watermelons, melons, etc.), Brassicaceae vegetables (radish, turnip, horseradish, kohlrabi, Chinese cabbage, cabbage) , Mustard, broccoli, cauliflower, etc.), asteraceae vegetables (burdock, shungiku, artichokes, lettuce, etc.), liliaceae vegetables (leek, onion, garlic, asparagus), celery family vegetables (carrot, parsley, celery, American scallop, etc.) ), Red crustacean vegetables (spinach, chard, etc.), persimmon vegetables (perilla, mint, basil, etc.), strawberry, sweet potato, yam, taro, etc.
Bridegroom,
Foliage plant,
Fruit trees; pears (apples, pears, Japanese pears, quince, quince, etc.), nuclear fruits (peaches, plums, nectarines, ume, sweet cherry, apricots, prunes, etc.), citrus (satsuma mandarin, orange, lemon, lime, grapefruit) ), Nuts (chestnut, walnut, hazel, almond, pistachio, cashew nut, macadamia nut, etc.), berries (blueberry, cranberry, blackberry, raspberry, etc.), grape, oyster, olive, loquat, banana, coffee, Date palm, coconut palm, etc.
Trees other than fruit trees: Cha, mulberry, flowering trees, street trees (ash, birch, dogwood, eucalyptus, ginkgo, lilac, maple, oak, poplar, redwood, fu, sycamore, zelkova, black bean, peach tree, Tsuga, rat, pine, Spruce, yew) etc.

  The crop includes a genetically modified crop.

  The arthropod control agent of the present invention can be mixed or used in combination with other insecticides, acaricides, nematicides, fungicides, plant growth regulators, herbicides and synergists. Examples of active ingredients of such insecticides, acaricides, nematicides, fungicides, plant growth regulators, herbicides and synergists are shown below.

Active Ingredients of Insecticides (1) Organophosphorus Compounds Acephate, Aluminum Phosphide, Butathiofos, Cadosafos, Chlorethoxyfos, Chlorfenvinphos, Chlorfenvinphos (Chlorpyrifos), Chlorpyrifos-methyl (Chlorpyrifos-methyl), Cyanophos (Cyanophos: CYAP), Diazinon (Diazinon), DCIP (Dichlorodiisopropylene ether), Diclofenthion (V: D) ), Dimethoate, dimethylvinphos, disulfoton, EPN, etion, ethoprofos, etrimfos, fention (MPP), EP, Phosthiazate, formothion, hydrogen phosphide, isofenphos, isoxathion, malathion, methulfenfos, methulfenfos, methulfenfos MTP), monocrotophos, nared (BRP), oxydeprofos (ESP), parathion, fosarone, phosmet (PMP), pirimiphosmethyl (pirimithiopimethiopimethiopimethiopimethiopimethiopimethiopimethiopimethypisonepimethypisonepimethypisonepimethypisonepimethypisonepimethypisonepimethypisonepimethypisonepimethypisone (Pyridafenthion), quinalphos, phentoate (PAP), profenofos, propopafos, prothiofos, pyraclofos, phosphite, sulthio Tebupirimfos, temefos, tetrachlorbinphos (tetrach1orvinphos), terbufos, thiomethon, trichlorfon (DEP), bamidithios (vamidothionate, vamidothionate) .
(2) Carbamate compounds alaniccarb, bendiocarb, benfuracarb, BPMC, carbaryl (carbary1), carbofuran, carbothofen, loecarb , Fenobucarb, phenothiocarb, phenoxycarb, furathiocarb, isoprocarb (MIPC), methocarb (metolcarb) hiocarb), NAC, oxamyl (oxamyl), pirimicarb (pirimicarb), propoxur (propoxur: PHC), XMC, thiodicarb (thiodicarb), xylylcarb (xylylcarb), and aldicarb (aldicarb).
(3) Pyrethroid compounds acrinathrin, allethrin, benfluthrin, beta-cyfluthrin, bifenthrin, cycloprotorin, fluprothrin , Cypermethrin, deltamethrin, esfenvalerate, etofenprox, fenpropathrin, fenvalerate, flucitrate lucytrinate, flufenprox, flumethrin, fluvalinate, halfenprox, imiprothrin, permethrin, praretrin, praretrin resmethrin), sigma-cypermethrin, silaflufen, tefluthrin, tralomethrin, transfluthrin, tetramethrin. ethrin), phenothrin, cyphenothrin, alpha-cypermethrin, zeta-cypermethrin, lambda cihalothrin (lambda-halothrin) ), Furamethrin, tau-fluvalinate, methfluthrin, profluthrin, dimethylfluthrin, 2,3,5,6-tetrafluoro-4- (methoxymethyl) benzyl EZ)-(1RS, 3RS; 1RS, 3S R) -2,2-dimethyl-3-prop-1-enylcyclopropanecarboxylate, 2,3,5,6-tetrafluoro-4-methylbenzyl (EZ)-(1RS, 3RS; 1RS, 3SR)- 2,2-dimethyl-3-prop-1-enylcyclopropanecarboxylate and 2,3,5,6-tetrafluoro-4- (methoxymethyl) benzyl (1RS, 3RS; 1RS, 3SR) -2,2 -Dimethyl-3- (2-methyl-1-propenyl) cyclopropanecarboxylate.
(4) Nereistoxin compounds Cartap, bensultap, thiocyclam, monosultap, and bisultap.
(5) Neonicotinoid compounds imidacloprid (imidac1oprid), nitenpyram (nitenpyram), acetamiprid (acetamipride), thiamethoxam, thiacloprid (thiacloprid), dinoteurin (dinothurine)
(6) Benzoylurea compound Chlorfluazuron, bistrifluron, diafenthiuron, diflubenzuron, fluazuron, flucycloxuron, flucyclolone (Flufenoxuron), hexaflumuron, lufenuron, novaluron, novifluuron, teflubenzuron, triflumuron, and triflumuron.
(7) Phenylpyrazole compounds Acetoprole, etiprole, fipronil, vaniliprole, pyriprole, and pyrafluprole.
(8) Bt toxin Live spores and produced crystal toxins derived from Bacillus thuringiensis, and mixtures thereof;
(9) Hydrazine compounds Chromafenozide, halofenozide, methoxyphenozide, and tebufenozide.
(10) Organochlorine compounds Aldrin, dieldrin, dienochlor, endosulfan, and methoxychlor.
(11) Other insecticide active ingredients Machine oil (nicotine-sulfate); avermectin (avermectin-B), bromopropyrate, buprofezin, chlorphenapyr Ritranol, cyromazine, DD (1,3-Dichloropropene), emamectin benzoate, fenazaquin, flupirahydroprene , Indoxacarb, methoxadiazone, milbemycin-A, pymetrozine, pyridalyl, pyriprosul, spiromidol, spinomidol tolfenpyrad, triazamate, flubendiamide, repimectin, arsenous acid, benclothiaz, lime nitrogen calcium lime ulfide, chlordane, DDT, DSP, flufenerium, flonicamid, flurimfen, formatenate, metam-ammonium, metam-ammonium sodium, methyl bromide, potassium oleate, protrifenbute, spiromesifen, sulfoxafluor, sulfur, metafluon, sulfur ), Spirotetramat (sp rotetramat), pyrifluquinazon (pyrifluquinazone), spinetoram (spinetoram), chlorantraniliprole (chlorantraniliprole), Toraropiriru (tralopyril), cyan tiger Niri Prowl (cyantraniliprole).

Active ingredients of acaricides: acequinocyl, amitraz, benzoximate, bifenaate, phenisobromolate (BS), chinomethionate (BS), chloromethionate (BS) chlorfenson, clofentezine, cyflumetofene, kelsen (dicofol), etoxazole, fenbutatin oxide, fenothiocarbene roximate, fluacrylpyrim, fluproxyfen, hexythiazox, propargite (BPPS), polynactin complex (pyridene), pyridaben (pyriben) (Tetradifon), spirodiclofen, spiromesifen, spirotetramat, amidoflumet, and cenopyrafen.

Active ingredients of nematicides DCIP, fostiazate, levamisole hydrochloride, methylisothiocyanate, morantel tartrate, and imiciafos.

Active ingredients of fungicides Propiconazole, Prothioconazole, Triadimenol, Prochloraz, Penconazole, Tebuconazole, Tebuconazole, Tebuconazole , Bromuconazole, epoxiconazole, difenoconazole, cyproconazole, metconazole, triflumazole, triflumizole Tetraconazole, microbutanil, fenbuconazole, hexaconazole, fluquinconazole, triticonazole, triticonazole, triticonazole, triticonazole Azole fungicidal compounds such as flutriafol;
Cyclic amine bactericidal compounds such as fenpropimorph, tridemorph, fenpropidin;
Benzimidazolic fungicidal compounds such as carbendezim, benomyl, thiabendazole, thiophanate-methyl;
Procymidone; cyprodinil; pyrimethanil; dietofencarb; thiuram; fluazilonyl; Captan; mepanipyrim; fenpiclonil; fludioxonil; diclofluraned; folppet; cresoxime- azoxystrobin; trifloxystrobin; fluoxastrobin; picoxystrobin; pyracrostrobin; dimoxystrobin; dimoxystrobin; dimoxystrobin; Pyribencarb; spiroxamine; quinoxyfen; fenhexamid; famoxadone; fenamidone; samamide; samamide; iprovalicarb; benthiavaricarb; cyazofamid; mandipropamid; boscaliden; (Bifafen); cyflufenamide; proquinazid; isotianil and thiadinil.

Active ingredients of plant growth regulators Ethephon, chlormequat-chloride, mepiquat-chloride, gibberellin A3 (Gibberellin A3), abscisic acid Kinetin, benzyladenine, 1,3-diphenylurea, forchlorfenuron, thidiazuron, 4-oxo-4- (2-phenylethyl) aminobutyric acid, 5- (trifluoro) Methyl) methyl benzo [b] thiophene-2-carboxylate and 5- (trifluoromethyl) benzo [b] thio Fen-2-carboxylic acid.

Active ingredient of herbicide (1) Phenoxy fatty acid herbicidal compound 2,4-PA, MCP, MCPB, phenthiol (phenothio1), mecoprop, fluroxypyr, triclopyr, clomeprop Naproanilide.
(2) Benzoic acid herbicidal compound 2,3,6-TBA, dicamba, clopyralid, picloram, aminopyralid, quinclorac, and quinmerac.
(3) Urea herbicidal compounds diuron, linuron, chlortoluron, isoproturon, fluometuron, isouron, tebuthiuron, tebuthiuron, metabenthuron , Cumyluron, daimuron, and methyl-daimuron.
(4) Triazine herbicidal compounds atrazine, ametrine, cyanazine, simazine, propazine, simetrin, dimethamethrin (dimethymetrine) ), Triaziflam, and indaziflam.
(5) Bipyridinium herbicidal compound paraquat and diquat.
(6) Hydroxybenzonitrile herbicidal compounds bromoxynil and ioxynil.
(7) Dinitroaniline herbicidal compounds pendimethalin, prodiamine, and trifluralin.
(8) Organic phosphorus herbicidal compounds amiprofos-methyl, butamifos, bensulide, piperophos, anilofos, glyphosate, glufosinate, glufosinate, glufosinate P (glufosinate-P), and bialaphos.
(9) Carbamate herbicidal compounds di-allate, tri-allate, EPTC, butyrate, beniocarb, esprocarb, molinate, dimipeperate (Swep), chlorpropham, phenmedifam, phenisopham, piributicarb, and asuram.
(10) Acid amide herbicidal compounds propanil, propyzamide, bromobutide, and etobanzanide.
(11) Chloroacetanilide herbicidal compounds acetochlor, acechlor, butachlor, dimethenamide, propachlor, metazachlor, metrachlor or totrachlor pretilachlor), tenylchlor (theny1ch1or), and petoxamide.
(12) Diphenyl ether herbicidal compounds aciflufen-sodium, bifenox, oxyfluorfen, lactofen, fomesafen, clomethoxythonifen, and clomethoxythonipheni.
(13) Cyclic imide herbicidal compounds oxadiazon, cinidone-ethyl, carfentrazone-ethyl, sulfentrazone, full-microlac-pentyl, flumi-lacyl-pentyl Oxazine (flumioxazin), pyraflufen-ethyl, oxadiargyl (oxadiargy1), pentoxazone (pentoxazone), fluthiacet-methyl (butafenzilben) zone), and saflufenacil (saflufenacil).
(14) Pyrazole herbicidal compounds benzofenap, pyrazolate, pyrazoxifene, topramzone, and pyrasulfotole.
(15) Triketone herbicidal compounds isoxaflutole, benzobicyclon, sulcotrione, mesotrione, tembotrione, and tefriltrione.
(16) Aryloxyphenoxypropionic acid herbicidal compound clodinafop-propargyl, cyhalofop-butyl, diclohop-methyl, phenoxaprop-ethyl, fenoxaprop-propyl Fluazifop-butyl, haloxyhop-methyl, and quizalofop-ethyl, metamihop.
(17) Trionoxime herbicidal compounds alloxydim-sodium, cetoxydim, butoxydim, crestodim, cloxydimim, cycloxidim, texydimym (Traxydim), and profoxydim.
(18) sulfonylurea herbicidal compounds chlorsulfuron, sulfomethuron-methyl, metsulfuron-methyl, chlorimuron-ethyl, tribenuron methyl (18) tribenuron-methyl, triasulfuron, bensulfuron-methyl, thifensulfuron-methyl, pyrazosulfuron-methyl, urmisyl Nicosulfuron (nico) ulfuron, amidosulfuron, cinosulfuron, imazosulfuron, rimsulfuron, halosulfuron (th), thulfuron (thulsulfuron), prosulfuron (thulsulfuron) , Triflusulfuron-methyl, flazasulfuron, cyclosulfamuron, flupirsulfuron, sulfosulfurium, sulfosulfurium Azulsulfuron, ethoxysulfuron, oxasulfuron, iodosulfuron-methyl-sodium, foramsulfuron, mesosulfuron, mesulfuron methyl Trisulfursulfuron, tritosulfuron, orthosulfamuron, flucetosulfuron, and propyrisulfuron.
(19) Imidazolinone herbicidal compounds imazametabenz-methyl, imazamethapyr, imazamox, imazapyr, and imazakin (p), imazaquin (p)
(20) Sulfonamide herbicidal compounds flumetslam, metosulam, dicloslam, floraslam, chloransrammethyl, penoxsulox, penoxsulox, and penoxsulox.
(21) Pyrimidinyloxybenzoic acid herbicidal compound pyrithiobac-sodium, bispyribac-sodium, pyriminobac-methy1, pyribenzoximid, pyrifalidomid And pyrimisulfan.
(22) Other herbicidal compounds bentazon, bromacil, terbacil, chlorthiamid, isoxaben, dinoseb, amitrole, cinmethyline, cinmethyline (cinthyl) tripiphane, dalapon (da1apon), diflufenzopyr sodium (diflufenzopyr-sodium), dithiopyr (dithiopyr), thiazopyr (thiazopyr), sodium flucarbazone (proflubazone) Nasset (mefenacet), flufenacet (flufenacet), fentrazamide (fentrazamide), caffenstrole (cafenstrom), indanophan (indanofan), oxadichromemephone (oxaneclomefone), fidarate (benduresate) (Norflurazon), flurtamon, diflufenican, picolinafen, beflubutamide, clomazone, amicarbazone , Pinoxaden (pinoxaden), pyraclonil (pyraclonil), pyroxasulfone (pyroxasulfone), thien-carbazone methyl (thiencarbazone-methyl), amino cyclo Pila crawl (aminocyclopyrachlor), type phen carbazone (ipfencarbazone), and Mechiozorin (methiozolin).

Active ingredient of synergist piperonyl butoxide, sesamex, sulfoxide, N- (2-ethylhexyl) -8,9,10-trinorborn-5-ene-2,3-di Carboximide (MGK 264), N-decrimimidazole (N-decylimidazole), WARF-anti-resistant (TBRF-antiresistant), TBPT, TPP, IBP, PSCP, methyl iodide (CH ₃ I), t-phenyl group Tenon (t-phenylbutone), diethyl maleate, DMC, FDMC, ETP, and ETN.

  Hereinafter, although this invention is demonstrated in more detail by a manufacture example, a formulation example, a test example, etc., this invention is not limited to these examples.

  First, the manufacture example of this invention compound is shown below.

Ｎ−（テトラヒドロフラン−３−イルメチル）−５−ペンチル−１，３，４−チアジアゾール−２−カルボキシアミド（以下、本発明化合物（１）と記す。）３３０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：０．９１（ｔ，３Ｈ）、１．３２−１．４５（ｍ，４Ｈ）、１．６６−１．７４（ｍ，１Ｈ）、１．７８−１．８８（ｍ，２Ｈ）、２．０４−２．１５（ｍ，１Ｈ）、２．５４−２．６６（ｍ，１Ｈ）、３．１４（ｔ，２Ｈ）、３．５０（ｔ，２Ｈ）、３．６０（ｄｄ，１Ｈ）、３．７４−３．８１（ｍ，１Ｈ）、３．８４−３．９６（ｍ，２Ｈ）、７．４５（ｂｒ ｓ，１Ｈ） Production Example 1
N- (tetrahydrofuran-3-ylmethyl) -5- (pent-1-ynyl) -1,3,4-thiadiazole-2-carboxamide (400 mg, 1.43 mmol) and palladium-carbon (100 mg) on ethanol (20 mL) ). After stirring at room temperature for 6 hours under a hydrogen atmosphere, insolubles were filtered off using Celite. The obtained filtrate was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography.

330 mg of N- (tetrahydrofuran-3-ylmethyl) -5-pentyl-1,3,4-thiadiazole-2-carboxamide (hereinafter referred to as the present compound (1)) was obtained.
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 0.91 (t, 3H), 1.32-1.45 (m, 4H), 1.66-1.74 (m, 1H), 1.78-1.88 (m, 2H), 2.04-2.15 (m, 1H), 2.54-2.66 (m, 1H), 3.14 (t, 2H), 3. 50 (t, 2H), 3.60 (dd, 1H), 3.74-3.81 (m, 1H), 3.84-3.96 (m, 2H), 7.45 (brs, 1H) )

で示される Ｎ−（テトラヒドロフラン−３−イルメチル）−５−（Ｚ−ペント−１−エニル）−１，３，４−チアジアゾール−２−カルボキシアミド（以下、本発明化合物（２）と記す。）３００ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：０．９８−１．０３（ｍ，３Ｈ）、１．５７−１．７５（ｍ，４Ｈ）、２．０６−２．１６（ｍ，１Ｈ）、２．４６−２．５４（ｍ，１Ｈ）、２．５６−２．６６（ｍ，１Ｈ）、３．４７−３．５４（ｍ，２Ｈ）、３．５８−３．６３（ｍ，１Ｈ）、３．７４−３．８１（ｍ，１Ｈ）、３．８４−３．９６（ｍ，２Ｈ）、６．２８（ｄｔ，１Ｈ）、６．８４（ｄｔ，１Ｈ）、７．４６（ｂｒｓ，１Ｈ） Production Example 2
N- (tetrahydrofuran-3-ylmethyl) -5- (pent-1-ynyl) -1,3,4-thiadiazole-2-carboxamide (400 mg, 1.43 mmol), palladium-carbon (100 mg) and 1-hexene (1 mL) was added to ethanol (20 mL). After stirring at room temperature for 1 hour under a hydrogen atmosphere, insolubles were filtered off using Celite. The obtained filtrate was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (Z-pent-1-enyl) -1,3,4-thiadiazole-2-carboxamide (hereinafter referred to as the present compound (2)) 300 mg was obtained.
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 0.98-1.03 (m, 3H), 1.57-1.75 (m, 4H), 2.06-2.16 (m , 1H), 2.46-2.54 (m, 1H), 2.56-2.66 (m, 1H), 3.47-3.54 (m, 2H), 3.58-3.63 (M, 1H), 3.74-3.81 (m, 1H), 3.84-3.96 (m, 2H), 6.28 (dt, 1H), 6.84 (dt, 1H), 7.46 (brs, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−１−メチル−３−プロピル−１Ｈ−ピラゾール−５−カルボキシアミド（以下、本発明化合物（３）と記す。）２．０２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９６（３Ｈ，ｔ），１．６４−１．６８（３Ｈ，ｍ），２．０５−２．１４（１Ｈ，ｍ），２．５６−２．５８（３Ｈ，ｍ），３．４１−３．４３（２Ｈ，ｍ），３．６１−３．６３（１Ｈ，ｍ），３．７５−３．７７（１Ｈ，ｍ），３．８２−３．８４（１Ｈ，ｍ），３．９２−３．９４（１Ｈ，ｍ），４．１１（３Ｈ，ｓ），６．１５（１Ｈ，ｓ），６．２６（１Ｈ，ｓ） Production Example 3
1-methyl-3-propyl-1H-pyrazole-5-carboxylic acid (1.68 g, 10 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (1.38 g, 10 mmol), triethylamine (1.01 g, 10 mmol) and 1-Hydroxybenzotriazole (0.15 g, 1.0 mmol) was added to chloroform (amylene-added product) (60 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.92 g, 10 mmol) at room temperature, and the mixture was stirred overnight at room temperature and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

2.02 g of N- (tetrahydrofuran-3-ylmethyl) -1-methyl-3-propyl-1H-pyrazole-5-carboxyamide (hereinafter referred to as the present compound (3)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.96 (3H, t), 1.64-1.68 (3H, m), 2.05-2.14 (1H, m) 2.56-2.58 (3H, m), 3.41-3.43 (2H, m), 3.61-3.63 (1H, m), 3.75-3.77 (1H, m), 3.82-3.84 (1H, m), 3.92-3.94 (1H, m), 4.11 (3H, s), 6.15 (1H, s), 6.26. (1H, s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−１−メチル−３−ブチル−１Ｈ−ピラゾール−５−カルボキシアミド（以下、本発明化合物（４）と記す。）２．３１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９３（３Ｈ，ｔ），１．３５−１．３９（２Ｈ，ｍ），１．５７−１．７２（３Ｈ，ｍ），２．０５−２．１４（１Ｈ，ｍ），２．５３−２．６２（３Ｈ，ｍ），３．４２（２Ｈ，ｔ），３．６１−３．６３（１Ｈ，ｍ），３．７４−３．７８（１Ｈ，ｍ），３．８２−３．８４（１Ｈ，ｍ），３．９２−３．９４（１Ｈ，ｍ），４．１０（３Ｈ，ｓ），６．１７（１Ｈ，ｂｒ ｓ），６．２６（１Ｈ，ｓ） Production Example 4
1-methyl-3-butyl-1H-pyrazole-5-carboxylic acid (1.82 g, 10 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (1.38 g, 10 mmol), triethylamine (1.01 g, 10 mmol) and 1-Hydroxybenzotriazole (0.15 g, 1.0 mmol) was added to chloroform (amylene-added product) (60 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.92 g, 10 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

2.31 g of N- (tetrahydrofuran-3-ylmethyl) -1-methyl-3-butyl-1H-pyrazole-5-carboxyamide (hereinafter referred to as the present compound (4)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.93 (3H, t), 1.35 to 1.39 (2H, m), 1.57-1.72 (3H, m) , 2.05-2.14 (1H, m), 2.53-2.62 (3H, m), 3.42 (2H, t), 3.61-3.63 (1H, m), 3 .74-3.78 (1H, m), 3.82-3.84 (1H, m), 3.92-3.94 (1H, m), 4.10 (3H, s), 6.17 (1H, br s), 6.26 (1H, s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−１−メチル−３−ペンチル−１Ｈ−ピラゾール−５−カルボキシアミド（以下、本発明化合物（５）と記す。）２．６１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９０（３Ｈ，ｔ），１．２９−１．３９（３Ｈ，ｍ），１．５９−１．７２（５Ｈ，ｍ），２．０５−２．１４（１Ｈ，ｍ），２．５３−２．６２（２Ｈ，ｍ），３．４２（２Ｈ，ｔ），３．６１−３．６３（１Ｈ，ｍ），３．７４−３．７６（１Ｈ，ｍ），３．７９−３．８５（１Ｈ，ｍ），３．９２−３．９４（１Ｈ，ｍ），４．１１（３Ｈ，ｓ），６．１５（１Ｈ，ｂｒ ｓ），６．２６（１Ｈ，ｓ） Production Example 5
1-methyl-3-pentyl-1H-pyrazole-5-carboxylic acid (1.82 g, 10 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (1.38 g, 10 mmol), triethylamine (1.01 g, 10 mmol) and 1-Hydroxybenzotriazole (0.15 g, 1.0 mmol) was added to chloroform (amylene-added product) (60 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.92 g, 10 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

2.61 g of N- (tetrahydrofuran-3-ylmethyl) -1-methyl-3-pentyl-1H-pyrazole-5-carboxamide (hereinafter referred to as the present compound (5)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.90 (3H, t), 1.29-1.39 (3H, m), 1.59-1.72 (5H, m) , 2.05-2.14 (1H, m), 2.53-2.62 (2H, m), 3.42 (2H, t), 3.61-3.63 (1H, m), 3 .74-3.76 (1H, m), 3.79-3.85 (1H, m), 3.92-3.94 (1H, m), 4.11 (3H, s), 6.15 (1H, br s), 6.26 (1H, s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−１−ブチル−５−メチル−１Ｈ−ピラゾール−４−カルボキシアミド（以下、本発明化合物（６）と記す。）２．１１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９７（３Ｈ，ｔ），１．３３−１．３７（２Ｈ，ｍ），１．６５−１．７３（１Ｈ，ｍ），１．７７−１．８１（２Ｈ，ｍ），２．０２−２．１２（１Ｈ，ｍ），２．２８（３Ｈ，ｓ），２．５６−２．６１（１Ｈ，ｍ），３．４０−３．４５（２Ｈ，ｍ），３．５７−３．６０（１Ｈ，ｍ），３．７３−３．７９（１Ｈ，ｍ），３．８６−３．９０（２Ｈ，ｍ），４．００（２Ｈ，ｔ），６．５２（１Ｈ，ｓ），６．９６ （１Ｈ，ｂｒ ｓ） Production Example 6
1-butyl-5-methyl-1H-pyrazole-4-carboxylic acid (1.82 g, 10 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (1.38 g, 10 mmol), triethylamine (1.01 g, 10 mmol) and 1-Hydroxybenzotriazole (0.15 g, 1.0 mmol) was added to chloroform (amylene-added product) (60 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.92 g, 10 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

2.11 g of N- (tetrahydrofuran-3-ylmethyl) -1-butyl-5-methyl-1H-pyrazole-4-carboxamide (hereinafter referred to as the present compound (6)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.97 (3H, t), 1.33-1.37 (2H, m), 1.65-1.73 (1H, m) 1.77-1.81 (2H, m), 2.02-2.12 (1H, m), 2.28 (3H, s), 2.56-2.61 (1H, m), 3 .40-3.45 (2H, m), 3.57-3.60 (1H, m), 3.73-3.79 (1H, m), 3.86-3.90 (2H, m) , 4.00 (2H, t), 6.52 (1H, s), 6.96 (1H, br s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−１−メチル−５−プロポキシ−１Ｈ−ピラゾール−３−カルボキシアミド（以下、本発明化合物（７）と記す。）１．６２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．０３（３Ｈ，ｔ），１．６６−１．７１（１Ｈ，ｍ），１．７５−１．８６（２Ｈ，ｍ），２．０５−２．０８（１Ｈ，ｍ），２．５３−２．６０（１Ｈ，ｍ），３．３９−３．４５（２Ｈ，ｍ），３．５７−３．５９（１Ｈ，ｍ），３．６５（３Ｈ，ｓ），３．７５−３．７７（１Ｈ，ｍ），３．８６−３．９０（２Ｈ，ｍ），４．０２（２Ｈ，ｔ），６．０４（１Ｈ，ｓ），６．９６（１Ｈ，ｂｒ ｓ） Production Example 7
1-methyl-5-propoxy-1H-pyrazole-3-carboxylic acid (1.82 g, 10 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (1.38 g, 10 mmol), triethylamine (1.01 g, 10 mmol) and 1-Hydroxybenzotriazole (0.15 g, 1.0 mmol) was added to chloroform (amylene-added product) (60 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.92 g, 10 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.62 g of N- (tetrahydrofuran-3-ylmethyl) -1-methyl-5-propoxy-1H-pyrazole-3-carboxamide (hereinafter referred to as the present compound (7)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.03 (3H, t), 1.66-1.71 (1H, m), 1.75-1.86 (2H, m) 2.05 to 2.08 (1H, m), 2.53 to 2.60 (1H, m), 3.39 to 3.45 (2H, m), 3.57 to 3.59 (1H, m), 3.65 (3H, s), 3.75-3.77 (1H, m), 3.86-3.90 (2H, m), 4.02 (2H, t), 6.04 (1H, s), 6.96 (1H, br s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−１−ブチル−１Ｈ−ピラゾール−３−カルボキシアミド（以下、本発明化合物（８）と記す。）０．８６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： ０．９３（３Ｈ，ｔ），１．３１−１．３５（２Ｈ，ｍ），１．６８−１．７０（１Ｈ，ｍ），１．７９−１．８６（２Ｈ，ｍ），２．０５−２．１４（１Ｈ，ｍ），２．５４−２．６４（１Ｈ，ｍ），３．４４（２Ｈ，ｔ），３．６３（１Ｈ，ｄｄ），３．７５−３．７７（１Ｈ，ｍ），３．８１−３．８６（１Ｈ，ｍ），３．９２−３．９４（１Ｈ，ｍ），４．５５（２Ｈ，ｔ），６．２２（１Ｈ，ｂｒ ｓ），６．４６（１Ｈ，ｄ），７．４６（１Ｈ，ｄ） Production Example 8
1-butyl-1H-pyrazole-3-carboxylic acid (0.82 g, 4.8 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.66 g, 4.8 mmol), triethylamine (0.48 g, 4.8 mmol) ) And 1-hydroxybenzotriazole (0.07 g, 0.48 mmol) were added to chloroform (amylene-added product) (30 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.92 g, 4.8 mmol) at room temperature, and the mixture was stirred overnight at room temperature and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.86 g of N- (tetrahydrofuran-3-ylmethyl) -1-butyl-1H-pyrazole-3-carboxamide (hereinafter referred to as the present compound (8)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.93 (3H, t), 1.31-1.35 (2H, m), 1.68-1.70 (1H, m) 1.79-1.86 (2H, m), 2.05-2.14 (1H, m), 2.54-2.64 (1H, m), 3.44 (2H, t), 3 .63 (1H, dd), 3.75-3.77 (1H, m), 3.81-3.86 (1H, m), 3.92-3.94 (1H, m), 4.55 (2H, t), 6.22 (1H, br s), 6.46 (1H, d), 7.46 (1H, d)

で示される１−ベンジル−１Ｈ−１，２，３−トリアゾール−４−カルボキシアミド（以下、本発明化合物（９）と記す。）０．８６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６４−１．７２（１Ｈ，ｍ），２．０３−２．１１（１Ｈ，ｍ），２．５４−２．５９（１Ｈ，ｍ），３．４６（２Ｈ，ｄｄ），３．５８（１Ｈ，ｄｄ），３．７５（１Ｈ，ｑ），３．９３−３．８４（２Ｈ，ｍ），５．５５（２Ｈ，ｓ），７．４１−７．２７（５Ｈ，ｍ），７．９７（１Ｈ，ｓ） Production Example 9
1-benzyl-1H-1,2,3-triazole-4-carboxylic acid (0.96 g, 4.7 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.71 g, 5.2 mmol), triethylamine (1 0.01 g, 10 mmol) and 1-hydroxybenzotriazole (0.08 g, 0.52 mmol) were added to chloroform (amylene-added product) (30 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.00 g, 4.2 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.86 g of 1-benzyl-1H-1,2,3-triazole-4-carboxamide (hereinafter referred to as the present compound (9)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.72 (1H, m), 2.03-2.11 (1H, m), 2.54-2.59 ( 1H, m), 3.46 (2H, dd), 3.58 (1H, dd), 3.75 (1H, q), 3.93-3.84 (2H, m), 5.55 (2H) , S), 7.41-7.27 (5H, m), 7.97 (1H, s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−プロピルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１０）と記す。）０．１０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．０１（３Ｈ，ｔ），１．６５−１．８２（３Ｈ，ｍ），２．０５−２．１３（１Ｈ，ｍ），２．５４−２．６４（１Ｈ，ｍ），２．７９（２Ｈ，ｔ），３．４１−３．５２（２Ｈ，ｍ），３．６０−３．６２（１Ｈ，ｍ），３．７６−３．９６（３Ｈ，ｍ），６．４６（１Ｈ，ｓ），７．０４（１Ｈ，ｂｒ ｓ） Production Example 10
5-propylisoxazole-3-carboxylic acid (0.25 g, 1.6 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.27 g, 1.9 mmol), triethylamine (0.19 g, 1.9 mmol) And 1-hydroxybenzotriazole (0.03 g, 0.19 mmol) was added to chloroform (amylene-added product) (10 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.36 g, 1.9 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.10 g of N- (tetrahydrofuran-3-ylmethyl) -5-propylisoxazole-3-carboxamide (hereinafter referred to as the present compound (10)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.01 (3H, t), 1.65 to 1.82 (3H, m), 2.05-2.13 (1H, m) , 2.54-2.64 (1H, m), 2.79 (2H, t), 3.41-3.52 (2H, m), 3.60-3.62 (1H, m), 3 .76-3.96 (3H, m), 6.46 (1H, s), 7.04 (1H, br s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−ブチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１１）と記す。）０．２８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９２（３Ｈ，ｔ），１．３４−１．３６（２Ｈ，ｍ），１．６９−１．７３（３Ｈ，ｍ），２．０８−２．１０（１Ｈ，ｍ），２．５９−２．６３（１Ｈ，ｍ），２．７７−２．７９（２Ｈ，ｍ），３．４６−３．４８（２Ｈ，ｍ），３．６２（１Ｈ，ｄｄ），３．７９（１Ｈ，ｄｄ），３．８６−３．９７（２Ｈ，ｍ），６．４６（１Ｈ，ｓ），７．１０（１Ｈ， ｂｒ ｓ） Production Example 11
5-butylisoxazole-3-carboxylic acid (0.50 g, 3.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.50 g, 3.6 mmol), triethylamine (0.36 g, 3.6 mmol) And 1-hydroxybenzotriazole (0.05 g, 0.36 mmol) were added to chloroform (amylene-added product) (20 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.69 g, 3.6 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.28 g of N- (tetrahydrofuran-3-ylmethyl) -5-butylisoxazole-3-carboxamide (hereinafter referred to as the present compound (11)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.92 (3H, t), 1.34-1.36 (2H, m), 1.69-1.73 (3H, m) 2.08-2.10 (1H, m), 2.59-2.63 (1H, m), 2.77-2.79 (2H, m), 3.46-3.48 (2H, m), 3.62 (1H, dd), 3.79 (1H, dd), 3.86-3.97 (2H, m), 6.46 (1H, s), 7.10 (1H, br) s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−ペンチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１２）と記す。）０．１０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９６−０．８９（３Ｈ，ｍ），１．４０−１．３１（４Ｈ，ｍ）１．７７−１．６５（３Ｈ，ｍ），２．０９（１Ｈ，ｔｔ），２．６１（１Ｈ，ｔｄ），２．８４−２．７６（２Ｈ，ｔ），３．４７（２Ｈ，ｄｔ），３．６２（１Ｈ，ｄｄ），３．７９（１Ｈ，ｄｄ），３．９７−３．８６（２Ｈ，ｍ），６．４６（１Ｈ，ｓ），７．１０（１Ｈ，ｂｒ ｓ） Production Example 12
5-pentylisoxazole-3-carboxylic acid (0.28 g, 1.5 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.25 g, 1.8 mmol), triethylamine (0.18 g, 1.8 mmol) And 1-hydroxybenzotriazole (0.03 g, 0.18 mmol) was added to chloroform (amylene-added product) (10 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.35 g, 1.8 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.10 g of N- (tetrahydrofuran-3-ylmethyl) -5-pentylisoxazole-3-carboxamide (hereinafter referred to as the present compound (12)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.96-0.89 (3H, m), 1.40-1.31 (4H, m) 1.77-1.65 (3H M), 2.09 (1H, tt), 2.61 (1H, td), 2.84-2.76 (2H, t), 3.47 (2H, dt), 3.62 (1H, dd), 3.79 (1H, dd), 3.97-3.86 (2H, m), 6.46 (1H, s), 7.10 (1H, br s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１３）と記す。）０．３５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６６−１．６９（１Ｈ，ｍ），２．０５−２．１３（１Ｈ，ｍ），２．５３−２．６３（１Ｈ，ｍ）， ３．４７−３．４９（２Ｈ，ｍ），３．５８−３．６０（１Ｈ，ｍ），３．７６−３．７８（１Ｈ，ｍ），３．８４−３．９５（２Ｈ，ｍ），４．６１（２Ｈ， ｓ），４．６５ （２Ｈ，ｓ），６．７３（１Ｈ，ｄ），６．９５（１Ｈ， ｂｒ ｓ），７．３１−７．４０（５Ｈ，ｍ） Production Example 13
5-Benzyloxymethylisoxazole-3-carboxylic acid (0.59 g, 2.5 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.39 g, 2.8 mmol), triethylamine (0.28 g, 2. 8 mmol) and 1-hydroxybenzotriazole (0.04 g, 0.28 mmol) were added to chloroform (amylene-added product) (15 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.54 g, 2.8 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.35 g of N- (tetrahydrofuran-3-ylmethyl) -5-benzyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (13)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.66 to 1.69 (1H, m), 2.05 to 2.13 (1H, m), 2.53 to 2.63 ( 1H, m), 3.47-3.49 (2H, m), 3.58-3.60 (1H, m), 3.76-3.78 (1H, m), 3.84-3. 95 (2H, m), 4.61 (2H, s), 4.65 (2H, s), 6.73 (1H, d), 6.95 (1H, br s), 7.31-7. 40 (5H, m)

で示されるＮ−（テトラヒドロピラン−２−イルメチル）−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１４）と記す。）０．３６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３０−１．３９（１Ｈ，ｍ），１．４５−１．７０（４Ｈ，ｍ），１．８４−１．８６（１Ｈ，ｍ），３．２３−３．２６（１Ｈ，ｍ），３．４０−３．５０（２Ｈ，ｍ），３．６８−３．７１（１Ｈ，ｍ），３．９８−４．００（１Ｈ，ｍ），４．６０（２Ｈ，ｓ），４．６４（２Ｈ，ｓ），６．７２（１Ｈ，ｓ），７．１８（１Ｈ，ｂｒ ｓ），７．３０−７．３９（５Ｈ，ｍ） Production Example 14
5-Benzyloxymethylisoxazole-3-carboxylic acid (0.35 g, 1.5 mmol), tetrahydropyran-2-ylmethylamine (0.21 g, 1.8 mmol) and 1-hydroxybenzotriazole (0.02 g) , 0.15 mmol) was added to chloroform (amylene-added product) (7.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.35 g, 1.8 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.36 g of N- (tetrahydropyran-2-ylmethyl) -5-benzyloxymethylisoxazole-3-carboxyamide (hereinafter referred to as the present compound (14)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.30-1.39 (1H, m), 1.45-1.70 (4H, m), 1.84-1.86 ( 1H, m), 3.23-3.26 (1H, m), 3.40-3.50 (2H, m), 3.68-3.71 (1H, m), 3.98-4. 00 (1H, m), 4.60 (2H, s), 4.64 (2H, s), 6.72 (1H, s), 7.18 (1H, br s), 7.30-7. 39 (5H, m)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１５）と記す。）０．３６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．３６−１．４０（２Ｈ，ｍ），１．６４−１．６７（２Ｈ，ｍ），１．８１−１．９２（１Ｈ，ｍ），３．３５−３．４０（４Ｈ，ｍ），３．９８−４．００（２Ｈ，ｍ），４．６２ （２Ｈ，ｓ），４．６５（２Ｈ，ｓ），６．７３（１Ｈ，ｓ），６．８９（１Ｈ，ｂｒ ｓ），７．３４−７．３８（５Ｈ，ｍ） Production Example 15
5-Benzyloxymethylisoxazole-3-carboxylic acid (0.35 g, 1.5 mmol), tetrahydropyran-4-ylmethylamine (0.21 g, 1.8 mmol) and 1-hydroxybenzotriazole (0.02 g) , 0.15 mmol) was added to chloroform (amylene-added product) (7.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.35 g, 1.8 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.36 g of N- (tetrahydropyran-4-ylmethyl) -5-benzyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (15)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.36 to 1.40 (2H, m), 1.64 to 1.67 (2H, m), 1.81-1.92 ( 1H, m), 3.35-3.40 (4H, m), 3.98-4.00 (2H, m), 4.62 (2H, s), 4.65 (2H, s), 6 .73 (1H, s), 6.89 (1H, br s), 7.34-7.38 (5H, m)

で示されるＮ−（１，３−ジオキソラニル−２−イルメチル）−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１６）と記す。）０．４４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： ３．６９−３．７０（２Ｈ，ｍ），３．８８−３．９６（２Ｈ，ｍ），４．００−４．０２（２Ｈ，ｍ），４．６０（２Ｈ，ｓ），４．６５（２Ｈ，ｓ），５．０７（１Ｈ，ｔｄ），６．７３（１Ｈ，ｄ），７．０３（１Ｈ，ｓ），７．３３−７．３８（５Ｈ，ｍ） Production Example 16
5-benzyloxymethylisoxazole-3-carboxylic acid (0.35 g, 1.5 mmol), 1,3-dioxolanyl-2-ylmethylamine (0.19 g, 1.8 mmol) and 1-hydroxybenzotriazole ( 0.02 g, 0.15 mmol) was added to chloroform (amylene-added product) (3.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.35 g, 15 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.44 g of N- (1,3-dioxolanyl-2-ylmethyl) -5-benzyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (16)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 3.69-3.70 (2H, m), 3.88-3.96 (2H, m), 4.00-4.02 ( 2H, m), 4.60 (2H, s), 4.65 (2H, s), 5.07 (1H, td), 6.73 (1H, d), 7.03 (1H, s), 7.33-7.38 (5H, m)

で示されるＮ−［２−（テトラヒドロフラン−２−イル）エチル］−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１７）と記す。）０．３４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．５０−１．５５（１Ｈ，ｍ），１．６９−１．７８（１Ｈ，ｍ），１．８５−１．９４（３Ｈ，ｍ），２．００−２．０８（１Ｈ，ｍ），３．４３−３．４８（１Ｈ，ｍ），３．６６−３．７９（２Ｈ，ｍ），３．９２−３．９６（２Ｈ，ｍ），４．６０（２Ｈ，ｓ），４．６４（２Ｈ，ｓ），６．７１（１Ｈ，ｓ），７．２９−７．３９（５Ｈ，ｍ），７．５３（１Ｈ，ｂｒ ｓ） Production Example 17
5-Benzyloxymethyl-isoxazole-3-carboxylic acid (0.35 g, 1.5 mmol), 2- (tetrahydrofuran-2-yl) ethylamine (0.21 g, 1.8 mmol) and 1-hydroxybenzotriazole (0. 02 g, 0.15 mmol) was added to chloroform (amylene-added product) (7.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.35 g, 1.8 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.34 g of N- [2- (tetrahydrofuran-2-yl) ethyl] -5-benzyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (17)) represented by the formula: .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.50-1.55 (1H, m), 1.69-1.78 (1H, m), 1.85-1.94 ( 3H, m), 2.00-2.08 (1H, m), 3.43-3.48 (1H, m), 3.66-3.79 (2H, m), 3.92-3. 96 (2H, m), 4.60 (2H, s), 4.64 (2H, s), 6.71 (1H, s), 7.29-7.39 (5H, m), 7.53 (1H, br s)

で示されるＮ−[２−（テトラヒドロピラン−４−イル）エチル]−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１８）と記す。）０．４３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３１−１．３４（２Ｈ，ｍ），１．５７−１．６４（５Ｈ，ｍ），３．３６−３．３９（２Ｈ，ｍ），３．４８−３．５０（２Ｈ，ｍ），３．９５（２Ｈ，ｄｄ），４．６１（２Ｈ，ｓ），４．６４（２Ｈ，ｓ），６．７２（１Ｈ，ｓ），６．８３（１Ｈ，ｓ），７．３０−７．３９（５Ｈ，ｍ） Production Example 18
5-benzyloxymethylisoxazole-3-carboxylic acid (0.35 g, 1.5 mmol), 2- (tetrahydropyran-4-yl) ethylamine (0.23 g, 1.8 mmol) and 1-hydroxybenzotriazole ( 0.02 g, 0.15 mmol) was added to chloroform (amylene-added product) (7.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.35 g, 1.8 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.43 g of N- [2- (tetrahydropyran-4-yl) ethyl] -5-benzyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (18)) represented by the formula: It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.31-1.34 (2H, m), 1.57-1.64 (5H, m), 3.36-3.39 ( 2H, m), 3.48-3.50 (2H, m), 3.95 (2H, dd), 4.61 (2H, s), 4.64 (2H, s), 6.72 (1H) , S), 6.83 (1H, s), 7.30-7.39 (5H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−シクロペンチルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１９）と記す。）０．１０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．５４−１．５９（２Ｈ，ｍ），１．６８−１．７２（７Ｈ，ｍ），２．０４−２．１３（１Ｈ，ｍ），２．５６−２．５８（１Ｈ，ｍ），３．４６（２Ｈ，ｔ），３．５７−３．６０（１Ｈ，ｍ），３．７５−３．７８（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），４．０３−４．０４（１Ｈ，ｍ），４．５８（２Ｈ，ｓ），６．６９（１Ｈ，ｓ），６．９３（１Ｈ，ｂｒ ｓ） Production Example 19
5-cyclopentyloxymethylisoxazole-3-carboxylic acid (0.26 g, 1.2 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.20 g, 1.5 mmol), triethylamine (0.15 g, 1.. 5 mmol) and 1-hydroxybenzotriazole (0.02 g, 0.15 mmol) were added to chloroform (amylene-added product) (15 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.28 g, 1.5 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.10 g of N- (tetrahydrofuran-3-ylmethyl) -5-cyclopentyloxymethylisoxazole-3-carboxamide represented by the following formula (19) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.54-1.59 (2H, m), 1.68-1.72 (7H, m), 2.04-2.13 ( 1H, m), 2.56-2.58 (1H, m), 3.46 (2H, t), 3.57-3.60 (1H, m), 3.75-3.78 (1H, m), 3.84-3.94 (2H, m), 4.03-4.04 (1H, m), 4.58 (2H, s), 6.69 (1H, s), 6.93. (1H, br s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−ナフチルメトキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２０）と記す。）０．３７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６７−１．７０（１Ｈ，ｍ），２．０５−２．１４（１Ｈ，ｍ），２．５６−２．６０（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５８−３．６０（１Ｈ，ｍ），３．７６−３．７８（１Ｈ，ｍ），３．８４−３．９５（２Ｈ，ｍ），４．６９（２Ｈ，ｓ），４．７７（２Ｈ，ｓ），６．７６（１Ｈ，ｓ），６．９４（１Ｈ，ｂｒ ｓ），７．４６−７．５３（３Ｈ，ｍ），７．８０−７．８７（４Ｈ，ｍ） Production Example 20
5- (2-naphthylmethoxymethyl) isoxazole-3-carboxylic acid (0.57 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.33 g, 2.4 mmol), triethylamine (0.24 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.24 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.37 g of N- (tetrahydrofuran-3-ylmethyl) -5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (20)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.67-1.70 (1H, m), 2.05-2.14 (1H, m), 2.56-2.60 ( 1H, m), 3.47 (2H, t), 3.58-3.60 (1H, m), 3.76-3.78 (1H, m), 3.84-3.95 (2H, m), 4.69 (2H, s), 4.77 (2H, s), 6.76 (1H, s), 6.94 (1H, br s), 7.46-7.53 (3H, m), 7.80-7.87 (4H, m)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−（２−ナフチルメトキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２１）と記す。）０．７４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３５−１．４１（２Ｈ，ｍ），１．６５−１．６９（２Ｈ，ｍ），１．８５−１．８８（１Ｈ，ｍ），３．３４−３．４２（４Ｈ，ｍ），３．９９（２Ｈ，ｄｄ），４．６９（２Ｈ，ｄ），４．７７（２Ｈ，ｓ），６．７５（１Ｈ，ｓ），６．８８（１Ｈ，ｂｒ ｓ），７．４６−７．５２（３Ｈ，ｍ），７．８０−７．８７（４Ｈ，ｍ） Production Example 21
5- (2-naphthylmethoxymethyl) isoxazole-3-carboxylic acid (0.53 g, 2.0 mmol), tetrahydropyran-4-ylmethylamine (0.28 g, 2.4 mmol) and 1-hydroxybenzotriazole (0 0.03 g, 0.24 mmol) was added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.74 g of N- (tetrahydropyran-4-ylmethyl) -5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (21)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.35 to 1.41 (2H, m), 1.65 to 1.69 (2H, m), 1.85 to 1.88 ( 1H, m), 3.34-3.42 (4H, m), 3.99 (2H, dd), 4.69 (2H, d), 4.77 (2H, s), 6.75 (1H) , S), 6.88 (1H, br s), 7.46-7.52 (3H, m), 7.80-7.87 (4H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−フェニルプロピル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２２）と記す。）０．４９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７２（１Ｈ，ｍ），２．０２−２．１３（３Ｈ，ｍ），２．５２−２．６２（１Ｈ，ｍ）， ２．６９（２Ｈ，ｔ），２．８０（２Ｈ，ｔ），３．４４−３．４７（２Ｈ，ｍ），３．５７−３．６０（１Ｈ，ｍ），３．７５−３．７８（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），６．４６（１Ｈ，ｓ），６．９３（１Ｈ，ｂｒ ｓ），７．１８−７．２２（３Ｈ，ｍ），７．２９−７．３２（２Ｈ，ｍ） Production Example 22
5- (3-phenylpropyl) isoxazole-3-carboxylic acid (0.46 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.33 g, 2.4 mmol), triethylamine (0.24 g, 2 .4 mmol) and 1-hydroxybenzotriazole (0.04 g, 0.24 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.49 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3-phenylpropyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (22)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.72 (1H, m), 2.02-2.13 (3H, m), 2.52-2.62 ( 1H, m), 2.69 (2H, t), 2.80 (2H, t), 3.44-3.47 (2H, m), 3.57-3.60 (1H, m), 3 .75-3.78 (1H, m), 3.84-3.94 (2H, m), 6.46 (1H, s), 6.93 (1H, br s), 7.18-7. 22 (3H, m), 7.29-7.32 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−フェニルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２３）と記す。）０．１５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６６−１．６９（１Ｈ，ｍ），２．０６−２．１４（１Ｈ，ｍ），２．５６−２．６０（１Ｈ，ｍ），３．４６（２Ｈ，ｔ），３．６０（１Ｈ，ｄｄ），３．７６−３．７８（１Ｈ，ｍ），３．８５−３．８７（１Ｈ，ｍ），３．９１−３．９３（１Ｈ，ｍ），５．２０（２Ｈ，ｓ），６．８０（１Ｈ，ｓ），６．９４−６．９７（３Ｈ，ｍ），７．００−７．０５（１Ｈ，ｍ），７．２９−７．３４（２Ｈ，ｍ） Production Example 23
5-phenyloxymethylisoxazole-3-carboxylic acid (0.31 g, 1.4 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.24 g, 1.7 mmol), triethylamine (0.17 g, 1. 7 mmol) and 1-hydroxybenzotriazole (0.02 g, 0.17 mmol) were added to chloroform (amylene-added product) (3 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.33 g, 1.7 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.15 g of N- (tetrahydrofuran-3-ylmethyl) -5-phenyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (23)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.66 to 1.69 (1H, m), 2.06-2.14 (1H, m), 2.56-2.60 ( 1H, m), 3.46 (2H, t), 3.60 (1H, dd), 3.76-3.78 (1H, m), 3.85-3.87 (1H, m), 3 91-3.93 (1H, m), 5.20 (2H, s), 6.80 (1H, s), 6.94-6.97 (3H, m), 7.00-7.05 (1H, m), 7.29-7.34 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−フェニルエチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２４）と記す。）０．１５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６５−１．６９（１Ｈ，ｍ），２．０４−２．１３（１Ｈ，ｍ），２．５３−２．６０（１Ｈ，ｍ），３．０１−３．０５（２Ｈ，ｍ），３．１０−３．１４（２Ｈ，ｍ），３．４３−３．４７（２Ｈ，ｍ），３．５７−３．５９（１Ｈ，ｍ），３．７５−３．７８（１Ｈ，ｍ），３．８５−３．８７（１Ｈ，ｍ），３．９０−３．９２（１Ｈ，ｍ），６．４１（１Ｈ，ｓ），６．９１（１Ｈ，ｂｒ ｓ），７．１８−７．１９（２Ｈ，ｍ），７．２２−７．２４（１Ｈ，ｍ），７．２９−７．３１（２Ｈ，ｍ） Production Example 24
5- (2-Phenylethyl) isoxazole-3-carboxylic acid (0.43 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.33 g, 2.4 mmol), triethylamine (0.24 g, 2 .4 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.24 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.15 g of N- (tetrahydrofuran-3-ylmethyl) -5- (2-phenylethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (24)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.65 to 1.69 (1H, m), 2.04-2.13 (1H, m), 2.53 to 2.60 ( 1H, m), 3.01-3.05 (2H, m), 3.10-3.14 (2H, m), 3.43-3.47 (2H, m), 3.57-3. 59 (1H, m), 3.75-3.78 (1H, m), 3.85-3.87 (1H, m), 3.90-3.92 (1H, m), 6.41 ( 1H, s), 6.91 (1H, br s), 7.18-7.19 (2H, m), 7.22-7.24 (1H, m), 7.29-7.31 (2H , M)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−フェニルエチル）オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２５）と記す。）０．３６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６５−１．６９（１Ｈ，ｍ），２．０８−２．１１（１Ｈ，ｍ），２．５４−２．６１（１Ｈ，ｍ），２．９２（２Ｈ，ｔ），３．４７（２Ｈ，ｄｔ），３．５９（１Ｈ，ｄｄ），３．７５−３．７７（３Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），４．６２（２Ｈ，ｄ），６．６４（１Ｈ，ｓ），６．９２（１Ｈ，ｂｒ ｓ），７．２１−７．２４（３Ｈ，ｍ），７．２９−７．３１（２Ｈ，ｍ） Production Example 25
5- (2-phenylethyl) oxymethylisoxazole-3-carboxylic acid (0.50 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.33 g, 2.4 mmol), triethylamine (0 .24 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.04 g, 0.24 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.36 g of N- (tetrahydrofuran-3-ylmethyl) -5- (2-phenylethyl) oxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (25)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.65 to 1.69 (1H, m), 2.08-2.11 (1H, m), 2.54-2.61 ( 1H, m), 2.92 (2H, t), 3.47 (2H, dt), 3.59 (1H, dd), 3.75-3.77 (3H, m), 3.84-3 .94 (2H, m), 4.62 (2H, d), 6.64 (1H, s), 6.92 (1H, br s), 7.21-7.24 (3H, m), 7 .29-7.31 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−ベンジルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２６）と記す。）０．３２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．６８（１Ｈ，ｍ），２．０３−２．１１（１Ｈ，ｍ），２．５２−２．５９（１Ｈ，ｍ），３．４４（２Ｈ，ｄｄ），３．５７（１Ｈ，ｄｄ），３．７４−３．７７（１Ｈ，ｍ），３．８２−３．９３（２Ｈ，ｍ），４．１２（２Ｈ，ｓ），６．３９（１Ｈ，ｓ），６．９０（１Ｈ，ｂｒ ｓ），７．２４−７．３７（５Ｈ，ｍ） Production Example 26
5-Benzylisoxazole-3-carboxylic acid (0.27 g, 1.3 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.22 g, 1.6 mmol), triethylamine (0.16 g, 1.6 mmol) 1-hydroxybenzotriazole (0.02 g, 0.16 mmol) was added to chloroform (amylene-added product) (3 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.31 g, 1.6 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.32 g of N- (tetrahydrofuran-3-ylmethyl) -5-benzylisoxazole-3-carboxamide (hereinafter referred to as the present compound (26)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.68 (1H, m), 2.03-2.11 (1H, m), 2.52-2.59 ( 1H, m), 3.44 (2H, dd), 3.57 (1H, dd), 3.74-3.77 (1H, m), 3.82-3.93 (2H, m), 4 .12 (2H, s), 6.39 (1H, s), 6.90 (1H, br s), 7.24-7.37 (5H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（１−ナフチルメトキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２７）と記す。）０．３１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６６−１．６９（１Ｈ，ｍ），２．０４−２．１３（１Ｈ，ｍ），２．５３−２．６３（１Ｈ，ｍ），３．４６（２Ｈ，ｔ），３．５８−３．６０（１Ｈ，ｍ），３．７５−３．７９（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），４．６８（２Ｈ，ｓ），５．０６（２Ｈ，ｓ），６．７２（１Ｈ，ｓ），６．９５（１Ｈ，ｂｒ ｓ），７．４３−７．５８（４Ｈ，ｍ），７．８４−７．８９（２Ｈ，ｍ），８．１１（１Ｈ，ｄ） Production Example 27
5- (1-naphthylmethoxymethyl) isoxazole-3-carboxylic acid (0.46 g, 1.6 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.26 g, 1.9 mmol), triethylamine (0.19 g, 1.9 mmol) and 1-hydroxybenzotriazole (0.02 g, 0.19 mmol) were added to chloroform (amylene-added product) (3 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.37 g, 1.9 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.31 g of N- (tetrahydrofuran-3-ylmethyl) -5- (1-naphthylmethoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (27)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.66 to 1.69 (1H, m), 2.04-2.13 (1H, m), 2.53 to 2.63 ( 1H, m), 3.46 (2H, t), 3.58-3.60 (1H, m), 3.75-3.79 (1H, m), 3.84-3.94 (2H, m), 4.68 (2H, s), 5.06 (2H, s), 6.72 (1H, s), 6.95 (1H, br s), 7.43-7.58 (4H, m), 7.84-7.89 (2H, m), 8.11 (1H, d)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−[１−（２−ナフチル）エチル]オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２８）と記す。）０．４２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．５７（３Ｈ，ｄ），１．６６−１．６９（１Ｈ，ｍ），２．０４−２．１３（１Ｈ，ｍ），２．５６−２．６１（１Ｈ，ｍ），３．４６（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７７（１Ｈ，ｄｄ），３．８４−３．９５（２Ｈ，ｍ），４．４９（２Ｈ，ｄｄ），４．７０（１Ｈ，ｑ），６．６９（１Ｈ，ｓ），６．９３（１Ｈ，ｂｒ ｓ），７．４８−７．５２（３Ｈ，ｍ），７．７６（１Ｈ，ｓ），７．８４−７．８９（３Ｈ，ｍ） Production Example 28
5- [1- (2-naphthyl) ethyl] oxymethylisoxazole-3-carboxylic acid (0.59 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.33 g, 2.4 mmol) , Triethylamine (0.24 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.24 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- [1- (2-naphthyl) ethyl] oxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (28)) 0. 42 g were obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.57 (3H, d), 1.66 to 1.69 (1H, m), 2.04-2.13 (1H, m) 2.56-2.61 (1H, m), 3.46 (2H, t), 3.59 (1H, dd), 3.77 (1H, dd), 3.84-3.95 (2H M), 4.49 (2H, dd), 4.70 (1H, q), 6.69 (1H, s), 6.93 (1H, br s), 7.48-7.52 (3H M), 7.76 (1H, s), 7.84-7.89 (3H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（４−メトキシメチル−２，３，５，６−テトラフルオロベンジル）オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２９）と記す。）０．１２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．６８（１Ｈ，ｍ），２．０３−２．１２（１Ｈ，ｍ），２．５１−２．６１（１Ｈ，ｍ），３．３９（３Ｈ，ｓ），３．４５（２Ｈ，ｔ），３．５８（１Ｈ，ｄｄ），３．７５（１Ｈ，ｄｄ），３．８３−３．８５（１Ｈ，ｍ），３．８９−３．９１（１Ｈ，ｍ），４．５７（２Ｈ，ｔ），４．６８（２Ｈ，ｓ），４．７１（２Ｈ，ｔ），６．７４（１Ｈ，ｓ），６．９４（１Ｈ，ｂｒ ｓ） Production Example 29
5- (4-methoxymethyl-2,3,5,6-tetrafluorobenzyl) oxymethylisoxazole-3-carboxylic acid (0.20 g, 0.6 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride ( 0.10 g, 0.9 mmol), triethylamine (0.07 g, 0.7 mmol) and 1-hydroxybenzotriazole (0.01 g, 0.07 mmol) were added to chloroform (amylene-added product) (2 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.13 g, 0.7 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (4-methoxymethyl-2,3,5,6-tetrafluorobenzyl) oxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound ( 29).) 0.12 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.68 (1H, m), 2.03-2.12 (1H, m), 2.51-2.61 ( 1H, m), 3.39 (3H, s), 3.45 (2H, t), 3.58 (1H, dd), 3.75 (1H, dd), 3.83-3.85 (1H M), 3.89-3.91 (1H, m), 4.57 (2H, t), 4.68 (2H, s), 4.71 (2H, t), 6.74 (1H, s), 6.94 (1H, br s)

で示されるＮ−[２−（テトラヒドロフラン−３−イル）エチル]−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（３０）と記す。）０．３４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．５３−１．６０（１Ｈ，ｍ），１．６４−１．７８（２Ｈ，ｍ），２．０５−２．１５（１Ｈ，ｍ），２．２１−２．３２（１Ｈ，ｍ），３．３９（１Ｈ，ｔ），３．４３−３．５４ （２Ｈ，ｍ），３．７６（１Ｈ，ｑ），３．８６−３．８９（１Ｈ，ｍ），３．９４（１Ｈ，ｔ），４．６１（２Ｈ，ｓ），４．６５（２Ｈ，ｓ），６．７２ （１Ｈ，ｓ），６．８５（１Ｈ，ｂｒｓ），７．３２−７．３７（５Ｈ，ｍ） Production Example 30
5-Benzyloxymethylisoxazole-3-carboxylic acid (0.35 g, 1.5 mmol), 2- (tetrahydrofuran-3-yl) ethylamine hydrochloride (0.27 g, 1.8 mmol) and 1-hydroxybenzotriazole (0.02 g, 0.15 mmol) was added to chloroform (amylene-added product) (7.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.35 g, 1.8 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.34 g of N- [2- (tetrahydrofuran-3-yl) ethyl] -5-benzyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (30)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.53-1.60 (1H, m), 1.64-1.78 (2H, m), 2.05-2.15 ( 1H, m), 2.21-2.32 (1H, m), 3.39 (1H, t), 3.43-3.54 (2H, m), 3.76 (1H, q), 3 86-3.89 (1H, m), 3.94 (1H, t), 4.61 (2H, s), 4.65 (2H, s), 6.72 (1H, s), 6. 85 (1H, brs), 7.32-7.37 (5H, m)

で示されるＮ−[（１，４−ジオキサン−２−イル）メチル]−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（３１）と記す。）０．３４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：３．３１−３．４０（２Ｈ，ｍ），３．５７−３．６６（２Ｈ，ｍ），３．７０−３．８３（５Ｈ，ｍ），４．６１（２Ｈ，ｓ），４．６５（２Ｈ，ｓ），６．７３（１Ｈ，ｔ），７．１４（１Ｈ，ｂｒ ｓ），７．３０−７．４０（５Ｈ，ｍ） Production Example 31
5-Benzyloxymethylisoxazole-3-carboxylic acid (0.35 g, 1.5 mmol), (1,4-dioxane-2-yl) methylamine (0.21 g, 1.8 mmol) and 1-hydroxybenzo Triazole (0.02 g, 0.15 mmol) was added to chloroform (amylene-added product) (7.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.35 g, 1.8 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.34 g of N-[(1,4-dioxan-2-yl) methyl] -5-benzyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (31)) represented by the formula: Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 3.31-3.40 (2H, m), 3.57-3.66 (2H, m), 3.70-3.83 ( 5H, m), 4.61 (2H, s), 4.65 (2H, s), 6.73 (1H, t), 7.14 (1H, br s), 7.30-7.40 ( 5H, m)

で示されるＮ−（テトラヒドロフラン−２−イルメチル）−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（３２）と記す。）０．３３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．５９−１．６２（１Ｈ，ｍ），１．８８−１．９５（２Ｈ，ｍ），１．９９−２．０１（１Ｈ，ｍ），３．４０−３．４３（１Ｈ，ｍ），３．６８−３．７１（１Ｈ，ｍ），３．７４−３．８０（１Ｈ，ｍ），３．８８−３．９１（１Ｈ，ｍ），４．０３−４．０８（１Ｈ，ｍ），４．６０（２Ｈ，ｓ），４．６４（２Ｈ，ｓ），６．７２（１Ｈ，ｓ），７．１３（１Ｈ，ｂｒ ｓ），７．３０−７．３９（５Ｈ，ｍ） Production Example 32
5-Benzyloxymethyl-isoxazole-3-carboxylic acid (0.30 g, 1.3 mmol), tetrahydrofuran-2-ylmethylamine (0.16 g, 1.5 mmol) and 1-hydroxybenzotriazole (0.02 g, 0 .01 mmol) was added to chloroform (amylene-added product) (3 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.30 g, 1.5 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.33 g of N- (tetrahydrofuran-2-ylmethyl) -5-benzyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (32)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.59-1.62 (1H, m), 1.88-1.95 (2H, m), 1.99-2.01 ( 1H, m), 3.40-3.43 (1H, m), 3.68-3.71 (1H, m), 3.74-3.80 (1H, m), 3.88-3. 91 (1H, m), 4.03-4.08 (1H, m), 4.60 (2H, s), 4.64 (2H, s), 6.72 (1H, s), 7.13 (1H, br s), 7.30-7.39 (5H, m)

で示されるＮ−［（Ｒ）−テトラヒドロフラン−３−イルメチル］−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（３３）と記す。）０．２６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６３−１．７２（１Ｈ，ｍ），２．０４−２．１３（１Ｈ，ｍ），２．５３−２．６３（１Ｈ，ｍ）， ３．４７−３．４９（２Ｈ，ｍ），３．５７−３．６１（１Ｈ，ｍ），３．７４−３．８０（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），４．６１（２Ｈ，ｓ），４．６５（２Ｈ，ｓ），６．７３（１Ｈ，ｓ），６．９９（１Ｈ，ｂｒ ｓ），７．３１−７．４０（５Ｈ，ｍ） Production Example 33
5-benzyloxymethylisoxazole-3-carboxylic acid (0.24 g, 1.0 mmol), (R) -tetrahydrofuran-3-ylmethylamine (0.13 g, 1.2 mmol), 1-hydroxybenzotriazole ( 0.01 g, 0.1 mmol) was added to chloroform (amylene-added product) (2.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.24 g, 1.2 mmol) at room temperature, and the mixture was stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was passed through a silica gel short column to remove impurities, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.26 g of N-[(R) -tetrahydrofuran-3-ylmethyl] -5-benzyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (33)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (1H, m), 2.04-2.13 (1H, m), 2.53-2.63 ( 1H, m), 3.47-3.49 (2H, m), 3.57-3.61 (1H, m), 3.74-3.80 (1H, m), 3.84-3. 94 (2H, m), 4.61 (2H, s), 4.65 (2H, s), 6.73 (1H, s), 6.99 (1H, br s), 7.31-7. 40 (5H, m)

で示されるＮ−［（Ｓ）−テトラヒドロフラン−３−イルメチル］−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（３４）と記す。）０．２３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６３−１．７２（１Ｈ，ｍ），２．０５−２．１３（１Ｈ，ｍ），２．５３−２．６３（１Ｈ，ｍ）， ３．４５−３．４８（２Ｈ，ｍ），３．５７−３．６１（１Ｈ，ｍ），３．７４−３．８０（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），４．６１（２Ｈ，ｓ），４．６５（２Ｈ，ｓ），６．７３（１Ｈ，ｓ），６．９８（１Ｈ，ｂｒ ｓ），７．３１−７．４０（５Ｈ，ｍ） Production Example 34
5-benzyloxymethylisoxazole-3-carboxylic acid (0.24 g, 1.0 mmol), (S) -tetrahydrofuran-3-ylmethylamine (0.13 g, 1.2 mmol) and 1-hydroxybenzotriazole ( 0.01 g, 0.1 mmol) was added to chloroform (amylene-added product) (2.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.24 g, 1.2 mmol) at room temperature, and the mixture was stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was passed through a silica gel short column to remove impurities, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.23 g of N-[(S) -tetrahydrofuran-3-ylmethyl] -5-benzyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (34)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (1H, m), 2.05-2.13 (1H, m), 2.53-2.63 ( 1H, m), 3.45-3.48 (2H, m), 3.57-3.61 (1H, m), 3.74-3.80 (1H, m), 3.84-3. 94 (2H, m), 4.61 (2H, s), 4.65 (2H, s), 6.73 (1H, s), 6.98 (1H, br s), 7.31-7. 40 (5H, m)

で示されるＮ−[４−（１，３−ジオキソリル）メチル]−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（３５）と記す。）０．２２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： ４．００（４Ｈ，ｓ），４．１３−４．１６（１Ｈ，ｍ），４．６１（２Ｈ，ｓ），４．６６（２Ｈ，ｓ），４．８０（１Ｈ，ｄ），５．０２（１Ｈ，ｄ），６．７３（１Ｈ，ｓ），７．３１−７．４０（５Ｈ，ｍ），７．６２（１Ｈ，ｂｒ ｓ） Production Example 35
5-benzyloxymethylisoxazole-3-carboxylic acid (0.24 g, 1.0 mmol), 1,3-dioxolan-4-ylmethylamine (0.13 g, 1.2 mmol) and 1-hydroxybenzotriazole ( 0.01 g, 0.1 mmol) was added to chloroform (amylene-added product) (2.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.24 g, 1.2 mmol) at room temperature, and the mixture was stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was passed through a silica gel short column to remove impurities, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.22 g of N- [4- (1,3-dioxolyl) methyl] -5-benzyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (35)) represented by the formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 4.00 (4H, s), 4.13-4.16 (1H, m), 4.61 (2H, s), 4.66 (2H, s), 4.80 (1H, d), 5.02 (1H, d), 6.73 (1H, s), 7.31-7.40 (5H, m), 7.62 ( 1H, br s)

で示されるＮ−（３−メチルテトラヒドロフラン−３−イルメチル）−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（３６）と記す。）０．３１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．１７（３Ｈ，ｓ），１．６７−１．７４（１Ｈ，ｍ），１．８６−１．９３（１Ｈ，ｍ），３．４５（１Ｈ，ｄ），３．４６−３．４８（２Ｈ，ｍ），３．７０（１Ｈ，ｄ），３．８５−３．９１（１Ｈ，ｍ），３．９４−３．９９（１Ｈ，ｍ），４．６１（２Ｈ，ｓ），４．６５（２Ｈ，ｓ），６．７３（１Ｈ，ｓ），７．０５（１Ｈ，ｂｒｓ），７．３１−７．４０（５Ｈ，ｍ） Production Example 36
5-Benzyloxymethylisoxazole-3-carboxylic acid (0.24 g, 1.0 mmol), (3-methyltetrahydrofuran-3-yl) methylamine (0.14 g, 1.2 mmol) and 1-hydroxybenzotriazole (0.01 g, 0.1 mmol) was added to chloroform (amylene-added product) (2.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.24 g, 1.2 mmol) at room temperature, and the mixture was stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was passed through a silica gel short column to remove impurities, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.31 g of N- (3-methyltetrahydrofuran-3-ylmethyl) -5-benzyloxymethylisoxazole-3-carboxyamide (hereinafter referred to as the present compound (36)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.17 (3H, s), 1.67-1.74 (1H, m), 1.86-1.93 (1H, m) 3.45 (1H, d), 3.46-3.48 (2H, m), 3.70 (1H, d), 3.85-3.91 (1H, m), 3.94-3 .99 (1H, m), 4.61 (2H, s), 4.65 (2H, s), 6.73 (1H, s), 7.05 (1H, brs), 7.31-7. 40 (5H, m)

で示されるＮ−（テトラヒドロピラン−３−イルメチル）−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（３７）と記す。）０．１９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．２８−１．３８（１Ｈ，ｍ），１．５５−１．７１（２Ｈ，ｍ），１．８６−１．９８（２Ｈ，ｍ），３．２３−３．２８（１Ｈ，ｍ），３．３５（２Ｈ，ｔ），３．４１−３．４７（１Ｈ，ｍ），３．８２−３．８６（１Ｈ，ｍ），３．８８−３．９２（１Ｈ，ｍ），４．６１（２Ｈ，ｓ），４．６５（２Ｈ，ｓ），６．７２（１Ｈ，ｄ），６．８６（１Ｈ，ｂｒｓ），７．３０−７．４０（５Ｈ，ｍ） Production Example 37
5-Benzyloxymethylisoxazole-3-carboxylic acid (0.15 g, 0.65 mmol), tetrahydropyran-3-ylmethylamine (0.09 g, 0.78 mmol) and 1-hydroxybenzotriazole (0.008 g , 0.06 mmol) was added to chloroform (amylene-added product) (1.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.15 g, 0.78 mmol) at room temperature, and the mixture was stirred at room temperature overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. did. The organic layer was passed through a silica gel short column to remove impurities, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.19 g of N- (tetrahydropyran-3-ylmethyl) -5-benzyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (37)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.28-1.38 (1H, m), 1.55-1.71 (2H, m), 1.86-1.98 ( 2H, m), 3.23-3.28 (1H, m), 3.35 (2H, t), 3.41-3.47 (1H, m), 3.82-3.86 (1H, m), 3.88-3.92 (1H, m), 4.61 (2H, s), 4.65 (2H, s), 6.72 (1H, d), 6.86 (1H, brs) ), 7.30-7.40 (5H, m)

で示されるＮ−[５−エチル−５−（１，３−ジオキサニルメチル）]−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（３８）と記す。）０．２６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： ０．９１（３Ｈ，ｔ），１．２９（２Ｈ，ｑ），３．５５（２Ｈ，ｄ），３．７０（２Ｈ，ｄ），３．８４（２Ｈ，ｄ），４．６１（２Ｈ，ｓ），４．６５（２Ｈ，ｓ），４．６７（１Ｈ，ｄ），５．０１（１Ｈ，ｄ），６．７３（１Ｈ，ｓ），７．１１（１Ｈ，ｂｒ ｓ），７．３０−７．４０（５Ｈ，ｍ） Production Example 38
5-Benzyloxymethylisoxazole-3-carboxylic acid (0.24 g, 1.0 mmol), 5-ethyl-1,3-dioxan-5-ylmethylamine (0.45 g, 1.2 mmol), 1-hydroxy Benzotriazole (0.01 g, 0.1 mmol) was added to chloroform (amylene-added product) (2.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.24 g, 1.2 mmol) at room temperature, and the mixture was stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was passed through a silica gel short column to remove impurities, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- [5-ethyl-5- (1,3-dioxanylmethyl)]-5-benzyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (38)) 0.26 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.91 (3H, t), 1.29 (2H, q), 3.55 (2H, d), 3.70 (2H, d) ), 3.84 (2H, d), 4.61 (2H, s), 4.65 (2H, s), 4.67 (1H, d), 5.01 (1H, d), 6.73. (1H, s), 7.11 (1H, br s), 7.30-7.40 (5H, m)

で示されるＮ−（１，１−ジオキソテトラヒドロチオフェン−３−イルメチル）−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（３９）と記す。）０．３０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．９６−２．０４（１Ｈ，ｍ），２．３４−２．４２（１Ｈ，ｍ），２．７７−２．８９（２Ｈ，ｍ），３．０３−３．１１（１Ｈ，ｍ），３．２２−３．２９（２Ｈ，ｍ），３．５１−３．６５（２Ｈ，ｍ），４．６１（２Ｈ，ｓ），４．６６（２Ｈ，ｓ），６．７２（１Ｈ，ｄ），７．１４（１Ｈ，ｂｒ ｓ），７．３０−７．４０（５Ｈ，ｍ） Production Example 39
5-benzyloxymethylisoxazole-3-carboxylic acid (0.24 g, 1.0 mmol), 3-aminomethylthiolane-1,1-dione (0.18 g, 1.2 mmol) and 1-hydroxybenzotriazole ( 0.01 g, 0.1 mmol) was added to chloroform (amylene-added product) (2.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.24 g, 1.2 mmol) at room temperature, and the mixture was stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was passed through a silica gel short column to remove impurities, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.30 g of N- (1,1-dioxotetrahydrothiophen-3-ylmethyl) -5-benzyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (39)) represented by the formula: Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.96-2.04 (1H, m), 2.34-2.42 (1H, m), 2.77-2.89 ( 2H, m), 3.03-3.11 (1H, m), 3.22-3.29 (2H, m), 3.51-3.65 (2H, m), 4.61 (2H, s), 4.66 (2H, s), 6.72 (1H, d), 7.14 (1H, br s), 7.30-7.40 (5H, m)

で示されるＮ−（チエタン−３−イル）−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（４０）と記す。）０．２２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： ３．３９−３．４９（４Ｈ，ｍ），４．６１（２Ｈ，ｓ），４．６５（２Ｈ，ｓ），５．３６−５．４７（１Ｈ，ｍ），６．７１（１Ｈ，ｓ），７．２２（１Ｈ，ｂｒ ｓ），７．３１−７．４０（５Ｈ，ｍ） Production Example 40
Thiethan-3-ylamine hydrobromide (0.21 g, 1.2 mmol) and triethylamine (0.17 mL, 1.2 mmol) were added to chloroform (amylene-added product) (2.5 mL). To the mixture was added 5-benzyloxymethylisoxazole-3-carboxylic acid (0.24 g, 1.0 mmol), 1-hydroxybenzotriazole (0.01 g, 0.1 mmol) and 1-ethyl-3- (3- Dimethylaminopropyl) carbodiimide hydrochloride (0.24 g, 1.2 mmol) was added, and the mixture was stirred overnight at room temperature, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was passed through a silica gel short column to remove impurities, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.22 g of N- (thietan-3-yl) -5-benzyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (40)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 3.39-3.49 (4H, m), 4.61 (2H, s), 4.65 (2H, s), 5.36 -5.47 (1H, m), 6.71 (1H, s), 7.22 (1H, brs), 7.31-7.40 (5H, m)

で示されるＮ−（１−オキソチエタン−３−イル）−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（４１）と記す。）０．０６ｇ及び下式

で示されるＮ−（１，１−ジオキソチエタン−３−イル）−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（４２）と記す。）０．０３ｇを得た。
本発明化合物（４１）
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： ３．３０−３．３７（２Ｈ，ｍ），４．１３−４．１９（２Ｈ，ｍ），４．５６−４．６３（１Ｈ，ｍ），４．６１（２Ｈ，ｓ），４．６６（２Ｈ，ｓ），６．７２（１Ｈ，ｓ），７．３１−７．４０（６Ｈ，ｍ）
本発明化合物（４２）
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： ４．１３−４．１９（２Ｈ，ｍ），４．５７−４．６５（２Ｈ，ｍ），４．６２（２Ｈ，ｓ），４．６６（２Ｈ，ｓ），４．８２−４．９０（１Ｈ，ｍ），６．７２（１Ｈ，ｓ），７．３１−７．４０（５Ｈ，ｍ），７．４３（１Ｈ，ｂｒ ｓ） Production Example 41
N- (thietan-3-yl) -5-benzyloxymethylisoxazole-3-carboxamide (0.13 g, 0.43 mmol) was dissolved in chloroform (5 mL) and treated with 70% m-chloroform under ice cooling. Perbenzoic acid (0.16 g, 0.65 mmol) was added and stirred for 2 hours. A 5% aqueous sodium sulfite solution (10 mL) was added to the mixture, and the mixture was stirred for 15 minutes. The separated organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (1-oxothietan-3-yl) -5-benzyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (41)) represented by the formula:

0.03-g of N- (1,1-dioxothietan-3-yl) -5-benzyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (42)) represented by the formula (1) was obtained.
Compound (41) of the present invention
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 3.30-3.37 (2H, m), 4.13-4.19 (2H, m), 4.56-4.63 ( 1H, m), 4.61 (2H, s), 4.66 (2H, s), 6.72 (1H, s), 7.31-7.40 (6H, m)
Compound (42) of the present invention
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 4.13-4.19 (2H, m), 4.57-4.65 (2H, m), 4.62 (2H, s) 4.66 (2H, s), 4.82-4.90 (1H, m), 6.72 (1H, s), 7.31-7.40 (5H, m), 7.43 (1H , Br s)

で示されるＮ−（テトラヒドロピラン−４−イル）−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（４３）と記す。）０．１８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．５６−１．６６（２Ｈ，ｍ），１．９６−２．０１（２Ｈ，ｍ），３．４９−３．５５（２Ｈ，ｍ），３．９８−４．０２（２Ｈ，ｍ），４．１１−４．２２（１Ｈ，ｍ），４．６１（２Ｈ，ｓ），４．６６（２Ｈ，ｓ），６．７１（１Ｈ，ｂｒ ｓ），６．７３（１Ｈ，ｓ），７．３０−７．４０（５Ｈ，ｍ） Production Example 42
5-Benzyloxymethylisoxazole-3-carboxylic acid (0.24 g, 1.0 mmol), 0.1 M tetrahydropyran-4-ylamine in tetrahydrofuran (12 mL, 1.2 mmol) and 1-hydroxybenzotriazole (0. 01 g, 0.1 mmol) was added to chloroform (amylene-added product) (2.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.24 g, 1.2 mmol) at room temperature, and the mixture was stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was passed through a silica gel short column to remove impurities, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.18 g of N- (tetrahydropyran-4-yl) -5-benzyloxymethylisoxazole-3-carboxyamide (hereinafter referred to as the present compound (43)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.56-1.66 (2H, m), 1.96-2.01 (2H, m), 3.49-3.55 ( 2H, m), 3.98-4.02 (2H, m), 4.11-4.22 (1H, m), 4.61 (2H, s), 4.66 (2H, s), 6 .71 (1H, br s), 6.73 (1H, s), 7.30-7.40 (5H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−フェノキシメチルチアゾール−２−カルボキシアミド（以下、本発明化合物（４７）と記す。）０．２２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６９−１．７３（１Ｈ，ｍ），２．０５−２．１５（１Ｈ，ｍ），２．５８−２．６５（１Ｈ，ｍ），３．４５−３．５１（２Ｈ，ｍ），３．６２（１Ｈ，ｄｄ），３．７８（１Ｈ，ｄｄ），３．８６−３．９５（２Ｈ，ｍ），５．２０（２Ｈ，ｓ），６．９９−７．０１（３Ｈ，ｍ），７．３１−７．３３（２Ｈ，ｍ），７．３９（１Ｈ，ｓ），７．５８（１Ｈ，ｓ） Production Example 43
5-phenoxymethylthiazole-2-carboxylic acid (0.28 g, 1.1 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.19 g, 1.4 mmol), triethylamine (0.14 g, 1.4 mmol) and 1-Hydroxybenzotriazole (0.02 g, 0.14 mmol) was added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.27 g, 1.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.22 g of N- (tetrahydrofuran-3-ylmethyl) -5-phenoxymethylthiazole-2-carboxamide (hereinafter referred to as the present compound (47)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.69-1.73 (1H, m), 2.05-2.15 (1H, m), 2.58-2.65 ( 1H, m), 3.45-3.51 (2H, m), 3.62 (1H, dd), 3.78 (1H, dd), 3.86-3.95 (2H, m), 5 .20 (2H, s), 6.99-7.01 (3H, m), 7.31-7.33 (2H, m), 7.39 (1H, s), 7.58 (1H, s) )

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−ベンジルオキシメチルチアゾール−２−カルボキシアミド（以下、本発明化合物（４８）と記す。）０．１１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６７−１．７２（１Ｈ，ｍ），２．０５−２．１３（１Ｈ，ｍ），２．５６−２．６３（１Ｈ，ｍ），３．４６−３．４９（２Ｈ，ｍ），３．６０（１Ｈ，ｄｄ），３．７７（１Ｈ，ｄｄ），３．８５−３．９４（２Ｈ，ｍ），４．６５（２Ｈ，ｓ），４．６７（２Ｈ，ｓ），７．３３−７．３７（６Ｈ，ｍ），７．４８（１Ｈ，ｓ） Production Example 44
5-Benzyloxymethylthiazole-2-carboxylic acid (0.11 g, 0.43 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.07 g, 0.51 mmol), triethylamine (0.05 g, 0.51 mmol) And 1-hydroxybenzotriazole (0.01 g, 0.05 mmol) were added to chloroform (amylene-added product) (2 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.10 g, 0.51 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.11 g of N- (tetrahydrofuran-3-ylmethyl) -5-benzyloxymethylthiazole-2-carboxamide (hereinafter referred to as the present compound (48)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.67-1.72 (1H, m), 2.05-2.13 (1H, m), 2.56-2.63 ( 1H, m), 3.46-3.49 (2H, m), 3.60 (1H, dd), 3.77 (1H, dd), 3.85-3.94 (2H, m), 4 .65 (2H, s), 4.67 (2H, s), 7.33-7.37 (6H, m), 7.48 (1H, s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−３−ベンジルオキシメチルイソキサゾール−５−カルボキシアミド（以下、本発明化合物（４９）と記す。）０．４２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６６−１．７２（１Ｈ，ｍ），２．０５−２．１５（１Ｈ，ｍ），２．５７−２．６１（１Ｈ，ｍ），３．４８（２Ｈ，ｄｄ），３．６１（１Ｈ，ｄｄ），３．７５−３．７９（１Ｈ，ｍ），３．８５−３．８７（１Ｈ，ｍ），３．９２−３．９４（１Ｈ，ｍ），４．５８（２Ｈ，ｓ），４．６５（２Ｈ，ｓ），６．６８（１Ｈ，ｓ），６．９９（１Ｈ，ｓ），７．３４−７．３６（５Ｈ，ｍ） Production Example 45
3-Benzyloxymethylisoxazole-5-carboxylic acid (0.46 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.33 g, 2.4 mmol), triethylamine (0.25 g, 2. mmol). 4 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.24 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.42 g of N- (tetrahydrofuran-3-ylmethyl) -3-benzyloxymethylisoxazole-5-carboxyamide (hereinafter referred to as the present compound (49)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.66-1.72 (1H, m), 2.05-2.15 (1H, m), 2.57-2.61 ( 1H, m), 3.48 (2H, dd), 3.61 (1H, dd), 3.75-3.79 (1H, m), 3.85-3.87 (1H, m), 3 .92-3.94 (1H, m), 4.58 (2H, s), 4.65 (2H, s), 6.68 (1H, s), 6.99 (1H, s), 7. 34-7.36 (5H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−ベンジルオキシメチル−１H-ピラゾール−３−カルボキシアミド（以下、本発明化合物（５０）と記す。）０．５１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６６−１．７１（１Ｈ，ｍ），２．０６−２．０９（１Ｈ，ｍ），２．５６−２．６２（１Ｈ，ｍ），３．３９−３．５１（２Ｈ，ｍ），３．６２（１Ｈ，ｄｄ），３．７５−３．７７（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），４．５７（２Ｈ，ｓ），４．６３（２Ｈ，ｓ），６．７１（１Ｈ，ｓ），７．０１（１Ｈ，ｓ），７．３３−７．３８（５Ｈ，ｍ） Production Example 46
5-Benzyloxymethyl-1H-pyrazole-3-carboxylic acid (0.50 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.33 g, 2.4 mmol), triethylamine (0.24 g, 2 .4 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.24 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.51 g of N- (tetrahydrofuran-3-ylmethyl) -5-benzyloxymethyl-1H-pyrazole-3-carboxamide (hereinafter referred to as the present compound (50)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.66-1.71 (1H, m), 2.06-2.09 (1H, m), 2.56-2.62 ( 1H, m), 3.39-3.51 (2H, m), 3.62 (1H, dd), 3.75-3.77 (1H, m), 3.84-3.94 (2H, m), 4.57 (2H, s), 4.63 (2H, s), 6.71 (1H, s), 7.01 (1H, s), 7.33-7.38 (5H, m )

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−１−ブチル−１H-ピラゾール−４−カルボキシアミド（以下、本発明化合物（５１）と記す。）０．３２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９４（３Ｈ，ｔ），１．２７−１．３７（２Ｈ，ｍ），１．６５−１．７０（１Ｈ，ｍ），１．８５（２Ｈ，ｔｔ），２．０４−２．１３（１Ｈ，ｍ），２．５５−２．６１（１Ｈ，ｍ），３．４３（２Ｈ，ｔ），３．６２（１Ｈ，ｄｄ），３．７５−３．７７（１Ｈ，ｍ），３．８４（１Ｈ，ｄｄ），３．９２（１Ｈ，ｔｄ），４．１３（２Ｈ，ｔ），５．９３（１Ｈ，ｓ），７．７１（１Ｈ，ｓ），７．８５（１Ｈ，ｓ） Production Example 47
1-butyl-1H-pyrazole-4-carboxylic acid (0.34 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.35 g, 2.5 mmol), triethylamine (0.25 g, 2.5 mmol) ) And 1-hydroxybenzotriazole (0.03 g, 0.25 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.48 g, 2.5 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.32 g of N- (tetrahydrofuran-3-ylmethyl) -1-butyl-1H-pyrazole-4-carboxamide (hereinafter referred to as the present compound (51)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.94 (3H, t), 1.27-1.37 (2H, m), 1.65-1.70 (1H, m) , 1.85 (2H, tt), 2.04-2.13 (1H, m), 2.55-2.61 (1H, m), 3.43 (2H, t), 3.62 (1H) , Dd), 3.75-3.77 (1H, m), 3.84 (1H, dd), 3.92 (1H, td), 4.13 (2H, t), 5.93 (1H, s), 7.71 (1H, s), 7.85 (1H, s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−３−ベンジルオキシメチル−１−メチル−１H-ピラゾール−５−カルボキシアミド（以下、本発明化合物（５２）と記す。）０．７１g及び下式

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−ベンジルオキシメチル−１−メチル−１H-ピラゾール−３−カルボキシアミド（以下、本発明化合物（５３）と記す。）０．６１gを得た。
本発明化合物（５２）
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６６−１．６８（１Ｈ，ｍ），２．０８−２．１１（１Ｈ，ｍ），２．５６−２．５９（１Ｈ，ｍ），３．４２（２Ｈ，ｔｚ），３．６１（１Ｈ，ｄｄ），３．７３−３．７９（１Ｈ，ｍ），３．８３（１Ｈ，ｄｄ），３．９０−３．９７（１Ｈ，ｍ），４．１５（３Ｈ，ｓ），４．５４（２Ｈ，ｓ），４．５８（２Ｈ，ｓ），６．１９（１Ｈ，ｓ），６．５２（１Ｈ，ｓ），７．２８−７．３８（５Ｈ，ｍ）
本発明化合物（５３）
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６８−１．７１（１Ｈ，ｍ），２．０３−２．１２（１Ｈ，ｍ），２．５６−２．６２（１Ｈ，ｍ），３．４１−３．４７（２Ｈ，ｍ），３．５９（１Ｈ，ｄｄ），３．７７（１Ｈ，ｄｄ），３．８５−３．９３（５Ｈ，ｍ），４．５０（２Ｈ，ｓ），４．５３（２Ｈ，ｓ），６．７６（１Ｈ，ｓ），６．９７（１Ｈ，ｓ），７．３２−７．３７（５Ｈ，ｍ） Production Example 48
56:44 mixture of 3-benzyloxymethyl-1-methyl-1H-pyrazole-5-carboxylic acid and 5-benzyloxymethyl-1-methyl-1H-pyrazole-3-carboxylic acid obtained in Reference Production Example 33 ( 1.47 g, 6.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.96 g, 7.0 mmol), triethylamine (0.71 g, 7.0 mmol) and 1-hydroxybenzotriazole (0.1 g, 0 0.7 mmol) was added to chloroform (amylene-added product) (10 mL). 1-Ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.34 g, 7.0 mmol) was added to the mixture at room temperature, and the mixture was stirred overnight at room temperature. Then, it concentrated under pressure reduction. Dilute hydrochloric acid was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -3-benzyloxymethyl-1-methyl-1H-pyrazole-5-carboxamide (hereinafter referred to as the present compound (52)) represented by the formula:

0.61 g of N- (tetrahydrofuran-3-ylmethyl) -5-benzyloxymethyl-1-methyl-1H-pyrazole-3-carboxamide (hereinafter referred to as the present compound (53)) represented by the formula (1) was obtained. .
Compound (52) of the present invention
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.66 to 1.68 (1H, m), 2.08 to 2.11 (1H, m), 2.56 to 2.59 ( 1H, m), 3.42 (2H, tz), 3.61 (1H, dd), 3.73-3.79 (1H, m), 3.83 (1H, dd), 3.90-3 .97 (1H, m), 4.15 (3H, s), 4.54 (2H, s), 4.58 (2H, s), 6.19 (1H, s), 6.52 (1H, s), 7.28-7.38 (5H, m)
The present compound (53)
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.68-1.71 (1H, m), 2.03-2.12 (1H, m), 2.56-2.62 ( 1H, m), 3.41-3.47 (2H, m), 3.59 (1H, dd), 3.77 (1H, dd), 3.85-3.93 (5H, m), 4 .50 (2H, s), 4.53 (2H, s), 6.76 (1H, s), 6.97 (1H, s), 7.32-7.37 (5H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−１−ブチル−１Ｈ−１，２，３−トリアゾール−４−カルボキシアミド（以下、本発明化合物（５４）と記す。）０．６３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： ０．９６（３Ｈ， ｔ），１．３０−１．３９（２Ｈ，ｍ），１．６５−１．７４（１Ｈ，ｍ）， １．９２−１．９９（２Ｈ，ｍ），２．０５−２．１３（１Ｈ，ｍ），２．５４−２．６３（１Ｈ，ｍ），３．４１−３．５２（２Ｈ，ｍ），３．５９−３．６３（１Ｈ，ｍ），３．７４−３．８０（１Ｈ，ｍ），３．８５−３．９５（２Ｈ，ｍ），４．４３（２Ｈ， ｔ），６．８５（１Ｈ， ｂｒ ｓ），８．０３（１Ｈ，ｓ） Production Example 49
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.54 g, 3.96 mmol) and triethylamine (0.40 g, 3.96 mmol) were added to chloroform (amylene-added product) (13 mL). To the mixture was added 1-butyl-1H-1,2,3-triazole-4-carboxylic acid (0.56 g, 3.30 mmol), 1-hydroxybenzotriazole (0.05 g, 0.33 mmol) and 1- Ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.76 g, 3.96 mmol) was added and stirred for 3 hours, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.63 g of N- (tetrahydrofuran-3-ylmethyl) -1-butyl-1H-1,2,3-triazole-4-carboxyamide (hereinafter referred to as the present compound (54)) represented by the formula .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.96 (3H, t), 1.30-1.39 (2H, m), 1.65-1.74 (1H, m) 1.92-1.99 (2H, m), 2.05-2.13 (1H, m), 2.54-2.63 (1H, m), 3.41-3.52 (2H, m), 3.59-3.63 (1H, m), 3.74-3.80 (1H, m), 3.85-3.95 (2H, m), 4.43 (2H, t) 6.85 (1H, br s), 8.03 (1H, s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−２−ブチル−２Ｈ−１，２，３−トリアゾール−４−カルボキシアミド（以下、本発明化合物（５５）と記す。）０．１１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： ０．９７（３Ｈ， ｔ），１．３１−１．４１（２Ｈ，ｍ），１．６５−１．７４（１Ｈ，ｍ）， １．８７−１．９５（２Ｈ，ｍ），２．０５−２．１３（１Ｈ，ｍ），２．５４−２．６４（１Ｈ，ｍ），３．４６−３．５０（２Ｈ，ｍ），３．５８−３．６１（１Ｈ，ｍ），３．７４−３．８０（１Ｈ，ｍ），３．８６−３．９４（２Ｈ，ｍ），４．４０（２Ｈ， ｔ），７．２８（１Ｈ， ｂｒ ｓ），８．０４（１Ｈ，ｓ） Production Example 50
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.20 g, 1.20 mmol) and triethylamine (0.12 g, 1.20 mmol) were added to chloroform (amylene-added product) (4 mL). To the mixture was added 2-butyl-2H-1,2,3-triazole-4-carboxylic acid (0.17 g, 1.00 mmol), 1-hydroxybenzotriazole (0.01 g, 0.10 mmol) and 1- Ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.23 g, 1.20 mmol) was added and stirred for 3 hours, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, and the filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.11 g of N- (tetrahydrofuran-3-ylmethyl) -2-butyl-2H-1,2,3-triazole-4-carboxyamide (hereinafter referred to as the present compound (55)) represented by the formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.97 (3H, t), 1.31-1.41 (2H, m), 1.65-1.74 (1H, m) , 1.87-1.95 (2H, m), 2.05-2.13 (1H, m), 2.54-2.64 (1H, m), 3.46-3.50 (2H, m), 3.58-3.61 (1H, m), 3.74-3.80 (1H, m), 3.86-3.94 (2H, m), 4.40 (2H, t) , 7.28 (1H, br s), 8.04 (1H, s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−２−ブチル−２Ｈ−テトラゾール−５−カルボキシアミド（以下、本発明化合物（５６）と記す。）０．５１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： ０．９７（３Ｈ， ｔ），１．３２−１．４１（２Ｈ，ｍ），１．６６−１．７５（１Ｈ，ｍ）， ２．０１−２．１３（３Ｈ，ｍ），２．５８−２．６８（１Ｈ，ｍ），３．５３−３．５６（２Ｈ，ｍ），３．６１−３．６４（１Ｈ，ｍ），３．７５−３．８０（１Ｈ，ｍ），３．８５−３．９６（２Ｈ，ｍ），４．６９（２Ｈ， ｔ），７．３１（１Ｈ，ｂｒ ｓ） Production Example 51
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.38 g, 2.75 mmol) and triethylamine (0.28 g, 2.75 mmol) were added to chloroform (amylene-added product) (8 mL). To the mixture was added 2-butyl-2H-tetrazole-5-carboxylic acid (0.39 g, 2.29 mmol), 1-hydroxybenzotriazole (0.03 g, 0.23 mmol) and 1-ethyl-3- (3 at room temperature. -Dimethylaminopropyl) carbodiimide hydrochloride (0.53 g, 2.75 mmol) was added, stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

In this way, 0.51 g of N- (tetrahydrofuran-3-ylmethyl) -2-butyl-2H-tetrazole-5-carboxamide (hereinafter referred to as the present compound (56)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.97 (3H, t), 1.32-1.41 (2H, m), 1.66-1.75 (1H, m) , 2.01-2.13 (3H, m), 2.58-2.68 (1H, m), 3.53-3.56 (2H, m), 3.61-3.64 (1H, m), 3.75-3.80 (1H, m), 3.85-3.96 (2H, m), 4.69 (2H, t), 7.31 (1H, br s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−ブチル−１，２，４−オキサジアゾール−３−カルボキシアミド（以下、本発明化合物（５７）と記す。）０．７６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９６（３Ｈ，ｔ），１．３８−１．４９（２Ｈ，ｍ），１．６２−１．７３（１Ｈ，ｍ），１．８０−１．８７（２Ｈ，ｍ），２．０５−２．１５（１Ｈ，ｍ），２．５５−２．６７（１Ｈ，ｍ），２．９５（２Ｈ，ｔ），３．４５−３．５５（２Ｈ，ｍ），３．６１（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８５（１Ｈ，ｄｄ），３．９２（１Ｈ，ｔｄ），７．１０（１Ｈ，ｂｒｓ） Production Example 52
5-butyl-1,2,4-oxadiazole-3-carboxylic acid (1.36 g, 8 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (1.65 g, 12 mmol), triethylamine (1.21 g, 12 mmol) ) And 1-hydroxybenzotriazole (0.11 g, 0.8 mmol) were added to chloroform (amylene-added product) (16 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.83 g, 12 mmol) at room temperature, and the mixture was stirred overnight, water was added, and the mixture was extracted 3 times with chloroform. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.76 g of N- (tetrahydrofuran-3-ylmethyl) -5-butyl-1,2,4-oxadiazole-3-carboxamide (hereinafter referred to as the present compound (57)) represented by the formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.96 (3H, t), 1.38-1.49 (2H, m), 1.62-1.73 (1H, m) , 1.80-1.87 (2H, m), 2.05-2.15 (1H, m), 2.55-2.67 (1H, m), 2.95 (2H, t), 3 .45-3.55 (2H, m), 3.61 (1H, dd), 3.73-3.80 (1H, m), 3.85 (1H, dd), 3.92 (1H, td ), 7.10 (1H, brs)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−３−ブチル−１，２，４−オキサジアゾール−５−カルボキシアミド（以下、本発明化合物（５８）と記す。）０．４３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９６（３Ｈ，ｔ），１．３６−１．４６（２Ｈ，ｍ），１．６４−１．７９（３Ｈ，ｍ），２．０７−２．１６（１Ｈ，ｍ），２．５８−２．６５（１Ｈ，ｍ），２．７９（２Ｈ，ｔ），３．４５−３．５５（２Ｈ，ｍ），３．６２（１Ｈ，ｄｄ），３．７４−３．８１（１Ｈ，ｍ），３．８５（１Ｈ，ｄｄ），３．９３（１Ｈ，ｔｄ），７．１９（１Ｈ，ｂｒｓ） Production Example 53
Ethyl 3-butyl-1,2,4-oxadiazole-5-carboxylate (0.40 g, 2 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (2.75 g, 20 mmol) and diisopropylethylamine (2.58 g) , 20 mmol) was added to ethanol (40 mL) and stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, water was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.43 g of N- (tetrahydrofuran-3-ylmethyl) -3-butyl-1,2,4-oxadiazole-5-carboxyamide (hereinafter referred to as the present compound (58)) represented by the formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.96 (3H, t), 1.36 to 1.46 (2H, m), 1.64 to 1.79 (3H, m) 2.07-2.16 (1H, m), 2.58-2.65 (1H, m), 2.79 (2H, t), 3.45-3.55 (2H, m), 3 .62 (1H, dd), 3.74-3.81 (1H, m), 3.85 (1H, dd), 3.93 (1H, td), 7.19 (1H, brs)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−２−ブチルオキサゾール−５−カルボキシアミド（以下、本発明化合物（５９）と記す。）０．１３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９５（３Ｈ，ｔ），１．３６−１．４５（２Ｈ，ｍ），１．６３−１．８０（３Ｈ，ｍ），２．０３−２．１３（１Ｈ，ｍ），２．５０−２．６３（１Ｈ，ｍ），２．７６（２Ｈ，ｔ），３．３７−３．５０（２Ｈ，ｍ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），７．０２（１Ｈ，ｂｒｓ），８．０８（１Ｈ，ｓ） Production Example 54
2-Butyloxazole-5-carboxylic acid (0.10 g, 0.6 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.12 g, 0.9 mmol), triethylamine (0.09 g, 0.9 mmol) and 1 -Hydroxybenzotriazole (0.01 g, 0.1 mmol) was added to chloroform (amylene-added product) (1.2 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.14 g, 0.7 mmol) at room temperature, and after stirring overnight, water was added and extracted three times with ethyl acetate. . The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.13 g of N- (tetrahydrofuran-3-ylmethyl) -2-butyloxazole-5-carboxyamide (hereinafter referred to as the present compound (59)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.95 (3H, t), 1.36 to 1.45 (2H, m), 1.63-1.80 (3H, m) , 2.03-2.13 (1H, m), 2.50-2.63 (1H, m), 2.76 (2H, t), 3.37-3.50 (2H, m), 3 .59 (1H, dd), 3.73-3.80 (1H, m), 3.84-3.94 (2H, m), 7.02 (1H, brs), 8.08 (1H, s) )

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−ブチルオキサゾール−２−カルボキシアミド（以下、本発明化合物（６０）と記す。）０．３９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９４（３Ｈ，ｔ），１．３３−１．４４（２Ｈ，ｍ），１．６３−１．７３（３Ｈ，ｍ），２．０４−２．１３（１Ｈ，ｍ），２．５２−２．６３（１Ｈ，ｍ），２．７３（２Ｈ，ｔ），３．４０−３．５１（２Ｈ，ｍ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８３−３．９５（２Ｈ，ｍ），６．８３（１Ｈ，ｂｒｓ），７．１２（１Ｈ，ｓ） Production Example 55
Ethyl 5-butyloxazole-2-carboxylate (0.39 g, 2 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (2.75 g, 20 mmol) and diisopropylethylamine (2.58 g, 20 mmol) in ethanol (40 mL). In addition, the mixture was stirred for 10 hours under reflux with heating, and then concentrated under reduced pressure. Water was added to the residue and extracted three times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.39 g of N- (tetrahydrofuran-3-ylmethyl) -5-butyloxazole-2-carboxyamide (hereinafter referred to as the present compound (60)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.94 (3H, t), 1.33-1.44 (2H, m), 1.63-1.73 (3H, m) , 2.04-2.13 (1H, m), 2.52-2.63 (1H, m), 2.73 (2H, t), 3.40-3.51 (2H, m), 3 .59 (1H, dd), 3.73-3.80 (1H, m), 3.83-3.95 (2H, m), 6.83 (1H, brs), 7.12 (1H, s) )

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−ベンジルイソチアゾール−３−カルボキシアミド（以下、本発明化合物（６１）と記す。）０．１２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：７．５７（１Ｈ，ｔ),７．３９−７．２１（６Ｈ，ｍ)，４．２４（２Ｈ，ｓ），３．９０（１Ｈ，ｔｄ），３．８６（１Ｈ，ｄｄ），３．７６（１Ｈ，ｄｄ），３．５９（１Ｈ，ｄｄ），３．４４(２Ｈ，ｔｄ)，２．６０−２．５４（１Ｈ，ｍ），２．１２−２．０３（１Ｈ，ｍ），１．７４−１．６０（１Ｈ，ｍ） Production Example 56
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.13 g, 0.93 mmol) was dissolved in 1 mL of chloroform (amylene-added product), triethylamine (0.13 mL, 0.93 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. To the mixture, 2.0 ml of a chloroform (amylene-added product) solution of 5-benzylisothiazole-3-carboxylic acid (0.17 g, 0.77 mmol) at room temperature, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide Hydrochloric acid salt (0.23 g, 0.93 mmol) and 1-hydroxybenzotriazole (0.01 g, 0.08 mmol) were added and stirred overnight, then 2 ml of 1N hydrochloric acid was added and extracted with chloroform. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to obtain the following formula:

0.12 g of N- (tetrahydrofuran-3-ylmethyl) -5-benzylisothiazole-3-carboxamide (hereinafter referred to as the present compound (61)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.57 (1H, t), 7.39-7.21 (6H, m), 4.24 (2H, s), 3.90 ( 1H, td), 3.86 (1H, dd), 3.76 (1H, dd), 3.59 (1H, dd), 3.44 (2H, td), 2.60-2.54 (1H , M), 2.12-2.03 (1H, m), 1.74-1.60 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−ブチルイソチアゾール−３−カルボキシアミド（以下、本発明化合物（６２）と記す。）０．０３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：７．５８−７．５６（１Ｈ，ｍ），７．４７−７．３２（１Ｈ，ｍ），３．９６−３．８５（２Ｈ，ｍ），３．７７（１Ｈ，ｄｄ），３．６０（１Ｈ，ｄｄ），３．４５（２Ｈ，ｔｄ)，２．９３（２Ｈ，ｔ），２．６４−２．５３（１Ｈ，ｍ)，２．１３−２．０４(１Ｈ，ｍ)，１．７０（３Ｈ，ｔｔ），１．４１（２Ｈ，ｔｄ），０．９５（３Ｈ，ｔ） Production Example 57
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.07 g, 0.48 mmol) was dissolved in 0.8 mL of chloroform (amylene-added product), triethylamine (0.07 mL, 0.48 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. did. To the mixture was added 1.2 ml of a solution of 5-butylisothiazole-3-carboxylic acid (0.08 g, 0.40 mmol) in chloroform (amylene-added product) at room temperature, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide. Hydrochloric acid salt (0.09 g, 0.48 mmol) and 1-hydroxybenzotriazole (0.005 g, 0.04 mmol) were added, and the mixture was stirred at room temperature overnight, followed by addition of 2 ml of 1N hydrochloric acid and extraction with chloroform. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to obtain the following formula:

0.03 g of N- (tetrahydrofuran-3-ylmethyl) -5-butylisothiazole-3-carboxamide (hereinafter referred to as the present compound (62)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.58-7.56 (1H, m), 7.47-7.32 (1H, m), 3.96-3.85 (2H M), 3.77 (1H, dd), 3.60 (1H, dd), 3.45 (2H, td), 2.93 (2H, t), 2.64-2.53 (1H, m), 2.13-2.04 (1H, m), 1.70 (3H, tt), 1.41 (2H, td), 0.95 (3H, t)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（４−トリフルオロメチルベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（６３）と記す。）０．４０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６５−１．７０（１Ｈ，ｍ），２．０５−２．１３（１Ｈ，ｍ），２．５５−２．６１（１Ｈ，ｍ），３．４７（２Ｈ，ｄｄ），３．６０（１Ｈ，ｄｄ），３．７７（１Ｈ，ｄｄ，），３．８６（１Ｈ，ｄｄ），３．９１−３．９３（１Ｈ，ｍ），４．６７（２Ｈ，ｓ），４．６９（２Ｈ，ｓ），６．７５（１Ｈ，ｓ），６．９４（１Ｈ，ｓ），７．４７（２Ｈ，ｄ），７．６３（２Ｈ，ｄ） Production Example 58
5-[(4-trifluoromethylbenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.60 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.33 g, 2.4 mmol), triethylamine (0.25 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.24 mmol) were added to 5 mL of chloroform (amylene-added product). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.40 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(4-trifluoromethylbenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (63)) represented by the formula: Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.65-1.70 (1H, m), 2.05-2.13 (1H, m), 2.55-2.61 ( 1H, m), 3.47 (2H, dd), 3.60 (1H, dd), 3.77 (1H, dd,), 3.86 (1H, dd), 3.91-3.93 ( 1H, m), 4.67 (2H, s), 4.69 (2H, s), 6.75 (1H, s), 6.94 (1H, s), 7.47 (2H, d), 7.63 (2H, d)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（３−トリフルオロメチルベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（６４）と記す。）０．２０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６４−１．７２（１Ｈ，ｍ），２．０８−２．１１（１Ｈ，ｍ），２．５５−２．６３（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７７（１Ｈ，ｄｄ），３．８４−３．９５（２Ｈ，ｍ），４．６６（２Ｈ，ｓ），４．７０（２Ｈ，ｓ），６．７５（１Ｈ，ｓ），６．９５（１Ｈ，ｓ），７．５０−７．５８（４Ｈ，ｍ） Production Example 59
5-[(3-trifluoromethylbenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.60 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.33 g, 2.4 mmol), triethylamine (0.25 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.24 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.20 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(3-trifluoromethylbenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (64)) represented by the formula: Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.72 (1H, m), 2.08-2.11 (1H, m), 2.55-2.63 ( 1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.77 (1H, dd), 3.84-3.95 (2H, m), 4.66 (2H) , S), 4.70 (2H, s), 6.75 (1H, s), 6.95 (1H, s), 7.50-7.58 (4H, m).

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（３−トリフルオロメチルベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（６５）と記す。）０．２１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３５−１．４１（２Ｈ，ｍ），１．６６−１．６８（２Ｈ，ｍ），１．８４−１．８８（１Ｈ，ｍ），３．３４−３．４２（４Ｈ，ｍ），３．９９（２Ｈ，ｄｄ），４．６６（２Ｈ，ｓ），４．７０（２Ｈ，ｓ），６．７５（１Ｈ，ｓ），６．８９（１Ｈ，ｓ），７．５０−７．５８（４Ｈ，ｍ） Production Example 60
5-[(3-trifluoromethylbenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.30 g, 1.0 mmol), tetrahydropyran-4-ylmethylamine (0.14 g, 1.2 mmol) and 1- Hydroxybenzotriazole (0.02 g, 0.12 mmol) was added to chloroform (amylene-added product) (2 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.23 g, 1.2 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydropyran-4-ylmethyl) -5-[(3-trifluoromethylbenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (65)) 0.21 g Got.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.35 to 1.41 (2H, m), 1.66 to 1.68 (2H, m), 1.84 to 1.88 ( 1H, m), 3.34-3.42 (4H, m), 3.99 (2H, dd), 4.66 (2H, s), 4.70 (2H, s), 6.75 (1H) , S), 6.89 (1H, s), 7.50-7.58 (4H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（２−クロロベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（６６）と記す。）３０５ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７０−１．６２（１Ｈ，ｍ），２．１１−２．０６（１Ｈ，ｍ），２．５８（１Ｈ，ｔ），３．４６（２Ｈ，ｔ），３．６０−３．５７（１Ｈ，ｍ），３．７９−３．７３（１Ｈ，ｍ），３．９４−３．８３（２Ｈ，ｍ），４．７２（４Ｈ，ｄ），６．７６（１Ｈ，ｓ），６．９４（ＮＨ，ｓ），７．３０−７．２７（２Ｈ，ｍ），７．３７（１Ｈ，ｄ），７．４７（１Ｈ，ｄ） Production Example 61
5-[(2-Chlorobenzyl) oxymethyl] isoxazole-3-carboxylic acid (500 mg, 1.87 mmol) and tetrahydrofuran-3-ylmethylamine (208 mg, 2.05 mmol) were added to dehydrated tetrahydrofuran (20 ml). The mixture was cooled to 0 ° C., hexafluorophosphoric acid (benzotriazol-1-yloxy) tripyrrolidinophosphonium (1.46 g, 2.80 mmol) was added, and the mixture was stirred at 0 ° C. for 16 hours. In addition, the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

305 mg of N- (tetrahydrofuran-3-ylmethyl) -5-[(2-chlorobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (66)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.70-1.62 (1H, m), 2.11-2.06 (1H, m), 2.58 (1H, t) 3.46 (2H, t), 3.60-3.57 (1H, m), 3.79-3.73 (1H, m), 3.94-3.83 (2H, m), 4 .72 (4H, d), 6.76 (1H, s), 6.94 (NH, s), 7.30-7.27 (2H, m), 7.37 (1H, d), 7. 47 (1H, d)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（２−クロロベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（６７）と記す。）３２０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４３−１．３２（２Ｈ，ｍ），１．６７（２Ｈ，ｄ），１．８９−１．８３（１Ｈ，ｍ），３．４１−３．３３（４Ｈ，Ｍ），３．９９（２Ｈ，ｄ），４．７２（４Ｈ，ｄ），６．７６（１Ｈ，ｓ），６．８９（ＮＨ，ｓ），７．３０−７．２３（２Ｈ，ｍ），７．３７（１Ｈ，ｄ），７．４７（１Ｈ，ｄ） Production Example 62
5-[(2-Chlorobenzyl) oxymethyl] isoxazole-3-carboxylic acid (500 mg, 1.87 mmol) and tetrahydropyran-4-ylmethylamine (237 mg, 2.05 mmol) were added to dehydrated tetrahydrofuran (20 ml). . The mixture was cooled to 0 ° C., hexafluorophosphoric acid (benzotriazol-1-yloxy) tripyrrolidinophosphonium (1.46 g, 2.80 mmol) was added, and the mixture was stirred at 0 ° C. for 16 hours. In addition, the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 320 mg of N- (tetrahydropyran-4-ylmethyl) -5-[(2-chlorobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (67)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.43-1.32 (2H, m), 1.67 (2H, d), 1.89-1.83 (1H, m) 3.41-3.33 (4H, M), 3.99 (2H, d), 4.72 (4H, d), 6.76 (1H, s), 6.89 (NH, s), 7.30-7.23 (2H, m), 7.37 (1H, d), 7.47 (1H, d)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（２−クロロベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（６８）と記す。）３５０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７０−１．６５（１Ｈ，ｍ），２．１１−２．０６（１Ｈ，ｍ），２．５９−２．５６（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．６１−３．５８（１Ｈ，ｍ），３．７９−３．７５（１Ｈ，ｍ），３．９４−３．８３（２Ｈ，ｍ），４．５８（２Ｈ，ｓ），４．６６（２Ｈ，ｓ），６．７３（１Ｈ，ｓ），６．９３（１Ｈ，ｂｒ．ｓ），７．２３−７．２０（１Ｈ，ｍ），７．２９（２Ｈ，ｄ），７．３４（１Ｈ，ｓ） Production Example 63
5-[(3-Chlorobenzyl) oxymethyl] isoxazole-3-carboxylic acid (500 mg, 1.87 mmol) and tetrahydrofuran-3-ylmethylamine (208 mg, 2.05 mmol) were added to dehydrated tetrahydrofuran (20 ml). The mixture was cooled to 0 ° C., hexafluorophosphoric acid (benzotriazol-1-yloxy) tripyrrolidinophosphonium (1.46 g, 2.80 mmol) was added, and the mixture was stirred at 0 ° C. for 16 hours. In addition, the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

350 mg of N- (tetrahydrofuran-3-ylmethyl) -5-[(2-chlorobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (68)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.70-1.65 (1H, m), 2.11-1.06 (1H, m), 2.59-2.56 ( 1H, m), 3.47 (2H, t), 3.61-3.58 (1H, m), 3.79-3.75 (1H, m), 3.94-3.83 (2H, m), 4.58 (2H, s), 4.66 (2H, s), 6.73 (1H, s), 6.93 (1H, br. s), 7.23-7.20 (1H) M), 7.29 (2H, d), 7.34 (1H, s)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（３−クロロベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（６９）と記す。）４００ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４７−１．３６（２Ｈ，ｍ），１．６８−１．５７（２Ｈ，ｍ），１．８６（１Ｈ，ｓ），３．４０−３．３５（４Ｈ，ｍ），３．９８（２Ｈ，ｄ），４．５７（２Ｈ，ｓ），４．６５（２Ｈ，ｓ），６．７３（１Ｈ，ｓ），６．８８（１Ｈ，ｓ），７．２１（１Ｈ，ｓ），７．３４−７．２９（３Ｈ，ｄ） Production Example 64
5-[(3-Chlorobenzyl) oxymethyl] isoxazole-3-carboxylic acid (500 mg, 1.87 mmol) and tetrahydropyran-4-ylmethylamine (237 mg, 2.05 mmol) were added to dehydrated tetrahydrofuran (20 ml). . The mixture was cooled to 0 ° C., hexafluorophosphoric acid (benzotriazol-1-yloxy) tripyrrolidinophosphonium (1.46 g, 2.80 mmol) was added, and the mixture was stirred at 0 ° C. for 16 hours. Extracted twice with ethyl. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 400 mg of N- (tetrahydropyran-4-ylmethyl) -5-[(3-chlorobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (69)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.47-1.36 (2H, m), 1.68-1.57 (2H, m), 1.86 (1H, s) 3.40-3.35 (4H, m), 3.98 (2H, d), 4.57 (2H, s), 4.65 (2H, s), 6.73 (1H, s), 6.88 (1H, s), 7.21 (1H, s), 7.34-7.29 (3H, d)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（４−クロロベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（７０）と記す。）０．４０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６８（１Ｈ，ｍ），２．０８（１Ｈ，ｍ），２．５７（１Ｈ，ｍ），３．４６（２Ｈ，ｔ），３．５９（１Ｈ，ｑ），３．８０（１Ｈ，ｑ），３．９４−３．８３（２Ｈ，ｍ），４．５６（２Ｈ，ｓ），４．６４（２Ｈ，ｓ），６．７３（１Ｈ，ｓ），６．９２（１Ｈ，ｓ），７．２７（２Ｈ，ｄ），７．３４（２Ｈ，ｄ） Production Example 65
5-[(4-Chlorobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 1.8 mmol) was added to chloroform (amylene-added product) (15 mL) and cooled to 0 ° C. Triethylamine (0.39 ml, 2.2 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.49 g, 2.2 mmol) and 1-hydroxybenzotriazole (0.30 g, 2.2 mmol) ) Was added and stirred for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.21 g, 2.1 mmol) was added to the mixture, stirred at room temperature for 12 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.40 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(4-chlorobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (70)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.68 (1H, m), 2.08 (1H, m), 2.57 (1H, m), 3.46 (2H, t ), 3.59 (1H, q), 3.80 (1H, q), 3.94-3.83 (2H, m), 4.56 (2H, s), 4.64 (2H, s) , 6.73 (1H, s), 6.92 (1H, s), 7.27 (2H, d), 7.34 (2H, d)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（４−クロロベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（７１）と記す。）０．２３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．３６（２Ｈ，ｑ），１．６６（２Ｈ，ｄ），１．８４（１Ｈ，ｍ），３．３７（４Ｈ，ｍ），３．９８（２Ｈ，ｄ），４．５６（２Ｈ，ｓ），４．６３（２Ｈ，ｓ），６．７２（１Ｈ，ｓ），６．８７（１Ｈ，Ｂｒｓ），７．２７（２Ｈ，ｄ），７．３６（２Ｈ，ｄ） Production Example 66
5-[(4-Chlorobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 1.8 mmol) was added to chloroform (amylene-added product) (15 mL) and cooled to 0 ° C. Triethylamine (0.39 ml, 2.2 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.49 g, 2.2 mmol) and 1-hydroxybenzotriazole (0.30 g, 2.2 mmol) ) Was added and stirred for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.21 g, 2.1 mmol) was added to the mixture, and the mixture was stirred at room temperature for 12 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.23 g of N- (tetrahydropyran-4-ylmethyl) -5-[(4-chlorobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (71)) represented by the formula: It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.36 (2H, q), 1.66 (2H, d), 1.84 (1H, m), 3.37 (4H, m ), 3.98 (2H, d), 4.56 (2H, s), 4.63 (2H, s), 6.72 (1H, s), 6.87 (1H, Brs), 7.27. (2H, d), 7.36 (2H, d)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（３，４−ジクロロベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（７２）と記す。）０．３０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７０−１．６５（１Ｈ，ｍ），２．１１−２．０６（１Ｈ，ｍ），２．５９−２．５６（１Ｈ，ｍ），３．４８−３．４５（２Ｈ，ｍ），３．７３−３．５７（１Ｈ，ｍ），３．７９−３．７５（１Ｈ，ｍ），３．９３−３．８３（２Ｈ，ｍ），４．５５（２Ｈ，ｓ），４．６６（２Ｈ，ｓ），６．７３（１Ｈ，ｓ），６．９２（１Ｈ，ｓ），７．１９−７．１６（１Ｈ，ｍ），７．４３（２Ｈ，ｄ） Production Example 67
5-[(3,4-dichlorobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 1.6 mmol) was added to chloroform (amylene-added product) (12 mL) and cooled to 0 ° C. Triethylamine (0.38 ml, 2.0 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.38 g, 2.0 mmol) and 1-hydroxybenzotriazole (0.27 g, 1.8 mmol) ) Was added and stirred for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.18 g, 1.8 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.30 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(3,4-dichlorobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (72)) represented by the formula: Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.70-1.65 (1H, m), 2.11-1.06 (1H, m), 2.59-2.56 ( 1H, m), 3.48-3.45 (2H, m), 3.73-3.57 (1H, m), 3.79-3.75 (1H, m), 3.93-3. 83 (2H, m), 4.55 (2H, s), 4.66 (2H, s), 6.73 (1H, s), 6.92 (1H, s), 7.19-7.16. (1H, m), 7.43 (2H, d)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（３，４−ジクロロベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（７３）と記す。）０．３４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．４３−１．３３（２Ｈ，ｍ），１．６７（２Ｈ，ｄ），１．８９−１．８３（１Ｈ，ｍ），３．４１−３．３３（４Ｈ，ｍ），４．５５（２Ｈ，ｓ），４．６６（２Ｈ，ｓ），６．７３（１Ｈ，ｓ），６．８７（１Ｈ，ｓ），７．１８−７．１６（１Ｈ，ｍ），７．４３（２Ｈ，ｄ） Production Example 68
5-[(3,4-dichlorobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 1.6 mmol) was added to chloroform (amylene-added product) (12 mL) and cooled to 0 ° C. Triethylamine (0.34 ml, 2.5 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.38 g, 2.0 mmol) and 1-hydroxybenzotriazole (0.27 g, 2.0 mmol) ) Was added and stirred for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.21 g, 2.1 mmol) was added to the mixture, and the mixture was stirred at room temperature for 12 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydropyran-4-ylmethyl) -5-[(3,4-dichlorobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (73)) 0.34 g Got.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.43-1.33 (2H, m), 1.67 (2H, d), 1.89-1.83 (1H, m) 3.41-3.33 (4H, m), 4.55 (2H, s), 4.66 (2H, s), 6.73 (1H, s), 6.87 (1H, s), 7.18-7.16 (1H, m), 7.43 (2H, d)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（３−フルオロベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（７４）と記す。）０．３１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７０−１．６５（１Ｈ，ｍ），２．１１−２．０６（１Ｈ，ｍ），２．５９−２．５６（１Ｈ，ｍ），３．４８−３．４５（２Ｈ，ｍ），３．６０−３．５７（１Ｈ，ｍ），３．７９−３．７３（１Ｈ，ｍ），３．９４−３．８３（２Ｈ，ｍ），４．５９（２Ｈ，ｓ），４．６６（２Ｈ，ｓ），６．７３（１Ｈ，ｓ），６．９３（１Ｈ，ｓ），７．１１−６．９８（３Ｈ，ｍ），７．３５−７．３０（１Ｈ，ｍ） Production Example 69
5-[(3-Fluorobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 2.0 mmol) was added to chloroform (amylene-added product) (12 mL) and cooled to 0 ° C. Triethylamine (0.40 ml, 3.0 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.32 g, 2.4 mmol) ) Was added and stirred for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.22 g, 2.2 mmol) was added to the mixture, stirred at room temperature for 12 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.31 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(3-fluorobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (74)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.70-1.65 (1H, m), 2.11-1.06 (1H, m), 2.59-2.56 ( 1H, m), 3.48-3.45 (2H, m), 3.60-3.57 (1H, m), 3.79-3.73 (1H, m), 3.94-3. 83 (2H, m), 4.59 (2H, s), 4.66 (2H, s), 6.73 (1H, s), 6.93 (1H, s), 7.11-6.98 (3H, m), 7.35-7.30 (1H, m)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（３−フルオロベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（７５）と記す。）０．３５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．４３−１．３２（２Ｈ，ｍ），１．６８−１．６５（２Ｈ，ｍ），１．８９−１．８２（１Ｈ，ｍ），３．４１−３．３３（４Ｈ，ｍ），４．００−３．９７（２Ｈ，ｍ），４．５９（２Ｈ，ｓ），４．６６（２Ｈ，ｓ），６．７３（１Ｈ，ｓ），６．８７（１Ｈ，ｓ），７．１１−６．９８（３Ｈ，ｍ），７．３５−７．３０（１Ｈ，ｍ） Production Example 70
5-[(3-Fluorobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 2.0 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., and triethylamine (0. 40 ml, 3.0 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.32 g, 2.4 mmol) were added, Stir for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.25 g, 2.2 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.35 g of N- (tetrahydropyran-4-ylmethyl) -5-[(3-fluorobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (75)) represented by It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.43-1.32 (2H, m), 1.68-1.65 (2H, m), 1.89-1.82 ( 1H, m), 3.41-3.33 (4H, m), 4.00-3.97 (2H, m), 4.59 (2H, s), 4.66 (2H, s), 6 .73 (1H, s), 6.87 (1H, s), 7.11-6.98 (3H, m), 7.35-7.30 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（３−ブロモベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（７６）と記す。）０．３１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６８（１Ｈ，ｍ），２．０８（１Ｈ，ｍ），２．５７（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｔ），３．７７（１Ｈ，ｑ），３．８５（２Ｈ，ｍ），４．５７（２Ｈ，ｓ），４．６６（２Ｈ，ｓ），６．７３（１Ｈ，ｓ），６．９３（１Ｈ，ｓ），７．２３（２Ｈ，ｍ），７．４４（１Ｈ，ｍ），７．５０（１Ｈ，ｓ） Production Example 71
5-[(3-Bromobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 1.6 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., and triethylamine (0. 33 ml, 2.4 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.37 g, 1.9 mmol) and 1-hydroxybenzotriazole (0.26 g, 1.9 mmol) were added, Stir for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.16 g, 1.6 mmol) was added to the mixture, and the mixture was stirred at room temperature for 12 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.31 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(3-bromobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (76)) represented by the formula: .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.68 (1H, m), 2.08 (1H, m), 2.57 (1H, m), 3.47 (2H, t ), 3.59 (1H, t), 3.77 (1H, q), 3.85 (2H, m), 4.57 (2H, s), 4.66 (2H, s), 6.73. (1H, s), 6.93 (1H, s), 7.23 (2H, m), 7.44 (1H, m), 7.50 (1H, s)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（３−ブロモベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（７７）と記す。）０．２６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．４０（２Ｈ，ｑ），１．６７（２Ｈ，ｄ），１．８５（１Ｈ，ｍ），３．３８（４Ｈ，ｍ），３．９８（２Ｈ，ｓ），４．５７（２Ｈ，ｓ），４．６５（２Ｈ，ｓ），６．７２（１Ｈ，ｓ），６．８７（１Ｈ，ｂｒ．ｓ），７．２１−７．２６（２Ｈ，ｍ），７．４５（１Ｈ，ｄ），７．５１（１Ｈ，ｓ） Production Example 72
5-[(3-Bromobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 2.0 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., and triethylamine (0. 40 ml, 3.0 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.32 g, 2.4 mmol) were added, Stir for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.25 g, 2.2 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.26 g of N- (tetrahydropyran-4-ylmethyl) -5-[(3-bromobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (77)) represented by It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.40 (2H, q), 1.67 (2H, d), 1.85 (1H, m), 3.38 (4H, m ), 3.98 (2H, s), 4.57 (2H, s), 4.65 (2H, s), 6.72 (1H, s), 6.87 (1H, br.s), 7 .21-7.26 (2H, m), 7.45 (1H, d), 7.51 (1H, s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（３−トリフルオロメトキシベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（７８）と記す。）０．３０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６４−１．７３（ｍ，１Ｈ），２．０８（ｍ，１Ｈ），２．５７（ｍ，１Ｈ），３．４７（ｔ，２Ｈ），３．５８（ｍ，１Ｈ），３．９５−３．７５（ｍ，２Ｈ），４．１６（ｓ，２Ｈ），４．６７（ｓ，２Ｈ），６．７３（ｓ，１Ｈ），６．９３（ｓ，１Ｈ），６．７２（ｓ，１Ｈ），７．１８（ｍ，２Ｈ），７．２８（ｄ，１Ｈ），７．３９（ｔ，１Ｈ） Production Example 73
5-[(3-trifluoromethoxybenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.70 g, 2.2 mmol) was added to chloroform (amylene-added product) (15 mL), cooled to 0 ° C., triethylamine ( 0.61 ml, 4.4 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.51 g, 2.6 mmol) and 1-hydroxybenzotriazole (0.36 g, 2.6 mmol). Added and stirred for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.24 g, 2.4 mmol) was added to the mixture, stirred at room temperature for 12 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.30 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(3-trifluoromethoxybenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (78)) represented by the formula: Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.73 (m, 1H), 2.08 (m, 1H), 2.57 (m, 1H), 3.47 (T, 2H), 3.58 (m, 1H), 3.95-3.75 (m, 2H), 4.16 (s, 2H), 4.67 (s, 2H), 6.73 ( s, 1H), 6.93 (s, 1H), 6.72 (s, 1H), 7.18 (m, 2H), 7.28 (d, 1H), 7.39 (t, 1H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（３−トリフルオロメトキシベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（７９）と記す。）０．３５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３９（ｑ，２Ｈ），１．６６（ｄ，２Ｈ），１．８６（ｍ，１Ｈ），３．３４−３．３３（ｍ，４Ｈ），３．９８（ｄｄ，２Ｈ），４．６１（ｓ，２Ｈ），４．６７（ｓ，２Ｈ），６．７３（ｓ，１Ｈ），６．８８（ｂｒｓ，１Ｈ），７．１８（ｍ，２Ｈ），７．２６（ｄ，１Ｈ），７．３９（ｔ，１Ｈ） Production Example 74
5-[(3-trifluoromethoxybenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 1.6 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., and triethylamine ( 0.44 ml, 3.2 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.36 g, 1.9 mmol) and 1-hydroxybenzotriazole (0.26 g, 1.9 mmol). Added and stirred for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.20 g, 1.7 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydropyran-4-ylmethyl) -5-[(3-trifluoromethoxybenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (79)) 0.35 g Got.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.39 (q, 2H), 1.66 (d, 2H), 1.86 (m, 1H), 3.34 to 3.33 (M, 4H), 3.98 (dd, 2H), 4.61 (s, 2H), 4.67 (s, 2H), 6.73 (s, 1H), 6.88 (brs, 1H) 7.18 (m, 2H), 7.26 (d, 1H), 7.39 (t, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（３−トリフルオロメチルチオベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（８０）と記す。）０．１５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７０−１．６５（ｍ，１Ｈ），２．１１−２．０６（ｍ，１Ｈ），２．５９−２．５６（ｍ，１Ｈ），３．４７（ｔ，２Ｈ），３．６１−３．５７（ｍ，１Ｈ），３．７９−３．７３（ｍ，１Ｈ），３．９２−３．８３（ｍ，２Ｈ），４．６３（ｓ，２Ｈ），４．６８（ｓ，２Ｈ），６．７３（ｓ，１Ｈ），６．９３（ｓ，１Ｈ），７．４８−７．４１（ｍ，２Ｈ），７．６３−７．６０（ｍ，２Ｈ） Production Example 75
5-[(3-trifluoromethylthiobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.30 g, 0.9 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., and triethylamine ( 0.18 ml, 1.4 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.26 g, 1.4 mmol) and 1-hydroxybenzotriazole (0.18 g, 1.4 mmol). Added and stirred for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.10 g, 1.0 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5-[(3-trifluoromethylthiobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (80)) represented by the formula: Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.70-1.65 (m, 1H), 2.11-1.06 (m, 1H), 2.59-2.56 ( m, 1H), 3.47 (t, 2H), 3.61-3.57 (m, 1H), 3.79-3.73 (m, 1H), 3.92-3.83 (m, 2H), 4.63 (s, 2H), 4.68 (s, 2H), 6.73 (s, 1H), 6.93 (s, 1H), 7.48-7.41 (m, 2H) ), 7.63-7.60 (m, 2H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（３−トリフルオロメチルチオベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（８１）と記す。）０．２３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４２−１．３６（ｍ，２Ｈ），１．６８−１．６５（ｍ，２Ｈ），１．８７−１．８４（ｍ，１Ｈ），３．４１−３．３３（ｍ，４Ｈ），４．００−３．９７（ｍ，２Ｈ），４．６２（ｓ，２Ｈ），４．６８（ｓ，２Ｈ），６．７３（ｓ，１Ｈ），６．８７（ｓ，１Ｈ），７．４８−７．４１（ｍ，２Ｈ），７．６３−７．６０（ｍ，２Ｈ） Production Example 76
5-[(3-trifluoromethylthiobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.30 g, 0.9 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., and triethylamine ( 0.18 ml, 1.4 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.26 g, 1.4 mmol) and 1-hydroxybenzotriazole (0.18 g, 1.4 mmol). Added and stirred for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.11 g, 1.0 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydropyran-4-ylmethyl) -5-[(3-trifluoromethylthiobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (81)) 0.23 g Got.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42-1.36 (m, 2H), 1.68-1.65 (m, 2H), 1.87-1.84 ( m, 1H), 3.41-3.33 (m, 4H), 4.00-3.97 (m, 2H), 4.62 (s, 2H), 4.68 (s, 2H), 6 .73 (s, 1H), 6.87 (s, 1H), 7.48-7.41 (m, 2H), 7.63-7.60 (m, 2H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（３−メチルベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（８２）と記す。）０．１５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７１−１．６３（１Ｈ，ｍ），２．１２−２．０５（１Ｈ，ｍ），２．３６（３Ｈ，ｓ），２．６０−２．５４（１Ｈ，ｍ），３．４６（２Ｈ，ｔ），３．６０−３．５７（１Ｈ，ｍ），３．７９−３．７３（１Ｈ，ｍ），３．９３−３．８５（２Ｈ，ｍ），４．５６（２Ｈ，ｓ），４．６３（２Ｈ，ｓ），６．７２（１Ｈ，ｓ），６．９５（１Ｈ，ｓ），７．１６−７．１２（３Ｈ，ｍ），７．２７−７．２３（１Ｈ，ｍ） Production Example 77
5-[(3-Methylbenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 2.0 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., and triethylamine (0. 40 ml, 3.0 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.58 g, 3.0 mmol) and 1-hydroxybenzotriazole (0.41 g, 3.0 mmol) were added, Stir for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.22 g, 2.2 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.15 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(3-methylbenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (82)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.71-1.63 (1H, m), 2.12 to 2.05 (1H, m), 2.36 (3H, s) , 2.60-2.54 (1H, m), 3.46 (2H, t), 3.60-3.57 (1H, m), 3.79-3.73 (1H, m), 3 .93-3.85 (2H, m), 4.56 (2H, s), 4.63 (2H, s), 6.72 (1H, s), 6.95 (1H, s), 7. 16-7.12 (3H, m), 7.27-7.23 (1H, m)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（３−メチルベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（８３）と記す。）０．３０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４３−１．３２（２Ｈ，ｍ），１．６５−１．５７（２Ｈ，ｍ），１．８８−１．８３（１Ｈ，ｍ），２．３６（３Ｈ，ｓ），３．４１−３．３３（４Ｈ，ｍ），４．００−３．９６（２Ｈ，ｍ），４．５６（２Ｈ，ｓ），４．６４（２Ｈ，ｓ），６．７２（１Ｈ，ｓ），６．８７（１Ｈ，ｓ），７．１６−７．１２（３Ｈ，ｍ），７．２７−７．２３（１Ｈ，ｍ） Production Example 78
5-[(3-Methylbenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 2.0 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., and triethylamine (0. 40 ml, 3.0 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.58 g, 3.0 mmol) and 1-hydroxybenzotriazole (0.41 g, 3.0 mmol) were added, Stir for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.26 g, 2.2 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.30 g of N- (tetrahydropyran-4-ylmethyl) -5-[(3-methylbenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (83)) represented by the formula: It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.43-1.32 (2H, m), 1.65-1.57 (2H, m), 1.88-1.83 ( 1H, m), 2.36 (3H, s), 3.41-3.33 (4H, m), 4.00-3.96 (2H, m), 4.56 (2H, s), 4 .64 (2H, s), 6.72 (1H, s), 6.87 (1H, s), 7.16-7.12 (3H, m), 7.27-7.23 (1H, m )

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（３−メトキシベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（８４）と記す。）０．３１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７０−１．６３（１Ｈ，ｍ），２．１０−２．０６（１Ｈ，ｍ），２．５９−２．５６（１Ｈ，ｍ），３．４６（２Ｈ，ｔ），３．６０−３．５７（１Ｈ，ｍ），３．９４−３．７３（６Ｈ，ｍ），４．５８（２Ｈ，ｓ），４．６４（２Ｈ，ｓ），６．７２（１Ｈ，ｓ），６．９４−６．８５（４Ｈ，ｍ），７．２９（１Ｈ，ｄ） Production Example 79
5-[(3-methoxybenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 1.9 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., triethylamine (0. 40 ml, 3.0 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.54 g, 2.9 mmol) and 1-hydroxybenzotriazole (0.38 g, 2.9 mmol) were added, Stir for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.21 g, 2.1 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.31 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(3-methoxybenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (84)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.70-1.63 (1H, m), 2.10-2.06 (1H, m), 2.59-2.56 ( 1H, m), 3.46 (2H, t), 3.60-3.57 (1H, m), 3.94-3.73 (6H, m), 4.58 (2H, s), 4 .64 (2H, s), 6.72 (1H, s), 6.94-6.85 (4H, m), 7.29 (1H, d)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（３−メトキシベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（８５）と記す。）０．３２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４３−１．３２（２Ｈ，ｍ），１．６８（２Ｈ，ｄ），１．８８−１．８３（１Ｈ，ｍ），３．４１−３．３３（４Ｈ，ｍ），３．８１（３Ｈ，ｓ），４．００−３．９６（２Ｈ，ｍ），４．５８（２Ｈ，ｓ），４．６４（２Ｈ，ｓ），６．７２（１Ｈ，ｓ），６．９２−６．８５（４Ｈ，ｍ），７．２９（１Ｈ，ｄ） Production Example 80
5-[(3-methoxybenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 1.9 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., triethylamine (0. 40 ml, 3.0 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.54 g, 2.9 mmol) and 1-hydroxybenzotriazole (0.38 g, 2.9 mmol) were added, Stir for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.26 g, 2.2 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.32 g of N- (tetrahydropyran-4-ylmethyl) -5-[(3-methoxybenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (85)) represented by It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.43-1.32 (2H, m), 1.68 (2H, d), 1.88-1.83 (1H, m) 3.41-3.33 (4H, m), 3.81 (3H, s), 4.00-3.96 (2H, m), 4.58 (2H, s), 4.64 (2H) , S), 6.72 (1H, s), 6.92-6.85 (4H, m), 7.29 (1H, d)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（３−シアノベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（８６）と記す。）０．３１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７０−１．６７（ｍ，１Ｈ），２．１１−２．０６（ｍ，１Ｈ），２．５９−２．５６（ｍ，１Ｈ），３．４７（ｔ，２Ｈ），３．６１−３．５７（ｍ，１Ｈ），３．７９−３．７５（ｍ，１Ｈ），３．９４−３．８３（ｍ，２Ｈ），４．６３（ｓ，２Ｈ），４．７０（ｓ，２Ｈ），６．７４（ｓ，１Ｈ），６．９３（ｓ，１Ｈ），７．５０−７．４６（ｍ，１Ｈ），７．６４−７．５７（ｍ，３Ｈ） Production Example 81
5-[(3-Cyanobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 1.9 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., and triethylamine (0. 40 ml, 3.0 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.54 g, 2.9 mmol) and 1-hydroxybenzotriazole (0.38 g, 2.9 mmol) were added, Stir for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.21 g, 2.1 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.31 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(3-cyanobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (86)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.70-1.67 (m, 1H), 2.11-1.06 (m, 1H), 2.59-2.56 ( m, 1H), 3.47 (t, 2H), 3.61-3.57 (m, 1H), 3.79-3.75 (m, 1H), 3.94-3.83 (m, 2H), 4.63 (s, 2H), 4.70 (s, 2H), 6.74 (s, 1H), 6.93 (s, 1H), 7.50-7.46 (m, 1H) ), 7.64-7.57 (m, 3H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（３−シアノベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（８７）と記す。）０．４０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４３−１．３３（ｍ，２Ｈ），１．６９−１．６５（ｍ，２Ｈ），１．８７−１．８４（ｍ，１Ｈ），３．４１−３．３４（ｍ，４Ｈ），４．０１−３．９７（ｍ，２Ｈ），４．６３（ｓ，２Ｈ），４．７０（ｓ，２Ｈ），６．７４（ｓ，１Ｈ），６．８８（ｓ，１Ｈ），７．５０−７．４６（ｍ，１Ｈ），７．６４−７．５７（ｍ，３Ｈ） Production Example 82
5-[(3-Cyanobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 1.9 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., and triethylamine (0. 40 ml, 3.0 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.54 g, 2.9 mmol) and 1-hydroxybenzotriazole (0.38 g, 2.9 mmol) were added, Stir for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.26 g, 2.2 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.40 g of N- (tetrahydropyran-4-ylmethyl) -5-[(3-cyanobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (87)) represented by the formula: It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.43-1.33 (m, 2H), 1.69-1.65 (m, 2H), 1.87-1.84 ( m, 1H), 3.41-3.34 (m, 4H), 4.01-3.97 (m, 2H), 4.63 (s, 2H), 4.70 (s, 2H), 6 .74 (s, 1H), 6.88 (s, 1H), 7.50-7.46 (m, 1H), 7.64-7.57 (m, 3H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（３−メチルチオベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（８８）と記す。）０．０５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６９（ｍ，１Ｈ），２．０９（ｑ，１Ｈ），２．４９（ｓ，３Ｈ），２．６１−２．５４（ｍ，１Ｈ），３．４８−３．４２（ｍ，２Ｈ），３．６０−３．５３（ｍ，１Ｈ），３．７９−３．７３（ｍ，１Ｈ），３．９５−３．８３（ｍ，２Ｈ），４．５７（ｓ，２Ｈ），４．６１（ｓ，２Ｈ），６．７２（ｓ，１Ｈ），６．９４（ｂｒｓ，１Ｈ），７．１１（ｄ，１Ｈ），７．２３−７．１９（ｍ，２Ｈ），７．３０（ｍ，１Ｈ） Production Example 83
5-[(3-Methylthiobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.35 g, 1.3 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., and triethylamine (0. 26 ml, 1.9 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.36 g, 1.9 mmol) and 1-hydroxybenzotriazole (0.25 g, 1.9 mmol) were added, Stir for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.14 g, 1.4 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.05 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(3-methylthiobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (88)) represented by the formula: .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.69 (m, 1H), 2.09 (q, 1H), 2.49 (s, 3H), 2.61-2.54 (M, 1H), 3.48-3.42 (m, 2H), 3.60-3.53 (m, 1H), 3.79-3.73 (m, 1H), 3.95-3 .83 (m, 2H), 4.57 (s, 2H), 4.61 (s, 2H), 6.72 (s, 1H), 6.94 (brs, 1H), 7.11 (d, 1H), 7.23-7.19 (m, 2H), 7.30 (m, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（４−フルオロベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（８９）と記す。）０．３１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６９−１．６５（ｍ，１Ｈ），２．１１−２．０６（ｍ，１Ｈ），２．５９−２．５６（ｍ，１Ｈ），３．４６（ｔ，２Ｈ），３．６０−３．５７（ｍ，１Ｈ），３．７９−３．７５（ｍ，１Ｈ），３．９４−３．８３（ｍ，２Ｈ），４．５６（ｓ，２Ｈ），４．６４（ｓ，２Ｈ），６．７２（ｓ，１Ｈ），６．９２（ｓ，１Ｈ），７．０７−７．０３（ｍ，２Ｈ），７．３３−７．３１（ｍ，２Ｈ） Production Example 84
5-[(4-Fluorobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.60 g, 2.4 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., and triethylamine (0. 50 ml, 3.6 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.68 g, 3.6 mmol) and 1-hydroxybenzotriazole (0.48 g, 3.6 mmol) were added, Stir for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.36 g, 3.6 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.31 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(4-fluorobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (89)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.69-1.65 (m, 1H), 2.11-1.06 (m, 1H), 2.59-2.56 ( m, 1H), 3.46 (t, 2H), 3.60-3.57 (m, 1H), 3.79-3.75 (m, 1H), 3.94-3.83 (m, 2H), 4.56 (s, 2H), 4.64 (s, 2H), 6.72 (s, 1H), 6.92 (s, 1H), 7.07-7.03 (m, 2H) ), 7.33-7.31 (m, 2H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（４−フルオロベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（９０）と記す。）０．３９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４３−１．３２（ｍ，２Ｈ），１．６８−１．６４（ｍ，２Ｈ），１．８９−１．８２（ｍ，１Ｈ），３．４１−３．３３（ｍ，４Ｈ），４．００−３．９７（ｍ，２Ｈ），４．５６（ｓ，２Ｈ），４．６４（ｓ，２Ｈ），６．７２（ｓ，１Ｈ），６．８８（ｓ，１Ｈ），７．０７−７．０３（ｍ，２Ｈ），７．３３−７．３０（ｍ，２Ｈ） Production Example 85
5-[(4-Fluorobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.60 g, 2.4 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., and triethylamine (0. 50 ml, 3.6 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.68 g, 3.6 mmol) and 1-hydroxybenzotriazole (0.48 g, 3.6 mmol) were added, Stir for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.30 g, 2.6 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.39 g of N- (tetrahydropyran-4-ylmethyl) -5-[(4-fluorobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (90)) represented by the formula: It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.43-1.32 (m, 2H), 1.68-1.64 (m, 2H), 1.89-1.82 ( m, 1H), 3.41-3.33 (m, 4H), 4.00-3.97 (m, 2H), 4.56 (s, 2H), 4.64 (s, 2H), 6 .72 (s, 1H), 6.88 (s, 1H), 7.07-7.03 (m, 2H), 7.33-7.30 (m, 2H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（４−ブロモベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（９１）と記す。）０．５０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７１−１．６３（ｍ，１Ｈ），２．１３−２．０４（ｍ，１Ｈ），２．６１−２．５４（ｍ，１Ｈ），３．４８−３．４５（ｔ，２Ｈ），３．６０−３．５７（ｍ，１Ｈ），３．７９−３．７３（ｍ，１Ｈ），３．９４−３．８３（ｍ，２Ｈ），４．５５（ｓ，１Ｈ），４．６４（ｓ，２Ｈ），６．７２（ｓ，１Ｈ），６．９４（ｂｒ，ｓ，１Ｈ），７．２２−７．２０（ｄ，２Ｈ），７．２６（ｓ，１Ｈ），７．５０−７．４８（ｄ，２Ｈ） Production Example 86
5-[(4-Bromobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.60 g, 1.9 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., and triethylamine (0. 54 ml, 3.8 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.44 g, 2.3 mmol) and 1-hydroxybenzotriazole (0.31 g, 2.3 mmol) were added, Stir for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.21 g, 2.1 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.50 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(4-bromobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (91)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.71-1.63 (m, 1H), 2.13-2.04 (m, 1H), 2.61-2.54 ( m, 1H), 3.48-3.45 (t, 2H), 3.60-3.57 (m, 1H), 3.79-3.73 (m, 1H), 3.94-3. 83 (m, 2H), 4.55 (s, 1H), 4.64 (s, 2H), 6.72 (s, 1H), 6.94 (br, s, 1H), 7.22-7 .20 (d, 2H), 7.26 (s, 1H), 7.50-7.48 (d, 2H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（４−ブロモベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（９２）と記す。）０．４０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４３−１．３２（ｍ，２Ｈ），１．６８−１．５９（ｍ，２Ｈ），１．８９−１．８３（ｍ，１Ｈ），３．４１−３．３４（ｍ，４Ｈ），４．００−３．９６（ｄｄ，２Ｈ），４．５５（ｓ，１Ｈ），４．６４（ｓ，２Ｈ），６．７２（ｓ，１Ｈ），６．８８（ｂｒｓ，１Ｈ），７．２３−７．２１（ｄ，２Ｈ），７．２６（ｓ，１Ｈ），７．５０−７．４８（ｄ，２Ｈ） Production Example 87
5-[(4-Bromobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.60 g, 1.9 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., and triethylamine (0. 54 ml, 3.8 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.44 g, 2.3 mmol) and 1-hydroxybenzotriazole (0.31 g, 2.3 mmol) were added, Stir for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.24 g, 2.1 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.40 g of N- (tetrahydropyran-4-ylmethyl) -5-[(4-bromobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (92)) represented by the formula: It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.43-1.32 (m, 2H), 1.68-1.59 (m, 2H), 1.89-1.83 ( m, 1H), 3.41-3.34 (m, 4H), 4.00-3.96 (dd, 2H), 4.55 (s, 1H), 4.64 (s, 2H), 6 72 (s, 1H), 6.88 (brs, 1H), 7.23-7.21 (d, 2H), 7.26 (s, 1H), 7.50-7.48 (d, 2H) )

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（４−トリフルオロメトキシベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（９３）と記す。）０．１７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７０−１．６５（ｍ，１Ｈ），２．１１−２．０６（ｍ，１Ｈ），２．５９−２．５６（ｍ，１Ｈ），３．４６（ｔ，２Ｈ），３．６０−３．５７（ｍ，１Ｈ），３．７９−３．７３（ｍ，１Ｈ），３．９４−３．８３（ｍ，２Ｈ），４．６０（ｓ，２Ｈ），４．６６（ｓ，２Ｈ），６．７３（ｓ，１Ｈ），６．９３（ｓ，１Ｈ），７．２１（ｄ，２Ｈ），７．３７（ｄ，２Ｈ） Production Example 88
5-[(4-trifluoromethoxybenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.30 g, 0.9 mmol) was added to chloroform (amylene-added product) (10 mL), cooled to 0 ° C., and triethylamine ( 0.20 ml, 1.4 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.27 g, 1.4 mmol) and 1-hydroxybenzotriazole (0.19 g, 1.4 mmol). Added and stirred for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.11 g, 1.1 mmol) was added to the mixture, and the mixture was stirred at room temperature for 16 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.17 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(4-trifluoromethoxybenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (93)) represented by the formula: Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.70-1.65 (m, 1H), 2.11-1.06 (m, 1H), 2.59-2.56 ( m, 1H), 3.46 (t, 2H), 3.60-3.57 (m, 1H), 3.79-3.73 (m, 1H), 3.94-3.83 (m, 2H), 4.60 (s, 2H), 4.66 (s, 2H), 6.73 (s, 1H), 6.93 (s, 1H), 7.21 (d, 2H), 7. 37 (d, 2H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（４−トリフルオロメトキシベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（９４）と記す。）０．１９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４２−１．３４（ｍ，２Ｈ），１．６８−１．６５（ｍ，２Ｈ），１．８７−１．８４（ｍ，１Ｈ），３．４１−３．３３（ｍ，４Ｈ），４．００−３．９７（ｍ，２Ｈ），４．６０（ｓ，２Ｈ），４．６６（ｓ，２Ｈ），６．７３（ｓ，１Ｈ），６．８７（ｓ，１Ｈ），７．２１（ｄ，２Ｈ），７．３７（ｄ，２Ｈ） Production Example 89
5-[(4-trifluoromethoxybenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.30 g, 0.9 mmol) was added to chloroform (amylene-added product) (10 mL), cooled to 0 ° C., and triethylamine ( 0.20 ml, 1.4 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.27 g, 1.4 mmol) and 1-hydroxybenzotriazole (0.19 g, 1.4 mmol). Added and stirred for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.12 g, 1.0 mmol) was added to the mixture, and the mixture was stirred at room temperature for 16 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydropyran-4-ylmethyl) -5-[(4-trifluoromethoxybenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (94)) 0.19 g Got.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42-1.34 (m, 2H), 1.68-1.65 (m, 2H), 1.87-1.84 ( m, 1H), 3.41-3.33 (m, 4H), 4.00-3.97 (m, 2H), 4.60 (s, 2H), 4.66 (s, 2H), 6 .73 (s, 1H), 6.87 (s, 1H), 7.21 (d, 2H), 7.37 (d, 2H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（４−トリフルオロメチルチオベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（９５）と記す。）０．１１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７０−１．６５（ｍ，１Ｈ），２．１１−２．０６（ｍ，１Ｈ），２．５９−２．５６（ｍ，１Ｈ），３．４７（ｔ，２Ｈ），３．６０−３．５７（ｍ，１Ｈ），３．７９−３．７３（ｍ，１Ｈ），３．９４−３．８３（ｍ，２Ｈ），４．６４（ｓ，２Ｈ），４．６９（ｓ，２Ｈ），６．７４（ｓ，１Ｈ），６．９２（ｓ，１Ｈ），７．４０（ｄ，２Ｈ），７．６５（ｄ，２Ｈ） Production Example 90
5-[(4-trifluoromethylthiobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 1.5 mmol) was added to chloroform (amylene-added product) (10 mL), cooled to 0 ° C., and triethylamine ( 0.30 ml, 2.3 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.43 g, 2.3 mmol) and 1-hydroxybenzotriazole (0.30 g, 2.3 mmol). Added and stirred for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.17 g, 1.7 mmol) was added to the mixture, and the mixture was stirred at room temperature for 16 hr. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.11 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(4-trifluoromethylthiobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (95)) represented by the formula: Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.70-1.65 (m, 1H), 2.11-1.06 (m, 1H), 2.59-2.56 ( m, 1H), 3.47 (t, 2H), 3.60-3.57 (m, 1H), 3.79-3.73 (m, 1H), 3.94-3.83 (m, 2H), 4.64 (s, 2H), 4.69 (s, 2H), 6.74 (s, 1H), 6.92 (s, 1H), 7.40 (d, 2H), 7. 65 (d, 2H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（４−トリフルオロメチルチオベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（９６）と記す。）０．１２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４２−１．３４（ｍ，２Ｈ），１．６５−１．６０（ｍ，２Ｈ），１．８７−１．８４（ｍ，１Ｈ），３．４１−３．３３（ｍ，４Ｈ），４．００−３．９６（ｍ，２Ｈ），４．６４（ｓ，２Ｈ），４．６９（ｓ，２Ｈ），６．７４（ｓ，１Ｈ），６．９２（ｓ，１Ｈ），７．４０（ｄ，２Ｈ），７．６５（ｄ，２Ｈ） Production Example 91
5-[(4-trifluoromethylthiobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 1.5 mmol) was added to chloroform (amylene-added product) (10 mL), cooled to 0 ° C., and triethylamine ( 0.30 ml, 2.3 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.43 g, 2.3 mmol) and 1-hydroxybenzotriazole (0.30 g, 2.3 mmol). Added and stirred for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.19 g, 1.7 mmol) was added to the mixture, and the mixture was stirred at room temperature for 16 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydropyran-4-ylmethyl) -5-[(4-trifluoromethylthiobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (96)) 0.12 g Got.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42-1.34 (m, 2H), 1.65-1.60 (m, 2H), 1.87-1.84 ( m, 1H), 3.41-3.33 (m, 4H), 4.00-3.96 (m, 2H), 4.64 (s, 2H), 4.69 (s, 2H), 6 .74 (s, 1H), 6.92 (s, 1H), 7.40 (d, 2H), 7.65 (d, 2H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（４−メチルベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（９７）と記す。）０．４４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６６（ｍ，１Ｈ），２．０８（ｍ，１Ｈ），２．３５（ｓ，３Ｈ），２．５７（ｍ，１Ｈ），３．４６（ｔ，２Ｈ），３．５９（ｍ，１Ｈ），３．８５（ｍ，３Ｈ），４．５６（ｓ，２Ｈ），４．６１（ｓ，２Ｈ），６．７１（ｓ，１Ｈ），６．９５（ｂｒｓ，１Ｈ），７．１７（ｄ，２Ｈ），７．２５（ｄ，２Ｈ） Production Example 92
5-[(4-Methylbenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.70 g, 2.8 mmol) was added to chloroform (amylene-added product) (20 mL), cooled to 0 ° C., and triethylamine (0. 79 ml, 5.7 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.65 g, 3.4 mmol) and 1-hydroxybenzotriazole (0.46 g, 3.4 mmol) were added, Stir for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.31 g, 3.1 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.44 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(4-methylbenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (97)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.66 (m, 1H), 2.08 (m, 1H), 2.35 (s, 3H), 2.57 (m, 1H) ), 3.46 (t, 2H), 3.59 (m, 1H), 3.85 (m, 3H), 4.56 (s, 2H), 4.61 (s, 2H), 6.71 (S, 1H), 6.95 (brs, 1H), 7.17 (d, 2H), 7.25 (d, 2H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（４−メチルベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（９８）と記す。）０．４５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３８（ｑ，２Ｈ），１．６６（ｄ，２Ｈ），１．８６（ｍ，１Ｈ），２．３５（ｓ，３Ｈ），３．３６（ｑ，４Ｈ），３．９８（ｄｄ，２Ｈ），４．５６（ｓ，２Ｈ），４．６１（ｓ，２Ｈ），６．７０（ｓ，１Ｈ），６．８１（ｂｒｓ，１Ｈ），７．１６（ｄ，２Ｈ），７．２４（ｄ，２Ｈ） Production Example 93
5-[(4-Methylbenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.70 g, 2.8 mmol) was added to chloroform (amylene-added product) (20 mL), cooled to 0 ° C., and triethylamine (0. 79 ml, 5.7 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.65 g, 3.4 mmol) and 1-hydroxybenzotriazole (0.46 g, 3.4 mmol) were added, Stir for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.49 g, 4.2 mmol) was added to the mixture, and the mixture was stirred at room temperature for 16 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.45 g of N- (tetrahydropyran-4-ylmethyl) -5-[(4-methylbenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (98)) represented by the formula: It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.38 (q, 2H), 1.66 (d, 2H), 1.86 (m, 1H), 2.35 (s, 3H ), 3.36 (q, 4H), 3.98 (dd, 2H), 4.56 (s, 2H), 4.61 (s, 2H), 6.70 (s, 1H), 6.81 (Brs, 1H), 7.16 (d, 2H), 7.24 (d, 2H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（４−メトキシベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（９９）と記す。）０．３０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７５−１．６（ｍ，１Ｈ），２．１５−２．０（ｍ，１Ｈ），２．６（ｔ，１Ｈ），３．４５（ｔ，２Ｈ），３．４（ｄｄ，１Ｈ），４．０−３．７（ｍ，６Ｈ），４．５（ｓ，２Ｈ），４．６５（ｓ，２Ｈ），６．７（ｓ，１Ｈ），６．９（ｄ，３Ｈ），７．３０（ｄ，２Ｈ） Production Example 94
5-[(4-Methoxybenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 1.9 mmol) was added to chloroform (amylene-added product) (15 mL), cooled to 0 ° C., and triethylamine (0. 40 ml, 2.8 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.44 g, 2.3 mmol) and 1-hydroxybenzotriazole (0.31 g, 2.3 mmol) were added, Stir for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.31 g, 3.1 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.30 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(4-methoxybenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (99)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.75-1.6 (m, 1H), 2.15-2.0 (m, 1H), 2.6 (t, 1H) , 3.45 (t, 2H), 3.4 (dd, 1H), 4.0-3.7 (m, 6H), 4.5 (s, 2H), 4.65 (s, 2H), 6.7 (s, 1H), 6.9 (d, 3H), 7.30 (d, 2H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（４−メトキシベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１００）と記す。）０．３１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４５−１．３（ｑ，２Ｈ），１．６５（ｄ，２Ｈ），１．９５−１．８（ｍ，１Ｈ），３．４５−３．３０（ｔ，４Ｈ），３．８（ｓ，３Ｈ），４．０（ｄｄ，２Ｈ），４．５（ｓ，２Ｈ），４．６５（ｓ，２Ｈ），６．７（ｓ，１Ｈ），６．９（ｄ，３Ｈ），７．３０（ｄ，２Ｈ） Production Example 95
5-[(4-Methoxybenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 1.9 mmol) was added to chloroform (amylene-added product) (15 mL), cooled to 0 ° C., and triethylamine (0. 40 ml, 2.8 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.44 g, 2.3 mmol) and 1-hydroxybenzotriazole (0.31 g, 2.3 mmol) were added, Stir for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.49 g, 4.2 mmol) was added to the mixture, and the mixture was stirred at room temperature for 16 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.31 g of N- (tetrahydropyran-4-ylmethyl) -5-[(4-methoxybenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (100)) represented by It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.45-1.3 (q, 2H), 1.65 (d, 2H), 1.95-1.8 (m, 1H) 3.45-3.30 (t, 4H), 3.8 (s, 3H), 4.0 (dd, 2H), 4.5 (s, 2H), 4.65 (s, 2H), 6.7 (s, 1H), 6.9 (d, 3H), 7.30 (d, 2H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（４−シアノベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１０１）と記す。）０．３５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７２−１．６３（ｍ，１Ｈ），２．１３−２．０４（ｍ，１Ｈ），２．５８（ｔ，１Ｈ），３．４７（ｔ，２Ｈ），３．６０（ｑ，１Ｈ），３．７５（ｑ，１Ｈ），３．９４−３．８３（ｍ，２Ｈ），４．６８（ｄ，４Ｈ），６．７５（ｓ，１Ｈ），６．９３（ｂｒｓ，１Ｈ），７．４５（ｄ，２Ｈ），７．６６（ｄ，２Ｈ） Production Example 96
5-[(4-Cyanobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.60 g, 2.3 mmol) was added to chloroform (amylene-added product) (15 mL), cooled to 0 ° C., and triethylamine (0. 48 ml, 3.5 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.58 g, 3.1 mmol) and 1-hydroxybenzotriazole (0.41 g, 3.1 mmol) were added, Stir for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.26 g, 2.6 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.35 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(4-cyanobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (101)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.72-1.63 (m, 1H), 2.13-2.04 (m, 1H), 2.58 (t, 1H) 3.47 (t, 2H), 3.60 (q, 1H), 3.75 (q, 1H), 3.94-3.83 (m, 2H), 4.68 (d, 4H), 6.75 (s, 1H), 6.93 (brs, 1H), 7.45 (d, 2H), 7.66 (d, 2H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（４−シアノベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１０２）と記す。）０．４５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４３−１．３３（ｄｄ，２Ｈ），１．６６（ｄｄ，２Ｈ），１．８８−１．８４（ｍ，１Ｈ），３．４１−３．３４（ｍ，４Ｈ），３．９９（ｄｄ，２Ｈ），４．６５（ｓ，２Ｈ），４．７（ｓ，２Ｈ），６．７４（ｓ，１Ｈ），６．８７（ｂｒｓ，１Ｈ），７．４５（ｄ，２Ｈ），７．６６（ｄ，２Ｈ） Production Example 97
5-[(4-Cyanobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.60 g, 2.3 mmol) was added to chloroform (amylene-added product) (15 mL), cooled to 0 ° C., and triethylamine (0. 48 ml, 3.5 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.58 g, 3.1 mmol) and 1-hydroxybenzotriazole (0.41 g, 3.1 mmol) were added, Stir for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.29 g, 2.6 mmol) was added to the mixture, and the mixture was stirred at room temperature for 16 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.45 g of N- (tetrahydropyran-4-ylmethyl) -5-[(4-cyanobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (102)) represented by the formula: It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.43-1.33 (dd, 2H), 1.66 (dd, 2H), 1.88-1.84 (m, 1H) 3.41-3.34 (m, 4H), 3.99 (dd, 2H), 4.65 (s, 2H), 4.7 (s, 2H), 6.74 (s, 1H), 6.87 (brs, 1H), 7.45 (d, 2H), 7.66 (d, 2H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（４−メチルチオベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１０３）と記す。）０．１１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６１−１．５６（ｍ，１Ｈ），１．９５−１．８９（ｍ，１Ｈ），２．４９−２．４６（ｍ，４Ｈ），３．２２（ｔ，２Ｈ），３．４６−３．４２（ｍ，１Ｈ），３．７３−３．５９（ｍ，３Ｈ），４．５２（ｓ，２Ｈ），４．６８（ｓ，２Ｈ），６．８１（ｓ，１Ｈ），７．３０−７．２３（ｍ，４Ｈ），８．９０（ｔ，１Ｈ） Production Example 98
5-[(4-Methylthiobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 1.8 mmol) was added to chloroform (amylene-added product) (15 mL), cooled to 0 ° C., and triethylamine (0. 50 ml, 2.7 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.51 g, 2.1 mmol) and 1-hydroxybenzotriazole (0.36 g, 2.7 mmol) are added, Stir for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.31 g, 3.1 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.11 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(4-methylthiobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (103)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.61-1.56 (m, 1H), 1.95-1.89 (m, 1H), 2.49-2.46 ( m, 4H), 3.22 (t, 2H), 3.46-3.42 (m, 1H), 3.73-3.59 (m, 3H), 4.52 (s, 2H), 4 .68 (s, 2H), 6.81 (s, 1H), 7.30-7.23 (m, 4H), 8.90 (t, 1H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（４−メチルチオベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１０４）と記す。）０．１７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．２３−１．１０（ｍ，２Ｈ），１．５８−１．５３（ｍ，２Ｈ），１．８２−１．７５（ｍ，１Ｈ），２．４９（ｓ，３Ｈ），３．１３（ｔ，２Ｈ），３．３１−３．２１（ｍ，２Ｈ），３．８５−３．８０（ｍ，２Ｈ），４．５２（ｓ，２Ｈ），４．６８（ｓ，２Ｈ），６．８０（ｓ，１Ｈ），７．３０−７．２３（ｍ，４Ｈ），８．８９（ｔ，１Ｈ） Production Example 99
5-[(4-Methylthiobenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 1.8 mmol) was added to chloroform (amylene-added product) (15 mL), cooled to 0 ° C., and triethylamine (0. 50 ml, 2.7 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.51 g, 2.1 mmol) and 1-hydroxybenzotriazole (0.36 g, 2.7 mmol) are added, Stir for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.49 g, 4.2 mmol) was added to the mixture, and the mixture was stirred at room temperature for 16 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.17 g of N- (tetrahydropyran-4-ylmethyl) -5-[(4-methylthiobenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (104)) represented by It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.23-1.10 (m, 2H), 1.58-1.53 (m, 2H), 1.82-1.75 ( m, 1H), 2.49 (s, 3H), 3.13 (t, 2H), 3.31-3.21 (m, 2H), 3.85-3.80 (m, 2H), 4 .52 (s, 2H), 4.68 (s, 2H), 6.80 (s, 1H), 7.30-7.23 (m, 4H), 8.89 (t, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（３，４−メチレンジオキシベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１０５）と記す。）０．３０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６６（ｍ，１Ｈ），２．０８（ｍ，１Ｈ），２．５７（ｍ，１Ｈ），３．４６（ｔ，２Ｈ），３．５９（ｍ，１Ｈ），３．７７（ｑ，１Ｈ），３．９４−３．８３（ｍ，２Ｈ），４．４９（ｓ，２Ｈ），４．６１（ｓ，２Ｈ），５．９６（ｓ，２Ｈ），６．７０（ｄ，１Ｈ），６．７９（ｓ，２Ｈ），６．８４（ｄ，１Ｈ），６．９０（ｂｒｓ，１Ｈ） Production Example 100
5-[(3,4-methylenedioxybenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.70 g, 2.5 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., Triethylamine (0.70 ml, 5.1 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.58 g, 3.0 mmol) and 1-hydroxybenzotriazole (0.41 g, 3.0 mmol) ) Was added and stirred for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.28 g, 2.8 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5-[(3,4-methylenedioxybenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (105)) 0. 30 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.66 (m, 1H), 2.08 (m, 1H), 2.57 (m, 1H), 3.46 (t, 2H) ), 3.59 (m, 1H), 3.77 (q, 1H), 3.94-3.83 (m, 2H), 4.49 (s, 2H), 4.61 (s, 2H) 5.96 (s, 2H), 6.70 (d, 1H), 6.79 (s, 2H), 6.84 (d, 1H), 6.90 (brs, 1H).

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（３，４−メチレンジオキシベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１０６）と記す。）０．４５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３８（ｍ，２Ｈ），１．６５（ｄ，２Ｈ），１．８６（ｍ，１Ｈ），３．３７（ｍ，４Ｈ），３．９９（ｄ，２Ｈ），４．４９（ｓ，２Ｈ），４．６０（ｓ，２Ｈ），５．９６（ｓ，２Ｈ），６．７０（ｓ，１Ｈ），６．７９（ｄ，２Ｈ），６．８７−６．８４（ｍ，２Ｈ） Production Example 101
5-[(3,4-methylenedioxybenzyl) oxymethyl] isoxazole-3-carboxylic acid (0.70 g, 2.5 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., Triethylamine (0.70 ml, 5.1 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.58 g, 3.0 mmol) and 1-hydroxybenzotriazole (0.41 g, 3.0 mmol) ) Was added and stirred for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.32 g, 2.8 mmol) was added to the mixture, stirred for 18 hours at room temperature, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydropyran-4-ylmethyl) -5-[(3,4-methylenedioxybenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (106)) 0 .45 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.38 (m, 2H), 1.65 (d, 2H), 1.86 (m, 1H), 3.37 (m, 4H) ), 3.99 (d, 2H), 4.49 (s, 2H), 4.60 (s, 2H), 5.96 (s, 2H), 6.70 (s, 1H), 6.79. (D, 2H), 6.87-6.84 (m, 2H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（チオフェン−３−イルメチル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１０７）と記す。）０．３１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７１−１．５６（１Ｈ，ｍ），２．１２−２．０５（１Ｈ，ｍ），２．６０−２．５４（１Ｈ，ｍ），３．４６（２Ｈ，ｔ），３．６０−３．５７（１Ｈ，ｍ），３．７９−３．７５（１Ｈ，ｍ），３．９４−３．８３（２Ｈ，ｍ），４．５３−４．５１（４Ｈ，ｍ），６．７０（１Ｈ，ｓ），６．９２（１Ｈ，ｓ），７．０９（１Ｈ，ｄ），７．２６（１Ｈ，ｓ），７．３４−７．３２（１Ｈ，ｍ） Production Example 102
5-[(thiophen-3-ylmethyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 2.1 mmol) was added to chloroform (amylene-added product) (10 mL), cooled to 0 ° C., and triethylamine (0 .42 ml, 3.1 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.60 g, 3.1 mmol) and 1-hydroxybenzotriazole (0.41 g, 3.0 mmol) were added. Stir for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.23 g, 2.3 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.31 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(thiophen-3-ylmethyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (107)) represented by the formula: It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.71-1.56 (1H, m), 2.12-2.05 (1H, m), 2.60-2.54 ( 1H, m), 3.46 (2H, t), 3.60-3.57 (1H, m), 3.79-3.75 (1H, m), 3.94-3.83 (2H, m), 4.53-4.51 (4H, m), 6.70 (1H, s), 6.92 (1H, s), 7.09 (1H, d), 7.26 (1H, s) ), 7.34-7.32 (1H, m)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（チオフェン−３−イルメチル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１０８）と記す。）０．３２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４２−１．３２（２Ｈ，ｍ），１．６８（２Ｈ，ｄ），１．９０−１．８１（１Ｈ，ｍ），３．４１−３．３３（４Ｈ，ｍ），４．００−３．９６（２Ｈ，ｍ），４．６３−４．６１（４Ｈ，ｍ），６．７０（１Ｈ，ｓ），６．８８（１Ｈ，ｓ），７．０８（１Ｈ，ｄ），７．２６（１Ｈ，ｓ），７．３４−７．３２（１Ｈ，ｍ） Production Example 103
5-[(thiophen-3-ylmethyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 2.1 mmol) was added to chloroform (amylene-added product) (10 mL), cooled to 0 ° C., and triethylamine (0 .42 ml, 3.1 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.60 g, 3.1 mmol) and 1-hydroxybenzotriazole (0.41 g, 3.0 mmol) were added. Stir for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.26 g, 2.3 mmol) was added to the mixture, stirred for 18 hours at room temperature, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.32 g of N- (tetrahydropyran-4-ylmethyl) -5-[(thiophen-3-ylmethyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (108)) Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42-1.32 (2H, m), 1.68 (2H, d), 1.90-1.81 (1H, m) , 3.41-3.33 (4H, m), 4.00-3.96 (2H, m), 4.63-4.61 (4H, m), 6.70 (1H, s), 6 .88 (1H, s), 7.08 (1H, d), 7.26 (1H, s), 7.34-7.32 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（２−クロロチオフェン−５−イルメチル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１０９）と記す。）０．１５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７１−１．６３（ｍ，１Ｈ），２．１０−２．０４（ｍ，１Ｈ），２．５９−２．５６（ｍ，１Ｈ），３．４８−３．４５（ｍ，２Ｈ），３．６０−３．５８（ｍ，１Ｈ），３．９４−３．８３（ｍ，３Ｈ），４．６５−４．６３（ｍ，４Ｈ），６．７１（ｓ，１Ｈ），６．８０（ｓ，２Ｈ），６．９４（ｓ，１Ｈ） Production Example 104
5-[(2-Chlorothiophen-5-ylmethyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 2.0 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., Triethylamine (0.40 ml, 2.9 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.56 g, 2.9 mmol) and 1-hydroxybenzotriazole (0.40 g, 2.9 mmol) ) Was added and stirred for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.22 g, 2.2 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5-[(2-chlorothiophen-5-ylmethyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (109)) 0. 15 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.71-1.63 (m, 1H), 2.10-2.04 (m, 1H), 2.59-2.56 ( m, 1H), 3.48-3.45 (m, 2H), 3.60-3.58 (m, 1H), 3.94-3.83 (m, 3H), 4.65-4. 63 (m, 4H), 6.71 (s, 1H), 6.80 (s, 2H), 6.94 (s, 1H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（２−クロロチオフェン−５−イルメチル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１１０）と記す。）０．１４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３２−１．４３（ｍ，２Ｈ），１．６５−１．６８（ｍ，２Ｈ），１．８４−１．８９（ｍ，１Ｈ），３．３３−３．４１（ｍ，４Ｈ），３．９６−３．５８４．０１（ｍ，２Ｈ），４．６４（ｓ,２Ｈ）,４．６５（ｓ,２Ｈ）,６．７１（ｓ，１Ｈ），６．８０（ｓ，２Ｈ），６．８７（ｂｒ．ｓ，１Ｈ） Production Example 105
5-[(2-Chlorothiophen-5-ylmethyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 2.0 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., Triethylamine (0.40 ml, 2.9 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.56 g, 2.9 mmol) and 1-hydroxybenzotriazole (0.40 g, 2.9 mmol) ) Was added and stirred for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.25 g, 2.2 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydropyran-4-ylmethyl) -5-[(2-chlorothiophen-5-ylmethyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (110)) 0 .14 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.32-1.43 (m, 2H), 1.65 to 1.68 (m, 2H), 1.84 to 1.89 ( m, 1H), 3.33-3.41 (m, 4H), 3.96-3.584.01 (m, 2H), 4.64 (s, 2H), 4.65 (s, 2H) 6.71 (s, 1H), 6.80 (s, 2H), 6.87 (br.s, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（ベンゾフラン−２−イルメチル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１１１）と記す。）０．１５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７１−１．６３（ｍ，１Ｈ），２．１２−２．０４（ｍ，１Ｈ），２．６０−２．５４（ｍ，１Ｈ），３．４６（ｔ，２Ｈ），３．６−３．５７（ｍ，１Ｈ），３．７４（ｑ，１Ｈ），３．９４−３．８３（ｍ，２Ｈ），４．７２（ｄ，４Ｈ），６．７５（ｓ，２Ｈ），６．９１（ｂｒｓ，１Ｈ），７．２３（ｄ，１Ｈ），７．３０（ｔ，１Ｈ），７．５（ｄ，１Ｈ），７．５６（ｄ，１Ｈ） Production Example 106
5-[(Benzofuran-2-ylmethyl) oxymethyl] isoxazole-3-carboxylic acid (0.35 g, 1.3 mmol) was added to chloroform (amylene-added product) (10 mL), cooled to 0 ° C., and triethylamine (0 .27 ml, 1.9 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.29 g, 1.5 mmol) and 1-hydroxybenzotriazole (0.21 g, 1.5 mmol) were added. Stir for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.14 g, 1.1 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.15 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(benzofuran-2-ylmethyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (111)) represented by the formula: It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.71-1.63 (m, 1H), 2.12-2.04 (m, 1H), 2.60-2.54 ( m, 1H), 3.46 (t, 2H), 3.6-3.57 (m, 1H), 3.74 (q, 1H), 3.94-3.83 (m, 2H), 4 .72 (d, 4H), 6.75 (s, 2H), 6.91 (brs, 1H), 7.23 (d, 1H), 7.30 (t, 1H), 7.5 (d, 1H), 7.56 (d, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（ベンゾチオフェン−２−イルメチル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１１２）と記す。）０．２３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７１−１．１９（ｍ，１Ｈ），２．１３−２．０４（ｍ，１Ｈ），２．５４−２．６０（ｍ，１Ｈ），３．４８−３．４２（ｍ，２Ｈ），３．６−３．５４（ｍ，１Ｈ），３．７４（ｑ，１Ｈ），３．９４−３．８４（ｍ，２Ｈ），４．６９（ｓ，２Ｈ），４．８６（ｓ，２Ｈ），６．７５（ｓ，１Ｈ），６．９２（ｂｒｓ，１Ｈ），７．３８−７．３２（ｍ，３Ｈ），７．７５（ｄｄ，１Ｈ），７．８４−７．８１（ｍ，１Ｈ） Production Example 107
5-[(Benzothiophen-2-ylmethyl) oxymethyl] isoxazole-3-carboxylic acid (0.52 g, 1.8 mmol) was added to chloroform (amylene-added product) (10 mL), cooled to 0 ° C., triethylamine ( 0.38 ml, 2.7 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.41 g, 2.2 mmol) and 1-hydroxybenzotriazole (0.29 g, 2.2 mmol). Added and stirred for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.20 g, 2.0 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.23 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(benzothiophen-2-ylmethyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (112)) represented by the formula: Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.71-1.19 (m, 1H), 2.13-2.04 (m, 1H), 2.54-2.60 ( m, 1H), 3.48-3.42 (m, 2H), 3.6-3.54 (m, 1H), 3.74 (q, 1H), 3.94-3.84 (m, 2H), 4.69 (s, 2H), 4.86 (s, 2H), 6.75 (s, 1H), 6.92 (brs, 1H), 7.38-7.32 (m, 3H) ), 7.75 (dd, 1H), 7.84-7.81 (m, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−フェニルベンジル）オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１１３）と記す。）０．２１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６３−１．７１（１Ｈ，ｍ），２．０４−２．１３（１Ｈ，ｍ），２．５２−２．６３（１Ｈ，ｍ）， ３．４５−３．４８（２Ｈ，ｍ），３．５７−３．６１（１Ｈ，ｍ），３．７４−３．７９（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），４．６８（２Ｈ， ｓ），４．６９ （２Ｈ，ｓ），６．７４（１Ｈ，ｓ），６．９５（１Ｈ， ｂｒ ｓ），７．３２−７．３８（２Ｈ，ｍ），７．４３−７．４７（３Ｈ，ｍ），７．５５−７．６１（４Ｈ，ｍ） Production Example 108
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.16 g, 1.2 mmol) and triethylamine (0.12 g, 1.2 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 5- (3-phenylbenzyl) oxymethylisoxazole-3-carboxylic acid (0.25 g, 0.8 mmol), 1-hydroxybenzotriazole (0.01 g, 0.08 mmol) and 1- Ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.22 g, 1.2 mmol) was added, stirred for 3 hours, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.21 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3-phenylbenzyl) oxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (113)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.71 (1H, m), 2.04-2.13 (1H, m), 2.52-2.63 ( 1H, m), 3.45-3.48 (2H, m), 3.57-3.61 (1H, m), 3.74-3.79 (1H, m), 3.84-3. 94 (2H, m), 4.68 (2H, s), 4.69 (2H, s), 6.74 (1H, s), 6.95 (1H, br s), 7.32-7. 38 (2H, m), 7.43-7.47 (3H, m), 7.55-7.61 (4H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−フェノキシベンジル）オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１１４）と記す。）０．５４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６３−１．７２（１Ｈ，ｍ），２．０４−２．１１（１Ｈ，ｍ），２．５３−２．６３（１Ｈ，ｍ）， ３．４５−３．４８（２Ｈ，ｍ），３．５７−３．６１（１Ｈ，ｍ），３．７４−３．７９（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），４．５７（２Ｈ， ｓ），４．６５ （２Ｈ，ｓ），６．７１（１Ｈ，ｓ），６．９４−７．０３（５Ｈ，ｍ），７．０７−７．１４（２Ｈ，ｍ），７．３０−７．３７（３Ｈ，ｍ） Production Example 109
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.23 g, 1.69 mmol) and triethylamine (0.17 g, 1.69 mmol) were added to chloroform (amylene-added product) (10 mL). To the mixture was added 5- (3-phenoxybenzyl) oxymethylisoxazole-3-carboxylic acid (0.46 g, 1.41 mmol), 1-hydroxybenzotriazole (0.02 g, 0.14 mmol) and 1- Ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.32 g, 1.69 mmol) was added, stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.54 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3-phenoxybenzyl) oxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (114)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (1H, m), 2.04-2.11 (1H, m), 2.53-2.63 ( 1H, m), 3.45-3.48 (2H, m), 3.57-3.61 (1H, m), 3.74-3.79 (1H, m), 3.84-3. 94 (2H, m), 4.57 (2H, s), 4.65 (2H, s), 6.71 (1H, s), 6.94-7.03 (5H, m), 7.07 -7.14 (2H, m), 7.30-7.37 (3H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（４−フェニルベンジル）オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１１５）と記す。）０．４２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６４−１．７２（１Ｈ，ｍ），２．０５−２．１３（１Ｈ，ｍ），２．５３−２．６３（１Ｈ，ｍ）， ３．４５−３．４９（２Ｈ，ｍ），３．５７−３．６１（１Ｈ，ｍ），３．７４−３．８０（１Ｈ，ｍ），３．８４−３．９５（２Ｈ，ｍ），４．６５（２Ｈ， ｓ），４．６９ （２Ｈ，ｓ），６．７５（１Ｈ，ｓ），６．９４（１Ｈ， ｂｒ ｓ），７．３４−７．３８（１Ｈ，ｍ），７．４２−７．４７（４Ｈ，ｍ），７．５８−７．６１（４Ｈ，ｍ） Production Example 110
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.24 g, 1.78 mmol) and triethylamine (0.18 g, 1.78 mmol) were added to chloroform (amylene-added product) (10 mL). To the mixture was added 5- (4-phenylbenzyl) oxymethylisoxazole-3-carboxylic acid (0.40 g, 1.19 mmol), 1-hydroxybenzotriazole (0.02 g, 0.18 mmol) and 1- Ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.34 g, 1.78 mmol) was added, stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.42 g of N- (tetrahydrofuran-3-ylmethyl) -5- (4-phenylbenzyl) oxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (115)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.72 (1H, m), 2.05-2.13 (1H, m), 2.53-2.63 ( 1H, m), 3.45-3.49 (2H, m), 3.57-3.61 (1H, m), 3.74-3.80 (1H, m), 3.84-3. 95 (2H, m), 4.65 (2H, s), 4.69 (2H, s), 6.75 (1H, s), 6.94 (1H, br s), 7.34-7. 38 (1H, m), 7.42-7.47 (4H, m), 7.58-7.61 (4H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−フェニルベンジル）オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１１６）と記す。）０．４０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６３−１．７２（１Ｈ，ｍ），２．０５−２．１３（１Ｈ，ｍ），２．５３−２．６３（１Ｈ，ｍ）， ３．４５−３．４８（２Ｈ，ｍ），３．５７−３．６１（１Ｈ，ｍ），３．７４−３．８０（１Ｈ，ｍ），３．８４−３．９５（２Ｈ，ｍ），４．５０（２Ｈ， ｓ），４．５６ （２Ｈ，ｓ），６．６１（１Ｈ，ｓ），６．９２（１Ｈ， ｂｒ ｓ），７．３０−７．４４（８Ｈ，ｍ），７．５１−７．５５（１Ｈ，ｍ） Production Example 111
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.24 g, 1.78 mmol) and triethylamine (0.18 g, 1.78 mmol) were added to chloroform (amylene-added product) (10 mL). To the mixture was added 5- (2-phenylbenzyl) oxymethylisoxazole-3-carboxylic acid (0.40 g, 1.19 mmol), 1-hydroxybenzotriazole (0.02 g, 0.18 mmol) and 1- Ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.34 g, 1.78 mmol) was added, stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.40 g of N- (tetrahydrofuran-3-ylmethyl) -5- (2-phenylbenzyl) oxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (116)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (1H, m), 2.05-2.13 (1H, m), 2.53-2.63 ( 1H, m), 3.45-3.48 (2H, m), 3.57-3.61 (1H, m), 3.74-3.80 (1H, m), 3.84-3. 95 (2H, m), 4.50 (2H, s), 4.56 (2H, s), 6.61 (1H, s), 6.92 (1H, br s), 7.30-7. 44 (8H, m), 7.51-7.55 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（４−フェノキシベンジル）オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１１７）と記す。）０．２９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６３−１．７２（１Ｈ，ｍ），２．０５−２．１３（１Ｈ，ｍ），２．５３−２．６３（１Ｈ，ｍ）， ３．４５−３．４９（２Ｈ，ｍ），３．５７−３．６１（１Ｈ，ｍ），３．７４−３．８０（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），４．５７（２Ｈ， ｓ），４．６６ （２Ｈ，ｓ），６．７３（１Ｈ，ｓ），６．９４（１Ｈ， ｂｒ ｓ），６．９９−７．０３（４Ｈ，ｍ），７．１０−７．１４（１Ｈ，ｍ），７．３０−７．３７（４Ｈ，ｍ） Production Example 112
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.23 g, 1.69 mmol) and triethylamine (0.17 g, 1.69 mmol) were added to chloroform (amylene-added product) (10 mL). To the mixture was added 5- (4-phenoxybenzyl) oxymethylisoxazole-3-carboxylic acid (0.46 g, 1.41 mmol), 1-hydroxybenzotriazole (0.02 g, 0.14 mmol) and 1- Ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.32 g, 1.69 mmol) was added, and the mixture was stirred at room temperature for 5 hours, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.29 g of N- (tetrahydrofuran-3-ylmethyl) -5- (4-phenoxybenzyl) oxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (117)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (1H, m), 2.05-2.13 (1H, m), 2.53-2.63 ( 1H, m), 3.45-3.49 (2H, m), 3.57-3.61 (1H, m), 3.74-3.80 (1H, m), 3.84-3. 94 (2H, m), 4.57 (2H, s), 4.66 (2H, s), 6.73 (1H, s), 6.94 (1H, br s), 699-7. 03 (4H, m), 7.10-7.14 (1H, m), 7.30-7.37 (4H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（１，２，３，４−テトラヒドロナフタレン−２−イルメチル）オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１１８）と記す。）０．５０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．４１−１．５１（１Ｈ，ｍ），１．６３−１．７０（１Ｈ，ｍ），１．９７−２．０５（１Ｈ，ｍ）， ２．０７−２．１１（２Ｈ，ｍ），２．４７−２．６３（２Ｈ，ｍ），２．８０−２．９１（３Ｈ，ｍ），３．４５−３．５１（４Ｈ，ｍ），３．５８−３．６１（１Ｈ，ｍ），３．７４−３．８０（１Ｈ，ｍ），３．８４−３．９５（２Ｈ，ｍ），４．６６（２Ｈ， ｓ），６．７２（１Ｈ，ｓ），６．９６（１Ｈ， ｂｒ ｓ），７．０７−７．１１（４Ｈ，ｍ） Production Example 113
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.29 g, 2.09 mmol) and triethylamine (0.21 g, 2.09 mmol) were added to chloroform (amylene-added product) (8 mL). To the mixture was added 5- (1,2,3,4-tetrahydronaphthalen-2-ylmethyl) oxymethylisoxazole-3-carboxylic acid (0.40 g, 1.39 mmol), 1-hydroxybenzotriazole (0 0.02 g, 0.14 mmol) and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.40 g, 2.09 mmol) were added, stirred at room temperature for 6 hours, diluted hydrochloric acid was added, and chloroform was added. Extracted twice. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (1,2,3,4-tetrahydronaphthalen-2-ylmethyl) oxymethylisoxazole-3-carboxamide represented by the formula (118) 0.50 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.41-1.51 (1H, m), 1.63-1.70 (1H, m), 1.97-2.05 ( 1H, m), 2.07-2.11 (2H, m), 2.47-2.63 (2H, m), 2.80-2.91 (3H, m), 3.45-3. 51 (4H, m), 3.58-3.61 (1H, m), 3.74-3.80 (1H, m), 3.84-3.95 (2H, m), 4.66 ( 2H, s), 6.72 (1H, s), 6.96 (1H, br s), 7.07-7.11 (4H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（５，６，７，８−テトラヒドロナフタレン−２−イルメチル）オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１１９）と記す。）０．８０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６４−１．７２（１Ｈ，ｍ），１．７８−１．８１（４Ｈ， ｍ），２．０４−２．１３（１Ｈ，ｍ），２．５３−２．６３（１Ｈ，ｍ）， ２．７６（４Ｈ， ｂｒ ｓ），３．４５−３．４８（２Ｈ，ｍ），３．５７−３．６１（１Ｈ，ｍ），３．７４−３．８０（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），４．５３（２Ｈ， ｓ），４．６２ （２Ｈ，ｓ），６．７１（１Ｈ，ｓ），６．９６（１Ｈ， ｂｒ ｓ），７．０４（１Ｈ，ｓ），７．０６（２Ｈ，ｓ） Production Example 114
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.55 g, 3.97 mmol) and triethylamine (0.40 g, 3.97 mmol) were added to chloroform (amylene-added product) (15 mL). To the mixture was added 5- (5,6,7,8-tetrahydronaphthalen-2-ylmethyl) oxymethylisoxazole-3-carboxylic acid (0.76 g, 2.65 mmol), 1-hydroxybenzotriazole (0 0.04 g, 0.26 mmol) and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.76 g, 3.97 mmol) were added, stirred at room temperature for 5 hours, diluted hydrochloric acid was added, and chloroform was added. Extracted twice. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (5,6,7,8-tetrahydronaphthalen-2-ylmethyl) oxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (119)) 0.80 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.72 (1H, m), 1.78-1.81 (4H, m), 2.04-2.13 ( 1H, m), 2.53-2.63 (1H, m), 2.76 (4H, br s), 3.45-3.48 (2H, m), 3.57-3.61 (1H M), 3.74-3.80 (1H, m), 3.84-3.94 (2H, m), 4.53 (2H, s), 4.62 (2H, s), 6. 71 (1H, s), 6.96 (1H, br s), 7.04 (1H, s), 7.06 (2H, s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（１，４−ベンゾジオキサン−２−イルメチル）オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１２０）と記す。）０．０８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６３−１．７２（１Ｈ，ｍ），２．０５−２．１３（１Ｈ，ｍ），２．５３−２．６３（１Ｈ，ｍ）， ３．４５−３．４８（２Ｈ，ｍ），３．５８−３．６１（１Ｈ，ｍ），３．７４−３．９４（５Ｈ，ｍ），４．０７−４．１１（１Ｈ， ｍ），４．２７−４．３０（１Ｈ， ｍ），４．３４−４．３９（１Ｈ， ｍ），４．７３ （２Ｈ，ｓ），６．７４（１Ｈ，ｓ），６．８３−６．９０（４Ｈ，ｍ），７．０３（１Ｈ， ｂｒ ｓ） Production Example 115
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.07 g, 0.49 mmol) and triethylamine (0.05 g, 0.49 mmol) were added to chloroform (amylene-added product) (3 mL). To the mixture was added 5- (1,4-benzodioxan-2-ylmethyl) oxymethylisoxazole-3-carboxylic acid (0.12 g, 0.41 mmol), 1-hydroxybenzotriazole (0.01 g, 0) at room temperature. 0.04 mmol) and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.10 g, 0.49 mmol) were added, and the mixture was stirred at room temperature for 6 hours, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. . The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (1,4-benzodioxan-2-ylmethyl) oxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (120)) 0.08 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (1H, m), 2.05-2.13 (1H, m), 2.53-2.63 ( 1H, m), 3.45-3.48 (2H, m), 3.58-3.61 (1H, m), 3.74-3.94 (5H, m), 4.07-4. 11 (1H, m), 4.27-4.30 (1H, m), 4.34-4.39 (1H, m), 4.73 (2H, s), 6.74 (1H, s) 6.83-6.90 (4H, m), 7.03 (1H, br s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−ベンジルオキシメチルベンジル）オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１２１）と記す。）０．４３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６２−１．７０（１Ｈ，ｍ），２．０２−２．１１（１Ｈ，ｍ），２．５１−２．６２（１Ｈ，ｍ）， ３．４３−３．４７（２Ｈ，ｍ），３．５６−３．６０（１Ｈ，ｍ），３．７２−３．７８（１Ｈ，ｍ），３．８２−３．９３（２Ｈ， ｍ），４．５６（２Ｈ， ｓ），４．５７（２Ｈ，ｓ），４．６０（２Ｈ， ｓ），４．６４（２Ｈ， ｓ），６．７３（１Ｈ，ｓ），７．０７（１Ｈ，ｂｒ ｓ），７．２６−７．３７（９Ｈ，ｍ） Production Example 116
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.19 g, 1.13 mmol) and triethylamine (0.14 g, 1.36 mmol) were added to chloroform (amylene-added product) (8 mL). To the mixture was added 5- (3-benzyloxymethylbenzyl) oxymethylisoxazole-3-carboxylic acid (0.40 g, 1.22 mmol), 1-hydroxybenzotriazole (0.02 g, 0.11 mmol) and 1-Ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.26 g, 1.36 mmol) was added, stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.43 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3-benzyloxymethylbenzyl) oxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (121)) represented by Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.70 (1H, m), 2.02-2.11 (1H, m), 2.51-2.62 ( 1H, m), 3.43-3.47 (2H, m), 3.56-3.60 (1H, m), 3.72-3.78 (1H, m), 3.82-3. 93 (2H, m), 4.56 (2H, s), 4.57 (2H, s), 4.60 (2H, s), 4.64 (2H, s), 6.73 (1H, s) ), 7.07 (1H, br s), 7.26-7.37 (9H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（１，３−ベンゾジオキソラン−２−イルメチル）オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１２２）と記す。）０．１０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６３−１．７１（１Ｈ，ｍ），２．０５−２．１３（１Ｈ，ｍ），２．５３−２．６３（１Ｈ，ｍ）， ３．４４−３．４８（２Ｈ，ｍ），３．５７−３．６０（１Ｈ，ｍ），３．７３−３．７９（１Ｈ，ｍ），３．８３−３．９４（４Ｈ，ｍ），４．１０−４．１５（１Ｈ， ｍ），４．７８ （２Ｈ，ｓ），６．２３−６．２５（１Ｈ，ｔ），６．７２（１Ｈ，ｓ），６．８２（４Ｈ，ｂｒ ｓ），６．９６（１Ｈ， ｂｒ ｓ） Production Example 117
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.06 g, 0.41 mmol) and triethylamine (0.04 g, 0.41 mmol) were added to chloroform (amylene-added product) (2 mL). To the mixture was added 5- (1,3-benzodioxolan-2-ylmethyl) oxymethylisoxazole-3-carboxylic acid (0.10 g, 0.34 mmol), 1-hydroxybenzotriazole (0.01 g, 0) at room temperature. 0.03 g) and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.08 g, 0.41 mmol) were added, and the mixture was stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (1,3-benzodioxolan-2-ylmethyl) oxymethylisoxazole-3-carboxyamide (hereinafter referred to as the present compound (122)) 0.10 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.71 (1H, m), 2.05-2.13 (1H, m), 2.53-2.63 ( 1H, m), 3.44-3.48 (2H, m), 3.57-3.60 (1H, m), 3.73-3.79 (1H, m), 3.83-3. 94 (4H, m), 4.10-4.15 (1H, m), 4.78 (2H, s), 6.23-6.25 (1H, t), 6.72 (1H, s) , 6.82 (4H, br s), 6.96 (1H, br s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−メチル−３−フェニルベンジル）オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１２３）と記す。）０．３８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６３−１．７２（１Ｈ，ｍ），２．０４−２．１３（１Ｈ，ｍ），２．２１（３Ｈ，ｓ），２．５２−２．６３（１Ｈ，ｍ）， ３．４５−３．４８（２Ｈ，ｍ），３．５７−３．６１（１Ｈ，ｍ），３．７４−３．７９（１Ｈ，ｍ），３．８３−３．９４（２Ｈ，ｍ），４．６７（２Ｈ，ｓ），４．７１ （２Ｈ，ｓ），６．７４（１Ｈ，ｓ），６．９６（１Ｈ， ｂｒ ｓ），７．２１−７．３０（４Ｈ，ｍ），７．３２−７．３６（２Ｈ，ｍ），７．３９−７．４３（２Ｈ，ｍ） Production Example 118
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.20 g, 1.48 mmol) and triethylamine (0.15 g, 1.48 mmol) were added to chloroform (amylene-added product) (8 mL). To the mixture was added 5- (2-methyl-3-phenylbenzyl) oxymethylisoxazole-3-carboxylic acid (0.40 g, 1.24 mmol), 1-hydroxybenzotriazole (0.02 g, 0.12 mmol) at room temperature. ) And 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.28 g, 1.48 mmol) were added and stirred for 3 hours, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (2-methyl-3-phenylbenzyl) oxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (123)) 0. 38 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (1H, m), 2.04-2.13 (1H, m), 2.21 (3H, s) , 2.52-2.63 (1H, m), 3.45-3.48 (2H, m), 3.57-3.61 (1H, m), 3.74-3.79 (1H, m), 3.83-3.94 (2H, m), 4.67 (2H, s), 4.71 (2H, s), 6.74 (1H, s), 6.96 (1H, br) s), 7.21-7.30 (4H, m), 7.32-7.36 (2H, m), 7.39-7.43 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（５−フェニルフルフリル）オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１２４）と記す。）０．３５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６４−１．７１（１Ｈ，ｍ），２．０３−２．１２（１Ｈ，ｍ），２．５１−２．６１（１Ｈ，ｍ）， ３．４３−３．４６（２Ｈ，ｍ），３．５６−３．６０（１Ｈ，ｍ），３．７３−３．７９（１Ｈ，ｍ），３．８３−３．９４（２Ｈ，ｍ），４．６０（２Ｈ， ｓ），４．６９ （２Ｈ，ｓ），６．４６（１Ｈ，ｄ），６．６２（１Ｈ，ｄ），６．７２（１Ｈ，ｓ），６．９１（１Ｈ， ｂｒ ｓ），７．２６−７．２９（１Ｈ，ｍ），７．３７−７．４１（２Ｈ，ｍ），７．６６−７．６８（２Ｈ，ｍ） Production Example 119
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.22 g, 1.60 mmol) and triethylamine (0.16 g, 1.60 mmol) were added to chloroform (amylene-added product) (8 mL). To the mixture was added 5- (5-phenylfurfuryl) oxymethylisoxazole-3-carboxylic acid (0.40 g, 1.34 mmol), 1-hydroxybenzotriazole (0.02 g, 0.13 mmol) and 1 at room temperature. -Ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.31 g, 1.60 mmol) was added, stirred for 3 hours, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.35 g of N- (tetrahydrofuran-3-ylmethyl) -5- (5-phenylfurfuryl) oxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (124)) represented by the formula: It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.71 (1H, m), 2.03-2.12 (1H, m), 2.51-2.61 ( 1H, m), 3.43-3.46 (2H, m), 3.56-3.60 (1H, m), 3.73-3.79 (1H, m), 3.83-3. 94 (2H, m), 4.60 (2H, s), 4.69 (2H, s), 6.46 (1H, d), 6.62 (1H, d), 6.72 (1H, s) ), 6.91 (1H, br s), 7.26-7.29 (1H, m), 7.37-7.41 (2H, m), 7.66-7.68 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−[（１−フェニルエチル）オキシメチル]イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１２５）と記す。）０．５１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４９（３Ｈ，ｄ），１．６６−１．６９（１Ｈ，ｍ），２．０４−２．１３（１Ｈ，ｍ），２．５３−２．６３（１Ｈ，ｍ），３．４６（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７７（１Ｈ，ｄｄ），３．８６（１Ｈ，ｄｄ），３．９２（１Ｈ，ｔｄ），４．４８（３Ｈ，ｄｄｄ），６．６７（１Ｈ，ｓ），６．９４（１Ｈ，ｓ），７．２９−７．４０（５Ｈ，ｍ） Production Example 120
5-[(1-phenylethyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.33 g, 2.4 mmol), triethylamine (0 .24 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.24 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.51 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(1-phenylethyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (125)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.49 (3H, d), 1.66 to 1.69 (1H, m), 2.04-2.13 (1H, m) , 2.53-2.63 (1H, m), 3.46 (2H, t), 3.59 (1H, dd), 3.77 (1H, dd), 3.86 (1H, dd), 3.92 (1H, td), 4.48 (3H, ddd), 6.67 (1H, s), 6.94 (1H, s), 7.29-7.40 (5H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−ジフェニルメトキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１２６）と記す。）０．３７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７２（１Ｈ，ｍ），２．０６−２．１３（１Ｈ，ｍ），２．５６−２．５９（１Ｈ，ｍ），３．４５−３．４８（２Ｈ，ｍ），３．５９（１Ｈ，ｄｄ），３．７６−３．７８（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），４．６４（２Ｈ，ｓ），５．４９（１Ｈ，ｓ），６．７３（１Ｈ，ｓ），６．９４（１Ｈ，ｓ），７．２７−７．３７（１０Ｈ，ｍ） Production Example 121
5-diphenylmethoxymethylisoxazole-3-carboxylic acid (0.62 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.33 g, 2.4 mmol), triethylamine (0.25 g, 2. mmol). 4 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.24 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.37 g of N- (tetrahydrofuran-3-ylmethyl) -5-diphenylmethoxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (126)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (1H, m), 2.06-2.13 (1H, m), 2.56 to 2.59 ( 1H, m), 3.45-3.48 (2H, m), 3.59 (1H, dd), 3.76-3.78 (1H, m), 3.84-3.94 (2H, m), 4.64 (2H, s), 5.49 (1H, s), 6.73 (1H, s), 6.94 (1H, s), 7.27-7.37 (10H, m )

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−[（１−フェニル−２，２，２−トリフルオロエチル）オキシメチル]イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１２７）と記す。）０．５１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６５−１．７２（１Ｈ，ｍ），２．０６−２．１３（１Ｈ，ｍ），２．５６−２．６０（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７４−３．８０（１Ｈ，ｍ），３．８６（１Ｈ，ｄｄ），３．９１−３．９３（１Ｈ，ｍ），４．６２−４．７６（３Ｈ，ｍ），６．７０−６．８０（１Ｈ，ｍ），６．９６（１Ｈ，ｂｒｓ），７．４１−７．４９（５Ｈ，ｍ） Production Example 122
5-[(1-Phenyl-2,2,2-trifluoroethyl) oxymethyl] isoxazole-3-carboxylic acid (0.50 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.33 g , 2.4 mmol), triethylamine (0.24 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.24 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5-[(1-phenyl-2,2,2-trifluoroethyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (127)) 0.51 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.65-1.72 (1H, m), 2.06-2.13 (1H, m), 2.56-2.60 ( 1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.74-3.80 (1H, m), 3.86 (1H, dd), 3.91-3 .93 (1H, m), 4.62-4.76 (3H, m), 6.70-6.80 (1H, m), 6.96 (1H, brs), 7.41-7.49 (5H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−[（２，２，２−トリフルオロエチル）オキシメチル]イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１２８）と記す。）０．３２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６４−１．７２（１Ｈ，ｍ），２．０６−２．１３（１Ｈ，ｍ），２．５３−２．６４（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．６０（１Ｈ，ｄｄ），３．７４−３．８０（１Ｈ，ｍ），３．８４−３．９６（４Ｈ，ｍ），４．８０（２Ｈ，ｓ），６．７８（１Ｈ，ｂｒｓ），７．００（１Ｈ，ｓ） Production Example 123
5-[(2,2,2-trifluoroethyl) oxymethyl] isoxazole-3-carboxylic acid (0.30 g, 1.3 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.22 g, 1.6 mmol) ), Triethylamine (0.16 g, 1.6 mmol) and 1-hydroxybenzotriazole (0.02 g, 0.16 mmol) were added to chloroform (amylene-added product) (4 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.31 g, 1.6 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5-[(2,2,2-trifluoroethyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (128)) 0 .32 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.72 (1H, m), 2.06-2.13 (1H, m), 2.53-2.64 ( 1H, m), 3.47 (2H, t), 3.60 (1H, dd), 3.74-3.80 (1H, m), 3.84-3.96 (4H, m), 4 .80 (2H, s), 6.78 (1H, brs), 7.00 (1H, s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−[１−（ベンジルオキシ）エチル]イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１２９）と記す。）０．５８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．５９（３Ｈ，ｄ），１．６３−１．７３（１Ｈ，ｍ），２．０７−２．１２（１Ｈ，ｍ），２．５５−２．６２（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．６０（１Ｈ，ｄｄ），３．７６−３．７８（１Ｈ，ｍ），３．８６（１Ｈ，ｄｄ），３．９１−３．９３（１Ｈ，ｍ），４．４７（１Ｈ，ｄ），４．６０（１Ｈ，ｄ），４．７０−４．７５（１Ｈ，ｍ），６．６９（１Ｈ，ｄ），６．９５（１Ｈ，ｓ），７．３０−７．３８（５Ｈ，ｍ） Production Example 124
5- [1- (benzyloxy) ethyl] isoxazole-3-carboxylic acid (0.60 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.33 g, 2.4 mmol), triethylamine (0. 24 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.24 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight at room temperature and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.58 g of N- (tetrahydrofuran-3-ylmethyl) -5- [1- (benzyloxy) ethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (129)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.59 (3H, d), 1.63-1.73 (1H, m), 2.07-2.12 (1H, m) 2.55-2.62 (1H, m), 3.47 (2H, t), 3.60 (1H, dd), 3.76-3.78 (1H, m), 3.86 (1H , Dd), 3.91-3.93 (1H, m), 4.47 (1H, d), 4.60 (1H, d), 4.70-4.75 (1H, m), 6. 69 (1H, d), 6.95 (1H, s), 7.30-7.38 (5H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（１−ベンジルオキシ−１−フェニルメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１３０）と記す。）０．４５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．６８（１Ｈ，ｍ），２．０２−２．１１（１Ｈ，ｍ），２．５５−２．５６（１Ｈ，ｍ），３．４２−３．４６（２Ｈ，ｍ），３．５７（１Ｈ，ｄｄ），３．７５（１Ｈ，ｄｄ），３．８４（１Ｈ，ｄｄ），３．８９−３．９１（１Ｈ，ｍ），４．６０（２Ｈ，ｄｄ），５．５７（１Ｈ，ｓ），６．６２（１Ｈ，ｓ），６．９１（１Ｈ，ｓ），７．３２−７．４４（１０Ｈ，ｍ） Production Example 125
5- (1-benzyloxy-1-phenylmethyl) isoxazole-3-carboxylic acid (0.44 g, 1.4 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.23 g, 1.7 mmol), triethylamine ( 0.17 g, 1.7 mmol) and 1-hydroxybenzotriazole (0.02 g, 0.17 mmol) were added to chloroform (amylene-added product) (4 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.32 g, 1.7 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.45 g of N- (tetrahydrofuran-3-ylmethyl) -5- (1-benzyloxy-1-phenylmethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (130)) represented by the formula: It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.68 (1H, m), 2.02-2.11 (1H, m), 2.55-2.56 ( 1H, m), 3.42-3.46 (2H, m), 3.57 (1H, dd), 3.75 (1H, dd), 3.84 (1H, dd), 3.89-3 .91 (1H, m), 4.60 (2H, dd), 5.57 (1H, s), 6.62 (1H, s), 6.91 (1H, s), 7.32-7. 44 (10H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−シクロペンチルメトキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１３１）と記す。）０．３３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．１８−１．２８（２Ｈ，ｍ），１．５０−１．６０（４Ｈ， ｍ），１．６４−１．７８（３Ｈ， ｍ），２．０５−２．２３（２Ｈ，ｍ），２．５３−２．６３（１Ｈ，ｍ）， ３．３９（２Ｈ，ｄ），３．４５−３．４８（２Ｈ，ｍ），３．５７−３．６１（１Ｈ，ｍ），３．７４−３．８０（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），４．６２（２Ｈ，ｓ），６．７０（１Ｈ，ｓ），６．９６（１Ｈ， ｂｒ ｓ） Production Example 126
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.20 g, 1.44 mmol) and triethylamine (0.15 g, 1.44 mmol) were added to chloroform (amylene-added product) (6 mL). To the mixture was added 5-cyclopentylmethoxymethylisoxazole-3-carboxylic acid (0.27 g, 1.20 mmol), 1-hydroxybenzotriazole (0.02 g, 0.12 mmol) and 1-ethyl-3- ( 3-Dimethylaminopropyl) carbodiimide hydrochloride (0.28 g, 1.44 mmol) was added and stirred for 5 hours, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.33 g of N- (tetrahydrofuran-3-ylmethyl) -5-cyclopentylmethoxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (131)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.18-1.28 (2H, m), 1.50-1.60 (4H, m), 1.64-1.78 ( 3H, m), 2.05-2.23 (2H, m), 2.53-2.63 (1H, m), 3.39 (2H, d), 3.45-3.48 (2H, m), 3.57-3.61 (1H, m), 3.74-3.80 (1H, m), 3.84-3.94 (2H, m), 4.62 (2H, s) , 6.70 (1H, s), 6.96 (1H, br s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−シクロペンチルエチル）オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（１３２）と記す。）０．８５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．０５−１．１３（２Ｈ，ｍ），１．４６−１．９０（１０Ｈ， ｍ），２．０５−２．１３（１Ｈ， ｍ），２．５３−２．６３（１Ｈ，ｍ）， ３．４５−３．４８（２Ｈ，ｍ），３．５２−３．５６（２Ｈ，ｍ），３．５７−３．６１（１Ｈ，ｍ），３．７４−３．８０（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），４．６１（２Ｈ，ｓ），６．７０（１Ｈ，ｓ），６．９４（１Ｈ， ｂｒ ｓ） Production Example 127
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.45 g, 3.26 mmol) and triethylamine (0.33 g, 3.26 mmol) were added to chloroform (amylene-added product) (13 mL). To the mixture was added 5- (2-cyclopentylethyl) oxymethylisoxazole-3-carboxylic acid (0.65 g, 2.72 mmol), 1-hydroxybenzotriazole (0.04 g, 0.27 mmol) and 1- Ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.63 g, 3.26 mmol) was added, and the mixture was stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.85 g of N- (tetrahydrofuran-3-ylmethyl) -5- (2-cyclopentylethyl) oxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (132)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.05-1.13 (2H, m), 1.46-1.90 (10H, m), 2.05-2.13 ( 1H, m), 2.53-2.63 (1H, m), 3.45-3.48 (2H, m), 3.52-3.56 (2H, m), 3.57-3. 61 (1H, m), 3.74-3.80 (1H, m), 3.84-3.94 (2H, m), 4.61 (2H, s), 6.70 (1H, s) , 6.94 (1H, br s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−フェニルプロピルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１３２）と記す。）０．３１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７０−１．６５（ｍ，１Ｈ），１．９６−１．８９（ｍ，２Ｈ），２．１０−２．０６（ｍ，１Ｈ），２．５９−２．５６（ｍ，１Ｈ），２．６９（ｔ，２Ｈ），３．４６（ｔ，２Ｈ），３．５２（ｔ，２Ｈ），３．５９−３．５７（ｍ，１Ｈ），３．７７−３．７３（ｍ，１Ｈ），３．９４−３．７９（ｍ，２Ｈ），４．６０（ｓ，２Ｈ），６．６９（ｓ，１Ｈ），６．９４（ｓ，１Ｈ），７．２０−７．１６（ｍ，３Ｈ），７．２９−７．２７（ｍ，２Ｈ） Production Example 128
5- (3-Phenylpropyloxymethyl) isoxazole-3-carboxylic acid (0.60 g, 2.3 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., triethylamine (0.48 ml, 3.4 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.66 g, 3.4 mmol) and 1-hydroxybenzotriazole (0.47 g, 3.4 mmol) are added for 10 minutes. Stir. Tetrahydrofuran-3-ylmethylamine (0.26 g, 2.5 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.31 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3-phenylpropyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (132)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.70-1.65 (m, 1H), 1.96-1.89 (m, 2H), 2.10-2.06 ( m, 1H), 2.59-2.56 (m, 1H), 2.69 (t, 2H), 3.46 (t, 2H), 3.52 (t, 2H), 3.59-3 .57 (m, 1H), 3.77-3.73 (m, 1H), 3.94-3.79 (m, 2H), 4.60 (s, 2H), 6.69 (s, 1H) ), 6.94 (s, 1H), 7.20-7.16 (m, 3H), 7.29-7.27 (m, 2H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−（３−フェニルプロピルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１３４）と記す。）０．３１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４３−１．３２（ｍ，２Ｈ），１．６８−１．６５（ｍ，２Ｈ），１．９６−１．８３（ｍ，３Ｈ），２．６９（ｔ，２Ｈ），３．４０−３．３３（ｍ，４Ｈ），３．５２（ｔ，２Ｈ），４．００−３．９６（ｍ，２Ｈ），４．６０（ｓ，２Ｈ），６．６９（ｓ，１Ｈ），６．８８（ｓ，１Ｈ），７．２０−７．１６（ｍ，３Ｈ），７．２９−７．２７（ｍ，２Ｈ） Production Example 129
5- (3-Phenylpropyloxymethyl) isoxazole-3-carboxylic acid (0.60 g, 2.3 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., triethylamine (0.48 ml, 3.4 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.66 g, 3.4 mmol) and 1-hydroxybenzotriazole (0.47 g, 3.4 mmol) are added for 10 minutes. Stir. Tetrahydropyran-4-ylmethylamine (0.29 g, 2.5 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.31 g of N- (tetrahydropyran-4-ylmethyl) -5- (3-phenylpropyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (134)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.43-1.32 (m, 2H), 1.68-1.65 (m, 2H), 1.96-1.83 ( m, 3H), 2.69 (t, 2H), 3.40-3.33 (m, 4H), 3.52 (t, 2H), 4.00-3.96 (m, 2H), 4 .60 (s, 2H), 6.69 (s, 1H), 6.88 (s, 1H), 7.20-7.16 (m, 3H), 7.29-7.27 (m, 2H) )

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（４−フェニルブチルオキシメチル）イソキサゾール−３−カルボン酸−３−カルボキシアミド（以下、本発明化合物（１３５）と記す。）０．５０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６８（ｍ，５Ｈ），２．０８（ｑ，１Ｈ），２．６４−２．５３（ｍ，３Ｈ），３．４６（ｔ，２Ｈ），３．５４（ｍ，３Ｈ），３．７５（ｑ，１Ｈ），３．９３−３．７９（ｍ，２Ｈ），４．５９（ｓ，２Ｈ），６．６８（ｓ，１Ｈ），６．９４（ｂｒｓ，１Ｈ），７．１７（ｄｄ，３Ｈ），７．２７（ｄｄ，１Ｈ），７．２９（ｄ，１Ｈ） Production Example 130
5- (4-Phenylbutyloxymethyl) isoxazole-3-carboxylic acid (0.50 g, 1.8 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., triethylamine (0.51 mL, 3.6 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.42 g, 2.2 mmol) and 1-hydroxybenzotriazole (0.29 g, 2.2 mmol) are added for 10 minutes. Stir. Tetrahydrofuran-3-ylmethylamine (0.20 g, 2.0 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (4-phenylbutyloxymethyl) isoxazole-3-carboxylic acid-3-carboxamide (hereinafter referred to as the present compound (135)) 0.50 g Got.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.68 (m, 5H), 2.08 (q, 1H), 2.64-2.53 (m, 3H), 3.46 (T, 2H), 3.54 (m, 3H), 3.75 (q, 1H), 3.93-3.79 (m, 2H), 4.59 (s, 2H), 6.68 ( s, 1H), 6.94 (brs, 1H), 7.17 (dd, 3H), 7.27 (dd, 1H), 7.29 (d, 1H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−（４−フェニルブチルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１３６）と記す。）０．３２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３８（ｑ，２Ｈ），１．６６（ｍ，６Ｈ），１．８２（ｍ，１Ｈ），２．６２（ｔ，２Ｈ），３．３６（ｍ，４Ｈ），３．５１（ｔ，２Ｈ），４．００（ｄ，２Ｈ），４．５９（ｓ，２Ｈ），６．６８（ｓ，１Ｈ），６．８７（ｂｒｓ，１Ｈ），７．１７（ｄ，３Ｈ），７．２７（ｄ，１Ｈ），７．２９（ｄ，１Ｈ）， Production Example 131
5- (4-Phenylbutyloxymethyl) isoxazole-3-carboxylic acid (0.50 g, 1.8 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., triethylamine (0.51 mL, 3.6 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.42 g, 2.2 mmol) and 1-hydroxybenzotriazole (0.29 g, 2.2 mmol) are added for 10 minutes. Stir. Tetrahydropyran-4-ylmethylamine (0.23 g, 2.0 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.32 g of N- (tetrahydropyran-4-ylmethyl) -5- (4-phenylbutyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (136)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.38 (q, 2H), 1.66 (m, 6H), 1.82 (m, 1H), 2.62 (t, 2H) ), 3.36 (m, 4H), 3.51 (t, 2H), 4.00 (d, 2H), 4.59 (s, 2H), 6.68 (s, 1H), 6.87. (Brs, 1H), 7.17 (d, 3H), 7.27 (d, 1H), 7.29 (d, 1H),

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（５−フェニルペンチルオキシメチル）イソキサゾール−３−カルボン酸−３−カルボキシアミド（以下、本発明化合物（１３７）と記す。）０．３０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４３−１．３６（ｍ，２Ｈ），１．６８−１．５４（ｍ，５Ｈ），２．１２−１．７１（ｍ，１Ｈ），２．６３−２．５４（ｍ，３Ｈ），３．５２−３．４４（ｍ，４Ｈ），３．６０−３．５６（ｍ，１Ｈ），３．７７−３．７３（ｍ，１Ｈ），４．００−３．７９（ｍ，２Ｈ），４．５９（ｓ，２Ｈ），６．６８（ｓ，１Ｈ），６．９１（ｍ，１Ｈ），７．１８−７．１５（ｍ，３Ｈ），７．２９−７．２５（ｍ，２Ｈ） Production Example 132
5- (5-Phenylpentyloxymethyl) isoxazole-3-carboxylic acid (0.50 g, 1.7 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., triethylamine (0.49 ml, 3.5 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.40 g, 2.1 mmol) and 1-hydroxybenzotriazole (0.28 g, 2.1 mmol) were added for 10 minutes. Stir. Tetrahydrofuran-3-ylmethylamine (0.19 g, 1.9 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (5-phenylpentyloxymethyl) isoxazole-3-carboxylic acid-3-carboxyamide (hereinafter referred to as the present compound (137)) 0.30 g Got.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.43-1.36 (m, 2H), 1.68-1.54 (m, 5H), 2.12-1.71 ( m, 1H), 2.63-2.54 (m, 3H), 3.52-3.44 (m, 4H), 3.60-3.56 (m, 1H), 3.77-3. 73 (m, 1H), 4.00-3.79 (m, 2H), 4.59 (s, 2H), 6.68 (s, 1H), 6.91 (m, 1H), 7.18 -7.15 (m, 3H), 7.29-7.25 (m, 2H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−（５−フェニルペンチルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１３８）と記す。）０．４２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４３−１．３２（ｍ，４Ｈ），１．６８−１．５８（ｍ，６Ｈ），１．８８−１．６８（ｍ，１Ｈ），２．６２−２．５９（ｔ，２Ｈ），３．４０−３．３３（ｍ，４Ｈ），３．５０−３．４９（ｍ，２Ｈ），４．００−３．５２（ｍ，２Ｈ），４．５９（ｓ，２Ｈ），６．６８（ｓ，１Ｈ），６．８７（ｍ，１Ｈ），７．１８−７．１５（ｍ，３Ｈ），７．２９−７．２５（ｍ，２Ｈ） Production Example 133
5- (5-Phenylpentyloxymethyl) isoxazole-3-carboxylic acid (0.50 g, 1.7 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., triethylamine (0.49 ml, 3.5 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.40 g, 2.1 mmol) and 1-hydroxybenzotriazole (0.28 g, 2.1 mmol) were added for 10 minutes. Stir. Tetrahydropyran-4-ylmethylamine (0.22 g, 1.9 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.42 g of N- (tetrahydropyran-4-ylmethyl) -5- (5-phenylpentyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (138)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.43-1.32 (m, 4H), 1.68-1.58 (m, 6H), 1.88-1.68 ( m, 1H), 2.62-2.59 (t, 2H), 3.40-3.33 (m, 4H), 3.50-3.49 (m, 2H), 4.00-3. 52 (m, 2H), 4.59 (s, 2H), 6.68 (s, 1H), 6.87 (m, 1H), 7.18-7.15 (m, 3H), 7.29 -7.25 (m, 2H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−ベンジルオキシプロピル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１３９）と記す。）０．４４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６４−１．７１（１Ｈ，ｍ），２．００−２．０３（２Ｈ，ｍ），２．０８−２．１１（１Ｈ，ｍ），２．５４−２．６０（１Ｈ，ｍ），２．９３（２Ｈ，ｔ），３．４３−３．４７（２Ｈ，ｍ），３．５２（２Ｈ，ｔ），３．５８（１Ｈ，ｄｄ），３．７６（１Ｈ，ｄｄ），３．８４−３．９４（２Ｈ，ｍ），４．５１（２Ｈ，ｓ），６．４３（１Ｈ，ｓ），６．９３（１Ｈ，ｓ），７．２８−７．４０（５Ｈ，ｍ） Production Example 134
5- (3-benzyloxypropyl) isoxazole-3-carboxylic acid (0.65 g, 2.5 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.43 g, 3.1 mmol), triethylamine (0.32 g, 3.1 mmol) and 1-hydroxybenzotriazole (0.04 g, 0.30 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.60 g, 3.1 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.44 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3-benzyloxypropyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (139)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.71 (1H, m), 2.00-2.03 (2H, m), 2.08-2.11 ( 1H, m), 2.54-2.60 (1H, m), 2.93 (2H, t), 3.43-3.47 (2H, m), 3.52 (2H, t), 3 .58 (1H, dd), 3.76 (1H, dd), 3.84-3.94 (2H, m), 4.51 (2H, s), 6.43 (1H, s), 6. 93 (1H, s), 7.28-7.40 (5H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−[４−ベンジルオキシブチル]イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１４０）と記す。）０．６２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６７−１．７０（４Ｈ，ｍ），１．７９−１．８７（１Ｈ，ｍ），２．０２−２．１３（１Ｈ，ｍ），２．５６−２．６１（１Ｈ，ｍ），２．８１（２Ｈ，ｔ），３．４５（２Ｈ，ｄｔ），３．４８−３．５２（２Ｈ，ｍ），３．５９（１Ｈ，ｄｄ），３．７７（１Ｈ，ｄｄ），３．８４−３．９５（２Ｈ，ｍ），４．５１（２Ｈ，ｓ），６．４５（１Ｈ，ｄ），６．９３（１Ｈ，ｓ），７．３０−７．４１（５Ｈ，ｍ） Production Example 135
5- [4-Benzyloxybutyl] isoxazole-3-carboxylic acid (0.42 g, 1.5 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.26 g, 1.9 mmol), triethylamine (0.19 g, 1.9 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.19 mmol) were added to chloroform (amylene-added product) (3 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.37 g, 1.9 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.62 g of N- (tetrahydrofuran-3-ylmethyl) -5- [4-benzyloxybutyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (140)) represented by the formula
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.67-1.70 (4H, m), 1.79-1.87 (1H, m), 2.02-2.13 ( 1H, m), 2.56-2.61 (1H, m), 2.81 (2H, t), 3.45 (2H, dt), 3.48-3.52 (2H, m), 3 .59 (1H, dd), 3.77 (1H, dd), 3.84-3.95 (2H, m), 4.51 (2H, s), 6.45 (1H, d), 6. 93 (1H, s), 7.30-7.41 (5H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（５−ベンジルオキシペンチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１４１）と記す。）０．５９ｇ及び下式

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（５−ヒドロキシペンチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１４２）と記す。）０．４３ｇを得た。
本発明化合物（１４１）
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３９−１．４０（４Ｈ，ｍ），１．６１−１．６４（１Ｈ，ｍ），１．６８−１．７３（２Ｈ，ｍ），２．０６−２．１１（１Ｈ，ｍ），２．５３−２．６０（１Ｈ，ｍ），２．７８（２Ｈ，ｔ），３．４５−３．４７（４Ｈ，ｍ），３．５８（１Ｈ，ｄｄ），３．７７（１Ｈ，ｔ），３．８６（１Ｈ，ｄｄ），３．８８−３．９３（１Ｈ，ｍ），４．５０（２Ｈ，ｓ），６．４３（１Ｈ，ｓ），６．９２（１Ｈ，ｓ），７．３４−７．３５（５Ｈ，ｍ）
本発明化合物（１４２）
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３８−１．４１（４Ｈ，ｍ），１．６２−１．６６（１Ｈ，ｍ），１．７０−１．７３（２Ｈ，ｍ），２．０９−２．１０（１Ｈ，ｍ），２．５６−２．６１（１Ｈ，ｍ），２．８０（２Ｈ，ｔ），３．４６（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７６（１Ｈ，ｄｄ），３．８４−３．９４（２Ｈ，ｍ），４．０５（２Ｈ，ｔ），６．４４（１Ｈ，ｓ），６．９３（１Ｈ，ｓ） Production Example 136
A mixture (1.33 g) of 5- (5-benzyloxypentyl) isoxazole-3-carboxylic acid and 5- (5-hydroxypentyl) isoxazole-3-carboxylic acid, tetrahydrofuran-3-ylmethylamine hydrochloride (1 .10 g, 8.0 mmol), triethylamine (0.81 g, 8.0 mmol) and 1-hydroxybenzotriazole (0.11 g, 0.80 mmol) were added to chloroform (amylene-added product) (25 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.54 g, 8.0 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (5-benzyloxypentyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (141)) represented by the formula:

0.43 g of N- (tetrahydrofuran-3-ylmethyl) -5- (5-hydroxypentyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (142)) represented by the formula (1) was obtained.
The present compound (141)
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.39.-1.40 (4H, m), 1.61-1.64 (1H, m), 1.68-1.73 ( 2H, m), 2.06-2.11 (1H, m), 2.53-2.60 (1H, m), 2.78 (2H, t), 3.45-3.47 (4H, m), 3.58 (1H, dd), 3.77 (1H, t), 3.86 (1H, dd), 3.88-3.93 (1H, m), 4.50 (2H, s) ), 6.43 (1H, s), 6.92 (1H, s), 7.34-7.35 (5H, m)
Compound (142) of the present invention
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.38-1.41 (4H, m), 1.62-1.66 (1H, m), 1.70-1.73 ( 2H, m), 2.09-2.10 (1H, m), 2.56-2.61 (1H, m), 2.80 (2H, t), 3.46 (2H, t), 3 .59 (1H, dd), 3.76 (1H, dd), 3.84-3.94 (2H, m), 4.05 (2H, t), 6.44 (1H, s), 6. 93 (1H, s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（６−ベンジルオキシヘキシル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１４３）と記す。）０．３２ｇ及び下式

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（６−ヒドロキシヘキシル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１４４）と記す。）０．１４ｇを得た。
本発明化合物（１４３）
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３７−１．４５（４Ｈ，ｍ），１．５６−１．６５（３Ｈ，ｍ），１．６６−１．７５（２Ｈ，ｍ），２．０４−２．１３（１Ｈ，ｍ），２．５４−２．６０（１Ｈ，ｍ），２．７８（２Ｈ，ｔ），３．４５−３．４７（４Ｈ，ｍ），３．５８（１Ｈ，ｄｄ），３．７６（１Ｈ，ｄｄ），３．８６（１Ｈ，ｄｄ），３．９０−３．９２（１Ｈ，ｍ），４．５１（２Ｈ，ｓ），６．４３（１Ｈ，ｓ），６．９４（１Ｈ，ｓ），７．２８−７．３７（５Ｈ，ｍ）
本発明化合物（１４４）
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３８（４Ｈ，ｔｄ），１．５７−１．６８（３Ｈ，ｍ），１．７１−１．７５（２Ｈ，ｍ），２．０４−２．１３（１Ｈ，ｍ），２．５２−２．６２（１Ｈ，ｍ），２．８０（２Ｈ，ｔ），３．４６（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７７（１Ｈ，ｄｄ），３．８６（１Ｈ，ｄｄ），３．９１（１Ｈ，ｔｄ），４．０５（２Ｈ，ｔ），６．４６（１Ｈ，ｓ），６．９５（１Ｈ，ｓ） Production Example 137
A mixture of 5- (6-benzyloxyhexyl) isoxazole-3-carboxylic acid and 5- (6-hydroxyhexyl) isoxazole-3-carboxylic acid (1.23 g), tetrahydrofuran-3-ylmethylamine hydrochloride (1. 10 g, 8.0 mmol), triethylamine (0.81 g, 8.0 mmol) and 1-hydroxybenzotriazole (0.11 g, 0.80 mmol) were added to chloroform (amylene-added product) (25 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.54 g, 8.0 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (6-benzyloxyhexyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (143)) represented by the formula:

0.14 g of N- (tetrahydrofuran-3-ylmethyl) -5- (6-hydroxyhexyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (144)) represented by the formula (1) was obtained.
Compound (143) of the present invention
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.37-1.45 (4H, m), 1.56-1.65 (3H, m), 1.66-1.75 ( 2H, m), 2.04-2.13 (1H, m), 2.54-2.60 (1H, m), 2.78 (2H, t), 3.45-3.47 (4H, m), 3.58 (1H, dd), 3.76 (1H, dd), 3.86 (1H, dd), 3.90-3.92 (1H, m), 4.51 (2H, s) ), 6.43 (1H, s), 6.94 (1H, s), 7.28-7.37 (5H, m)
The present compound (144)
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.38 (4H, td), 1.57-1.68 (3H, m), 1.71-1.75 (2H, m) , 2.04-2.13 (1H, m), 2.52-2.62 (1H, m), 2.80 (2H, t), 3.46 (2H, t), 3.59 (1H , Dd), 3.77 (1H, dd), 3.86 (1H, dd), 3.91 (1H, td), 4.05 (2H, t), 6.46 (1H, s), 6 .95 (1H, s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−フェノキシプロピル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１４５）と記す。）０．５１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６４−１．７０（１Ｈ，ｍ），２．０４−２．１２（１Ｈ，ｍ），２．１８−２．２２（２Ｈ，ｍ），２．５２−２．６２（１Ｈ，ｍ），３．０３（２Ｈ，ｔ），３．４３−３．４７（２Ｈ，ｍ），３．５９（１Ｈ，ｄｄ），３．７６（１Ｈ，ｄｄ），３．８３−３．９４（２Ｈ，ｍ），４．０２（２Ｈ，ｔ），６．５０（１Ｈ，ｓ），６．８８−６．９０（２Ｈ，ｍ），６．９４−６．９８（１Ｈ，ｍ），７．００（１Ｈ，ｓ），７．２８−７．３０（２Ｈ，ｍ） Production Example 138
5- (3-phenoxypropyl) isoxazole-3-carboxylic acid (0.50 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.33 g, 2.4 mmol), triethylamine (0.25 g, 2 .4 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.24 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.51 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3-phenoxypropyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (145)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.70 (1H, m), 2.04-2.12 (1H, m), 2.18-2.22 ( 2H, m), 2.52-2.62 (1H, m), 3.03 (2H, t), 3.43-3.47 (2H, m), 3.59 (1H, dd), 3 .76 (1H, dd), 3.83-3.94 (2H, m), 4.02 (2H, t), 6.50 (1H, s), 6.88-6.90 (2H, m ), 6.94-6.98 (1H, m), 7.00 (1H, s), 7.28-7.30 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（４−フェノキシブチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１４６）と記す。）０．５１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６６−１．６９（１Ｈ，ｍ），１．８３−１．９８（４Ｈ，ｍ），２．０８−２．１１（１Ｈ，ｍ），２．５４−２．６１（１Ｈ，ｍ），２．８９（２Ｈ，ｔ），３．４４−３．４７（２Ｈ，ｍ），３．５９（１Ｈ，ｄｄ），３．７７（１Ｈ，ｄｄ），３．８４−３．９４（２Ｈ，ｍ），３．９９（２Ｈ，ｔ），６．４８（１Ｈ，ｓ），６．８９（２Ｈ，ｄｄｄ），６．９５（２Ｈ，ｄｑ），７．２７−７．３１（２Ｈ，ｍ） Production Example 139
5- (4-phenoxybutyl) isoxazole-3-carboxylic acid (0.52 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.33 g, 2.4 mmol), triethylamine (0.25 g, 2 .4 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.24 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.51 g of N- (tetrahydrofuran-3-ylmethyl) -5- (4-phenoxybutyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (146)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.66 to 1.69 (1H, m), 1.83-1.98 (4H, m), 2.08 to 2.11. 1H, m), 2.54-2.61 (1H, m), 2.89 (2H, t), 3.44-3.47 (2H, m), 3.59 (1H, dd), 3 .77 (1H, dd), 3.84-3.94 (2H, m), 3.99 (2H, t), 6.48 (1H, s), 6.89 (2H, ddd), 6. 95 (2H, dq), 7.27-7.31 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（５−フェノキシペンチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１４７）と記す。）０．８１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．５５−１．５９（２Ｈ，ｍ），１．６５−１．７１（１Ｈ，ｍ），１．７６−１．８６（４Ｈ，ｍ），２．０４−２．１３（１Ｈ，ｍ），２．５２−２．６２（１Ｈ，ｍ），２．８３（２Ｈ，ｔ），３．４６（２Ｈ，ｄｄ），３．５９（１Ｈ，ｄｄ），３．７６（１Ｈ，ｄｄ），３．８６（１Ｈ，ｄｄ），３．９１（１Ｈ，ｔｄ），３．９６（２Ｈ，ｔ），６．４６（１Ｈ，ｓ），６．８７−６．９６（４Ｈ，ｍ），７．２７−７．２９（２Ｈ，ｍ） Production Example 140
5- (5-phenoxypentyl) isoxazole-3-carboxylic acid (0.70 g, 2.5 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.42 g, 3.0 mmol), triethylamine (0.31 g, 3 0.0 mmol) and 1-hydroxybenzotriazole (0.04 g, 0.30 mmol) were added to chloroform (amylene-added product) (8 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.58 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.81 g of N- (tetrahydrofuran-3-ylmethyl) -5- (5-phenoxypentyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (147)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.55-1.59 (2H, m), 1.65-1.71 (1H, m), 1.76-1.86 4H, m), 2.04-2.13 (1H, m), 2.52-2.62 (1H, m), 2.83 (2H, t), 3.46 (2H, dd), 3 .59 (1H, dd), 3.76 (1H, dd), 3.86 (1H, dd), 3.91 (1H, td), 3.96 (2H, t), 6.46 (1H, s), 6.87-6.96 (4H, m), 7.27-7.29 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（６−フェノキシヘキシル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１４８）と記す。）０．７７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４０−１．５６（４Ｈ，ｍ），１．６４−１．６８（１Ｈ，ｍ），１．７２−１．８２（４Ｈ，ｍ），２．０４−２．１３（１Ｈ，ｍ），２．５２−２．６２（１Ｈ，ｍ），２．８１（２Ｈ，ｔ），３．４６（２Ｈ，ｄｔ），３．５８（１Ｈ，ｄｄ），３．７３−３．７９（１Ｈ，ｍ），３．８６（１Ｈ，ｄｄ），３．８８−３．９３（１Ｈ，ｍ），３．９５（２Ｈ，ｔ），６．４５（１Ｈ，ｓ），６．８７−６．９５（４Ｈ，ｍ），７．２７−７．２９（２Ｈ，ｍ） Production Example 141
5- (6-phenoxyhexyl) isoxazole-3-carboxylic acid (0.72 g, 2.5 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.42 g, 3.0 mmol), triethylamine (0.31 g, 3 0.0 mmol) and 1-hydroxybenzotriazole (0.04 g, 0.30 mmol) were added to chloroform (amylene-added product) (8 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.58 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.77 g of N- (tetrahydrofuran-3-ylmethyl) -5- (6-phenoxyhexyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (148)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.40-1.56 (4H, m), 1.64-1.68 (1H, m), 1.72-1.82 ( 4H, m), 2.04-2.13 (1H, m), 2.52-2.62 (1H, m), 2.81 (2H, t), 3.46 (2H, dt), 3 .58 (1H, dd), 3.73-3.79 (1H, m), 3.86 (1H, dd), 3.88-3.93 (1H, m), 3.95 (2H, t ), 6.45 (1H, s), 6.87-6.95 (4H, m), 7.27-7.29 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−フェノキシエチルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１４９）と記す。）１．６０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６６−１．６９（１Ｈ，ｍ），２．０５−２．１３（１Ｈ，ｍ），２．５６−２．６０（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５６−３．６１（１Ｈ，ｍ），３．７４−３．８０（１Ｈ，ｍ），３．８４−３．８８（１Ｈ，ｍ），３．９１−３．９３（３Ｈ，ｍ），４．１５−４．１７（２Ｈ，ｍ），４．７７（２Ｈ，ｓ），６．７６（１Ｈ，ｓ），６．９０−７．００（４Ｈ，ｍ），７．２７−７．３２（２Ｈ，ｍ） Production Example 142
5- (2-phenoxyethyloxymethyl) isoxazole-3-carboxylic acid (1.40 g, 5.3 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.88 g, 6.4 mmol), triethylamine (0.65 g) , 6.4 mmol) and 1-hydroxybenzotriazole (0.08 g, 0.64 mmol) were added to chloroform (amylene-added product) (20 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.23 g, 6.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.60 g of N- (tetrahydrofuran-3-ylmethyl) -5- (2-phenoxyethyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (149)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.66 to 1.69 (1H, m), 2.05-2.13 (1H, m), 2.56-2.60 ( 1H, m), 3.47 (2H, t), 3.56-3.61 (1H, m), 3.74-3.80 (1H, m), 3.84-3.88 (1H, m), 3.91-3.93 (3H, m), 4.15-4.17 (2H, m), 4.77 (2H, s), 6.76 (1H, s), 6.90. -7.00 (4H, m), 7.27-7.32 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−[７−（２−キノリルオキシ）ヘプチル]イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１５０）と記す。）０．５１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４０−１．４４（４Ｈ，ｍ），１．４７−１．５１（２Ｈ，ｍ），１．６６−１．７４（３Ｈ，ｍ），１．７９−１．８６（２Ｈ，ｍ），２．０４−２．１２（１Ｈ，ｍ），２．５２−２．６０（１Ｈ，ｍ），２．７９（２Ｈ，ｔ），３．４３−３．４７（２Ｈ，ｍ），３．５８（１Ｈ，ｄｄ），３．７３−３．７９（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），４．４６（２Ｈ，ｔ），６．４４（１Ｈ，ｓ），６．８９（１Ｈ，ｄ），６．９２（１Ｈ，ｓ），７．３４−７．３８（１Ｈ，ｍ），７．５９−７．６３（１Ｈ，ｍ），７．７１（１Ｈ，ｄｄ），７．８２（１Ｈ，ｄ），７．９７（１Ｈ，ｄ） Production Example 143
5- [7- (2-quinolyloxy) heptyl] isoxazole-3-carboxylic acid (0.50 g, 1.4 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.33 g, 2.4 mmol), triethylamine (0 .24 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.24 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.51 g of N- (tetrahydrofuran-3-ylmethyl) -5- [7- (2-quinolyloxy) heptyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (150)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.40-1.44 (4H, m), 1.47-1.51 (2H, m), 1.66-1.74 ( 3H, m), 1.79-1.86 (2H, m), 2.04-2.12 (1H, m), 2.52-2.60 (1H, m), 2.79 (2H, t), 3.43-3.47 (2H, m), 3.58 (1H, dd), 3.73-3.79 (1H, m), 3.84-3.94 (2H, m) 4.46 (2H, t), 6.44 (1H, s), 6.89 (1H, d), 6.92 (1H, s), 7.34-7.38 (1H, m), 7.59-7.63 (1H, m), 7.71 (1H, dd), 7.82 (1H, d), 7.97 (1H, d)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（１−フルオロブチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１５１）と記す。）１６６ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．００（ｔ，３Ｈ），１．４３−１．５６（ｍ，２Ｈ），１．６３−１．７２（ｍ，１Ｈ），１．８７−２．１５（ｍ，３Ｈ），２．５４−２．６３（ｍ，１Ｈ），３．４５−３．５０（ｍ，２Ｈ），３．５９（ｄｄ，１Ｈ），３．７３−３．８０（ｍ，１Ｈ），３．８３−３．９５（ｍ，２Ｈ），５．５９（ｄｄｄ，１Ｈ），６．７５−６．７７（ｍ，１Ｈ），６．９４（ｂｒｓ，１Ｈ） Production Example 144
5- (1-fluorobutyl) isoxazole-3-carboxylic acid (120 mg, 0.64 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (114 mg, 0.83 mmol), triethylamine (0.23 mL, 1.65 mmol) and 1-hydroxybenzotriazole (9 mg, 0.06 mmol) was added to chloroform (amylene-added product) (3 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (160 mg, 0.83 mmol) at room temperature, stirred overnight, then concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography. The following formula

166 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (1-fluorobutyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (151)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.00 (t, 3H), 1.43-1.56 (m, 2H), 1.63-1.72 (m, 1H) 1.87-2.15 (m, 3H), 2.54-2.63 (m, 1H), 3.45-3.50 (m, 2H), 3.59 (dd, 1H), 3 .73-3.80 (m, 1H), 3.83-3.95 (m, 2H), 5.59 (ddd, 1H), 6.75-6.77 (m, 1H), 6.94 (Brs, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（ヒドロキシフェニルメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１５２）と記す。）２．７８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６４−１．６７（１Ｈ，ｍ），２．０３−２．１２（１Ｈ，ｍ），２．５３−２．５９（１Ｈ，ｍ），３．４３−３．４６（２Ｈ，ｍ），３．５８（１Ｈ，ｄｄ），３．７６（１Ｈ，ｄｄ），３．８４（１Ｈ，ｄｄ），３．８９−３．９１（１Ｈ，ｍ），５．９７（１Ｈ，ｓ），６．６１（１Ｈ，ｓ），６．９５（１Ｈ，ｓ），７．３７−７．４５（５Ｈ，ｍ） Production Example 145
5- (hydroxyphenylmethyl) isoxazole-3-carboxylic acid (2.56 g, 10.4 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (1.77 g, 13.0 mmol), triethylamine (1.31 g, 13. 0 mmol) and 1-hydroxybenzotriazole (0.18 g, 1.3 mmol) were added to chloroform (amylene-added product) (13 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (2.42 g, 13.0 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

2.78 g of N- (tetrahydrofuran-3-ylmethyl) -5- (hydroxyphenylmethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (152)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64 to 1.67 (1H, m), 2.03 to 2.12 (1H, m), 2.53 to 2.59 ( 1H, m), 3.43-3.46 (2H, m), 3.58 (1H, dd), 3.76 (1H, dd), 3.84 (1H, dd), 3.89-3 .91 (1H, m), 5.97 (1H, s), 6.61 (1H, s), 6.95 (1H, s), 7.37-7.45 (5H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（１−フルオロ−１−フェニルメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１５４）と記す。）２００ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６１−１．７７（ｍ，１Ｈ），２．０３−２．１３（ｍ，１Ｈ），２．５２−２．６２（ｍ，１Ｈ），３．４３−３．４８（ｍ，２Ｈ），３．５８（ｄｄ，１Ｈ），３．７２−３．７９（ｍ，1Ｈ），３．８２−３．９５（ｍ，２Ｈ），６．５４（ｄ，１Ｈ），６．６４−６．６７（ｍ，１Ｈ），６．９２（ｂｒｓ，１Ｈ），７．４２−７．４５（ｍ，５Ｈ） Production Example 146
5- (1-Fluoro-1-phenylmethyl) isoxazole-3-carboxylic acid (250 mg, 1.13 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (202 mg, 1.47 mmol), triethylamine (0.41 mL, 2 .94 mmol) and 1-hydroxybenzotriazole (15 mg, 0.11 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (282 mg, 1.47 mmol) at room temperature, and the mixture was stirred overnight, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

200 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (1-fluoro-1-phenylmethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (154)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.61-1.77 (m, 1H), 2.03-2.13 (m, 1H), 2.52-2.62 ( m, 1H), 3.43-3.48 (m, 2H), 3.58 (dd, 1H), 3.72-3.79 (m, 1H), 3.82-3.95 (m, 2H), 6.54 (d, 1H), 6.64-6.67 (m, 1H), 6.92 (brs, 1H), 7.42-7.45 (m, 5H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（１，１−ジフルオロ−１−フェニルメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１５５）と記す。）１９０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６１−１．７２（ｍ，１Ｈ），２．０３−２．１４（ｍ，１Ｈ），２．５２−２．６２（ｍ，１Ｈ），３．４４−３．４９（ｍ，２Ｈ），３．５８（ｄｄ，Ｊ＝８．８，５．２Ｈｚ，１Ｈ），３．７２−３．７９（ｍ，1Ｈ），３．８２−３．８６（ｍ，１Ｈ），３．８８−３．９４（ｍ，１Ｈ），６．８６−６．８８（ｍ，１Ｈ），６．９２（ｂｒｓ，１Ｈ），７．４６−７．６１（ｍ，５Ｈ） Production Example 147
To a toluene solution (10 mL) of 5- (1,1-difluoro-1-phenylmethyl) isoxazole-3-carboxylic acid chloride (<0.60 mmol) was added tetrahydrofuran-3-ylmethylamine hydrochloride (200 mg, 1.45 mmol). ) And 1 mol / L aqueous sodium hydroxide solution (10 mL) were added simultaneously under ice water cooling. After stirring vigorously for 1 hour under ice water cooling, the reaction mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

190 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (1,1-difluoro-1-phenylmethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (155)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.61-1.72 (m, 1H), 2.03-2.14 (m, 1H), 2.52-2.62 ( m, 1H), 3.44-3.49 (m, 2H), 3.58 (dd, J = 8.8, 5.2 Hz, 1H), 3.72-3.79 (m, 1H), 3.82-3.86 (m, 1H), 3.88-3.94 (m, 1H), 6.86-6.88 (m, 1H), 6.92 (brs, 1H), 7. 46-7.61 (m, 5H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（１−フェニル−シクロプロピル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１５６）と記す。）５０４ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４１−１．４６（ｍ，２Ｈ），１．６０−１．７０（ｍ，３Ｈ），２．０１−２．１１（ｍ，１Ｈ），２．４９−２．５９（ｍ，１Ｈ），３．３９−３．４４（ｍ，２Ｈ），３．５６（ｄｄ，Ｊ＝８．９，５．３Ｈｚ，１Ｈ），３．７１−３．７８（ｍ，1Ｈ），３．８０−３．９２（ｍ，２Ｈ），６．１３（ｓ，１Ｈ），６．８６（ｂｒｓ，１Ｈ），７．２９−７．４２（ｍ，５Ｈ） Production Example 148
To a toluene solution (20 mL) of 5- (1-phenylcyclopropyl) isoxazole-3-carboxylic acid chloride (<1.83 mmol) was added tetrahydrofuran-3-ylmethylamine hydrochloride (250 mg, 1.82 mmol) and 1 mol / L. Aqueous sodium hydroxide (20 mL) was added simultaneously with ice water cooling. After stirring vigorously for 30 minutes under ice water cooling, the reaction mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

504 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (1-phenyl-cyclopropyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (156)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.41-1.46 (m, 2H), 1.60-1.70 (m, 3H), 2.01-2.11. m, 1H), 2.49-2.59 (m, 1H), 3.39-3.44 (m, 2H), 3.56 (dd, J = 8.9, 5.3 Hz, 1H), 3.71-3.78 (m, 1H), 3.80-3.92 (m, 2H), 6.13 (s, 1H), 6.86 (brs, 1H), 7.29-7. 42 (m, 5H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−トリフルオロメチルベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１５７）と記す。）１３０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６１−１．７３（ｍ，１Ｈ），２．０１−２．１４（ｍ，１Ｈ），２．４９−２．６３（ｍ，１Ｈ），３．４１−３．４６（ｍ，２Ｈ），３．５７（ｄｄ，Ｊ＝８．９，５．３Ｈｚ，１Ｈ），３．７２−３．７９（ｍ，１Ｈ），３．８２−３．９４（ｍ，２Ｈ），４．３１（ｓ，２Ｈ），６．３４（ｓ，１Ｈ），６．９０（ｂｒｓ，１Ｈ），７．３４−７．３８（ｍ，１Ｈ），７．３９−７．４５（ｍ、１Ｈ），７．５１−７．５６（ｍ，１Ｈ），７．６８−７．７２（ｍ，１Ｈ）． Production Example 149
5- (2-trifluoromethylbenzyl) isoxazole-3-carboxylic acid (380 mg, 1.40 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (239 mg, 1.74 mmol), triethylamine (0.46 mL, 3.28 mmol) ) And 1-hydroxybenzotriazole (18 mg, 0.13 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (295 mg, 1.54 mmol) at room temperature, and the mixture was stirred for 5.5 hours and then concentrated under reduced pressure. Water was added to the concentrate and extracted once with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

130 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (2-trifluoromethylbenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (157)) represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.61-1.73 (m, 1H), 2.01-2.14 (m, 1H), 2.49-2.63 ( m, 1H), 3.41-3.46 (m, 2H), 3.57 (dd, J = 8.9, 5.3 Hz, 1H), 3.72-3.79 (m, 1H), 3.82-3.94 (m, 2H), 4.31 (s, 2H), 6.34 (s, 1H), 6.90 (brs, 1H), 7.34-7.38 (m, 1H), 7.39-7.45 (m, 1H), 7.51-7.56 (m, 1H), 7.68-7.72 (m, 1H).

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−トリフルオロメチルベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１５８）と記す。）１３０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６１−１．７１（ｍ，１Ｈ），２．０３−２．１２（ｍ，１Ｈ），２．５２−２．６１（ｍ，１Ｈ），３．４５（ｄｄ，Ｊ＝６．６，６．６Ｈｚ，２Ｈ），３．５８（ｄｄ，Ｊ＝８．７，５．３Ｈｚ，１Ｈ），３．７２−３．７９（ｍ，１Ｈ），３．８２−３．９４（ｍ，２Ｈ），４．１９（ｓ，２Ｈ），６．４３（ｓ，１Ｈ），６．９０（ｂｒｓ，１Ｈ），７．４３−７．５９（ｍ，４Ｈ） Production Example 150
5- (3-trifluoromethylbenzyl) isoxazole-3-carboxylic acid (242 mg, 0.89 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (155 mg, 1.15 mmol), triethylamine (0.32 mL, 2.30 mmol) ) And 1-hydroxybenzotriazole (15 mg, 0.11 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (220 mg, 1.15 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 130 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (3-trifluoromethylbenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (158)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.61-1.71 (m, 1H), 2.03-2.12 (m, 1H), 2.52-2.61 ( m, 1H), 3.45 (dd, J = 6.6, 6.6 Hz, 2H), 3.58 (dd, J = 8.7, 5.3 Hz, 1H), 3.72-3.79. (M, 1H), 3.82-3.94 (m, 2H), 4.19 (s, 2H), 6.43 (s, 1H), 6.90 (brs, 1H), 7.43- 7.59 (m, 4H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（ナフタレン−２−イルメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１５９）と記す。）１６６ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７２（ｍ，１Ｈ），２．０２−２．１２（ｍ，１Ｈ），２．５２−２．６１（ｍ，１Ｈ），３．４１−３．４６（ｍ，２Ｈ），３．５７（ｄｄ，Ｊ＝９．０，５．３Ｈｚ，１Ｈ），３．７２−３．７９（ｍ，１Ｈ），３．８２−３．９３（ｍ，２Ｈ），４．２９（ｓ，２Ｈ），６．４３（ｄ，Ｊ＝３．９Ｈｚ，１Ｈ），６．９０（ｂｒｓ，１Ｈ），７．３４−７．３８（ｍ，１Ｈ），７．４６−７．５３（ｍ、２Ｈ），７．７１（ｓ，１Ｈ），７．７８−７．８６（ｍ，３Ｈ） Production Example 151
5- (Naphthalen-2-ylmethyl) isoxazole-3-carboxylic acid (204 mg, 0.81 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (204 mg, 1.48 mmol), triethylamine (0.38 mL, 2.75 mmol) And 1-hydroxybenzotriazole (14 mg, 0.11 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (264 mg, 1.38 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

166 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (naphthalen-2-ylmethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (159)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.72 (m, 1H), 2.02-2.12 (m, 1H), 2.52-2.61 ( m, 1H), 3.41-3.46 (m, 2H), 3.57 (dd, J = 9.0, 5.3 Hz, 1H), 3.72-3.79 (m, 1H), 3.82-3.93 (m, 2H), 4.29 (s, 2H), 6.43 (d, J = 3.9 Hz, 1H), 6.90 (brs, 1H), 7.34- 7.38 (m, 1H), 7.46-7.53 (m, 2H), 7.71 (s, 1H), 7.78-7.86 (m, 3H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（ナフタレン−１−イルメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１６０）と記す。）９５ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．５７−１．６７（ｍ，１Ｈ），１．９９−２．０８（ｍ，１Ｈ），２．４８−２．６０（ｍ，１Ｈ），３．３６−３．４４（ｍ，２Ｈ），３．５２−３．５７（ｍ，１Ｈ），３．６９−３．９３（ｍ，３Ｈ），４．５５（ｓ，２Ｈ），６．２７（ｓ，１Ｈ），６．９６（ｂｒｓ，１Ｈ），７．３７−７．５４（ｍ，４Ｈ），７．８０−７．８５（ｍ、１Ｈ），７．８６−７．９２（ｍ，２Ｈ） Production Example 152
5- (Naphthalen-1-ylmethyl) isoxazole-3-carboxylic acid (123 mg, 0.49 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (123 mg, 0.90 mmol), triethylamine (0.23 mL, 1.66 mmol) And 1-hydroxybenzotriazole (9 mg, 0.06 mmol) was added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (159 mg, 0.83 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

95 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (naphthalen-1-ylmethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (160)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.57-1.67 (m, 1H), 1.99-2.08 (m, 1H), 2.48-2.60 ( m, 1H), 3.36-3.44 (m, 2H), 3.52-3.57 (m, 1H), 3.69-3.93 (m, 3H), 4.55 (s, 2H), 6.27 (s, 1H), 6.96 (brs, 1H), 7.37-7.54 (m, 4H), 7.80-7.85 (m, 1H), 7.86. -7.92 (m, 2H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（ベンゾ［ｂ］チオフェン−２−イルメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１６１）と記す。）１０４ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７１（ｍ，１Ｈ），２．０３−２．１３（ｍ，１Ｈ），２．５０−２．６３（ｍ，１Ｈ），３．４３−３．４８（ｍ，２Ｈ），３．５８（ｄｄ，Ｊ＝８．９，５．３Ｈｚ，１Ｈ），３．７２−３．７９（ｍ，１Ｈ），３．８２−３．９４（ｍ，２Ｈ），４．４１（ｓ，２Ｈ），６．５８（ｓ，１Ｈ），６．９１（ｓ，１Ｈ），７．１６（ｓ，１Ｈ），７．２９−７．３７（ｍ，２Ｈ），７．６９−７．７３（ｍ，１Ｈ），７．７６−７．８１（ｍ，１Ｈ） Production Example 153
To a toluene solution (10 mL) of 5- (benzo [b] thiophen-2-ylmethyl) isoxazole-3-carboxylic acid chloride (<0.38 mmol) was added tetrahydrofuran-3-ylmethylamine hydrochloride (150 mg, 1.09 mmol). And 1 mol / L aqueous sodium hydroxide solution (8 mL) were added simultaneously under ice water cooling. After stirring vigorously for 30 minutes under ice water cooling, the reaction mixture was extracted once with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

104 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (benzo [b] thiophen-2-ylmethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (161)) represented by formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.71 (m, 1H), 2.03-2.13 (m, 1H), 2.50-2.63 ( m, 1H), 3.43-3.48 (m, 2H), 3.58 (dd, J = 8.9, 5.3 Hz, 1H), 3.72-3.79 (m, 1H), 3.82-3.94 (m, 2H), 4.41 (s, 2H), 6.58 (s, 1H), 6.91 (s, 1H), 7.16 (s, 1H), 7 .29-7.37 (m, 2H), 7.69-7.73 (m, 1H), 7.76-7.81 (m, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（４−フェノキシベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１６２）と記す。）０．３４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６２−１．７０（１Ｈ，ｍ），２．０３−２．１２（１Ｈ，ｍ），２．５１−２．６１（１Ｈ，ｍ）， ３．４３−３．４６（２Ｈ，ｍ），３．５６−３．６０（１Ｈ，ｍ），３．７３−３．７９（１Ｈ，ｍ），３．８３−３．９２（２Ｈ， ｍ），４．０９（２Ｈ， ｓ），６．４１（１Ｈ，ｓ），６．９６−７．０２（５Ｈ，ｍ），７．０９−７．１４（１Ｈ，ｍ），７．２０−７．２２（２Ｈ，ｍ）７．３２−７．３７（２Ｈ，ｍ） Production Example 154
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.20 g, 1.46 mmol) and triethylamine (0.15 g, 1.46 mmol) were added to chloroform (amylene-added product) (7 mL). To the mixture at room temperature 5- (4-phenoxybenzyl) isoxazole-3-carboxylic acid (0.36 g, 1.22 mmol), 1-hydroxybenzotriazole (0.02 g, 0.12 mmol) and 1-ethyl-3- (3-Dimethylaminopropyl) carbodiimide hydrochloride (0.28 g, 1.46 mmol) was added, and the mixture was stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.34 g of N- (tetrahydrofuran-3-ylmethyl) -5- (4-phenoxybenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (162)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.70 (1H, m), 2.03-2.12 (1H, m), 2.51-2.61 ( 1H, m), 3.43-3.46 (2H, m), 3.56-3.60 (1H, m), 3.73-3.79 (1H, m), 3.83-3. 92 (2H, m), 4.09 (2H, s), 6.41 (1H, s), 6.96-7.02 (5H, m), 7.09-7.14 (1H, m) 7.20-7.22 (2H, m) 7.32-7.37 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−フェノキシベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１６３）と記す。）０．３１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６２−１．７１（１Ｈ，ｍ），２．０３−２．１１（１Ｈ，ｍ），２．５１−２．６１（１Ｈ，ｍ）， ３．４３−３．４６（２Ｈ，ｍ），３．５６−３．５９（１Ｈ，ｍ），３．７３−３．７９（１Ｈ，ｍ），３．８２−３．９４（２Ｈ， ｍ），４．０８（２Ｈ， ｓ），６．４１（１Ｈ，ｓ），６．９０−７．０２（６Ｈ，ｍ），７．１０−７．１４（１Ｈ，ｍ），７．２８−７．３７（３Ｈ，ｍ） Production Example 155
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.17 g, 1.22 mmol) and triethylamine (0.12 g, 1.22 mmol) were added to chloroform (amylene-added product) (6 mL). To the mixture at room temperature 5- (3-phenoxybenzyl) isoxazole-3-carboxylic acid (0.30 g, 1.02 mmol), 1-hydroxybenzotriazole (0.01 g, 0.10 mmol) and 1-ethyl-3- (3-Dimethylaminopropyl) carbodiimide hydrochloride (0.23 g, 1.22 mmol) was added and stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.31 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3-phenoxybenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (163)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.71 (1H, m), 2.03-2.11 (1H, m), 2.51-2.61 ( 1H, m), 3.43-3.46 (2H, m), 3.56-3.59 (1H, m), 3.73-3.79 (1H, m), 3.82-3. 94 (2H, m), 4.08 (2H, s), 6.41 (1H, s), 6.90-7.02 (6H, m), 7.10-7.14 (1H, m) , 7.28-7.37 (3H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−（５−ベンジルオキシメチル−４−ホルミル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１６５）と記す。）２．４６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６５−１．７５（ｍ，１Ｈ），２．０７−２．１６（ｍ，１Ｈ），２．５６−２．６８（ｍ，１Ｈ），３．４７−３．５４（ｍ，２Ｈ），３．６２（ｄｄ，Ｊ＝９．０，５．１Ｈｚ，１Ｈ），３．７４−３．８２（ｍ，1Ｈ），３．８４−３．９７（ｍ，２Ｈ），４．６７（ｓ，２Ｈ），４．９７（ｓ，２Ｈ），７．３０−７．４３（ｍ，６Ｈ），１０．４０（ｓ，１Ｈ） Production Example 156
To a solution of N- (tetrahydrofuran-3-ylmethyl)-(5-benzyloxymethyl) isoxazole-3-carboxamide (3.16 g, 9.99 mmol) in tetrahydrofuran (50 mL) was added 1 at −50 ° C. or lower under a nitrogen atmosphere. .64 mol / Ln-butyllithium hexane solution (15.2 mL, 25.0 mmol) was added dropwise. After stirring at −60 ° C. or lower for 1 hour, an N, N-dimethylformamide (3 mL) solution was added to the reaction mixture, and the mixture was stirred in the range of −60 ° C. to 10 ° C. for 1.5 hours. / L hydrochloric acid (about 20 mL) was poured and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl)-(5-benzyloxymethyl-4-formyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (165)) 2 was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.65-1.75 (m, 1H), 2.07-2.16 (m, 1H), 2.56-2.68 ( m, 1H), 3.47-3.54 (m, 2H), 3.62 (dd, J = 9.0, 5.1 Hz, 1H), 3.74-3.82 (m, 1H), 3.84-3.97 (m, 2H), 4.67 (s, 2H), 4.97 (s, 2H), 7.30-7.43 (m, 6H), 10.40 (s, 1H)

で示される５−ベンジルオキシメチル−３−［Ｎ−（３−テトラヒドロフラニルメチル）カルバモイル］イソキサゾール−４−カルボン酸（以下、本発明化合物（１６６）と記す。）２．００ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６４−１．７７（ｍ，１Ｈ），２．０９−２．２０（ｍ，１Ｈ），２．５８−２．７０（ｍ，１Ｈ），３．５２−３．５７（ｍ，２Ｈ），３．６４（ｄｄ，Ｊ＝９．２，４．６Ｈｚ，１Ｈ），３．７５−３．８８（ｍ，２Ｈ），３．９２−３．９９（ｍ，１Ｈ），４．６９（ｓ，２Ｈ），５．１３（ｓ，２Ｈ），７．２８−７．４０（ｍ，６Ｈ），７．５６（ｂｒｓ，１Ｈ） Production Example 157
To a solution of N- (tetrahydrofuran-3-ylmethyl)-(5-benzyloxymethyl) isoxazole-3-carboxamide (2.50 g, 7.90 mmol) in tetrahydrofuran (40 mL) at −50 ° C. or lower in a nitrogen atmosphere A .58 mol / L-n-butyllithium hexane solution (12.5 mL, 19.8 mmol) was added dropwise and stirred at −60 ° C. or lower for 30 minutes, and then carbon dioxide was introduced into the reaction mixture. Stir at 0 ° C. for 2 hours. Next, 1 mol / L hydrochloric acid (about 20 mL) was poured under ice cooling, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue is suspended in diisopropyl ether and collected by filtration.

2.00 g of 5-benzyloxymethyl-3- [N- (3-tetrahydrofuranylmethyl) carbamoyl] isoxazole-4-carboxylic acid (hereinafter referred to as the present compound (166)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.77 (m, 1H), 2.09-2.20 (m, 1H), 2.58-2.70 ( m, 1H), 3.52-3.57 (m, 2H), 3.64 (dd, J = 9.2, 4.6 Hz, 1H), 3.75-3.88 (m, 2H), 3.92-3.99 (m, 1H), 4.69 (s, 2H), 5.13 (s, 2H), 7.28-7.40 (m, 6H), 7.56 (brs, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−（５−ベンジルオキシメチル−４−メトキシカルボニル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１６７）と記す。）２２３ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６５−１．７５（ｍ，１Ｈ），２．０６−２．１５（ｍ，１Ｈ），２．５５−２．６６（ｍ，１Ｈ），３．４７−３．５３（ｍ，２Ｈ），３．６０（ｄｄ，Ｊ＝８．７，５．５Ｈｚ，１Ｈ），３．７４−３．８１（ｍ，１Ｈ），３．８７（ｓ，３Ｈ），３．８５−３．９５（ｍ，２Ｈ），４．６４（ｓ，２Ｈ），４．８８（ｓ，２Ｈ），７．３０−７．４０（ｍ，５Ｈ），７．９５（ｂｒｓ，１Ｈ） Production Example 158
To a solution of 5-benzyloxymethyl-3- [N- (3-tetrahydrofuranylmethyl) carbamoyl] isoxazole-4-carboxylic acid (<1.00 mmol) in ethyl acetate (15 mL) was added N, N-dimethylformamide (7 mg, 0.10 mmol) and oxalyl chloride (0.17 mL, 2.00 mmol) were added, and the mixture was stirred at room temperature for 10 minutes, then methanol (5 mL) was added, and the mixture was further stirred for 10 minutes and concentrated under reduced pressure. The concentrate was diluted with ethyl acetate, washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

223 mg of N- (tetrahydrofuran-3-ylmethyl)-(5-benzyloxymethyl-4-methoxycarbonyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (167)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.65-1.75 (m, 1H), 2.06-2.15 (m, 1H), 2.55-2.66 ( m, 1H), 3.47-3.53 (m, 2H), 3.60 (dd, J = 8.7, 5.5 Hz, 1H), 3.74-3.81 (m, 1H), 3.87 (s, 3H), 3.85-3.95 (m, 2H), 4.64 (s, 2H), 4.88 (s, 2H), 7.30-7.40 (m, 5H), 7.95 (brs, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−（５−ベンジルオキシメチル−４−カルバモイル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１６８）と記す。）２６５ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７３（ｍ，１Ｈ），２．０７−２．１７（ｍ，１Ｈ），２．５５−２．６６（ｍ，１Ｈ），３．４６−３．５１（ｍ，２Ｈ），３．６２（ｄｄ，Ｊ＝８．９，５．０Ｈｚ，１Ｈ），３．７４−３．８１（ｍ，１Ｈ），３．８３−３．８８（ｍ，１Ｈ），３．９０−３．９７（ｍ，１Ｈ），４．６８（ｓ，２Ｈ），５．１４（ｓ，２Ｈ），５．６１（ｂｒｓ，１Ｈ），７．２９−７．４３（ｍ，６Ｈ），９．８１（ｂｒｓ，１Ｈ） Production Example 159
To a solution of 5-benzyloxymethyl-3- [N- (3-tetrahydrofuranylmethyl) carbamoyl] isoxazole-4-carboxylic acid (<1.00 mmol) in ethyl acetate (15 mL) was added N, N-dimethylformamide (7 mg, 0.10 mmol) and oxalyl chloride (0.17 mL, 2.00 mmol) were added, and the mixture was stirred at room temperature for 10 minutes. Then, 28% aqueous ammonia solution (10 mL) was added, and the mixture was further stirred for 10 minutes and diluted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

265 mg of N- (tetrahydrofuran-3-ylmethyl)-(5-benzyloxymethyl-4-carbamoyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (168)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.73 (m, 1H), 2.07-2.17 (m, 1H), 2.55-2.66 ( m, 1H), 3.46-3.51 (m, 2H), 3.62 (dd, J = 8.9, 5.0 Hz, 1H), 3.74-3.81 (m, 1H), 3.83-3.88 (m, 1H), 3.90-3.97 (m, 1H), 4.68 (s, 2H), 5.14 (s, 2H), 5.61 (brs, 1H), 7.29-7.43 (m, 6H), 9.81 (brs, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−（５−ベンジルオキシメチル−４−メチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１６９）と記す。）４００ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７２（ｍ，１Ｈ），２．０４−２．１４（ｍ，１Ｈ），２．２４（ｓ，３Ｈ），２．５３−２．６１（ｍ，１Ｈ），３．４２−３．４７（ｍ，２Ｈ），３．５８（ｄｄ，１Ｈ），３．７４−３．８０（ｍ，１Ｈ），３．８４−３．９５（ｍ，２Ｈ），４．５７（ｓ，２Ｈ），４．５９（ｓ，２Ｈ），６．９５（ｂｒｓ，１Ｈ），７．２９−７．４０（ｍ，５Ｈ） Production Example 160
Dithiocarboxylic acid 4-O- {5-benzyloxymethyl-3- [N- (3-tetrahydrofuranylmethyl) carbamoyl] isoxazolylmethyl} ester S-methyl ester (680 mg, 1.56 mmol) in toluene (20 mL) ) To the solution was added tributyltin hydride (544 mg, 1.87 mmol) and azobisisobutyronitrile (51 mg, 0.32 mmol). After stirring at 90 ° C. for 30 minutes, the mixture was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 400 mg of N- (tetrahydrofuran-3-ylmethyl)-(5-benzyloxymethyl-4-methyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (169)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (m, 1H), 2.04-2.14 (m, 1H), 2.24 (s, 3H) 2.53-2.61 (m, 1H), 3.42-3.47 (m, 2H), 3.58 (dd, 1H), 3.74-3.80 (m, 1H), 3 84-3.95 (m, 2H), 4.57 (s, 2H), 4.59 (s, 2H), 6.95 (brs, 1H), 7.29-7.40 (m, 5H) )

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−（５−ベンジルオキシメチル−４−フルオロメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１７０）と記す。）１２４ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７３（ｍ，１Ｈ），２．０２−２．１４（ｍ，１Ｈ），２．５２−２．６３（ｍ，１Ｈ），３．４３−３．４８（ｍ，２Ｈ），３．５９（ｄｄ，１Ｈ），３．７３−３．８０（ｍ，１Ｈ），３．８５（ｄｄ，１Ｈ），３．８８−３．９５（ｍ，１Ｈ），４．６１（ｓ，２Ｈ），４．７２（ｄ，２Ｈ），５．６２（ｄ，２Ｈ），６．９８（ｂｒｓ，１Ｈ），７．２９−７．４１（ｍ，５Ｈ） Production Example 161
To a solution of N- (tetrahydrofuran-3-ylmethyl)-(5-benzyloxymethyl-4-hydroxymethyl) isoxazole-3-carboxamide (400 mg, 1.16 mmol) in toluene (8 mL) was added bis (2 -Methoxyethyl) aminosulfur trifluoride (0.28 mL, 1.50 mmol) was added. The mixture was stirred for 30 minutes under cooling with ice water and then diluted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

124 mg of N- (tetrahydrofuran-3-ylmethyl)-(5-benzyloxymethyl-4-fluoromethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (170)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.73 (m, 1H), 2.02-2.14 (m, 1H), 2.52-2.63 ( m, 1H), 3.43-3.48 (m, 2H), 3.59 (dd, 1H), 3.73-3.80 (m, 1H), 3.85 (dd, 1H), 3 88-3.95 (m, 1H), 4.61 (s, 2H), 4.72 (d, 2H), 5.62 (d, 2H), 6.98 (brs, 1H), 7. 29-7.41 (m, 5H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−（５−ベンジルオキシメチル−４−ジフルオロメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１７１）と記す。）３４０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７２（ｍ，１Ｈ），２．０５−２．１５（ｍ，１Ｈ），２．５３−２．６５（ｍ，１Ｈ），３．４４−３．４９（ｍ，２Ｈ），３．６０（ｄｄ，１Ｈ），３．７４−３．８０（ｍ，１Ｈ），３．８３−３．８７（ｍ，１Ｈ），３．８９−３．９５（ｍ，１Ｈ），４．６３（ｓ，２Ｈ），４．８０−４．８１（ｍ，２Ｈ），６．９７（ｂｒｓ，１Ｈ），７．２８（ｔ，１Ｈ），７．２９−７．４０（ｍ，５Ｈ） Production Example 162
To a solution of N- (tetrahydrofuran-3-ylmethyl)-(5-benzyloxymethyl-4-formyl) isoxazole-3-carboxamide (400 mg, 1.16 mmol) in toluene (4 mL) was added bis (2-methoxyethyl) amino. Sulfur trifluoride (0.64 mL, 3.49 mmol) was added. The mixture was stirred at room temperature for 2 hours and diluted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

340 mg of N- (tetrahydrofuran-3-ylmethyl)-(5-benzyloxymethyl-4-difluoromethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (171)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (m, 1H), 2.05-2.15 (m, 1H), 2.53-2.65 ( m, 1H), 3.44-3.49 (m, 2H), 3.60 (dd, 1H), 3.74-3.80 (m, 1H), 3.83-3.87 (m, 1H), 3.89-3.95 (m, 1H), 4.63 (s, 2H), 4.80-4.81 (m, 2H), 6.97 (brs, 1H), 7.28. (T, 1H), 7.29-7.40 (m, 5H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−［５−ベンジルオキシメチル−４−（１−フルオロエチル）］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１７２）と記す。）４６０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７４（ｍ，１Ｈ），２．０６−２．１４（ｍ，１Ｈ），２．５２−２．６２（ｍ，１Ｈ），３．４１−３．４７（ｍ，２Ｈ），３．５８（ｄｄ，１Ｈ），３．７３−３．８０（ｍ，１Ｈ），３．８２−３．９６（ｍ，２Ｈ），４．６１（ｓ，２Ｈ），４．７１（ｄ，１Ｈ），４．７９（ｄ，１Ｈ），６．１９（ｍ，１Ｈ），６．９８（ｂｒｓ，１Ｈ），７．３５（ｍ，５Ｈ） Production Example 163
To a solution of N- (tetrahydrofuran-3-ylmethyl)-[5-benzyloxymethyl-4- (1-hydroxyethyl)] isoxazole-3-carboxamide (550 mg, 1.53 mmol) in dichloromethane (10 mL) was added bis (2 -Methoxyethyl) aminosulfur trifluoride (0.42 mL, 2.29 mmol) was added. The mixture was stirred at room temperature for 4 hours and 30 minutes, and then diluted with ethyl acetate. The organic layer was washed successively with aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

460 mg of N- (tetrahydrofuran-3-ylmethyl)-[5-benzyloxymethyl-4- (1-fluoroethyl)] isoxazole-3-carboxamide (hereinafter referred to as the present compound (172)) represented by the formula: Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.74 (m, 1H), 2.06-2.14 (m, 1H), 2.52-2.62 ( m, 1H), 3.41-3.47 (m, 2H), 3.58 (dd, 1H), 3.73-3.80 (m, 1H), 3.82-3.96 (m, 2H), 4.61 (s, 2H), 4.71 (d, 1H), 4.79 (d, 1H), 6.19 (m, 1H), 6.98 (brs, 1H), 7. 35 (m, 5H)

で示されるジチオカルボン酸 ４−Ｏ−｛５−ベンジルオキシメチル−３−［Ｎ−（３−テトラヒドロフラニルメチル）カルバモイル］イソキサゾリルメチル｝エステル Ｓ−メチルエステル（以下、本発明化合物（１７３）と記す。）８４０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７２（ｍ，１Ｈ），２．０６−２．１４（ｍ，１Ｈ），２．５４（ｓ，３Ｈ），２．５６−２．６２（ｍ，１Ｈ），３．４３−３．４８（ｍ，２Ｈ），３．５９（ｄｄ，１Ｈ），３．７３−３．８０（ｍ，１Ｈ），３．８３−３．９５（ｍ，２Ｈ），４．６０（ｓ，２Ｈ），４．７２（ｓ，２Ｈ），５．８０（ｓ，２Ｈ），６．９４（ｂｒｓ，１Ｈ），７．２９−７．３９（ｍ，５Ｈ） Production Example 164
To a solution of N- (tetrahydrofuran-3-ylmethyl)-(5-benzyloxymethyl-4-hydroxymethyl) isoxazole-3-carboxamide (780 mg, 2.25 mmol) in tetrahydrofuran (20 mL) was added 60% hydrogen under ice water cooling. Sodium chloride (108 mg, 2.70 mmol) was added. After stirring for 15 minutes under cooling with ice water, carbon disulfide (0.8 mL) was added, and after stirring for another 10 minutes, methyl iodide (0.8 mL) was added. After stirring for 10 minutes under cooling with ice water, water was added, and the mixture was extracted once with a mixed solution of ethyl acetate and hexane. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Dithiocarboxylic acid 4-O- {5-benzyloxymethyl-3- [N- (3-tetrahydrofuranylmethyl) carbamoyl] isoxazolylmethyl} ester S-methyl ester (hereinafter referred to as the present compound (173)) ) 840 mg was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.72 (m, 1H), 2.06-2.14 (m, 1H), 2.54 (s, 3H) 2.56-2.62 (m, 1H), 3.43-3.48 (m, 2H), 3.59 (dd, 1H), 3.73-3.80 (m, 1H), 3 8.3-3.95 (m, 2H), 4.60 (s, 2H), 4.72 (s, 2H), 5.80 (s, 2H), 6.94 (brs, 1H), 7. 29-7.39 (m, 5H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−（５−ベンジルオキシメチル−４−ヒドロキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１７４）と記す。）６４０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７３（ｍ，１Ｈ），２．０６−２．１６（ｍ，１Ｈ），２．５５−２．６５（ｍ，１Ｈ），３．４６−３．５１（ｍ，２Ｈ），３．６１（ｄｄ，１Ｈ），３．７４−３．８１（ｍ，１Ｈ），３．８３−３．８８（ｍ，１Ｈ），３．９０−３．９６（ｍ，１Ｈ），４．５６−４．６６（ｍ，７Ｈ），７．１５（ｂｒｓ，１Ｈ），７．３０−７．４１（ｍ，５Ｈ） Production Example 165
A solution of N- (tetrahydrofuran-3-ylmethyl)-(5-benzyloxymethyl-4-formyl) isoxazole-3-carboxamide (800 mg, 2.32 mmol) in methanol (16 mL) was cooled with ice water and sodium borohydride ( 400 mg, 10.6 mmol) was added. After stirring for 30 minutes under cooling with ice water, the reaction mixture was diluted with toluene and concentrated under reduced pressure. A 1 mol / L sodium hydroxide aqueous solution was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

640 mg of N- (tetrahydrofuran-3-ylmethyl)-(5-benzyloxymethyl-4-hydroxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (174)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.73 (m, 1H), 2.06-2.16 (m, 1H), 2.55-2.65 ( m, 1H), 3.46-3.51 (m, 2H), 3.61 (dd, 1H), 3.74-3.81 (m, 1H), 3.83-3.88 (m, 1H), 3.90-3.96 (m, 1H), 4.56-4.66 (m, 7H), 7.15 (brs, 1H), 7.30-7.41 (m, 5H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−［５−ベンジルオキシメチル−４−（１−ヒドロキシエチル）］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１７５）と記す。）７５１ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．５０（ｄ，Ｊ＝６．６Ｈｚ，３Ｈ），１．６４−１．７３（ｍ，１Ｈ），２．０６−２．１６（ｍ，１Ｈ），２．５３−２．６５（ｍ，１Ｈ），３．４６−３．５１（ｍ，２Ｈ），３．５８−３．６３（ｍ，１Ｈ），３．７４−３．８１（ｍ，１Ｈ），３．８３−３．８８（ｍ，１Ｈ），３．９０−３．９７（ｍ，１Ｈ），４．５３−４．６７（ｍ，４Ｈ），４．８５−４．９３（ｍ，１Ｈ），５．２３−５．２６（ｍ，１Ｈ），７．２２（ｂｒｓ，１Ｈ），７．３０−７．４２（ｍ，５Ｈ） Production Example 166
A solution of N- (tetrahydrofuran-3-ylmethyl)-(5-benzyloxymethyl-4-formyl) isoxazole-3-carboxamide (900 mg, 2.61 mmol) in tetrahydrofuran (20 mL) was cooled to 0.98 mol / L with ice water. -Methylmagnesium bromide tetrahydrofuran solution (8.0 mL, 7.84 mmol) was added. The reaction mixture stirred at room temperature for 1 hour was poured into ice and diluted hydrochloric acid, and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl)-[5-benzyloxymethyl-4- (1-hydroxyethyl)] isoxazole-3-carboxamide (hereinafter referred to as the present compound (175)) represented by the formula: Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.50 (d, J = 6.6 Hz, 3H), 1.64-1.73 (m, 1H), 2.06-2. 16 (m, 1H), 2.53-2.65 (m, 1H), 3.46-3.51 (m, 2H), 3.58-3.63 (m, 1H), 3.74- 3.81 (m, 1H), 3.83-3.88 (m, 1H), 3.90-3.97 (m, 1H), 4.53-4.67 (m, 4H), 4. 85-4.93 (m, 1H), 5.23-5.26 (m, 1H), 7.22 (brs, 1H), 7.30-7.42 (m, 5H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−クロロフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１７６）と記す。）０．２７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．５６（１Ｈ，ｍ），１．９１（１Ｈ，ｍ），２．４４（１Ｈ，ｍ），３．２２（２Ｈ，ｔ），３．４５（１Ｈ，ｍ），３．７６−３．６５（３Ｈ，ｍ），５．４５（２Ｈ，ｓ），６．９２（１Ｈ，ｓ），７．０３（１Ｈ，ｍ），７．３２（２Ｈ，ｍ），７．４７（１Ｈ，ｄ），８．９７（１Ｈ，ｔ） Production Example 167
5- (2-Chlorophenoxymethyl) isoxazole-3-carboxylic acid (1.0 g, 4.0 mmol) was added to dehydrated N, N-dimethylformamide (5 mL) and cooled to 0 ° C. Triethylamine (1.10 ml, 7.9 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.50 g, 7.9 mmol) and 1-hydroxybenzotriazole (1.07 g, 7.9 mmol) ) Was added and stirred for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.44 g, 4.0 mmol) was added to the mixture, and the mixture was stirred at room temperature for 4 hr. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.27 g of N- (tetrahydrofuran-3-ylmethyl) -5- (2-chlorophenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (176)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.56 (1H, m), 1.91 (1H, m), 2.44 (1H, m), 3.22 (2H, t ), 3.45 (1H, m), 3.76-3.65 (3H, m), 5.45 (2H, s), 6.92 (1H, s), 7.03 (1H, m) , 7.32 (2H, m), 7.47 (1H, d), 8.97 (1H, t)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−（２−クロロフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１７７）と記す。）０．４０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．１８（２Ｈ，ｍ），１．５４（２Ｈ，ｄ），１．７７（１Ｈ，ｍ），３．１３（２Ｈ，ｔ），３．２４（２Ｈ，ｔ），３．８４（２Ｈ，ｄ），５．４９（２Ｈ，ｓ），６．９１（１Ｈ，ｓ），７．０２（１Ｈ，ｍ），７．３３（２Ｈ，ｍ），７．４７（１Ｈ，ｄ），８．８４（１Ｈ，ｔ） Production Example 168
5- (2-Chlorophenoxymethyl) isoxazole-3-carboxylic acid (1.2 g, 4.7 mmol) was added to dehydrated N, N-dimethylformamide (6 mL) and cooled to 0 ° C. Triethylamine (1.33 ml, 9.5 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.08 g, 5.7 mmol) and 1-hydroxybenzotriazole (0.77 g, 7.9 mmol) ) Was added and stirred for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.60 g, 5.9 mmol) was added to the mixture, and the mixture was stirred at room temperature for 4 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.40 g of N- (tetrahydropyran-4-ylmethyl) -5- (2-chlorophenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (177)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.18 (2H, m), 1.54 (2H, d), 1.77 (1H, m), 3.13 (2H, t ), 3.24 (2H, t), 3.84 (2H, d), 5.49 (2H, s), 6.91 (1H, s), 7.02 (1H, m), 7.33 (2H, m), 7.47 (1H, d), 8.84 (1H, t)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−クロロフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１７８）と記す。）０．２５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６４（１Ｈ．ｍ），２．０９（１Ｈ，ｍ），２．５７（１Ｈ，ｍ），３．４６（２Ｈ，ｔ），３．５８（１Ｈ，ｑ），３．９５−３．７２（３Ｈ，ｍ），５．１８（２Ｈ，ｓ），６．８４（２Ｈ，ｍ），６．９６（２Ｈ，ｍ），７．２２（１Ｈ，ｄ） Production Example 169
5- (3-Chlorophenoxymethyl) isoxazole-3-carboxylic acid (1.0 g, 4.0 mmol) was added to dehydrated N, N-dimethylformamide (10 mL), cooled to 0 ° C., and triethylamine (1.10 mL, 7.9 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.50 g, 7.9 mmol) and 1-hydroxybenzotriazole (1.07 g, 7.9 mmol) were added for 10 minutes. Stir. Tetrahydrofuran-3-ylmethylamine (0.44 g, 4.0 mmol) was added to the mixture, and the mixture was stirred at room temperature for 4 hr. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (3-chlorophenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (178)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64 (1H.m), 2.09 (1H, m), 2.57 (1H, m), 3.46 (2H, t ), 3.58 (1H, q), 3.95-3.72 (3H, m), 5.18 (2H, s), 6.84 (2H, m), 6.96 (2H, m) , 7.22 (1H, d)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−（３−クロロフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１７９）と記す。）０．４０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４４−１．３０（２Ｈ，ｍ），１．６６（２Ｈ，ｄ），１．８３（１Ｈ，ｍ），３．３７（４Ｈ，ｍ），４．０（２Ｈ，ｄ），５．１７（２Ｈ，ｓ），６．８４（２Ｈ，ｍ），６．９９（２Ｈ，ｔ），７．２２（１Ｈ，ｄ） Production Example 170
5- (3-Chlorophenoxymethyl) isoxazole-3-carboxylic acid (1.0 g, 4.0 mmol) was added to dehydrated N, N-dimethylformamide (10 mL), cooled to 0 ° C., and triethylamine (1.10 mL, 7.9 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.50 g, 7.9 mmol) and 1-hydroxybenzotriazole (1.07 g, 7.9 mmol) were added for 10 minutes. Stir. Tetrahydropyran-4-ylmethylamine (0.50 g, 4.3 mmol) was added to the mixture, and the mixture was stirred at room temperature for 4 hr. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.40 g of N- (tetrahydropyran-4-ylmethyl) -5- (3-chlorophenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (179)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.44 to 1.30 (2H, m), 1.66 (2H, d), 1.83 (1H, m), 3.37 (4H, m), 4.0 (2H, d), 5.17 (2H, s), 6.84 (2H, m), 6.99 (2H, t), 7.22 (1H, d)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（４−クロロフェノキシ）メチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１８０）と記す。）３０５ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６４−１．７０（１Ｈ．ｍ），２．０６−２．１２（１Ｈ，ｍ），２．５５−２．６０（１Ｈ，ｍ），３．４６（２Ｈ，ｔ），３．５８（１Ｈ，ｄｄ），３．７５−３．９５（３Ｈ，ｍ），５．２６（２Ｈ，ｓ），６．７８（１Ｈ，ｓ），６．８７−６．９１（３Ｈ，ｍ），７．２５−７．２８（２Ｈ，ｍ） Production Example 171
5-[(4-Chlorophenoxy) methyl] isoxazole-3-carboxylic acid (500 mg, 1.87 mmol) and tetrahydrofuran-3-ylmethylamine (208 mg, 2.05 mmol) were added to dehydrated tetrahydrofuran (20 ml) and 0 ° C. Then, hexafluorophosphoric acid (benzotriazol-1-yloxy) tripyrrolidinophosphonium (1.46 g, 2.80 mmol) was added, and the mixture was stirred at 0 ° C. for 16 hours. The mixture was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

305 mg of N- (tetrahydrofuran-3-ylmethyl) -5-[(4-chlorophenoxy) methyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (180)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.70 (1H.m), 2.06-2.12 (1H, m), 2.55-2.60 ( 1H, m), 3.46 (2H, t), 3.58 (1H, dd), 3.75-3.95 (3H, m), 5.26 (2H, s), 6.78 (1H , S), 6.87-6.91 (3H, m), 7.25-7.28 (2H, m)

で示されるＮ−（テトラヒドロフピラン−４−イルメチル）−５−［（４−クロロフェノキシ）メチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１８１）と記す。）３２０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４２−１．３５（２Ｈ，ｍ），１．６（２Ｈ，ｄ），１．８５（１Ｈ，ｍ），３．３７（４Ｈ，ｍ），４．０（２Ｈ，ｄ），５．１８（２Ｈ，ｓ），６．７７（１Ｈ，ｓ），６．８７−６．８９（３Ｈ，ｍ），７．２６（２Ｈ，ｄ） Production Example 172
5-[(4-Chlorophenoxy) methyl] isoxazole-3-carboxylic acid (500 mg, 1.87 mmol) and tetrahydropyran-4-ylmethylamine (237 mg, 2.05 mmol) were added to dehydrated tetrahydrofuran (20 ml). The mixture was cooled to 0 ° C., hexafluorophosphoric acid (benzotriazol-1-yloxy) tripyrrolidinophosphonium (1.46 g, 2.80 mmol) was added, and the mixture was stirred at 0 ° C. for 16 hours. The mixture was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 320 mg of N- (tetrahydrofupyran-4-ylmethyl) -5-[(4-chlorophenoxy) methyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (181)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42-1.35 (2H, m), 1.6 (2H, d), 1.85 (1H, m), 3.37 (4H, m), 4.0 (2H, d), 5.18 (2H, s), 6.77 (1H, s), 6.87-6.89 (3H, m), 7.26 ( 2H, d)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（３，４−ジクロロフェノキシ）メチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１８２）と記す。）４００ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７０−１．６０（１Ｈ，ｍ），２．２０−２．０（１Ｈ，ｍ），２．６（１Ｈ，ｔ），３．４５（１Ｈ，ｔ），３．６２（１Ｈ，ｍ），３．７５（１Ｈ，ｑ），３．９５−３．８０（２Ｈ，ｍ），５．２０（２Ｈ，ｓ），６．８５−６．７８（２Ｈ，ｍ），６．９８−６．８８（１Ｈ，Ｂｒｓ），７．０８（１Ｈ，ｄ），７．３６（１Ｈ，ｄ） Production Example 173
5-[(3,4-dichlorophenoxy) methyl] isoxazole-3-carboxylic acid (500 mg, 1.74 mmol) and tetrahydrofuran-3-ylmethylamine (211 mg, 2.09 mmol) were added to dehydrated tetrahydrofuran (30 ml), After cooling to 0 ° C. and adding hexafluorophosphoric acid (benzotriazol-1-yloxy) tripyrrolidinophosphonium (1.35 g, 2.61 mmol), the mixture was stirred at 0 ° C. for 16 hours. The mixture was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 400 mg of N- (tetrahydrofuran-3-ylmethyl) -5-[(3,4-dichlorophenoxy) methyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (182)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.70-1.60 (1H, m), 2.20-2.0 (1H, m), 2.6 (1H, t) 3.45 (1H, t), 3.62 (1H, m), 3.75 (1H, q), 3.95-3.80 (2H, m), 5.20 (2H, s), 6.85-6.78 (2H, m), 6.98-6.88 (1H, Brs), 7.08 (1H, d), 7.36 (1H, d)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（３，４−ジクロロフェノキシ）メチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１８３）と記す。）３００ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３５−１．４８（２Ｈ，ｍ），１．６５−１．６８（２Ｈ，ｄ），１．８５−８６（１Ｈ，ｍ），３．３３−３．４１（４Ｈ，ｍ），４．００（２Ｈ，ｄｄ），５．１６（２Ｈ，ｓ），６．８３（２Ｈ，ｍ），６．８６（１Ｈ,ｂｒ．ｓ）,７．０６（１Ｈ,ｄ） Production Example 174
5-[(3,4-Dichlorophenoxy) methyl] isoxazole-3-carboxylic acid (400 mg, 1.39 mmol) and tetrahydropyran-4-ylmethylamine (193 mg, 1.67 mmol) were added to dehydrated tetrahydrofuran (30 ml). After cooling to 0 ° C. and adding hexafluorophosphoric acid (benzotriazol-1-yloxy) tripyrrolidinophosphonium (1.00 g, 2.00 mmol), the mixture was stirred at 0 ° C. for 16 hours. The mixture was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

300 mg of N- (tetrahydropyran-4-ylmethyl) -5-[(3,4-dichlorophenoxy) methyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (183)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.35 to 1.48 (2H, m), 1.65 to 1.68 (2H, d), 1.85 to 86 (1H, m), 3.33-3.41 (4H, m), 4.00 (2H, dd), 5.16 (2H, s), 6.83 (2H, m), 6.86 (1H, br) .S), 7.06 (1H, d)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（４−フルオロフェノキシ）メチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１８４）と記す。）３２０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７８−１．６０（１Ｈ，ｍ），２．１８−２．０（１Ｈ，ｍ），２．６（１Ｈ，ｔ），３．４８（２Ｈ，ｔ），３．６６−３．５２（１Ｈ，ｍ），３．８０−３．７０（３Ｈ，ｍ），５．１６（２Ｈ，ｓ），６．７８（１Ｈ，ｓ），７．６０−６．６０（５Ｈ，ｍ） Production Example 175
5-[(4-Fluorophenoxy) methyl] isoxazole-3-carboxylic acid (500 mg, 2.18 mmol) and tetrahydrofuran-3-ylmethylamine (211 mg, 2.09 mmol) were added to dehydrated tetrahydrofuran (30 ml) at 0 ° C. Then, hexafluorophosphoric acid (benzotriazol-1-yloxy) tripyrrolidinophosphonium (1.35 g, 2.61 mmol) was added, and the mixture was stirred at 0 ° C. for 16 hours. The mixture was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 320 mg of N- (tetrahydrofuran-3-ylmethyl) -5-[(4-fluorophenoxy) methyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (184)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.78-1.60 (1H, m), 2.18-2.0 (1H, m), 2.6 (1H, t) 3.48 (2H, t), 3.66-3.52 (1H, m), 3.80-3.70 (3H, m), 5.16 (2H, s), 6.78 (1H , S), 7.60-6.60 (5H, m)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−［（４−フルオロフェノキシ）メチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１８５）と記す。）２５０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４５−１．３０（２Ｈ，ｍ），１．６５（２Ｈ，ｄ），１．９５−１．８（１Ｈ，ｍ），３．４５−３．３０（４Ｈ，ｍ），４．０（２Ｈ，ｄｄ），５．３（２Ｈ，ｓ），６．７８（１Ｈ，ｓ），６．９６−６．８２（３Ｈ，ｍ），７．０６−６．９８（２Ｈ，ｍ） Production Example 176
5-[(4-Fluorophenoxy) methyl] isoxazole-3-carboxylic acid (500 mg, 2.18 mmol) and tetrahydropyran-4-ylmethylamine (660 mg, 6.60 mmol) were added to dehydrated tetrahydrofuran (30 ml). The mixture was cooled to 0 ° C., hexafluorophosphoric acid (benzotriazol-1-yloxy) tripyrrolidinophosphonium (1.80 g, 3.50 mmol) was added, and the mixture was stirred at 0 ° C. for 16 hours. The mixture was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 250 mg of N- (tetrahydropyran-4-ylmethyl) -5-[(4-fluorophenoxy) methyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (185)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.45-1.30 (2H, m), 1.65 (2H, d), 1.95-1.8 (1H, m) 3.45-3.30 (4H, m), 4.0 (2H, dd), 5.3 (2H, s), 6.78 (1H, s), 6.96-6.82 (3H , M), 7.06-6.98 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（４−ブロモフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１８６）と記す。）０．２５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．５８（１Ｈ，ｍ），１．９１（１Ｈ，ｍ），２．４６（１Ｈ，ｍ），３．２２（２Ｈ，ｔ），３．４４（１Ｈ，ｄｄ），３．６８（３Ｈ，ｍ），５．５３（２Ｈ，ｓ），６．９１（１Ｈ，ｓ），７．０４（２Ｈ，ｄ），７．４９（２Ｈ，ｄ），８．９２（１Ｈ，ｔ） Production Example 177
5- (4-Bromophenoxymethyl) isoxazole-3-carboxylic acid (0.50 g, 1.7 mmol) was added to chloroform (amylene-added product) (10 mL), cooled to 0 ° C., and triethylamine (0.30 mL, 2 0.5 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.48 g, 2.5 mmol) and 1-hydroxybenzotriazole (0.34 g, 2.5 mmol) were added and stirred for 10 minutes. did. Tetrahydrofuran-3-ylmethylamine (0.19 g, 1.8 mmol) was added to the mixture, and the mixture was stirred at room temperature for 4 hr. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (4-bromophenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (186)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.58 (1H, m), 1.91 (1H, m), 2.46 (1H, m), 3.22 (2H, t ), 3.44 (1H, dd), 3.68 (3H, m), 5.53 (2H, s), 6.91 (1H, s), 7.04 (2H, d), 7.49 (2H, d), 8.92 (1H, t)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−（４−ブロモフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１８７）と記す。）０．２９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．１８（２Ｈ，ｍ），１．５３（２Ｈ，ｄ），１．７８（１Ｈ，ｍ），３．１３（２Ｈ，ｔ），３．２０（２Ｈ，ｔ），３．８４（２Ｈ，ｄ），５．３５（２Ｈ，ｓ），６．９０（１Ｈ，ｓ），７．０４（２Ｈ，ｄ），７．４９（２Ｈ，ｄ），８．８２（１Ｈ，ｔ） Production Example 178

N- (tetrahydropyran-4-ylmethyl) -5- (4-bromophenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (187)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.18 (2H, m), 1.53 (2H, d), 1.78 (1H, m), 3.13 (2H, t ), 3.20 (2H, t), 3.84 (2H, d), 5.35 (2H, s), 6.90 (1H, s), 7.04 (2H, d), 7.49. (2H, d), 8.82 (1H, t)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（４−トリフルオロメチルフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１８８）と記す。）０．１６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６９−１．６５（ｍ，１Ｈ），２．１１−２．０６（ｍ，１Ｈ），２．５９−２．５６（ｍ，１Ｈ），３．４６（ｔ，２Ｈ），３．６１−３．５７（ｍ，１Ｈ），３．７９−３．７５（ｍ，１Ｈ），３．９２−３．８３（ｍ，２Ｈ），５．２４（ｓ，２Ｈ），６．８１（ｓ，１Ｈ），６．９２（ｓ，１Ｈ），７．０３（ｄ，２Ｈ），７．５８（ｄ，２Ｈ） Production Example 179
5- (4-Trifluoromethylphenoxymethyl) isoxazole-3-carboxylic acid (0.60 g, 2.1 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., and triethylamine (0.43 mL). , 3.1 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.60 g, 3.1 mmol) and 1-hydroxybenzotriazole (0.42 g, 3.1 mmol) were added and 10 Stir for minutes. Tetrahydrofuran-3-ylmethylamine (0.23 g, 2.3 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.16 g of N- (tetrahydrofuran-3-ylmethyl) -5- (4-trifluoromethylphenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (188)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.69-1.65 (m, 1H), 2.11-1.06 (m, 1H), 2.59-2.56 ( m, 1H), 3.46 (t, 2H), 3.61-3.57 (m, 1H), 3.79-3.75 (m, 1H), 3.92-3.83 (m, 2H), 5.24 (s, 2H), 6.81 (s, 1H), 6.92 (s, 1H), 7.03 (d, 2H), 7.58 (d, 2H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−（４−トリフルオロメチルフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１８９）と記す。）０．２５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４３−１．３２（ｍ，２Ｈ），１．６８−１．６４（ｍ，２Ｈ），１．８８−１．８３（ｍ，１Ｈ），３．４１−３．３３（ｍ，４Ｈ），４．００−３．９６（ｍ，２Ｈ），５．２４（ｓ，２Ｈ），６．８０（ｓ，１Ｈ），６．８６（ｓ，１Ｈ），７．０２（ｄ，２Ｈ），７．５８（ｄ，２Ｈ） Production Example 180
5- (4-Trifluoromethylphenoxymethyl) isoxazole-3-carboxylic acid (0.60 g, 2.1 mmol) was added to chloroform (amylene-added product) (12 mL) and cooled to 0 ° C. Triethylamine (0.43 ml, 3.1 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.60 g, 3.1 mmol) and 1-hydroxybenzotriazole (0.42 g, 3.1 mmol) ) Was added and stirred for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.26 g, 2.3 mmol) was added to the mixture, and the mixture was stirred at room temperature for 4 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.25 g of N- (tetrahydropyran-4-ylmethyl) -5- (4-trifluoromethylphenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (189)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.43-1.32 (m, 2H), 1.68-1.64 (m, 2H), 1.88-1.83 ( m, 1H), 3.41-3.33 (m, 4H), 4.00-3.96 (m, 2H), 5.24 (s, 2H), 6.80 (s, 1H), 6 .86 (s, 1H), 7.02 (d, 2H), 7.58 (d, 2H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（４−トリフルオロメトキシフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１９０）と記す。）０．４０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．２５−１．１（ｍ，１Ｈ），２．１５−２．０（ｍ，１Ｈ），２．６−２．５（ｍ，１Ｈ），３．４５（ｔ，２Ｈ），３．６（ｑ，１Ｈ），３．８−３．６（ｍ，１Ｈ），４．０−３．８（ｍ，２Ｈ），５．２（ｓ，２Ｈ），６．８（ｓ，１Ｈ），７．０−６．８６（ｍ，３Ｈ），７．１８（ｄ，２Ｈ） Production Example 181
5- (4-Trifluoromethoxyphenoxymethyl) isoxazole-3-carboxylic acid (0.60 g, 2.0 mmol) was added to chloroform (amylene-added product) (15 mL), cooled to 0 ° C., and triethylamine (0.40 ml). , 3.0 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.45 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.32 g, 2.4 mmol) were added, 10 Stir for minutes. Tetrahydrofuran-3-ylmethylamine (0.22 g, 2.2 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.40 g of N- (tetrahydrofuran-3-ylmethyl) -5- (4-trifluoromethoxyphenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (190)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.25-1.1 (m, 1H), 2.15-2.0 (m, 1H), 2.6-2.5 ( m, 1H), 3.45 (t, 2H), 3.6 (q, 1H), 3.8-3.6 (m, 1H), 4.0-3.8 (m, 2H), 5 .2 (s, 2H), 6.8 (s, 1H), 7.0-6.86 (m, 3H), 7.18 (d, 2H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−（４−トリフルオロメトキシフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１９１）と記す。）０．０６６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４３−１．３２（２Ｈ，ｍ），１．６７（２Ｈ，ｄ），１．８５（１Ｈ，ｍ），３．３７（４Ｈ，ｍ），３．９８（２Ｈ，ｄ），５．１９（２Ｈ，ｓ），６．７９（１Ｈ，ｓ），６．８７（１Ｈ，ｔ），６．９３（２Ｈ，ｄ），７．１７（２Ｈ，ｄ） Production Example 182
5- (4-Trifluoromethoxyphenoxymethyl) isoxazole-3-carboxylic acid (0.10 g, 0.33 mmol) was added to chloroform (amylene-added product) (3 mL), cooled to 0 ° C., and triethylamine (0.069 mL). , 0.5 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.76 g, 0.40 mmol) and 1-hydroxybenzotriazole (0.053 g, 0.40 mmol). Stir for minutes. Tetrahydropyran-4-ylmethylamine (0.042 g, 0.37 mmol) was added to the mixture, and the mixture was stirred at room temperature for 4 hr. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.066 g of N- (tetrahydropyran-4-ylmethyl) -5- (4-trifluoromethoxyphenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (191)) represented by the formula: .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.43-1.32 (2H, m), 1.67 (2H, d), 1.85 (1H, m), 3.37 (4H, m), 3.98 (2H, d), 5.19 (2H, s), 6.79 (1H, s), 6.87 (1H, t), 6.93 (2H, d) , 7.17 (2H, d)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（４−トリフルオロメチルチオフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１９２）と記す。）０．３１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７１−１．６１（１Ｈ，ｍ），２．１１−２．０４（１Ｈ，ｍ），２．６１−２．５４（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．６１−３．５７（１Ｈ，ｍ），３．７９−３．７３（１Ｈ，ｍ），３．９４−３．８３（２Ｈ，ｍ），５．２１（２Ｈ，ｓ），６．８１（１Ｈ，ｓ），６．９５（１Ｈ，Ｂｒｓ），７．００−６．９７（２Ｈ，ｄ），７．６１（２Ｈ，ｄ） Production Example 183
5- (4-Trifluoromethylthiophenoxymethyl) isoxazole-3-carboxylic acid (0.50 g, 1.6 mmol) was added to chloroform (amylene added product) (10 mL), cooled to 0 ° C., and triethylamine (0.30 mL). , 2.4 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.45 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.32 g, 2.4 mmol) were added and 10 Stir for minutes. Tetrahydrofuran-3-ylmethylamine (0.17 g, 1.7 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.31 g of N- (tetrahydrofuran-3-ylmethyl) -5- (4-trifluoromethylthiophenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (192)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.71-1.61 (1H, m), 2.11-2.04 (1H, m), 2.61-2.54 ( 1H, m), 3.47 (2H, t), 3.61-3.57 (1H, m), 3.79-3.73 (1H, m), 3.94-3.83 (2H, m), 5.21 (2H, s), 6.81 (1H, s), 6.95 (1H, Brs), 7.00-6.97 (2H, d), 7.61 (2H, d) )

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−（４−トリフルオロメチルチオフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１９１）と記す。）０．３１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４３−１．３２（２Ｈ，ｍ），１．５８（２Ｈ，ｄ），１．８９−１．８３（１Ｈ，ｍ），３．４１−３．３３（４Ｈ，ｍ），４．００−３．９６（２Ｈ，ｍ），５．２１（２Ｈ，ｓ），６．８１（１Ｈ，ｓ），６．８８（１Ｈ，ｓ），６．９９（２Ｈ，ｄ），７．６１（２Ｈ，ｄ） Production Example 184
5- (4-Trifluoromethylthiophenoxymethyl) isoxazole-3-carboxylic acid (0.50 g, 1.6 mmol) was added to chloroform (amylene added product) (10 mL), cooled to 0 ° C., and triethylamine (0.30 mL). , 2.4 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.45 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.32 g, 2.4 mmol) were added and 10 Stir for minutes. Tetrahydropyran-4-ylmethylamine (0.20 g, 1.7 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.31 g of N- (tetrahydropyran-4-ylmethyl) -5- (4-trifluoromethylthiophenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (191)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.43-1.32 (2H, m), 1.58 (2H, d), 1.89-1.83 (1H, m) 3.41-3.33 (4H, m), 4.00-3.96 (2H, m), 5.21 (2H, s), 6.81 (1H, s), 6.88 (1H) , S), 6.99 (2H, d), 7.61 (2H, d)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−フルオロフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１９４）と記す。）０．５１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６８（ｍ，１Ｈ），２．０９（ｍ，１Ｈ），２．５７（ｍ，１Ｈ），３．４６（ｑ，２Ｈ），３．５９（ｑ，１Ｈ），３．７７（ｑ，１Ｈ），３．８８（ｍ，２Ｈ），５．１７（ｓ，２Ｈ），６．６７（ｄｄ，１Ｈ），６．７３（ｍ，２Ｈ），６．７９（ｓ，１Ｈ），６．９３（ｂｒｓ，１Ｈ），７．２６（ｄ，１Ｈ） Production Example 185
5- (3-Fluorophenoxymethyl) isoxazole-3-carboxylic acid (0.70 g, 3.0 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., and triethylamine (0.82 mL, 5 0.9 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.68 g, 3.5 mmol) and 1-hydroxybenzotriazole (0.48 g, 3.5 mmol) were added and stirred for 10 minutes. did. Tetrahydrofuran-3-ylmethylamine (0.33 g, 3.2 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.51 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3-fluorophenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (194)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.68 (m, 1H), 2.09 (m, 1H), 2.57 (m, 1H), 3.46 (q, 2H) ), 3.59 (q, 1H), 3.77 (q, 1H), 3.88 (m, 2H), 5.17 (s, 2H), 6.67 (dd, 1H), 6.73 (M, 2H), 6.79 (s, 1H), 6.93 (brs, 1H), 7.26 (d, 1H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−（３−フルオロフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１９５）と記す。）０．５３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３８（ｑ，２Ｈ），１．６５（ｍ，２Ｈ），１．８６（ｍ，１Ｈ），３．３７（ｍ，４Ｈ），３．９８（ｄｄ，２Ｈ），５．１７（ｓ，２Ｈ），６．６７（ｄｄ，１Ｈ），６．７２（ｍ，２Ｈ），６．７９（ｓ，１Ｈ），６．８８（ｂｒｓ，１Ｈ），７．２６（ｄ，１Ｈ） Production Example 186
5- (3-Fluorophenoxymethyl) isoxazole-3-carboxylic acid (0.70 g, 3.0 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., and triethylamine (0.82 mL, 5 0.9 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.68 g, 3.5 mmol) and 1-hydroxybenzotriazole (0.48 g, 3.5 mmol) were added and stirred for 10 minutes. did. Tetrahydropyran-4-ylmethylamine (0.37 g, 3.2 mmol) was added to the mixture, stirred for 18 hours at room temperature, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Thus, 0.53 g of N- (tetrahydropyran-4-ylmethyl) -5- (3-fluorophenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (195)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.38 (q, 2H), 1.65 (m, 2H), 1.86 (m, 1H), 3.37 (m, 4H) ), 3.98 (dd, 2H), 5.17 (s, 2H), 6.67 (dd, 1H), 6.72 (m, 2H), 6.79 (s, 1H), 6.88 (Brs, 1H), 7.26 (d, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−ブロモフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１９６）と記す。）０．４４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７０−１．６４（ｍ，１Ｈ），２．１２−２．０６（ｍ，１Ｈ），２．６０−２．５５（ｍ，１Ｈ），３．４９−３．４４（ｔ，２Ｈ），３．６１−３．５６（ｍ，１Ｈ），３．９５−３．７２（ｍ，３Ｈ），５．１７（ｓ，２Ｈ），６．７９（ｓ，１Ｈ），６．９２−６．８７（ｍ，２Ｈ），７．１８−７．１１（ｍ，３Ｈ） Production Example 187
5- (3-Bromophenoxymethyl) isoxazole-3-carboxylic acid (0.60 g, 1.9 mmol) was added to chloroform (amylene-added product) (15 mL), cooled to 0 ° C., and triethylamine (0.53 mL, 3 .8 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.44 g, 2.3 mmol) and 1-hydroxybenzotriazole (0.31 g, 2.3 mmol) were added and stirred for 10 minutes. did. Tetrahydrofuran-3-ylmethylamine (0.21 g, 2.1 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.44 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3-bromophenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (196)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.70-1.64 (m, 1H), 2.12-2.06 (m, 1H), 2.60-2.55 ( m, 1H), 3.49-3.44 (t, 2H), 3.61-3.56 (m, 1H), 3.95-3.72 (m, 3H), 5.17 (s, 2H), 6.79 (s, 1H), 6.92-6.87 (m, 2H), 7.18-7.11 (m, 3H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−（３−ブロモフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１９７）と記す。）０．５２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３８（ｑ，２Ｈ），１．６８−１．６４（ｄｄ，２Ｈ），１．８６（ｍ，１Ｈ），３．４１−３．３２（ｍ，４Ｈ），４．０１−３．９６（ｄｄ，２Ｈ），５．１７（ｓ，２Ｈ），６．７８（ｓ，１Ｈ），６．８９−６．８７（ｄ，２Ｈ），７．１７−７．１１（ｍ，３Ｈ） Production Example 188
5- (3-Bromophenoxymethyl) isoxazole-3-carboxylic acid (0.60 g, 1.9 mmol) was added to chloroform (amylene-added product) (15 mL), cooled to 0 ° C., and triethylamine (0.53 mL, 3 .8 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.44 g, 2.3 mmol) and 1-hydroxybenzotriazole (0.31 g, 2.3 mmol) were added and stirred for 10 minutes. did. Tetrahydropyran-4-ylmethylamine (0.24 g, 2.1 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Thus, 0.52 g of N- (tetrahydropyran-4-ylmethyl) -5- (3-bromophenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (197)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.38 (q, 2H), 1.68-1.64 (dd, 2H), 1.86 (m, 1H), 3.41 -3.32 (m, 4H), 4.01-3.96 (dd, 2H), 5.17 (s, 2H), 6.78 (s, 1H), 6.89-6.87 (d , 2H), 7.17-7.11 (m, 3H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−トリフルオロメチルフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１９８）と記す。）０．３４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：
１．７−１．６（ｍ，１Ｈ），２．１５−２．０（ｍ，１Ｈ），２．６（ｑ，１Ｈ），３．４５（ｔ，２Ｈ），３．６（ｄｄ，１Ｈ），３．７５（ｑ，１Ｈ）．４．０−３．８（ｍ，２Ｈ），５．３（ｓ，２Ｈ），６．８（ｓ，１Ｈ），６．９４（ｂｒｓ，１Ｈ），７．１４（ｄ，１Ｈ），７．２（ｓ，１Ｈ），７．３（ｄ，１Ｈ），７．４４（ｔ，１Ｈ） Production Example 189
5- (3-trifluoromethylphenoxymethyl) isoxazole-3-carboxylic acid (0.50 g, 1.7 mmol) was added to chloroform (amylene-added product) (15 mL), cooled to 0 ° C., and triethylamine (0.36 mL). , 2.6 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.40 g, 2.1 mmol) and 1-hydroxybenzotriazole (0.28 g, 2.1 mmol). Stir for minutes. Tetrahydrofuran-3-ylmethylamine (0.19 g, 1.9 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.34 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3-trifluoromethylphenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (198)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)):
1.7-1.6 (m, 1H), 2.15-2.0 (m, 1H), 2.6 (q, 1H), 3.45 (t, 2H), 3.6 (dd, 1H), 3.75 (q, 1H). 4.0-3.8 (m, 2H), 5.3 (s, 2H), 6.8 (s, 1H), 6.94 (brs, 1H), 7.14 (d, 1H), 7 .2 (s, 1H), 7.3 (d, 1H), 7.44 (t, 1H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−（３−トリフルオロメチルフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（１９９）と記す。）０．３４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４５−１．３（ｍ，２Ｈ），１．６５（ｄ，２Ｈ），１．９−１．８（ｍ，１Ｈ），３．４−３．３（ｍ，４Ｈ）．４．０（ｄｄ，２Ｈ），５．２５（ｓ，２Ｈ），６．８（ｓ，１Ｈ），６．８４（ｂｒｓ，１Ｈ），７．１４（ｄ，１Ｈ），７．２（ｓ，１Ｈ），７．３（ｄ，１Ｈ），７．４４（ｔ，１Ｈ） Production Example 190
5- (3-trifluoromethylphenoxymethyl) isoxazole-3-carboxylic acid (0.50 g, 1.7 mmol) was added to chloroform (amylene-added product) (15 mL), cooled to 0 ° C., and triethylamine (0.36 mL). , 2.6 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.40 g, 2.1 mmol) and 1-hydroxybenzotriazole (0.28 g, 2.1 mmol). Stir for minutes. Tetrahydropyran-4-ylmethylamine (0.22 g, 1.9 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.34 g of N- (tetrahydropyran-4-ylmethyl) -5- (3-trifluoromethylphenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (199)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.45-1.3 (m, 2H), 1.65 (d, 2H), 1.9-1.8 (m, 1H) , 3.4-3.3 (m, 4H). 4.0 (dd, 2H), 5.25 (s, 2H), 6.8 (s, 1H), 6.84 (brs, 1H), 7.14 (d, 1H), 7.2 (s , 1H), 7.3 (d, 1H), 7.44 (t, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−トリフルオロメトキシフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２００）と記す。）０．３２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６７（ｍ，１Ｈ），２．０８（ｍ，１Ｈ），２．５７（ｍ，１Ｈ），３．４６（ｔ，２Ｈ），３．５８（ｍ，１Ｈ），３．８５（ｍ，３Ｈ），５．１９（ｓ，２Ｈ），６．８２（ｄ，２Ｈ），６．８８（ｄ，３Ｈ），７．３２（ｔ，１Ｈ） Production Example 191
5- (3-trifluoromethoxyphenoxymethyl) isoxazole-3-carboxylic acid (0.60 g, 2.0 mmol) was added to chloroform (amylene-added product) (15 mL), cooled to 0 ° C., and triethylamine (0.56 mL). , 4.0 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.32 g, 2.4 mmol) were added and 10 Stir for minutes. Tetrahydrofuran-3-ylmethylamine (0.22 g, 2.2 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.32 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3-trifluoromethoxyphenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (200)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.67 (m, 1H), 2.08 (m, 1H), 2.57 (m, 1H), 3.46 (t, 2H) ), 3.58 (m, 1H), 3.85 (m, 3H), 5.19 (s, 2H), 6.82 (d, 2H), 6.88 (d, 3H), 7.32 (T, 1H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−（３−トリフルオロメトキシフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２０１）と記す。）０．３１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３７（ｍ，２Ｈ），１．６６（ｄ，２Ｈ），１．８６（ｍ，１Ｈ），３．３６（ｓ，４Ｈ），４．０（ｄ，２Ｈ），５．１９（ｓ，２Ｈ），６．８０（ｓ,１Ｈ）,６．８２−６．９１（ｍ，４Ｈ），７．３２（ｔ，１Ｈ） Production Example 192
5- (3-trifluoromethoxyphenoxymethyl) isoxazole-3-carboxylic acid (0.60 g, 2.0 mmol) was added to chloroform (amylene-added product) (15 mL), cooled to 0 ° C., and triethylamine (0.56 mL). , 4.0 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.32 g, 2.4 mmol) were added and 10 Stir for minutes. Tetrahydropyran-4-ylmethylamine (0.34 g, 3.0 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.31 g of N- (tetrahydropyran-4-ylmethyl) -5- (3-trifluoromethoxyphenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (201)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.37 (m, 2H), 1.66 (d, 2H), 1.86 (m, 1H), 3.36 (s, 4H ), 4.0 (d, 2H), 5.19 (s, 2H), 6.80 (s, 1H), 6.82-6.91 (m, 4H), 7.32 (t, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−トリフルオロメチルチオフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２０２）と記す。）０．４０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６７（１Ｈ，ｑ），２．０９（ｑ，１Ｈ），２．５７（ｔ，１Ｈ），３．４７（ｔ，２Ｈ），３．６１−３．５７（ｍ，１Ｈ），３．７６（ｑ，１Ｈ），３．９４−３．７９（ｍ，２Ｈ），５．２（ｓ，２Ｈ），６．８（ｓ，１Ｈ），６．９４（ｂｒｓ，１Ｈ），７．０９−７．０７（ｍ，１Ｈ），７．２６−７．２４（ｍ，１Ｈ），７．３９−７．３０（ｍ，２Ｈ） Production Example 193
5- (3-trifluoromethylthiophenoxymethyl) isoxazole-3-carboxylic acid (0.60 g, 1.9 mmol) was added to chloroform (amylene-added product) (15 mL), cooled to 0 ° C., and triethylamine (0.40 mL). , 2.8 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.43 g, 2.3 mmol) and 1-hydroxybenzotriazole (0.31 g, 2.3 mmol). Stir for minutes. Tetrahydrofuran-3-ylmethylamine (0.21 g, 2.1 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.40 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3-trifluoromethylthiophenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (202)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.67 (1H, q), 2.09 (q, 1H), 2.57 (t, 1H), 3.47 (t, 2H) ), 3.61-3.57 (m, 1H), 3.76 (q, 1H), 3.94-3.79 (m, 2H), 5.2 (s, 2H), 6.8 ( s, 1H), 6.94 (brs, 1H), 7.09-7.07 (m, 1H), 7.26-7.24 (m, 1H), 7.39-7.30 (m, 2H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−（３−トリフルオロメチルチオフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２０３）と記す。）０．３０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４５−１．３（ｍ，２Ｈ），１．７５−１．６５（ｍ，２Ｈ），１．９５−１．８（ｍ，１Ｈ），３．５−３．３（ｍ，４Ｈ），４．０（ｄｄ，２Ｈ），５．２（ｓ，２Ｈ），６．８（ｓ，１Ｈ），６．９（ｂｒｓ，１Ｈ），７．１−７．０６（ｍ，１Ｈ），７．２７−７．２２（ｍ，１Ｈ），７．４−７．３０（ｍ，２Ｈ） Production Example 194
5- (3-trifluoromethylthiophenoxymethyl) isoxazole-3-carboxylic acid (0.60 g, 1.9 mmol) was added to chloroform (amylene-added product) (15 mL), cooled to 0 ° C., and triethylamine (0.40 mL). , 2.8 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.43 g, 2.3 mmol) and 1-hydroxybenzotriazole (0.31 g, 2.3 mmol). Stir for minutes. Tetrahydropyran-4-ylmethylamine (0.24 g, 2.1 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.30 g of N- (tetrahydropyran-4-ylmethyl) -5- (3-trifluoromethylthiophenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (203)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.45-1.3 (m, 2H), 1.75-1.65 (m, 2H), 1.95-1.8 ( m, 1H), 3.5-3.3 (m, 4H), 4.0 (dd, 2H), 5.2 (s, 2H), 6.8 (s, 1H), 6.9 (brs) , 1H), 7.1-7.06 (m, 1H), 7.27-7.22 (m, 1H), 7.4-7.30 (m, 2H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−[５−（１，３−ベンゾジオキソラニル）オキシメチル]イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２０４）と記す。）０．３０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６９−１．６４（１Ｈ，ｍ），２．１０−２．０６（１Ｈ，ｍ），２．５９−２．５５（１Ｈ，ｍ），３．４６（２Ｈ，ｔ），３．６０−３．５６（１Ｈ，ｍ），３．７９−３．７５（１Ｈ，ｍ），３．９４−３．８３（２Ｈ，ｍ），５．１１（２Ｈ，ｓ），５．９３（２Ｈ，ｓ），６．３８−６．３５（１Ｈ，ｍ），６．５３（１Ｈ，ｄ），６．７０（１Ｈ，ｄ），６．７６（１Ｈ，ｓ），６．９５（１Ｈ，ｓ） Production Example 195
5- [5- (1,3-Benzodioxolanyl) oxymethyl] isoxazole-3-carboxylic acid (0.60 g, 2.2 mmol) was added to chloroform (amylene-added product) (12 mL) and cooled to 0 ° C. Triethylamine (0.48 ml, 3.4 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.52 g, 2.7 mmol) and 1-hydroxybenzotriazole (0.37 g, 2 .7 mmol) was added and stirred for 10 minutes. Tetrahydrofuran-3-ylmethylamine (0.25 g, 2.5 mmol) was added to the mixture, stirred at room temperature for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- [5- (1,3-benzodioxolanyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (204)) 0.30 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.69-1.64 (1H, m), 2.10-2.06 (1H, m), 2.59-2.55 ( 1H, m), 3.46 (2H, t), 3.60-3.56 (1H, m), 3.79-3.75 (1H, m), 3.94-3.83 (2H, m), 5.11 (2H, s), 5.93 (2H, s), 6.38-6.35 (1H, m), 6.53 (1H, d), 6.70 (1H, d) ), 6.76 (1H, s), 6.95 (1H, s)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−[５−（１，３−ベンゾジオキソラニル）オキシメチル]イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２０５）と記す。）０．３８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４２−１．３２（２Ｈ，ｍ），１．６６（２Ｈ，ｄ），１．８７−１．８３（１Ｈ，ｍ），３．４１−３．３３（４Ｈ，ｍ），４．００−３．９６（２Ｈ，ｍ），５．１１（２Ｈ，ｓ），５．９３（２Ｈ，ｓ），６．３８−６．３５（１Ｈ，ｍ），６．５２（１Ｈ，ｄ），６．７０（１Ｈ，ｄ），６．７５（１Ｈ，ｓ），６．８６（１Ｈ，ｓ） Production Example 196
5- [5- (1,3-Benzodioxolanyl) oxymethyl] isoxazole-3-carboxylic acid (0.60 g, 2.2 mmol) was added to chloroform (amylene-added product) (12 mL) and cooled to 0 ° C. Triethylamine (0.48 ml, 3.4 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.52 g, 2.7 mmol) and 1-hydroxybenzotriazole (0.37 g, 2 .7 mmol) was added and stirred for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.28 g, 2.5 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydropyran-4-ylmethyl) -5- [5- (1,3-benzodioxolanyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (205)). ) 0.38 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42-1.32 (2H, m), 1.66 (2H, d), 1.87-1.83 (1H, m) 3.41-3.33 (4H, m), 4.00-3.96 (2H, m), 5.11 (2H, s), 5.93 (2H, s), 6.38-6. .35 (1H, m), 6.52 (1H, d), 6.70 (1H, d), 6.75 (1H, s), 6.86 (1H, s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３，４−ジメトキシフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２０６）と記す。）０．４０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６７（ｑ，１Ｈ），２．０８（ｑ，１Ｈ），２．５７（ｔ，１Ｈ），３．４６（ｔ，２Ｈ），３．５８（ｑ，１Ｈ），３．７６（ｑ，１Ｈ），３．９４−３．８３（ｍ，８Ｈ），５．１５（ｓ，２Ｈ），６．４５−６．４３（ｄｄ，１Ｈ），６．５７（ｄ，１Ｈ），６．７８−６．７６（ｍ，２Ｈ），６．９３（ｓ，１Ｈ） Production Example 197
5- (3,4-Dimethoxyphenoxymethyl) isoxazole-3-carboxylic acid (0.60 g, 2.1 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., and triethylamine (0.45 mL). , 3.2 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.49 g, 2.6 mmol) and 1-hydroxybenzotriazole (0.35 g, 2.6 mmol). Stir for minutes. Tetrahydrofuran-3-ylmethylamine (0.24 g, 2.4 mmol) was added to the mixture, and the mixture was stirred at room temperature for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.40 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3,4-dimethoxyphenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (206)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.67 (q, 1H), 2.08 (q, 1H), 2.57 (t, 1H), 3.46 (t, 2H) ), 3.58 (q, 1H), 3.76 (q, 1H), 3.94-3.83 (m, 8H), 5.15 (s, 2H), 6.45-6.43 ( dd, 1H), 6.57 (d, 1H), 6.78-6.76 (m, 2H), 6.93 (s, 1H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−（３，４−ジメトキシフェノキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２０７）と記す。）０．４２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４３−１．３２（ｑｄ，２Ｈ），１．６８−１．６５（ｄｄ，２Ｈ），１．８８−１．８３（ｍ，１Ｈ），３．４１−３．３３（ｍ，４Ｈ），３．８４（ｓ，３Ｈ），３．８６（ｓ，３Ｈ），４．００−３．９７（ｄｄ，２Ｈ），５．１４（ｓ，２Ｈ），６．４５−６．４３ｄｄ，１Ｈ），６．６５（ｄ，１Ｈ），６．７８−６．７６（ｍ，２Ｈ），６．８７（ｂｒｓ，１Ｈ） Production Example 198
5- (3,4-Dimethoxyphenoxymethyl) isoxazole-3-carboxylic acid (0.60 g, 2.1 mmol) was added to chloroform (amylene-added product) (12 mL), cooled to 0 ° C., and triethylamine (0.45 mL). , 3.2 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.49 g, 2.6 mmol) and 1-hydroxybenzotriazole (0.35 g, 2.6 mmol). Stir for minutes. Tetrahydropyran-4-ylmethylamine (0.27 g, 2.4 mmol) was added to the mixture, stirred for 18 hours at room temperature, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.42 g of N- (tetrahydropyran-4-ylmethyl) -5- (3,4-dimethoxyphenoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (207)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.43-1.32 (qd, 2H), 1.68-1.65 (dd, 2H), 1.88-1.83 ( m, 1H), 3.41-3.33 (m, 4H), 3.84 (s, 3H), 3.86 (s, 3H), 4.00-3.97 (dd, 2H), 5 .14 (s, 2H), 6.45-6.43dd, 1H), 6.65 (d, 1H), 6.78-6.76 (m, 2H), 6.87 (brs, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−４−ホルミル−５−(２−ナフチルメトキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２０８）と記す。）１．８１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６４−１．７４（ｍ，１Ｈ），２．０６−２．１６（ｍ，１Ｈ），２．５４−２．６５（ｍ，１Ｈ），３．４５−３．５１（ｍ，２Ｈ），３．６０（ｄｄ，１Ｈ），３．７４−３．８１（ｍ，1Ｈ），３．８４−３．９７（ｍ，２Ｈ），４．８３（ｓ，２Ｈ），５．０１（ｓ，２Ｈ），７．３１（ｂｒｓ，１Ｈ），７．４５−７．５２（ｍ，３Ｈ），７．７９−７．８８（ｍ，４Ｈ），１０．３８（ｓ，１Ｈ） Production Example 199
A solution of N- (tetrahydrofuran-3-ylmethyl) -5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (2.00 g, 5.46 mmol) in tetrahydrofuran (40 mL) under a nitrogen atmosphere at −60 ° C. or lower. 1.64 mol / L-n-butyllithium hexane solution (8.3 mL, 13.7 mmol) was added dropwise. The mixture was stirred at −60 ° C. or lower for 30 minutes, N, N-dimethylformamide (5 mL) was added, and the mixture was stirred at −60 ° C. to 20 ° C. for 2 hours. Extracted twice with ethyl. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.81 g of N- (tetrahydrofuran-3-ylmethyl) -4-formyl-5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (208)) represented by the formula It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.74 (m, 1H), 2.06-2.16 (m, 1H), 2.54-2.65 ( m, 1H), 3.45-3.51 (m, 2H), 3.60 (dd, 1H), 3.74-3.81 (m, 1H), 3.84-3.97 (m, 2H), 4.83 (s, 2H), 5.01 (s, 2H), 7.31 (brs, 1H), 7.45-7.52 (m, 3H), 7.79-7.88. (M, 4H), 10.38 (s, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−４−ヒドロキシメチル−５−(２−ナフチルメトキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２０９）と記す。）１．４０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７３（ｍ，１Ｈ），２．０６−２．１５（ｍ，１Ｈ），２．５３−２．６４（ｍ，１Ｈ），３．４６−３．５０（ｍ，２Ｈ），３．６１（ｄｄ，１Ｈ），３．７４−３．８１（ｍ，1Ｈ），３．８３−３．８８（ｍ，１Ｈ），３．９０−３．９６（ｍ，１Ｈ），４．５６−４．６４（ｍ，３Ｈ），４．６８（ｓ，２Ｈ），４．７４（ｓ，２Ｈ），７．１４（ｂｒｓ，１Ｈ），７．４５−７．５２（ｍ，３Ｈ），７．７９（ｓ，１Ｈ），７．８２−７．８８（ｍ，３Ｈ） Production Example 200
Hydrogen-cooled solution of N- (tetrahydrofuran-3-ylmethyl) -4-formyl-5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (1.51 g, 3.83 mmol) in methanol (15 mL) under ice water cooling. Sodium borohydride (580 mg, 15.3 mmol) was added. The mixture was stirred for 15 minutes under cooling with ice water, further stirred at room temperature for 1 hour and 15 minutes, diluted with toluene, and concentrated under reduced pressure. Under ice water cooling, the concentrate was added to 1 mol / L hydrochloric acid and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.40 g of N- (tetrahydrofuran-3-ylmethyl) -4-hydroxymethyl-5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (209)) Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.73 (m, 1H), 2.06-2.15 (m, 1H), 2.53-2.64 ( m, 1H), 3.46-3.50 (m, 2H), 3.61 (dd, 1H), 3.74-3.81 (m, 1H), 3.83-3.88 (m, 1H), 3.90-3.96 (m, 1H), 4.56-4.64 (m, 3H), 4.68 (s, 2H), 4.74 (s, 2H), 7.14 (Brs, 1H), 7.45-7.52 (m, 3H), 7.79 (s, 1H), 7.82-7.88 (m, 3H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−１−ヒドロキシエチル−５−(２−ナフチルメトキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２１０）と記す。）２６０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．５１（ｄ，Ｊ ＝ ６．6 Hz，３Ｈ），１．６３−１．７５（ｍ，１Ｈ），２．０７−２．１５（ｍ，１Ｈ），２．５４−２．６４（ｍ，１Ｈ），３．４７−３．５１（ｍ，２Ｈ），３．５９−３．６３（ｍ，１Ｈ），３．７４−３．９７（ｍ，３Ｈ），４．６３−５．０１（ｍ，５Ｈ），５．２６（ｄ，Ｊ ＝ １１．０Ｈｚ，１Ｈ），７．２２（ｂｒｓ，１Ｈ），７．４５−７．５２（ｍ，３Ｈ），７．７９（ｓ，１Ｈ），７．８２−７．８９（ｍ，３Ｈ） Production Example 201
0.98 mol of N- (tetrahydrofuran-3-ylmethyl) -4-formyl-5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (300 mg, 0.76 mmol) in tetrahydrofuran (15 mL) was cooled with ice water. / L-methylmagnesium bromide tetrahydrofuran solution (2.8 mL, 2.66 mmol) was added, and the mixture was stirred at room temperature for 1.5 hours, poured into 1 mol / L hydrochloric acid, and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

260 mg of N- (tetrahydrofuran-3-ylmethyl) -1-hydroxyethyl-5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (210)) represented by the formula: .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.51 (d, J = 6.6 Hz, 3H), 1.63-1.75 (m, 1H), 2.07-2 .15 (m, 1H), 2.54-2.64 (m, 1H), 3.47-3.51 (m, 2H), 3.59-3.63 (m, 1H), 3.74 -3.97 (m, 3H), 4.63-5.01 (m, 5H), 5.26 (d, J = 11.0 Hz, 1H), 7.22 (brs, 1H), 7.45 -7.52 (m, 3H), 7.79 (s, 1H), 7.82-7.89 (m, 3H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−４−フルオロメチル−５−(２−ナフチルメトキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２１１）と記す。）１８０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６１−１．７５（ｍ，１Ｈ），２．０６−２．１４（ｍ，１Ｈ），２．５２−２．６４（ｍ，１Ｈ），３．４２−３．４８（ｍ，２Ｈ），３．５６−３．６１（ｍ，１Ｈ），３．７３−３．８０（ｍ，1Ｈ），３．８３−３．９６（ｍ，２Ｈ），４．７６（ｄ，２Ｈ），４．７７（ｓ，２Ｈ），５．６４（ｄ，２Ｈ），６．９４（ｂｒｓ，１Ｈ），７．４５−７．５３（ｍ，３Ｈ），７．７９−７．８８（ｍ，４Ｈ） Production Example 202
To a solution of N- (tetrahydrofuran-3-ylmethyl) -4-hydroxymethyl-5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (400 mg, 1.01 mmol) in toluene (10 mL) was bis (2-methoxyethyl). ) Aminosulfur trifluoride (0.24 mL, 1.31 mmol) was added, and the mixture was stirred at room temperature for 1.5 hours, poured into 1 mol / L hydrochloric acid under ice water cooling, and extracted twice with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

180 mg of N- (tetrahydrofuran-3-ylmethyl) -4-fluoromethyl-5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (211)) represented by .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.61-1.75 (m, 1H), 2.06-2.14 (m, 1H), 2.52-2.64 ( m, 1H), 3.42-3.48 (m, 2H), 3.56-3.61 (m, 1H), 3.73-3.80 (m, 1H), 3.83-3. 96 (m, 2H), 4.76 (d, 2H), 4.77 (s, 2H), 5.64 (d, 2H), 6.94 (brs, 1H), 7.45-7.53 (M, 3H), 7.79-7.88 (m, 4H)

で示されるジチオカルボン酸 ４−Ｏ−｛５−(２−ナフチルメトキシメチル）−３−［（３−テトラヒドロフラニルメチル）カルバモイル］イソキサゾリルメチル｝エステル Ｓ−メチルエステル（以下、本発明化合物（２１２）と記す。）８８４ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７２（ｍ，１Ｈ），２．０６−２．１３（ｍ，１Ｈ），２．５０（ｓ，３Ｈ），２．５３−２．６３（ｍ，１Ｈ），３．４３−３．４８（ｍ，２Ｈ），３．５８（ｄｄ，１Ｈ），３．７３−３．８０（ｍ，1Ｈ），３．８３−３．９５（ｍ，２Ｈ），４．７６（ｓ，４Ｈ），５．８１（ｓ，２Ｈ），６．９１（ｂｒｓ，１Ｈ），７．４４−７．５２（ｍ，３Ｈ），７．７８（ｓ，１Ｈ），７．８１−７．８６（ｍ，３Ｈ） Production Example 203
To a solution of N- (tetrahydrofuran-3-ylmethyl) -4-hydroxymethyl-5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (800 mg, 2.02 mmol) in tetrahydrofuran (20 mL) was added 55% sodium hydride ( 106 mg, 2.42 mmol) was added, and the mixture was stirred at room temperature for 15 minutes. Under ice-water cooling, carbon disulfide (0.8 mL) was added to the reaction mixture, and the mixture was stirred for 10 minutes. Then, methyl iodide (0.8 mL) was added, and the mixture was further stirred for 10 minutes. The reaction mixture was diluted with toluene and concentrated under reduced pressure. The concentrate was added to 1 mol / L hydrochloric acid under cooling with ice water, and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Dithiocarboxylic acid 4-O- {5- (2-naphthylmethoxymethyl) -3-[(3-tetrahydrofuranylmethyl) carbamoyl] isoxazolylmethyl} ester S-methyl ester (hereinafter referred to as the compound of the present invention) (Described as (212).) 884 mg was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.72 (m, 1H), 2.06-2.13 (m, 1H), 2.50 (s, 3H) 2.53-2.63 (m, 1H), 3.43-3.48 (m, 2H), 3.58 (dd, 1H), 3.73-3.80 (m, 1H), 3 8.3-3.95 (m, 2H), 4.76 (s, 4H), 5.81 (s, 2H), 6.91 (brs, 1H), 7.44-7.52 (m, 3H) ), 7.78 (s, 1H), 7.81-7.86 (m, 3H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−４−メチル−５−(２−ナフチルメトキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２１３）と記す。）４００ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７４（ｍ，１Ｈ），２．０６−２．１４（ｍ，１Ｈ），２．２５（ｓ，３Ｈ），２．５３−２．６２（ｍ，１Ｈ），３．４１−３．４８（ｍ，２Ｈ），３．５６−３．６１（ｍ，１Ｈ），３．７４−３．８１（ｍ，1Ｈ），３．８４−３．９６（ｍ，２Ｈ），４．６３（ｓ，２Ｈ），４．７４（ｓ，２Ｈ），６．９４（ｂｒｓ，１Ｈ），７．４５−７．５４（ｍ，３Ｈ），７．７９（ｓ，１Ｈ），７．８２−７．８８（ｍ，３Ｈ） Production Example 204
Dithiocarboxylic acid 4-O- {5- (2-naphthylmethoxymethyl) -3-[(3-tetrahydrofuranylmethyl) carbamoyl] isoxazolylmethyl} ester S-methyl ester (880 mg, 1.81 mmol) in toluene To the (20 mL) solution, tributyltin hydride (632 mg, 2.17 mmol) and azobisisobutyronitrile (59 mg, 0.36 mmol) were added. The mixture was stirred at 90 to 95 ° C. for 30 minutes and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 400 mg of N- (tetrahydrofuran-3-ylmethyl) -4-methyl-5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (213)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.74 (m, 1H), 2.06-2.14 (m, 1H), 2.25 (s, 3H) , 2.53-2.62 (m, 1H), 3.41-3.48 (m, 2H), 3.56-3.61 (m, 1H), 3.74-3.81 (m, 1H), 3.84-3.96 (m, 2H), 4.63 (s, 2H), 4.74 (s, 2H), 6.94 (brs, 1H), 7.45-7.54. (M, 3H), 7.79 (s, 1H), 7.82-7.88 (m, 3H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−フルオロベンジルオキシメチル）−４−ホルミルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２１４）と記す。）２．３０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６５−１．７４（ｍ，１Ｈ），２．０７−２．１７（ｍ，１Ｈ），２．５７−２．６６（ｍ，１Ｈ），３．４８−３．５４（ｍ，２Ｈ），３．６２（ｄｄ，１Ｈ），３．７５−３．８１（ｍ，1Ｈ），３．８４−３．９８（ｍ，２Ｈ），４．６６（ｓ，２Ｈ），４．９９（ｓ，２Ｈ），６．９８−７．１４（ｍ，３Ｈ），７．３０−７．３６（ｍ，２Ｈ），１０．４２（ｓ，１Ｈ） Production Example 205
A solution of N- (tetrahydrofuran-3-ylmethyl) -5- (3-fluorobenzyloxymethyl) isoxazole-3-carboxamide (2.38 g, 7.12 mmol) in tetrahydrofuran (70 mL) at −65 ° C. or lower in a nitrogen atmosphere Then, a 1.58 mol / L-n-butyllithium hexane solution (9.7 mL, 15.3 mmol) was added dropwise. Stir at −60 ° C. or lower for 30 minutes, add N, N-dimethylformamide (5 mL), stir at −65 ° C. to −60 ° C. for 30 minutes, pour into 1 mol / L hydrochloric acid with cooling, Extracted once. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (3-fluorobenzyloxymethyl) -4-formylisoxazole-3-carboxamide (hereinafter referred to as the present compound (214)) 2. 30 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.65-1.74 (m, 1H), 2.07-2.17 (m, 1H), 2.57-2.66 ( m, 1H), 3.48-3.54 (m, 2H), 3.62 (dd, 1H), 3.75-3.81 (m, 1H), 3.84-3.98 (m, 2H), 4.66 (s, 2H), 4.99 (s, 2H), 6.98-7.14 (m, 3H), 7.30-7.36 (m, 2H), 10.42. (S, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−フルオロベンジルオキシメチル）−４−ヒドロキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２１５）と記す。）１．４６ｇを得た。
ＭＳ（ＥＳＩ）ｍ／ｚ ３６５（［Ｍ＋Ｈ］^＋） Production Example 206
To a solution of N- (tetrahydrofuran-3-ylmethyl) -5- (3-fluorobenzyloxymethyl) -4-formylisoxazole-3-carboxamide (2.30 g, 6.38 mmol) in methanol (23 mL) was cooled with ice water. Then, sodium borohydride (500 mg, 13.2 mmol) was added, stirred for 30 minutes under cooling with ice water, diluted with toluene, and concentrated under reduced pressure. The concentrate was poured into 1 mol / L hydrochloric acid and extracted twice with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (3-fluorobenzyloxymethyl) -4-hydroxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (215)) 1 .46 g was obtained.
MS (ESI) m / z 365 ([M + H] ⁺ )

で示されるジチオカルボン酸 ４−Ｏ−{５−（３−フルオロベンジルオキシメチル）−３−［（テトラヒドロフラン−３−イルメチル）カルバモイル］イソキサゾリルメチル}エステル Ｓ−メチルエステル（以下、本発明化合物（２１６）と記す。）１．４０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７２（ｍ，１Ｈ），２．０６−２．１４（ｍ，１Ｈ），２．５５（ｓ，３Ｈ），２．５６−２．６２（ｍ，１Ｈ），３．４４−３．４９（ｍ，２Ｈ），３．５６−３．６１（ｍ，１Ｈ），３．７３−３．８１（ｍ，1Ｈ），３．８３−３．９５（ｍ，２Ｈ），４．５９（ｓ，２Ｈ），４．７４（ｓ，２Ｈ），５．８２（ｓ，２Ｈ），６．９０−７．１５（ｍ，４Ｈ），７．２９−７．３６（ｍ，１Ｈ） Production Example 207
To a solution of N- (tetrahydrofuran-3-ylmethyl) -5- (3-fluorobenzyloxymethyl) -4-hydroxymethylisoxazole-3-carboxamide (1.46 g, 4.03 mmol) in tetrahydrofuran (25 mL), Under water cooling, 55% sodium hydride (211 mg, 4.83 mmol) was added and stirred for 25 minutes. Under cooling with ice water, carbon disulfide (1.2 mL) was added, stirred for 20 minutes, and further methyl iodide (1.2 mL) was added. After stirring for 30 minutes under cooling with ice water, the reaction mixture was poured into 1 mol / L hydrochloric acid and extracted once with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Dithiocarboxylic acid 4-O- {5- (3-fluorobenzyloxymethyl) -3-[(tetrahydrofuran-3-ylmethyl) carbamoyl] isoxazolylmethyl} ester S-methyl ester (hereinafter referred to as the present invention) Compound (216).) 1.40 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (m, 1H), 2.06-2.14 (m, 1H), 2.55 (s, 3H) 2.56-2.62 (m, 1H), 3.44-3.49 (m, 2H), 3.56-3.61 (m, 1H), 3.73-3.81 (m, 1H), 3.83-3.95 (m, 2H), 4.59 (s, 2H), 4.74 (s, 2H), 5.82 (s, 2H), 6.90-7.15. (M, 4H), 7.29-7.36 (m, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−フルオロベンジルオキシメチル）−４−メチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２１７）と記す。）５００ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７３（ｍ，１Ｈ），２．０４−２．１３（ｍ，１Ｈ），２．２５（ｓ，３Ｈ），２．５３−２．６３（ｍ，１Ｈ），３．４２−３．４８（ｍ，２Ｈ），３．５９（ｄｄ，１Ｈ），３．７４−３．８０（ｍ，1Ｈ），３．８４−３．９５（ｍ，２Ｈ），４．５６（ｓ，２Ｈ），４．６１（ｓ，２Ｈ），６．９２−７．１３（ｍ，４Ｈ），７．２９−７．３６（ｍ，１Ｈ） Production Example 208
Dithiocarboxylic acid 4-O- {5- (3-fluorobenzyloxymethyl) -3-[(tetrahydrofuran-3-ylmethyl) carbamoyl] isoxazolylmethyl} ester S-methyl ester (1.38 g, 3.04 mmol) ) In toluene (20 mL) was added tributyltin hydride (1.33 g, 4.55 mmol) and azobisisobutyronitrile (50 mg, 0.30 mmol). The mixture was stirred for 2 hours 30 minutes in the range of 95 ° C. to 100 ° C., and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (3-fluorobenzyloxymethyl) -4-methylisoxazole-3-carboxamide (hereinafter referred to as the present compound (217)) represented by Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.73 (m, 1H), 2.04-2.13 (m, 1H), 2.25 (s, 3H) 2.53-2.63 (m, 1H), 3.42-3.48 (m, 2H), 3.59 (dd, 1H), 3.74-3.80 (m, 1H), 3 84-3.95 (m, 2H), 4.56 (s, 2H), 4.61 (s, 2H), 6.92-7.13 (m, 4H), 7.29-7.36 (M, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−４−ホルミル−５−（３−フェニルプロピル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２１８）と記す。）１．００ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６４−１．７５（ｍ，１Ｈ），２．０７−２．１６（ｍ，３Ｈ），２．５５−２．６５（ｍ，１Ｈ），２．６７−２．７４（ｍ，２Ｈ），３．１４−３．１９（ｍ，２Ｈ），３．４７−３．５２（ｍ，２Ｈ），３．６１（ｄｄ，１Ｈ），３．７４−３．８１（ｍ，1Ｈ），３．８４−３．９７（ｍ
，２Ｈ），７．１５−７．３４（ｍ，６Ｈ），１０．３７（ｓ，１Ｈ） Production Example 209
To a solution of N- (tetrahydrofuran-3-ylmethyl) -5- (3-phenylpropyl) isoxazole-3-carboxamide (1.02 g, 2.80 mmol) in tetrahydrofuran (20 mL) at −45 ° C. or lower under a nitrogen atmosphere. A 1.58 mol / L-n-butyllithium hexane solution (4.4 mL, 7.00 mmol) was added dropwise. The mixture was stirred at −45 ° C. to −60 ° C. for 30 minutes, N, N-dimethylformamide (2.5 mL) was added, and further stirred at −60 ° C. to room temperature for 11.5 hours, and then cooled to 1 mol / L hydrochloric acid. Poured and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.00 g of N- (tetrahydrofuran-3-ylmethyl) -4-formyl-5- (3-phenylpropyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (218)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.75 (m, 1H), 2.07-2.16 (m, 3H), 2.55-2.65 ( m, 1H), 2.67-2.74 (m, 2H), 3.14-3.19 (m, 2H), 3.47-3.52 (m, 2H), 3.61 (dd, 1H), 3.74-3.81 (m, 1H), 3.84-3.97 (m
, 2H), 7.15-7.34 (m, 6H), 10.37 (s, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−４−ヒドロキシメチル−５−（３−フェニルプロピル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２１９）と記す。）８９０ｍｇを得た。
ＭＳ（ＥＳＩ）ｍ／ｚ ３４５（［Ｍ＋Ｈ］^＋） Production Example 210
Hydrogenation of N- (tetrahydrofuran-3-ylmethyl) -4-formyl-5- (3-phenylpropyl) isoxazole-3-carboxamide (1.00 g, 2.55 mmol) in methanol (15 mL) under water cooling Sodium boron (250 mg, 6.61 mmol) was added. The mixture was stirred for 1.5 hours under cooling with water, diluted with toluene, and concentrated under reduced pressure. The concentrate was diluted with ethyl acetate, washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

890 mg of N- (tetrahydrofuran-3-ylmethyl) -4-hydroxymethyl-5- (3-phenylpropyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (219)) represented by the formula:
MS (ESI) m / z 345 ([M + H] ⁺ )

で示されるジチオカルボン酸 ４−Ｏ−{５−（３−フェニルプロピル）−３−［（テトラヒドロフラン−３−イルメチル）カルバモイル］イソキサゾリルメチル}エステル Ｓ−メチルエステル（以下、本発明化合物（２２０）と記す。）８６９ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７３（ｍ，１Ｈ），２．０１−２．１４（ｍ，３Ｈ），２．５５（ｓ，３Ｈ），２．５６−２．６２（ｍ，１Ｈ），２．６５−２．７３（ｍ，２Ｈ），２．８４−２．９０（ｍ，２Ｈ），３．４２−３．４８（ｍ，２Ｈ），３．５６−３．６１（ｍ，１Ｈ），３．７３−３．８０（ｍ，1Ｈ），３．８３−３．９５（ｍ，２Ｈ），５．７２（ｓ，２Ｈ），６．９１（ｂｒｓ，１Ｈ），７．１６−７．２３（ｍ，３Ｈ），７．２７−７．３２（ｍ，２Ｈ） Production Example 211
To a solution of N- (tetrahydrofuran-3-ylmethyl) -4-hydroxymethyl-5- (3-phenylpropyl) isoxazole-3-carboxamide (890 mg, 2.24 mmol) in tetrahydrofuran (20 mL) was added 55% under cooling with water. Sodium hydride (117 mg, 2.69 mmol) was added and stirred for 25 minutes. Under cooling with ice water, carbon disulfide (0.8 mL) was added, stirred for 15 minutes, methyl iodide (0.8 mL) was added, stirred for further 15 minutes under cooling with ice water, poured into 1 mol / L hydrochloric acid, ethyl acetate Extracted once. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Dithiocarboxylic acid 4-O- {5- (3-phenylpropyl) -3-[(tetrahydrofuran-3-ylmethyl) carbamoyl] isoxazolylmethyl} ester S-methyl ester (hereinafter referred to as the present compound ( 220).) 869 mg was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.73 (m, 1H), 2.01-2.14 (m, 3H), 2.55 (s, 3H) 2.56-2.62 (m, 1H), 2.65-2.73 (m, 2H), 2.84-2.90 (m, 2H), 3.42-3.48 (m, 2H), 3.56-3.61 (m, 1H), 3.73-3.80 (m, 1H), 3.83-3.95 (m, 2H), 5.72 (s, 2H) 6.91 (brs, 1H), 7.16-7.23 (m, 3H), 7.27-7.32 (m, 2H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−４−メチル−５−（３−フェニルプロピル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２２１）と記す。）２９０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７３（ｍ，１Ｈ），１．９９−２．１２（ｍ，３Ｈ），２．１４（ｓ，３Ｈ），２．５２−２．６２（ｍ，１Ｈ），２．６３−２．６９（ｍ，２Ｈ），２．７０−２．７６（ｍ，２Ｈ），３．３８−３．４９（ｍ，２Ｈ），３．５８（ｄ，１Ｈ），３．７３−３．８０（ｍ，1Ｈ），３．８３−３．９４（ｍ，２Ｈ），６．９３（ｂｒｓ，１Ｈ），７．１６−７．２３（ｍ，３Ｈ），７．２７−７．３２（ｍ，２Ｈ） Production Example 212
Dithiocarboxylic acid 4-O- {5- (3-phenylpropyl) -3-[(tetrahydrofuran-3-ylmethyl) carbamoyl] isoxazolylmethyl} ester S-methyl ester (869 mg, 1.79 mmol) in toluene ( 20 mL) solution was added tributyltin hydride (938 mg, 2.69 mmol) and azobisisobutyronitrile (29 mg, 0.18 mmol). The mixture was stirred at 95 to 100 ° C. for 2 hours, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 290 mg of N- (tetrahydrofuran-3-ylmethyl) -4-methyl-5- (3-phenylpropyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (221)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.73 (m, 1H), 1.99-2.12 (m, 3H), 2.14 (s, 3H) , 2.52-2.62 (m, 1H), 2.62-2.69 (m, 2H), 2.70-2.76 (m, 2H), 3.38-3.49 (m, 2H), 3.58 (d, 1H), 3.73-3.80 (m, 1H), 3.83-3.94 (m, 2H), 6.93 (brs, 1H), 7.16. -7.23 (m, 3H), 7.27-7.32 (m, 2H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−４−ホルミル−５−(２−ナフチルメトキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２２２）と記す。）１．３３ｇを粗生成物として得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３０−１．４５（ｍ，２Ｈ），１．６０−１．７１（ｍ，２Ｈ），１．８０−１．９１（ｍ，１Ｈ），３．３４−３．４０（ｍ，４Ｈ），３．９５−４．０３（ｍ，２Ｈ），４．６０（ｓ，２Ｈ），４．６７（ｓ，２Ｈ），６．７６（ｂｒｓ，１Ｈ），７．４６−７．５３（ｍ，３Ｈ），７．８０−７．８８（ｍ，４Ｈ），１０．３９（ｓ，１Ｈ） Production Example 213
To a solution of N- (tetrahydropyran-4-ylmethyl) -5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (1.00 g, 2.63 mmol) in tetrahydrofuran (20 mL) at −45 ° C. under a nitrogen atmosphere. A 1.58 mol / L-n-butyllithium hexane solution (4.2 mL, 6.57 mmol) was added dropwise below. The mixture was stirred at -50 ° C to -60 ° C for 40 minutes, N, N-dimethylformamide (5 mL) was added, and the mixture was further stirred at -60 ° C to room temperature for 1 hour, and then poured into 1 mol / L hydrochloric acid with cooling. And extracted twice. The organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

N- (tetrahydropyran-4-ylmethyl) -4-formyl-5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (222)) 1.33 g of Obtained as a crude product.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.30-1.45 (m, 2H), 1.60-1.71 (m, 2H), 1.80-1.91 ( m, 1H), 3.34-3.40 (m, 4H), 3.95-4.03 (m, 2H), 4.60 (s, 2H), 4.67 (s, 2H), 6 .76 (brs, 1H), 7.46-7.53 (m, 3H), 7.80-7.88 (m, 4H), 10.39 (s, 1H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−４−ヒドロキシメチル−５−(２−ナフチルメトキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２２３）と記す。）９５０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３２−１．４５（ｍ，２Ｈ），１．５９（ｓ，１Ｈ），１．６３−１．７１（ｍ，２Ｈ），１．８２−１．９４（ｍ，１Ｈ），３．３３−３．４３（ｍ，４Ｈ），３．９７−４．０４（ｍ，２Ｈ），４．６２（ｓ，２Ｈ），４．６７（ｓ，２Ｈ），４．７４（ｓ，２Ｈ），７．０８（ｂｒｓ，１Ｈ），７．４５−７．５３（ｍ，３Ｈ），７．７８−７．８８（ｍ，４Ｈ） Production Example 214
Of crude N- (tetrahydropyran-4-ylmethyl) -4-formyl-5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (1.33 g, <3.26 mmol) obtained in Preparation Example 213 Sodium borohydride (580 mg, 15.3 mmol) was added to a methanol (20 mL) solution under ice water cooling, and the mixture was stirred for 1 hour, diluted with toluene, and concentrated under reduced pressure. Under cooling, the concentrate was poured into 1 mol / L hydrochloric acid and extracted twice with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

950 mg of N- (tetrahydropyran-4-ylmethyl) -4-hydroxymethyl-5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (223)) represented by the formula: It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.32-1.45 (m, 2H), 1.59 (s, 1H), 1.63-1.71 (m, 2H) , 1.82-1.94 (m, 1H), 3.33-3.43 (m, 4H), 3.97-4.04 (m, 2H), 4.62 (s, 2H), 4 .67 (s, 2H), 4.74 (s, 2H), 7.08 (brs, 1H), 7.45-7.53 (m, 3H), 7.78-7.88 (m, 4H) )

で示されるジチオカルボン酸 ４−Ｏ−｛５−(２−ナフチルメトキシメチル）−３−［（テトラヒドロピラン−４−イルメチル）カルバモイル］イソキサゾリルメチル｝エステル Ｓ−メチルエステル（以下、本発明化合物（２２４）と記す。）１．０６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３０−１．４４（ｍ，２Ｈ），１．６２−１．７１（ｍ，２Ｈ），１．８０−１．９３（ｍ，１Ｈ），２．５０（ｓ，３Ｈ），３．３０−３．４２（ｍ，４Ｈ），３．９５−４．０２（ｍ，２Ｈ），４．７６（ｓ，４Ｈ），５．８１（ｓ，２Ｈ），６．８６（ｂｒｓ，１Ｈ），７．４４−７．５３（ｍ，３Ｈ），７．７７−７．８８（ｍ，４Ｈ） Production Example 215
55% sodium hydride in a solution of N- (tetrahydropyran-4-ylmethyl) -4-hydroxymethyl-5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (950 mg, 2.31 mmol) in tetrahydrofuran (20 mL) (121 mg, 2.78 mmol) was added, and the mixture was stirred at room temperature for 20 minutes. After cooling with ice water, carbon disulfide (1 mL) was added, and the mixture was further stirred for 15 minutes. Methyl iodide (1 mL) was added to the reaction mixture, and the mixture was stirred for 30 minutes, poured into 1 mol / L hydrochloric acid with cooling with ice water, and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Dithiocarboxylic acid 4-O- {5- (2-naphthylmethoxymethyl) -3-[(tetrahydropyran-4-ylmethyl) carbamoyl] isoxazolylmethyl} ester S-methyl ester (hereinafter referred to as the present invention) 1.06 g of compound (224) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.30-1.44 (m, 2H), 1.62-1.71 (m, 2H), 1.80-1.93 ( m, 1H), 2.50 (s, 3H), 3.30-3.42 (m, 4H), 3.95-4.02 (m, 2H), 4.76 (s, 4H), 5 .81 (s, 2H), 6.86 (brs, 1H), 7.44-7.53 (m, 3H), 7.77-7.88 (m, 4H)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−４−メチル−５−(２−ナフチルメトキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２２５）と記す。）３８０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３２−１．４３（ｍ，２Ｈ），１．６４−１．７０（ｍ，２Ｈ），１．８０−１．９１（ｍ，１Ｈ），２．２５（ｓ，３Ｈ），３．３３−３．４３（ｍ，４Ｈ），３．９６−４．０２（ｍ，２Ｈ），４．６３（ｓ，２Ｈ），４．７３（ｓ，２Ｈ），６．９０（ｂｒｓ，１Ｈ），７．４５−７．５２（ｍ，３Ｈ），７．７８−７．８８（ｍ，４Ｈ）
製造例２１７
５−［（２−メチルベンジル）オキシメチル］イソキサゾール−３−カルボン酸（１．１５ｇ，４．７ｍｍｏｌ）をクロロホルム（アミレン添加品）（１０ｍＬ）に加え、０℃に冷却し、トリエチルアミン（０．５７ml，５．６ｍｍｏｌ）、１−エチル−３−（３−ジメチルアミノプロピル）カルボジイミド塩酸塩（１．０８ｇ，５．６ｍｍｏｌ）及び１−ヒドロキシベンゾトリアゾール（０．０８ｇ，０．６ｍｍｏｌ）を加え、１０分間攪拌した。混合物にテトラヒドロピラン−４−イルメチルアミン（０．７７ｇ，５．６ｍｍｏｌ）を加え、室温で１６時間攪拌した後、水を加え、酢酸エチルで２回抽出した。有機層を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した後、減圧下で濃縮した。残渣をシリカゲルカラムクロマトグラフィーに付し、下式

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（２−メチルベンジル）オキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２２６）と記す。）０．９６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７２（１Ｈ，ｍ），２．０８−２．１１（１Ｈ，ｍ），２．３４（３Ｈ，ｓ），２．５５−２．６１（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７５−３．７９（１Ｈ，ｍ），３．８５−３．８７（１Ｈ，ｍ），３．９１−３．９３（１Ｈ，ｍ），４．６１（２Ｈ，ｓ），４．６５（２Ｈ，ｓ），６．７２（１Ｈ，ｓ），６．９６（１Ｈ，ｓ），７．２０−７．２３（３Ｈ，ｍ），７．３０−７．３１（１Ｈ，ｍ） Production Example 216
Dithiocarboxylic acid 4-O- {5- (2-naphthylmethoxymethyl) -3-[(tetrahydropyran-4-ylmethyl) carbamoyl] isoxazolylmethyl} ester S-methyl ester (1.06 g, 2.12 mmol ) In toluene (20 mL) was added tributyltin hydride (740 mg, 2.54 mmol) and azobisisobutyronitrile (70 mg, 0.42 mmol). The mixture was stirred at 90 to 100 ° C. for 1 hour and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

380 mg of N- (tetrahydropyran-4-ylmethyl) -4-methyl-5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (225)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.32-1.43 (m, 2H), 1.64-1.70 (m, 2H), 1.80-1.91 ( m, 1H), 2.25 (s, 3H), 3.33-3.43 (m, 4H), 3.96-4.02 (m, 2H), 4.63 (s, 2H), 4 .73 (s, 2H), 6.90 (brs, 1H), 7.45-7.52 (m, 3H), 7.78-7.88 (m, 4H)
Production Example 217
5-[(2-Methylbenzyl) oxymethyl] isoxazole-3-carboxylic acid (1.15 g, 4.7 mmol) was added to chloroform (amylene-added product) (10 mL), cooled to 0 ° C., triethylamine (0. 57 ml, 5.6 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.08 g, 5.6 mmol) and 1-hydroxybenzotriazole (0.08 g, 0.6 mmol) were added, Stir for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.77 g, 5.6 mmol) was added to the mixture, and the mixture was stirred at room temperature for 16 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.96 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(2-methylbenzyl) oxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (226)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (1H, m), 2.08-2.11 (1H, m), 2.34 (3H, s) 2.55-2.61 (1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.75-3.79 (1H, m), 3.85-3 .87 (1H, m), 3.91-3.93 (1H, m), 4.61 (2H, s), 4.65 (2H, s), 6.72 (1H, s), 6. 96 (1H, s), 7.20-7.23 (3H, m), 7.30-7.31 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−メトキシベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２２７）と記す。）１．０２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６７−１．７２（１Ｈ，ｍ），２．０８−２．１１（１Ｈ，ｍ），２．５５−２．６２（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７４−３．８０（１Ｈ，ｍ），３．８５−３．８７（４Ｈ，ｍ），３．９１−３．９３（１Ｈ，ｍ），４．６５（２Ｈ，ｓ），４．６９（２Ｈ，ｓ），６．７５（１Ｈ，ｓ），６．８９（１Ｈ，ｄ），６．９６−６．９８（２Ｈ，ｍ），７．２８−７．３７（２Ｈ，ｍ） Production Example 218
5-[(2-methoxybenzyl) oxymethyl] isoxazole-3-carboxylic acid (1.13 g, 4.7 mmol) was added to chloroform (amylene-added product) (10 mL), cooled to 0 ° C., triethylamine (0. 57 ml, 5.6 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.08 g, 5.6 mmol) and 1-hydroxybenzotriazole (0.08 g, 0.6 mmol) were added, Stir for 10 minutes. Tetrahydropyran-4-ylmethylamine (0.77 g, 5.6 mmol) was added to the mixture, and the mixture was stirred at room temperature for 16 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.02 g of N- (tetrahydrofuran-3-ylmethyl) -5- (2-methoxybenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (227)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.67-1.72 (1H, m), 2.08-2.11 (1H, m), 2.55-2.62 ( 1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.74-3.80 (1H, m), 3.85-3.87 (4H, m), 3 91-3.93 (1H, m), 4.65 (2H, s), 4.69 (2H, s), 6.75 (1H, s), 6.89 (1H, d), 6. 96-6.98 (2H, m), 7.28-7.37 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［３−（２−ナフチル）プロピル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２２８）と記す。）０．４９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６６−１．７３（１Ｈ，ｍ），２．０６−２．１９（３Ｈ，ｍ），２．５４−２．６１（１Ｈ，ｍ），２．８３−２．８７（４Ｈ，ｍ），３．４６（２Ｈ，ｔ），３．５８−３．６０（１Ｈ，ｍ），３．７５−３．７９（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），６．４８（１Ｈ，ｓ），６．９３（１Ｈ，ｓ），７．３２（１Ｈ，ｄｄ），７．４２−７．４９（２Ｈ，ｍ），７．６２（１Ｈ，ｓ），７．７８−７．８３（３Ｈ，ｍ） Production Example 219
5- [3- (2-naphthyl) propyl] isoxazole-3-carboxylic acid (0.56 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.33 g, 2.4 mmol), triethylamine (0 .25 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.24 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.49 g of N- (tetrahydrofuran-3-ylmethyl) -5- [3- (2-naphthyl) propyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (228)) represented by the formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.66-1.73 (1H, m), 2.06-2.19 (3H, m), 2.54-2.61 ( 1H, m), 2.83-2.87 (4H, m), 3.46 (2H, t), 3.58-3.60 (1H, m), 3.75-3.79 (1H, m), 3.84-3.94 (2H, m), 6.48 (1H, s), 6.93 (1H, s), 7.32 (1H, dd), 7.42-7.49. (2H, m), 7.62 (1H, s), 7.78-7.83 (3H, m)

で示されるＮ−（１，３−ジオキソラン−４−イルメチル）−５−［３−（２−ナフチル）プロピル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２２９）と記す。）０．５１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：２．１３−２．１８（２Ｈ，ｍ），２．８４−２．８８（４Ｈ，ｍ），３．９９−４．００（４Ｈ，ｍ），４．１１−４．１６（１Ｈ，ｍ），４．８０（１Ｈ，ｄ），５．０２（１Ｈ，ｄ），６．４８（１Ｈ，ｓ），７．３３（１Ｈ，ｄｄ），７．４２−７．４９（２Ｈ，ｍ），７．６０−７．６２（２Ｈ，ｍ），７．７８−７．８３（３Ｈ，ｍ） Production Example 220
5- [3- (2-naphthyl) propyl] isoxazole-3-carboxylic acid (0.56 g, 2.0 mmol), 1,3-dioxolan-4-ylmethylamine (0.24 g, 2.4 mmol), triethylamine (0.25 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.24 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (1,3-dioxolan-4-ylmethyl) -5- [3- (2-naphthyl) propyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (229)) 0. 51 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 2.13-2.18 (2H, m), 2.84-2.88 (4H, m), 3.99-4.00 ( 4H, m), 4.11-4.16 (1H, m), 4.80 (1H, d), 5.02 (1H, d), 6.48 (1H, s), 7.33 (1H , Dd), 7.42-7.49 (2H, m), 7.60-7.62 (2H, m), 7.78-7.83 (3H, m).

で示されるＮ−（１，４−ジオキサン−２−イルメチル）−５−［３−（２−ナフチル）プロピル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２３０）と記す。）０．５７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：２．１２−２．１７（２Ｈ，ｍ），２．８５（４Ｈ，ｑ），３．３３−３．３８（２Ｈ，ｍ），３．５８−３．６６（２Ｈ，ｍ），３．７３−３．８０（５Ｈ，ｍ），６．４７（１Ｈ，ｓ），７．１０（１Ｈ，ｓ），７．３２（１Ｈ，ｄｄ），７．４１−７．４９（２Ｈ，ｍ），７．６２（１Ｈ，ｓ），７．７８−７．８３（３Ｈ，ｍ）． Production Example 221
5- [3- (2-naphthyl) propyl] isoxazole-3-carboxylic acid (0.56 g, 2.0 mmol), 1,4-dioxan-2-ylmethylamine (0.24 g, 2.4 mmol), triethylamine (0.25 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.24 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (1,4-dioxan-2-ylmethyl) -5- [3- (2-naphthyl) propyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (230)) 0. 57 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 2.12-2.17 (2H, m), 2.85 (4H, q), 3.33-3.38 (2H, m) 3.58-3.66 (2H, m), 3.73-3.80 (5H, m), 6.47 (1H, s), 7.10 (1H, s), 7.32 (1H , Dd), 7.41-7.49 (2H, m), 7.62 (1H, s), 7.78-7.83 (3H, m).

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［５−（２，２−ジフルオロ−１，３−ベンゾジオキソラニル）プロピル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２３１）と記す。）０．５７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６６−１．６９（１Ｈ，ｍ），１．９９−２．１３（３Ｈ，ｍ），２．５３−２．６３（１Ｈ，ｍ），２．６８（２Ｈ，ｔ），２．８１（２Ｈ，ｔ），３．４６（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７６（１Ｈ，ｑ），３．８４−３．９４（２Ｈ，ｍ），６．４６（１Ｈ，ｓ），６．８６−６．９９（４Ｈ，ｍ） Production Example 222
5- {3- [5- (2,2-difluoro-1,3-benzodioxolanyl)] propyl} isoxazole-3-carboxylic acid (0.58 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine Hydrochloride (0.33 g, 2.4 mmol), triethylamine (0.25 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.24 mmol) were added to chloroform (amylene added product) (5 mL). . To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- [5- (2,2-difluoro-1,3-benzodioxolanyl) propyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (231) ) 0.57 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.66 to 1.69 (1H, m), 1.99-2.13 (3H, m), 2.53 to 2.63 ( 1H, m), 2.68 (2H, t), 2.81 (2H, t), 3.46 (2H, t), 3.59 (1H, dd), 3.76 (1H, q), 3.84-3.94 (2H, m), 6.46 (1H, s), 6.86-6.99 (4H, m)

で示されるＮ−（１，４−ジオキサン−２−イルメチル）−５−［３−（５−（２，２−ジフルオロ−１，３−ベンゾジオキソラニル））プロピル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２３２）と記す。）０．５０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．９９−２．０６（２Ｈ，ｍ），２．６７−２．７１（２Ｈ，ｍ），２．８０（２Ｈ，ｔ），３．３０−３．４０（２Ｈ，ｍ），３．５７−３．６６（２Ｈ，ｍ），３．７０−３．８３（５Ｈ，ｍ），６．４６（１Ｈ，ｄ），６．８７（２Ｈ，ｔｄ），６．９７（１Ｈ，ｄ），７．１０（１Ｈ，ｓ） Production Example 223
5- {3- [5- (2,2-difluoro-1,3-benzodioxolanyl)] propyl} isoxazole-3-carboxylic acid (0.52 g, 1.8 mmol), 1,4-dioxane-2 -Ylmethylamine (0.24 g, 2.4 mmol), triethylamine (0.25 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.24 mmol) in chloroform (amylene-added product) (5 mL) added. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (1,4-Dioxane-2-ylmethyl) -5- [3- (5- (2,2-difluoro-1,3-benzodioxolanyl)) propyl] isoxazole-3-carboxamide represented by (Hereinafter referred to as the present compound (232).) 0.50 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.99-2.06 (2H, m), 2.67-2.71 (2H, m), 2.80 (2H, t) 3.30-3.40 (2H, m), 3.57-3.66 (2H, m), 3.70-3.83 (5H, m), 6.46 (1H, d), 6 .87 (2H, td), 6.97 (1H, d), 7.10 (1H, s)

で示されるＮ−（１，４−ジオキサン−２−イルメチル）−５−（２−ナフチルメチル）オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２３３）と記す。）０．５１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：３．３１−３．４１（２Ｈ，ｍ），３．５８−３．６７（２Ｈ，ｍ），３．７０−３．８３（５Ｈ，ｍ），４．６９（２Ｈ，ｄ），４．７７（２Ｈ，ｓ），６．７５（１Ｈ，ｓ），７．１３（１Ｈ，ｓ），７．４６−７．５３（３Ｈ，ｍ），７．８２−７．８４（４Ｈ，ｍ） Production Example 224
5- (2-Naphtylmethyl) oxymethylisoxazole-3-carboxylic acid (0.57 g, 2.0 mmol), 1,4-dioxane-2-ylmethylamine (0.24 g, 2.4 mmol) and 1 -Hydroxybenzotriazole (0.03 g, 0.24 mmol) was added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (1,4-dioxan-2-ylmethyl) -5- (2-naphthylmethyl) oxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (233)) 0. 51 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 3.31-3.41 (2H, m), 3.58-3.67 (2H, m), 3.70-3.83 ( 5H, m), 4.69 (2H, d), 4.77 (2H, s), 6.75 (1H, s), 7.13 (1H, s), 7.46-7.53 (3H , M), 7.82-7.84 (4H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［３−（１，３−ベンゾジオキソラン−５−イル）プロピル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２３４）と記す。）０．５７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７２（１Ｈ，ｍ），１．９５−２．０３（２Ｈ，ｍ），２．０４−２．１１（１Ｈ，ｍ），２．５５−２．６２（３Ｈ，ｍ），２．７８（２Ｈ，ｔ），３．４４−３．４６（２Ｈ，ｍ），３．５８−３．６０（１Ｈ，ｍ），３．７２−３．７８（１Ｈ，ｍ），３．８２−３．９３（２Ｈ，ｍ），５．９２（２Ｈ，ｓ），６．４６（１Ｈ，ｓ），６．６１−６．６５（２Ｈ，ｍ），６．７３（１Ｈ，ｄ），７．２２（１Ｈ，ｓ） Production Example 225
5- [3- (1,3-Benzodioxolan-5-yl) propyl] isoxazole-3-carboxylic acid (0.55 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.33 g, 2 0.4 mmol), triethylamine (0.25 g, 2.4 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.24 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- [3- (1,3-benzodioxolan-5-yl) propyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (234)). ) 0.57 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (1H, m), 1.95-2.03 (2H, m), 2.04-2.11 ( 1H, m), 2.55-2.62 (3H, m), 2.78 (2H, t), 3.44-3.46 (2H, m), 3.58-3.60 (1H, m), 3.72-3.78 (1H, m), 3.82-3.93 (2H, m), 5.92 (2H, s), 6.46 (1H, s), 6.61. -6.65 (2H, m), 6.73 (1H, d), 7.22 (1H, s)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−（３−フェニルプロピル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２３５）と記す。）
０．４９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３４−１．４１（２Ｈ，ｍ），１．６５−１．６９（２Ｈ，ｍ），１．８１−１．９１（１Ｈ，ｍ），２．０２−２．０９（２Ｈ，ｍ），２．６９（２Ｈ，ｔ），２．８０（２Ｈ，ｔ），３．３４−３．３９（４Ｈ，ｍ），３．９７−４．００（２Ｈ，ｍ），６．４６（１Ｈ，ｓ），６．８９（１Ｈ，ｓ），７．１７−７．２３（３Ｈ，ｍ），７．２９−７．３１（２Ｈ，ｍ） Production Example 226
5- (3-Phenylpropyl) isoxazole-3-carboxylic acid (0.46 g, 2.0 mmol), tetrahydropyran-4-ylmethylamine (0.29 g, 2.5 mmol), triethylamine (0.24 g, 2.. 4 mmol) and 1-hydroxybenzotriazole (0.04 g, 0.24 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydropyran-4-ylmethyl) -5- (3-phenylpropyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (235))
0.49 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.34-1.41 (2H, m), 1.65-1.69 (2H, m), 1.81-1.91 ( 1H, m), 2.02-2.09 (2H, m), 2.69 (2H, t), 2.80 (2H, t), 3.34-3.39 (4H, m), 3 97-4.00 (2H, m), 6.46 (1H, s), 6.89 (1H, s), 7.17-7.23 (3H, m), 7.29-7.31. (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−[５−（２，２−ジフルオロ−１，３−ベンゾジオキソラニル）]メトキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２３６）と記す。）０．７４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６６−１．７１（１Ｈ，ｍ），２．０５−２．１５（１Ｈ，ｍ），２．５５−２．６２（１Ｈ，ｍ），３．４６−３．４９（２Ｈ，ｍ），３．６０（１Ｈ，ｄｄ），３．７４−３．８０（１Ｈ，ｍ），３．８６（１Ｈ，ｄｄ），３．９３（１Ｈ，ｔｄ），４．５７（２Ｈ，ｓ），４．６６（２Ｈ，ｓ），６．７４（１Ｈ，ｓ），６．９７（１Ｈ，ｂｒｓ），７．０４−７．１０（３Ｈ，ｍ） Production Example 227
5- [5- (2,2-difluoro-1,3-benzodioxolanyl)] methoxymethylisoxazole-3-carboxylic acid (0.69 g, 2.2 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride Salt (0.36 g, 2.7 mmol), triethylamine (0.27 g, 2.7 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.27 mmol) were added to chloroform (amylene-added product) (7 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.52 g, 2.7 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- [5- (2,2-difluoro-1,3-benzodioxolanyl)] methoxymethylisoxazole-3-carboxamide (hereinafter referred to as the present invention) 0.74 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.66-1.71 (1H, m), 2.05-2.15 (1H, m), 2.55-2.62 ( 1H, m), 3.46-3.49 (2H, m), 3.60 (1H, dd), 3.74-3.80 (1H, m), 3.86 (1H, dd), 3 .93 (1H, td), 4.57 (2H, s), 4.66 (2H, s), 6.74 (1H, s), 6.97 (1H, brs), 7.04-7. 10 (3H, m)

で示されるＮ−（テトラヒドロピラン−４−イルメチル）−５−[５−（２，２−ジフルオロ−１，３−ベンゾジオキソラニル）]メトキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２３７）と記す。）０．６４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３７−１．４２（２Ｈ，ｍ），１．６８−１．６９（２Ｈ，ｍ），１．８３−１．８９（１Ｈ，ｍ），３．３４−３．４２（４Ｈ，ｍ），３．９９（２Ｈ，ｄｄ），４．５７（２Ｈ，ｓ），４．６５（２Ｈ，ｄ），６．７３（１Ｈ，ｓ），６．９０（１Ｈ，ｓ），７．０４−７．１０（３Ｈ，ｍ） Production Example 228
5- [5- (2,2-difluoro-1,3-benzodioxolanyl)] methoxymethylisoxazole-3-carboxylic acid (0.69 g, 2.2 mmol), tetrahydropyran-4-ylmethylamine (0.31 g, 2.7 mmol), triethylamine (0.27 g, 2.7 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.27 mmol) were added to chloroform (amylene-added product) (7 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.52 g, 2.7 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydropyran-4-ylmethyl) -5- [5- (2,2-difluoro-1,3-benzodioxolanyl)] methoxymethylisoxazole-3-carboxamide (hereinafter referred to as the present invention) 0.64 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.37-1.42 (2H, m), 1.68-1.69 (2H, m), 1.83-1.89 ( 1H, m), 3.34-3.42 (4H, m), 3.99 (2H, dd), 4.57 (2H, s), 4.65 (2H, d), 6.73 (1H) , S), 6.90 (1H, s), 7.04-7.10 (3H, m)

で示されるＮ−（３−メチルオキセタン−３−イルメチル）−５−[５−（２，２−ジフルオロ−１，３−ベンゾジオキソラニル）]メトキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２３８）と記す。）０．６４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３７（３Ｈ，ｓ），３．６６（２Ｈ，ｄ），４．４３（２Ｈ，ｄ），４．５４（２Ｈ，ｄ），４．５７（２Ｈ，ｓ），４．６６（２Ｈ，ｓ），６．７５（１Ｈ，ｓ），７．０７（４Ｈ，ｔ） Production Example 229
5- [5- (2,2-Difluoro-1,3-benzodioxolanyl)] methoxymethylisoxazole-3-carboxylic acid (0.69 g, 2.2 mmol), 3-methyloxetane-3-yl Methylamine (0.31 g, 2.7 mmol), triethylamine (0.27 g, 2.7 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.27 mmol) were added to chloroform (amylene-added product) (7 mL). . To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.52 g, 2.7 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (3-methyloxetane-3-ylmethyl) -5- [5- (2,2-difluoro-1,3-benzodioxolanyl)] methoxymethylisoxazole-3-carboxamide represented by , Described as the present compound (238).) 0.64 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.37 (3H, s), 3.66 (2H, d), 4.43 (2H, d), 4.54 (2H, d ), 4.57 (2H, s), 4.66 (2H, s), 6.75 (1H, s), 7.07 (4H, t)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（５，６，７，８−テトラヒドロナフタレン−２−イル）オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２３９）と記す。）０．４０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６１−１．７１（１Ｈ，ｍ），１．７６−１．７９（４Ｈ， ｂｒ ｍ），２．０４−２．１３（１Ｈ，ｍ），２．５２−２．６２（１Ｈ，ｍ）， ２．７０−２．７３（４Ｈ， ｂｒ ｍ），３．４４−３．４８（２Ｈ，ｍ），３．５７−３．６０（１Ｈ，ｍ），３．７３−３．７９（１Ｈ，ｍ），３．８３−３．９４（２Ｈ，ｍ），５．１５ （２Ｈ，ｓ），６．６５（１Ｈ，ｂｒ ｓ），６．６９（１Ｈ，ｄｄ），６．７７（１Ｈ， ｓ），６．９６（１Ｈ，ｂｒ ｓ），６．９９（１Ｈ，ｄ） Production Example 230
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.24 g, 1.75 mmol) and triethylamine (0.18 g, 1.75 mmol) were added to chloroform (amylene-added product) (8 mL). To the mixture was added 5- (5,6,7,8-tetrahydronaphthalen-2-yl) oxymethylisoxazole-3-carboxylic acid (0.40 g, 1.46 mmol), 1-hydroxybenzotriazole (0 0.02 g, 0.18 mmol) and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.34 g, 1.75 mmol) were added, stirred for 5 hours, diluted hydrochloric acid was added, and chloroform was added twice. Extracted. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (5,6,7,8-tetrahydronaphthalen-2-yl) oxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (239)) 0.40 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.61-1.71 (1H, m), 1.76-1.79 (4H, br m), 2.04-2.13 (1H, m), 2.52-2.62 (1H, m), 2.70-2.73 (4H, br m), 3.44-3.48 (2H, m), 3.57- 3.60 (1H, m), 3.73-3.79 (1H, m), 3.83-3.94 (2H, m), 5.15 (2H, s), 6.65 (1H, br s), 6.69 (1H, dd), 6.77 (1H, s), 6.96 (1H, br s), 6.99 (1H, d)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−フェニル−２−プロピニル）オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２４０）と記す。）０．７６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６３−１．７１（１Ｈ，ｍ），２．０４−２．１２（１Ｈ，ｍ），２．５４−２．６１（１Ｈ，ｍ）， ３．４４−３．４８（２Ｈ，ｍ），３．５７−３．６１（１Ｈ，ｍ），３．７４−３．７９（１Ｈ，ｍ），３．８３−３．９２（２Ｈ，ｍ），４．４７（２Ｈ， ｓ），４．８１ （２Ｈ，ｓ），６．７８（１Ｈ，ｓ），６．９９（１Ｈ， ｂｒ ｓ），７．３２−７．３６（３Ｈ，ｍ），７．４４−７．４７（２Ｈ，ｍ） Production Example 231
Iodobenzene (0.66 g, 3.22 mmol) and dichlorobistriphenylphosphine palladium (0.11 g, 0.16 mmol) were added to tetrahydrofuran (25 mL). To the mixture was added copper iodide (0.06 g, 0.32 mmol), diisopropylamine (0.39 g, 3.86 mmol) and N- (tetrahydrofuran-3-ylmethyl) -5-propargyloxymethylisoxazole-3 at room temperature. -Carboxamide (0.85 g, 3.22 mmol) was added, stirred for 5 hours, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (3-phenyl-2-propynyl) oxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (240)) 0.76 g Got.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.71 (1H, m), 2.04-2.12 (1H, m), 2.54-2.61 ( 1H, m), 3.44-3.48 (2H, m), 3.57-3.61 (1H, m), 3.74-3.79 (1H, m), 3.83-3. 92 (2H, m), 4.47 (2H, s), 4.81 (2H, s), 6.78 (1H, s), 6.99 (1H, br s), 7.32-7. 36 (3H, m), 7.44-7.47 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（５−フェニル−２−チエニルメチル）オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２４１）と記す。）０．２５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６３−１．７２（１Ｈ，ｍ），２．０４−２．１３（１Ｈ，ｍ），２．５２−２．６２（１Ｈ，ｍ）， ３．４５−３．４８（２Ｈ，ｍ），３．５７−３．６１（１Ｈ，ｍ），３．７４−３．７９（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），４．６８（２Ｈ， ｓ），４．７６ （２Ｈ，ｓ），６．７４（１Ｈ，ｓ），６．９４（１Ｈ，ｂｒ ），６．０１（１Ｈ，ｄ），７．１９（１Ｈ，ｄ），７．２８−７．３１（１Ｈ，ｍ），７．３６−７．４０（２Ｈ，ｍ），７．５６−７．６０（２Ｈ，ｍ） Production Example 232
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.13 g, 0.95 mmol) and triethylamine (0.10 g, 0.95 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 5- (5-phenyl-2-thienylmethyl) oxymethylisoxazole-3-carboxylic acid (0.25 g, 0.79 mmol), 1-hydroxybenzotriazole (0.01 g, 0.08 mmol) at room temperature. ) And 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.18 g, 0.95 mmol) were added, and the mixture was stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (5-phenyl-2-thienylmethyl) oxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (241)) 0. 25 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (1H, m), 2.04-2.13 (1H, m), 2.52-2.62 ( 1H, m), 3.45-3.48 (2H, m), 3.57-3.61 (1H, m), 3.74-3.79 (1H, m), 3.84-3. 94 (2H, m), 4.68 (2H, s), 4.76 (2H, s), 6.74 (1H, s), 6.94 (1H, br), 6.01 (1H, d) ), 7.19 (1H, d), 7.28-7.31 (1H, m), 7.36-7.40 (2H, m), 7.56-7.60 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−フェニル−（Ｅ）−２−プロペニル）オキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２４２）と記す。）０．２５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６４−１．７２（１Ｈ，ｍ），２．０５−２．１３（１Ｈ，ｍ），２．５３−２．６３（１Ｈ，ｍ）， ３．４５−３．４８（２Ｈ，ｍ），３．５７−３．６１（１Ｈ，ｍ），３．７４−３．８０（１Ｈ，ｍ），３．８４−３．９５（２Ｈ，ｍ），４．２５（２Ｈ， ｄ），４．６８（２Ｈ，ｓ），６．２４−６．３１（１Ｈ，ｍ），６．６５（１Ｈ，ｄ），６．７４（１Ｈ，ｓ），６．９５（１Ｈ，ｂｒ ｓ），７．２５−７．２８（１Ｈ，ｍ），７．３２−７．３５（２Ｈ，ｍ），７．３９−７．４１（２Ｈ，ｍ） Production Example 233
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.16 g, 1.16 mmol) and triethylamine (0.12 g, 1.16 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 5- (3-phenyl- (E) -2-propenyl) oxymethylisoxazole-3-carboxylic acid (0.25 g, 0.96 mmol), 1-hydroxybenzotriazole (0.01 g, 0.10 mmol) and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.22 g, 1.16 mmol) were added, and the mixture was stirred overnight at room temperature, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. did. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (3-phenyl- (E) -2-propenyl) oxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (242)). ) 0.25 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.72 (1H, m), 2.05-2.13 (1H, m), 2.53-2.63 ( 1H, m), 3.45-3.48 (2H, m), 3.57-3.61 (1H, m), 3.74-3.80 (1H, m), 3.84-3. 95 (2H, m), 4.25 (2H, d), 4.68 (2H, s), 6.24-6.31 (1H, m), 6.65 (1H, d), 6.74. (1H, s), 6.95 (1H, br s), 7.25-7.28 (1H, m), 7.32-7.35 (2H, m), 7.39-7.41 ( 2H, m)

で示される７−（３−キノリル）−２，４−ジオキソへプタン酸エチル１．０５ｇを得た。
７−（３−キノリル）−２，４−ジオキソへプタン酸エチル（１．０５ｇ，３．３ｍｍｏｌ）をエタノール（１０ｍｌ）に溶解し、ヒドロキシルアミン塩酸塩（０．４７ｇ，６．７ｍｍｏｌ）を加え、窒素雰囲気下、８時間加熱還流した。反応混合物を室温まで冷却し、水１０ｍｌ及び水酸化カリウム０．９４ｇ，１６．８ｍｍｏｌ）を加え、室温で４時間攪拌した。１規定塩酸水溶液２０ｍｌを加えた後、減圧下で濃縮した。得られた固体にクロロホルム（アミレン添加品）（１０ｍＬ）及びトリエチルアミン（０．６８ｇ，６．７ｍｍｏｌ）を加え、無水硫酸ナトリウムで乾燥した。クロロホルム溶液にテトラヒドロフラン−３−イルメチルアミン塩酸塩（０．５１ｇ，３．７ｍｍｏｌ）及び１−ヒドロキシベンゾトリアゾール（０．０５ｇ，０．３７ｍｍｏｌ）を加え、さらに室温で１−エチル−３−（３−ジメチルアミノプロピル）カルボジイミド塩酸塩（０．７１ｇ，３．７ｍｍｏｌ）を加え、室温で一晩攪拌した後、減圧下で濃縮した。濃縮物に希塩酸を加え、酢酸エチルで２回抽出した。有機層を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した後、減圧下で濃縮した。残渣をシリカゲルカラムクロマトグラフィーに付し、下式

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［３−（３−キノリル）プロピル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２４３）と記す。）０．１６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６５−１．７２（１Ｈ，ｍ），２．０６−２．１４（１Ｈ，ｍ），２．１９（２Ｈ，ｄｄ），２．５４−２．６１（１Ｈ，ｍ），２．８８−２．９０（４Ｈ，ｍ），３．４６（２Ｈ，ｔ），３．５８−３．６０（１Ｈ，ｍ），３．７４−３．８０（１Ｈ，ｍ），３．８４−３．９５（２Ｈ，ｍ），６．５０（１Ｈ，ｓ），６．９３（１Ｈ，ｓ），７．５４−７．５６（１Ｈ，ｍ），７．６７−７．７１（１Ｈ，ｍ），７．７９（１Ｈ，ｄ），７．９５（１Ｈ，ｄ），８．１０（１Ｈ，ｄ），８．７９（１Ｈ，ｄ） Production Example 234
5- (3-quinolyl) pentan-2-one (3.60 g, 16.9 mmol) and diethyl oxalate (2.71 g, 18.6 mmol)) were dissolved in ethanol (37 ml) and dissolved at 0 ° C. under a nitrogen atmosphere. Cooled to. Sodium ethoxide (20% ethanol solution, 6.37 g, 18.6 mmol) was added dropwise to the mixture over 30 minutes, and the mixture was stirred overnight at room temperature and then concentrated under reduced pressure. A saturated aqueous ammonium chloride solution was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 1.05 g of ethyl 7- (3-quinolyl) -2,4-dioxoheptanoate represented by the formula:
Ethyl 7- (3-quinolyl) -2,4-dioxoheptanoate (1.05 g, 3.3 mmol) was dissolved in ethanol (10 ml) and hydroxylamine hydrochloride (0.47 g, 6.7 mmol) was added. The mixture was heated to reflux for 8 hours under a nitrogen atmosphere. The reaction mixture was cooled to room temperature, 10 ml of water and 0.94 g of potassium hydroxide (16.8 mmol) were added, and the mixture was stirred at room temperature for 4 hours. After adding 20 ml of 1N hydrochloric acid aqueous solution, the mixture was concentrated under reduced pressure. Chloroform (amylene-added product) (10 mL) and triethylamine (0.68 g, 6.7 mmol) were added to the obtained solid and dried over anhydrous sodium sulfate. Tetrahydrofuran-3-ylmethylamine hydrochloride (0.51 g, 3.7 mmol) and 1-hydroxybenzotriazole (0.05 g, 0.37 mmol) were added to the chloroform solution, and 1-ethyl-3- (3 -Dimethylaminopropyl) carbodiimide hydrochloride (0.71 g, 3.7 mmol) was added, and the mixture was stirred overnight at room temperature and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.16 g of N- (tetrahydrofuran-3-ylmethyl) -5- [3- (3-quinolyl) propyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (243)) represented by the formula: .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.65-1.72 (1H, m), 2.06-2.14 (1H, m), 2.19 (2H, dd) , 2.54-2.61 (1H, m), 2.88-2.90 (4H, m), 3.46 (2H, t), 3.58-3.60 (1H, m), 3 .74-3.80 (1H, m), 3.84-3.95 (2H, m), 6.50 (1H, s), 6.93 (1H, s), 7.54-7.56 (1H, m), 7.67-7.71 (1H, m), 7.79 (1H, d), 7.95 (1H, d), 8.10 (1H, d), 8.79 ( 1H, d)

Ｎ−（テトラヒドロフラン−３−イルメチル）−４−クロロ−３−（２−ナフチルメチル）オキシメチル−１−メチル−１H-ピラゾール−５−カルボキシアミド（以下、本発明化合物（２４４）と記す。）を得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６４−１．７２（１Ｈ，ｍ），２．０１−２．０８（１Ｈ，ｍ），２．５５−２．６１（１Ｈ，ｍ），３．３６−３．４９（２Ｈ，ｍ），３．５９（１Ｈ，ｄｄ），３．７７（１Ｈ，q），３．８３−３．９４（５Ｈ，ｄｄ），４．５９（２Ｈ，ｓ），４．６５（２Ｈ，ｓ），６．８９（１Ｈ，ｂｒ．ｓ），７．４１−７．４４（１Ｈ，ｍ），７．４７−７．５１（２Ｈ，ｍ），７．７７−７．８５（４Ｈ，ｍ） Production Example 235
4-chloro-3- (2-naphthylmethoxymethyl) -1-methyl-1H-pyrazole-5-carboxylic acid (0.72 g, 2.2 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.36 g, 2.6 mmol), triethylamine (0.27 g, 2.6 mmol) and 1-hydroxybenzotriazole (0.04 g, 0.26 mmol) were added to chloroform (amylene-added product) (5.4 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.50 g, 2.6 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -4-chloro-3- (2-naphthylmethyl) oxymethyl-1-methyl-1H-pyrazole-5-carboxamide (hereinafter referred to as the present compound (244)) Got.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.72 (1H, m), 2.01-2.08 (1H, m), 2.55-2.61 ( 1H, m), 3.36-3.49 (2H, m), 3.59 (1H, dd), 3.77 (1H, q), 3.83-3.94 (5H, dd), 4 .59 (2H, s), 4.65 (2H, s), 6.89 (1H, br. S), 7.41-7.44 (1H, m), 7.47-7.51 (2H , M), 7.77-7.85 (4H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−[３−（２−フルオロフェニル）プロピル]イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２４５）と記す。）１．９４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６３−１．７２（１Ｈ，ｍ），２．０１−２．１２（３Ｈ，ｍ），２．５２−２．６３（１Ｈ，ｍ），２．７１−２．７５（２Ｈ，ｍ），２．８０−２．８４（２Ｈ，ｍ），３．４４−３．４７（２Ｈ，ｍ），３．５７−３．６０（１Ｈ，ｍ），３．７３−３．７９（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），６．４７（１Ｈ，ｓ），６．９８（１Ｈ，ｂｒｓ），７．００−７．０９（２Ｈ，ｍ），７．１６−７．２２（２Ｈ，ｍ） Production Example 236
Tetrahydrofuran-3-ylmethylamine hydrochloride (1.32 g, 9.6 mmol) and triethylamine (1.34 mL, 9.6 mmol) were added to chloroform (amylene-added product) (20 mL), and the mixture was stirred at room temperature for 30 minutes. To the mixture was added 5- [3- (2-fluorophenyl) propyl] isoxazole-3-carboxylic acid (2.0 g, 8.0 mmol), 1-hydroxybenzotriazole (0.1 g, 0.8 mmol) and 1 at room temperature. -Ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.8 g, 9.6 mmol) was added, and the mixture was stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.94 g of N- (tetrahydrofuran-3-ylmethyl) -5- [3- (2-fluorophenyl) propyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (245)) represented by the formula: It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (1H, m), 2.01-2.12 (3H, m), 2.52-2.63 ( 1H, m), 2.71-2.75 (2H, m), 2.80-2.84 (2H, m), 3.44-3.47 (2H, m), 3.57-3. 60 (1H, m), 3.73-3.79 (1H, m), 3.84-3.94 (2H, m), 6.47 (1H, s), 6.98 (1H, brs) , 7.00-7.09 (2H, m), 7.16-7.22 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−[３−（３，４−ジクロロフェニル）プロピル]イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２４６）と記す。）０．３３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７３（１Ｈ，ｍ），２．０５−２．１４（３Ｈ，ｍ），２．５２−２．６２（１Ｈ，ｍ），２．６５（２Ｈ，ｔ），２．８１（２Ｈ，ｔ），３．４６（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８３−３．９５（２Ｈ，ｍ），６．４６（１Ｈ，ｓ），６．９２（１Ｈ，ｂｒ ｓ），７．０１（１Ｈ，ｄｄ），７．２６−７．２９（１Ｈ，ｍ），７．３６（１Ｈ，ｄ） Production Example 237
5- [3- (3,4-Dichlorophenyl) propyl] isoxazole-3-carboxylic acid (0.60 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.41 g, 3.0 mmol), triethylamine (0.30 g, 3.0 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.2 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.33 g of N- (tetrahydrofuran-3-ylmethyl) -5- [3- (3,4-dichlorophenyl) propyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (246)) represented by the formula: Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.73 (1H, m), 2.05-2.14 (3H, m), 2.52-2.62 ( 1H, m), 2.65 (2H, t), 2.81 (2H, t), 3.46 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H M), 3.83-3.95 (2H, m), 6.46 (1H, s), 6.92 (1H, br s), 7.01 (1H, dd), 7.26-7. .29 (1H, m), 7.36 (1H, d)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−[３−（６−メトキシ−２−ナフチル）プロピル]イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２４７）と記す。）０．４８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６１−１．７２（１Ｈ，ｍ），２．０１−２．１７（３Ｈ，ｍ），２．５０−２．６３（１Ｈ，ｍ），２．８２（４Ｈ，ｔ），３．４５（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８３−３．９５（２Ｈ，ｍ），３．９２（３Ｈ，ｓ），６．４７（１Ｈ，ｓ），６．９３（１Ｈ，ｂｒ ｓ），７．１０−７．１６（２Ｈ，ｍ），７．２６−７．３０（１Ｈ，ｍ），７．５４（１Ｈ，ｓ），７．６６−７．７１（２Ｈ，ｍ） Production Example 238
5- [3- (6-Methoxy-2-naphthyl) propyl] isoxazole-3-carboxylic acid (0.62 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.41 g, 3.0 mmol) , Triethylamine (0.30 g, 3.0 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.2 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- [3- (6-methoxy-2-naphthyl) propyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (247)) 0. 48 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.61-1.72 (1H, m), 2.01-2.17 (3H, m), 2.50-2.63 ( 1H, m), 2.82 (4H, t), 3.45 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H, m), 3.83-3 .95 (2H, m), 3.92 (3H, s), 6.47 (1H, s), 6.93 (1H, br s), 7.10-7.16 (2H, m), 7 .26-7.30 (1H, m), 7.54 (1H, s), 7.66-7.71 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−ブロモプロピル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２４８）と記す。）０．９１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６３−１．７２（１Ｈ， ｍ），２．０４−２．１３（１Ｈ，ｍ），２．２４−２．３０（２Ｈ，ｍ）， ２．５２−２．６３（１Ｈ，ｍ）， ２．９９−３．０３（２Ｈ，ｔ）， ３．４５−３．４８（４Ｈ，ｍ），３．５７−３．６１（１Ｈ，ｍ），３．７４−３．７９（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），６．５１（１Ｈ， ｓ），６．９３ （１Ｈ，ｂｒ ｓ） Production Example 239
Tetrahydrofuran-3-ylmethylamine hydrochloride (0.65 g, 4.70 mmol) and triethylamine (0.48 g, 4.70 mmol) were added to chloroform (amylene-added product) (20 mL). To the mixture was added 5- (3-bromopropyl) isoxazole-3-carboxylic acid (1.00 g, 4.27 mmol), 1-hydroxybenzotriazole (0.06 g, 0.43 mmol) and 1-ethyl-3- at room temperature. (3-Dimethylaminopropyl) carbodiimide hydrochloride (0.98 g, 5.13 mmol) was added, stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.91 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3-bromopropyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (248)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (1H, m), 2.04-2.13 (1H, m), 2.24-2.30 ( 2H, m), 2.52-2.63 (1H, m), 2.99-3.03 (2H, t), 3.45-3.48 (4H, m), 3.57-3. 61 (1H, m), 3.74-3.79 (1H, m), 3.84-3.94 (2H, m), 6.51 (1H, s), 6.93 (1H, br s )

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−フルオロベンジルオキシメチル）−４−エチニルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２４９）と記す。）０．２０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６４−１．７２（ｍ，１Ｈ），２．０４−２．１３（ｍ，１Ｈ），２．５６−２．６３（ｍ，１Ｈ），３．３９（ｓ，１Ｈ），３．４２−３．５３（ｍ，２Ｈ），３．５７−３．６１（ｍ，１Ｈ），３．７３−３．７９（ｍ，1Ｈ），３．８３−３．９４（ｍ，２Ｈ），４．６９（ｓ，２Ｈ），４．７６（ｓ，２Ｈ），６．９０（ｂｒｓ，１Ｈ），７．０４−７．０９（ｍ，１Ｈ），７．１３−７．１７（ｍ，１Ｈ），７．２８−７．３４（ｍ，１Ｈ），７．４１−７．４５（ｍ，１Ｈ） Production Example 240
N- (tetrahydrofuran-3-ylmethyl) -5- (2-fluorobenzyloxymethyl) -4-trimethylsilanylethynylisoxazole-3-carboxamide (0.29 g, 0.67 mmol) in methanol (10 mL) Was added with potassium carbonate (0.2 g, 1.44 mmol), stirred at room temperature for 1 hour, poured into 1 mol / L hydrochloric acid, and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained solid was washed with hexane, and this was obtained by suction filtration.

N- (tetrahydrofuran-3-ylmethyl) -5- (2-fluorobenzyloxymethyl) -4-ethynylisoxazole-3-carboxamide (hereinafter referred to as the present compound (249)) 0. 20 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.72 (m, 1H), 2.04-2.13 (m, 1H), 2.56-2.63 ( m, 1H), 3.39 (s, 1H), 3.42-3.53 (m, 2H), 3.57-3.61 (m, 1H), 3.73-3.79 (m, 1H), 3.83-3.94 (m, 2H), 4.69 (s, 2H), 4.76 (s, 2H), 6.90 (brs, 1H), 7.04-7.09 (M, 1H), 7.13-7.17 (m, 1H), 7.28-7.34 (m, 1H), 7.41-7.45 (m, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−ナフチルメトキシメチル）−４−エチニルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２５０）と記す。）０．２０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７２（ｍ，１Ｈ），２．０４−２．１２（ｍ，１Ｈ），２．５６−２．６３（ｍ，１Ｈ），３．３７（ｓ，１Ｈ），３．４１−３．５２（ｍ，２Ｈ），３．５７−３．６１（ｍ，１Ｈ），３．７３−３．７９（ｍ，1Ｈ），３．８３−３．９４（ｍ，２Ｈ），４．７５（ｓ，２Ｈ），４．７８（ｓ，２Ｈ），６．８７（ｂｒｓ，１Ｈ），７．４７−７．５２（ｍ，３Ｈ），７．８２−７．８６（ｍ，４Ｈ） Production Example 241
N- (tetrahydrofuran-3-ylmethyl) -5- (naphthalen-2-ylmethoxymethyl) -4-trimethylsilanylethynylisoxazole-3-carboxamide (0.35 g, 0.76 mmol) in methanol (10 mL) To the solution was added potassium carbonate (0.22 g, 1.59 mmol), stirred at room temperature for 1 hour, poured into 1 mol / L hydrochloric acid, and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained solid was washed with hexane, and this was obtained by suction filtration.

N- (tetrahydrofuran-3-ylmethyl) -5- (2-naphthylmethoxymethyl) -4-ethynylisoxazole-3-carboxamide (hereinafter referred to as the present compound (250)) 0.20 g Got.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (m, 1H), 2.04-2.12 (m, 1H), 2.56-2.63 ( m, 1H), 3.37 (s, 1H), 3.41-3.52 (m, 2H), 3.57-3.61 (m, 1H), 3.73-3.79 (m, 1H), 3.83-3.94 (m, 2H), 4.75 (s, 2H), 4.78 (s, 2H), 6.87 (brs, 1H), 7.47-7.52. (M, 3H), 7.82-7.86 (m, 4H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−[３−（３−フルオロフェニル）プロピル]イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２５１）と記す。）０．２２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７３（１Ｈ，ｍ），２．００−２．１３（３Ｈ，ｍ），２．５２−２．６２（１Ｈ，ｍ），２．６９（２Ｈ，ｔ），２．８１（２Ｈ，ｔ），３．４６（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８３−３．９５（２Ｈ，ｍ），６．４６（１Ｈ，ｓ），６．８５−６．９８（４Ｈ，ｍ），７．２２−７．２９（１Ｈ，ｍ） Production Example 242
5- [3- (3-fluorophenyl) propyl] isoxazole-3-carboxylic acid (0.25 g, 1.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.21 g, 1.5 mmol), triethylamine ( 0.15 g, 1.5 mmol) and 1-hydroxybenzotriazole (0.01 g, 0.1 mmol) were added to chloroform (amylene-added product) (2.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.23 g, 1.2 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.22 g of N- (tetrahydrofuran-3-ylmethyl) -5- [3- (3-fluorophenyl) propyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (251)) represented by the formula: It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.73 (1H, m), 2.00-2.13 (3H, m), 2.52-2.62 ( 1H, m), 2.69 (2H, t), 2.81 (2H, t), 3.46 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H , M), 3.83-3.95 (2H, m), 6.46 (1H, s), 6.85-6.98 (4H, m), 7.22-7.29 (1H, m )

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−（４−クロロフェニル）プロピル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２５２）と記す。）０．７８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７３（１Ｈ，ｍ），１．９９−２．１５（３Ｈ，ｍ），２．５３−２．６３（１Ｈ，ｍ），２．６６（２Ｈ，ｔ），２．８０（２Ｈ，ｔ），３．４６（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８３−３．９５（２Ｈ，ｍ），６．４６（１Ｈ，ｓ），６．９２（１Ｈ，ｂｒ ｓ），７．１１（２Ｈ，ｄ），７．２７（２Ｈ，ｄ） Production Example 243
5- [3- (4-Chlorophenyl) propyl] isoxazole-3-carboxylic acid (0.78 g, 2.9 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.60 g, 4.4 mmol), triethylamine (0 .44 g, 4.4 mmol) and 1-hydroxybenzotriazole (0.04 g, 0.3 mmol) were added to a mixed solvent of chloroform (amylene-added product) (4 mL) and tetrahydrofuran (4 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.67 g, 3.5 mmol) at room temperature, and the mixture was stirred at room temperature overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.78 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3- (4-chlorophenyl) propyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (252)) represented by the formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.73 (1H, m), 1.99-2.15 (3H, m), 2.53-2.63 ( 1H, m), 2.66 (2H, t), 2.80 (2H, t), 3.46 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H M), 3.83-3.95 (2H, m), 6.46 (1H, s), 6.92 (1H, br s), 7.11 (2H, d), 7.27 (2H) , D)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（２−ナフチルメチル）チオメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２５３）と記す。）４８０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．６３−１．７５（１Ｈ，ｍ），２．０４−２．１５（１Ｈ，ｍ），２．５２−２．６２（１Ｈ，ｍ），３．４２−３．５０（２Ｈ，ｍ），３．５７−３．６７（３Ｈ，ｍ），３．７３−３．９８（５Ｈ，ｍ），６．５９（１Ｈ，ｓ），６．８９（１Ｈ，ｂｒ ｓ），７．４５−７．５６（３Ｈ，ｍ），７．６９（１Ｈ，ｓ），７．７９−７．８８（３Ｈ，ｍ） Production Example 244
To a solution of 3-[(2-naphthylmethyl) thiomethyl] isoxazole-3-carboxylic acid chloride (<3.67 mmol) obtained in Reference Production Example 197 in ethyl acetate (30 mL), tetrahydrofuran-3-ylmethylamine hydrochloride ( 1.00 g, 7.26 mmol) and a 1 mol / L aqueous sodium hydroxide solution (16 mL) were added simultaneously at room temperature. After vigorously stirring at room temperature for 1 hour, a 1 mol / L aqueous sodium hydroxide solution was added. The separated organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

480 mg of N- (tetrahydrofuran-3-ylmethyl) -5-[(2-naphthylmethyl) thiomethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (253)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.75 (1H, m), 2.04-2.15 (1H, m), 2.52-2.62 ( 1H, m), 3.42-3.50 (2H, m), 3.57-3.67 (3H, m), 3.73-3.98 (5H, m), 6.59 (1H, s), 6.89 (1H, br s), 7.45-7.56 (3H, m), 7.69 (1H, s), 7.79-7.88 (3H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−ベンジルチオメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２５４）と記す。）３６０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６４−１．７３（１Ｈ，ｍ），２．０５−２．１５（１Ｈ，ｍ），２．５４−２．６３（１Ｈ，ｍ），３．４５−３．５０（２Ｈ，ｍ），３．６０（１Ｈ，ｄｄ），３．６４（２Ｈ，ｓ），３．７４（２Ｈ，ｓ），３．７６−３．８１（１Ｈ，ｍ），３．８４−３．９６（２Ｈ，ｍ），６．５７（１Ｈ，ｓ），６．９５（１Ｈ，ｓ）７．２７−７．３７（５Ｈ，ｍ） Production Example 245
5-Benzylthiomethylisoxazole-3-carboxylic acid (510 mg, 2.05 mmol) was added to chloroform (amylene-added product) (5 mL). To this, triethylamine (0.86 mL, 6.14 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (451 mg, 2.36 mmol), 1-hydroxybenzotriazole (28 mg, 0.21 mmol) And tetrahydrofuran-3-ylmethylamine hydrochloride (366 mg, 2.66 mmol) was added, and the mixture was stirred at room temperature for 11 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 1 mol / L hydrochloric acid, aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

360 mg of N- (tetrahydrofuran-3-ylmethyl) -5-benzylthiomethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (254)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.73 (1H, m), 2.05-2.15 (1H, m), 2.54-2.63 ( 1H, m), 3.45-3.50 (2H, m), 3.60 (1H, dd), 3.64 (2H, s), 3.74 (2H, s), 3.76-3 .81 (1H, m), 3.84-3.96 (2H, m), 6.57 (1H, s), 6.95 (1H, s) 7.27-7.37 (5H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−ナフチルメトキシメチル）−４−フルオロイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２５５）と記す。）０．０８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７１（ｍ，１Ｈ），２．０３−２．１２（ｍ，１Ｈ），２．５４−２．６１（ｍ，１Ｈ），３．４２−３．５０（ｍ，２Ｈ），３．５７−３．６１（ｍ，１Ｈ），３．７３−３．７９（ｍ，1Ｈ），３．８２−３．９４（ｍ，２Ｈ），４．６８（ｓ，２Ｈ），４．７５（ｓ，２Ｈ），６．８６（ｂｒｓ，１Ｈ），７．４５−７．５１（ｍ，３Ｈ），７．７９−７．８６（ｍ，４Ｈ） Production Example 246
To a solution of N- (tetrahydrofuran-3-ylmethyl) -5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (0.5 g, 1.36 mmol) in tetrahydrofuran (6 mL) at −65 ° C. or lower under a nitrogen atmosphere. Then, 1.6 mol / L-n-butyllithium hexane solution (1.9 mL, 3.00 mmol) was added dropwise. After stirring at −60 ° C. or lower for 1 hour, a solution of N-fluorobenzenesulfonimide (1.29 g, 4.09 mmol) in tetrahydrofuran (4 mL) was added and stirred overnight while gradually returning to room temperature. Under ice-cooling, the reaction mixture was poured into 1 mol / L hydrochloric acid, and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (2-naphthylmethoxymethyl) -4-fluoroisoxazole-3-carboxamide (hereinafter referred to as the present compound (255)) 0.08 g Got.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.71 (m, 1H), 2.03-2.12 (m, 1H), 2.54-2.61 ( m, 1H), 3.42-3.50 (m, 2H), 3.57-3.61 (m, 1H), 3.73-3.79 (m, 1H), 3.82-3. 94 (m, 2H), 4.68 (s, 2H), 4.75 (s, 2H), 6.86 (brs, 1H), 7.45-7.51 (m, 3H), 7.79 -7.86 (m, 4H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−ナフチルメトキシメチル）−４−ブロモイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２５６）と記す。）０．３６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６５−１．７１（ｍ，１Ｈ），２．０４−２．１３（ｍ，１Ｈ），２．５５−２．６１（ｍ，１Ｈ），３．４０−３．５１（ｍ，２Ｈ），３．５７−３．６１（ｍ，１Ｈ），３．７３−３．７９（ｍ，1Ｈ），３．８３−３．９４（ｍ，２Ｈ），４．７０（ｓ，２Ｈ），４．７６（ｓ，２Ｈ），６．８７（ｂｒｓ，１Ｈ），７．４７−７．５１（ｍ，３Ｈ），７．８１−７．８６（ｍ，４Ｈ） Production Example 247
To a solution of N- (tetrahydrofuran-3-ylmethyl) -5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (0.5 g, 1.36 mmol) in tetrahydrofuran (6 mL) at −65 ° C. or lower under a nitrogen atmosphere. Then, 1.6 mol / L-n-butyllithium hexane solution (1.9 mL, 3.00 mmol) was added dropwise. After stirring at −60 ° C. or lower for 1 hour, a solution of bromotrichloromethane (0.40 mL, 4.09 mmol) in tetrahydrofuran (1 mL) was added, and the mixture was stirred at −65 ° C. to −60 ° C. for 3 hours. Under ice-cooling, the reaction mixture was poured into 1 mol / L hydrochloric acid, and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (2-naphthylmethoxymethyl) -4-bromoisoxazole-3-carboxamide (hereinafter referred to as the present compound (256)) 0.36 g Got.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.65-1.71 (m, 1H), 2.04-2.13 (m, 1H), 2.55-2.61 ( m, 1H), 3.40-3.51 (m, 2H), 3.57-3.61 (m, 1H), 3.73-3.79 (m, 1H), 3.83-3. 94 (m, 2H), 4.70 (s, 2H), 4.76 (s, 2H), 6.87 (brs, 1H), 7.47-7.51 (m, 3H), 7.81 -7.86 (m, 4H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−フルオロ−２−ナフチルメトキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２５７）と記す。）０．０６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７３（１Ｈ，ｍ），２．０５−２．１３（１Ｈ，ｍ），２．５２−２．６４（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８３−３．９５（２Ｈ，ｍ），４．７６（２Ｈ，ｓ），４．８３（２Ｈ，ｓ），６．７８（１Ｈ，ｓ），６．９５（１Ｈ，ｂｒ ｓ），７．４３−７．５５（３Ｈ，ｍ），７．７６−７．９０（３Ｈ，ｍ） Production Example 248
5- (3-Fluoro-2-naphthylmethoxymethyl) isoxazole-3-carboxylic acid (0.48 g, 1.6 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.83 g, 6.0 mmol), triethylamine ( 0.61 g, 6.0 mmol) and 1-hydroxybenzotriazole (0.06 g, 0.4 mmol) were added to a mixed solvent of chloroform (amylene-added product) (4 mL) and tetrahydrofuran (4 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.92 g, 4.8 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.06 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3-fluoro-2-naphthylmethoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (257)) represented by the formula: It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.73 (1H, m), 2.05-2.13 (1H, m), 2.52-2.64 ( 1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H, m), 3.83-3.95 (2H, m), 4 .76 (2H, s), 4.83 (2H, s), 6.78 (1H, s), 6.95 (1H, br s), 7.43-7.55 (3H, m), 7 .76-7.90 (3H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（１−フルオロ−２−ナフチルメトキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２５８）と記す。）０．０７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７３（１Ｈ，ｍ），２．０３−２．１４（１Ｈ，ｍ），２．５２−２．６３（１Ｈ，ｍ），３．４６（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８３−３．９５（２Ｈ，ｍ），４．６９（２Ｈ，ｓ），４．８６（２Ｈ，ｓ），６．７６（１Ｈ，ｓ），６．９３（１Ｈ，ｂｒ ｓ），７．４６−７．５２（１Ｈ，ｍ），７．５２−７．５９（２Ｈ，ｍ），７．６６（１Ｈ，ｄ），７．８１−７．８８（１Ｈ，ｍ），８．０７−８．１４（１Ｈ，ｍ） Production Example 249
5- (1-fluoro-2-naphthylmethoxymethyl) isoxazole-3-carboxylic acid (0.59 g, 1.5 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.83 g, 6.0 mmol), triethylamine ( 0.61 g, 6.0 mmol) and 1-hydroxybenzotriazole (0.06 g, 0.4 mmol) were added to a mixed solvent of chloroform (amylene-added product) (4 mL) and tetrahydrofuran (4 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.92 g, 4.8 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.07 g of N- (tetrahydrofuran-3-ylmethyl) -5- (1-fluoro-2-naphthylmethoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (258)) represented by the formula: It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.73 (1H, m), 2.03-2.14 (1H, m), 2.52-2.63 ( 1H, m), 3.46 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H, m), 3.83-3.95 (2H, m), 4 .69 (2H, s), 4.86 (2H, s), 6.76 (1H, s), 6.93 (1H, br s), 7.46-7.52 (1H, m), 7 .52-7.59 (2H, m), 7.66 (1H, d), 7.81-7.88 (1H, m), 8.07-8.14 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２，５−ジフルオロベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２５９）と記す。）０．１７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７３（１Ｈ，ｍ），２．０５−２．１４（１Ｈ，ｍ），２．５３−２．６４（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８３−３．９５（２Ｈ，ｍ），４．６５（２Ｈ，ｓ），４．７１（２Ｈ，ｓ），６．７６（１Ｈ，ｓ），６．９５（１Ｈ，ｂｒ ｓ），６．９５−７．０６（２Ｈ，ｍ），７．１２−７．１７（１Ｈ，ｍ） Production Example 250
5- (2,5-difluorobenzyloxymethyl) isoxazole-3-carboxylic acid (0.54 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.41 g, 3.0 mmol), triethylamine (0 .30 g, 3.0 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.2 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.17 g of N- (tetrahydrofuran-3-ylmethyl) -5- (2,5-difluorobenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (259)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.73 (1H, m), 2.05-2.14 (1H, m), 2.53-2.64 ( 1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H, m), 3.83-3.95 (2H, m), 4 .65 (2H, s), 4.71 (2H, s), 6.76 (1H, s), 6.95 (1H, br s), 6.95-7.06 (2H, m), 7 .12-7.17 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（４−クロロ−２−フルオロベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２６０）と記す。）０．８５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７２（１Ｈ，ｍ），２．０５−２．１４（１Ｈ，ｍ），２．５２−２．６３（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８３−３．９５（２Ｈ，ｍ），４．６３（２Ｈ，ｓ），４．６８（２Ｈ，ｓ），６．７４（１Ｈ，ｓ），６．９４（１Ｈ，ｂｒ ｓ），７．１０（１Ｈ，ｄｄ），７．１６（１Ｈ，ｄｄ），７．３６（１Ｈ，ｔ） Production Example 251
5- (4-chloro-2-fluorobenzyloxymethyl) isoxazole-3-carboxylic acid (1.30 g, 4.6 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.94 g, 6.8 mmol), triethylamine (0.95 mL, 6.8 mmol) and 1-hydroxybenzotriazole (0.06 g, 0.5 mmol) were added to chloroform (amylene-added product) (10 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.05 g, 5.5 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.85 g of N- (tetrahydrofuran-3-ylmethyl) -5- (4-chloro-2-fluorobenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (260)) Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.72 (1H, m), 2.05-2.14 (1H, m), 2.52-2.63 ( 1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H, m), 3.83-3.95 (2H, m), 4 .63 (2H, s), 4.68 (2H, s), 6.74 (1H, s), 6.94 (1H, br s), 7.10 (1H, dd), 7.16 (1H , Dd), 7.36 (1H, t)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−クロロ−４−フルオロベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２６１）と記す。）０．２９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７３（１Ｈ，ｍ），２．０４−２．１５（１Ｈ，ｍ），２．５３−２．６３（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８４−３．９５（２Ｈ，ｍ），４．５４（２Ｈ，ｓ），４．６６（２Ｈ，ｓ），６．７３（１Ｈ，ｓ），６．９３（１Ｈ，ｂｒ ｓ），７．１３（１Ｈ，ｔ），７．１８−７．２４（１Ｈ，ｍ），７．４０（１Ｈ，ｄｄ） Production Example 252
5- (3-chloro-4-fluorobenzyloxymethyl) isoxazole-3-carboxylic acid (2.55 g, 8.9 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (1.84 g, 13.4 mmol), triethylamine (1.87 mL, 13.4 mmol) and 1-hydroxybenzotriazole (0.12 g, 0.9 mmol) were added to chloroform (amylene-added product) (20 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (2.05 g, 10.7 mmol) at room temperature, stirred overnight, and concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.29 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3-chloro-4-fluorobenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (261)) represented by the formula: Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.73 (1H, m), 2.04-2.15 (1H, m), 2.53-2.63 ( 1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H, m), 3.84-3.95 (2H, m), 4 .54 (2H, s), 4.66 (2H, s), 6.73 (1H, s), 6.93 (1H, br s), 7.13 (1H, t), 7.18-7 .24 (1H, m), 7.40 (1H, dd)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３，５−ジブロモベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２６２）と記す。）０．４６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７３（１Ｈ，ｍ），２．０４−２．１４（１Ｈ，ｍ），２．５３−２．６４（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７２−３．８１（１Ｈ，ｍ），３．８３−３．９６（２Ｈ，ｍ），４．５４（２Ｈ，ｓ），４．６７（２Ｈ，ｓ），６．７４（１Ｈ，ｓ），６．９５（１Ｈ，ｂｒ ｓ），７．４２（２Ｈ，ｓ），７．６１（１Ｈ，ｓ） Production Example 253
5- (3,5-dibromobenzyloxymethyl) isoxazole-3-carboxylic acid (3.25 g, 8.3 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (1.37 g, 10.0 mmol), triethylamine (1 .74 mL, 12.5 mmol) and 1-hydroxybenzotriazole (0.11 g, 0.8 mmol) were added to chloroform (amylene-added product) (20 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.91 g, 10.0 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.46 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3,5-dibromobenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (262)) represented by the formula: .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.73 (1H, m), 2.04-2.14 (1H, m), 2.53-2.64 ( 1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.72-3.81 (1H, m), 3.83-3.96 (2H, m), 4 .54 (2H, s), 4.67 (2H, s), 6.74 (1H, s), 6.95 (1H, br s), 7.42 (2H, s), 7.61 (1H) , S)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３，４−ジフルオロベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２６３）と記す。）０．３６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７５（１Ｈ，ｍ），２．０５−２．１４（１Ｈ，ｍ），２．５２−２．６４（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８３−３．９５（２Ｈ，ｍ），４．５５（２Ｈ，ｓ），４．６６（２Ｈ，ｓ），６．７４（１Ｈ，ｓ），６．９４（１Ｈ，ｂｒ ｓ），７．０３−７．０８（１Ｈ，ｍ），７．１１−７．２２（２Ｈ，ｍ） Production Example 254
5- (3,4-difluorobenzyloxymethyl) isoxazole-3-carboxylic acid (0.54 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.41 g, 3.0 mmol), triethylamine (0 .30 g, 3.0 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.2 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.36 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3,4-difluorobenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (263)) represented by the formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.75 (1H, m), 2.05-2.14 (1H, m), 2.52-2.64 ( 1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H, m), 3.83-3.95 (2H, m), 4 .55 (2H, s), 4.66 (2H, s), 6.74 (1H, s), 6.94 (1H, br s), 7.03-7.08 (1H, m), 7 .11-7.22 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−フルオロベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２６４）と記す。）０．４４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７３（１Ｈ，ｍ），２．０５−２．１４（１Ｈ，ｍ），２．５２−２．６３（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８３−３．９５（２Ｈ，ｍ），４．６８（２Ｈ，ｓ），４．６９（２Ｈ，ｓ），６．７４（１Ｈ，ｓ），６．９５（１Ｈ，ｂｒ ｓ），７．０３−７．１０（１Ｈ，ｍ），７．１３−７．１９（１Ｈ，ｍ），７．２８−７．３５（１Ｈ，ｍ），７．３８−７．４５（１Ｈ，ｍ） Production Example 255
5- (2-fluorobenzyloxymethyl) isoxazole-3-carboxylic acid (0.75 g, 3.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.62 g, 4.5 mmol), triethylamine (0.46 g) , 4.5 mmol) and 1-hydroxybenzotriazole (0.04 g, 0.3 mmol) were added to chloroform (amylene-added product) (7.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.69 g, 3.6 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.44 g of N- (tetrahydrofuran-3-ylmethyl) -5- (2-fluorobenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (264)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.73 (1H, m), 2.05-2.14 (1H, m), 2.52-2.63 ( 1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H, m), 3.83-3.95 (2H, m), 4 .68 (2H, s), 4.69 (2H, s), 6.74 (1H, s), 6.95 (1H, br s), 7.03-7.10 (1H, m), 7 .13-7.19 (1H, m), 7.28-7.35 (1H, m), 7.38-7.45 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−ブロモベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２６５）と記す。）０．２３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７３（１Ｈ，ｍ），２．０５−２．１４（１Ｈ，ｍ），２．５３−２．６３（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８３−３．９５（２Ｈ，ｍ），４．６９（２Ｈ，ｓ），４．７４（２Ｈ，ｓ），６．７７（１Ｈ，ｓ），６．９５（１Ｈ，ｂｒ ｓ），７．１８（１Ｈ，ｄｔ），７．３４（１Ｈ，ｄｔ），７．４７（１Ｈ，ｄｄ），７．５６（１Ｈ，ｄｄ） Production Example 256
5- (2-bromobenzyloxymethyl) isoxazole-3-carboxylic acid (0.94 g, 3.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.62 g, 4.5 mmol), triethylamine (0.46 g) , 4.5 mmol) and 1-hydroxybenzotriazole (0.04 g, 0.3 mmol) were added to chloroform (amylene-added product) (7.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.69 g, 3.6 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.23 g of N- (tetrahydrofuran-3-ylmethyl) -5- (2-bromobenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (265)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.73 (1H, m), 2.05-2.14 (1H, m), 2.53-2.63 ( 1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H, m), 3.83-3.95 (2H, m), 4 .69 (2H, s), 4.74 (2H, s), 6.77 (1H, s), 6.95 (1H, br s), 7.18 (1H, dt), 7.34 (1H , Dt), 7.47 (1H, dd), 7.56 (1H, dd)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３，５−ジフルオロベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２６６）と記す。）０．２６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７４（１Ｈ，ｍ），２．０６−２．１４（１Ｈ，ｍ），２．５３−２．６４（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８３−３．９５（２Ｈ，ｍ），４．５８（２Ｈ，ｓ），４．６８（２Ｈ，ｓ），６．７２−６．７９（１Ｈ，ｍ），６．７５（１Ｈ，ｓ），６．８４−６．９１（２Ｈ，ｍ），６．９４（１Ｈ，ｂｒ ｓ） Production Example 257
5- (3,5-difluorobenzyloxymethyl) isoxazole-3-carboxylic acid (1.35 g, 5.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (1.03 g, 7.5 mmol), triethylamine (0 .76 g, 7.5 mmol) and 1-hydroxybenzotriazole (0.07 g, 0.5 mmol) were added to chloroform (amylene-added product) (12.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.15 g, 6.0 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.26 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3,5-difluorobenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (266)) represented by the formula: .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.74 (1H, m), 2.06-2.14 (1H, m), 2.53-2.64 ( 1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H, m), 3.83-3.95 (2H, m), 4 .58 (2H, s), 4.68 (2H, s), 6.72-6.79 (1H, m), 6.75 (1H, s), 6.84-6.91 (2H, m ), 6.94 (1H, br s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３，４，５−トリフルオロベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２６７）と記す。）０．２５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７３（１Ｈ，ｍ），２．０４−２．１４（１Ｈ，ｍ），２．５３−２．６４（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８１（１Ｈ，ｍ），３．８３−３．９５（２Ｈ，ｍ），４．５３（２Ｈ，ｓ），４．６８（２Ｈ，ｓ），６．７５（１Ｈ，ｓ），６．９３−７．０２（２Ｈ，ｍ），６．９６（１Ｈ，ｂｒ ｓ） Production Example 258
5- (3,4,5-trifluorobenzyloxymethyl) isoxazole-3-carboxylic acid (0.86 g, 3.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.62 g, 4.5 mmol), Triethylamine (0.46 g, 4.5 mmol) and 1-hydroxybenzotriazole (0.04 g, 0.3 mmol) were added to chloroform (amylene-added product) (7.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.69 g, 3.6 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (3,4,5-trifluorobenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (267)) 0.25 g Got.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.73 (1H, m), 2.04-2.14 (1H, m), 2.53-2.64 ( 1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.73-3.81 (1H, m), 3.83-3.95 (2H, m), 4 .53 (2H, s), 4.68 (2H, s), 6.75 (1H, s), 6.93-7.02 (2H, m), 6.96 (1H, br s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−クロロ−５−フルオロベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２６８）と記す。）０．４０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７２（１Ｈ，ｍ），２．０７−２．１３（１Ｈ，ｍ），２．５３−２．６３（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），４．５７（２Ｈ，ｓ），４．６８（２Ｈ，ｓ），６．７４（１Ｈ，ｓ），６．９３（１Ｈ，ｂｒ ｓ），６．９７（１Ｈ，ｄ），７．０４（１Ｈ，ｄｔ），７．１３（１Ｈ，ｓ） Production Example 259
5- (3-chloro-5-fluorobenzyloxymethyl) isoxazole-3-carboxylic acid (1.04 g, 3.6 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.75 g, 5.5 mmol), triethylamine (0.76 mL, 5.5 mmol) and 1-hydroxybenzotriazole (0.05 g, 0.4 mmol) were added to chloroform (amylene-added product) (10 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.84 g, 4.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.40 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3-chloro-5-fluorobenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (268)) represented by the formula: Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (1H, m), 2.07-2.13 (1H, m), 2.53-2.63 ( 1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H, m), 3.84-3.94 (2H, m), 4 .57 (2H, s), 4.68 (2H, s), 6.74 (1H, s), 6.93 (1H, br s), 6.97 (1H, d), 7.04 (1H , Dt), 7.13 (1H, s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２，３，５，６−テトラフルオロベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２６９）と記す。）０．０６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７３（１Ｈ，ｍ），２．０５−２．１４（１Ｈ，ｍ），２．５２−２．６３（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８３−３．９５（２Ｈ，ｍ），４．７０（２Ｈ，ｓ），４．７２（２Ｈ，ｄｔ），６．７６（１Ｈ，ｓ），６．９４（１Ｈ，ｂｒ ｓ），７．０４−７．１６（１Ｈ，ｍ） Production Example 260
5- (2,3,5,6-tetrafluorobenzyloxymethyl) isoxazole-3-carboxylic acid (0.18 g, 0.6 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.21 g, 1.5 mmol) ), Triethylamine (0.15 g, 1.5 mmol) and 1-hydroxybenzotriazole (0.01 g, 0.1 mmol) were added to chloroform (amylene-added product) (2.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.23 g, 1.2 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (2,3,5,6-tetrafluorobenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (269)) 0 0.06 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.73 (1H, m), 2.05-2.14 (1H, m), 2.52-2.63 ( 1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H, m), 3.83-3.95 (2H, m), 4 .70 (2H, s), 4.72 (2H, dt), 6.76 (1H, s), 6.94 (1H, br s), 7.04-7.16 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２，３，４−トリフルオロベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２７０）と記す。）０．２４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７３（１Ｈ，ｍ），２．０５−２．１４（１Ｈ，ｍ），２．５２−２．６４（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８３−３．９５（２Ｈ，ｍ），４．６４（２Ｈ，ｓ），４．６９（２Ｈ，ｓ），６．７５（１Ｈ，ｓ），６．９５（１Ｈ，ｂｒ ｓ），６．９５−７．０１（１Ｈ，ｍ），７．１０−７．１８（１Ｈ，ｍ） Production Example 261
5- (2,3,4-trifluorobenzyloxymethyl) isoxazole-3-carboxylic acid (0.57 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.41 g, 3.0 mmol), Triethylamine (0.30 g, 3.0 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.2 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight at room temperature and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (2,3,4-trifluorobenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (270)) 0.24 g Got.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.73 (1H, m), 2.05-2.14 (1H, m), 2.52-2.64 ( 1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H, m), 3.83-3.95 (2H, m), 4 .64 (2H, s), 4.69 (2H, s), 6.75 (1H, s), 6.95 (1H, br s), 6.95-7.01 (1H, m), 7 .10-7.18 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３，５−ジメチルベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２７１）と記す。）０．３１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７２（１Ｈ，ｍ），２．０５−２．１２（１Ｈ，ｍ），２．３２（６Ｈ，ｓ），２．５５−２．６１（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．７９（１Ｈ，ｍ），３．８４−３．９４（２Ｈ，ｍ），４．５３（２Ｈ，ｓ），４．６３（２Ｈ，ｓ），６．７２（１Ｈ，ｓ），６．９３（１Ｈ，ｂｒ ｓ），６．９６（３Ｈ，ｓ） Production Example 262
5- (3,5-dimethylbenzyloxymethyl) isoxazole-3-carboxylic acid (1.06 g, 4.1 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.84 g, 6.1 mmol), triethylamine (0 .85 mL, 6.1 mmol) and 1-hydroxybenzotriazole (0.05 g, 0.4 mmol) were added to chloroform (amylene-added product) (10 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.93 g, 4.9 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.31 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3,5-dimethylbenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (271)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (1H, m), 2.05-2.12 (1H, m), 2.32 (6H, s) 2.55-2.61 (1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.73-3.79 (1H, m), 3.84-3 .94 (2H, m), 4.53 (2H, s), 4.63 (2H, s), 6.72 (1H, s), 6.93 (1H, br s), 6.96 (3H) , S)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（４−ブロモ−３−フルオロベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２７２）と記す。）０．５９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７５（１Ｈ，ｍ），２．０４−２．１４（１Ｈ，ｍ），２．５２−２．６４（１Ｈ，ｍ），３．４８（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８２−３．９４（２Ｈ，ｍ），４．５６（２Ｈ，ｓ），４．６６（２Ｈ，ｓ），６．７３（１Ｈ，ｓ），６．９２（１Ｈ，ｂｒ ｓ），７．０１（１Ｈ，ｄ），７．１３（１Ｈ，ｄ），７．５３（１Ｈ，ｔ） Production Example 263
5- (4-Bromo-3-fluorobenzyloxymethyl) isoxazole-3-carboxylic acid (1.42 g, 4.3 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.89 g, 6.5 mmol), triethylamine (0.90 mL, 6.5 mmol) and 1-hydroxybenzotriazole (0.06 g, 0.4 mmol) were added to chloroform (amylene-added product) (10 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.99 g, 5.2 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.59 g of N- (tetrahydrofuran-3-ylmethyl) -5- (4-bromo-3-fluorobenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (272)) represented by the formula: Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.75 (1H, m), 2.04-2.14 (1H, m), 2.52-2.64 ( 1H, m), 3.48 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H, m), 3.82-3.94 (2H, m), 4 .56 (2H, s), 4.66 (2H, s), 6.73 (1H, s), 6.92 (1H, br s), 7.01 (1H, d), 7.13 (1H , D), 7.53 (1H, t)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（４−メチル−２，３，５，６−テトラフルオロベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２７３）と記す。）０．０６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７４（１Ｈ，ｍ），２．０４−２．１５（１Ｈ，ｍ），２．２９（３Ｈ，ｓ），２．５３−２．６５（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．６１（１Ｈ，ｄｄ），３．７４−３．８２（１Ｈ，ｍ），３．８４−３．９７（２Ｈ，ｍ），４．６８（２Ｈ，ｓ），４．７１（２Ｈ，ｓ），６．７６（１Ｈ，ｓ），７．０１（１Ｈ，ｂｒ ｓ） Production Example 264
5- (4-Methyl-2,3,5,6-tetrafluorobenzyloxymethyl) isoxazole-3-carboxylic acid (0.29 g, 0.9 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.21 g) , 1.5 mmol), triethylamine (0.15 g, 1.5 mmol) and 1-hydroxybenzotriazole (0.01 g, 0.1 mmol) were added to chloroform (amylene-added product) (2.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.23 g, 1.2 mmol) at room temperature, and the mixture was stirred overnight at room temperature and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (4-methyl-2,3,5,6-tetrafluorobenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (273)) 0.06 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.74 (1H, m), 2.04-2.15 (1H, m), 2.29 (3H, s) 2.53-2.65 (1H, m), 3.47 (2H, t), 3.61 (1H, dd), 3.74-3.82 (1H, m), 3.84-3 .97 (2H, m), 4.68 (2H, s), 4.71 (2H, s), 6.76 (1H, s), 7.01 (1H, br s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２，３−ジフルオロベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２７４）と記す。）０．２５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７３（１Ｈ，ｍ），２．０５−２．１５（１Ｈ，ｍ），２．５３−２．６４（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８１（１Ｈ，ｍ），３．８３−３．９６（２Ｈ，ｍ），４．６９（２Ｈ，ｓ），４．７０（２Ｈ，ｓ），６．７５（１Ｈ，ｓ），６．９４（１Ｈ，ｂｒ ｓ），７．０７−７．２２（３Ｈ，ｍ） Production Example 265
5- (2,3-difluorobenzyloxymethyl) isoxazole-3-carboxylic acid (0.54 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.41 g, 3.0 mmol), triethylamine (0 .30 g, 3.0 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.2 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.25 g of N- (tetrahydrofuran-3-ylmethyl) -5- (2,3-difluorobenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (274)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.73 (1H, m), 2.05-2.15 (1H, m), 2.53-2.64 ( 1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.73-3.81 (1H, m), 3.83-3.96 (2H, m), 4 .69 (2H, s), 4.70 (2H, s), 6.75 (1H, s), 6.94 (1H, br s), 7.07-7.22 (3H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２，６−ジフルオロベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２７５）と記す。）０．３４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７３（１Ｈ，ｍ），２．０４−２．１４（１Ｈ，ｍ），２．５２−２．６３（１Ｈ，ｍ），３．４６（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８３−３．９５（２Ｈ，ｍ），４．６８（２Ｈ，ｓ），４．７０（２Ｈ，ｓ），６．７４（１Ｈ，ｓ），６．９３（１Ｈ，ｂｒ ｓ），６．９３（２Ｈ，ｔ），７．２８−７．３７（１Ｈ，ｍ） Production Example 266
5- (2,6-difluorobenzyloxymethyl) isoxazole-3-carboxylic acid (0.54 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.41 g, 3.0 mmol), triethylamine (0 .30 g, 3.0 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.2 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.34 g of N- (tetrahydrofuran-3-ylmethyl) -5- (2,6-difluorobenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (275)) represented by the formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.73 (1H, m), 2.04-2.14 (1H, m), 2.52-2.63 ( 1H, m), 3.46 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H, m), 3.83-3.95 (2H, m), 4 .68 (2H, s), 4.70 (2H, s), 6.74 (1H, s), 6.93 (1H, br s), 6.93 (2H, t), 7.28-7 .37 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（４−クロロ−３−フルオロベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２７６）と記す。）０．１８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７４（１Ｈ，ｍ），２．０５−２．１４（１Ｈ，ｍ），２．５２−２．６４（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８３−３．９５（２Ｈ，ｍ），４．５７（２Ｈ，ｓ），４．６７（２Ｈ，ｓ），６．７４（１Ｈ，ｓ），６．９４（１Ｈ，ｂｒ ｓ），７．０４−７．０８（１Ｈ，ｍ），７．１６（１Ｈ，ｄｄ），７．３８（１Ｈ，ｔ） Production Example 267
5- (4-chloro-3-fluorobenzyloxymethyl) isoxazole-3-carboxylic acid (0.54 g, 2.0 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.41 g, 3.0 mmol), triethylamine (0.30 g, 3.0 mmol) and 1-hydroxybenzotriazole (0.03 g, 0.2 mmol) were added to chloroform (amylene-added product) (5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.18 g of N- (tetrahydrofuran-3-ylmethyl) -5- (4-chloro-3-fluorobenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (276)) represented by the formula: Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.74 (1H, m), 2.05-2.14 (1H, m), 2.52-2.64 ( 1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H, m), 3.83-3.95 (2H, m), 4 .57 (2H, s), 4.67 (2H, s), 6.74 (1H, s), 6.94 (1H, br s), 7.04-7.08 (1H, m), 7 .16 (1H, dd), 7.38 (1H, t)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−フルオロ−４−メトキシベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２７７）と記す。）０．３８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７３（１Ｈ，ｍ），２．０４−２．１４（１Ｈ，ｍ），２．５２−２．６３（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８３−３．９５（２Ｈ，ｍ），３．８９（３Ｈ，ｓ），４．５２（２Ｈ，ｓ），４．６３（２Ｈ，ｓ），６．７２（１Ｈ，ｓ），６．９３（１Ｈ，ｂｒ ｓ），６．９４（１Ｈ，ｔ），７．０４（１Ｈ，ｄ），７．０９（１Ｈ，ｄｄ） Production Example 268
5- (3-Fluoro-4-methoxybenzyloxymethyl) isoxazole-3-carboxylic acid (1.10 g, 3.9 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.81 g, 5.9 mmol), triethylamine (0.82 mL, 5.9 mmol) and 1-hydroxybenzotriazole (0.05 g, 0.4 mmol) were added to chloroform (amylene-added product) (10 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.90 g, 4.7 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.38 g of N- (tetrahydrofuran-3-ylmethyl) -5- (3-fluoro-4-methoxybenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (277)) represented by the formula: Obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.73 (1H, m), 2.04-2.14 (1H, m), 2.52-2.63 ( 1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H, m), 3.83-3.95 (2H, m), 3 .89 (3H, s), 4.52 (2H, s), 4.63 (2H, s), 6.72 (1H, s), 6.93 (1H, br s), 6.94 (1H) , T), 7.04 (1H, d), 7.09 (1H, dd)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２，４−ジフルオロベンジルオキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２７８）と記す。）０．７８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７２（１Ｈ，ｍ），２．０４−２．１４（１Ｈ，ｍ），２．５２−２．６３（１Ｈ，ｍ），３．４７（２Ｈ，ｔ），３．５９（１Ｈ，ｄｄ），３．７３−３．８０（１Ｈ，ｍ），３．８３−３．９５（２Ｈ，ｍ），４．６２（２Ｈ，ｓ），４．６８（２Ｈ，ｓ），６．７４（１Ｈ，ｓ），６．８１（１Ｈ，ｄｔ），６．８９（１Ｈ，ｄｔ），６．９３（１Ｈ，ｂｒ ｓ），７．３５−７．４２（１Ｈ，ｍ） Production Example 269
5- (2,4-difluorobenzyloxymethyl) isoxazole-3-carboxylic acid (1.20 g, 4.5 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (0.92 g, 6.7 mmol), triethylamine (0 .93 mL, 6.7 mmol) and 1-hydroxybenzotriazole (0.06 g, 0.4 mmol) were added to chloroform (amylene-added product) (10 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.03 g, 5.4 mmol) at room temperature, and the mixture was stirred overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.78 g of N- (tetrahydrofuran-3-ylmethyl) -5- (2,4-difluorobenzyloxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (278)) represented by formula (1) was obtained. .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (1H, m), 2.04-2.14 (1H, m), 2.52-2.63 ( 1H, m), 3.47 (2H, t), 3.59 (1H, dd), 3.73-3.80 (1H, m), 3.83-3.95 (2H, m), 4 .62 (2H, s), 4.68 (2H, s), 6.74 (1H, s), 6.81 (1H, dt), 6.89 (1H, dt), 6.93 (1H, br s), 7.35-7.42 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−４−ホルミル−５−[３−（２−フルオロフェニル）プロピル]イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２７９）と記す。）０．８２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６７−１．７３（ｍ，１Ｈ），２．０６−２．１６（ｍ，３Ｈ），２．５５−２．６６（ｍ，１Ｈ），２．７２−２．７６（ｍ，２Ｈ），３．１７−３．２１（ｍ，２Ｈ），３．４８−３．５１（ｍ，２Ｈ），３．６０−３．６３（ｍ，１Ｈ），３．７５−３．７９（ｍ，1Ｈ），３．８１−３．９６（ｍ，２Ｈ），６．９９−７．０８（ｍ，２Ｈ），７．１７−７．２２（ｍ、２Ｈ），１０．３９（ｓ，１Ｈ） Production Example 270
To a solution of N- (tetrahydrofuran-3-ylmethyl) -5- [3- (2-fluorophenyl) propyl] isoxazole-3-carboxamide (1.75 g, 5.25 mmol) in tetrahydrofuran (26 mL) under a nitrogen atmosphere, A 1.6 mol / L-n-butyllithium hexane solution (7.2 mL, 11.55 mmol) was added dropwise at −45 ° C. or lower, and the mixture was stirred at −45 ° C. to −60 ° C. for 1 hour, and then N, N-dimethylformamide. (1.2 mL) was added, and the mixture was further stirred at −60 ° C. to room temperature for 11.5 hours. Under ice-cooling, the reaction mixture was poured into 1 mol / L hydrochloric acid, and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -4-formyl-5- [3- (2-fluorophenyl) propyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (279)) 0 .82 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.67-1.73 (m, 1H), 2.06-2.16 (m, 3H), 2.55-2.66 ( m, 1H), 2.72-2.76 (m, 2H), 3.17-3.21 (m, 2H), 3.48-3.51 (m, 2H), 3.60-3. 63 (m, 1H), 3.75-3.79 (m, 1H), 3.81-3.96 (m, 2H), 6.99-7.08 (m, 2H), 7.17- 7.22 (m, 2H), 10.39 (s, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−４−ヒドロキシメチル−５−[３−（２−フルオロフェニル）プロピル]イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２８０）と記す。）０．６８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６７−１．７１（ｍ，１Ｈ），２．００−２．１３（ｍ，３Ｈ），２．５７−２．６１（ｍ，１Ｈ），２．６８−２．７２（ｍ，２Ｈ），２．７９−２．８２（ｍ，２Ｈ），３．４６−３．４９（ｍ，２Ｈ），３．５９−３．６２（ｍ，１Ｈ），３．７４−３．８０（ｍ，1Ｈ），３．８３−３．８６（ｍ，１Ｈ），３．８７−３．９５（ｍ，１Ｈ），４．４９−４．５０（ｍ，２Ｈ），４．５８−４．６２（ｍ，１Ｈ），７．００−７．０９（ｍ，２Ｈ），７．１５−７．２２（ｍ、３Ｈ） Production Example 271
N- (tetrahydrofuran-3-ylmethyl) -4-formyl-5- [3- (2-fluorophenyl) propyl] isoxazole-3-carboxamide (0.78 g, 2.18 mmol) in methanol (4.5 mL) To the solution, sodium borohydride (0.25 g, 6.55 mmol) was added under ice-cooling, stirred for 1.5 hours under ice-cooling, poured into 1 mol / L hydrochloric acid, and extracted twice with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -4-hydroxymethyl-5- [3- (2-fluorophenyl) propyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (280)) 0.68 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.67-1.71 (m, 1H), 2.00-2.13 (m, 3H), 2.57-2.61 ( m, 1H), 2.68-2.72 (m, 2H), 2.79-2.82 (m, 2H), 3.46-3.49 (m, 2H), 3.59-3. 62 (m, 1H), 3.74-3.80 (m, 1H), 3.83-3.86 (m, 1H), 3.87-3.95 (m, 1H), 4.49- 4.50 (m, 2H), 4.58-4.62 (m, 1H), 7.00-7.09 (m, 2H), 7.15-7.22 (m, 3H)

で示されるジチオカルボン酸 ４−Ｏ−{５−[３−（２−フルオロフェニル）プロピル]−３−［（３−テトラヒドロフリルメチル）カルバモイル］イソキサゾリルメチル}エステル Ｓ−メチルエステル（以下、本発明化合物（２８１）と記す。）０．６７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６５−１．７１（ｍ，１Ｈ），２．０１−２．１３（ｍ，３Ｈ），２．５４（ｓ，３Ｈ），２．５６−２．６０（ｍ，１Ｈ），２．７０−２．７４（ｍ，２Ｈ），２．８７−２．９１（ｍ，２Ｈ），３．４３−３．４７（ｍ，２Ｈ），３．５７−３．６０（ｍ，１Ｈ），３．７３−３．７９（ｍ，1Ｈ），３．８４−３．９４（ｍ，２Ｈ），５．７４（ｓ，２Ｈ），６．９３（ｂｒｓ，１Ｈ），７．０２−７．０５（ｍ，１Ｈ），７．０７−７．０８（ｍ，１Ｈ），７．１６−７．２２（ｍ，２Ｈ） Production Example 272
To a solution of N- (tetrahydrofuran-3-ylmethyl) -4-hydroxymethyl-5- [3- (2-fluorophenyl) propyl] isoxazole-3-carboxamide (0.67 g, 1.87 mmol) in tetrahydrofuran (8 mL). Under ice cooling, 60% sodium hydride (0.08 g, 2.06 mmol) was added and stirred for about 30 minutes. Under cooling with ice water, carbon disulfide (0.28 mL) was added, followed by methyl iodide (0.35 mL), diluted with toluene, and concentrated under reduced pressure. The residue was added to 1 mol / L hydrochloric acid, and acetic acid was added. Extracted twice with ethyl. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Dithiocarboxylic acid 4-O- {5- [3- (2-fluorophenyl) propyl] -3-[(3-tetrahydrofurylmethyl) carbamoyl] isoxazolylmethyl} ester S-methyl ester (hereinafter referred to as This is referred to as the present compound (281).) 0.67 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.65-1.71 (m, 1H), 2.01-2.13 (m, 3H), 2.54 (s, 3H) 2.56-2.60 (m, 1H), 2.70-2.74 (m, 2H), 2.87-2.91 (m, 2H), 3.43-3.47 (m, 2H), 3.57-3.60 (m, 1H), 3.73-3.79 (m, 1H), 3.84-3.94 (m, 2H), 5.74 (s, 2H) 6.93 (brs, 1H), 7.02-7.05 (m, 1H), 7.07-7.08 (m, 1H), 7.16-7.22 (m, 2H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−４−メチル−５−[３−（２−フルオロフェニル）プロピル]イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２８２）と記す。）０．３０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７２（ｍ，１Ｈ），１．９９−２．１２（ｍ，３Ｈ），２．１５（ｓ，３Ｈ），２．５４−２．６１（ｍ，１Ｈ），２．６８−２．７１（ｍ，２Ｈ），２．７３−２．７７（ｍ，２Ｈ），３．４２−３．４６（ｍ，２Ｈ），３．５６−３．６０（ｍ，１Ｈ），３．７４−３．７９（ｍ，1Ｈ），３．８４−３．９４（ｍ，２Ｈ），６．９６（ｂｒｓ，１Ｈ），７．００−７．０８（ｍ，２Ｈ），７．１５−７．２２（ｍ，２Ｈ） Production Example 273
Dithiocarboxylic acid 4-O- {5- [3- (2-fluorophenyl) propyl] -3-[(3-tetrahydrofurylmethyl) carbamoyl] isoxazolylmethyl} ester S-methyl ester (0.59 g, 1.30 mmol) in toluene (5 mL) was added tributyltin hydride (0.52 mL, 1.95 mmol) and azobisisobutyronitrile (0.04 g, 0.26 mmol). The mixture was stirred at 95 ° C. to 100 ° C. for 3 hours and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -4-methyl-5- [3- (2-fluorophenyl) propyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (282)) 0 .30 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (m, 1H), 1.99-2.12 (m, 3H), 2.15 (s, 3H) , 2.54-2.61 (m, 1H), 2.68-2.71 (m, 2H), 2.73-2.77 (m, 2H), 3.42-3.46 (m, 2H), 3.56-3.60 (m, 1H), 3.74-3.79 (m, 1H), 3.84-3.94 (m, 2H), 6.96 (brs, 1H) , 7.00-7.08 (m, 2H), 7.15-7.22 (m, 2H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−フルオロベンジルオキシメチル）−４−ホルミルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２８３）と記す。）０．５３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６５−１．７４（ｍ，１Ｈ），２．０８−２．１６（ｍ，１Ｈ），２．５８−２．６４（ｍ，１Ｈ），３．４９−３．５２（ｍ，２Ｈ），３．６０−３．６４（ｍ，１Ｈ），３．７５−３．８１（ｍ，1Ｈ），３．８５−３．９６（ｍ，２Ｈ），４．７４（ｓ，２Ｈ），５．０１（ｓ，２Ｈ），７．０４−７．０９（ｍ，１Ｈ），７．１４−７．１７（ｍ，１Ｈ），７．２９−７．４４（ｍ，３Ｈ），１０．４１（ｓ，１Ｈ） Production Example 274
To a solution of N- (tetrahydrofuran-3-ylmethyl) -5- (2-fluorobenzyloxymethyl) isoxazole-3-carboxamide (1.2 g, 3.58 mmol) in tetrahydrofuran (18 mL) at −65 ° C. under a nitrogen atmosphere. A 1.6 mol / L-n-butyllithium hexane solution (4.9 mL, 7.89 mmol) was added dropwise below. After stirring at −60 ° C. or lower for 30 minutes, N, N-dimethylformamide (0.84 mL) was added, and the mixture was further stirred at −65 ° C. to −60 ° C. for 5 hours. Under ice-cooling, the reaction mixture was poured into 1 mol / L hydrochloric acid, and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (2-fluorobenzyloxymethyl) -4-formylisoxazole-3-carboxamide (hereinafter referred to as the present compound (283)) 0. 53 g were obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.65-1.74 (m, 1H), 2.08-2.16 (m, 1H), 2.58-2.64 ( m, 1H), 3.49-3.52 (m, 2H), 3.60-3.64 (m, 1H), 3.75-3.81 (m, 1H), 3.85-3. 96 (m, 2H), 4.74 (s, 2H), 5.01 (s, 2H), 7.04-7.09 (m, 1H), 7.14-7.17 (m, 1H) , 7.29-7.44 (m, 3H), 10.41 (s, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−フルオロベンジルオキシメチル）−４−ヒドロキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２８４）と記す。）０．４５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６４−１．７２（ｍ，１Ｈ），２．０６−２．１５（ｍ，１Ｈ），２．５６−２．６２（ｍ，１Ｈ），３．４６−３．５０（ｍ，２Ｈ），３．５９−３．６２（ｍ，１Ｈ），３．７４−３．８０（ｍ，1Ｈ），３．８３−３．８７（ｍ，１Ｈ），３．９０−３．９６（ｍ，１Ｈ），４．５８−４．６５（ｍ，５Ｈ），４．６９（ｓ，２Ｈ），７．０５−７．０９（ｍ，１Ｈ），７．１４−７．１５（ｍ、１Ｈ），７．１７（ｂｒｓ，１Ｈ），７．２２−７．３５（ｍ，１Ｈ），７．３８−７．４１（ｍ，１Ｈ） Production Example 275
To a solution of N- (tetrahydrofuran-3-ylmethyl) -5- (2-fluorobenzyloxymethyl) -4-formylisoxazole-3-carboxamide (0.5 g, 1.38 mmol) in methanol (3 mL) was cooled with ice water. Under, sodium borohydride (0.16 g, 4.14 mmol) was added. After stirring for 3 hours under cooling with ice water, the reaction mixture was poured into 1 mol / L hydrochloric acid and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (2-fluorobenzyloxymethyl) -4-hydroxymethylisoxazole-3-carboxyamide (hereinafter referred to as the present compound (284)) 0 .45 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.72 (m, 1H), 2.06-2.15 (m, 1H), 2.56-2.62 ( m, 1H), 3.46-3.50 (m, 2H), 3.59-3.62 (m, 1H), 3.74-3.80 (m, 1H), 3.83-3. 87 (m, 1H), 3.90-3.96 (m, 1H), 4.58-4.65 (m, 5H), 4.69 (s, 2H), 7.05-7.09 ( m, 1H), 7.14-7.15 (m, 1H), 7.17 (brs, 1H), 7.22-7.35 (m, 1H), 7.38-7.41 (m, 1H)

で示されるジチオカルボン酸 ４−Ｏ−{５−（２−フルオロベンジルオキシメチル）−３−［（テトラヒドロフラン−３−イルメチル）カルバモイル］イソキサゾリルメチル}エステル Ｓ−メチルエステル（以下、本発明化合物（２８５）と記す。）０．３９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７１（ｍ，１Ｈ），２．０６−２．１３（ｍ，１Ｈ），２．５３（ｓ，３Ｈ），２．５６−２．６１（ｍ，１Ｈ），３．４４−３．４７（ｍ，２Ｈ），３．５７−３．６１（ｍ，１Ｈ），３．７４−３．７９（ｍ，1Ｈ），３．８３−３．９４（ｍ，２Ｈ），４．６７（ｓ，２Ｈ），４．７８（ｓ，２Ｈ），５．８２（ｓ，２Ｈ），６．９８（ｂｒｓ，１Ｈ），７．０３−７．０８（ｍ，１Ｈ），７．１２−７．１６（ｍ，１Ｈ），７．２８−７．３３（ｍ，１Ｈ），７．３８−７．４２（ｍ，１Ｈ） Production Example 276
To a solution of N- (tetrahydrofuran-3-ylmethyl) -5- (2-fluorobenzyloxymethyl) -4-hydroxymethylisoxazole-3-carboxamide (0.45 g, 1.2 mmol) in tetrahydrofuran (5 mL), Under water cooling, 60% sodium hydride (0.05 g, 1.34 mmol) was added and stirred for 25 minutes. Under ice water cooling, carbon disulfide (0.18 mL) was added, followed by methyl iodide (0.23 mL). After stirring for 2 hours under cooling with ice water, the reaction mixture was diluted with toluene and concentrated under reduced pressure. The residue was poured into 1 mol / L hydrochloric acid and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Dithiocarboxylic acid 4-O- {5- (2-fluorobenzyloxymethyl) -3-[(tetrahydrofuran-3-ylmethyl) carbamoyl] isoxazolylmethyl} ester S-methyl ester (hereinafter referred to as the present invention) Compound (285).) 0.39 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.71 (m, 1H), 2.06-2.13 (m, 1H), 2.53 (s, 3H) , 2.56-2.61 (m, 1H), 3.44-3.47 (m, 2H), 3.57-3.61 (m, 1H), 3.74-3.79 (m, 1H), 3.83-3.94 (m, 2H), 4.67 (s, 2H), 4.78 (s, 2H), 5.82 (s, 2H), 6.98 (brs, 1H) ), 7.03-7.08 (m, 1H), 7.12-7.16 (m, 1H), 7.28-7.33 (m, 1H), 7.38-7.42 (m , 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−フルオロベンジルオキシメチル）−４−メチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２８６）と記す。）０．２２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７２（ｍ，１Ｈ），２．０４−２．１３（ｍ，１Ｈ），２．２５（ｓ，３Ｈ），２．５４−２．６１（ｍ，１Ｈ），３．４３−３．４６（ｍ，２Ｈ），３．５７−３．６０（ｍ，１Ｈ），３．７４−３．８０（ｍ，1Ｈ），３．８４−３．９４（ｍ，２Ｈ），４．６３（ｓ，４Ｈ），７．００（ｂｒｓ，１Ｈ），７．０４−７．０９（ｍ，１Ｈ），７．１３−７．１７（ｍ，１Ｈ），７．２８−７．３４（ｍ，１Ｈ），７．３８−７．４２（ｍ，１Ｈ） Production Example 277
Dithiocarboxylic acid 4-O- {5- (2-fluorobenzyloxymethyl) -3-[(tetrahydrofuran-3-ylmethyl) carbamoyl] isoxazolylmethyl} ester S-methyl ester (0.37 g, 0.81 mmol) ) In toluene (3 mL) was added tributyltin hydride (0.32 mL, 1.22 mmol) and azobisisobutyronitrile (0.03 g, 0.16 mmol). The mixture was stirred at 95 to 100 ° C. for 2 hours, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (2-fluorobenzyloxymethyl) -4-methylisoxazole-3-carboxamide (hereinafter referred to as the present compound (286)) 0. 22 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.72 (m, 1H), 2.04-2.13 (m, 1H), 2.25 (s, 3H) , 2.54-2.61 (m, 1H), 3.43-3.46 (m, 2H), 3.57-3.60 (m, 1H), 3.74-3.80 (m, 1H), 3.84-3.94 (m, 2H), 4.63 (s, 4H), 7.00 (brs, 1H), 7.04-7.09 (m, 1H), 7.13 -7.17 (m, 1H), 7.28-7.34 (m, 1H), 7.38-7.42 (m, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−４−ホルミル−５−［３−（２−ナフチル）プロピル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２８７）と記す。）１．８８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１０．３５（１Ｈ，ｓ），７．７８（３Ｈ，ｄ），７．６１（１Ｈ，ｓ），７．４５（２Ｈ，ｄｄｄ），７．３２（１Ｈ，ｄｄ），７．２０−７．１０（１Ｈ，ｍ），３．９３（１Ｈ，ｔｄ），３．８６（１Ｈ，ｄｄ），３．７７（１Ｈ，ｄｄ），３．６０（１Ｈ， ｄｄ），３．４７（２Ｈ，ｔ），３．２１（２Ｈ，ｔ），２．８８（２Ｈ，ｔ），２．６２−２．５５（１Ｈ，ｍ），２．２１（２Ｈ，ｄｔ），２．１５−２．０６（１Ｈ，ｍ），１．７２−１．６１（１Ｈ，ｍ） Production Example 278
To a solution of N- (tetrahydrofuran-3-ylmethyl) -5- [3- (2-naphthyl) propyl] isoxazole-3-carboxamide (2.22 g, 6.09 mmol) in tetrahydrofuran (30 mL) under a nitrogen atmosphere, A 2.6 mol / L-n-butyllithium hexane solution (5.2 mL, 13.4 mmol) was added dropwise at 60 ° C. or lower, and the mixture was stirred at −30 ° C. to −60 ° C. for 30 minutes, and then at 0 ° C. to −30 ° C. Stir for another 30 minutes. N, N-dimethylformamide (1.4 mL) was added to the reaction mixture at −60 ° C. or lower, stirred at −60 ° C. to room temperature for 2 hours, cooled to −40 ° C., and 30 mL of 1 mol / L hydrochloric acid was poured into the reaction mixture. Extracted with ethyl. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -4-formyl-5- [3- (2-naphthyl) propyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (287)). 88 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 10.35 (1H, s), 7.78 (3H, d), 7.61 (1H, s), 7.45 (2H, ddd) ), 7.32 (1H, dd), 7.20-7.10 (1H, m), 3.93 (1H, td), 3.86 (1H, dd), 3.77 (1H, dd) , 3.60 (1H, dd), 3.47 (2H, t), 3.21 (2H, t), 2.88 (2H, t), 2.62-2.55 (1H, m), 2.21 (2H, dt), 2.15-2.06 (1H, m), 1.72-1.61 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−４−ヒドロキシメチル−５−［３−（２−ナフチル）プロピル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２８８）と記す。）の粗生成物１．８１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．８４−７．７６（３Ｈ，ｍ），７．６１（１Ｈ，ｓ），７．４５（２Ｈ，ｄｔｄ），７．３３−７．３０（１Ｈ， ｍ），７．１６−７．０６（１Ｈ，ｍ），４．５９（１Ｈ，ｔ），４．４８（２Ｈ，ｄ），３．９３（１Ｈ，ｔｄ），３．８５（１Ｈ，ｄｄ），３．７７（１Ｈ，ｄｔ），３．６０（１Ｈ，ｄｄ），３．４７（２Ｈ，ｄｄ），２．８５−２．８０（４Ｈ，ｍ），２．６３−２．５３（１Ｈ，ｍ），２．２１−２．０７（３Ｈ，ｍ），１．７５−１．６２（１Ｈ，ｍ） Production Example 279
Ice-water cooling of a solution of N- (tetrahydrofuran-3-ylmethyl) -4-formyl-5- [3- (2-naphthyl) propyl] isoxazole-3-carboxamide (1.88 g, 4.79 mmol) in methanol (11 mL) Below, sodium borohydride (648 mg, 17.1 mmol) was added. After stirring for 30 minutes under cooling with ice water, the mixture was stirred for 30 minutes at room temperature. Under cooling with ice water, 1 mol / L hydrochloric acid was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

N- (tetrahydrofuran-3-ylmethyl) -4-hydroxymethyl-5- [3- (2-naphthyl) propyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (288)). 1.81 g of crude product was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.84-7.76 (3H, m), 7.61 (1H, s), 7.45 (2H, dtd), 7.33 -7.30 (1H, m), 7.16-7.06 (1H, m), 4.59 (1H, t), 4.48 (2H, d), 3.93 (1H, td), 3.85 (1H, dd), 3.77 (1H, dt), 3.60 (1H, dd), 3.47 (2H, dd), 2.85-2.80 (4H, m), 2 .63-2.53 (1H, m), 2.21-2.07 (3H, m), 1.75-1.62 (1H, m)

で示されるジチオカルボン酸 ４−Ｏ−{５−［３−（２−ナフチル）プロピル］−３−［（テトラヒドロフラン−３−イルメチル）カルバモイル］イソキサゾリルメチル}エステル Ｓ−メチルエステル（以下、本発明化合物（２８９）と記す。）１．８４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．８２−７．７７（３Ｈ，ｍ），７．６１（１Ｈ，ｓ），７．４８−７．４１（２Ｈ，ｍ），７．３２（１Ｈ，ｄｄ），６．９４−６．８３（１Ｈ，ｍ），５．７３（２Ｈ，ｓ），３．９１（１Ｈ，ｔｄ），３．８５（１Ｈ，ｄｄ），３．７６（１Ｈ，ｔｄ），３．５８（１Ｈ，ｄｄ），３．４６−３．４３（２Ｈ，ｍ），２．８８（４Ｈ，ｔｄ），２．５７（１Ｈ，ｄｔ），２．５２（３Ｈ，ｓ），２．１９−２．１１（２Ｈ，ｍ），２．１２−２．０６（１Ｈ，ｍ），１．６７（１Ｈ，ｔｔ） Production Example 280
To a solution of N- (tetrahydrofuran-3-ylmethyl) -4-formyl-5- [3- (2-naphthyl) propyl] isoxazole-3-carboxamide (1.81 g, 4.59 mmol) in tetrahydrofuran (20 mL) was added ice water. Under cooling, 55% sodium hydride (220 mg, 5.05 mmol) was added, and the mixture was stirred for 30 minutes under cooling with ice water. Under cooling with ice water, carbon disulfide (0.7 mL) was added, stirred for 40 minutes, and then methyl iodide (0.86 mL) was added. The mixture was stirred for 40 minutes under cooling with ice water, diluted with toluene, and concentrated under reduced pressure. 1 mol / L hydrochloric acid was added to the concentrate, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Dithiocarboxylic acid 4-O- {5- [3- (2-naphthyl) propyl] -3-[(tetrahydrofuran-3-ylmethyl) carbamoyl] isoxazolylmethyl} ester S-methyl ester (hereinafter referred to as 1.84 g of the compound of the present invention (described as 289) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.82-7.77 (3H, m), 7.61 (1H, s), 7.48-7.41 (2H, m) 7.32 (1H, dd), 6.94-6.83 (1H, m), 5.73 (2H, s), 3.91 (1H, td), 3.85 (1H, dd), 3.76 (1H, td), 3.58 (1H, dd), 3.46-3.43 (2H, m), 2.88 (4H, td), 2.57 (1H, dt), 2 .52 (3H, s), 2.19-2.11 (2H, m), 2.12-2.06 (1H, m), 1.67 (1H, tt)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−４−メチル−５−［３−（２−ナフチル）プロピル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２９０）と記す。）１．００ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．８４−７．７４（３Ｈ，ｍ），７．６１（１Ｈ，ｓ），７．４５（２Ｈ，ｄｔｄ），７．３２（１Ｈ，ｄｄ），６．９６−６．８５（１Ｈ，ｍ），３．９１（１Ｈ，ｔｄ），３．８６（１Ｈ，ｄｄ），３．８０−３．７４（１Ｈ，ｍ），３．５８（１Ｈ，ｄｄ），３．４３（２Ｈ，ｄｑ），２．８２（２Ｈ，ｔ），２．７６（２Ｈ，ｔ），２．６２−２．５２（１Ｈ，ｍ），２．１４（３Ｈ，ｓ），２．１２−２．０６（３Ｈ，ｍ），１．６８（１Ｈ，ｄｔ） Production Example 281
Dithiocarboxylic acid 4-O- {5- [3- (2-naphthyl) propyl] -3-[(tetrahydrofuran-3-ylmethyl) carbamoyl] isoxazolylmethyl} ester S-methyl ester (1.84 g, 4 .03 mmol) in toluene (13 mL) were added tributyltin hydride (1.5 mL, 6.05 mmol) and azobisisobutyronitrile (132 mg, 0.81 mmol). The mixture was stirred at 90 to 100 ° C. for 2 hours, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -4-methyl-5- [3- (2-naphthyl) propyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (290)). 00 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.84-7.74 (3H, m), 7.61 (1H, s), 7.45 (2H, dtd), 7.32 (1H, dd), 6.96-6.85 (1H, m), 3.91 (1H, td), 3.86 (1H, dd), 3.80-3.74 (1H, m), 3.58 (1H, dd), 3.43 (2H, dq), 2.82 (2H, t), 2.76 (2H, t), 2.62-2.52 (1H, m), 2 .14 (3H, s), 2.12-2.06 (3H, m), 1.68 (1H, dt)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−４−ホルミル−５−(３−フルオロベンジル)イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２９１）と記す。）１５４ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １０．４７（１Ｈ，ｓ），７．２９（１Ｈ，ｔｄ），７．１２（２Ｈ，ｄｔ）７．０５（１Ｈ，ｄｔ），６．９７（１Ｈ，ｔｄｄ），４．４８（２Ｈ，ｓ），３．９３（１Ｈ，ｔｄ），３．８５（１Ｈ，ｄｄ），３．７７（１Ｈ，ｔｄ），３．６１（１Ｈ，ｄｄ），３．４８（２Ｈ，ｔ），２．６４−２．５４（１Ｈ，ｍ），２．１５−２．０６（１Ｈ，ｍ），１．７３−１．６３（１Ｈ，ｍ） Production Example 282
To a solution of N- (tetrahydrofuran-3-ylmethyl) -5- (3-fluorobenzyl) isoxazole-3-carboxamide (1.22 g, 4.0 mmol) in tetrahydrofuran (20 mL) at −60 ° C. or lower under a nitrogen atmosphere. A 1.64 mol / L-n-butyllithium hexane solution (5.5 mL, 8.8 mmol) was added dropwise over 10 minutes, stirred at −60 ° C. or lower for 30 minutes, and then N, N-dimethylformamide (1.0 mL). ) And further stirred at -60 ° C to 20 ° C for 2 hours. Under ice-cooling, 16 mL of 1 mol / L hydrochloric acid was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

154 mg of N- (tetrahydrofuran-3-ylmethyl) -4-formyl-5- (3-fluorobenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (291)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 10.47 (1H, s), 7.29 (1H, td), 7.12 (2H, dt) 7.05 (1H, dt) 6.97 (1H, tdd), 4.48 (2H, s), 3.93 (1H, td), 3.85 (1H, dd), 3.77 (1H, td), 3.61 ( 1H, dd), 3.48 (2H, t), 2.64-2.54 (1H, m), 2.15-2.06 (1H, m), 1.73-1.63 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−４−ヒドロキシメチル−５−(３−フルオロベンジル)イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２９２）と記す。）の粗生成物２４５ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．２９（２Ｈ，ｄｄ），７．１８−７．１０（１Ｈ，ｍ），７．００−６．９８（１Ｈ，ｍ），６．９６（１Ｈ，ｄｄ），６．９３−６．９０（１Ｈ，ｍ），４．５６（２Ｈ，ｓ），４．１３（２Ｈ，ｓ），３．９３（１Ｈ，ｔｄ），３．８５（１Ｈ，ｄｄ），３．７７（１Ｈ，ｄｄ），３．６０（１Ｈ，ｄｄ），３．４８（２Ｈ，ｄｄ），２．６２−２．５５（１Ｈ，ｍ），２．１１（１Ｈ，ｔｔ），１．７３−１．６３（１Ｈ，ｍ）. Production Example 283
Hydrogenation of N- (tetrahydrofuran-3-ylmethyl) -4-formyl-5- (3-fluorobenzyl) isoxazole-3-carboxamide (230 mg, 1.0 mmol) in methanol (1.4 mL) under ice water cooling Sodium boron (80 mg, 3.0 mmol) was added. The mixture was stirred at room temperature for 1 hour under cooling with ice water. Under cooling with ice water, 1 mol / L hydrochloric acid was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure.

245 mg of a crude product of N- (tetrahydrofuran-3-ylmethyl) -4-hydroxymethyl-5- (3-fluorobenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (292)) Got.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.29 (2H, dd), 7.18-7.10 (1H, m), 7.00-6.98 (1H, m) , 6.96 (1H, dd), 6.93-6.90 (1H, m), 4.56 (2H, s), 4.13 (2H, s), 3.93 (1H, td), 3.85 (1H, dd), 3.77 (1H, dd), 3.60 (1H, dd), 3.48 (2H, dd), 2.62-2.55 (1H, m), 2 .11 (1H, tt), 1.73-1.63 (1H, m).

で示されるジチオカルボン酸 ４−Ｏ−｛５−(３−フルオロベンジル)−３−［（３−テトラヒドロフリルメチル）カルバモイル］イソキサゾリルメチル｝エステル Ｓ−メチルエステル（以下、本発明化合物（２９３）と記す。）２２０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．３４−７．２７（１Ｈ，ｍ），７．０８−６．８９（４Ｈ，ｍ），５．７７（２Ｈ，ｓ），４．２１（２Ｈ，ｓ），３．９１（１Ｈ，ｔｄ），３．８５（１Ｈ，ｄｄ），３．７６（１Ｈ，ｔｄ），３．５８（１Ｈ，ｄｄ），３．４５（２Ｈ，ｔ），２．５８（１Ｈ，ｔｔ），２．５４（３Ｈ，ｓ），２．１３−２．０４（１Ｈ，ｍ），１．７２−１．６２（１Ｈ，ｍ） Production Example 284
To a solution of N- (tetrahydrofuran-3-ylmethyl) -4-hydroxymethyl-5- (3-fluorobenzyl) isoxazole-3-carboxamide (245 mg, 0.70 mmol) in tetrahydrofuran (3.0 mL) was cooled with ice water. 55% sodium hydride (34 mg, 0.77 mmol) was added, and the mixture was stirred for 40 minutes under cooling with ice water. Under cooling with ice water, carbon disulfide (0.1 mL) was added, and the mixture was stirred at the same temperature for 30 minutes. Then, methyl iodide (0.13 mL) was added, and the mixture was further stirred for 30 minutes. The reaction mixture was diluted with toluene and concentrated under reduced pressure. 1 mol / L hydrochloric acid was added to the concentrate, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Dithiocarboxylic acid 4-O- {5- (3-fluorobenzyl) -3-[(3-tetrahydrofurylmethyl) carbamoyl] isoxazolylmethyl} ester S-methyl ester (hereinafter referred to as the present compound ( 293).) 220 mg was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.34-7.27 (1H, m), 7.08-6.89 (4H, m), 5.77 (2H, s) , 4.21 (2H, s), 3.91 (1H, td), 3.85 (1H, dd), 3.76 (1H, td), 3.58 (1H, dd), 3.45 ( 2H, t), 2.58 (1H, tt), 2.54 (3H, s), 2.13-2.04 (1H, m), 1.72-1.62 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−４−メチル−５−(３−フルオロベンジル)イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２９４）と記す。）９２ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．３１−７．２５（１Ｈ，ｍ），７．０１−６．８７（４Ｈ，ｍ），４．０７（２Ｈ，ｓ），３．９１（１Ｈ，ｔｄ），３．８５（１Ｈ，ｄｄ），３．７６（１Ｈ，ｄｄ），３．５８（１Ｈ，ｄｄ），３．４９−３．３８（２Ｈ，ｍ），２．６２−２．５１（１Ｈ，ｍ），２．２０（３Ｈ，ｓ），２．１４−２．０３（１Ｈ，ｍ），１．６７（１Ｈ，ｔｔ） Production Example 285
Dithiocarboxylic acid 4-O- {5- (3-fluorobenzyl) -3-[(3-tetrahydrofurylmethyl) carbamoyl] isoxazolylmethyl} ester S-methyl ester (220 mg, 0.518 mmol) in toluene ( To the 1.7 mL) solution, tributyltin hydride (0.2 mL, 0.777 mmol) and azobisisobutyronitrile (17 mg, 0.104 mmol) were added. After stirring at 90 ° C. to 95 ° C. for 2 hours, tributyltin hydride (0.2 mL, 0.777 mmol) and azobisisobutyronitrile (34 mg, 0.208 mmol) were added. The mixture was stirred at 90 to 95 ° C. for 1 hour and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -4-methyl-5- (3-fluorobenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (294)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.31-7.25 (1H, m), 7.01-6.87 (4H, m), 4.07 (2H, s) , 3.91 (1H, td), 3.85 (1H, dd), 3.76 (1H, dd), 3.58 (1H, dd), 3.49-3.38 (2H, m), 2.62-2.51 (1H, m), 2.20 (3H, s), 2.14-2.03 (1H, m), 1.67 (1H, tt)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−ナフチルメトキシメチル）−４−ヨードイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２９５）と記す。）０．７８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６３−１．７１（ｍ，１Ｈ），２．０４−２．１５（ｍ，１Ｈ），２．５５−２．６２（ｍ，１Ｈ），３．４３−３．４７（ｍ，２Ｈ），３．５７−３．６１（ｍ，１Ｈ），３．７４−３．８０（ｍ，1Ｈ），３．８３−３．９５（ｍ，２Ｈ），４．７３（ｓ，２Ｈ），４．７７（ｓ，２Ｈ），６．９１（ｂｒｓ，１Ｈ），７．４８−７．５２（ｍ，３Ｈ），７．８２−７．８７（ｍ，４Ｈ） Production Example 286
To a solution of N- (tetrahydrofuran-3-ylmethyl) -5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (1.5 g, 4.09 mmol) in tetrahydrofuran (15 mL) at −65 ° C. or lower in a nitrogen atmosphere. 1.6 mol / L-n-butyllithium hexane solution (5.6 mL, 9.00 mmol) was added dropwise. After stirring at −60 ° C. or lower for 1 hour, a solution of iodine (3.11 g, 12.28 mmol) in tetrahydrofuran (5 mL) was added to the reaction mixture, and the mixture was stirred overnight while gradually returning to room temperature. Under ice-cooling, the reaction mixture was poured into 1 mol / L hydrochloric acid, and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (2-naphthylmethoxymethyl) -4-iodoisoxazole-3-carboxamide (hereinafter referred to as the present compound (295)) 0.78 g Got.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.63-1.71 (m, 1H), 2.04-2.15 (m, 1H), 2.55-2.62 ( m, 1H), 3.43-3.47 (m, 2H), 3.57-3.61 (m, 1H), 3.74-3.80 (m, 1H), 3.83-3. 95 (m, 2H), 4.73 (s, 2H), 4.77 (s, 2H), 6.91 (brs, 1H), 7.48-7.52 (m, 3H), 7.82 -7.87 (m, 4H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−フルオロベンジルオキシメチル）−４−ブロモイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２９６）と記す。）０．２５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６４−１．７２（ｍ，１Ｈ），２．０６−２．１３（ｍ，１Ｈ），２．５６−２．６３（ｍ，１Ｈ），３．４５−３．５１（ｍ，２Ｈ），３．５８−３．６１（ｍ，１Ｈ），３．７４−３．７９（ｍ，1Ｈ），３．８３−３．９５（ｍ，２Ｈ），４．７０（ｓ，２Ｈ），４．７１（ｓ，２Ｈ），６．９３（ｂｒｓ，１Ｈ），７．０４−７．０９（ｍ，１Ｈ），７．１３−７．１７（ｍ，１Ｈ），７．２８−７．３４（ｍ，１Ｈ），７．４０−７．４４（ｍ，１Ｈ） Production Example 287
A solution of N- (tetrahydrofuran-3-ylmethyl) -5- (2-fluorobenzyloxymethyl) isoxazole-3-carboxamide (0.4 g, 1.19 mmol) in tetrahydrofuran (5 mL) at −65 ° C. under a nitrogen atmosphere. A 1.6 mol / L-n-butyllithium hexane solution (1.6 mL, 2.63 mmol) was added dropwise below, and the mixture was stirred at −60 ° C. or lower for 1 hour, and then bromotrichloromethane (0.35 mL, 3.58 mmol). Of tetrahydrofuran (1 mL) was added, and the mixture was stirred at −65 ° C. to −60 ° C. for 3 hours. Under ice-cooling, the reaction mixture was poured into 1 mol / L hydrochloric acid, and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (2-fluorobenzyloxymethyl) -4-bromoisoxazole-3-carboxamide (hereinafter referred to as the present compound (296)) 0. 25 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.72 (m, 1H), 2.06-2.13 (m, 1H), 2.56-2.63 ( m, 1H), 3.45-3.51 (m, 2H), 3.58-3.61 (m, 1H), 3.74-3.79 (m, 1H), 3.83-3. 95 (m, 2H), 4.70 (s, 2H), 4.71 (s, 2H), 6.93 (brs, 1H), 7.04-7.09 (m, 1H), 7.13 -7.17 (m, 1H), 7.28-7.34 (m, 1H), 7.40-7.44 (m, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−フルオロベンジルオキシメチル）−４−ヨードイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２９７）と記す。）０．１９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６４−１．７２（ｍ，１Ｈ），２．０６−２．１３（ｍ，１Ｈ），２．５６−２．６３（ｍ，１Ｈ），３．４４−３．４８（ｍ，２Ｈ），３．５８−３．６１（ｍ，１Ｈ），３．７４−３．７９（ｍ，1Ｈ），３．８３−３．９５（ｍ，２Ｈ），４．６８（ｓ，２Ｈ），４．７４（ｓ，２Ｈ），６．９７（ｂｒｓ，１Ｈ），７．０４−７．０９（ｍ，１Ｈ），７．１４−７．１７（ｍ，１Ｈ），７．２８−７．３４（ｍ，１Ｈ），７．４１−７．４６（ｍ，１Ｈ） Production Example 288
A solution of N- (tetrahydrofuran-3-ylmethyl) -5- (2-fluorobenzyloxymethyl) isoxazole-3-carboxamide (0.4 g, 1.19 mmol) in tetrahydrofuran (5 mL) at −65 ° C. under a nitrogen atmosphere. A 1.6 mol / L-n-butyllithium hexane solution (1.6 mL, 2.63 mmol) was added dropwise below, and the mixture was stirred at −60 ° C. or lower for 1 hour, and then iodine (0.91 g, 3.58 mmol) in tetrahydrofuran. (1 mL) solution was added and stirred at −65 ° C. to −60 ° C. for 3 hours. Under ice-cooling, the reaction mixture was poured into 1 mol / L hydrochloric acid, and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (2-fluorobenzyloxymethyl) -4-iodoisoxazole-3-carboxamide (hereinafter referred to as the present compound (297)) 0. 19 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.72 (m, 1H), 2.06-2.13 (m, 1H), 2.56-2.63 ( m, 1H), 3.44-3.48 (m, 2H), 3.58-3.61 (m, 1H), 3.74-3.79 (m, 1H), 3.83-3. 95 (m, 2H), 4.68 (s, 2H), 4.74 (s, 2H), 6.97 (brs, 1H), 7.04-7.09 (m, 1H), 7.14 -7.17 (m, 1H), 7.28-7.34 (m, 1H), 7.41-7.46 (m, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−フルオロベンジルオキシメチル）−４−フルオロイソキサゾール−３−カルボキシアミド（以下、本発明化合物（２９８）と記す。）０．０６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６４−１．７２（ｍ，１Ｈ），２．０５−２．１４（ｍ，１Ｈ），２．５６−２．６２（ｍ，１Ｈ），３．４６−３．５０（ｍ，２Ｈ），３．５８−３．６２（ｍ，１Ｈ），３．７４−３．８０（ｍ，1Ｈ），３．８３−３．９５（ｍ，２Ｈ），４．６８（ｓ，２Ｈ），４．７０（ｓ，２Ｈ），６．８３（ｂｒｓ，１Ｈ），７．０５−７．０９（ｍ，１Ｈ），７．１３−７．１７（ｍ，１Ｈ），７．２９−７．３４（ｍ，１Ｈ），７．３９−７．４２（ｍ，１Ｈ） Production Example 289
A solution of N- (tetrahydrofuran-3-ylmethyl) -5- (2-fluorobenzyloxymethyl) isoxazole-3-carboxamide (0.4 g, 1.19 mmol) in tetrahydrofuran (5 mL) at −65 ° C. under a nitrogen atmosphere. A 1.6 mol / L-n-butyllithium hexane solution (1.6 mL, 2.63 mmol) was added dropwise below, and the mixture was stirred at −60 ° C. or lower for 1 hour, and then N-fluorobenzenesulfonimide (1.13 g, 3 (.58 mmol) in tetrahydrofuran (3 mL) was added, and the mixture was stirred at −65 ° C. to −60 ° C. for 3 hours. Under ice-cooling, the reaction mixture was poured into 1 mol / L hydrochloric acid, and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (2-fluorobenzyloxymethyl) -4-fluoroisoxazole-3-carboxamide (hereinafter referred to as the present compound (298)) 0. 06 g was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.64-1.72 (m, 1H), 2.05-2.14 (m, 1H), 2.56-2.62 ( m, 1H), 3.46-3.50 (m, 2H), 3.58-3.62 (m, 1H), 3.74-3.80 (m, 1H), 3.83-3. 95 (m, 2H), 4.68 (s, 2H), 4.70 (s, 2H), 6.83 (brs, 1H), 7.05-7.09 (m, 1H), 7.13 -7.17 (m, 1H), 7.29-7.34 (m, 1H), 7.39-7.42 (m, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（１，３−ベンゾジオキソラン−５−イルメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（２９９）と記す。）５３０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７１（１Ｈ，ｍ），２．０２−２．１２（１Ｈ，ｍ），２．５０−２．６２（１Ｈ，ｍ），３．４４（２Ｈ，ｄｄ），３．５２（１Ｈ，ｄｄ），３．７６（１Ｈ，ｄｄ），３．８１−３．９２（２Ｈ，ｍ），４．０２（２Ｈ，ｓ），５．９５（２Ｈ，ｓ），６．３９（１Ｈ，ｓ），６．６８−６．７３（２Ｈ，ｍ），６．７５−６．９５（１Ｈ，ｍ），６．８９（１Ｈ，ｂｒ ｓ） Production Example 290
5- (1,3-benzodioxolan-5-ylmethyl) isoxazole-3-carboxylic acid (600 mg, 2.42 mmol), tetrahydrofuran-3-ylmethylamine (270 mg, 2.67 mmol) and 1-hydroxybenzotriazole (393 mg) , 2.91 mmol) was added to dichloromethane (15 mL) and stirred at 0 ° C. for 30 minutes. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (556 mg, 2.91 mmol) at room temperature, and the mixture was stirred for 16 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 0.5 mol / L hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

530 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (1,3-benzodioxolan-5-ylmethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (299)) represented by the formula: .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.71 (1H, m), 2.02-2.12 (1H, m), 2.50-2.62 ( 1H, m), 3.44 (2H, dd), 3.52 (1H, dd), 3.76 (1H, dd), 3.81-3.92 (2H, m), 4.02 (2H) , S), 5.95 (2H, s), 6.39 (1H, s), 6.68-6.73 (2H, m), 6.75-6.95 (1H, m), 6. 89 (1H, br s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３，５−ジフルオロベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３０５）と記す。）４６０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７１（１Ｈ，ｍ），２．０２−２．１４（１Ｈ，ｍ），２．５０−２．６２（１Ｈ，ｍ），３．４５（２Ｈ，ｄｄ），３．５８（１Ｈ，ｄｄ），３．７６（１Ｈ，ｄｄ），３．８１−３．９５（２Ｈ，ｍ），４．１１（２Ｈ，ｓ），６．４７（１Ｈ，ｓ），６．７１−６．８２（３Ｈ，ｍ），６．９０（１Ｈ，ｂｒ ｓ） Production Example 291
5- (3,5-difluorobenzyl) isoxazole-3-carboxylic acid (600 mg, 2.51 mmol), tetrahydrofuran-3-ylmethylamine (279 mg, 2.76 mmol) and 1-hydroxybenzotriazole (407 mg, 3.01 mmol) ) Was added to dichloromethane (15 mL) and stirred at 0 ° C. for 30 minutes. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (577 mg, 3.01 mmol) at room temperature, the mixture was stirred for 16 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 0.5 mol / L hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

460 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (3,5-difluorobenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (305)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.71 (1H, m), 2.02-2.14 (1H, m), 2.50-2.62 ( 1H, m), 3.45 (2H, dd), 3.58 (1H, dd), 3.76 (1H, dd), 3.81-3.95 (2H, m), 4.11 (2H) , S), 6.47 (1H, s), 6.71-6.82 (3H, m), 6.90 (1H, br s)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３，４−ジフルオロベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３０６）と記す。）５１０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６１−１．７１（１Ｈ，ｍ），２．０２−２．１２（１Ｈ，ｍ），２．５０−２．６１（１Ｈ，ｍ），３．４５（２Ｈ，ｄｄ），３．５８（１Ｈ，ｄｄ），３．７６（１Ｈ，ｄｄ），３．８０−３．９２（２Ｈ，ｍ），４．０９（２Ｈ，ｓ），６．４３（１Ｈ，ｓ），６．８９（１Ｈ，ｂｒ ｓ），６．９４−７．００（１Ｈ，ｍ），７．０３−７．１８（２Ｈ，ｍ） Production Example 292
5- (3,4-difluorobenzyl) isoxazole-3-carboxylic acid (600 mg, 2.51 mmol), tetrahydrofuran-3-ylmethylamine (279 mg, 2.76 mmol) and 1-hydroxybenzotriazole (407 mg, 3.01 mmol) ) Was added to dichloromethane (15 mL) and stirred at 0 ° C. for 30 minutes. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (577 mg, 3.01 mmol) at room temperature, the mixture was stirred for 16 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 0.5 mol / L hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Thus, 510 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (3,4-difluorobenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (306)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.61-1.71 (1H, m), 2.02-2.12 (1H, m), 2.50-2.61 ( 1H, m), 3.45 (2H, dd), 3.58 (1H, dd), 3.76 (1H, dd), 3.80-3.92 (2H, m), 4.09 (2H) , S), 6.43 (1H, s), 6.89 (1H, br s), 6.94-7.00 (1H, m), 7.03-7.18 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３，５−ジクロロベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３０７）と記す。）５０５ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６１−１．７２（１Ｈ，ｍ），２．０２−２．１２（１Ｈ，ｍ），２．５０−２．６２（１Ｈ，ｍ），３．４５（２Ｈ，ｄｄ），３．５８（１Ｈ，ｄｄ），３．７６（１Ｈ，ｄｄ），３．８１−３．９３（２Ｈ，ｍ），４．０８（２Ｈ，ｓ），６．４５（１Ｈ，ｓ），６．９０（１Ｈ，ｂｒ ｓ），７．１４（２Ｈ，ｄ），７．３０（１Ｈ，ｄｄ） Production Example 293
5- (3,5-dichlorobenzyl) isoxazole-3-carboxylic acid (600 mg, 2.2 mmol), 3-tetrahydrofurylmethylamine (245 mg, 2.42 mmol) and 1-hydroxybenzotriazole (357 mg, 2.65 mmol) Was added to dichloromethane (15 mL) and stirred at 0 ° C. for 30 minutes. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (506 mg, 2.65 mmol) at room temperature, and the mixture was stirred for 16 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 0.5 mol / L hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

505 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (3,5-dichlorobenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (307)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.61-1.72 (1H, m), 2.02-2.12 (1H, m), 2.50-2.62 ( 1H, m), 3.45 (2H, dd), 3.58 (1H, dd), 3.76 (1H, dd), 3.81-3.93 (2H, m), 4.08 (2H) , S), 6.45 (1H, s), 6.90 (1H, br s), 7.14 (2H, d), 7.30 (1H, dd)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−チエニルメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３０８）と記す。）３５０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７２（１Ｈ，ｍ），２．００−２．１４（１Ｈ，ｍ），２．４９−２．６２（１Ｈ，ｍ），３．４５（２Ｈ，ｄｄ），３．５７（１Ｈ，ｄｄ），３．７６（１Ｈ，ｄｄ），３．８５−３．９５（２Ｈ，ｍ），４．３３（２Ｈ，ｓ），６．４９（１Ｈ，ｓ），６．９０（１Ｈ，ｂｒ ｓ），６．９２−７．０１（２Ｈ，ｍ），７．２０−７．２５（１Ｈ，ｍ） Production Example 294
5- (2-thienylmethyl) isoxazole-3-carboxylic acid (500 mg, 2.09 mmol), tetrahydrofuran-3-ylmethylamine (232 mg, 2.3 mmol) and 1-hydroxybenzotriazole (339 mg, 2.5 mmol). Added to dichloromethane (15 mL) and stirred at 0 ° C. for 30 minutes. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (480 mg, 2.5 mmol) at room temperature, and the mixture was stirred for 16 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 0.5 mol / L hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Thus, 350 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (2-thienylmethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (308)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.72 (1H, m), 2.00-2.14 (1H, m), 2.49-2.62 ( 1H, m), 3.45 (2H, dd), 3.57 (1H, dd), 3.76 (1H, dd), 3.85-3.95 (2H, m), 4.33 (2H) , S), 6.49 (1H, s), 6.90 (1H, br s), 6.92-7.01 (2H, m), 7.20-7.25 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−チエニルメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３０９）と記す。）５２０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．５９−１．７２（１Ｈ，ｍ），２．００−２．１５（１Ｈ，ｍ），２．５０−２．６０（１Ｈ，ｍ），３．４５（２Ｈ，ｄｄ），３．５７（１Ｈ，ｄｄ），３．７３（１Ｈ，ｄｄ），３．８１−３．９５（２Ｈ，ｍ），４．１５（２Ｈ，ｓ），６．４３（１Ｈ，ｓ），６．９０（１Ｈ，ｂｒ ｓ），６．９５−７．０２（１Ｈ，ｍ），７．０８−７．１６（１Ｈ，ｍ），７．２９−７．３６（１Ｈ，ｍ） Production Example 296
5- (3-thienylmethyl) isoxazole-3-carboxylic acid (600 mg, 2.87 mmol), tetrahydrofuran-3-ylmethylamine (319 mg, 2.3 mmol) and 1-hydroxybenzotriazole (465 mg, 3.44 mmol). Added to dichloromethane (15 mL) and stirred at 0 ° C. for 30 minutes. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (657 mg, 3.44 mmol) at room temperature, and the mixture was stirred for 16 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 0.5 mol / L hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

520 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (3-thienylmethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (309)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.59-1.72 (1H, m), 2.00-2.15 (1H, m), 2.50-2.60 ( 1H, m), 3.45 (2H, dd), 3.57 (1H, dd), 3.73 (1H, dd), 3.81-3.95 (2H, m), 4.15 (2H) , S), 6.43 (1H, s), 6.90 (1H, br s), 6.95-7.02 (1H, m), 7.08-7.16 (1H, m), 7 .29-7.36 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−フリルメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３１０）と記す。）３３０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７１（１Ｈ，ｍ），２．０２−２．１２（１Ｈ，ｍ），２．５０−２．６１（１Ｈ，ｍ），３．４５（２Ｈ，ｄｄ），３．５７（１Ｈ，ｄｄ），３．７６（１Ｈ，ｄｄ），３．８１−３．９２（２Ｈ，ｍ），４．３３（２Ｈ，ｓ），６．４９（１Ｈ，ｓ），６．８９（１Ｈ，ｂｒｓ），６．９２−７．００（２Ｈ，ｍ），７．２０−７．２２（１Ｈ，ｍ） Production Example 297
5- (2-furylmethyl) isoxazole-3-carboxylic acid (500 mg, 2.59 mmol), tetrahydrofuran-3-ylmethylamine (288 mg, 2.84 mmol) and 1-hydroxybenzotriazole (420 mg, 3.1 mmol). Added to dichloromethane (20 mL) and stirred at 0 ° C. for 30 minutes. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (601 mg, 3.1 mmol) at room temperature, and the mixture was stirred for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 0.5 mol / L hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

In this way, 330 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (2-furylmethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (310)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.71 (1H, m), 2.02-2.12 (1H, m), 2.50-2.61 ( 1H, m), 3.45 (2H, dd), 3.57 (1H, dd), 3.76 (1H, dd), 3.81-3.92 (2H, m), 4.33 (2H , S), 6.49 (1H, s), 6.89 (1H, brs), 6.92-7.00 (2H, m), 7.20-7.22 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−フリルメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３１１）と記す。）３１０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７１（１Ｈ，ｍ），２．０２−２．１２（１Ｈ，ｍ），２．５０−２．６１（１Ｈ，ｍ），３．４５（２Ｈ，ｄｄ），３．５７（１Ｈ，ｄｄ），３．７６（１Ｈ，ｄｄ），３．８１−３．９２（２Ｈ，ｍ），４．１５（２Ｈ，ｓ），６．４３（１Ｈ，ｓ），６．８９（１Ｈ，ｂｒｓ），６．９６−７．０２（１Ｈ，ｍ），７．１０−７．１４（１Ｈ，ｍ），７．３０−７．３４（１Ｈ，ｍ） Production Example 298
5- (3-furylmethyl) isoxazole-3-carboxylic acid (500 mg, 2.59 mmol), tetrahydrofuran-3-ylmethylamine (288 mg, 2.84 mmol) and 1-hydroxybenzotriazole (420 mg, 3.1 mmol). Added to dichloromethane (20 mL) and stirred at 0 ° C. for 30 minutes. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (601 mg, 3.1 mmol) at room temperature, and the mixture was stirred for 18 hours. Water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 0.5 mol / L hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

310 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (3-furylmethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (311)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.71 (1H, m), 2.02-2.12 (1H, m), 2.50-2.61 ( 1H, m), 3.45 (2H, dd), 3.57 (1H, dd), 3.76 (1H, dd), 3.81-3.92 (2H, m), 4.15 (2H) , S), 6.43 (1H, s), 6.89 (1H, brs), 6.96-7.02 (1H, m), 7.10-7.14 (1H, m), 7. 30-7.34 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−メトキシベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３１２）と記す。）６０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７１（１Ｈ，ｍ），２．０１−２．１２（１Ｈ，ｍ），２．５０−２．６１（１Ｈ，ｍ），３．４４（２Ｈ，ｄｄ），３．５７（１Ｈ，ｄｄ），３．７１−３．９４（３Ｈ，ｍ），３．８０（３Ｈ，ｓ），４．０８（２Ｈ，ｓ），６．４１（１Ｈ，ｓ），６．７６−６．８５（３Ｈ，ｍ），６．８９（１Ｈ，ｂｒ ｓ），７．２１−７．３０（１Ｈ，ｍ） Production Example 299
5- (3-methoxybenzyl) isoxazole-3-carboxylic acid (100 mg, 0.43 mmol), tetrahydrofuran-3-ylmethylamine (279 mg, 2.76 mmol), 1-hydroxybenzotriazole (69 mg, 0.51 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (98 mg, 0.51 mmol) and triethylamine (0.09 mL, 0.68 mmol) were added to chloroform (amylene-added product) (4 mL) at 0 ° C., Stir for 10 minutes at the same temperature. Then, it stirred at room temperature for 18 hours. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

60 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (3-methoxybenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (312)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.71 (1H, m), 2.01-2.12 (1H, m), 2.50-2.61 ( 1H, m), 3.44 (2H, dd), 3.57 (1H, dd), 3.71-3.94 (3H, m), 3.80 (3H, s), 4.08 (2H) , S), 6.41 (1H, s), 6.76-6.85 (3H, m), 6.89 (1H, br s), 7.21-7.30 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−トリフルオロメトキシベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３１３）と記す。）７８ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７４（１Ｈ，ｍ），２．００−２．１５（１Ｈ，ｍ），２．５０−２．６２（１Ｈ，ｍ），３．４５（２Ｈ，ｄｄ），３．５７（１Ｈ，ｄｄ），３．７０−３．９５（３Ｈ，ｍ），４．１４（２Ｈ，ｓ），６．４３（１Ｈ，ｓ），６．９０（１Ｈ，ｂｒ ｓ），７．０８−７．２２（３Ｈ，ｍ），７．３３−７．４２（１Ｈ，ｍ） Production Example 300
5- (3-trifluoromethoxybenzyl) isoxazole-3-carboxylic acid (100 mg, 0.35 mmol), tetrahydrofuran-3-ylmethylamine (39 mg, 0.38 mmol) and 1-hydroxybenzotriazole (55 mg, 0.41 mmol) ) Was added to dichloromethane (5 mL) and stirred at 0 ° C. for 30 minutes. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (65 mg, 0.41 mmol) at room temperature, and the mixture was stirred for 16 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 0.5 mol / L hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

78 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (3-trifluoromethoxybenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (313)) represented by formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.74 (1H, m), 2.00-2.15 (1H, m), 2.50-2.62 ( 1H, m), 3.45 (2H, dd), 3.57 (1H, dd), 3.70-3.95 (3H, m), 4.14 (2H, s), 6.43 (1H , S), 6.90 (1H, br s), 7.08-7.22 (3H, m), 7.33-7.42 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（４−メトキシベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３１４）と記す。）４８０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７１（１Ｈ，ｍ），２．０２−２．１２（１Ｈ，ｍ），２．５０−２．６１（１Ｈ，ｍ），３．４４（２Ｈ，ｄｄ），３．５６（１Ｈ，ｄｄ），３．７１−３．９３（３Ｈ，ｍ），３．８０（３Ｈ，ｓ），４．０５（２Ｈ，ｓ），６．３６（１Ｈ，ｓ），６．８４−６．９２（３Ｈ，ｍ），７．１３−７．１９（２Ｈ，ｍ） Production Example 301
5- (4-methoxybenzyl) isoxazole-3-carboxylic acid (600 mg, 2.57 mmol), tetrahydrofuran-3-ylmethylamine (286 mg, 2.83 mmol) and 1-hydroxybenzotriazole (416 mg, 3.08 mmol). Added to dichloromethane (15 mL) and stirred at 0 ° C. for 30 minutes. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (588 mg, 3.08 mmol) at room temperature, and the mixture was stirred for 16 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 0.5 mol / L hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

480 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (4-methoxybenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (314)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.71 (1H, m), 2.02-2.12 (1H, m), 2.50-2.61 ( 1H, m), 3.44 (2H, dd), 3.56 (1H, dd), 3.71-3.93 (3H, m), 3.80 (3H, s), 4.05 (2H) , S), 6.36 (1H, s), 6.84-6.92 (3H, m), 7.13-7.19 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（４−トリフルオロメトキシベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３１５）と記す。）３２０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７１（１Ｈ，ｍ），２．００−２．１２（１Ｈ，ｍ），２．５０−２．６１（１Ｈ，ｍ），３．４５（２Ｈ，ｄｄ），３．５７（１Ｈ，ｄｄ），３．７６（１Ｈ，ｄｄ），３．８０−３．９２（２Ｈ，ｍ），４．１３（２Ｈ，ｓ），６．４２（１Ｈ，ｓ），６．８９（１Ｈ，ｂｒ ｓ），７．１６−７．２２（２Ｈ，ｍ），７．２５−７．３２（２Ｈ，ｍ） Production Example 302
5- (4-trifluoromethoxybenzyl) isoxazole-3-carboxylic acid (500 mg, 1.74 mmol), tetrahydrofuran-3-ylmethylamine (194 mg, 1.91 mmol) and 1-hydroxybenzotriazole (282 mg, 2.09 mmol) ) Was added to dichloromethane (15 mL) and stirred at 0 ° C. for 30 minutes. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (399 mg, 2.1 mmol) at room temperature, the mixture was stirred for 16 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 0.5 mol / L hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

320 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (4-trifluoromethoxybenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (315)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.71 (1H, m), 2.00-2.12 (1H, m), 2.50-2.61 ( 1H, m), 3.45 (2H, dd), 3.57 (1H, dd), 3.76 (1H, dd), 3.80-3.92 (2H, m), 4.13 (2H) , S), 6.42 (1H, s), 6.89 (1H, br s), 7.16-7.22 (2H, m), 7.25-7.32 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（４−トリフルオロメチルベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３１６）と記す。）５１０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７１（１Ｈ，ｍ），２．０２−２．１２（１Ｈ，ｍ），２．５０−２．６１（１Ｈ，ｍ），３．４５（２Ｈ，ｄｄ），３．５７（１Ｈ，ｄｄ），３．７６（１Ｈ，ｄｄ），３．８０−３．９５（２Ｈ，ｍ），４．１９（２Ｈ，ｓ），６．４３（１Ｈ，ｓ），６．８９（１Ｈ，ｂｒ ｓ），７．３５−７．４０（２Ｈ，ｍ），７．５８−７．６４（２Ｈ，ｍ） Production Example 303
5- (4-trifluoromethylbenzyl) isoxazole-3-carboxylic acid (600 mg, 2.20 mmol), tetrahydrofuran-3-ylmethylamine (245 mg, 2.40 mmol) and 1-hydroxybenzotriazole (505 mg, 2.65 mmol) ) Was added to dichloromethane (10 mL) and stirred at 0 ° C. for 30 minutes. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (577 mg, 3.01 mmol) at room temperature, the mixture was stirred for 16 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 0.5 mol / L hydrochloric acid and saturated brine. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Thus, 510 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (4-trifluoromethylbenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (316)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.71 (1H, m), 2.02-2.12 (1H, m), 2.50-2.61 ( 1H, m), 3.45 (2H, dd), 3.57 (1H, dd), 3.76 (1H, dd), 3.80-3.95 (2H, m), 4.19 (2H) , S), 6.43 (1H, s), 6.89 (1H, br s), 7.35-7.40 (2H, m), 7.58-7.64 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−メトキシベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３１７）と記す。）５３６ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７１（１Ｈ，ｍ），２．００−２．１２（１Ｈ，ｍ），２．４８−２．６２（１Ｈ，ｍ），３．４３（２Ｈ，ｄｄ），３．５６（１Ｈ，ｄｄ），３．７０−３．９５（３Ｈ，ｍ），３．８２（３Ｈ，ｓ），４．１０（２Ｈ，ｓ），６．３３（１Ｈ，ｓ），６．８２−６．９５（３Ｈ，ｍ），７．１２−７．２０（１Ｈ，ｍ），７．２６−７．３２（１Ｈ，ｍ） Production Example 304
5- (2-methoxybenzyl) isoxazole-3-carboxylic acid (600 mg, 2.57 mmol), tetrahydrofuran-3-ylmethylamine (286 mg, 2.83 mmol) and 1-hydroxybenzotriazole (416 mg, 3.08 mmol). Added to dichloromethane (15 mL) and stirred at 0 ° C. for 30 minutes. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (588 mg, 3.08 mmol) at room temperature, and the mixture was stirred for 16 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 0.5 mol / L hydrochloric acid and saturated brine. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

536 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (2-methoxybenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (317)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.71 (1H, m), 2.00-2.12 (1H, m), 2.48-2.62 ( 1H, m), 3.43 (2H, dd), 3.56 (1H, dd), 3.70-3.95 (3H, m), 3.82 (3H, s), 4.10 (2H) , S), 6.33 (1H, s), 6.82-6.95 (3H, m), 7.12-7.20 (1H, m), 7.26-7.32 (1H, m )

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−フルオロベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３１８）と記す。）６２ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７２（１Ｈ，ｍ），２．０１−２．１３（１Ｈ，ｍ），２．４８−２．６３（１Ｈ，ｍ），３．４０−３．５０（２Ｈ，ｍ），３．５５−３．６０（１Ｈ，ｍ），３．７２−３．８０（１Ｈ，ｍ），３．８１−３．９５（２Ｈ，ｍ），４．１１（２Ｈ，ｓ），６．４３（１Ｈ，ｓ），６．９１（１Ｈ，ｂｒ ｓ），６．９２−７．０６（３Ｈ，ｍ），７．２７−７．３６（１Ｈ，ｍ） Production Example 305
5- (3-Fluorobenzyl) isoxazole-3-carboxylic acid (100 mg, 0.45 mmol), 1-hydroxybenzotriazole (73 mg, 0.54 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride Salt (103 mg, 0.50 mmol) and triethylamine (0.09 mL, 0.68 mmol) were added to chloroform (amylene-added product) (4 mL) at 0 ° C., and the mixture was stirred at the same temperature for 10 minutes. Tetrahydrofuran-3-ylmethylamine (50 mg, 0.50 mmol) was added to the mixture at room temperature, stirred for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

62 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (3-fluorobenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (318)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.72 (1H, m), 2.01-2.13 (1H, m), 2.48-2.63 ( 1H, m), 3.40-3.50 (2H, m), 3.55-3.60 (1H, m), 3.72-3.80 (1H, m), 3.81-3. 95 (2H, m), 4.11 (2H, s), 6.43 (1H, s), 6.91 (1H, br s), 6.92-7.06 (3H, m), 7. 27-7.36 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（４−フルオロベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３１９）と記す。）８０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７２（１Ｈ，ｍ），２．０１−２．１３（１Ｈ，ｍ），２．４８−２．６３（１Ｈ，ｍ），３．４０−３．４８（２Ｈ，ｍ），３．５５−３．６０（１Ｈ，ｍ），３．７０−３．７９（１Ｈ，ｍ），３．８０−３．９５（２Ｈ，ｍ），４．０９（２Ｈ，ｓ），６．３９（１Ｈ，ｓ），６．８９（１Ｈ，ｂｒ ｓ），７．００−７．０６（２Ｈ，ｍ），７．１８−７．２４（２Ｈ，ｍ） Production Example 306
5- (4-Fluorobenzyl) isoxazole-3-carboxylic acid (100 mg, 0.45 mmol), 1-hydroxybenzotriazole (73 mg, 0.54 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride Salt (103 mg, 0.50 mmol) and triethylamine (0.09 mL, 0.68 mmol) were added to chloroform (amylene-added product) (4 mL) at 0 ° C., and the mixture was stirred at the same temperature for 10 minutes. Tetrahydrofuran-3-ylmethylamine (50 mg, 0.50 mmol) was added to the mixture at room temperature, stirred for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

80 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (4-fluorobenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (319)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.72 (1H, m), 2.01-2.13 (1H, m), 2.48-2.63 ( 1H, m), 3.40-3.48 (2H, m), 3.55-3.60 (1H, m), 3.70-3.79 (1H, m), 3.80-3. 95 (2H, m), 4.09 (2H, s), 6.39 (1H, s), 6.89 (1H, br s), 7.00-7.06 (2H, m), 7. 18-7.24 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−フルオロベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３２０）と記す。）４５０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７２（１Ｈ，ｍ），２．０１−２．１３（１Ｈ，ｍ），２．４８−２．６３（１Ｈ，ｍ），３．４０−３．４８（２Ｈ，ｍ），３．５５−３．６０（１Ｈ，ｍ），３．７０−３．７９（１Ｈ，ｍ），３．８０−３．９５（２Ｈ，ｍ），４．１５（２Ｈ，ｓ），６．４１（１Ｈ，ｓ），６．９０（１Ｈ，ｂｒ ｓ），７．０４−７．１６（２Ｈ，ｍ），７．２１−７．３５（２Ｈ，ｍ） Production Example 307
5- (2-fluorobenzyl) isoxazole-3-carboxylic acid (600 mg, 2.71 mmol), 1-hydroxybenzotriazole (438 mg, 3.25 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride Salt (621 mg, 3.25 mmol) and triethylamine (0.57 mL, 4.07 mmol) were added to chloroform (amylene-added product) (10 mL) at 0 ° C., and the mixture was stirred at the same temperature for 10 minutes. Tetrahydrofuran-3-ylmethylamine (301 mg, 2.98 mmol) was added to the mixture at room temperature, stirred for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

450 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (2-fluorobenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (320)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.72 (1H, m), 2.01-2.13 (1H, m), 2.48-2.63 ( 1H, m), 3.40-3.48 (2H, m), 3.55-3.60 (1H, m), 3.70-3.79 (1H, m), 3.80-3. 95 (2H, m), 4.15 (2H, s), 6.41 (1H, s), 6.90 (1H, br s), 7.04-7.16 (2H, m), 7. 21-7.35 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−クロロベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３２１）と記す。）４７ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７２（１Ｈ，ｍ），２．０５−２．１３（１Ｈ，ｍ），２．５０−２．６２（１Ｈ，ｍ），３．４０−３．５０（２Ｈ，ｍ），３．５５−３．６２（１Ｈ，ｍ），３．７２−３．８０（１Ｈ，ｍ），３．８０−３．９５（２Ｈ，ｍ），４．１０（２Ｈ，ｓ），６．４３（１Ｈ，ｓ），６．８９（１Ｈ，ｂｒ ｓ），７．１０−７．１７（１Ｈ，ｍ），７．２２−７．３２（３Ｈ，ｍ） Production Example 308
5- (3-chlorobenzyl) isoxazole-3-carboxylic acid (100 mg, 0.42 mmol), 1-hydroxybenzotriazole (69 mg, 0.51 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride Salt (98 mg, 0.51 mmol) and triethylamine (0.09 mL, 0.64 mmol) were added to chloroform (amylene-added product) (4 mL) at 0 ° C., and the mixture was stirred at the same temperature for 10 minutes. Tetrahydrofuran-3-ylmethylamine (48 mg, 0.47 mmol) was added to the mixture at room temperature, stirred for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

47 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (3-chlorobenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (321)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.72 (1H, m), 2.05-2.13 (1H, m), 2.50-2.62 ( 1H, m), 3.40-3.50 (2H, m), 3.55-3.62 (1H, m), 3.72-3.80 (1H, m), 3.80-3. 95 (2H, m), 4.10 (2H, s), 6.43 (1H, s), 6.89 (1H, br s), 7.10-7.17 (1H, m), 7. 22-7.32 (3H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（４−クロロベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３２２）と記す。）７０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．５８−１．７１（１Ｈ，ｍ），２．００−２．１２（１Ｈ，ｍ），２．５０−２．６２（１Ｈ，ｍ），３．４０−３．４９（２Ｈ，ｍ），３．５３−３．６０（１Ｈ，ｍ），３．７０−３．８０（１Ｈ，ｍ），３．８１−３．９５（２Ｈ，ｍ），４．０９（２Ｈ，ｓ），６．４０（１Ｈ，ｓ），６．８９（１Ｈ，ｂｒ ｓ），７．１８（２Ｈ，ｄ），７．３１（２Ｈ，ｄ） Production Example 309
5- (4-Chlorobenzyl) isoxazole-3-carboxylic acid (100 mg, 0.42 mmol), tetrahydrofuran-3-ylmethylamine (52 mg, 0.50 mmol) and 1-hydroxybenzotriazole (6 mg, 0.04 mmol). It added to chloroform (amylene addition product) (3 mL) at 0 degreeC, and stirred for 10 minutes at the same temperature. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (97 mg, 0.50 mmol) at room temperature, and the mixture was stirred for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 0.5 mol / L hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

70 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (4-chlorobenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (322)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.58-1.71 (1H, m), 2.00-2.12 (1H, m), 2.50-2.62 ( 1H, m), 3.40-3.49 (2H, m), 3.53-3.60 (1H, m), 3.70-3.80 (1H, m), 3.81-3. 95 (2H, m), 4.09 (2H, s), 6.40 (1H, s), 6.89 (1H, br s), 7.18 (2H, d), 7.31 (2H, d)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−クロロベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３２３）と記す。）６７ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７２（１Ｈ，ｍ），２．０１−２．１２（１Ｈ，ｍ），２．５０−２．６２（１Ｈ，ｍ），３．４０−３．４８（２Ｈ，ｍ），３．５４−３．６０（１Ｈ，ｍ），３．７１−３．８０（１Ｈ，ｍ），３．８０−３．９５（２Ｈ，ｍ），４．２５（２Ｈ，ｓ），６．３９（１Ｈ，ｓ），６．９０（１Ｈ，ｂｒ ｓ），７．２１−７．３２（３Ｈ，ｍ），７．３７−７．４５（１Ｈ，ｍ） Production Example 310
5- (2-chlorobenzyl) isoxazole-3-carboxylic acid (100 mg, 0.42 mmol), tetrahydrofuran-3-ylmethylamine (52 mg, 0.50 mmol) and 1-hydroxybenzotriazole (6 mg, 0.04 mmol). It added to chloroform (amylene addition product) (3 mL) at 0 degreeC, and stirred for 10 minutes at the same temperature. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (97 mg, 0.50 mmol) at room temperature, and the mixture was stirred for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 0.5 mol / L hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

67 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (2-chlorobenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (323)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.72 (1H, m), 2.01-2.12 (1H, m), 2.50-2.62 ( 1H, m), 3.40-3.48 (2H, m), 3.54-3.60 (1H, m), 3.71-3.80 (1H, m), 3.80-3. 95 (2H, m), 4.25 (2H, s), 6.39 (1H, s), 6.90 (1H, br s), 7.21-7.32 (3H, m), 7. 37-7.45 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２，３，４−トリフルオロベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３２４）と記す。）３２０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７１（１Ｈ，ｍ），２．０２−２．１２（１Ｈ，ｍ），２．５０−２．６２（１Ｈ，ｍ），３．４５（２Ｈ，ｄｄ），３．５７（１Ｈ，ｄｄ），３．７６（１Ｈ，ｄｄ），３．８１−３．９３（２Ｈ，ｍ），４．１５（２Ｈ，ｓ），６．４５（１Ｈ，ｍ），６．８９（１Ｈ，ｂｒ ｓ），６．９１−７．０２（２Ｈ，ｍ） Production Example 311
5- (2,3,4-trifluorobenzyl) isoxazole-3-carboxylic acid (450 mg, 1.75 mmol), tetrahydrofuran-3-ylmethylamine (195 mg, 1.93 mmol) and 1-hydroxybenzotriazole (284 mg, 2.1 mmol) was added to dichloromethane (10 mL) and stirred at 0 ° C. for 30 minutes. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (401 mg, 2.10 mmol) at room temperature, the mixture was stirred for 16 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 0.5 mol / L hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

320 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (2,3,4-trifluorobenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (324)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.71 (1H, m), 2.02-2.12 (1H, m), 2.50-2.62 ( 1H, m), 3.45 (2H, dd), 3.57 (1H, dd), 3.76 (1H, dd), 3.81-3.93 (2H, m), 4.15 (2H) , S), 6.45 (1H, m), 6.89 (1H, br s), 6.91-7.02 (2H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３，４−ジクロロベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３２５）と記す。）５２０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７１（１Ｈ，ｍ），２．０５−２．１２（１Ｈ，ｍ），２．５０−２．６１（１Ｈ，ｍ），３．４５（２Ｈ，ｄｄ），３．５７（１Ｈ，ｄｄ），３．７６（１Ｈ，ｄｄ），３．８１−３．９２（２Ｈ，ｍ），４．０８（２Ｈ，ｓ），６．４４（１Ｈ，ｓ），６．８９（１Ｈ，ｂｒ ｓ），７．０９（１Ｈ，ｄｄ），７．３４（１Ｈ，ｄ），７．４２（１Ｈ，ｄ） Production Example 312
5- (3,4-dichlorobenzyl) isoxazole-3-carboxylic acid (600 mg, 2.20 mmol), tetrahydrofuran-3-ylmethylamine (245 mg, 2.42 mmol) and 1-hydroxybenzotriazole (357 mg, 2.64 mmol) ) Was added to dichloromethane (15 mL) and stirred at 0 ° C. for 30 minutes. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (505 mg, 2.64 mmol) at room temperature, and the mixture was stirred for 16 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 0.5 mol / L hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

520 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (3,4-dichlorobenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (325)) represented by formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.71 (1H, m), 2.05-2.12 (1H, m), 2.50-2.61 ( 1H, m), 3.45 (2H, dd), 3.57 (1H, dd), 3.76 (1H, dd), 3.81-3.92 (2H, m), 4.08 (2H) , S), 6.44 (1H, s), 6.89 (1H, br s), 7.09 (1H, dd), 7.34 (1H, d), 7.42 (1H, d)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−フェニルベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３２６）と記す。）３００ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７１（１Ｈ，ｍ），２．００−２．１２（１Ｈ，ｍ），２．４８−２．６１（１Ｈ，ｍ），３．４３（２Ｈ，ｄｄ），３．５６（１Ｈ，ｄｄ），３．７５（１Ｈ，ｄｄ），３．８１−３．９２（２Ｈ，ｍ），４．０６（２Ｈ，ｓ），６．２２（１Ｈ，ｓ），６．８６（１Ｈ，ｂｒ ｓ），７．２０−７．４６（９Ｈ，ｍ） Production Example 313
5- (2-phenylbenzyl) isoxazole-3-carboxylic acid (500 mg, 1.79 mmol), 1-hydroxybenzotriazole (290 mg, 2.15 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride Salt (410 mg, 2.15 mmol) and triethylamine (0.37 mL, 2.68 mmol) were added to chloroform (amylene-added product) (20 mL) at 0 ° C., and the mixture was stirred at the same temperature for 10 minutes. Tetrahydrofuran-3-ylmethylamine (199 mg, 1.97 mmol) was added to the mixture at room temperature, stirred for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

300 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (2-phenylbenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (326)) represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.71 (1H, m), 2.00-2.12 (1H, m), 2.48-2.61 ( 1H, m), 3.43 (2H, dd), 3.56 (1H, dd), 3.75 (1H, dd), 3.81-3.92 (2H, m), 4.06 (2H) , S), 6.22 (1H, s), 6.86 (1H, br s), 7.20-7.46 (9H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−フェニルベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３２７）と記す。）３００ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．５８−１．７２（１Ｈ，ｍ），１．９８−２．１２（１Ｈ，ｍ），２．４５−２．６２（１Ｈ，ｍ），３．３８−３．４９（２Ｈ，ｍ），３．５２−３．６２（１Ｈ，ｍ），３．７０−３．９５（３Ｈ，ｍ），４．１８（２Ｈ，ｓ），６．４４（１Ｈ，ｓ），６．８９（１Ｈ，ｂｒ ｓ），７．２０−７．６０（９Ｈ，ｍ） Production Example 314
5- (3-phenylbenzyl) isoxazole-3-carboxylic acid (500 mg, 1.79 mmol), 1-hydroxybenzotriazole (290 mg, 2.15 mmol), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride Salt (410 mg, 2.15 mmol) and triethylamine (0.37 mL, 2.68 mmol) were added to chloroform (amylene-added product) (12 mL) at 0 ° C., and the mixture was stirred at the same temperature for 10 minutes. Tetrahydrofuran-3-ylmethylamine (199 mg, 1.97 mmol) was added to the mixture at room temperature, stirred for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 300 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (3-phenylbenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (327)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.58-1.72 (1H, m), 1.98-2.12 (1H, m), 2.45-2.62 ( 1H, m), 3.38-3.49 (2H, m), 3.52-3.62 (1H, m), 3.70-3.95 (3H, m), 4.18 (2H, s), 6.44 (1H, s), 6.89 (1H, br s), 7.20-7.60 (9H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（３−メチルベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３２８）と記す。）５３ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７２（１Ｈ，ｍ），２．００−２．１２（１Ｈ，ｍ），２．３４（３Ｈ，ｓ），２．４８−２．６２（１Ｈ，ｍ），３．４０−３．４８（２Ｈ，ｍ），３．５２−３．６０（１Ｈ，ｍ），３．７０−３．８０（１Ｈ，ｍ），３．８１−３．９５（２Ｈ，ｍ），４．０７（２Ｈ，ｓ），６．３９（１Ｈ，ｓ），６．８９（１Ｈ，ｂｒ ｓ），７．００−７．１５（３Ｈ，ｍ），７．２０−７．２６（１Ｈ，ｍ） Production Example 315
5- (3-methylbenzyl) isoxazole-3-carboxylic acid (100 mg, 0.42 mmol), tetrahydrofuran-3-ylmethylamine (52 mg, 0.50 mmol), triethylamine (0.15 mL, 1.05 mmol) and 1- Hydroxybenzotriazole (6 mg, 0.04 mmol) was added to chloroform (amylene-added product) (3 mL) at 0 ° C., and the mixture was stirred at the same temperature for 10 minutes. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (97 mg, 0.50 mmol) at room temperature, and the mixture was stirred for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 0.5 mol / L hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

53 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (3-methylbenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (328)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.72 (1H, m), 2.00-2.12 (1H, m), 2.34 (3H, s) 2.48-2.62 (1H, m), 3.40-3.48 (2H, m), 3.52-3.60 (1H, m), 3.70-3.80 (1H, m), 3.81-3.95 (2H, m), 4.07 (2H, s), 6.39 (1H, s), 6.89 (1H, br s), 7.00-7. 15 (3H, m), 7.20-7.26 (1H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（４−メチルベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３２９）と記す。）４９ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７０（１Ｈ，ｍ），２．０１−２．１２（１Ｈ，ｍ），２．３４（３Ｈ，ｓ），２．５０−２．６２（１Ｈ，ｍ），３．４０−３．４８（２Ｈ，ｍ），３．５５−３．６０（１Ｈ，ｍ），３．７２−３．８０（１Ｈ，ｍ），３．８１−３．９２（２Ｈ，ｍ），４．０７（２Ｈ，ｓ），６．３７（１Ｈ，ｓ），６．８９（１Ｈ，ｂｒ ｓ），７．１０−７．１８（４Ｈ，ｍ） Production Example 316
5- (4-methylbenzyl) isoxazole-3-carboxylic acid (100 mg, 0.42 mmol), tetrahydrofuran-3-ylmethylamine (52 mg, 0.50 mmol), triethylamine (0.15 mL, 1.05 mmol) and 1- Hydroxybenzotriazole (6 mg, 0.04 mmol) was added to chloroform (amylene-added product) (3 mL) at 0 ° C., and the mixture was stirred at the same temperature for 10 minutes. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (97 mg, 0.50 mmol) at room temperature, and the mixture was stirred for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 0.5 mol / L hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

49 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (4-methylbenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (329)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.70 (1H, m), 2.01-2.12 (1H, m), 2.34 (3H, s) , 2.50-2.62 (1H, m), 3.40-3.48 (2H, m), 3.55-3.60 (1H, m), 3.72-3.80 (1H, m), 3.81-3.92 (2H, m), 4.07 (2H, s), 6.37 (1H, s), 6.89 (1H, br s), 7.10-7. 18 (4H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−メチルベンジル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３３０）と記す。）４５ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６０−１．７１（１Ｈ，ｍ），２．００−２．１２（１Ｈ，ｍ），２．２９（３Ｈ，ｓ），２．４８−２．６０（１Ｈ，ｍ），３．４０−３．４８（２Ｈ，ｍ），３．５５−３．６０（１Ｈ，ｍ），３．７２−３．８０（１Ｈ，ｍ），３．８１−３．９３（２Ｈ，ｍ），４．１０（２Ｈ，ｓ），６．２８（１Ｈ，ｓ），６．８９（１Ｈ，ｂｒ ｓ），７．１４−７．２２（４Ｈ，ｍ） Production Example 317
5- (2-methylbenzyl) isoxazole-3-carboxylic acid (100 mg, 0.42 mmol), tetrahydrofuran-3-ylmethylamine (52 mg, 0.50 mmol), triethylamine (0.15 mL, 1.05 mmol) and 1- Hydroxybenzotriazole (6 mg, 0.04 mmol) was added to chloroform (amylene-added product) (3 mL) at 0 ° C., and the mixture was stirred at the same temperature for 10 minutes. To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (97 mg, 0.50 mmol) at room temperature, and the mixture was stirred for 18 hours, water was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed successively with 0.5 mol / L hydrochloric acid and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

45 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (2-methylbenzyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (330)) represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.60-1.71 (1H, m), 2.00-2.12 (1H, m), 2.29 (3H, s) , 2.48-2.60 (1H, m), 3.40-3.48 (2H, m), 3.55-3.60 (1H, m), 3.72-3.80 (1H, m), 3.81-3.93 (2H, m), 4.10 (2H, s), 6.28 (1H, s), 6.89 (1H, br s), 7.14-7. 22 (4H, m)

で示されるＮ−（３−メチルオキセタン−３−イルメチル）−５−［３−（２−ナフチル）プロピル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３３２）と記す。）０．４９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３６（３Ｈ，ｓ），２．１０−２．１８（２Ｈ，ｍ），２．８２−２．８８（４Ｈ，ｍ），３．６５（２Ｈ，ｄ），４．４１（２Ｈ，ｄ），４．５４（２Ｈ，ｄ），６．４９（１Ｈ，ｓ），７．０７（１Ｈ，ｂｒｓ），７．３１−７．３３（１Ｈ，ｍ），７．４１−７．４９（２Ｈ，ｍ），７．６２（１Ｈ，ｓ），７．７７−７．８２（３Ｈ，ｍ） Production Example 318
5- [3- (2-naphthyl) propyl] isoxazole-3-carboxylic acid (0.42 g, 1.5 mmol), (3-methyloxetan-3-yl) methylamine (0.18 g, 1.8 mmol) and 1-Hydroxybenzotriazole (0.02 g, 0.15 mmol) was added to chloroform (amylene-added product) (5.0 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.34 g, 1.8 mmol) at room temperature, and the mixture was stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was passed through a silica gel short column to remove impurities, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (3-methyloxetane-3-ylmethyl) -5- [3- (2-naphthyl) propyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (332)) 0.49 g Got.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.36 (3H, s), 2.10-2.18 (2H, m), 2.82-2.88 (4H, m) 3.65 (2H, d), 4.41 (2H, d), 4.54 (2H, d), 6.49 (1H, s), 7.07 (1H, brs), 7.31- 7.33 (1H, m), 7.41-7.49 (2H, m), 7.62 (1H, s), 7.77-7.82 (3H, m)

で示されるＮ−（３−メチルオキセタン−３−イルメチル）−５−（２−ナフチルメトキシメチル）イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３３３）と記す。）０．６７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３６（３Ｈ，ｓ），３．６６（２Ｈ，ｄ），４．４２（２Ｈ，ｄ），４．５４（２Ｈ，ｄ），４．６８（２Ｈ，ｓ），４．７７（２Ｈ，ｓ），６．７６（１Ｈ，ｓ），７．１０（１Ｈ，ｂｒｓ），７．４６−７．５２（３Ｈ，ｍ），７．７９（１Ｈ，ｓ），７．８３−７．８７（３Ｈ，ｍ） Production Example 319
5- (2-naphthylmethoxymethyl) isoxazole-3-carboxylic acid (0.57 g, 2.0 mmol), (3-methyloxetane-3-yl) methylamine (0.24 g, 2.4 mmol) and 1-hydroxy Benzotriazole (0.03 g, 0.2 mmol) was added to chloroform (amylene-added product) (6.0 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.46 g, 2.4 mmol) at room temperature, and the mixture was stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was passed through a silica gel short column to remove impurities, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.67 g of N- (3-methyloxetane-3-ylmethyl) -5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (hereinafter referred to as the present compound (333)) represented by the formula: .
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.36 (3H, s), 3.66 (2H, d), 4.42 (2H, d), 4.54 (2H, d ), 4.68 (2H, s), 4.77 (2H, s), 6.76 (1H, s), 7.10 (1H, brs), 7.46-7.52 (3H, m) , 7.79 (1H, s), 7.83-7.87 (3H, m)

で示されるＮ−（３−メチルオキセタン−３−イルメチル）−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（３３４）と記す。）０．２９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．３７（３Ｈ，ｓ），３．６６（２Ｈ，ｄ），４．４２（２Ｈ，ｄ），４．５４（２Ｈ，ｄ），４．６１（２Ｈ，ｓ），４．６５（２Ｈ，ｓ），６．７４（１Ｈ，ｓ），７．０８（１Ｈ，ｂｒｓ），７．３１−７．４０（５Ｈ，ｍ） Production Example 320
5-Benzyloxymethylisoxazole-3-carboxylic acid (0.24 g, 1.0 mmol), (3-methyloxetane-3-yl) methylamine (0.12 g, 1.2 mmol) and 1-hydroxybenzotriazole (0.01 g, 0.1 mmol) was added to chloroform (amylene-added product) (2.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.24 g, 1.2 mmol) at room temperature, and the mixture was stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was passed through a silica gel short column to remove impurities, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.29 g of N- (3-methyloxetane-3-ylmethyl) -5-benzyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (334)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.37 (3H, s), 3.66 (2H, d), 4.42 (2H, d), 4.54 (2H, d ), 4.61 (2H, s), 4.65 (2H, s), 6.74 (1H, s), 7.08 (1H, brs), 7.31-7.40 (5H, m)

で示されるＮ−（２，２−ジメチルテトラヒドロピラン-４-イル）−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（３３５）と記す。）０．２９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．２６（３Ｈ，ｓ），１．２９（３Ｈ，ｓ），１．３３−１．４０（１Ｈ，ｍ），１．４１−１．５２（１Ｈ，ｍ），１．８９−２．００（２Ｈ，ｍ），３．７２−３．８４（２Ｈ，ｍ），４．２７−４．３８（１Ｈ，ｍ），４．６１（２Ｈ，ｓ），４．６５（２Ｈ，ｓ），６．６２（１Ｈ，ｂｒ ｓ），６．７２（１Ｈ，ｓ），７．３０−７．４０（５Ｈ，ｍ） Production Example 321
5-benzyloxymethylisoxazole-3-carboxylic acid (0.24 g, 1.0 mmol), 4-amino-2,2-dimethyltetrahydropyran (0.18 ml, 1.2 mmol) and 1-hydroxybenzotriazole ( 0.01 g, 0.1 mmol) was added to chloroform (amylene-added product) (2.5 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.24 g, 1.2 mmol) at room temperature, and the mixture was stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was passed through a silica gel short column to remove impurities, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.29 g of N- (2,2-dimethyltetrahydropyran-4-yl) -5-benzyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (335)) represented by the formula: It was.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.26 (3H, s), 1.29 (3H, s), 1.33-1.40 (1H, m), 1.41 -1.52 (1H, m), 1.89-2.00 (2H, m), 3.72-3.84 (2H, m), 4.27-4.38 (1H, m), 4 .61 (2H, s), 4.65 (2H, s), 6.62 (1H, br s), 6.72 (1H, s), 7.30-7.40 (5H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−［（５−ベンゾチオフェニル）メトキシメチル］イソキサゾール−３−カルボキシアミド（以下、本発明化合物（３３６）と記す。）０．１３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）： ７．８８（１Ｈ，ｄ）,７．８０（１Ｈ，ｓ）,７．４８（１Ｈ，ｄ）,７．３４（２Ｈ，ｄｔ）,６．９７−６．９０（１Ｈ，ｍ）,６．７４（１Ｈ，ｓ）,４．７３（２Ｈ，ｓ）,４．６７（２Ｈ，ｓ）,３．９２（１Ｈ，ｔｄ）,３．８６（１Ｈ，ｄｄ）,３．７７（１Ｈ，ｄｄ），３.５９（１Ｈ，ｄｄ）,３．４７（２Ｈ，ｔ）,２．６３−２．５３（１Ｈ，ｍ）,２．１０（１Ｈ，ｔｔ）,１．６８（１Ｈ，ｔｔ） Production Example 322
To 2.0 ml of a chloroform (amylene-added product) solution of 5-[(5-benzothiophenyl) methoxymethyl] isoxazole-3-carboxylic acid (0.24 g, 0.83 mmol) was added 1-hydroxybenzotriazole (0.01 g). , 0.08 mmol) and stirred at room temperature for 15 minutes. Tetrahydrofuran-3-ylmethylamine hydrochloride (0.14 g, 1.0 mmol) and triethylamine (0.14 mL, 1.0 mmol) were added to the mixture at room temperature, and the mixture was stirred for 30 minutes. Furthermore, 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.19 g, 1.0 mmol) was added at room temperature, and the mixture was stirred overnight, followed by addition of 1N hydrochloric acid and extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.13 g of N- (tetrahydrofuran-3-ylmethyl) -5-[(5-benzothiophenyl) methoxymethyl] isoxazole-3-carboxamide (hereinafter referred to as the present compound (336)) represented by the formula: It was.
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.88 (1H, d), 7.80 (1H, s), 7.48 (1H, d), 7.34 (2H, dt) 6.97-6.90 (1H, m), 6.74 (1H, s), 4.73 (2H, s), 4.67 (2H, s), 3.92 (1H, td), 3.86 (1H, dd), 3.77 (1H, dd), 3.59 (1H, dd), 3.47 (2H, t), 2.63-2.53 (1H, m), 2 .10 (1H, tt), 1.68 (1H, tt)

で示されるＮ−（オキセタン−３−イルメチル）−５−ベンジルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（３３７）と記す。）０．１９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：３．２３−３．３３（１Ｈ，ｍ），３．７５（２Ｈ，ｔ），４．４７（２Ｈ，ｔ），４．６１（２Ｈ，ｓ），４．６５（２Ｈ，ｓ），４．８１−４．８４（２Ｈ，ｍ），６．７３（１Ｈ，ｓ），７．０５（１Ｈ，ｂｒｓ），７．３０−７．４０（５Ｈ，ｍ） Production Example 323
3-Aminomethyloxetane hydrochloride (0.15 g, 1.2 mmol) and triethylamine (0.17 mL, 1.2 mmol) were added to chloroform (amylene-added product) (2.5 mL), and the mixture was stirred at room temperature for 30 minutes. To the mixture at room temperature 5-benzyloxymethylisoxazole-3-carboxylic acid (0.24 g, 1.0 mmol), 1-hydroxybenzotriazole (0.01 g, 0.1 mmol) and 1-ethyl-3- ( 3-Dimethylaminopropyl) carbodiimide hydrochloride (0.24 g, 1.2 mmol) was added and stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with chloroform. The organic layer was passed through a silica gel short column to remove impurities, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.19 g of N- (oxetane-3-ylmethyl) -5-benzyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (337)) represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 3.23-3.33 (1H, m), 3.75 (2H, t), 4.47 (2H, t), 4.61 (2H, s), 4.65 (2H, s), 4.81-4.84 (2H, m), 6.73 (1H, s), 7.05 (1H, brs), 7.30- 7.40 (5H, m)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−ナフチルメトキシメチル）−４−エチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（３３８）と記す。）０．０１６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．１９（ｔ，３Ｈ），１．６５−１．７２（ｍ，１Ｈ），２．０４−２．１３（ｍ，１Ｈ），２．５６−２．６１（ｍ，１Ｈ），２．７１（ｑ，２Ｈ），３．４４−３．４９（ｍ，２Ｈ），３．５７−３．６２（ｍ，１Ｈ），３．７４−３．８０（ｍ，1Ｈ），３．８４−３．９４（ｍ，２Ｈ），４．６３（ｓ，２Ｈ），４．７４（ｓ，２Ｈ），６．９７（ｂｒｓ，１Ｈ），７．４４−７．５１（ｍ，３Ｈ），７．７５−７．８７（ｍ，４Ｈ）
製造例３２５
５−プロパルギルオキシメチルイソキサゾール−３−カルボン酸（２．８８ｇ，１５．９ｍｍｏｌ）、テトラヒドロフラン−３−イルメチルアミン塩酸塩（２．７２ｇ，１９．８ｍｍｏｌ）、トリエチルアミン（１．９４ｇ，１９．８ｍｍｏｌ）および１−ヒドロキシベンゾトリアゾール（０．２２ｇ，１．５９ｍｍｏｌ）をクロロホルム（アミレン添加品）（３０ｍＬ）に加えた。混合物に、室温で１−エチル−３−（３−ジメチルアミノプロピル）カルボジイミド塩酸塩（３．８０ｇ，１９．８ｍｍｏｌ）を加えた後、室温で一晩攪拌し、減圧下濃縮した。濃縮物に希塩酸を加え、酢酸エチルで２回抽出した。有機層を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した後、減圧下濃縮した。残渣をシリカゲルカラムクロマトグラフィーに付し、下式

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−プロパルギルオキシメチルイソキサゾール−３−カルボキシアミド（以下、本発明化合物（３３９）と記す。）２．９５gを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６２−１．７３（ｍ，１Ｈ），２．０４−２．１４（ｍ，１Ｈ），２．５２−２．６３（ｍ，２Ｈ），３．４４−３．４９（ｍ，２Ｈ），３．５９（ｄｄ，１Ｈ），３．７３−３．８０（ｍ，1Ｈ），３．８３−３．９５（ｍ，２Ｈ），４．２５（ｄ，２Ｈ），４．７５（ｄ，２Ｈ），６．７５（ｓ，１Ｈ），６．９４（ｂｒ ｓ，１Ｈ） Production Example 324
To a solution of N- (tetrahydrofuran-3-ylmethyl) -5- (2-naphthylmethoxymethyl) isoxazole-3-carboxamide (0.5 g, 1.36 mmol) in tetrahydrofuran (7 mL) at −65 ° C. or lower in a nitrogen atmosphere. 1.6 mol / L-n-butyllithium hexane solution (1.9 mL, 3.00 mmol) was added dropwise and stirred at −60 ° C. or lower for 1 hour, and then iodoethane (0.14 mL, 1.77 mmol) was added. The mixture was stirred overnight while gradually returning to room temperature. Under ice-cooling, the reaction mixture was poured into 1 mol / L hydrochloric acid, and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5- (2-naphthylmethoxymethyl) -4-ethylisoxazole-3-carboxamide represented by the formula (hereinafter referred to as the present compound (338)) 0.016 g Got.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.19 (t, 3H), 1.65-1.72 (m, 1H), 2.04-2.13 (m, 1H) 2.56-2.61 (m, 1H), 2.71 (q, 2H), 3.44-3.49 (m, 2H), 3.57-3.62 (m, 1H), 3 74-3.80 (m, 1H), 3.84-3.94 (m, 2H), 4.63 (s, 2H), 4.74 (s, 2H), 6.97 (brs, 1H) ), 7.44-7.51 (m, 3H), 7.75-7.87 (m, 4H)
Production Example 325
5-propargyloxymethylisoxazole-3-carboxylic acid (2.88 g, 15.9 mmol), tetrahydrofuran-3-ylmethylamine hydrochloride (2.72 g, 19.8 mmol), triethylamine (1.94 g, 19. 8 mmol) and 1-hydroxybenzotriazole (0.22 g, 1.59 mmol) were added to chloroform (amylene-added product) (30 mL). To the mixture was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (3.80 g, 19.8 mmol) at room temperature, and the mixture was stirred overnight at room temperature and concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

N- (tetrahydrofuran-3-ylmethyl) -5-propargyloxymethylisoxazole-3-carboxamide (hereinafter referred to as the present compound (339)) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.62-1.73 (m, 1H), 2.04-2.14 (m, 1H), 2.52-2.63 ( m, 2H), 3.44-3.49 (m, 2H), 3.59 (dd, 1H), 3.73-3.80 (m, 1H), 3.83-3.95 (m, 2H), 4.25 (d, 2H), 4.75 (d, 2H), 6.75 (s, 1H), 6.94 (brs, 1H)

Next, production examples of intermediate compounds are shown as reference production examples. Here, Et represents an ethyl group.

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（ペント−１−イニル）−１，３，４−チアジアゾール−２−カルボキシアミド８５０ｍｇを粗生成物として得た。該粗生成物はそのまま次の反応に供した。 Reference production example 1
To a solution of ethyl 5-pent-1-ynyl-1,3,4-thiadiazole-2-carboxylate (950 mg, 4.24 mmol) in N, N-dimethylformamide (6 mL), triethylamine (1.6 mL) and tetrahydrofuran- 3-ylmethylamine hydrochloride (1.12 g, 8.14 mmol) was added. The mixture was stirred at 40 ° C. for 20 minutes under ultrasonic irradiation, cooled, diluted with ethyl acetate, washed successively with 3% hydrochloric acid and saturated brine, and the organic layer was dried over anhydrous sodium sulfate. Concentrate under reduced pressure and subject the residue to silica gel column chromatography.

As a crude product, 850 mg of N- (tetrahydrofuran-3-ylmethyl) -5- (pent-1-ynyl) -1,3,4-thiadiazole-2-carboxamide represented by the formula: The crude product was directly subjected to the next reaction.

で示される５−ペント−１−イニル−１，３，４−チアジアゾール−２−カルボン酸エチルエステル０．９５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．０７（ｔ，３Ｈ）、１．４６（ｔ，３Ｈ）、１．７０（ｍ，２Ｈ）、２．５１（ｔ，２Ｈ）、４．５２（ｑ，２Ｈ） Reference production example 2
5-chloro-1,3,4-thiadiazole-2-carboxylic acid ethyl ester (1.00 g, 5.19 mmol), 1-pentyne (530 mg, 7.79 mmol), triethylamine (2.9 mL, 20.8 mmol), Copper iodide (20 mg, 0.10 mmol) and dichlorobis (triphenylphosphine) palladium (73 mg, 0.10 mmol) were added, and the mixture was stirred at room temperature for 7 hours and 30 minutes in a nitrogen atmosphere. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with aqueous ammonia, 1.5% hydrochloric acid and saturated brine, and dried over anhydrous sodium sulfate. The residue was subjected to silica gel column chromatography.

0.95 g of 5-pent-1-ynyl-1,3,4-thiadiazole-2-carboxylic acid ethyl ester represented by
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.07 (t, 3H), 1.46 (t, 3H), 1.70 (m, 2H), 2.51 (t, 2H) 4.52 (q, 2H)

で示される５−プロピル−イソキサゾール−３−カルボン酸エチル０．６６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．００（３Ｈ，ｔ），１．４２（３Ｈ，ｔ），１．７６（２Ｈ，ｄｔ），２．７８（２Ｈ，ｔ），４．４３（２Ｈ，ｑ），６．４２（１Ｈ，ｓ） Reference production example 3
2-Chloro-2- (hydroxyimino) ethyl acetate (4.54 g, 30 mmol) and 1-pentyne (1.70 g, 25 mmol) were added to N, N-dimethylformamide (50 mL), and triethylamine (3. (03 g, 30 mmol) was added, and the mixture was stirred overnight at room temperature. Dilute hydrochloric acid was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.66 g of ethyl 5-propyl-isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.00 (3H, t), 1.42 (3H, t), 1.76 (2H, dt), 2.78 (2H, t ), 4.43 (2H, q), 6.42 (1H, s)

で示される５−プロピルイソキサゾール−３−カルボン酸０．２７ｇを得た。得られたカルボン酸は精製することなく次の反応に供した。 Reference production example 4
Ethyl 5-propylisoxazole-3-carboxylate (0.66 g, 3.6 mmol) was added to ethanol (20 mL), and potassium hydroxide (0.40 g, 7.2 mmol) and water (10 mL) were added. After stirring overnight at room temperature, the mixture was concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

Thus, 0.27 g of 5-propylisoxazole-3-carboxylic acid represented by the following formula was obtained. The obtained carboxylic acid was subjected to the next reaction without purification.

で示される５−ブチルイソキサゾール−３−カルボン酸エチル０．７１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： ０．９５（３Ｈ，ｔ），１．４０（５Ｈ，ｍ），１．７４−１．６７（２Ｈ，ｍ），２．８０（２Ｈ，ｔ），４．４３（２Ｈ，ｑ），６．４０（１Ｈ，ｓ） Reference production example 5
2-Chloro-2- (hydroxyimino) ethyl acetate (4.54 g, 30 mmol), 1-hexyne (2.05 g, 25 mmol) was added to N, N-dimethylformamide (50 mL). Triethylamine (3.03 g, 30 mmol) was added to the mixture at room temperature, and the mixture was stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 0.71 g of ethyl 5-butylisoxazole-3-carboxylate represented by formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.95 (3H, t), 1.40 (5H, m), 1.74-1.67 (2H, m), 2.80 (2H, t), 4.43 (2H, q), 6.40 (1H, s)

で示される５−ブチルイソキサゾール−３−カルボン酸０．５０ｇを得た。得られたカルボン酸は精製することなく次の反応に供した。 Reference production example 6
Ethyl 5-butylisoxazole-3-carboxylate (0.71 g, 3.6 mmol) was added to ethanol (20 mL), and potassium hydroxide (0.40 g, 7.2 mmol) and water (10 mL) were added. After stirring overnight at room temperature, the mixture was concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

Thus, 0.50 g of 5-butylisoxazole-3-carboxylic acid represented by the formula (1) was obtained. The obtained carboxylic acid was subjected to the next reaction without purification.

で示される５−ペンチルイソキサゾール−３−カルボン酸エチルの粗生成物を得た。該粗生成物をエタノール（８０ｍＬ）に加え、水酸化カリウム（１．６８ｇ，３０ｍｍｏｌ）及び水（４０ｍＬ）を加えた後、室温で一晩攪拌した。その後、減圧下で濃縮した。濃縮物に希塩酸を加え、酢酸エチルで２回抽出した。有機層を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した後、減圧下で濃縮し、下式

で示される５−ペンチルイソキサゾール−３−カルボン酸０．２８ｇを得た。得られたカルボン酸は精製することなく次の反応に供した。 Reference production example 7
2-Chloro-2- (hydroxyimino) ethyl acetate (4.54 g, 30 mmol), 1-heptin (2.40 g, 25 mmol) was added to N, N-dimethylformamide (50 mL). Triethylamine (3.03 g, 30 mmol) was added to the mixture at room temperature, and the mixture was stirred overnight, diluted hydrochloric acid was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

To give a crude product of ethyl 5-pentylisoxazole-3-carboxylate. The crude product was added to ethanol (80 mL), potassium hydroxide (1.68 g, 30 mmol) and water (40 mL) were added, and the mixture was stirred overnight at room temperature. Then, it concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

0.28 g of 5-pentylisoxazole-3-carboxylic acid represented by The obtained carboxylic acid was subjected to the next reaction without purification.

で示される５−ベンジルオキシメチルイソキサゾール−３−カルボン酸エチル５．３７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４２（３Ｈ，ｔ），４．４５（２Ｈ，ｑ），４．６２（２Ｈ，ｓ），４．６７（２Ｈ，ｓ），６．７０ （１Ｈ，ｄ），７．３３−７．３９（５Ｈ，ｍ） Reference production example 8
Ethyl nitroacetate (4.80 g, 40 mmol), benzylpropargyl ether (3.55 g, 27 mmol) and 1,4-diazabicyclo [2.2.2] octane (0.61 g, 5.4 mmol) were mixed with chloroform (amylene-added product). ) (10 mL). The mixture was heated to reflux for 48 hours, cooled to room temperature, diluted hydrochloric acid was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Thus, 5.37 g of ethyl 5-benzyloxymethylisoxazole-3-carboxylate represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42 (3H, t), 4.45 (2H, q), 4.62 (2H, s), 4.67 (2H, s) ), 6.70 (1H, d), 7.33-7.39 (5H, m)

で示される５−ベンジルオキシメチルイソキサゾール−３−カルボン酸８．２７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．４０−７．３２（５Ｈ，ｍ），６．７５（１Ｈ，ｄ），４．６９（２Ｈ，ｓ），４．６４（２Ｈ，ｓ） Reference production example 9
Ethyl 5-benzyloxymethylisoxazole-3-carboxylate (10.9 g, 42 mmol) was added to ethanol (80 mL), and potassium hydroxide (3.49 g, 62.3 mmol) and water (40 mL) were added. After stirring overnight at room temperature, the mixture was concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and then crystallized with t-butyl methyl ether / hexane.

As a result, 8.27 g of 5-benzyloxymethylisoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.40-7.32 (5H, m), 6.75 (1H, d), 4.69 (2H, s), 4.64 (2H, s)

で示される５−シクロペンチルオキシメチルイソキサゾール−３−カルボン酸エチル０．３６ｇを得た。得られたカルボン酸は精製することなく次の反応に供した。 Reference production example 10
Ethyl nitroacetate (0.96 g, 8.2 mmol), cyclopentylpropargyl ether (0.81 g, 6.5 mmol) and 1,4-diazabicyclo [2.2.2] octane (0.18 g, 1.6 mmol) in chloroform (Amylene-added product) (2 mL), refluxed for 24 hours, cooled to room temperature, diluted hydrochloric acid was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

As a result, 0.36 g of ethyl 5-cyclopentyloxymethylisoxazole-3-carboxylate was obtained. The obtained carboxylic acid was subjected to the next reaction without purification.

で示される５−シクロペンチルオキシメチルイソキサゾール−３−カルボン酸０．２６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．５５−１．５７（２Ｈ，ｍ），１．６８−１．８０（６Ｈ，ｍ），４．０５−４．０６（１Ｈ，ｍ），４．６２（２Ｈ，ｓ），６．７２（１Ｈ，ｓ） Reference production example 11
Ethyl 5-cyclopentyloxymethylisoxazole-3-carboxylate (0.36 g) was added to ethanol (2 mL), and potassium hydroxide (0.18 g, 1.5 mmol) and water (1 mL) were further added at room temperature. After stirring overnight, it was concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.26 g of 5-cyclopentyloxymethylisoxazole-3-carboxylic acid represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.55-1.57 (2H, m), 1.68-1.80 (6H, m), 4.05-4.06 ( 1H, m), 4.62 (2H, s), 6.72 (1H, s)

で示される５−（２−ナフチルメトキシメチル）イソキサゾール−３−カルボン酸エチル１．５８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： １．４２（３Ｈ，ｔ），４．４５（２Ｈ，ｑ），４．７０（２Ｈ，ｄ），４．７８（２Ｈ，ｓ），６．７２（１Ｈ，ｓ），７．４６−７．５１（３Ｈ，ｍ），７．８３−７．８５（４Ｈ，ｍ） Reference production example 12
Add ethyl nitroacetate (1.49 g, 12.5 mmol), (2-naphthylmethyl) propargyl ether (1.96 g, 10 mmol) and 1,4-diazabicyclo [2.2.2] octane (0.56 g, 5 mmol). The mixture was added to chloroform (amylene-added product) (3 mL), heated to reflux for 24 hours, cooled to room temperature, diluted hydrochloric acid was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Thus, 1.58 g of ethyl 5- (2-naphthylmethoxymethyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42 (3H, t), 4.45 (2H, q), 4.70 (2H, d), 4.78 (2H, s) ), 6.72 (1H, s), 7.46-7.51 (3H, m), 7.83-7.85 (4H, m)

で示される５−（２−ナフチルメトキシメチル）イソキサゾール−３−カルボン酸１．２３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））： ４．７２（２Ｈ，ｄ），４．８０（２Ｈ，ｓ），６．７７（１Ｈ，ｓ），７．４７−７．５２（３Ｈ，ｍ），７．８３−７．８６（４Ｈ，ｍ） Reference production example 13
Ethyl 5- (2-naphthylmethoxymethyl) isoxazole-3-carboxylate (1.58 g, 5.1 mmol) was added to ethanol (60 mL), followed by potassium hydroxide (0.58 g, 10.2 mmol) and water (10 mL). ) And stirred at room temperature overnight, and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and then crystallized with t-butyl methyl ether / hexane.

As a result, 1.23 g of 5- (2-naphthylmethoxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 4.72 (2H, d), 4.80 (2H, s), 6.77 (1H, s), 7.47-7.52 (3H, m), 7.83-7.86 (4H, m)

で示される５−（３−フェニルプロピル）イソキサゾール−３−カルボン酸エチル１．１５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４２（３Ｈ，ｔ），２．０４−２．０８（２Ｈ，ｍ），２．７０（２Ｈ，ｔ），２．８２（２Ｈ，ｔ），４．４４（２Ｈ，ｑ），６．４２（１Ｈ，ｓ），７．１９−７．２１（３Ｈ，ｍ），７．２９−７．３２（２Ｈ，ｍ） Reference production example 14
Ethyl nitroacetate (1.49 g, 40 mmol), 5-phenyl-1-pentyne (1.44 g, 10.0 mmol) and 1,4-diazabicyclo [2.2.2] octane (0.56 g, 5.0 mmol) Was added to chloroform (amylene-added product) (3 mL) and heated to reflux for 12 hours. To the mixture was added ethyl nitroacetate (1.49 g, 40 mmol), and the mixture was further heated to reflux for 12 hours, cooled to room temperature, diluted hydrochloric acid was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.15 g of ethyl 5- (3-phenylpropyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42 (3H, t), 2.04-2.08 (2H, m), 2.70 (2H, t), 2.82 (2H, t), 4.44 (2H, q), 6.42 (1H, s), 7.19-7.21 (3H, m), 7.29-7.32 (2H, m)

で示される５−（３−フェニルプロピル）イソキサゾール−３−カルボン酸０．９２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：２．０４−２．１２（２Ｈ，ｍ），２．７１（２Ｈ，ｔ），２．８４（２Ｈ，ｔ），６．４７（１Ｈ，ｓ），７．２０−７．２２（３Ｈ，ｍ），７．３０−７．３３（２Ｈ，ｍ） Reference production example 15
Ethyl 5- (3-phenylpropyl) isoxazole-3-carboxylate (1.15 g, 4.4 mmol) was added to ethanol (8 mL), followed by potassium hydroxide (0.49 g, 8.8 mmol) and water (4 mL). After stirring at room temperature overnight, the mixture was concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and then crystallized with t-butyl methyl ether / hexane.

0.92 g of 5- (3-phenylpropyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 2.04-2.12 (2H, m), 2.71 (2H, t), 2.84 (2H, t), 6.47 (1H, s), 7.20-7.22 (3H, m), 7.30-7.33 (2H, m)

で示される５−フェノキシメチルイソキサゾール−３−カルボン酸エチル１．１３ｇを得た。得られたカルボン酸は精製することなく次の反応に供した。 Reference Production Example 16
Ethyl nitroacetate (1.49 g, 12.5 mmol), phenylpropargyl ether (1.32 g, 10.0 mmol) and 1,4-diazabicyclo [2.2.2] octane (0.56 g, 5.0 mmol) in chloroform (Amylene added product) (3 mL) and heated to reflux for 24 hours. The mixture was cooled to room temperature, diluted hydrochloric acid was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

To obtain 1.13 g of ethyl 5-phenoxymethylisoxazole-3-carboxylate represented by the formula: The obtained carboxylic acid was subjected to the next reaction without purification.

で示される５−フェノキシメチルイソキサゾール−３−カルボン酸０．３１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：５．２４（２Ｈ，ｓ），６．８２（１Ｈ，ｓ），６．９５−７．０６（３Ｈ，ｍ），７．３２−７．３４（２Ｈ，ｍ） Reference Production Example 17
Ethyl 5-phenoxymethylisoxazole-3-carboxylate (1.13 g) obtained in Reference Production Example 16 was added to ethanol (10 mL), and potassium hydroxide (0.61 g, 11.0 mmol) and water ( 5 mL) and stirred at room temperature overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 0.31 g of 5-phenoxymethylisoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 5.24 (2H, s), 6.82 (1H, s), 6.95-7.06 (3H, m), 7.32 -7.34 (2H, m)

で示される５−（２−フェニルエチル）イソキサゾール−３−カルボン酸エチル１．５１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４１（３Ｈ，ｔ），３．０２−３．０６（２Ｈ，ｍ），３．１２−３．１４（２Ｈ，ｍ），４．４３（２Ｈ，ｑ），６．３６（１Ｈ，ｄ），７．１７−７．１９（２Ｈ，ｍ），７．２２−７．２４（１Ｈ，ｍ），７．２９−７．３１（２Ｈ，ｍ） Reference Production Example 18
Ethyl nitroacetate (1.49 g, 40 mmol), 4-phenyl-1-butyne (1.30 g, 10.0 mmol) and 1,4-diazabicyclo [2.2.2] octane (0.56 g, 5.0 mmol) Was added to chloroform (amylene-added product) (3 mL) and heated to reflux for 12 hours. To the mixture was added ethyl nitroacetate (1.49 g, 40 mmol), heated to reflux for 12 hours, cooled to room temperature, diluted hydrochloric acid was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Thus, 1.51 g of ethyl 5- (2-phenylethyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.41 (3H, t), 3.02-3.06 (2H, m), 3.12-3.14 (2H, m) 4.43 (2H, q), 6.36 (1H, d), 7.17-7.19 (2H, m), 7.22-7.24 (1H, m), 7.29-7. .31 (2H, m)

で示される５−（２−フェニルエチル）イソキサゾール−３−カルボン酸０．９２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：３．０５−３．０８（２Ｈ， ｍ），３．１３−３．１８（２Ｈ，ｍ），６．４１（１Ｈ，ｓ），７．１８−７．１９（２Ｈ，ｍ），７．２３−７．２４（１Ｈ，ｍ），７．２９−７．３４（２Ｈ，ｍ） Reference Production Example 19
Ethyl 5- (2-phenylethyl) isoxazole-3-carboxylate (1.15 g, 4.4 mmol) was added to ethanol (8 mL), followed by potassium hydroxide (0.49 g, 8.8 mmol) and water (4 mL). After stirring at room temperature overnight, the mixture was concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and then crystallized with t-butyl methyl ether / hexane.

0.92 g of 5- (2-phenylethyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 3.05-3.08 (2H, m), 3.13-3.18 (2H, m), 6.41 (1H, s) 7.18-7.19 (2H, m), 7.23-7.24 (1H, m), 7.29-7.34 (2H, m)

で示される５−（２−フェニルエトキシメチル）イソキサゾール−３−カルボン酸エチル２．６２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４２（３Ｈ，ｔ），２．９２（２Ｈ，ｔ），３．７５（２Ｈ，ｔ），４．４４（２Ｈ，ｑ），４．６４（２Ｈ，ｄ），６．５７（１Ｈ，ｓ），７．２３−７．３０（５Ｈ，ｍ） Reference Production Example 20
Ethyl nitroacetate (1.49 g, 40 mmol), (2-phenylethyl) propargyl ether (1.60 g, 10.0 mmol) and 1,4-diazabicyclo [2.2.2] octane (0.56 g, 5.0 mmol) ) Was added to chloroform (amylene-added product) (3 mL) and heated to reflux for 12 hours. To the mixture was added ethyl nitroacetate (1.49 g, 40 mmol), heated to reflux for 12 hours, cooled to room temperature, diluted hydrochloric acid was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 2.62 g of ethyl 5- (2-phenylethoxymethyl) isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42 (3H, t), 2.92 (2H, t), 3.75 (2H, t), 4.44 (2H, q ), 4.64 (2H, d), 6.57 (1H, s), 7.23-7.30 (5H, m)

で示される５−（２−フェニルエトキシメチル）イソキサゾール−３−カルボン酸１．８６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：２．９３（２Ｈ，ｔ），３．７８（２Ｈ，ｔ），４．６６（２Ｈ，ｓ），６．６２（１Ｈ，ｓ），７．２１−７．３３（５Ｈ，ｍ） Reference Production Example 21
Ethyl 5- (2-phenylethoxymethyl) isoxazole-3-carboxylate (2.62 g, 9.5 mmol) was added to ethanol (20 mL), followed by potassium hydroxide (0.1.08 g, 19.0 mmol) and water. (10 mL) was added, and the mixture was stirred overnight at room temperature, and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and then crystallized with t-butyl methyl ether / hexane.

1.86 g of 5- (2-phenylethoxymethyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 2.93 (2H, t), 3.78 (2H, t), 4.66 (2H, s), 6.62 (1H, s ), 7.21-7.33 (5H, m)

で示される５−ベンジルイソキサゾール−３−カルボン酸エチル５．３７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３８（３Ｈ，ｔ），４．１２（２Ｈ，Ｓ），４．３９（２Ｈ，ｑ），６．３２（１Ｈ，ｓ），７．２３−７．３５（５Ｈ，ｍ） Reference Production Example 22
Ethyl nitroacetate (1.49 g, 12.5 mmol), 2-phenylpropyne (1.16 g, 10 mmol) and 1,4-diazabicyclo [2.2.2] octane (0.56 g, 5.0 mmol) in chloroform ( (Amylene added product) (3 mL) and heated to reflux for 24 hours. Ethyl nitroacetate (1.49 g, 12.5 mmol) was added to the mixture, heated under reflux for 24 hours, cooled to room temperature, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Thus, 5.37 g of ethyl 5-benzylisoxazole-3-carboxylate represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.38 (3H, t), 4.12 (2H, S), 4.39 (2H, q), 6.32 (1H, s) ), 7.23-7.35 (5H, m)

で示される５−ベンジルオキシメチルイソキサゾール−３−カルボン酸２７０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：４．１４（２Ｈ，Ｓ），６．３８（１Ｈ，ｓ），７．２９−７．３６（５Ｈ，ｍ） Reference Production Example 23
Ethyl 5-benzylisoxazole-3-carboxylate (563 mg, 2 mmol) was added to ethanol (8 mL), potassium hydroxide (560 mg, 10 mmol) and water (2 mL) were added, and the mixture was stirred overnight at room temperature. Concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and then crystallized with t-butyl methyl ether / hexane.

270 mg of 5-benzyloxymethylisoxazole-3-carboxylic acid represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 4.14 (2H, S), 6.38 (1H, s), 7.29-7.36 (5H, m)

で示される５−（１−ナフチルメトキシメチル）イソキサゾール−３−カルボン酸エチル０．５２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４１（３Ｈ，ｔ），４．４２（２Ｈ，ｑ），４．６８（２Ｈ，Ｓ），５．０６（２Ｈ，ｓ），６．６７（１Ｈ，ｓ），７．４５−７．５３（４Ｈ，ｍ），７．８３−７．８６（２Ｈ，ｍ），７．８９（１Ｈ，ｄ） Reference Production Example 24
Ethyl nitroacetate (1.49 g, 12.5 mmol), (1-naphthylmethyl) propargyl ether (1.96 g, 10 mmol) and 1,4-diazabicyclo [2.2.2] octane (0.56 g, 5.0 mmol) ) Was added to chloroform (amylene-added product) (3 mL), heated under reflux for 24 hours, cooled to room temperature, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

In this manner, 0.52 g of ethyl 5- (1-naphthylmethoxymethyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.41 (3H, t), 4.42 (2H, q), 4.68 (2H, S), 5.06 (2H, s) ), 6.67 (1H, s), 7.45-7.53 (4H, m), 7.83-7.86 (2H, m), 7.89 (1H, d)

で示される５−（１−ナフチルメトキシメチル）イソキサゾール−３−カルボン酸４６０ｍｇを得た。得られたカルボン酸は生成することなく次の工程に用いた。 Reference Production Example 25
Ethyl 5- (1-naphthylmethoxymethyl) isoxazole-3-carboxylate (520 mg, 1.7 mmol) was added to ethanol (8 mL), and potassium hydroxide (469 mg, 8.4 mmol) and water (2 mL) were added. After stirring overnight at room temperature, the mixture was concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

460 mg of 5- (1-naphthylmethoxymethyl) isoxazole-3-carboxylic acid represented by The obtained carboxylic acid was used in the next step without being produced.

で示される５−［１−（２−ナフチル）エトキシメチル］イソキサゾール−３−カルボン酸エチル４．２９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４０（３Ｈ，ｔ），１．５６（３Ｈ，ｄ），４．４２−４．５５（４Ｈ，ｍ），４．６８（１Ｈ，ｑ），６．６８（１Ｈ，ｍ），７．４７−７．５１（３Ｈ，ｍ），７．７４（１Ｈ，ｂｒ．Ｓ），７．８２−７．８８（３Ｈ，ｍ） Reference Production Example 26
Ethyl nitroacetate (3.0 g, 25.0 mmol), [1- (2-naphthyl) ethyl] propargyl ether (4.2 g, 20 mmol) and 1,4-diazabicyclo [2.2.2] octane (0.45 g , 4.0 mmol) was added to chloroform (amylene-added product) (7 mL), heated under reflux for 24 hours, cooled to room temperature, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Thus, 4.29 g of ethyl 5- [1- (2-naphthyl) ethoxymethyl] isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.40 (3H, t), 1.56 (3H, d), 4.42 to 4.55 (4H, m), 4.68 (1H, q), 6.68 (1H, m), 7.47-7.51 (3H, m), 7.74 (1H, br. S), 7.82-7.88 (3H, m )

で示される５−［１−（２−ナフチル）エトキシメチル］イソキサゾール−３−カルボン酸３．３１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．５９（３Ｈ，ｄ），４．５２（２Ｈ，ｑ），４．７１（１Ｈ，ｑ），６．７１（１Ｈ，ｍ），７．５０−７．５２（３Ｈ，ｍ），７．７６（１Ｈ，ｂｒ．ｓ），７．８４−７．９０（３Ｈ，ｍ） Reference Production Example 27
Ethyl 5- [1- (2-naphthyl) ethoxymethyl] isoxazole-3-carboxylate (4.29 g, 13.2 mmol) is added to ethanol (40 mL), followed by potassium hydroxide (2.24 g, 40.0 mmol). And water (10 mL) were added, and the mixture was stirred overnight at room temperature, and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

In this manner, 3.31 g of 5- [1- (2-naphthyl) ethoxymethyl] isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.59 (3H, d), 4.52 (2H, q), 4.71 (1H, q), 6.71 (1H, m ), 7.50-7.52 (3H, m), 7.76 (1H, br.s), 7.84-7.90 (3H, m)

で示される５−フェノキシメチル−２−チアゾールカルボン酸０．２８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：５．２８（２Ｈ，ｓ），６．９６−７．０１（３Ｈ，ｍ），７．２７−７．３３（２Ｈ，ｍ），７．７３（１Ｈ，ｓ） Reference Production Example 28
Phenol (0.21 g, 2.2 mmol) was dissolved in dimethyl sulfoxide (2 ml), potassium hydroxide (0.11 g, 2.1 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. To the mixture was added ethyl 5-chloromethyl-2-thiazolecarboxylate (0.41 g, 2.0 mmol), stirred at 60 ° C. for 8 hours, cooled to room temperature, and potassium hydroxide (0.59 g, 10.5 mmol). ) And water (10 mL) were added. The reaction mixture was stirred at room temperature overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

0.28 g of 5-phenoxymethyl-2-thiazolecarboxylic acid represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 5.28 (2H, s), 6.96-7.01 (3H, m), 7.27-7.33 (2H, m) , 7.73 (1H, s)

で示される５−ベンジルオキシメチル−２−チアゾールカルボン酸０．１１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：４．６６（２Ｈ，ｓ），４．７９（２Ｈ，ｄ），７．３０−７．３６（５Ｈ，ｍ），７．６５（１Ｈ，ｄ） Reference Production Example 29
Benzyl alcohol (0.86 g, 8.0 mmol) was dissolved in dimethyl sulfoxide (8 ml), potassium hydroxide (0.45 g, 8.0 mmol) was added, and the mixture was stirred at room temperature for 30 minutes, and then 5-chloromethyl-2 -Ethyl thiazolecarboxylate (0.82 g, 4.0 mmol) was added, and the mixture was stirred at 60 ° C for 8 hours. The mixture was cooled to room temperature, potassium hydroxide (2.1 g, 40 mmol) and water (40 mL) were added, and the mixture was stirred at room temperature overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

As a result, 0.11 g of 5-benzyloxymethyl-2-thiazolecarboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 4.66 (2H, s), 4.79 (2H, d), 7.30-7.36 (5H, m), 7.65 (1H, d)

で示される５−ベンジルオキシ−２，４−ジオキソペンタン酸エチル６．３１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３７（３Ｈ，ｔ），４．１６（２Ｈ，ｓ），４．３４（２Ｈ，ｑ），４．６２（２Ｈ，ｓ），６．６７（１Ｈ，ｓ），７．２５−７．３９（５Ｈ，ｍ） Reference Production Example 30
Benzyloxyacetone (5.15 g, 32.0 mmol) and diethyl oxalate (4.64 g, 32.0 mmol) were added to ethanol (32 mL), cooled to −20 ° C., and 20% sodium ethoxide (10.89 g, 32 mmol) was added dropwise over 30 minutes, and then the mixture was warmed to room temperature and stirred for 18 hours. The mixture was concentrated under reduced pressure, diluted hydrochloric acid was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography.

6.31 g of ethyl 5-benzyloxy-2,4-dioxopentanoate represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.37 (3H, t), 4.16 (2H, s), 4.34 (2H, q), 4.62 (2H, s) ), 6.67 (1H, s), 7.25-7.39 (5H, m)

で示される５−ベンジルオキシメチル−１Ｈ−ピラゾール−３−カルボン酸エチル１．６５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３８（３Ｈ，ｔ），４．３７（２Ｈ，ｑ），４．５６（２Ｈ，ｓ），４．６０（２Ｈ，ｓ），６．８１（１Ｈ，ｓ），７．２５−７．３６（５Ｈ，ｍ） Reference Production Example 31
Ethyl 5-benzyloxy-2,4-dioxopentanoate (2.64 g, 10.0 mmol) and hydrazine monohydrate (0.50 g, 10.0 mmol) were added to ethanol (20 mL) and added at 60 ° C. for 8 hours. After stirring for hours, it was cooled to room temperature and concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography.

1.65 g of ethyl 5-benzyloxymethyl-1H-pyrazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.38 (3H, t), 4.37 (2H, q), 4.56 (2H, s), 4.60 (2H, s) ), 6.81 (1H, s), 7.25-7.36 (5H, m)

で示される５−ベンジルオキシメチル−１Ｈ−ピラゾール−３−カルボン酸４８１ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：４．５９（２Ｈ，ｓ），４．６３（２Ｈ，ｓ），６．８３（１Ｈ，ｓ），７．３４−７．３７（５Ｈ，ｍ） Reference Production Example 32
Ethyl 5-benzyloxymethyl-1H-pyrazole-3-carboxylate (580 mg, 2.5 mmol) was added to ethanol (10 mL), and potassium hydroxide (560 mg, 10.0 mmol) and water (2.5 mL) were added. The mixture was stirred overnight at room temperature and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

As a result, 481 mg of 5-benzyloxymethyl-1H-pyrazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 4.59 (2H, s), 4.63 (2H, s), 6.83 (1H, s), 7.34-7.37 (5H, m)

で示される３−ベンジルオキシメチル−１−メチル−１H-ピラゾール−５−カルボン酸と下式

５−ベンジルオキシメチル−１−メチル−１H-ピラゾール−３−カルボン酸の５６：４４混合物１．４７ｇを得た。このものは混合物のまま次の反応に供した。
３−ベンジルオキシメチル−１−メチル−１H-ピラゾール−５−カルボン酸 ^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：４．１６（３Ｈ，ｓ），４．５４（２Ｈ，ｓ），４．５７（２Ｈ，ｓ），６．９７（１Ｈ，ｓ），７．３３−７．３６（５Ｈ，ｍ）
５−ベンジルオキシメチル−１−メチル−１H-ピラゾール−３−カルボン酸 ^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：３．９５（３Ｈ，ｓ），４．５１（２Ｈ，ｓ），４．５３（２Ｈ，ｓ），６．８１（１Ｈ，ｓ），７．３３−７．３６（５Ｈ，ｍ） Reference Production Example 33
Under a nitrogen atmosphere, ethyl 3-benzyloxymethylpyrazole-5-carboxylate (1.26 g, 5.4 mmol) was added to dry N, N-dimethylformamide (15 ml). Potassium carbonate (0.75 g, 5.4 mmol) and iodomethane (1.53 g, 10.8 mmol) were added, and the mixture was stirred at 60 ° C. for 12 hours. The reaction mixture was cooled to room temperature, poured into 1N hydrochloric acid, extracted twice with ethyl acetate, the organic layer was washed with water and saturated brine, and dried over sodium sulfate. The solvent was concentrated under reduced pressure, and the residue was added to ethanol (25 mL), potassium hydroxide (1.51 g, 27.0 mmol) and water (7 mL) were added, and the mixture was stirred at room temperature for 18 hr. Then, it concentrated under pressure reduction. Dilute hydrochloric acid was added to the reaction mixture, the mixture was cooled to 0 ° C., and the precipitated solid was filtered. The solid is dried under reduced pressure.

And 3-benzyloxymethyl-1-methyl-1H-pyrazole-5-carboxylic acid represented by the following formula:

1.47 g of a 56:44 mixture of 5-benzyloxymethyl-1-methyl-1H-pyrazole-3-carboxylic acid was obtained. This was used in the next reaction as a mixture.
3-Benzyloxymethyl-1-methyl-1H-pyrazole-5-carboxylic acid ¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 4.16 (3H, s), 4.54 (2H, s ), 4.57 (2H, s), 6.97 (1H, s), 7.33-7.36 (5H, m)
5-Benzyloxymethyl-1-methyl-1H-pyrazole-3-carboxylic acid ¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 3.95 (3H, s), 4.51 (2H, s ), 4.53 (2H, s), 6.81 (1H, s), 7.33-7.36 (5H, m)

で示される５−ベンジルイソチアゾール−３−カルボン酸０．１３ｇを得た。得られたカルボン酸は精製することなく製造例５６にて用いた。 Reference Production Example 34
Ethyl 5-benzylisothiazole-3-carboxylate (0.23 g, 0.9 mmol) was added to ethanol (3.7 mL), followed by potassium hydroxide (0.10 g, 1.9 mmol) and water (1.9 mL). After stirring at room temperature for 2 hours, the mixture was heated to 40 ° C. and stirred for 1 hour. 2N hydrochloric acid was added to the mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure.

0.13 g of 5-benzylisothiazole-3-carboxylic acid represented by The obtained carboxylic acid was used in Production Example 56 without purification.

で示される５−ベンジルイソチアゾール−３−カルボン酸エチル２３０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：７．５５（１Ｈ，ｔ），７．３９−７．２３（５Ｈ，ｍ），４．４２（２Ｈ，ｑ），４．２６−４．２４（２Ｈ，ｂｒ），１．４１（３Ｈ，ｔ） Reference Production Example 35
2-Oxo-1,3,4-oxathiazole-5-carboxylate (0.70 g, 4.0 mmol) and 3-phenyl-1-propyne (2.0 g, 17 mmol) were added to 1,2-dichlorobenzene (11 mL). ). After stirring in a sealed tube at 200 degrees for 54 hours, it was subjected to silica gel column chromatography.

As a result, 230 mg of ethyl 5-benzylisothiazole-3-carboxylate represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.55 (1H, t), 7.39-7.23 (5H, m), 4.42 (2H, q), 4.26- 4.24 (2H, br), 1.41 (3H, t)

で示される５−ブチルイソチアゾール−３−カルボン酸０．０８ｇを得た。得られたカルボン酸は精製することなく製造例５７に用いた。 Reference Production Example 36
Ethyl 5-butylisothiazole-3-carboxylate (0.09 g, 0.4 mmol) was added to ethanol (1.6 mL), followed by potassium hydroxide (0.05 g, 0.8 mmol) and water (0.5 mL). After stirring at room temperature for 2 hours, 2N hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure.

As a result, 0.08 g of 5-butylisothiazole-3-carboxylic acid represented by the following formula was obtained. The obtained carboxylic acid was used in Production Example 57 without purification.

で示される５−ブチルイソチアゾール−３−カルボン酸エチル８５ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：７．５６（１Ｈ， ｔ），４．４３（２Ｈ，ｑ），２．９４（２Ｈ， ｔ），１．７５−１．６８ （２Ｈ，ｍ），１．４８−１．３７（４Ｈ，ｍ），０．９５（３Ｈ，ｔ） Reference Production Example 37
2-Oxo-1,3,4-oxathiazole-5-carboxylate (0.70 g, 4.0 mmol) and 1-hexyne (1.8 ml, 16 mmol) were dissolved in 11 ml of 1,2-dichlorobenzene. After stirring for 26.5 hours at 200 degrees in a sealed tube, it was subjected to silica gel column chromatography.

85 mg of ethyl 5-butylisothiazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 7.56 (1H, t), 4.43 (2H, q), 2.94 (2H, t), 1.75-1.68 ( 2H, m), 1.48-1.37 (4H, m), 0.95 (3H, t)

で示される（４−トリフルオロメチルベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル２．２５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４３（３Ｈ，ｔ），４．４３（２Ｈ，ｑ），４．６７（２Ｈ，ｓ），４．７１（２Ｈ，ｓ），６．７２（１Ｈ，ｓ），７．５３−７．６１（４Ｈ，ｍ） Reference Production Example 38
Ethyl nitroacetate (2.14 g, 0 mmol), 4-trifluoromethylbenzylpropargyl ether (2.14 g, 10 mmol) and 1,4-diazabicyclo [2.2.2] octane (0.22 g, 2 mmol) in chloroform ( (Amylene-added product) (3 mL), heated under reflux for 48 hours, cooled to room temperature, diluted hydrochloric acid was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

To 2.25 g of ethyl (4-trifluoromethylbenzyloxymethyl) isoxazole-3-carboxylate represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.43 (3H, t), 4.43 (2H, q), 4.67 (2H, s), 4.71 (2H, s) ), 6.72 (1H, s), 7.53-7.61 (4H, m)

で示される５−（４−トリフルオロメチルベンジルオキシメチル）イソキサゾール−３−カルボン酸１．８１ｇを得た。得られたカルボン酸は精製することなく製造例６１に用いた。 Reference Production Example 39
Ethyl 5- (4-trifluoromethylbenzyl) isoxazole-3-carboxylate (2.25 g, 7.5 mmol) is added to ethanol (75 mL), potassium hydroxide (0.83 g, 14.9 mmol) and water (15 mL). ) And then stirred overnight at room temperature. Then, it concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

Thus, 1.81 g of 5- (4-trifluoromethylbenzyloxymethyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained. The obtained carboxylic acid was used in Production Example 61 without purification.

で示される５−（３−トリフルオロメチルベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル５．３７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４１（３Ｈ，ｔ），４．４３（２Ｈ，ｑ），４．６５（２Ｈ，ｓ），４．７０（２Ｈ，ｓ），６．７０（１Ｈ，ｓ），７．４６−７．６０（４Ｈ，ｍ） Reference Production Example 40
Add ethyl nitroacetate (4.80 g, 40 mmol), 3-trifluoromethylbenzylpropargyl ether (3.55 g, 27 mmol) and 1,4-diazabicyclo [2.2.2] octane (0.61 g, 5.4 mmol). It was added to chloroform (amylene-added product) (10 mL) and heated to reflux for 48 hours. Thereafter, the mixture was cooled to room temperature, diluted hydrochloric acid was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 5.37 g of ethyl 5- (3-trifluoromethylbenzyloxymethyl) isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.41 (3H, t), 4.43 (2H, q), 4.65 (2H, s), 4.70 (2H, s) ), 6.70 (1H, s), 7.46-7.60 (4H, m)

で示される５−（３−トリフルオロメチルベンジルオキシメチル）イソキサゾール−３−カルボン酸２．６６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：４．６８（２Ｈ，ｓ），４．７３（２Ｈ，ｄ），６．７７（１Ｈ，ｓ），７．５１−７．５９（４Ｈ，ｍ） Reference Production Example 41
Ethyl 5- (3-trifluoromethylbenzyloxymethyl) isoxazole-3-carboxylate (3.26 g, 10 mmol) is added to ethanol (60 mL), potassium hydroxide (1.15 g, 20.5 mmol) and water (12 mL). ) And stirred at room temperature overnight, and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and then crystallized with t-butyl methyl ether / hexane.

As a result, 2.66 g of 5- (3-trifluoromethylbenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 4.68 (2H, s), 4.73 (2H, d), 6.77 (1H, s), 7.51-7.59 (4H, m)

で示される５−ヒドロキシメチルイソキサゾール−３−カルボン酸エチル１８０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：６．６７（ｓ，１Ｈ），４．８３（ｄ，２Ｈ），４．４３（ｑ，２Ｈ），２．６５（ｂｒｓ，１Ｈ），１．４１（ｔ，３Ｈ） Reference Production Example 42
Add ethyl nitroacetate (198 mL, 1.78 mol), propargyl alcohol (100 g, 1.78 mmol) and 1,4-diazabicyclo [2.2.2] octane (20.0 g, 178.3 mmol) to ethanol (1 L). And heated at 80 ° C. for 16 hours. Then, it cooled to room temperature and concentrated the solvent under reduced pressure. The residue was subjected to silica gel column chromatography.

180 g of ethyl 5-hydroxymethylisoxazole-3-carboxylate represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 6.67 (s, 1H), 4.83 (d, 2H), 4.43 (q, 2H), 2.65 (brs, 1H) ), 1.41 (t, 3H)

で示される５−（２−クロロベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル３．９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．４８（ｄ，１Ｈ），７．３８（ｄ，１Ｈ），７．３１−７．２３（ｍ，２Ｈ），６．７３（ｓ，１Ｈ），４．７５（ｓ，２Ｈ），４．７１（ｓ，２Ｈ），４．４５（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference Production Example 43
Under a nitrogen atmosphere, 60% sodium hydride (2.45 g, 61.40 mmol) was added to dry N, N-dimethylformamide (40 ml) cooled to 0 ° C. and ethyl 5-hydroxymethylisoxazole-3-carboxylate. A solution of (7 g, 40.89 mmol) in dry N, N-dimethylformamide (30 ml) was added dropwise over 15 minutes, and the mixture was further stirred for 30 minutes. 2-Chlorobenzyl bromide (8.4 g, 40.93 mmol) was added and the reaction mixture was warmed to room temperature and stirred for 16 hours. The reaction mixture was poured into a saturated aqueous ammonium chloride solution and extracted twice with ethyl acetate. The organic layer was washed with water and saturated brine, and then dried over anhydrous sodium sulfate. After concentrating the solvent under reduced pressure, the residue was subjected to silica gel column chromatography.

As a result, 3.9 g of ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.48 (d, 1H), 7.38 (d, 1H), 7.31-7.23 (m, 2H), 6.73 (S, 1H), 4.75 (s, 2H), 4.71 (s, 2H), 4.45 (q, 2H), 1.42 (t, 3H)

で示される５−（２−クロロフェノキシメチル）イソキサゾール−３−カルボン酸２．９ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．１（ｂｒｓ，１Ｈ），７．５２−７．４６（ｍ，２Ｈ），７．３８−７．３２（ｍ，２Ｈ），６．８９（ｓ，１Ｈ），４．７９（ｓ，２Ｈ），４．６６（ｓ，２Ｈ） Reference Production Example 44
Ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate (4.0 g, 13.55 mmol) was added to ethanol (50 mL), 2N sodium hydroxide (30 mL) was added, and then at room temperature for 16 hours. Stir. Then, it concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, cooled to 0 ° C., and the precipitated solid was filtered. The solid is dried under reduced pressure

As a result, 2.9 g of 5- (2-chlorophenoxymethyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.1 (brs, 1H), 7.52-7.46 (m, 2H), 7.38-7.32 (m, 2H) ), 6.89 (s, 1H), 4.79 (s, 2H), 4.66 (s, 2H)

で示される５−（３−クロロベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル4.4 gを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．３４−７．２１（ｍ，４Ｈ），６．７０（ｓ，１Ｈ），４．６７（ｓ，２Ｈ），４．５８（ｓ，２Ｈ），４．４４（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference Production Example 45
In Reference Production Example 43, 3-chlorobenzyl bromide (8.4 g, 40.93 mmol) was used instead of 2-chlorobenzyl bromide, and the same reaction was carried out.

4.4 g of ethyl 5- (3-chlorobenzyloxymethyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.34-7.21 (m, 4H), 6.70 (s, 1H), 4.67 (s, 2H), 4.58 (S, 2H), 4.44 (q, 2H), 1.42 (t, 3H)

で示される５−（３−クロロベンジルオキシメチル）イソキサゾール−３−カルボン酸4.4 gを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．４２−７．３６（ｍ，３Ｈ），７．３１（ｄ，１Ｈ），６．８１（ｓ，１Ｈ），４．７５（ｓ，２Ｈ），４．５９（ｓ，２Ｈ） Reference Production Example 46
In Reference Production Example 44, instead of ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate, ethyl 5- (3-chlorobenzyloxymethyl) isoxazole-3-carboxylate 4.9 g, 16.61 mmol) Using the same reaction,

4.4 g of 5- (3-chlorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 14.0 (brs, 1H), 7.42-7.36 (m, 3H), 7.31 (d, 1H), 6.81 (S, 1H), 4.75 (s, 2H), 4.59 (s, 2H)

で示される５−（４−クロロベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル1.7 gを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．３４（ｄ，２Ｈ），７．２９（ｄ，２Ｈ），６．６８（ｓ，１Ｈ），４．６５（ｓ，２Ｈ），４．５７（ｓ，２Ｈ），４．４５（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference Production Example 47
In Reference Production Example 43, 4-chlorobenzyl bromide (3.69 g, 17.9 mmol) was used instead of 2-chlorobenzyl bromide, and the same reaction was carried out.

1.7 g of ethyl 5- (4-chlorobenzyloxymethyl) isoxazole-3-carboxylate represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.34 (d, 2H), 7.29 (d, 2H), 6.68 (s, 1H), 4.65 (s, 2H) ), 4.57 (s, 2H), 4.45 (q, 2H), 1.42 (t, 3H)

で示される５−（４−クロロベンジルオキシメチル）イソキサゾール−３−カルボン酸1.5 gを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．４４−７．３６（ｍ，４Ｈ），６．８６（ｓ，１Ｈ），４．７２（ｓ，２Ｈ），４．５７（ｓ，２Ｈ） Reference production example 48
In Reference Production Example 44, instead of ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate, ethyl 5- (4-chlorobenzyloxymethyl) isoxazole-3-carboxylate (2.3 g, 7.79 mmol) The same reaction is carried out using

Thus, 1.5 g of 5- (4-chlorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 14.0 (brs, 1H), 7.44-7.36 (m, 4H), 6.86 (s, 1H), 4.72 (S, 2H), 4.57 (s, 2H)

で示される５−（３，４−ジクロロベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル1.7gを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．４８（ｄ，２Ｈ），７．２０（ｄｄ，１Ｈ），６．７（ｓ，１Ｈ），４．７（ｓ，２Ｈ），４．６（ｓ，２Ｈ），４．４５（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference Production Example 49
In Reference Production Example 43, 3,4-dichlorobenzyl bromide (3.5 g, 14.6 mmol) was used instead of 2-chlorobenzyl bromide, and the same reaction was performed.

Thus, 1.7 g of ethyl 5- (3,4-dichlorobenzyloxymethyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.48 (d, 2H), 7.20 (dd, 1H), 6.7 (s, 1H), 4.7 (s, 2H) ), 4.6 (s, 2H), 4.45 (q, 2H), 1.42 (t, 3H)

で示される５−（３，４−ジクロロベンジルオキシメチル）イソキサゾール−３−カルボン酸1.7gを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．７０−７．６０（ｍ，２Ｈ），７．４０−７．３０（ｄｄ，１Ｈ），６．９０（ｓ，１Ｈ），４．７５（ｓ，２Ｈ），４．６０（ｓ，２Ｈ） Reference production example 50
In Reference Preparation Example 44, instead of ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate, ethyl 5- (3,4-dichlorobenzyloxymethyl) isoxazole-3-carboxylate (1.7 g, 3.34 The reaction is carried out in the same manner using

Thus, 1.7 g of 5- (3,4-dichlorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 14.0 (brs, 1H), 7.70-7.60 (m, 2H), 7.40-7.30 (dd, 1H) 6.90 (s, 1H), 4.75 (s, 2H), 4.60 (s, 2H)

で示される５−（３−フルオロベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル1.1gを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．２８−７．３８（ｍ，１Ｈ），７．０４−７．０６（ｍ，２Ｈ），６．９６−７．０４（ｍ，１Ｈ），６．７０（ｓ，１Ｈ），４．７０（ｓ，２Ｈ），４．６０（ｓ，２Ｈ），４．４５（ｑ，２Ｈ），１．４５（ｔ，３Ｈ） Reference Production Example 51
In Reference Production Example 43, 3-fluorobenzyl bromide (3.97 g, 21.0 mmol) was used instead of 2-chlorobenzyl bromide, and a similar reaction was performed.

Thus, 1.1 g of ethyl 5- (3-fluorobenzyloxymethyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.28-7.38 (m, 1H), 7.04-7.06 (m, 2H), 6.96-7.04 ( m, 1H), 6.70 (s, 1H), 4.70 (s, 2H), 4.60 (s, 2H), 4.45 (q, 2H), 1.45 (t, 3H)

で示される５−（３−フルオロベンジルオキシメチル）イソキサゾール−３−カルボン酸０．９ gを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．３７−７．３２（ｍ，１Ｈ），７．１３−７．６．９８（ｍ，３Ｈ），６．７８（ｓ，１Ｈ），４．７０（ｓ，２Ｈ），４．６２（ｓ，２Ｈ） Reference Production Example 52
In Reference Production Example 44, instead of ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate, ethyl 5- (3-fluorobenzyloxymethyl) isoxazole-3-carboxylate (1.1 g, 3.34 mmol) The same reaction is carried out using

As a result, 0.9 g of 5- (3-fluorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.37-7.32 (m, 1H), 7.13-7.6.98 (m, 3H), 6.78 (s, 1H), 4.70 (s, 2H), 4.62 (s, 2H)

で示される５−（３−ブロモベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル1.54 gを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．５０（ｓ，１Ｈ），７．４４（ｄ，１Ｈ），７．２５（ｄ，２Ｈ），６．７０（ｓ，１Ｈ），４．６７（ｓ，２Ｈ），４．５７（ｓ，２Ｈ），４．４５（ｑ，２Ｈ），１．４３（ｔ，３Ｈ） Reference Production Example 53
In Reference Production Example 43, 3-bromobenzyl bromide (3.52 g, 14.1 mmol) was used instead of 2-chlorobenzyl bromide, and the reaction was carried out in the same manner.

Thus, 1.54 g of ethyl 5- (3-bromobenzyloxymethyl) isoxazole-3-carboxylate represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.50 (s, 1H), 7.44 (d, 1H), 7.25 (d, 2H), 6.70 (s, 1H) ), 4.67 (s, 2H), 4.57 (s, 2H), 4.45 (q, 2H), 1.43 (t, 3H)

で示される５−（３−ブロモシベンジルオキシメチル）イソキサゾール−３−カルボン酸1.4 gを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．５２（ｍ，２Ｈ），７．３３（ｍ，２Ｈ），６．８８（ｓ，１Ｈ），４．７０（ｓ，２Ｈ），４．６０（ｓ，２Ｈ） Reference production example 54
In Reference Production Example 44, instead of ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate, ethyl 5- (3-bromobenzyloxymethyl) isoxazole-3-carboxylate (2.2 g, 6.47 mmol) The same reaction is carried out using

Thus, 1.4 g of 5- (3-bromosibenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.0 (brs, 1H), 7.52 (m, 2H), 7.33 (m, 2H), 6.88 (s, 1H), 4.70 (s, 2H), 4.60 (s, 2H)

で示される５−（３−トリフルオロメトキシベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル1.2 gを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．３８（ｔ，１Ｈ），７．２７（ｄ，１Ｈ），７．２１（ｓ，１Ｈ），７．１７（ｄ，１Ｈ），６．７（ｓ，１Ｈ），４．７０（ｓ，２Ｈ），４．６２（ｓ，２Ｈ），４．４４（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference Production Example 55
In Reference Production Example 43, 3-trifluoromethoxybenzyl bromide (3.0 g, 11.68 mmol) was used instead of 2-chlorobenzyl bromide, and the same reaction was performed.

As a result, 1.2 g of ethyl 5- (3-trifluoromethoxybenzyloxymethyl) isoxazole-3-carboxylate represented by formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.38 (t, 1H), 7.27 (d, 1H), 7.21 (s, 1H), 7.17 (d, 1H) ), 6.7 (s, 1H), 4.70 (s, 2H), 4.62 (s, 2H), 4.44 (q, 2H), 1.42 (t, 3H)

で示される５−（３−トリフルオロメトキシベンジルオキシメチル）イソキサゾール−３−カルボン酸1.１gを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．５０（ｔ，１Ｈ），７．３８（ｄ，１Ｈ），７．３３−７．２９（ｔ，２Ｈ），６．８７（ｓ，１Ｈ）４．７５（ｓ，２Ｈ），４．６３（ｔ，２Ｈ） Reference production example 56
In Reference Production Example 44, instead of ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate, ethyl 5- (3-trifluoromethoxybenzyloxymethyl) isoxazole-3-carboxylate (1.8 g, 5.21 The reaction is carried out in the same manner using

Thus, 1.1 g of 5- (3-trifluoromethoxybenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 14.0 (brs, 1H), 7.50 (t, 1H), 7.38 (d, 1H), 7.33-7.29 (T, 2H), 6.87 (s, 1H) 4.75 (s, 2H), 4.63 (t, 2H)

で示される５−（３−トリフルオロメチルチオベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル０．２gを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．６２（ｍ，２Ｈ），７．４５（ｍ，２Ｈ），６．７０（ｓ，１Ｈ），４．６９（ｓ，２Ｈ），４．６３（ｓ，２Ｈ），４．４４（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference Production Example 57
In Reference Production Example 43, 3-trifluoromethylthiobenzyl bromide (3.5 g, 13.45 mmol) was used instead of 2-chlorobenzyl bromide, and the same reaction was performed.

0.2 g of ethyl 5- (3-trifluoromethylthiobenzyloxymethyl) isoxazole-3-carboxylate represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.62 (m, 2H), 7.45 (m, 2H), 6.70 (s, 1H), 4.69 (s, 2H) ), 4.63 (s, 2H), 4.44 (q, 2H), 1.42 (t, 3H)

で示される５−（３−トリフルオロメチルチオベンジルオキシメチル）イソキサゾール−３−カルボン酸１２８ｍgを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．６７（ｄ，２Ｈ），７．５６（ｑ，２Ｈ），６．８７（ｓ，１Ｈ），４．７６（ｓ，２Ｈ），４．６５（ｓ，２Ｈ） Reference Production Example 58
In Reference Production Example 44, ethyl 5- (3-trifluoromethylthiobenzyloxymethyl) isoxazole-3-carboxylate (500 mg, 1.38) instead of ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate The reaction is carried out in the same manner using

As a result, 128 mg of 5- (3-trifluoromethylthiobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 14.0 (brs, 1H), 7.67 (d, 2H), 7.56 (q, 2H), 6.87 (s, 1H ), 4.76 (s, 2H), 4.65 (s, 2H)

で示される５−（３−メチルベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル１．６gを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．２７−７．２３（ｍ，１Ｈ），７．１６−７．１２（ｍ，３Ｈ），６．６９（ｓ，１Ｈ），４．６５（ｓ，２Ｈ），４．５７（ｓ，２Ｈ），４．４４（ｑ，２Ｈ），２．３６（ｓ，３Ｈ），１．４２（ｔ，３Ｈ） Reference Production Example 59
In Reference Production Example 43, 3-methylbenzyl bromide (2.7 g, 14.61 mmol) was used instead of 2-chlorobenzyl bromide, and the same reaction was performed.

1.6 g of ethyl 5- (3-methylbenzyloxymethyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.27-7.23 (m, 1H), 7.16-7.12 (m, 3H), 6.69 (s, 1H) 4.65 (s, 2H), 4.57 (s, 2H), 4.44 (q, 2H), 2.36 (s, 3H), 1.42 (t, 3H)

で示される５−（３−メチルベンジルオキシメチル）イソキサゾール−３−カルボン酸１．５gを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．２４（ｔ，１Ｈ），７．１５−７．１３（ｍ，３Ｈ），６．８５（ｓ，１Ｈ），４．６９（ｓ，２Ｈ），４．５３（ｓ，２Ｈ），２．３０（ｓ，３Ｈ） Reference Production Example 60
In Reference Production Example 44, instead of ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate, ethyl 5- (3-methylbenzyloxymethyl) isoxazole-3-carboxylate (2.2 g, 7.75 mmol) The same reaction is carried out using

Thus, 1.5 g of 5- (3-methylbenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.0 (brs, 1H), 7.24 (t, 1H), 7.15-7.13 (m, 3H), 6. 85 (s, 1H), 4.69 (s, 2H), 4.53 (s, 2H), 2.30 (s, 3H)

で示される５−（３−メトキシベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル１．６gを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．３０−７．２８（ｍ，１Ｈ），６．９３−６．８５（ｍ，３Ｈ），６．６９（ｓ，１Ｈ），４．６５（ｓ，２Ｈ），４．５９（ｓ，２Ｈ），４．４４（ｑ，２Ｈ），３．８２（ｓ，３Ｈ），１．４２（ｔ，３Ｈ） Reference Production Example 61
In Reference Production Example 43, 3-methoxybenzyl bromide (2.93 g, 14.61 mmol) was used instead of 2-chlorobenzyl bromide, and a similar reaction was performed.

1.6 g of ethyl 5- (3-methoxybenzyloxymethyl) isoxazole-3-carboxylate represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.30-7.28 (m, 1H), 6.93-6.85 (m, 3H), 6.69 (s, 1H) , 4.65 (s, 2H), 4.59 (s, 2H), 4.44 (q, 2H), 3.82 (s, 3H), 1.42 (t, 3H)

で示される５−（３−メトキシベンジルオキシメチル）イソキサゾール−３−カルボン酸１．２gを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．２７（ｔ，１Ｈ），６．９２−６．８６（ｍ，４Ｈ），４．７０（ｓ，２Ｈ），４．５４（ｓ，２Ｈ）３．７５（ｓ，３Ｈ） Reference Production Example 62
In Reference Production Example 44, instead of ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate, ethyl 5- (3-methoxybenzyloxymethyl) isoxazole-3-carboxylate (2.2 g, 7.75 mmol) ) Using the following formula

Thus, 1.2 g of 5- (3-methoxybenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.0 (brs, 1H), 7.27 (t, 1H), 6.92-6.86 (m, 4H), 4. 70 (s, 2H), 4.54 (s, 2H) 3.75 (s, 3H)

で示される５−（３−シアノベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル０．３５gを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．６０（ｍ，３Ｈ），７．５０（ｔ，１Ｈ），６．７２（ｓ，１Ｈ），４．７２（ｓ，２Ｈ），４．６３（ｓ，２Ｈ），４．４６（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference Production Example 63
In Reference Production Example 43, 3-cyanobenzyl bromide (1.13 g, 5.84 mmol) was used instead of 2-chlorobenzyl bromide, and the same reaction was performed.

As a result, 0.35 g of ethyl 5- (3-cyanobenzyloxymethyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.60 (m, 3H), 7.50 (t, 1H), 6.72 (s, 1H), 4.72 (s, 2H) ), 4.63 (s, 2H), 4.46 (q, 2H), 1.42 (t, 3H)

で示される５−（３−シアノベンジルオキシメチル）イソキサゾール−３−カルボン酸１．５gを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．７９（ｍ，２Ｈ），７．７１−７．６９（ｄ，１Ｈ），７．６０−７．５６（ｄ，１Ｈ），６．９０（ｓ，１Ｈ），４．７５（ｓ，２Ｈ），４．６３（ｓ，２Ｈ） Reference production example 64
In Reference Production Example 44, instead of ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate, ethyl 5- (3-cyanobenzyloxymethyl) isoxazole-3-carboxylate (2.1 g, 7.34 mmol) And using lithium hydroxide (308 mg, 7.34 mmol) in place of potassium hydroxide,

Thus, 1.5 g of 5- (3-cyanobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 14.0 (brs, 1H), 7.79 (m, 2H), 7.71-7.69 (d, 1H), 7.60 -7.56 (d, 1H), 6.90 (s, 1H), 4.75 (s, 2H), 4.63 (s, 2H)

で示される５−（３−メチルチオベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル０．７gを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．３７−７．３１（ｍ，４Ｈ），６．６９（ｓ，１Ｈ）４．６７（ｓ，２Ｈ），４．６０（ｓ，２Ｈ），４．４８（ｓ，２Ｈ），２．５０（ｓ，３Ｈ）１．４２（ｔ，３Ｈ） Reference Production Example 65
In Reference Production Example 43, 3-methylthiobenzyl bromide (2.6 g, 12.28 mmol) was used instead of 2-chlorobenzyl bromide, and the same reaction was carried out.

0.7 g of ethyl 5- (3-methylthiobenzyloxymethyl) isoxazole-3-carboxylate represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.37-7.31 (m, 4H), 6.69 (s, 1H) 4.67 (s, 2H), 4.60 ( s, 2H), 4.48 (s, 2H), 2.50 (s, 3H) 1.42 (t, 3H)

で示される５−（３−メチルチオベンジルオキシメチル）イソキサゾール−３−カルボン酸３５０ｍgを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１４．４（ｂｒｓ，１Ｈ），７．４０−７．０（ｍ，４Ｈ），６．８０（ｍ，１Ｈ），４．８０−４．４０（ｍ，４Ｈ），２．４０（ｓ，３Ｈ） Reference production example 66
In Reference Production Example 44, instead of ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate, ethyl 5- (3-methylthiobenzyloxymethyl) isoxazole-3-carboxylate (735 mg, 2.39 mmol) ) Using the following formula

As a result, 350 mg of 5- (3-methylthiobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 14.4 (brs, 1H), 7.40-7.0 (m, 4H), 6.80 (m, 1H), 4.80 -4.40 (m, 4H), 2.40 (s, 3H)

で示される５−（４−フルオロベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル１．８gを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．３４−７．２９（２Ｈ，ｍ），７．０８−７．０２（２Ｈ，ｍ），６．６８（１Ｈ，ｓ），４．６５（２Ｈ，ｓ），４．５７（２Ｈ，ｓ），４．４５（２Ｈ，ｑ），１．４２（３Ｈ，ｔ） Reference Production Example 67
In Reference Production Example 43, 4-fluorobenzyl bromide (3.3 g, 17.54 mmol) was used instead of 2-chlorobenzyl bromide, and the same reaction was performed.

Thus, 1.8 g of ethyl 5- (4-fluorobenzyloxymethyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.34-7.29 (2H, m), 7.08-7.02 (2H, m), 6.68 (1H, s) 4.65 (2H, s), 4.57 (2H, s), 4.45 (2H, q), 1.42 (3H, t)

で示される５−（４−フルオロベンジルオキシメチル）イソキサゾール−３−カルボン酸１．８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．４２−７．３７（ｍ，２Ｈ），７．２１−７．１５（ｍ，２Ｈ），６．８５（ｓ，１Ｈ）４．７０（ｓ，２Ｈ）４．５５（ｔ，２Ｈ） Reference production example 68

Thus, 1.8 g of 5- (4-fluorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 14.0 (brs, 1H), 7.42-7.37 (m, 2H), 7.21-7.15 (m, 2H) 6.85 (s, 1H) 4.70 (s, 2H) 4.55 (t, 2H)

で示される５−（４−ブロモベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル１．８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．４８（ｄ，２Ｈ），７．２３（ｔ，，２Ｈ），６．６８（ｓ，１Ｈ），４．６６（ｓ，２Ｈ），４．５９（ｓ，２Ｈ），４．４３（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference Production Example 69
In Reference Production Example 43, 4-bromobenzyl bromide (5.22 g, 21.03 mmol) was used instead of 2-chlorobenzyl bromide, and the same reaction was carried out.

As a result, 1.8 g of ethyl 5- (4-bromobenzyloxymethyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.48 (d, 2H), 7.23 (t ,, 2H), 6.68 (s, 1H), 4.66 (s, 2H), 4.59 (s, 2H), 4.43 (q, 2H), 1.42 (t, 3H)

で示される５−（４−ブロモベンジルオキシメチル）イソキサゾール−３−カルボン酸２．０ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．３５（ｄｄ，２Ｈ），７．３１（ｄｄ，２Ｈ），６．８６（ｓ，１Ｈ），４．７１（ｓ，２Ｈ）４．５５（ｓ，２Ｈ） Reference production example 70
In Reference Production Example 44, instead of ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate, ethyl 5- (4-bromobenzyloxymethyl) isoxazole-3-carboxylate (2.4 g, 7.05 mmol) The same reaction is carried out using

2.0 g of 5- (4-bromobenzyloxymethyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.0 (brs, 1H), 7.35 (dd, 2H), 7.31 (dd, 2H), 6.86 (s, 1H), 4.71 (s, 2H) 4.55 (s, 2H)

で示される５−（４−トリフルオロメトキシベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル２．４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．３８（ｄ，２Ｈ），７．２２（ｄ，２Ｈ），６．６９（ｓ，１Ｈ），４．６８（ｓ，２Ｈ），４．６０（ｓ，２Ｈ），４．４５（ｑ，２Ｈ），１．４３（ｔ，３Ｈ） Reference production example 71
In Reference Production Example 43, 4-trifluoromethoxybenzyl bromide (4.1 g, 16.37 mmol) was used instead of 2-chlorobenzyl bromide, and the reaction was carried out in the same manner.

Thus, 2.4 g of ethyl 5- (4-trifluoromethoxybenzyloxymethyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.38 (d, 2H), 7.22 (d, 2H), 6.69 (s, 1H), 4.68 (s, 2H) ), 4.60 (s, 2H), 4.45 (q, 2H), 1.43 (t, 3H)

で示される５−（４−トリフルオロメトキシベンジルオキシメチル）イソキサゾール−３−カルボン酸２．４ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．４８（ｄ，２Ｈ），７．３５（ｄ，２Ｈ），６．８７（ｓ，１Ｈ），４．７４（ｓ，２Ｈ），４．６１（ｓ，２Ｈ） Reference production example 72
In Reference Production Example 44, instead of ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate, ethyl 5- (4-trifluoromethoxybenzyloxymethyl) isoxazole-3-carboxylate (2.8 g, 8.11 The reaction is carried out in the same manner using

Thus, 2.4 g of 5- (4-trifluoromethoxybenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.0 (brs, 1H), 7.48 (d, 2H), 7.35 (d, 2H), 6.87 (s, 1H), 4.74 (s, 2H), 4.61 (s, 2H)

で示される５−（４−トリフルオロメチルチオベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル１．４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．６５（ｄ，２Ｈ），７．４０（ｄ，２Ｈ），６．７０（ｓ，１Ｈ），４．７０（ｓ，２Ｈ），４．６４（ｓ，２Ｈ），４．４５（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference production example 73
In Reference Production Example 43, 4-trifluoromethylthiobenzyl bromide (3.96 g, 14.61 mmol) was used instead of 2-chlorobenzyl bromide, and the reaction was carried out in the same manner.

1.4 g of ethyl 5- (4-trifluoromethylthiobenzyloxymethyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.65 (d, 2H), 7.40 (d, 2H), 6.70 (s, 1H), 4.70 (s, 2H) ), 4.64 (s, 2H), 4.45 (q, 2H), 1.42 (t, 3H)

で示される５−（４−トリフルオロメチルチオベンジルオキシメチル）イソキサゾール−３−カルボン酸１．２ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．７２（ｄ，２Ｈ），７．５１（ｄ，２Ｈ），６．８８（ｓ，１Ｈ）４．７６（ｓ，２Ｈ），４．６６（ｓ，２Ｈ） Reference production example 74
In Reference Production Example 44, instead of ethyl 5- (2-chlorobenzyl) oxymethylisoxazole-3-carboxylate, ethyl 5- (4-trifluoromethylthiobenzyl) oxymethylisoxazole-3-carboxylate ( 1.7 g, 4.70 mmol)

Thus, 1.2 g of 5- (4-trifluoromethylthiobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.0 (brs, 1H), 7.72 (d, 2H), 7.51 (d, 2H), 6.88 (s, 1H) 4.76 (s, 2H), 4.66 (s, 2H)

で示される５−（４−メチルベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル３．３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．３２（ｄ，２Ｈ），７．１７（ｄ，２Ｈ），６．６４（ｓ，１Ｈ），４．６３（ｓ，２Ｈ），４．５２（ｓ，２Ｈ，４．４３（ｑ，２Ｈ），２．３５（ｓ，３Ｈ），１．４２（ｔ，３Ｈ） Reference production example 75
In Reference Production Example 43, 4-methylbenzyl bromide (5.16 g, 28.04 mmol) was used instead of 2-chlorobenzyl bromide, and the same reaction was carried out.

Then, 3.3 g of ethyl 5- (4-methylbenzyloxymethyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.32 (d, 2H), 7.17 (d, 2H), 6.64 (s, 1H), 4.63 (s, 2H) ), 4.52 (s, 2H, 4.43 (q, 2H), 2.35 (s, 3H), 1.42 (t, 3H)

で示される５−（４−メチルベンジルオキシメチル）イソキサゾール−３−カルボン酸２．８ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．２３（ｄ，２Ｈ），７．１７（ｄ，２Ｈ），６．８４（ｓ，１Ｈ）４．６７（ｓ，２Ｈ），４．５１（ｓ，２Ｈ），２．２９（ｓ，３Ｈ） Reference production example 76
In Reference Production Example 44, instead of ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate, ethyl 5- (4-methylbenzyloxymethyl) isoxazole-3-carboxylate (4.0 g, 14.54 mmol) The same reaction is carried out using

As a result, 2.8 g of 5- (4-methylbenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.0 (brs, 1H), 7.23 (d, 2H), 7.17 (d, 2H), 6.84 (s, 1H) 4.67 (s, 2H), 4.51 (s, 2H), 2.29 (s, 3H)

で示される５−（４−メトキシベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル２．５ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：７．３０（ｄ，２Ｈ），６．９０（ｄ，２Ｈ），６．７０（ｓ，１Ｈ），４．６５（ｓ，２Ｈ），４．５５（ｓ，２Ｈ），４．４５（ｑ，２Ｈ），３．７０（ｓ，３Ｈ），１．４０（ｔ，３Ｈ） Reference Production Example 77
In Reference Production Example 43, 4-methoxybenzyl bromide (4.1 g, 20.46 mmol) was used instead of 2-chlorobenzyl bromide, and the same reaction was performed.

Thus, 2.5 g of ethyl 5- (4-methoxybenzyloxymethyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 7.30 (d, 2H), 6.90 (d, 2H), 6.70 (s, 1H), 4.65 (s, 2H), 4.55 (s, 2H), 4.45 (q, 2H), 3.70 (s, 3H), 1.40 (t, 3H)

で示される５−（４−メトキシベンジルオキシメチル）イソキサゾール−３−カルボン酸２．０ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．２８（ｄ，２Ｈ），６．９６−６．８８（ｄｄ，２Ｈ），６．８４（ｓ，１Ｈ），４．６８（ｓ，２Ｈ），４．５０（ｓ，２Ｈ），３．７６（ｓ，３Ｈ） Reference production example 78
In Reference Production Example 44, instead of ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate, ethyl 5- (4-methoxybenzyloxymethyl) isoxazole-3-carboxylate (2.5 g, 8.59 mmol) The same reaction is carried out using

2.0 g of 5- (4-methoxybenzyloxymethyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.0 (brs, 1H), 7.28 (d, 2H), 6.96-6.88 (dd, 2H), 6. 84 (s, 1H), 4.68 (s, 2H), 4.50 (s, 2H), 3.76 (s, 3H)

で示される５−（４−シアノベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル２．８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．６７（ｄ，２Ｈ），７．４７（ｄ，２Ｈ），６．７１（ｓ，１Ｈ），４．７２（ｓ，２Ｈ），４．６６（ｓ，２Ｈ），４．４４（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference Production Example 79
In Reference Production Example 43, 4-cyanobenzyl bromide (4 g, 23.40 mmol) was used instead of 2-chlorobenzyl bromide, and the same reaction was performed.

As a result, 2.8 g of ethyl 5- (4-cyanobenzyloxymethyl) isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.67 (d, 2H), 7.47 (d, 2H), 6.71 (s, 1H), 4.72 (s, 2H) ), 4.66 (s, 2H), 4.44 (q, 2H), 1.42 (t, 3H)

で示される５−（４−シアノベンジルオキシメチル）イソキサゾール−３−カルボン酸２．１ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．８３（ｄ，２Ｈ），７．５５（ｄ，２Ｈ），６．８８（ｓ，１Ｈ），４．７６（ｓ，２Ｈ），４．６８（ｓ，２Ｈ） Reference production example 80
In Reference Production Example 44, instead of ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate, ethyl 5- (4-cyanobenzyloxymethyl) isoxazole-3-carboxylate (2.8 g, 9.79 mmol) Using lithium hydroxide (411 mg, 9.79 mmol) instead of potassium hydroxide,

2.1 g of 5- (4-cyanobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.0 (brs, 1H), 7.83 (d, 2H), 7.55 (d, 2H), 6.88 (s, 1H), 4.76 (s, 2H), 4.68 (s, 2H)

で示される５−（４−メチルチオベンジルオキシメチル）イソキサゾール−３−カルボン酸エチル１．３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．３０−７．２３（ｍ，４Ｈ），６．９２（ｓ，１Ｈ），４．７０（ｓ，２Ｈ），４．５２（ｓ，２Ｈ），４．３９（ｑ，２Ｈ），２．５１−２．４６（ｍ，３Ｈ），１．３２（ｔ，３Ｈ） Reference production example 81
In Reference Production Example 43, 4-methylthiobenzyl bromide (2.5 g, 11.69 mmol) was used instead of 2-chlorobenzyl bromide, and the same reaction was performed.

As a result, 1.3 g of ethyl 5- (4-methylthiobenzyloxymethyl) isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.30-7.23 (m, 4H), 6.92 (s, 1H), 4.70 (s, 2H), 4.52 (S, 2H), 4.39 (q, 2H), 2.51-2.46 (m, 3H), 1.32 (t, 3H)

で示される５−（４−メチルチオベンジルオキシメチル）イソキサゾール−３−カルボン酸１．２ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．０（Ｂｒｓ，１Ｈ），７．３０−７．２３（ｍ，４Ｈ），６．８４（ｓ，１Ｈ）４．６５（ｓ，２Ｈ），４．５２（ｓ，２Ｈ），２．４９−２．４６（ｍ，３Ｈ） Reference production example 82
In Reference Production Example 44, instead of ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate, ethyl 5- (4-methylthiobenzyloxymethyl) isoxazole-3-carboxylate (1.5 g, 4.88 mmol) The same reaction is carried out using

Thus, 1.2 g of 5- (4-methylthiobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.0 (Brs, 1H), 7.30-7.23 (m, 4H), 6.84 (s, 1H) 4.65 (S, 2H), 4.52 (s, 2H), 2.49-2.46 (m, 3H)

で示される４−［５−（１，３−ベンゾジオキソラニル）メトキシメチル］イソキサゾール−３−カルボン酸エチル４．０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：６．８４（ｓ，１Ｈ），６．７９（ｄ，２Ｈ），６．６７（ｓ，１Ｈ），５．９９（ｓ，２Ｈ），４．６２（ｓ，２Ｈ），４．６０（ｓ，２Ｈ），４．４８（ｑ，２Ｈ），１．４２（ｔ，３Ｈ）． Reference production example 83
In Reference Production Example 43, 4-bromomethyl-1,3-benzodioxole (8 g, 37.2 mmol) was used instead of 2-chlorobenzyl bromide, and the reaction was carried out in the same manner.

4.0 g of ethyl 4- [5- (1,3-benzodioxolanyl) methoxymethyl] isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 6.84 (s, 1H), 6.79 (d, 2H), 6.67 (s, 1H), 5.99 (s, 2H) ), 4.62 (s, 2H), 4.60 (s, 2H), 4.48 (q, 2H), 1.42 (t, 3H).

で示される５−［５−（１，３−ベンゾジオキソラニル）メトキシメチル］イソキサゾール−３−カルボン酸３．０ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），６．８１（ｍ，４Ｈ），６．０８（ｓ，２Ｈ）４．６６（ｓ，２Ｈ）４．４６（ｓ，２Ｈ） Reference production example 84
In Reference Preparation Example 44, instead of ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate, 4- [5- (1,3-benzodioxolanyl) methoxymethyl] isoxazole-3-carboxylic acid Ethyl (4 g, 14.4 mmol) was used for the same reaction,

Thus, 3.0 g of 5- [5- (1,3-benzodioxolanyl) methoxymethyl] isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.0 (brs, 1H), 6.81 (m, 4H), 6.08 (s, 2H) 4.66 (s, 2H) 4.46 (s, 2H)

で示される５−（チオフェン−３−イルメチル）オキシメチルイソキサゾール−３−カルボン酸エチル１．６５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．３４−７．３２（ｍ，１Ｈ），７．２６（ｓ，１Ｈ），７．０８（ｄ，１Ｈ），６．６７（ｓ，１Ｈ），４．６４−４．６２（ｍ，４Ｈ），４．４４（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference production example 85
Under a nitrogen atmosphere, 60% sodium hydride (1.05 g, 26.31 mmol) was added to dehydrated N, N-dimethylformamide (10 ml) cooled to 0 ° C. and ethyl 5-hydroxymethylisoxazole-3-carboxylate. A solution of (3.0 g, 17.54 mmol) in dehydrated N, N-dimethylformamide (20 ml) was added dropwise over 10 minutes, and the mixture was further stirred for 30 minutes. A solution of 3- (bromomethyl) thiophene (3.1 g, 17.54 mmol) in dry N, N-dimethylformamide (3 ml) was added, the reaction mixture was warmed to room temperature, stirred for 16 hours, and then added to saturated aqueous ammonium chloride solution. The mixture was extracted twice with ethyl acetate, and the organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.65 g of ethyl 5- (thiophen-3-ylmethyl) oxymethylisoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.34-7.32 (m, 1H), 7.26 (s, 1H), 7.08 (d, 1H), 6.67 (S, 1H), 4.64-4.62 (m, 4H), 4.44 (q, 2H), 1.42 (t, 3H)

で示される５−（チオフェン−３−イルメチル）オキシメチルイソキサゾール−３−カルボン酸１．６ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．５４−７．５２（ｍ，１Ｈ），７．４８（ｄ，１Ｈ），７．１０−７．０８（ｍ，１Ｈ），６．８４（ｓ，１Ｈ），４．６８（ｓ，２Ｈ），４．５６（ｓ，２Ｈ） Reference production example 86
Ethyl 5- (thiophen-3-ylmethyl) oxymethylisoxazole-3-carboxylate (4.0 g, 13.55 mmol) was added to ethanol (50 mL), and 2N sodium hydroxide (30 mL) was added, followed by room temperature. For 16 hours. Then, it concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, cooled to 0 ° C., and the precipitated solid was filtered. The solid is dried under reduced pressure

1.6 g of 5- (thiophen-3-ylmethyl) oxymethylisoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.0 (brs, 1H), 7.54-7.52 (m, 1H), 7.48 (d, 1H), 7. 10-7.08 (m, 1H), 6.84 (s, 1H), 4.68 (s, 2H), 4.56 (s, 2H)

で示される５−（５−クロロチオフェン−２−イルメチル）オキシメチルイソキサゾール−３−カルボン酸エチル２．６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：６．８０（ｍ，２Ｈ），６．６８（ｓ，１Ｈ），４．６５（ｓ，４Ｈ），４．４３（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference production example 87
Under a nitrogen atmosphere, 60% sodium hydride (1.40 g, 35.08 mmol) was added to dehydrated N, N-dimethylformamide (20 ml) cooled to 0 ° C. and ethyl 5-hydroxymethylisoxazole-3-carboxylate. A solution of dehydrated N, N-dimethylformamide (10 ml) in (4.0 g, 23.39 mmol) was added dropwise over 10 minutes, and the mixture was further stirred for 30 minutes. A solution of 2-bromomethyl-5-chlorothiophene (3.9 g, 23.39 mmol) in dehydrated N, N-dimethylformamide (10 ml) was added, and the mixture was warmed to room temperature and stirred for 16 hours. The reaction mixture was added to saturated aqueous ammonium chloride solution and extracted twice with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 2.6 g of ethyl 5- (5-chlorothiophen-2-ylmethyl) oxymethylisoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 6.80 (m, 2H), 6.68 (s, 1H), 4.65 (s, 4H), 4.43 (q, 2H) ), 1.42 (t, 3H)

で示される５−（５−クロロチオフェン−２−イルメチル）オキシメチルイソキサゾール−３−カルボン酸２．５ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．０３−６．９９（ｍ，２Ｈ），６．８５（ｓ，１Ｈ）４．７０−４．６８（ｍ，４Ｈ） Reference production example 88
Ethyl 5- (5-chlorothiophen-2-ylmethyl) oxymethylisoxazole-3-carboxylate (3.0 g, 9.96 mmol) was added to ethanol (30 mL), followed by 2N sodium hydroxide (15 mL). The mixture was stirred at room temperature for 16 hours and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, cooled to 0 ° C., and the precipitated solid was filtered. The obtained solid was dried under reduced pressure,

Thus, 2.5 g of 5- (5-chlorothiophen-2-ylmethyl) oxymethylisoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.0 (brs, 1H), 7.03-6.99 (m, 2H), 6.85 (s, 1H) 4.70 -4.68 (m, 4H)

で示される５−（ベンゾフラン−２−イルメトキシメチル）イソキサゾール−３−カルボン酸エチル０．４０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．５６（ｄ，１Ｈ），７．４８（ｄ，１Ｈ），７．３２−７．２８（ｍ，１Ｈ），７．２６−７．２１（ｍ，１Ｈ），６．７４（ｓ，１Ｈ），６．７０（ｓ，１Ｈ），４．６２（ｓ，２Ｈ），４．４４（ｓ２Ｈ），４．１２（ｑ，２Ｈ），１．４（ｔ，３Ｈ）． Reference production example 89
Under a nitrogen atmosphere, 60% sodium hydride (0.44 g, 11.4 mmol) was added to dehydrated N, N-dimethylformamide (4 ml) cooled to 0 ° C. and ethyl 5-hydroxymethylisoxazole-3-carboxylate. A solution of dehydrated N, N-dimethylformamide (5 ml) in (1.3 g, 7.60 mmol) was added dropwise and stirred for another 30 minutes. A solution of 2-bromomethylbenzofuran (1.56 g, 7.60 mmol) in dehydrated N, N-dimethylformamide (5 ml) was added, the temperature was raised to room temperature, and the mixture was stirred for 16 hours. And extracted twice. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 0.40 g of ethyl 5- (benzofuran-2-ylmethoxymethyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.56 (d, 1H), 7.48 (d, 1H), 7.32-7.28 (m, 1H), 7.26 -7.21 (m, 1H), 6.74 (s, 1H), 6.70 (s, 1H), 4.62 (s, 2H), 4.44 (s2H), 4.12 (q, 2H), 1.4 (t, 3H).

で示される５−（ベンゾフラン−２−イルメトキシメチル）イソキサゾール−３−カルボン酸０．３５ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．６４（ｄ，１Ｈ），７．５６（ｄ，１Ｈ），７．３２（ｔ，１Ｈ），７．２５（ｔ，１Ｈ），６．９７（ｓ，１Ｈ）６．８７（ｓ，１Ｈ），４．７６（ｓ，２Ｈ），４．７１（ｓ，２Ｈ） Reference production example 90
Ethyl 5- (benzofuran-2-ylmethoxymethyl) isoxazole-3-carboxylate (0.66 g, 1.99 mmol) was added to ethanol (6 mL) followed by 2N sodium hydroxide (3 mL) at room temperature. After stirring for hours, the mixture was concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, cooled to 0 ° C., and the precipitated solid was filtered. The obtained solid was dried under reduced pressure,

As a result, 0.35 g of 5- (benzofuran-2-ylmethoxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.0 (brs, 1H), 7.64 (d, 1H), 7.56 (d, 1H), 7.32 (t, 1H), 7.25 (t, 1H), 6.97 (s, 1H) 6.87 (s, 1H), 4.76 (s, 2H), 4.71 (s, 2H)

で示される５−（ベンゾチオフェン−２−イルメトキシメチル）イソキサゾール−３−カルボン酸エチル１．０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．８２（ｄ，１Ｈ），７．７５（ｄ，１Ｈ），７．３４−７．３１（ｍ，２Ｈ），７．２０（ｍ，１Ｈ），６．７０（ｓ，１Ｈ），４．９０（ｓ，２Ｈ），４．７０（ｓ，２Ｈ），４．４５（ｑ，２Ｈ），１．４０（ｓ，３Ｈ） Reference production example 91
Under a nitrogen atmosphere, 60% sodium hydride (1.04 g, 26.3 mmol) was added to dehydrated N, N-dimethylformamide (10 ml) cooled to 0 ° C. and ethyl 5-hydroxymethylisoxazole-3-carboxylate. A solution of dehydrated N, N-dimethylformamide (10 ml) in (3.0 g, 17.54 mmol) was added dropwise and stirred for another 30 minutes. A solution of 2-bromomethylbenzothiophene (4.0 g, 17.54 mmol) in dehydrated N, N-dimethylformamide (5 ml) was added, the temperature was raised to room temperature, and the mixture was stirred for 16 hours. Extracted twice with ethyl. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.0 g of ethyl 5- (benzothiophen-2-ylmethoxymethyl) isoxazole-3-carboxylate represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.82 (d, 1H), 7.75 (d, 1H), 7.34-7.31 (m, 2H), 7.20 (M, 1H), 6.70 (s, 1H), 4.90 (s, 2H), 4.70 (s, 2H), 4.45 (q, 2H), 1.40 (s, 3H)

で示される５−（ベンゾチオフェン−２−イルメトキシメチル）イソキサゾール−３−カルボン酸０．３５ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．９７−７．９４（ｍ，１Ｈ），７．８４−７．８１（ｍ，１Ｈ），７．４３（ｓ，１Ｈ），７．４０−７．３２（ｍ，２Ｈ），６．８８（ｓ，１Ｈ），４．８７（ｓ，２Ｈ），４．７６（ｓ，２Ｈ） Reference production example 92
Ethyl 5- (benzothiophen-2-ylmethoxymethyl) isoxazole-3-carboxylate (1.0 g, 3.1 mmol) was added to ethanol (10 mL), 2N sodium hydroxide (5 mL) was further added, and 16 hours at room temperature. After stirring for hours, the mixture was concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, cooled to 0 ° C., and the precipitated solid was filtered. The obtained solid was dried under reduced pressure,

As a result, 0.35 g of 5- (benzothiophen-2-ylmethoxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.0 (brs, 1H), 7.97-7.94 (m, 1H), 7.84-7.81 (m, 1H) ), 7.43 (s, 1H), 7.40-7.32 (m, 2H), 6.88 (s, 1H), 4.87 (s, 2H), 4.76 (s, 2H)

で示される５−（１−フェニルエトキシメチル）イソキサゾール−３−カルボン酸エチル０．８６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４０（３Ｈ，ｔ），１．４７（３Ｈ，ｄ），４．４２−４．５５（４Ｈ，ｍ），４．５２（１Ｈ，ｑ），６．６３（１Ｈ，ｓ），７．３３−７．３７（５Ｈ，ｍ） Reference Production Example 93
Ethyl nitroacetate (1.49 g, 12.5 mmol), (1-phenylethyl) propargyl ether (1.6 g, 10 mmol) and 1,4-diazabicyclo [2.2.2] octane (0.22 g, 2.0 mmol) ) Was added to chloroform (amylene-added product) (3 mL). The mixture was heated to reflux for 24 hours, ethyl nitroacetate (1.49 g, 12.5 mmol) was added, and the mixture was further heated to reflux for 4 hours, then cooled to room temperature and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.86 g of ethyl 5- (1-phenylethoxymethyl) isoxazole-3-carboxylate represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.40 (3H, t), 1.47 (3H, d), 4.42 to 4.55 (4H, m), 4.52 (1H, q), 6.63 (1H, s), 7.33-7.37 (5H, m)

で示される５−（１−フェニルエトキシメチル）イソキサゾール−３−カルボン酸０．５０ｇを得た。得られたカルボン酸は精製することなく製造例１２３に用いた。 Reference production example 94
Ethyl 5- (1-phenylethoxymethyl) isoxazole-3-carboxylate (0.86 g, 3.12 mmol) was added to ethanol (10 mL), and potassium hydroxide (1.40 g, 25 mmol) and water (2 mL) were added. The mixture was stirred overnight at room temperature, and concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

Thus, 0.50 g of 5- (1-phenylethoxymethyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained. The obtained carboxylic acid was used in Production Example 123 without purification.

で示される５−（１，１−ジフェニルメトキシメチル）イソキサゾール−３−カルボン酸エチル０．８６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４１（３Ｈ，ｔ），４．４１−４．５５（２Ｈ，ｑ），４．６４（２Ｈ，ｓ），５．４７（１Ｈ，ｓ），６．６９（１Ｈ，ｓ），７．２５−７．３４（１０Ｈ，ｍ） Reference production example 95
Ethyl nitroacetate (1.49 g, 12.5 mmol), 1,1-diphenylmethylpropargyl ether (1.6 g, 10 mmol) and 1,4-diazabicyclo [2.2.2] octane (0.22 g, 2.0 mmol) ) Was added to chloroform (amylene-added product) (3 mL). The mixture was heated under reflux for 24 hours, ethyl nitroacetate (1.49 g, 12.5 mmol) was added, and the mixture was further heated under reflux for 4 hours, then cooled to room temperature and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 0.86 g of ethyl 5- (1,1-diphenylmethoxymethyl) isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.41 (3H, t), 4.41-4.55 (2H, q), 4.64 (2H, s), 5.47 (1H, s), 6.69 (1H, s), 7.25-7.34 (10H, m)

で示される５−５−（１，１−ジフェニルメトキシメチル）イソキサゾール−３−カルボン酸１．３６ｇを得た。得られたカルボン酸は精製することなく製造例１２４に用いた。 Reference production example 96
Ethyl 5- (1,1-diphenylmethoxymethyl) isoxazole-3-carboxylate (1.75 g, 5.2 mmol) was added to ethanol (50 mL), followed by potassium hydroxide (1.46 g, 26 mmol) and water (10 mL). ) And stirred at room temperature overnight, and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

1.35 g of 5-5- (1,1-diphenylmethoxymethyl) isoxazole-3-carboxylic acid represented by The obtained carboxylic acid was used in Production Example 124 without purification.

で示される５−（２，２，２−トリフルオロ−１−フェニルエトキシメチル）イソキサゾール−３−カルボン酸エチル１．０２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４１（３Ｈ，ｔ），４．４３（２Ｈ，ｑ），４．６５−４．７６（３Ｈ，ｍ），６．７０（１Ｈ，ｓ），７．４３（５Ｈ，ｍ） Reference Production Example 97
Ethyl nitroacetate (1.49 g, 12.5 mmol), (2,2,2-trifluoro-1-phenylethyl) propargyl ether (2.14 g, 10 mmol) and 1,4-diazabicyclo [2.2.2] Octane (0.22 g, 2.0 mmol) was added to chloroform (amylene-added product) (3 mL). The mixture was heated to reflux for 24 hours, ethyl nitroacetate (1.49 g, 12.5 mmol) was added, and the mixture was further heated to reflux for 4 hours, then cooled to room temperature and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

In this manner, 1.02 g of ethyl 5- (2,2,2-trifluoro-1-phenylethoxymethyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.41 (3H, t), 4.43 (2H, q), 4.65-4.76 (3H, m), 6.70 (1H, s), 7.43 (5H, m)

で示される５−（２，２，２−トリフルオロ−１−フェニルエトキシメチル）イソキサゾール−３−カルボン酸０．９８ｇを得た。得られたカルボン酸は精製することなく製造例１２５に用いた。 Reference production example 98
Ethyl 5- (2,2,2-trifluoro-1-phenylethoxymethyl) isoxazole-3-carboxylate (1.02 g, 3.09 mmol) was added to ethanol (15 mL), and potassium hydroxide (0.35 g) was added. , 6.2 mmol) and water (3 mL) were added, and the mixture was stirred at room temperature overnight and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

0.98 g of 5- (2,2,2-trifluoro-1-phenylethoxymethyl) isoxazole-3-carboxylic acid represented by The obtained carboxylic acid was used in Production Example 125 without purification.

で示される５−（２，２，２−トリフルオロエトキシメチル）イソキサゾール−３−カルボン酸エチル１．０２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４１（３Ｈ，ｔ），３．９１（２Ｈ，ｑ），４．４３（２Ｈ，ｑ），４．８０（２Ｈ，ｓ），６．７３（１Ｈ，ｓ） Reference Production Example 99
Under a nitrogen atmosphere, ethyl 5-hydroxymethylisoxazole-3-carboxylate (1.71 g, 10.0 mmol), 2,2,2-trifluoroethylmethanesulfonic acid ester (5.34 g, 30 mmol), N, N-dimethylformamide (30 ml) and 60% sodium hydride (0.48 g, 12.0 mmol) were mixed at 0 ° C., warmed to room temperature and stirred for 16 hours. And extracted twice. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.02 g of ethyl 5- (2,2,2-trifluoroethoxymethyl) isoxazole-3-carboxylate represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.41 (3H, t), 3.91 (2H, q), 4.43 (2H, q), 4.80 (2H, s) ), 6.73 (1H, s)

で示される５−（２，２，２−トリフルオロエトキシメチル）イソキサゾール−３−カルボン酸０．９８ｇを得た。得られたカルボン酸は精製することなく製造例１２６にて用いた。 Reference production example 100
Ethyl 5- (2,2,2-trifluoroethoxymethyl) isoxazole-3-carboxylate (1.02 g, 3.09 mmol) was added to ethanol (15 mL), and potassium hydroxide (0.35 g, 6.2 mmol) was added. ) And water (3 mL) were added, and the mixture was stirred overnight at room temperature and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

0.98 g of 5- (2,2,2-trifluoroethoxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained. The obtained carboxylic acid was used in Production Example 126 without purification.

で示される５−（１−ヒドロキシエチル）イソキサゾール−３−カルボン酸エチル７．２５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４０（３Ｈ，ｔ），１．６１（３Ｈ，ｄ），４．４２（２Ｈ，ｑ），５．０５（１Ｈ，ｑ），６．６１（１Ｈ，ｓ） Reference production example 101
Ethyl nitroacetate (14.8 g, 125 mmol), 3-butyn-2-ol (7.0 g, 100 mmol) and 1,4-diazabicyclo [2.2.2] octane (2.24 g, 20 mmol) in ethanol (50 ml) ) And heated at 80 ° C. for 48 hours, cooled to room temperature, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

7.25 g of ethyl 5- (1-hydroxyethyl) isoxazole-3-carboxylate represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.40 (3H, t), 1.61 (3H, d), 4.42 (2H, q), 5.05 (1H, q ), 6.61 (1H, s)

で示される５−[１−（ベンジルオキシ）エチル]イソキサゾール−３−カルボン酸エチル１．２９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．５５−１．６１（６Ｈ，ｔ），４．４１−４．６０（４Ｈ，m），４．６９−４．７４（１Ｈ，m），６．６４（１Ｈ，ｓ），７．３２−７．３８（５Ｈ，m） Reference production example 102
Under nitrogen atmosphere, ethyl 5- (1-hydroxyethyl) isoxazole-3-carboxylate (1.85 g, 10.0 mmol), benzyl bromide (3.42 g, 12.0 mmol), N, N-dimethylformamide (20 ml) 60% sodium hydride (0.49 g, 12.0 mmol) was mixed at 0 ° C., warmed to room temperature, stirred for 16 hours, added to 1N hydrochloric acid, and extracted twice with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

To 1.29 g of ethyl 5- [1- (benzyloxy) ethyl] isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.55-1.61 (6H, t), 4.41-4.60 (4H, m), 4.69-4.74 ( 1H, m), 6.64 (1H, s), 7.32-7.38 (5H, m)

で示される５−[１−（ベンジルオキシ）エチル]イソキサゾール−３−カルボン酸１．００ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．５８（３Ｈ，d），３．３８―３．６２（２Ｈ，dd），４．７５（１Ｈ，ｑ），６．６８（１Ｈ，ｓ），７．３２−７．３４（５Ｈ，m） Reference production example 103
Ethyl 5- [1- (benzyloxy) ethyl] isoxazole-3-carboxylate (1.29 g, 4.7 mmol) was added to ethanol (20 mL), followed by potassium hydroxide (0.79 g, 14.1 mmol) and water. (4 mL) was added, and the mixture was stirred overnight at room temperature, and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

1.00 g of 5- [1- (benzyloxy) ethyl] isoxazole-3-carboxylic acid represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.58 (3H, d), 3.38-3.62 (2H, dd), 4.75 (1H, q), 6.68 (1H, s), 7.32-7.34 (5H, m)

で示される５−（１−ベンジルオキシ−１−フェニルメチル）イソキサゾール−３−カルボン酸０．４４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：４．５７（２H，dd），４．７０（１Ｈ，s），６．６０（１Ｈ，ｓ），７．３３−７．４０（５Ｈ，m） Reference production example 104
Under nitrogen atmosphere at 0 ° C., ethyl 5- (1-hydroxy-1-phenylmethyl) isoxazole-3-carboxylate (1.24 g, 5.0 mmol), benzyl bromide (1.03 g, 6.0 mmol), N, N-dimethylformamide (10 ml) and 60% sodium hydride (0.24 g, 6.0 mmol) were mixed, warmed to room temperature, stirred for 16 hours, added to 1N hydrochloric acid, and extracted twice with ethyl acetate. . The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was added to ethanol (10 mL), potassium hydroxide (0.49 g, 8.80 mmol) and water (2 mL) were added, and the mixture was stirred overnight at room temperature, and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

0.44 g of 5- (1-benzyloxy-1-phenylmethyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 4.57 (2H, dd), 4.70 (1H, s), 6.60 (1H, s), 7.33-7.40 (5H, m)

で示される５−（３−フェニルプロボキシメチル）イソキサゾール−３−カルボン酸エチル１．９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．３０−７．２５（ｍ，２Ｈ），７．２０−７．１５（ｍ，３Ｈ），６．６５（ｓ，１Ｈ），４．６１（ｓ，２Ｈ），４．４０（ｑ，２Ｈ），３．５３（ｔ，２Ｈ），２．７０（ｔ，２Ｈ），１．９８−１．８８（ｍ，２Ｈ），１．４２（ｔ，３Ｈ） Reference production example 105
Under a nitrogen atmosphere, 60% sodium hydride (1.04 g, 26.0 mmol) was added to dehydrated N, N-dimethylformamide (10 ml) cooled to 0 ° C. and ethyl 5-hydroxymethylisoxazole-3-carboxylate. A solution of dehydrated N, N-dimethylformamide (10 ml) in (3.0 g, 17.54 mmol) was added dropwise and stirred for another 30 minutes. A solution of 1-bromo-3-phenylpropane (3.5 g, 17.54 mmol) in dehydrated N, N-dimethylformamide (5 ml) was added, the mixture was warmed to room temperature and stirred for 16 hours, and then added to a saturated aqueous ammonium chloride solution. And extracted twice with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 1.9 g of ethyl 5- (3-phenylpropoxymethyl) isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.30-7.25 (m, 2H), 7.20-7.15 (m, 3H), 6.65 (s, 1H) 4.61 (s, 2H), 4.40 (q, 2H), 3.53 (t, 2H), 2.70 (t, 2H), 1.98-1.88 (m, 2H), 1.42 (t, 3H)

で示される５−（３−フェニルプロポキシメチル）イソキサゾール−３−カルボン酸１．８０ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．２８−７．１３（ｍ，５Ｈ），６．８２（ｓ，１Ｈ），４．６４（ｓ，２Ｈ），３．４６（ｔ，２Ｈ），２．６１（ｔ，２Ｈ），１．８６−１．７７（ｍ，２Ｈ） Reference production example 106
Ethyl 5- (3-phenylpropoxymethyl) isoxazole-3-carboxylate (2.5 g, 8.7 mmol) was added to ethanol (20 mL), 2N sodium hydroxide (15 mL) was further added, and the mixture was stirred at room temperature for 16 hours. Then, it concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, cooled to 0 ° C., and the precipitated solid was filtered. The obtained solid was dried under reduced pressure,

To 1.80 g of 5- (3-phenylpropoxymethyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.0 (brs, 1H), 7.28-7.13 (m, 5H), 6.82 (s, 1H), 4. 64 (s, 2H), 3.46 (t, 2H), 2.61 (t, 2H), 1.86-1.77 (m, 2H)

で示される５−（４−フェニルブトキシメチル）イソキサゾール−３−カルボン酸エチル１．６５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．２７（ｍ，２Ｈ），７．１７（ｍ，３Ｈ），６．６５（ｓ，１Ｈ），４．６０（ｓ，２Ｈ），４．４５（ｑ，２Ｈ），３．５３（ｔ，２Ｈ），２．６３（ｔ，２Ｈ），１．６８（ｍ，４Ｈ），１．４６（ｔ，３Ｈ） Reference production example 107
Under a nitrogen atmosphere, 60% sodium hydride (1.04 g, 26.0 mmol) was added to dehydrated N, N-dimethylformamide (10 ml) cooled to 0 ° C. and ethyl 5-hydroxymethylisoxazole-3-carboxylate. A solution of dehydrated N, N-dimethylformamide (10 ml) in (3.0 g, 17.54 mmol) was added dropwise and stirred for another 30 minutes. A solution of 1-bromo-4-phenylbutane (3.73 g, 17.54 mmol) in dehydrated N, N-dimethylformamide (5 ml) was added, and the mixture was warmed to room temperature and stirred for 16 hours, and then added to a saturated aqueous ammonium chloride solution. And extracted twice with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.65 g of ethyl 5- (4-phenylbutoxymethyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.27 (m, 2H), 7.17 (m, 3H), 6.65 (s, 1H), 4.60 (s, 2H) ), 4.45 (q, 2H), 3.53 (t, 2H), 2.63 (t, 2H), 1.68 (m, 4H), 1.46 (t, 3H)

で示される５−（４−フェニルブトキシメチル）イソキサゾール−３−カルボン酸１．８０ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：７．２９−７．２１（ｍ，５Ｈ），６．８０（ｓ，１Ｈ），４．６２（ｓ，２Ｈ），３．５０−３．３１（ｔ，２Ｈ），２．５８−２．４８（ｍ，３Ｈ），１．６２−１．５０（ｍ，４Ｈ） Reference production example 108
Ethyl 5- (4-phenylbutoxymethyl) isoxazole-3-carboxylate (2.5 g, 8.7 mmol) was added to ethanol (20 mL), 2N sodium hydroxide (15 mL) was further added, and the mixture was stirred at room temperature for 16 hours. Then, it concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, cooled to 0 ° C., and the precipitated solid was filtered. The obtained solid was dried under reduced pressure,

As a result, 1.80 g of 5- (4-phenylbutoxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 7.29-7.21 (m, 5H), 6.80 (s, 1H), 4.62 (s, 2H), 3. 50-3.31 (t, 2H), 2.58-2.48 (m, 3H), 1.62-1.50 (m, 4H)

で示される５−（５−フェニルペンチルオキシメチル）イソキサゾール−３−カルボン酸エチル１．６５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．２９（ｍ，２Ｈ），７．１７（ｍ，３Ｈ），６．６５（ｓ，１Ｈ），４．６１（ｓ，２Ｈ），４．４４（ｔ，２Ｈ），３．５１（ｔ，２Ｈ），２．６１（ｔ，２Ｈ），１．６２（ｍ，４Ｈ），１．４２（ｔ，５Ｈ） Reference Production Example 109
Under a nitrogen atmosphere, 60% sodium hydride (1.04 g, 26.0 mmol) was added to dehydrated N, N-dimethylformamide (10 ml) cooled to 0 ° C. and ethyl 5-hydroxymethylisoxazole-3-carboxylate. A solution of dehydrated N, N-dimethylformamide (10 ml) in (3.0 g, 17.54 mmol) was added dropwise and stirred for another 30 minutes. A solution of 1-bromo-5-phenylpentane (3.90 g, 17.54 mmol) in dehydrated N, N-dimethylformamide (5 ml) was added, the mixture was warmed to room temperature and stirred for 16 hours, and then added to a saturated aqueous ammonium chloride solution. And extracted twice with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.65 g of ethyl 5- (5-phenylpentyloxymethyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.29 (m, 2H), 7.17 (m, 3H), 6.65 (s, 1H), 4.61 (s, 2H) ), 4.44 (t, 2H), 3.51 (t, 2H), 2.61 (t, 2H), 1.62 (m, 4H), 1.42 (t, 5H)

で示される５−（５−フェニルペンチルオキシメチル）イソキサゾール−３−カルボン酸１．５０ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：14.0(s,1H),7.28-7.23(m,2H),7.18-7.16(m,3H),6.8(s,1H),4.62(s,2H),3.48-3.43(t,2H),2.57-2.49(m,2H),1.60-1.50(m,4H),1.35-1.25(m,2H) Reference Production Example 110
Ethyl 5- (5-phenylpentyloxymethyl) isoxazole-3-carboxylate (2.2 g, 6.9 mmol) was added to an ethanol: water = 2: 1 mixed solution (26 mL), and 2N sodium hydroxide (14 mL) was added. After stirring at room temperature for 16 hours, the mixture was concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, cooled to 0 ° C., and the precipitated solid was filtered. The obtained solid was dried under reduced pressure,

1.50 g of 5- (5-phenylpentyloxymethyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.0 (s, 1H), 7.28-7.23 (m, 2H), 7.18-7.16 (m, 3H), 6.8 (s, 1H), 4.62 (s, 2H), 3.48-3.43 (t, 2H), 2.57-2.49 (m, 2H), 1.60-1.50 (m, 4H), 1.35-1.25 (m, 2H)

で示される５−（３−ヒドロキシプロピル）イソキサゾール−３−カルボン酸エチル８．６１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４０（３Ｈ，ｔ），１．９７−２．０３（２Ｈ，m），２．９３（２Ｈ，t），３．７１−３．７２（２Ｈ，m），４．４１（２H，q），６．４３（１Ｈ，ｓ） Reference Production Example 111
Ethyl nitroacetate (9.56 g, 80 mmol), 4-pentyn-1-ol (6.73 g, 80 mmol) and 1,4-diazabicyclo [2.2.2] octane (1.79 g, 16.0 mmol) in ethanol. (40 ml). The mixture was heated at 80 ° C. for 48 hours, cooled to room temperature, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 8.61 g of ethyl 5- (3-hydroxypropyl) isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.40 (3H, t), 1.97-2.03 (2H, m), 2.93 (2H, t), 3.71 -3.72 (2H, m), 4.41 (2H, q), 6.43 (1H, s)

で示される５−（３−ベンジルオキシプロピル）イソキサゾール−３−カルボン酸エチル０．９１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４０（３H，t），１．９８−２．０３（２Ｈ，m），２．９０−２．９４（２Ｈ，m），３．４９（２Ｈ，t），４．３９（２H，q），４．４８（２H，s），６．３７（１Ｈ，ｓ），７．２７−７．３６（５Ｈ，m） Reference production example 112
Under nitrogen atmosphere, ethyl 5- (3-hydroxypropyl) isoxazole-3-carboxylate (1.99 g, 10.0 mmol), benzyl bromide (1.71 g, 10.0 mmol), N, N-dimethylformamide (10 ml) 60% sodium hydride (0.40 g, 10.0 mmol) was mixed at 0 ° C., warmed to room temperature, stirred for 16 hours, added to 1N hydrochloric acid, and extracted twice with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.91 g of ethyl 5- (3-benzyloxypropyl) isoxazole-3-carboxylate represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.40 (3H, t), 1.98-2.03 (2H, m), 2.90-2.94 (2H, m) 3.49 (2H, t), 4.39 (2H, q), 4.48 (2H, s), 6.37 (1H, s), 7.27-7.36 (5H, m).

で示される５−（３−ベンジルオキシプロピル）イソキサゾール−３−カルボン酸０．６５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：２．００−２．０４（２Ｈ，m），２．９５（２Ｈ，t），３．５２（２Ｈ，t），４．５０（２H，s），６．４１（１Ｈ，ｓ），７．２７−７．３６（５Ｈ，m） Reference production example 113
Ethyl 5- (3-benzyloxypropyl) isoxazole-3-carboxylate (0.91 g, 3.1 mmol) was added to ethanol (10 mL), followed by potassium hydroxide (0.53 g, 9.5 mmol) and water (2 mL). ) And stirred at room temperature overnight, and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

0.65 g of 5- (3-benzyloxypropyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 2.00 to 2.04 (2H, m), 2.95 (2H, t), 3.52 (2H, t), 4.50 (2H, s), 6.41 (1H, s), 7.27-7.36 (5H, m)

で示される５−（４−ヒドロキシブチル）イソキサゾール−３−カルボン酸エチル８．６１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４２（３Ｈ，ｔ），１．６１−１．６９（２H，m），１．８０−１．８８（２Ｈ，m），２．８６（２Ｈ，t），３．７０（２Ｈ，t），４．４３（２H，q），６．４４（１Ｈ，ｓ） Reference production example 114
Ethyl nitroacetate (9.56 g, 80 mmol), 5-hexyn-1-ol (7.85 g, 80 mmol) and 1,4-diazabicyclo [2.2.2] octane (1.79 g, 16.0 mmol) in ethanol (40 ml). The mixture was heated at 80 ° C. for 48 hours, cooled to room temperature, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 8.61 g of ethyl 5- (4-hydroxybutyl) isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42 (3H, t), 1.61-1.69 (2H, m), 1.80-1.88 (2H, m) , 2.86 (2H, t), 3.70 (2H, t), 4.43 (2H, q), 6.44 (1H, s)

で示される５−（４−ベンジルオキシブチル）イソキサゾール−３−カルボン酸エチル０．７８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４０（３H，t），１．６６−１．６９（２H，m），１．７７−１．８３（２Ｈ，m），２．７８−２．８３（２Ｈ，m），３．４７（２Ｈ，t），４．４１（２H，q），４．４８（２H，s），６．４０（１Ｈ，ｓ），７．２６−７．３７（５Ｈ，m） Reference production example 115
Under nitrogen atmosphere, ethyl 5- (4-hydroxybutyl) isoxazole-3-carboxylate (2.13 g, 10.0 mmol), benzyl bromide (1.71 g, 10.0 mmol), N, N-dimethylformamide (10 ml) 60% sodium hydride (0.40 g, 10.0 mmol) was mixed at 0 ° C., warmed to room temperature, stirred for 16 hours, added to 1N hydrochloric acid, and extracted twice with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 0.78 g of ethyl 5- (4-benzyloxybutyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.40 (3H, t), 1.66 to 1.69 (2H, m), 1.77-1.83 (2H, m) , 2.78-2.83 (2H, m), 3.47 (2H, t), 4.41 (2H, q), 4.48 (2H, s), 6.40 (1H, s), 7.26-7.37 (5H, m)

で示される５−（４−ベンジルオキシブチル）イソキサゾール−３−カルボン酸０．４２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．６８−１．７０（２H，m），１．７９−１．８７（２Ｈ，m），２．８３（２Ｈ，t），３．５０（２Ｈ，t），４．５０（２H，s），６．４４（１Ｈ，ｓ），７．２６−７．３７（５Ｈ，m） Reference production example 116
Ethyl 5- (4-benzyloxybutyl) isoxazole-3-carboxylate (0.78 g, 2.6 mmol) was added to ethanol (10 mL), followed by potassium hydroxide (0.58 g, 10.4 mmol) and water (2 mL). ) And stirred at room temperature overnight, and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

0.42 g of 5- (4-benzyloxybutyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.68-1.70 (2H, m), 1.79-1.87 (2H, m), 2.83 (2H, t) , 3.50 (2H, t), 4.50 (2H, s), 6.44 (1H, s), 7.26-7.37 (5H, m)

で示される５−（５−ヒドロキシペンチル）イソキサゾール−３−カルボン酸エチル２．５９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４０（３Ｈ，ｔ），１．４２−１．４７（２H，m），１．５６−１．６３（２H，m），１．７１−１．７９（２Ｈ，m），２．８１（２Ｈ，t），３．６２（２Ｈ，q），４．４１（２H，q），６．４０（１Ｈ，ｓ） Reference Production Example 117
Ethyl nitroacetate (7.89 g, 66 mmol), 6-heptin-1-ol 5.95 g, 53 mmol) and 1,4-diazabicyclo [2.2.2] octane (1.19 g, 10.6 mmol) in ethanol ( 40 ml). The mixture was heated at 80 ° C. for 24 hours, cooled to room temperature, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

To give 2.59 g of ethyl 5- (5-hydroxypentyl) isoxazole-3-carboxylate
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.40 (3H, t), 1.42-1.47 (2H, m), 1.56-1.63 (2H, m) , 1.71-1.79 (2H, m), 2.81 (2H, t), 3.62 (2H, q), 4.41 (2H, q), 6.40 (1H, s)

で示される５−（５−ベンジルオキシペンチル）イソキサゾール−３−カルボン酸の粗生成物１．３４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４２―１．４６（２H，m），１．６２−１．６５（２H，m），１．７０−１．７４（２Ｈ，m），２．７６−２．８１（２Ｈ，m），３．４３−３．４７（２Ｈ，m），４．４８（２H，s），６．３９（１Ｈ，ｓ），７．３１−７．３７（５Ｈ，m） Reference production example 118
Under nitrogen atmosphere, ethyl 5- (5-hydroxypentyl) isoxazole-3-carboxylate (1.14 g, 5.0 mmol), benzyl bromide (0.86 g, 5.0 mmol), N, N-dimethylformamide (5 ml) And 60% sodium hydride (0.2 g, 5.0 mmol) were mixed at 0 ° C., warmed to room temperature, stirred for 16 hours, added to 1N hydrochloric acid, and extracted twice with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was added to ethanol (20 mL), potassium hydroxide (1.12 g, 20 mmol) and water (4 mL) were added, and the mixture was stirred overnight at room temperature, and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

1.34 g of a crude product of 5- (5-benzyloxypentyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42-1.46 (2H, m), 1.62-1.65 (2H, m), 1.70-1.74 ( 2H, m), 2.76-2.81 (2H, m), 3.43-3.47 (2H, m), 4.48 (2H, s), 6.39 (1H, s), 7 .31-7.37 (5H, m)

で示される５−（６−ヒドロキシヘキシル）イソキサゾール−３−カルボン酸エチル９．６７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３７−１．４１（７Ｈ，ｔ），１．５４−１．５９（２H，m），１．７０−１．７６（２Ｈ，m），２．７９（２Ｈ，t），３．６１（２Ｈ，t），４．４１（２H，q），６．３９（１Ｈ，ｓ） Reference Production Example 119
Ethyl nitroacetate (8.60 g, 72.3 mmol), 7-octin-1-ol (7.63 g, 57.8 mmol) and 1,4-diazabicyclo [2.2.2] octane (1.30 g, 11. 6 mmol) was added to ethanol (25 ml). The mixture was heated at 80 ° C. for 48 hours, cooled to room temperature, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 9.67 g of ethyl 5- (6-hydroxyhexyl) isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.37-1.41 (7H, t), 1.54-1.59 (2H, m), 1.70-1.76 ( 2H, m), 2.79 (2H, t), 3.61 (2H, t), 4.41 (2H, q), 6.39 (1H, s)

で示される５−（６−ベンジルオキシヘキシル）イソキサゾール−３−カルボン酸を含む粗生成物１．２３ｇを得た。該粗生成物は精製することなく製造例１４０に用いた。 Reference production example 120
Under nitrogen atmosphere, ethyl 5- (6-hydroxyhexyl) isoxazole-3-carboxylate (1.14 g, 5.0 mmol), benzyl bromide (0.86 g, 5.0 mmol), N, N-dimethylformamide (5 ml) And 60% sodium hydride (0.2 g, 5.0 mmol) were mixed at 0 ° C., warmed to room temperature, stirred for 16 hours, added to 1N hydrochloric acid, and extracted twice with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was added to ethanol (20 mL), potassium hydroxide (1.12 g, 20 mmol) and water (4 mL) were added, and the mixture was stirred overnight at room temperature, and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

As a result, 1.23 g of a crude product containing 5- (6-benzyloxyhexyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained. The crude product was used in Production Example 140 without purification.

で示される５−（３−フェノキシプロピル）イソキサゾール−３−カルボン酸０．４９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：２．１８−２．２５（２Ｈ，m），３．０５（２Ｈ，t），４．０１（２Ｈ，t），６．４９（１Ｈ，ｓ），６．８１−６．９７（３Ｈ，m），７．２１−７．３０（２H，m） Reference production example 121
Under a nitrogen atmosphere, ethyl 5- (3-hydroxypropyl) isoxazole-3-carboxylate (1.99 g, 10.0 mmol), triphenylphosphine (5.38 g, 20.0 mmol) and phenol (1.88 g, 20. 0 mmol) was added to dehydrated tetrahydrofuran (50 ml). A solution of diethyl azodicarboxylate in tetrahydrofuran (2.2 M, 10 ml, 22.0 mmol) was added dropwise over 30 minutes, and the mixture was stirred at room temperature for 24 hours. Tert-butyl methyl ether was added to the reaction mixture, and the solid was removed by filtration. After the filtrate was concentrated under reduced pressure, ethanol (20 mL) was added to the residue, potassium hydroxide (1.12 g, 20 mmol) and water (2 mL) were added, and the mixture was stirred overnight at room temperature, and then concentrated under reduced pressure. Water was added to the concentrate, washed with tert-butyl methyl ether, diluted hydrochloric acid was added to the aqueous layer, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

0.49 g of 5- (3-phenoxypropyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 2.18-2.25 (2H, m), 3.05 (2H, t), 4.01 (2H, t), 6.49 (1H, s), 6.81-6.97 (3H, m), 7.21-7.30 (2H, m)

で示される５−（４−フェノキシブチル）イソキサゾール−３−カルボン酸エチル１．７２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４０（３H，t），１．８３−１．９５（４Ｈ，m），２．８９（２Ｈ，t），３．９８（２Ｈ，t），４．４１（２H，q），６．４４（１Ｈ，ｓ），６．８１−６．９５（３Ｈ，m），７．２１−７．２９（２H，m） Reference Production Example 122
Under nitrogen atmosphere, ethyl 5- (4-hydroxybutyl) isoxazole-3-carboxylate (1.48 g, 6.9 mmol), triphenylphosphine (3.74 g, 13.9 mmol) and phenol (1.31 g, 13. 9 mmol) was added to dehydrated tetrahydrofuran (69 ml). A tetrahydrofuran solution of diethyl azodicarboxylate (2.2 M, 6.4 ml, 13.9 mmol) was added dropwise over 30 minutes, and the mixture was stirred at room temperature for 24 hours. The reaction mixture was added to dilute hydrochloric acid, extracted with ethyl acetate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Thus, 1.72 g of ethyl 5- (4-phenoxybutyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.40 (3H, t), 1.83-1.95 (4H, m), 2.89 (2H, t), 3.98 (2H, t), 4.41 (2H, q), 6.44 (1H, s), 6.81-6.95 (3H, m), 7.21-7.29 (2H, m)

で示される５−（４−フェノキシブチル）イソキサゾール−３−カルボン酸３．６４ｇを含む粗生成物を得た。該粗生成物は精製することなく次の工程に用いた。 Reference Production Example 123
Ethyl 5- (4-phenoxybutyl) isoxazole-3-carboxylate (1.72 g, 5.94 mmol) was added to ethanol (10 mL), and potassium hydroxide (0.67 g, 11.9 mmol) and water (2 mL) were added. After stirring at room temperature overnight, the mixture was concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

A crude product containing 3.64 g of 5- (4-phenoxybutyl) isoxazole-3-carboxylic acid represented by the following formula was obtained. The crude product was used in the next step without purification.

で示される５−（５−フェノキシペンチル）イソキサゾール−３−カルボン酸エチル１．１９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４０（３Ｈ，m），１．５５−１．５８（２H，m），１．７７−１．８５（４Ｈ，m），２．８３（２H，t），３．９３（２H，t），４．４１（２H，q），６．４１（１H，s），６．８１−６．９２（３H，m），７．２１−７．２９（２H，m）． Reference production example 124
Under a nitrogen atmosphere, ethyl 5- (5-hydroxypentyl) isoxazole-3-carboxylate (1.14 g, 5.0 mmol), triphenylphosphine (2.69 g, 10.0 mmol) and phenol (1.31 g, 13. 9 mmol) was added to dehydrated tetrahydrofuran (69 ml). A tetrahydrofuran solution of diethyl azodicarboxylate (2.2 M, 6.4 ml, 13.9 mmol) was added dropwise over 30 minutes, and the mixture was stirred at room temperature for 24 hours. The reaction mixture was added to dilute hydrochloric acid, extracted with ethyl acetate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.19 g of ethyl 5- (5-phenoxypentyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.40 (3H, m), 1.55-1.58 (2H, m), 1.77-1.85 (4H, m) , 2.83 (2H, t), 3.93 (2H, t), 4.41 (2H, q), 6.41 (1H, s), 6.81-6.92 (3H, m), 7.2-21.29 (2H, m).

で示される５−（５−フェノキシペンチル）イソキサゾール−３−カルボン酸０．７０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．５４−１．６０（２H，m），１．７７−１．８４（４Ｈ，m），２．８６（２H，t），３．９６（２H，t），６．４７（１H，s），６．８１−６．９２（３H，m），７．２１−７．２９（２H，m） Reference production example 125
Ethanol (10 mL) was added to ethyl 5- (5-phenoxypentyl) isoxazole-3-carboxylate (1.19 g, 3.92 mmol), and potassium hydroxide (0.67 g, 11.9 mmol) and water (2 mL) were added. After stirring at room temperature overnight, the mixture was concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

In this way, 0.70 g of 5- (5-phenoxypentyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.54-1.60 (2H, m), 1.77-1.84 (4H, m), 2.86 (2H, t) 3.96 (2H, t), 6.47 (1H, s), 6.81-6.92 (3H, m), 7.21-7.29 (2H, m)

で示される５−（６−フェノキシヘキシル）イソキサゾール−３−カルボン酸エチル１．４１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４０−１．５２（７Ｈ，m），１．７１−１．７９（４H，m），２．８０（２Ｈ，t），３．９４（２H，t），４．４１（２H，q），６．４０（１H，s），６．８１−６．９３（３H，m），７．２１−７．２８（２H，m） Reference Production Example 126
Under a nitrogen atmosphere, ethyl 5- (6-hydroxyhexyl) isoxazole-3-carboxylate (1.21 g, 5.0 mmol), triphenylphosphine (2.69 g, 10.0 mmol) and phenol (1.31 g, 13. 9 mmol) was added to dehydrated tetrahydrofuran (69 ml). A tetrahydrofuran solution of diethyl azodicarboxylate (2.2 M, 6.4 ml, 13.9 mmol) was added dropwise over 30 minutes, and the mixture was stirred at room temperature for 24 hours. The reaction mixture was added to dilute hydrochloric acid, extracted with ethyl acetate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.41 g of ethyl 5- (6-phenoxyhexyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.40-1.52 (7H, m), 1.71-1.79 (4H, m), 2.80 (2H, t) , 3.94 (2H, t), 4.41 (2H, q), 6.40 (1H, s), 6.81-6.93 (3H, m), 7.21-7.28 (2H , M)

で示される５−（６−フェノキシヘキシル）イソキサゾール−３−カルボン酸１．３２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４２−１．５３（４Ｈ，m），１．７２−１．８０（４H，m），２．８１（２Ｈ，t），３．９４（２H，t），６．４５（１H，s），６．８３−６．９２（３H，m），７．２３−７．２８（２H，m） Reference Production Example 127
Ethanol (10 mL) is added to ethyl 5- (6-phenoxyhexyl) isoxazole-3-carboxylate (1.41 g, 4.64 mmol), and potassium hydroxide (1.29 g, 23 mmol) and water (2 mL) are added. The mixture was stirred overnight at room temperature and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

Thus, 1.32 g of 5- (6-phenoxyhexyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42-1.53 (4H, m), 1.72-1.80 (4H, m), 2.81 (2H, t) , 3.94 (2H, t), 6.45 (1H, s), 6.83-6.92 (3H, m), 7.23-7.28 (2H, m)

で示される５−（２−フェノキシエトキシメチル）イソキサゾール−３−カルボン酸エチル１．５６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４０（３H，ｔ），３．９１（２H，t），４．１５（２H，ｔ），４．４２（２H，q），４．７７（２H，s），６．７１（１H，s），６．８９（２H，d），６．９５（１H，t），７．２４−７．２９（２H、m） Reference production example 128
Add ethyl nitroacetate (2.11 g, 17.7 mmol), (2-phenoxyethyl) propargyl ether (1.96 g, 10 mmol) and 1,4-diazabicyclo [2.2.2] octane (0.56 g, 5 mmol). The mixture was added to chloroform (amylene-added product) (3 mL), heated to reflux for 24 hours, cooled to room temperature, diluted hydrochloric acid was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Thus, 1.56 g of ethyl 5- (2-phenoxyethoxymethyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.40 (3H, t), 3.91 (2H, t), 4.15 (2H, t), 4.42 (2H, q ), 4.77 (2H, s), 6.71 (1H, s), 6.89 (2H, d), 6.95 (1H, t), 7.24-7.29 (2H, m)

で示される５−（２−フェノキシエトシメチル）イソキサゾール−３−カルボン酸１．４０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：３．９１（２H，t），４．１６（２H，ｔ），４．７９（２H，s），６．７６（１H，s），６．８９（２H，d），６．９５（１H，t），７．２４−７．３０（２H、m） Reference Production Example 129
Ethyl 5- (2-phenoxyethoxymethyl) isoxazole-3-carboxylate (1.56 g, 2.6 mmol) was added to ethanol (10 mL), followed by potassium hydroxide (0.58 g, 10.4 mmol) and water (2 mL). ) And stirred at room temperature overnight, and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

As a result, 1.40 g of 5- (2-phenoxyethoxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 3.91 (2H, t), 4.16 (2H, t), 4.79 (2H, s), 6.76 (1H, s) ), 6.89 (2H, d), 6.95 (1H, t), 7.24-7.30 (2H, m)

で示される５−（２−クロロフェノキシメチル）イソキサゾール−３−カルボン酸エチル５．５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．４０（ｄ，１Ｈ），７．２２（ｔ，１Ｈ），６．９７（ｍ，２Ｈ），６．８１（ｓ，１Ｈ），５．２７（ｓ，２Ｈ），４．５０（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference Production Example 130
A solution obtained by adding ethyl 5-hydroxymethylisoxazole-3-carboxylate (7 g, 40.89 mmol) and 2-chlorophenol (4.59 mL, 44.98 mmol) to dehydrated tetrahydrofuran (70 ml) was brought to 0 ° C. Cool and add triphenylphosphine (11.47 mL, 81.78 mmol), triethylamine (11.47 mL, 81.78 mmol) and diisopropyl azodicarboxylate (12.33 g, 61.33 mmol) under a nitrogen atmosphere. The reaction mixture was warmed to room temperature, stirred for 2 hours, poured into water, and extracted twice with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 5.5 g of ethyl 5- (2-chlorophenoxymethyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.40 (d, 1H), 7.22 (t, 1H), 6.97 (m, 2H), 6.81 (s, 1H) ), 5.27 (s, 2H), 4.50 (q, 2H), 1.42 (t, 3H)

で示される５−（２−クロロフェノキシメチル）イソキサゾール−３−カルボン酸３．８ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．１（ｂｒｓ，１Ｈ），７．４６（ｄ，１Ｈ），７．３６−７．３０（ｍ，２Ｈ），７．０２（ｔ，１Ｈ），６．９５（ｓ，１Ｈ），５．４５（ｓ，２Ｈ） Reference Production Example 131
Ethyl 5- (2-chlorophenoxymethyl) isoxazole-3-carboxylate (5.5 g, 19.57 mmol) was added to ethanol (55 mL), followed by lithium hydroxide (2.46 g, 58.7 mmol) and water (27 0.5 mL) and stirred at room temperature for 16 hours and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, cooled to 0 ° C., and the precipitated solid was filtered. The obtained solid was dried under reduced pressure,

As a result, 3.8 g of 5- (2-chlorophenoxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.1 (brs, 1H), 7.46 (d, 1H), 7.36-7.30 (m, 2H), 7. 02 (t, 1H), 6.95 (s, 1H), 5.45 (s, 2H)

で示される５−（３−クロロフェノキシメチル）イソキサゾール−３−カルボン酸エチル５．５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．２３（ｔ，１Ｈ），７．０１（ｄ，１Ｈ），６．９６（ｓ，１Ｈ），６．８４（ｄ，１Ｈ），６．７６（ｓ，１Ｈ），５．１９（ｓ，２Ｈ），４．４５（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference Production Example 132
In Reference Production Example 130, 3-chlorophenol (4.59 mL, 44.98 mmol) was used instead of 2-chlorophenol, and the reaction was performed in the same manner.

As a result, 5.5 g of ethyl 5- (3-chlorophenoxymethyl) isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.23 (t, 1H), 7.01 (d, 1H), 6.96 (s, 1H), 6.84 (d, 1H) ), 6.76 (s, 1H), 5.19 (s, 2H), 4.45 (q, 2H), 1.42 (t, 3H)

で示される５−（３−クロロフェノキシメチル）イソキサゾール−３−カルボン酸４．３ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．２（ｂｒｓ，１Ｈ），７．３２（ｔ，１Ｈ），７．１６（ｓ，１Ｈ），７．０４（ｍ，３Ｈ），５．３６（ｓ，２Ｈ） Reference Production Example 133
In Reference Production Example 131, ethyl 5- (3-chlorophenoxymethyl) isoxazole-3-carboxylate (5.5 g, 19.57 mmol) was used instead of ethyl 5- (2-chlorophenoxymethyl) isoxazole-3-carboxylate. In the same way,

Thus, 4.3 g of 5- (3-chlorophenoxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.2 (brs, 1H), 7.32 (t, 1H), 7.16 (s, 1H), 7.04 (m, 3H), 5.36 (s, 2H)

で示される５−（４−クロロフェノキシメチル）イソキサゾール−３−カルボン酸エチル２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．２７（ｄ，２Ｈ），６．８９（ｄ，２Ｈ），６．７４（ｓ，１Ｈ），５．１８（ｓ，２Ｈ），４．４５（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference Production Example 134
In Reference Production Example 130, 4-chlorophenol (4.59 mL, 44.98 mmol) was used instead of 2-chlorophenol, and the reaction was performed in the same manner.

2 g of ethyl 5- (4-chlorophenoxymethyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.27 (d, 2H), 6.89 (d, 2H), 6.74 (s, 1H), 5.18 (s, 2H) ), 4.45 (q, 2H), 1.42 (t, 3H)

で示される５−（４−クロロフェノキシメチル）イソキサゾール−３−カルボン酸１．６ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．２（ｂｒｓ，１Ｈ），７．３６（ｄ，２Ｈ），７．０９（ｄ，２Ｈ），６．９５（ｓ，１Ｈ），５．３５（ｓ，２Ｈ） Reference Production Example 135
In Reference Production Example 131, ethyl 5- (4-chlorophenoxymethyl) isoxazole-3-carboxylate (2 g, 7.11 mmol) was used instead of ethyl 5- (2-chlorophenoxymethyl) isoxazole-3-carboxylate. In the same way,

1.6 g of 5- (4-chlorophenoxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.2 (brs, 1H), 7.36 (d, 2H), 7.09 (d, 2H), 6.95 (s, 1H), 5.35 (s, 2H)

で示される５−（３，４−ジクロロフェノキシメチル）イソキサゾール−３−カルボン酸エチル５．０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．３７（ｄ，１Ｈ），７．０７（ｄ，１Ｈ），６．８２（ｄｄ，１Ｈ），６．７５（ｓ，１Ｈ），５．１８（ｓ，２Ｈ），４．５０（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference Production Example 136
In Reference Production Example 130, 3,4-dichlorophenol (7.3 g, 44.98 mmol) was used instead of 2-chlorophenol, and the reaction was performed in the same manner.

Thus, 5.0 g of ethyl 5- (3,4-dichlorophenoxymethyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.37 (d, 1H), 7.07 (d, 1H), 6.82 (dd, 1H), 6.75 (s, 1H ), 5.18 (s, 2H), 4.50 (q, 2H), 1.42 (t, 3H)

で示される５−（３，４−ジクロロフェノキシメチル）イソキサゾール−３−カルボン酸３．５ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．２（ｂｒｓ，１Ｈ），７．５７（ｄ，１Ｈ），７．４２（ｄ，１Ｈ），７．１（ｄｄ，１Ｈ），６．９７（ｓ，１Ｈ），５．４０（ｓ，２Ｈ） Reference Production Example 137
In Reference Production Example 131, instead of ethyl 5- (2-chlorophenoxymethyl) isoxazole-3-carboxylate, ethyl 5- (3,4-dichlorophenoxymethyl) isoxazole-3-carboxylate (5.0 g, 15.8 mmol) The same reaction is carried out using

Thus, 3.5 g of 5- (3,4-dichlorophenoxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.2 (brs, 1H), 7.57 (d, 1H), 7.42 (d, 1H), 7.1 (dd, 1H), 6.97 (s, 1H), 5.40 (s, 2H)

で示される５−（４−フルオロフェノキシメチル）イソキサゾール−３−カルボン酸エチル２．７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：６．９８（ｄ，２Ｈ），６．９２（ｄ，２Ｈ），６．７４（ｓ，１Ｈ），５．１７（ｓ，２Ｈ），４．４５（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference Production Example 138
In Reference Production Example 130, 4-fluorophenol (5.0 g, 44.98 mmol) was used instead of 2-chlorophenol, and the same reaction was performed.

As a result, 2.7 g of ethyl 5- (4-fluorophenoxymethyl) isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 6.98 (d, 2H), 6.92 (d, 2H), 6.74 (s, 1H), 5.17 (s, 2H) ), 4.45 (q, 2H), 1.42 (t, 3H)

で示される５−（４−フルオロフェノキシ）メチルイソキサゾール−３−カルボン酸１．７ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．２（ｂｒｓ，１Ｈ），７．１５（ｍ，２Ｈ），７．０７（ｍ，２Ｈ），６．９４（ｓ，１Ｈ），５．３２（ｓ，２Ｈ） Reference Production Example 139
In Reference Production Example 131, ethyl 5- (4-fluorophenoxymethyl) isoxazole-3-carboxylate (5.3 g, 20 mmol) was used instead of ethyl 5- (2-chlorophenoxymethyl) isoxazole-3-carboxylate. In the same way,

Then, 1.7 g of 5- (4-fluorophenoxy) methylisoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.2 (brs, 1H), 7.15 (m, 2H), 7.07 (m, 2H), 6.94 (s, 1H), 5.32 (s, 2H)

で示される５−（４−ブロモフェノキシメチル）イソキサゾール−３−カルボン酸エチル７．０ｇを得た。
５−（４−ブロモフェノキシメチル）イソキサゾール−３−カルボン酸エチルは精製することなく５−（４−ブロモフェノキシメチル）イソキサゾール−３−カルボン酸の製造に使用した。 Reference production example 140
In Reference Production Example 130, 4-bromophenol (7 g, 40.89 mmol) was used instead of 2-chlorophenol, and the reaction was performed in the same manner.

As a result, 7.0 g of ethyl 5- (4-bromophenoxymethyl) isoxazole-3-carboxylate was obtained.
Ethyl 5- (4-bromophenoxymethyl) isoxazole-3-carboxylate was used for the preparation of 5- (4-bromophenoxymethyl) isoxazole-3-carboxylic acid without purification.

で示される５−（４−ブロモフェノキシメチル）イソキサゾール−３−カルボン酸３．０ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．１（ｂｒｓ，１Ｈ），７．４８（ｄ，２Ｈ），７．０５（ｄ，２Ｈ），６．９６（ｓ，１Ｈ），５．５０（ｓ，２Ｈ） Reference Production Example 141
In Reference Production Example 131, ethyl 5- (4-bromophenoxymethyl) isoxazole-3-carboxylate (7 g, 21.47 mmol) was used instead of ethyl 5- (2-chlorophenoxymethyl) isoxazole-3-carboxylate. In the same way,

Thus, 3.0 g of 5- (4-bromophenoxymethyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.1 (brs, 1H), 7.48 (d, 2H), 7.05 (d, 2H), 6.96 (s, 1H), 5.50 (s, 2H)

で示される５−（４−トリフルオロメチルフェノキシメチル）イソキサゾール−３−カルボン酸エチル２．４を得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．５８（ｄ，２Ｈ），７．０２（ｄ，２Ｈ），６．７７（ｓ，１Ｈ），５．４５（ｓ，２Ｈ），４．４４（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference Production Example 142
In Reference Production Example 130, 4-trifluoromethylphenol (3.12 g, 19.29 mmol) was used instead of 2-chlorophenol, and the same reaction was performed.

Thus, 2.4 of ethyl 5- (4-trifluoromethylphenoxymethyl) isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.58 (d, 2H), 7.02 (d, 2H), 6.77 (s, 1H), 5.45 (s, 2H) ), 4.44 (q, 2H), 1.42 (t, 3H)

で示される５−（４−トリフルオロメチルフェノキシメチル）イソキサゾール−３−カルボン酸２．６ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．７０（ｄ，２Ｈ），７．２５（ｄ，２Ｈ），６．９９（ｓ，１Ｈ），５．４６（ｓ，２Ｈ） Reference Production Example 143
In Reference Production Example 131, instead of ethyl 5- (2-chlorophenoxymethyl) isoxazole-3-carboxylate, ethyl 5- (4-trifluoromethylphenoxymethyl) isoxazole-3-carboxylate (3.2 g, 10.15 mmol) The same reaction is carried out using

As a result, 2.6 g of 5- (4-trifluoromethylphenoxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.0 (brs, 1H), 7.70 (d, 2H), 7.25 (d, 2H), 6.99 (s, 1H), 5.46 (s, 2H)

で示される５−（４−トリフルオロメトキシフェノキシメチル）イソキサゾール−３−カルボン酸エチル６００ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．１６（ｄ，２Ｈ），６．９５（ｄ，２Ｈ），６．７６（ｓ，１Ｈ），５．２０（ｓ，２Ｈ），４．４５（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference Production Example 144
In Reference Production Example 130, 4-trifluoromethoxyphenol (0.837 mL, 6.43 mmol) was used instead of 2-chlorophenol, and the same reaction was performed.

As a result, 600 mg of ethyl 5- (4-trifluoromethoxyphenoxymethyl) isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.16 (d, 2H), 6.95 (d, 2H), 6.76 (s, 1H), 5.20 (s, 2H) ), 4.45 (q, 2H), 1.42 (t, 3H)

で示される５−（４−トリフルオロメトキシフェノキシメチル）イソキサゾール−３−カルボン酸５００ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１４．１（ｂｒｓ，１Ｈ），７．３２（ｄ，２Ｈ），７．１６（ｄ，２Ｈ），６．９７（ｓ，１Ｈ），５．３８（ｓ，２Ｈ） Reference Production Example 145
In Reference Production Example 131, instead of ethyl 5- (2-chlorophenoxymethyl) isoxazole-3-carboxylate, ethyl 5- (4-trifluoromethoxyphenoxymethyl) isoxazole-3-carboxylate (600 mg, 1.812 mmol) The same reaction is carried out using

500 mg of 5- (4-trifluoromethoxyphenoxymethyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 14.1 (brs, 1H), 7.32 (d, 2H), 7.16 (d, 2H), 6.97 (s, 1H) ), 5.38 (s, 2H)

で示される５−（４−トリフルオロメチルチオフェノキシメチル）イソキサゾール−３−カルボン酸エチル１．０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．１６（ｄ，２Ｈ），６．９５（ｄ，２Ｈ），６．７６（ｓ，１Ｈ），５．２０（ｓ，２Ｈ），４．４５（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference Production Example 146
In Reference Production Example 130, 4- (trifluoromethylthio) phenol (1.24 g, 6.427 mmol) was used instead of 2-chlorophenol, and the same reaction was performed.

1.0 g of ethyl 5- (4-trifluoromethylthiophenoxymethyl) isoxazole-3-carboxylate represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.16 (d, 2H), 6.95 (d, 2H), 6.76 (s, 1H), 5.20 (s, 2H) ), 4.45 (q, 2H), 1.42 (t, 3H)

で示される５−（４−トリフルオロメチルチオフェノキシメチル）イソキサゾール−３−カルボン酸３．０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１４．１０（ｂｒｓ，１Ｈ），７．６８（ｄ，２Ｈ），７．２１（ｄ，２Ｈ），６．９８（ｓ，１Ｈ），５．４３（ｓ，２Ｈ） Reference Production Example 147
In Reference Production Example 131, instead of ethyl 5- (2-chlorophenoxymethyl) isoxazole-3-carboxylate, ethyl 5- (4-trifluoromethylthiophenoxymethyl) isoxazole-3-carboxylate (4.5 g, 12.9 mmol) The same reaction is carried out using

Thus, 3.0 g of 5- (4-trifluoromethylthiophenoxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 14.10 (brs, 1H), 7.68 (d, 2H), 7.21 (d, 2H), 6.98 (s, 1H) ), 5.43 (s, 2H)

で示される５−（３−フルオロフェノキシメチル）イソキサゾール−３−カルボン酸エチル４．１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：６．７６（ｍ，５Ｈ），５．２０（ｓ，２Ｈ），４．４５（ｑ，２Ｈ），１．４１（ｔ，３Ｈ）． Reference production example 148
In Reference Production Example 130, 3-fluorophenol (4.32 g, 38.5 mmol) was used instead of 2-chlorophenol, and the same reaction was performed.

4.1 g of ethyl 5- (3-fluorophenoxymethyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 6.76 (m, 5H), 5.20 (s, 2H), 4.45 (q, 2H), 1.41 (t, 3H) ).

で示される５−（３−フルオロフェノキシメチル）イソキサゾール−３−カルボン酸３．２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．３４（ｑ，１Ｈ），６．９３（ｍ，４Ｈ）５．３７（ｓ，２Ｈ） Reference Production Example 149
In Reference Production Example 131, ethyl 5- (3-fluorophenoxymethyl) isoxazole-3-carboxylate (4.5 g, 17.30 mmol) was used instead of ethyl 5- (2-chlorophenoxymethyl) isoxazole-3-carboxylate. In the same way,

Thus, 3.2 g of 5- (3-fluorophenoxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 14.0 (brs, 1H), 7.34 (q, 1H), 6.93 (m, 4H) 5.37 (s, 2H)

で示される５−（３−ブロモフェノキシメチル）イソキサゾール−３−カルボン酸エチル３．６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．１６（ｍ，２Ｈ），７．１２（ｓ，１Ｈ），６．９０−６．８７（ｍ，１Ｈ），６．７６（ｓ，１Ｈ），５．４０（ｓ，２Ｈ），４．４８−４．４２（ｑ，２Ｈ），１．４４−１．４０（ｔ，３Ｈ） Reference production example 150
In Reference Production Example 130, 3-bromophenol (6.6 g, 38.58 mmol) was used instead of 2-chlorophenol, and the reaction was performed in the same manner.

3.6 g of ethyl 5- (3-bromophenoxymethyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.16 (m, 2H), 7.12 (s, 1H), 6.90-6.87 (m, 1H), 6.76 (S, 1H), 5.40 (s, 2H), 4.48-4.42 (q, 2H), 1.44-1.40 (t, 3H)

で示される５−（３−ブロモフェノキシメチル）イソキサゾール−３−カルボン酸３．４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｓ，１Ｈ），７．３１（ｓ，１Ｈ），７．２６（ｄ，１Ｈ），７．１９（ｄ，１Ｈ），７．０８（ｄ，１Ｈ），６．９６（ｓ，１Ｈ），５．３８（ｓ，２Ｈ） Reference Production Example 151
In Reference Production Example 131, ethyl 5- (3-bromophenoxymethyl) isoxazole-3-carboxylate (4.2 g, 12.88 mmol) was used instead of ethyl 5- (2-chlorophenoxymethyl) isoxazole-3-carboxylate. In the same way,

In this way, 3.4 g of 5- (3-bromophenoxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 14.0 (s, 1H), 7.31 (s, 1H), 7.26 (d, 1H), 7.19 (d, 1H) ), 7.08 (d, 1H), 6.96 (s, 1H), 5.38 (s, 2H)

で示される５−（３−トリフルオロメチルフェノキシメチル）イソキサゾール−３−カルボン酸エチル２．２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．５０−７．４０（ｍ，１Ｈ），７．３６−７．２６（ｍ，１Ｈ），７．２０（ｓ，１Ｈ），７．２６−７．１（ｄｄ，１Ｈ），６．８０（ｓ，１Ｈ），５．２５（ｓ，２Ｈ），４．４５（ｑ，２Ｈ），１．４０（ｔ，３Ｈ） Reference production example 152
In Reference Production Example 130, 3-trifluoromethylphenol (2.65 g, 16.3 mmol) was used instead of 2-chlorophenol, and the same reaction was performed.

Thus, 2.2 g of ethyl 5- (3-trifluoromethylphenoxymethyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.50-7.40 (m, 1H), 7.36-7.26 (m, 1H), 7.20 (s, 1H) 7.26-7.1 (dd, 1H), 6.80 (s, 1H), 5.25 (s, 2H), 4.45 (q, 2H), 1.40 (t, 3H)

で示される５−（３−トリフルオロメチルフェノキシメチル）イソキサゾール−３−カルボン酸１．９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．５８（ｔ，１Ｈ），７．４６−７．２８（ｍ，３Ｈ），７．０（ｓ，１Ｈ），５．５０（ｓ，２Ｈ） Reference production example 153
In Reference Production Example 131, instead of ethyl 5- (2-chlorophenoxymethyl) isoxazole-3-carboxylate, ethyl 5- (3-trifluoromethylphenoxymethyl) isoxazole-3-carboxylate (2.7 g, 8.57 mmol) The same reaction is carried out using

As a result, 1.9 g of 5- (3-trifluoromethylphenoxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 14.0 (brs, 1H), 7.58 (t, 1H), 7.46-7.28 (m, 3H), 7.0 (S, 1H), 5.50 (s, 2H)

で示される５−（３−トリフルオロメトキシフェノキシメチル）イソキサゾール−３−カルボン酸エチル３．０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．３２（ｔ，１Ｈ），６．８９（ｔ，２Ｈ），６．８１（ｍ，２Ｈ），５．２（ｓ，２Ｈ），４．４５（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference production example 154
In Reference Production Example 130, 3-trifluoromethoxyphenol (3.42 g, 19.29 mmol) was used instead of 2-chlorophenol, and the same reaction was performed.

As a result, 3.0 g of ethyl 5- (3-trifluoromethoxyphenoxymethyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.32 (t, 1H), 6.89 (t, 2H), 6.81 (m, 2H), 5.2 (s, 2H) ), 4.45 (q, 2H), 1.42 (t, 3H)

で示される５−（３−トリフルオロメトキシフェノキシメチル）イソキサゾール−３−カルボン酸３．２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），７．４５（ｔ，１Ｈ），７．１２（ｄ，２Ｈ），７．０１（ｄ，２Ｈ）５．４１（ｓ，２Ｈ） Reference production example 155
In Reference Production Example 131, instead of ethyl 5- (2-chlorophenoxymethyl) isoxazole-3-carboxylate, ethyl 5- (3-trifluoromethoxyphenoxymethyl) isoxazole-3-carboxylate (4.0 g, 12.08 mmol) The same reaction is carried out using

Thus, 3.2 g of 5- (3-trifluoromethoxyphenoxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 14.0 (brs, 1H), 7.45 (t, 1H), 7.12 (d, 2H), 7.01 (d, 2H) ) 5.41 (s, 2H)

で示される５−（３−トリフルオロメチルチオフェノキシメチル）イソキサゾール−３−カルボン酸エチル１．８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．３８（ｓ，１Ｈ），７．３６（ｓ，１Ｈ），７．２６（ｓ，１Ｈ），７．１０（ｄ，１Ｈ），６．７８（ｓ，１Ｈ），５．２３（ｓ，２Ｈ），４．４５（ｑ，２Ｈ），１．４２（ｔ，３Ｈ） Reference Production Example 156
In Reference Production Example 130, 3- (trifluoromethylthio) phenol (1.49 g, 7.68 mmol) was used instead of 2-chlorophenol, and the same reaction was performed.

Thus, 1.8 g of ethyl 5- (3-trifluoromethylthiophenoxymethyl) isoxazole-3-carboxylate represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.38 (s, 1H), 7.36 (s, 1H), 7.26 (s, 1H), 7.10 (d, 1H) ), 6.78 (s, 1H), 5.23 (s, 2H), 4.45 (q, 2H), 1.42 (t, 3H)

で示される５−（３−トリフルオロメチルチオフェノキシメチル）イソキサゾール−３−カルボン酸１．２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１４．２（ｂｒｓ，１Ｈ），７．５（ｔ，１Ｈ），７．４０（ｓ，１Ｈ），７．３６−７．３１（ｍ，２Ｈ），６．９８（ｓ，１Ｈ），５．４３（ｓ，２Ｈ） Reference Production Example 157
In Reference Production Example 131, instead of ethyl 5- (2-chlorophenoxymethyl) isoxazole-3-carboxylate, ethyl 5- (3-trifluoromethylthiophenoxymethyl) isoxazole-3-carboxylate (1.7 g, 4.91 mmol) The same reaction is carried out using

As a result, 1.2 g of 5- (3-trifluoromethylthiophenoxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 14.2 (brs, 1H), 7.5 (t, 1H), 7.40 (s, 1H), 7.36-7.31 (M, 2H), 6.98 (s, 1H), 5.43 (s, 2H)

で示される５−［５−（１，３−ベンゾジオキソラニル）オキシメチル］イソキサゾール−３−カルボン酸エチル４．３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：６．７３−６．６９（ｍ，２Ｈ），６．５３−６．５２（ｄ，１Ｈ），６．３７−６．３５（ｍ，１Ｈ），５．９０（ｓ，２Ｈ），５．１２（ｓ，２Ｈ），４．４７−４．４１（ｑ，２Ｈ），１．４３−１．３９（ｑ，３Ｈ） Reference Production Example 158
In Reference Production Example 130, sesamol (6.21 g, 45.02 mmol) was used instead of 2-chlorophenol, and the reaction was performed in the same manner.

4.3 g of ethyl 5- [5- (1,3-benzodioxolanyl) oxymethyl] isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 6.73-6.69 (m, 2H), 6.53-6.52 (d, 1H), 6.37-6.35 ( m, 1H), 5.90 (s, 2H), 5.12 (s, 2H), 4.47-4.41 (q, 2H), 1.43-1.39 (q, 3H)

で示される５−［５−（１，３−ベンゾジオキソラニル）オキシメチル］イソキサゾール−３−カルボン酸２．２ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．０（ｂｒｓ，１Ｈ），６．９２（ｓ，１Ｈ），６．８４−６．８１（ｄ，１Ｈ），６．７６（ｄ，１Ｈ），６．５０−６．４７（ｍ，１Ｈ），５．９７（ｓ，２Ｈ），５．２８（ｓ，２Ｈ） Reference Production Example 159
In Reference Production Example 131, 5-[(5- (1,3-benzodioxolanyl) oxymethyl] isoxazole-3-carboxylic acid instead of ethyl 5- (2-chlorophenoxymethyl) isoxazole-3-carboxylate Ethyl (5 g, 17.18 mmol) was used for the same reaction, and the following formula

Thus, 2.2 g of 5- [5- (1,3-benzodioxolanyl) oxymethyl] isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.0 (brs, 1H), 6.92 (s, 1H), 6.84-6.81 (d, 1H), 6. 76 (d, 1H), 6.50-6.47 (m, 1H), 5.97 (s, 2H), 5.28 (s, 2H)

で示される５−（３，４−ジメトキシフェノキシメチル）イソキサゾール−３−カルボン酸エチル１．９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：６．８５−６．７０（ｍ，２Ｈ），６．６０（ｄ，１Ｈ），６．４５（ｄｄ，１Ｈ），５．１５（ｓ，２Ｈ），４．４５（ｑ，２Ｈ），３．８６（ｓ，３Ｈ），３．８４（ｓ，３Ｈ），１．４２（ｔ，３Ｈ） Reference production example 160
In Reference Production Example 130, 3,4-dimethoxyphenol (1.3 g, 8.54 mmol) was used instead of 2-chlorophenol, and the reaction was performed in the same manner.

As a result, 1.9 g of ethyl 5- (3,4-dimethoxyphenoxymethyl) isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 6.85-6.70 (m, 2H), 6.60 (d, 1H), 6.45 (dd, 1H), 5.15 (S, 2H), 4.45 (q, 2H), 3.86 (s, 3H), 3.84 (s, 3H), 1.42 (t, 3H)

で示される５−（３，４−ジメトキシフェノキシ）メチルイソキサゾール−３−カルボン酸１．６ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ６、ＴＭＳ、δ（ｐｐｍ））：１４．１（ｂｒｓ，１Ｈ），６．９２（ｓ，１Ｈ），６．８６（ｄ，２Ｈ），６．７０（ｄ，１Ｈ），６．５８（ｄｄ，１Ｈ），５．３０（ｓ，１Ｈ），３．５６（ｓ，３Ｈ），３．４０（ｓ，３Ｈ） Reference Production Example 161
In Reference Production Example 131, instead of ethyl 5- (2-chlorophenoxymethyl) isoxazole-3-carboxylate, ethyl 5- (3,4-dimethoxyphenoxy) methylisoxazole-3-carboxylate (1.9 g, 6.18) The reaction is carried out in the same manner using

1.6 g of 5- (3,4-dimethoxyphenoxy) methylisoxazole-3-carboxylic acid represented by
¹ H-NMR (DMSO-d6, TMS, δ (ppm)): 14.1 (brs, 1H), 6.92 (s, 1H), 6.86 (d, 2H), 6.70 (d, 1H), 6.58 (dd, 1H), 5.30 (s, 1H), 3.56 (s, 3H), 3.40 (s, 3H)

で示される５−（２−ナフチル）ペンタン−２−オン３．４７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．９８（２Ｈ，ｄｔ），２．０６（３Ｈ，ｓ），２．４４（２Ｈ，ｔ），２．７６（２Ｈ，ｔ），７．２９（１Ｈ，ｄｄ），７．４０−７．４４（３Ｈ，ｍ），７．５８（１Ｈ，ｓ），７．７４―７．７９（３Ｈ，ｍ） Reference Production Example 162
2-bromonaphthalene (4.14 g, 20.0 mmol), 4-penten-2-ol (2.60 g, 30.0 mmol), palladium acetate (2.00 g, 9.0 mmol), tetrabutylammonium chloride (11. 1 g, 40.0 mmol), lithium chloride (0.85 g, 20.0 mmol) and lithium acetate dihydrate (5.20 g, 50.0 mmol) were added to N, N-dimethylformamide (40 ml) under a nitrogen atmosphere. , And stirred at 100 ° C. for 72 hours. The reaction mixture was cooled to room temperature and added to 1N hydrochloric acid, and then the solid was removed by filtration through celite and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Thus, 3.47 g of 5- (2-naphthyl) pentan-2-one represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.98 (2H, dt), 2.06 (3H, s), 2.44 (2H, t), 2.76 (2H, t ), 7.29 (1H, dd), 7.40-7.44 (3H, m), 7.58 (1H, s), 7.74-7.79 (3H, m)

で示される７−（２−ナフチル）−２，４−ジオキソへプタン酸エチル４．４８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３５（３Ｈ、ｔ），２．０８（２Ｈ，ｔ），２．５３（２Ｈ，ｔ），２．８３（２Ｈ，ｔ），４．３７（２Ｈ，ｑ），６．３２（１Ｈ，ｓ），７．３０（１Ｈ，ｄｄ），７．４０−７．４７（３Ｈ，ｍ），７．６０（１Ｈ，ｓ），７．７５―７．７８１（３Ｈ，ｍ） Reference Production Example 163
5- (2-Naphtyl) pentan-2-one (3.47 g, 16.3 mmol) and diethyl oxalate (2.40 g, 16.3 mmol)) were dissolved in ethanol (33 ml) and dissolved in a nitrogen atmosphere at 0 ° C. Cooled to. Sodium ethoxide (20% ethanol solution, 5.58 g, 16.3 mmol) was added dropwise to the cooled solution over 30 minutes, and the mixture was stirred overnight at room temperature and then concentrated under reduced pressure. 1N hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

4.48 g of ethyl 7- (2-naphthyl) -2,4-dioxoheptanoate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.35 (3H, t), 2.08 (2H, t), 2.53 (2H, t), 2.83 (2H, t ), 4.37 (2H, q), 6.32 (1H, s), 7.30 (1H, dd), 7.40-7.47 (3H, m), 7.60 (1H, s) , 7.75-7.781 (3H, m)

で示される５−［３−（２−ナフチル）プロピル］イソキサゾール−３−カルボン酸エチル３．１４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４２（３Ｈ、ｔ），２．１５（２Ｈ，ｄｔ），２．８３−２．８８（４Ｈ，ｍ），４．４３（２Ｈ，ｑ），６．４３（１Ｈ，ｓ），７．３３（１Ｈ，ｄｄ），７．４２−７．４９（３Ｈ，ｍ），７．６２（１Ｈ，ｓ），７．７８―７．８３（３Ｈ，ｍ） Reference Production Example 164
Dissolve ethyl 7- (2-naphthyl) -2,4-dioxoheptanoate (4.48 g, 15.0 mmol) in ethanol (30 ml) and add hydroxylamine hydrochloride (1.15 g, 16.5 mmol). The mixture was heated to reflux for 6 hours under a nitrogen atmosphere. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. 1N hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

3.14 g of ethyl 5- [3- (2-naphthyl) propyl] isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42 (3H, t), 2.15 (2H, dt), 2.83-2.88 (4H, m), 4.43 (2H, q), 6.43 (1H, s), 7.33 (1H, dd), 7.42-7.49 (3H, m), 7.62 (1H, s), 7.78- 7.83 (3H, m)

で示される５−［３−（２−ナフチル）プロピル］イソキサゾール−３−カルボン酸２．１９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：２．１５―２．１９（２Ｈ，ｍ），２．８４−２．８７（４Ｈ，ｍ），６．４５（１Ｈ，ｓ），７．３０（１Ｈ，ｄｄ），７．４０−７．４８（３Ｈ，ｍ），７．６１（１Ｈ，ｓ），７．７６―７．８１（３Ｈ，ｍ） Reference Production Example 165
Ethyl 5- [3- (2-naphthyl) propyl] isoxazole-3-carboxylate (3.14 g, 10.1 mmol) was dissolved in ethanol (50 ml), water (10 ml) and potassium hydroxide (2.85 g, 50.7 mmol) was added, and the mixture was stirred at room temperature for 1 hour and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

2.19 g of 5- [3- (2-naphthyl) propyl] isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 2.15-2.19 (2H, m), 2.84-2.87 (4H, m), 6.45 (1H, s) 7.30 (1H, dd), 7.40-7.48 (3H, m), 7.61 (1H, s), 7.76-7.81 (3H, m)

で示される５−［５−（２，２−ジフルオロ−１，３−ベンゾジオキソラニル）］ペンタン−２−オン２．９５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．８６（２Ｈ，ｄｔ），２．１２（３Ｈ，ｓ），２．４２（２Ｈ，ｔ），２．５９（２Ｈ，ｔ），６．８３−６．９５（３Ｈ，ｍ） Reference Production Example 166
5-Bromo-2,2-difluoro-1,3-benzodioxole (4.74 g, 20.0 mmol), 4-penten-2-ol (2.60 g, 30.0 mmol), palladium acetate (2. 00 g, 9.0 mmol), tetrabutylammonium chloride (11.1 g, 40.0 mmol), lithium chloride (0.85 g, 20.0 mmol) and lithium acetate dihydrate (5.20 g, 50.0 mmol) with N, In addition to N-dimethylformamide (40 ml), the mixture was stirred at 100 ° C. for 72 hours under a nitrogen atmosphere. The mixture was cooled to room temperature and added to 1N hydrochloric acid, then the solid was filtered off through celite and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

To obtain 2.95 g of 5- [5- (2,2-difluoro-1,3-benzodioxolanyl)] pentan-2-one represented by the following formula.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.86 (2H, dt), 2.12 (3H, s), 2.42 (2H, t), 2.59 (2H, t ), 6.83-6.95 (3H, m)

で示される７−［５−（２，２−ジフルオロ−１，３−ベンゾジオキソラニル）］−２，４−ジオキソへプタン酸エチル２．８４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３６（３Ｈ，ｔ），１．９５（２Ｈ，ｄｔ），２．４９（２Ｈ，ｔ），２．６４（２Ｈ，ｔ），４．３３（２Ｈ，ｑ），６．３３（１Ｈ，ｓ），６．８４−６．９５（３Ｈ，ｍ） Reference Production Example 167
5- [5- (2,2-difluoro-1,3-benzodioxolanyl)] pentan-2-one (2.84 g, 11.7 mmol) and diethyl oxalate (1.88 g, 12.9 mmol)) Was dissolved in ethanol (26 ml) and cooled to 0 ° C. under a nitrogen atmosphere. Sodium ethoxide (20% ethanol solution, 4.39 g, 12.9 mmol) was added dropwise to the cooled solution over 30 minutes, and the mixture was stirred overnight at room temperature and then concentrated under reduced pressure. 1N hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Then, 2.84 g of ethyl 7- [5- (2,2-difluoro-1,3-benzodioxolanyl)]-2,4-dioxoheptanoate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.36 (3H, t), 1.95 (2H, dt), 2.49 (2H, t), 2.64 (2H, t ), 4.33 (2H, q), 6.33 (1H, s), 6.84-6.95 (3H, m)

で示される５−［３−（２，２−ジフルオロ−１，３−ベンゾジオキソラン−５−イル）プロピル］イソキサゾール−３−カルボン酸エチル２．６７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４０（３Ｈ，ｔ），２．０２（２Ｈ，ｄｔ），２．６７（２Ｈ，ｔ），２．８０（２Ｈ，ｔ），４．４１（２Ｈ，ｑ），６．４１（１Ｈ，ｓ），６．８４−６．９７（３Ｈ，ｍ） Reference Production Example 168
7- [5- (2,2-difluoro-1,3-benzodioxolanyl)]-2,4-dioxoheptanoate (2.84 g, 8.3 mmol) was dissolved in ethanol (20 ml); Hydroxylamine hydrochloride (0.68 g, 9.3 mmol) was added, and the mixture was heated to reflux for 6 hours under a nitrogen atmosphere. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. 1N hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Thus, 2.67 g of ethyl 5- [3- (2,2-difluoro-1,3-benzodioxolan-5-yl) propyl] isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.40 (3H, t), 2.02 (2H, dt), 2.67 (2H, t), 2.80 (2H, t ), 4.41 (2H, q), 6.41 (1H, s), 6.84-6.97 (3H, m)

で示される５−［３−（２，２−ジフルオロ−１，３−ベンゾジオキソランー５−イル）プロピル］イソキサゾール−３−カルボン酸１．１０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：２．０４（２Ｈ，ｄｔ），２．６８（２Ｈ，ｔ），２．８３（２Ｈ，ｔ），６．４７（１Ｈ，ｓ），６．８５−６．９８（３Ｈ，ｍ） Reference Production Example 169
5- [3- (2,2-difluoro-1,3-benzodioxolan-5-yl) propyl] isoxazole-3-carboxylate (2.67 g, 7.8 mmol) was dissolved in ethanol (20 ml); Water (10 ml) and potassium hydroxide (1.32 g, 23.6 mmol) were added, and the mixture was stirred at room temperature for 1 hour, and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.10 g of 5- [3- (2,2-difluoro-1,3-benzodioxolan-5-yl) propyl] isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 2.04 (2H, dt), 2.68 (2H, t), 2.83 (2H, t), 6.47 (1H, s ), 6.85-6.98 (3H, m)

で示される５−（１，３−ベンゾジオキソランー５−イル）ペンタン−２−オン１．８２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．８４（２Ｈ，ｄｔ），２．１１（３Ｈ，ｓ），２．４１（２Ｈ，ｔ），２．５２（２Ｈ，ｔ），５．９１（２Ｈ，ｓ），６．５８−６．７２（３Ｈ，ｍ） Reference production example 170
5-bromo-1,3-benzodioxolane (4.02 g, 20.0 mmol), 4-penten-2-ol (2.60 g, 30.0 mmol), palladium acetate (2.00 g, 9.0 mmol), chloride Tetrabutylammonium (11.1 g, 40.0 mmol), lithium chloride (0.85 g, 20.0 mmol) and lithium acetate dihydrate (5.20 g, 50.0 mmol) were added to N, N-dimethylformamide (40 ml). In addition, the mixture was stirred at 100 ° C. for 72 hours under a nitrogen atmosphere. The mixture was cooled to room temperature and added to 1N hydrochloric acid, then the solid was filtered off through celite and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 1.82 g of 5- (1,3-benzodioxolan-5-yl) pentan-2-one represented by formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.84 (2H, dt), 2.11 (3H, s), 2.41 (2H, t), 2.52 (2H, t ), 5.91 (2H, s), 6.58-6.72 (3H, m)

で示される７−（１，３−ベンゾジオキソランー５−イル）−２，４−ジオキソへプタン酸エチル２．８４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３６（３Ｈ，ｔ），１．９３（２Ｈ，ｄｔ），２．４７（２Ｈ，ｔ），２．５７（２Ｈ，ｔ），４．３３（２Ｈ，ｑ），５．９１（２Ｈ，ｓ），６．３２（１Ｈ，ｓ），６．６０−６．７２（３Ｈ，ｍ） Reference Production Example 171
5- (1,3-benzodioxolan-5-yl) pentan-2-one (2.84 g, 11.7 mmol) and diethyl oxalate (1.88 g, 12.9 mmol)) were dissolved in ethanol (26 ml). The mixture was cooled to 0 ° C. under a nitrogen atmosphere, and sodium ethoxide (20% ethanol solution, 4.39 g, 12.9 mmol) was added dropwise thereto over 30 minutes, followed by stirring at room temperature overnight. 1N Hydrochloric acid was added to the concentrate obtained by concentration under reduced pressure, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Then, 2.84 g of ethyl 7- (1,3-benzodioxolan-5-yl) -2,4-dioxoheptanoate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.36 (3H, t), 1.93 (2H, dt), 2.47 (2H, t), 2.57 (2H, t ), 4.33 (2H, q), 5.91 (2H, s), 6.32 (1H, s), 6.60-6.72 (3H, m)

で示される５−［３−（１，３−ベンゾジオキソラン−５−イル）プロピル］イソキサゾール−３−カルボン酸１．１０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：２．０１（２Ｈ，ｄｔ），２．６１（２Ｈ，ｔ），２．８１（２Ｈ，ｔ），５．９２（２Ｈ，ｓ），６．４５（１Ｈ，ｓ），６．６２−６．７４（３Ｈ，ｍ） Reference Production Example 172
Ethyl 7- (1,3-benzodioxolan-5-yl) -2,4-dioxoheptanoate (2.84 g, 8.3 mmol) was dissolved in ethanol (20 ml) and hydroxylamine hydrochloride (0.68 g , 9.3 mmol) was added, and the mixture was heated to reflux for 6 hours under a nitrogen atmosphere. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. 1N hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in ethanol (20 ml), water (10 ml) and potassium hydroxide (1.32 g, 23.6 mmol) were added, and the mixture was stirred at room temperature for 1 hour and concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.10 g of 5- [3- (1,3-benzodioxolan-5-yl) propyl] isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 2.01 (2H, dt), 2.61 (2H, t), 2.81 (2H, t), 5.92 (2H, s ), 6.45 (1H, s), 6.62-6.74 (3H, m)

で示される５−［（２，２−ジフルオロ−１，３−ベンゾジオキソラン−５−イル）メトキシメチル）イソキサゾール−３−カルボン酸２．０７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：４．５７（２Ｈ，ｓ），４．６６（２Ｈ，ｓ），６．７１（１Ｈ，ｓ），７．０３（２Ｈ，ｓ），７．０９（１Ｈ，ｓ） Reference Production Example 173
Under a nitrogen atmosphere, ethyl 5-hydroxymethylisoxazole-3-carboxylate (1.85 g, 10.0 mmol), 5-bromomethyl-2,2-difluoro-1,3-benzodioxolane (3.21 g, 12. 0 mmol) was dissolved in N, N-dimethylformamide (20 ml), 60% sodium hydride (0.49 g, 12.3 mmol) was added at 0 ° C., and the mixture was warmed to room temperature and stirred for 16 hours. The reaction mixture was poured into 1N hydrochloric acid and extracted twice with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was added to ethanol (40 mL), potassium hydroxide (2.24 g, 40.0 mmol) and water (10 mL) were added, and the mixture was stirred overnight at room temperature, and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

2.07 g of 5-[(2,2-difluoro-1,3-benzodioxolan-5-yl) methoxymethyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 4.57 (2H, s), 4.66 (2H, s), 6.71 (1H, s), 7.03 (2H, s) ), 7.09 (1H, s)

で示される５−（２−フルオロフェニル）ペンタン−２−オン９．１０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．８６−１．９４（２Ｈ，ｍ），２．１３（３Ｈ，ｓ），２．４６（２Ｈ，ｔ），２．６６（２Ｈ，ｔ），６．９８−７．０８（２Ｈ，ｍ），７．１５−７．２１（２Ｈ，ｍ） Reference Production Example 174
2-Fluoro-1-bromobenzene (14.02 g, 80.1 mmol), 4-penten-2-ol (10.35 g, 120.1 mmol), palladium acetate (8.09 g, 36.05 mmol), tetrabutyl chloride Ammonium (44.53 g, 160.2 mmol), lithium chloride (3.40 g, 80.1 mmol) and lithium acetate dihydrate (20.43 g, 200.2 mmol) were added to N, N-dimethylformamide (160 ml). The mixture was stirred at 100 ° C. for 30 hours in a nitrogen atmosphere. The mixture was cooled to room temperature and added to 1N hydrochloric acid, and then the solid was removed by filtration through celite and extracted three times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

9.10 g of 5- (2-fluorophenyl) pentan-2-one represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.86-1.94 (2H, m), 2.13 (3H, s), 2.46 (2H, t), 2.66 (2H, t), 6.98-7.08 (2H, m), 7.15-7.21 (2H, m)

で示される７−（２−フルオロフェニル）−２，４−ジオキソへプタン酸エチル１０．４９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３６−１．４０（３Ｈ，ｍ），１．９５−２．０３（２Ｈ，ｍ），２．５３（２Ｈ，ｔ），２．７１（２Ｈ，ｔ），４．３１−４．３９（２Ｈ，ｍ），６．３６（１Ｈ，ｓ），６．９８−７．０９（２Ｈ，ｍ），７．１５−７．２２（２Ｈ，ｍ） Reference Production Example 175
5- (2-Fluorophenyl) pentan-2-one (9.08 g, 50.3 mmol) and diethyl oxalate (8.2 mL, 60.4 mmol) were dissolved in ethanol (84 ml), and −10 Cooled to ° C. Sodium ethoxide (20% ethanol solution, 17.1 g, 50.3 mmol) was added dropwise thereto over 30 minutes, and the mixture was stirred overnight at room temperature and then concentrated under reduced pressure. 1N Hydrochloric acid was added to the reaction mixture, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

10-49 g of ethyl 7- (2-fluorophenyl) -2,4-dioxoheptanoate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.36 to 1.40 (3H, m), 1.95 to 2.03 (2H, m), 2.53 (2H, t) , 2.71 (2H, t), 4.31-4.39 (2H, m), 6.36 (1H, s), 6.98-7.09 (2H, m), 7.15-7 .22 (2H, m)

で示される５−［３−（２−フルオロフェニル）プロピル］イソキサゾール−３−カルボン酸エチル４．４０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４１（３Ｈ，ｔ），２．０２−２．０９（２Ｈ，ｍ），２．７３（２Ｈ，ｔ），２．８４（２Ｈ，ｔ），４．４４（２Ｈ，ｑ），６．４４（１Ｈ，ｓ），７．００−７．０９（２Ｈ，ｍ），７．１５−７．２３（２Ｈ，ｍ） Reference Production Example 176
Ethyl 7- (2-fluorophenyl) -2,4-dioxoheptanoate (10.48 g, 37.3 mmol) was dissolved in ethanol (124 ml) and hydroxylamine hydrochloride (5.2 g, 74.7 mmol) was dissolved. In addition, the mixture was heated to reflux for 12 hours under a nitrogen atmosphere. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. 1N Hydrochloric acid was added to the concentrate, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Thus, 4.40 g of ethyl 5- [3- (2-fluorophenyl) propyl] isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.41 (3H, t), 2.02-2.09 (2H, m), 2.73 (2H, t), 2.84 (2H, t), 4.44 (2H, q), 6.44 (1H, s), 7.00-7.09 (2H, m), 7.15-7.23 (2H, m)

で示される５−［３−（２−フルオロフェニル）プロピル］イソキサゾール−３−カルボン酸２．４２ｇを得た。このものは精製することなく次の反応に供した。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：２．０３−２．１１（２Ｈ，ｍ），２．７５（２Ｈ，ｔ），２．８６（２Ｈ，ｔ），５．６４（１Ｈ，ｂｒ），６．４９（１Ｈ，ｓ），７．０１−７．１０（２Ｈ，ｍ），７．１６−７．２３（２Ｈ，ｍ） Reference Production Example 177
Ethyl 5- [3- (2-fluorophenyl) propyl] isoxazole-3-carboxylate (3.0 g, 10.8 mmol) is dissolved in ethanol (40 mL) and potassium hydroxide (1.21 g, 21.6 mmol) is dissolved. Was added at room temperature and stirred for 2 hours, and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the residue to adjust the pH to 2, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

Thus, 2.42 g of 5- [3- (2-fluorophenyl) propyl] isoxazole-3-carboxylic acid represented by the following formula was obtained. This was subjected to the next reaction without purification.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 2.03-2.11 (2H, m), 2.75 (2H, t), 2.86 (2H, t), 5.64 (1H, br), 6.49 (1H, s), 7.01-7.10 (2H, m), 7.16-7.23 (2H, m)

で示される５−（３，４−ジクロロフェニル）ペンタン−２−オン３．３５ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．８３−１．９４（２Ｈ，ｍ），２．１３（３Ｈ，ｓ），２．４４（２Ｈ，ｔ），２．５８（２Ｈ，ｔ），７．０１（１Ｈ，ｄｄ），７．２６（１Ｈ，ｄ），７．３４（１Ｈ，ｄ） Reference Production Example 178
3,4-dichlorobromobenzene (4.52 g, 20.0 mmol), 4-penten-2-ol (2.58 g, 30.0 mmol), palladium acetate (2.02 g, 9.0 mmol), tetrabutylammonium chloride (11.12 g, 40.0 mmol), lithium chloride (0.85 g, 20.0 mmol) and lithium acetate dihydrate (5.10 g, 50.0 mmol) were added to N, N-dimethylformamide (40 ml), The mixture was stirred at 100 ° C. for 30 hours under a nitrogen atmosphere. The mixture was cooled to room temperature and added to 1N hydrochloric acid, and then the solid was removed by filtration through celite and extracted three times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

Thus, 3.35 g of 5- (3,4-dichlorophenyl) pentan-2-one represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.83-1.94 (2H, m), 2.13 (3H, s), 2.44 (2H, t), 2.58 (2H, t), 7.01 (1H, dd), 7.26 (1H, d), 7.34 (1H, d)

で示される７−（３，４−ジクロロフェニル）−２，４−ジオキソへプタン酸エチル１．５８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３８（３Ｈ，ｔ），１．９２−２．０２（２Ｈ，ｍ），２．５１（２Ｈ，ｔ），２．６３（２Ｈ，ｔ），４．３７（２Ｈ，ｑ），６．３４（１Ｈ，ｓ），７．０２（１Ｈ，ｄｄ），７．２７（１Ｈ，ｄ），７．３６（１Ｈ，ｄ） Reference Production Example 179
5- (3,4-Dichlorophenyl) pentan-2-one (2.31 g, 10.0 mmol) and diethyl oxalate (1.75 g, 12.0 mmol) were dissolved in ethanol (20 ml) and 0. Cooled to ° C. Sodium ethoxide (20% ethanol solution, 3.40 g, 10.0 mmol) was added dropwise thereto over 30 minutes, and the mixture was stirred overnight at room temperature and then concentrated under reduced pressure. 1N Hydrochloric acid was added to the concentrate, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

In this manner, 1.58 g of ethyl 7- (3,4-dichlorophenyl) -2,4-dioxoheptanoate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.38 (3H, t), 1.92-2.02 (2H, m), 2.51 (2H, t), 2.63 (2H, t), 4.37 (2H, q), 6.34 (1H, s), 7.02 (1H, dd), 7.27 (1H, d), 7.36 (1H, d)

で示される５−［３−（３，４−ジクロロフェニル）プロピル］イソキサゾール−３−カルボン酸エチル１．２４ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４２（３Ｈ，ｔ），１．９９−２．０８（２Ｈ，ｍ），２．６５（２Ｈ，ｔ），２．８２（２Ｈ，ｔ），４．４４（２Ｈ，ｑ），６．４３（１Ｈ，ｓ），７．０１（１Ｈ，ｄｄ），７．２７（１Ｈ，ｄ），７．３６（１Ｈ，ｄ） Reference production example 180
Ethyl 7- (3,4-dichlorophenyl) -2,4-dioxoheptanoate (1.58 g, 2.8 mmol) was dissolved in ethanol (15 ml) and hydroxylamine hydrochloride (0.72 g, 10.4 mmol) was dissolved. And heated to reflux under a nitrogen atmosphere for 12 hours. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. 1N Hydrochloric acid was added to the concentrate, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

To 1.24 g of ethyl 5- [3- (3,4-dichlorophenyl) propyl] isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42 (3H, t), 1.99-2.08 (2H, m), 2.65 (2H, t), 2.82 (2H, t), 4.44 (2H, q), 6.43 (1H, s), 7.01 (1H, dd), 7.27 (1H, d), 7.36 (1H, d)

で示される５−［３−（３，４−ジクロロフェニル）プロピル］イソキサゾール−３−カルボン酸０．９８ｇを得た。このものは精製することなく次の反応に供した。 Reference Production Example 181
Ethyl 5- [3- (3,4-dichlorophenyl) propyl] isoxazole-3-carboxylate (0.99 g, 3.0 mmol) was dissolved in ethanol (6 ml) and potassium hydroxide (0.84 g, 15.0 mmol). ) In water (3 mL) was added at room temperature and stirred at 80 ° C. for 4 hours. Water was added to the reaction mixture and concentrated under reduced pressure. To the concentrate was added tert-butyl methyl ether, and the aqueous layer was separated. Dilute hydrochloric acid was added to the obtained aqueous layer, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

0.98 g of 5- [3- (3,4-dichlorophenyl) propyl] isoxazole-3-carboxylic acid represented by the following formula was obtained. This was subjected to the next reaction without purification.

で示される７−（６−メトキシ−２−ナフチル）−２，４−ジオキソへプタン酸エチル１．３３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３７（３Ｈ，ｔ），２．０２−２．１２（２Ｈ，ｍ），２．５３（２Ｈ，ｔ），２．８０（２Ｈ，ｔ），３．９２（３Ｈ，ｓ），４．３４（２Ｈ，ｑ），６．３３（１Ｈ，ｓ），７．１０−７．１５（２Ｈ，ｍ），７．２６−７．３０（１Ｈ，ｍ），７．５４（１Ｈ，ｓ），７．６５−７．７１（２Ｈ，ｍ） Reference production example 182
5- (6-Methoxy-2-naphthyl) pentan-2-one (1.78 g, 7.3 mmol) and diethyl oxalate (1.29 g, 8.8 mmol) were dissolved in ethanol (15 ml) under a nitrogen atmosphere. And cooled to 0 ° C. Sodium ethoxide (20% ethanol solution, 2.48 g, 7.3 mmol) was added dropwise thereto over 20 minutes, and the mixture was stirred overnight at room temperature and then concentrated under reduced pressure. 1N Hydrochloric acid was added to the concentrate, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.33 g of ethyl 7- (6-methoxy-2-naphthyl) -2,4-dioxoheptanoate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.37 (3H, t), 2.02-2.12 (2H, m), 2.53 (2H, t), 2.80 (2H, t), 3.92 (3H, s), 4.34 (2H, q), 6.33 (1H, s), 7.10-7.15 (2H, m), 7.26- 7.30 (1H, m), 7.54 (1H, s), 7.65-7.71 (2H, m)

で示される５−［３−（６−メトキシ−２−ナフチル）プロピル］イソキサゾール−３−カルボン酸エチル０．９８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４２（３Ｈ，ｔ），２．０８−２．１８（２Ｈ，ｍ），２．６２（２Ｈ，ｔ），２．８４（２Ｈ，ｔ），３．９２（３Ｈ，ｓ），４．４３（２Ｈ，ｑ），６．４３（１Ｈ，ｓ），７．１０−７．１６（２Ｈ，ｍ），７．２６−７．３０（１Ｈ，ｍ），７．５４（１Ｈ，ｓ），７．６６−７．７１（２Ｈ，ｍ） Reference Production Example 183
Ethyl 7- (6-methoxy-2-naphthyl) -2,4-dioxoheptanoate (1.33 g, 3.9 mmol) was dissolved in ethanol (12 ml) and hydroxylamine hydrochloride (0.59 g, 8. 5 mmol) was added, and the mixture was heated to reflux for 8 hours under a nitrogen atmosphere. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. 1N Hydrochloric acid was added to the concentrate, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 0.98 g of ethyl 5- [3- (6-methoxy-2-naphthyl) propyl] isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42 (3H, t), 2.08-2.18 (2H, m), 2.62 (2H, t), 2.84 (2H, t), 3.92 (3H, s), 4.43 (2H, q), 6.43 (1H, s), 7.10-7.16 (2H, m), 7.26- 7.30 (1H, m), 7.54 (1H, s), 7.66-7.71 (2H, m)

で示される５−［３−（６−メトキシ−２−ナフチル）プロピル］イソキサゾール−３−カルボン酸０．７３ｇを得た。このものは精製することなく次の反応に供した。 Reference Production Example 184
Ethyl 5- [3- (6-methoxy-2-naphthyl) propyl] isoxazole-3-carboxylate (0.98 g, 2.9 mmol) is dissolved in ethanol (6 ml) and potassium hydroxide (0.81 g, 14 .4 mmol) in water (3 mL) was added at room temperature and stirred at 80 ° C. for 3 hours. Water was added to the reaction mixture and concentrated under reduced pressure. To the concentrate was added tert-butyl methyl ether, and the aqueous layer was separated. Dilute hydrochloric acid was added to the obtained aqueous layer, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

In this manner, 0.73 g of 5- [3- (6-methoxy-2-naphthyl) propyl] isoxazole-3-carboxylic acid represented by the following formula was obtained. This was subjected to the next reaction without purification.

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−フルオロベンジルオキシメチル）−４−トリメチルシラニルエチニルイソキサゾール−３−カルボキシアミド０．４０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．２５（ｓ，９Ｈ），１．６３−１．７１（ｍ，１Ｈ），２．０６−２．１３（ｍ，１Ｈ），２．５６−２．６２（ｍ，１Ｈ），３．４６−３．５０（ｍ，２Ｈ），３．５７−３．６０（ｍ，１Ｈ），３．７３−３．７９（ｍ，1Ｈ），３．８４−３．９４（ｍ，２Ｈ），４．６９（ｓ，２Ｈ），４．７４（ｓ，２Ｈ），６．９６（ｂｒｓ，１Ｈ），７．０４−７．０８（ｍ，１Ｈ），７．１３−７．１７（ｍ，１Ｈ），７．２８−７．３３（ｍ，１Ｈ），７．４１−７．４５（ｍ，１Ｈ） Reference Production Example 185
N- (tetrahydrofuran-3-ylmethyl) -5- (2-fluorobenzyloxymethyl) -4-iodoisoxazole-3-carboxamide (0.64 g, 1.40 mmol) in N, N-dimethylformamide (3 mL) ) To the solution were added triethylamine (1.4 mL), bis (triphenylphosphine) palladium (II) dichloride (0.05 g, 0.07 mmol) and copper iodide (0.03 g, 0.14 mmol), and ice-cooled. And placed under a nitrogen atmosphere. Subsequently, trimethylsilylacetylene (0.21 mL, 1.55 mmol) was added dropwise, and the mixture was stirred for 1 hour while gradually returning to room temperature. The mixture was filtered through celite and the filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.40 g of N- (tetrahydrofuran-3-ylmethyl) -5- (2-fluorobenzyloxymethyl) -4-trimethylsilanylethynylisoxazole-3-carboxamide represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.25 (s, 9H), 1.63-1.71 (m, 1H), 2.06-2.13 (m, 1H) , 2.56-2.62 (m, 1H), 3.46-3.50 (m, 2H), 3.57-3.60 (m, 1H), 3.73-3.79 (m, 1H), 3.84-3.94 (m, 2H), 4.69 (s, 2H), 4.74 (s, 2H), 6.96 (brs, 1H), 7.04-7.08 (M, 1H), 7.13-7.17 (m, 1H), 7.28-7.33 (m, 1H), 7.41-7.45 (m, 1H)

で示されるＮ−（テトラヒドロフラン−３−イルメチル）−５−（２−ナフチルメトキシメチル）−４−トリメチルシラニルエチニルイソキサゾール−３−カルボキシアミド０．３６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．２２（ｓ，９Ｈ），１．６２−１．７１（ｍ，１Ｈ），２．０４−２．１５（ｍ，１Ｈ），２．５７−２．６１（ｍ，１Ｈ），３．４５−３．４９（ｍ，２Ｈ），３．５６−３．６０（ｍ，１Ｈ），３．７３−３．７９（ｍ，1Ｈ），３．８３−３．９４（ｍ，２Ｈ），４．７４（ｓ，２Ｈ），４．７８（ｓ，２Ｈ），６．９１（ｂｒｓ，１Ｈ），７．４７−７．５０（ｍ，３Ｈ），７．８１−７．８６（ｍ，４Ｈ） Reference Production Example 186
N- (tetrahydrofuran-3-ylmethyl) -5- (2-naphthylmethoxymethyl) -4-iodoisoxazole-3-carboxamide (0.62 g, 1.26 mmol) in N, N-dimethylformamide (2. 5 mL) solution was added triethylamine (1.26 mL), bis (triphenylphosphine) palladium (II) dichloride (0.04 g, 0.06 mmol) and copper iodide (0.02 g, 0.12 mmol), and ice-cooled. And placed under a nitrogen atmosphere. Subsequently, trimethylsilylacetylene (0.19 mL, 1.38 mmol) was added dropwise, and the mixture was stirred for 7 hours while gradually returning to room temperature. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.36 g of N- (tetrahydrofuran-3-ylmethyl) -5- (2-naphthylmethoxymethyl) -4-trimethylsilanylethynylisoxazole-3-carboxamide represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.22 (s, 9H), 1.62-1.71 (m, 1H), 2.04-2.15 (m, 1H) 2.57-2.61 (m, 1H), 3.45-3.49 (m, 2H), 3.56-3.60 (m, 1H), 3.73-3.79 (m, 1H), 3.83-3.94 (m, 2H), 4.74 (s, 2H), 4.78 (s, 2H), 6.91 (brs, 1H), 7.47-7.50. (M, 3H), 7.81-7.86 (m, 4H)

で示される５−（３−フルオロフェニル）ペンタン−２−オン２．１３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．８５−１．９４（２Ｈ，ｍ），２．１３（３Ｈ，ｓ），２．４４（２Ｈ，ｔ），２．６２（２Ｈ，ｔ），６．８５−６．９６（３Ｈ，ｍ），７．２０−７．２６（１Ｈ，ｍ） Reference Production Example 187
3-fluorobromobenzene (3.50 g, 20.0 mmol), 4-penten-2-ol (2.58 g, 30.0 mmol), palladium acetate (2.02 g, 9.0 mmol), tetrabutylammonium chloride (11 .12 g, 40.0 mmol), lithium chloride (0.85 g, 20.0 mmol) and lithium acetate dihydrate (5.10 g, 50.0 mmol) were added to N, N-dimethylformamide (40 ml) in a nitrogen atmosphere. The mixture was stirred at 100 ° C. for 30 hours. The mixture was cooled to room temperature and added to 1N hydrochloric acid, and then the solid was removed by filtration through celite and extracted three times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

To give 2.13 g of 5- (3-fluorophenyl) pentan-2-one.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.85-1.94 (2H, m), 2.13 (3H, s), 2.44 (2H, t), 2.62 (2H, t), 6.85-6.96 (3H, m), 7.20-7.26 (1H, m)

で示される７−（３−フルオロフェニル）−２，４−ジオキソへプタン酸エチル２．０２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３８（３Ｈ，ｔ），１．９３−２．０３（２Ｈ，ｍ），２．６１（２Ｈ，ｔ），２．６７（２Ｈ，ｔ），４．３６（２Ｈ，ｑ），６．３４（１Ｈ，ｓ），６．８６−６．９７（３Ｈ，ｍ），７．２０−７．２６（１Ｈ，ｍ） Reference Production Example 188
5- (3-Fluorophenyl) pentan-2-one (2.13 g, 11.8 mmol) and diethyl oxalate (2.08 g, 14.2 mmol) were dissolved in ethanol (20 ml), and −10 Cooled to ° C. Sodium ethoxide (20% ethanol solution, 4.01 g, 11.8 mmol) was added dropwise thereto over 30 minutes, and the mixture was stirred overnight at room temperature and then concentrated under reduced pressure. 1N Hydrochloric acid was added to the concentrate, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 2.02 g of ethyl 7- (3-fluorophenyl) -2,4-dioxoheptanoate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.38 (3H, t), 1.93-2.03 (2H, m), 2.61 (2H, t), 2.67 (2H, t), 4.36 (2H, q), 6.34 (1H, s), 6.86-6.97 (3H, m), 7.20-7.26 (1H, m)

で示される５−［３−（３−フルオロフェニル）プロピル］イソキサゾール−３−カルボン酸エチル０．４９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４２（３Ｈ，ｔ），２．０１−２．１０（２Ｈ，ｍ），２．６９（２Ｈ，ｔ），２．８２（２Ｈ，ｔ），４．４４（２Ｈ，ｑ），６．４２（１Ｈ，ｓ），６．８６−６．９７（３Ｈ，ｍ），７．２３−７．３０（１Ｈ，ｍ） Reference Production Example 189
Ethyl 7- (3-fluorophenyl) -2,4-dioxoheptanoate (2.02 g, 7.2 mmol) was dissolved in ethanol (24 ml) and hydroxylamine hydrochloride (1.11 g, 16.0 mmol) was dissolved. In addition, the mixture was heated to reflux for 12 hours under a nitrogen atmosphere. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. 1N Hydrochloric acid was added to the concentrate, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 0.49 g of ethyl 5- [3- (3-fluorophenyl) propyl] isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42 (3H, t), 2.01-2.10 (2H, m), 2.69 (2H, t), 2.82 (2H, t), 4.44 (2H, q), 6.42 (1H, s), 6.86-6.97 (3H, m), 7.23-7.30 (1H, m)

で示される５−［３−（３−フルオロフェニル）プロピル］イソキサゾール−３−カルボン酸０．４３ｇを得た。このものは精製することなく次の反応に供した。 Reference production example 190
Ethyl 5- [3- (3-fluorophenyl) propyl] isoxazole-3-carboxylate (0.49 g, 1.8 mmol) is dissolved in ethanol (3.6 ml) and potassium hydroxide (0.49 g, 8. 8 mmol) in water (1.8 mL) was added at room temperature, and the mixture was stirred at 80 ° C. for 3 hours. Water was added to the reaction mixture and concentrated under reduced pressure. To the concentrate was added tert-butyl methyl ether, and the aqueous layer was separated. Dilute hydrochloric acid was added to the obtained aqueous layer, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

0.43 g of 5- [3- (3-fluorophenyl) propyl] isoxazole-3-carboxylic acid represented by This was subjected to the next reaction without purification.

で示される５−（４−クロロフェニル）ペンタン−２−オン２．４９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．８３−１．９２（２Ｈ，ｍ），２．１２（３Ｈ，ｓ），２．４３（２Ｈ，ｔ），２．５９（２Ｈ，ｔ），７．１０（２Ｈ，ｄｔ），７．２５（２Ｈ，ｄｔ）． Reference production example 191
4-chloro-1-bromobenzene (3.83 g, 20.0 mmol), 4-penten-2-ol (2.07 g, 24.0 mmol), palladium acetate (2.02 g, 9.0 mmol), tetrabutyl chloride Ammonium (11.12 g, 40.0 mmol), lithium chloride (0.85 g, 20.0 mmol) and lithium acetate dihydrate (5.10 g, 50.0 mmol) were added to N, N-dimethylformamide (40 ml). The mixture was stirred at 100 ° C. for 30 hours in a nitrogen atmosphere. The mixture was cooled to room temperature and added to 1N hydrochloric acid, and then the solid was removed by filtration through celite and extracted three times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 2.49 g of 5- (4-chlorophenyl) pentan-2-one was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.83-1.92 (2H, m), 2.12 (3H, s), 2.43 (2H, t), 2.59 (2H, t), 7.10 (2H, dt), 7.25 (2H, dt).

で示される７−（４−クロロフェニル）−２，４−ジオキソへプタン酸エチル１．７０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．３８（３Ｈ，ｔ），１．９２−２．０２（２Ｈ，ｍ），２．５０（２Ｈ，ｔ），２．６４（２Ｈ，ｔ），４．３５（２Ｈ，ｑ），６．３４（１Ｈ，ｓ），７．１１（２Ｈ，ｄｔ），７．２６（２Ｈ，ｄｔ）． Reference production example 192
5- (4-Chlorophenyl) pentan-2-one (1.97 g, 10.0 mmol) and diethyl oxalate (1.75 g, 12.0 mmol) were dissolved in ethanol (20 ml), and the mixture was heated to 0 ° C. under a nitrogen atmosphere. Cooled down. Sodium ethoxide (20% ethanol solution, 3.40 g, 10.0 mmol) was added dropwise thereto over 30 minutes, and the mixture was stirred overnight at room temperature and then concentrated under reduced pressure. 1N Hydrochloric acid was added to the concentrate, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.70 g of ethyl 7- (4-chlorophenyl) -2,4-dioxoheptanoate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.38 (3H, t), 1.92-2.02 (2H, m), 2.50 (2H, t), 2.64 (2H, t), 4.35 (2H, q), 6.34 (1H, s), 7.11 (2H, dt), 7.26 (2H, dt).

で示される５−［３−（４−クロロフェニル）プロピル］イソキサゾール−３−カルボン酸エチル０．９６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４２（３Ｈ，ｔ），１．９９−２．０８（２Ｈ，ｍ），２．６４（２Ｈ，ｔ），２．８１（２Ｈ，ｔ），４．４４（２Ｈ，ｑ），６．４１（１Ｈ，ｓ），７．１０（２Ｈ，ｄｔ），７．２７（２Ｈ，ｄｔ）． Reference production example 193
Dissolve ethyl 7- (4-chlorophenyl) -2,4-dioxoheptanoate (1.57 g, 5.3 mmol) in ethanol (15 ml) and add hydroxylamine hydrochloride (0.74 g, 10.6 mmol). The mixture was heated to reflux for 8 hours under a nitrogen atmosphere. The reaction mixture was cooled to room temperature and then concentrated under reduced pressure. 1N Hydrochloric acid was added to the concentrate, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 0.96 g of ethyl 5- [3- (4-chlorophenyl) propyl] isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42 (3H, t), 1.99-2.08 (2H, m), 2.64 (2H, t), 2.81 (2H, t), 4.44 (2H, q), 6.41 (1H, s), 7.10 (2H, dt), 7.27 (2H, dt).

で示される５−［３−（４−クロロフェニル）プロピル］イソキサゾール−３−カルボン酸０．８６ｇを得た。このものは精製することなく次の反応に供した。 Reference production example 194
Ethyl 5- [3- (4-chlorophenyl) propyl] isoxazole-3-carboxylate (0.96 g, 3.3 mmol) was dissolved in ethanol (8 ml) and potassium hydroxide (0.92 g, 16.4 mmol) was dissolved. An aqueous solution dissolved in water (4 mL) was added at room temperature, and the mixture was stirred at 80 ° C. for 3 hours. Water was added to the reaction mixture and concentrated under reduced pressure. To the concentrate was added tert-butyl methyl ether, and the aqueous layer was separated. Dilute hydrochloric acid was added to the obtained aqueous layer, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

0.86 g of 5- [3- (4-chlorophenyl) propyl] isoxazole-3-carboxylic acid represented by This was subjected to the next reaction without purification.

で示される５−メタンスルホニルオキシメチルイソキサゾール−３−カルボン酸エチル６．０２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４３（３Ｈ，ｔ）３．０９（３Ｈ，ｓ），４．４６（２Ｈ，ｑ），５．３６（２Ｈ，ｓ），６．８７（１Ｈ，ｓ）． Reference production example 195
Methanesulfonyl was added to a chloroform solution (amylene-added product, 100 mL) of ethyl 5-hydroxymethylisoxazole-3-carboxylate (5.12 g, 29.92 mmol) and triethylamine (2.66 mL, 34.40 mmol) under ice water cooling. Chloride (5.42 mL, 38.90 mmol) was added, and the mixture was stirred at room temperature or lower for 2 hours, poured into ice water, and extracted twice with chloroform. The organic layer was washed with saturated brine, dried over magnesium sulfate, concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography.

As a result, 6.02 g of ethyl 5-methanesulfonyloxymethylisoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.43 (3H, t) 3.09 (3H, s), 4.46 (2H, q), 5.36 (2H, s) , 6.87 (1H, s).

で示される５−（２−ナフチルメチルチオメチル）イソキサゾール−３−カルボン酸エチル１．２０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４２（ｔ，Ｊ ＝ ７．２Ｈｚ，３Ｈ），３．６５（ｓ，２Ｈ），３．９１（ｓ，２Ｈ），４．４４（ｑ，Ｊ ＝ ７．２Ｈｚ，２Ｈ），６．５３（ｓ，１Ｈ），７．５３−７．４５（ｍ，３Ｈ），７．７０（ｓ，１Ｈ），７．７９−７．８５（ｍ，３Ｈ）． Reference production example 196
To a solution of ethyl 5-methanesulfonyloxymethylisoxazole-3-carboxylate (1.43 g, 5.71 mmol) in tetrahydrofuran (5 mL) and acetonitrile (5 mL) was added potassium carbonate (0.79 g, 5.71 mmol) and 2 -Naphthylmethanethiol (1.00 g, 5.71 mmol) was added. The mixture was stirred at room temperature for 2 hours and concentrated under reduced pressure, and ethyl acetate and water were added to the resulting residue. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.20 g of ethyl 5- (2-naphthylmethylthiomethyl) isoxazole-3-carboxylate represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42 (t, J = 7.2 Hz, 3H), 3.65 (s, 2H), 3.91 (s, 2H), 4 .44 (q, J = 7.2 Hz, 2H), 6.53 (s, 1H), 7.53-7.45 (m, 3H), 7.70 (s, 1H), 7.79-7 .85 (m, 3H).

で示される５−（２−ナフチルメチルチオメチル）イソキサゾール−３−カルボン酸クロリドの酢酸エチル溶液（＜３．６７ｍｍｏｌ）を得た。 Reference Production Example 197
Ethyl 5- (2-naphthylmethylthiomethyl) isoxazole-3-carboxylate (1.20 g, 3.67 mmol) is added to a mixture of tetrahydrofuran (20 mL) and 1 mol / L aqueous sodium hydroxide solution (20 mL) and 30 minutes at room temperature. After stirring, the mixture was acidified with concentrated hydrochloric acid and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained solid was dissolved in ethyl acetate (35 mL), and N, N-dimethylformamide (about 0.1 mL) and oxalyl chloride (about 0.5 mL) were added. After stirring at room temperature for 20 minutes and concentrating under reduced pressure, the residue was diluted with ethyl acetate (30 mL) to obtain the following formula:

An ethyl acetate solution (<3.67 mmol) of 5- (2-naphthylmethylthiomethyl) isoxazole-3-carboxylic acid chloride represented by the following formula was obtained.

で示される５−ベンジルチオメチルイソキサゾール−３−カルボン酸５１５ｍｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６、ＴＭＳ、δ（ｐｐｍ））：３．８０（ｓ，２Ｈ），３．８９（ｓ，２Ｈ），６．６６（ｓ，１Ｈ），７．２２−７．３６（ｍ，５Ｈ）． Reference production example 198
To a solution of ethyl 5-methanesulfonyloxymethylisoxazole-3-carboxylate (600 mg, 2.41 mmol) in N, N-dimethylformamide (2.4 mL), potassium carbonate (416 mg, 3.01 mmol) and benzyl mercaptan (374 mg). , 3.01 mmol), and the mixture was stirred at room temperature for 2 hours and diluted with ethyl acetate. The reaction mixture was washed with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and ethyl 5-benzylthiomethylisoxazole-3-carboxylate. 620 mg was obtained. Tetrahydrofuran (15 mL) and 1 mol / L aqueous sodium hydroxide solution (15 mL) were added, and the mixture was stirred at room temperature for 30 min. Then, tert-butyl methyl ether and water were added to make the aqueous layer acidic with concentrated hydrochloric acid. Extracted twice with ethyl. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue is suspended in tert-butyl methyl ether and filtered to give the following formula:

Thus, 515 mg of 5-benzylthiomethylisoxazole-3-carboxylic acid represented by
¹ H-NMR (DMSO-d ₆ , TMS, δ (ppm)): 3.80 (s, 2H), 3.89 (s, 2H), 6.66 (s, 1H), 7.22-7 .36 (m, 5H).

で示される５−（３−フルオロ−２−ナフチルメトキシメチル）イソキサゾール−３−カルボン酸０．４８ｇを得た。このものは精製することなく次の反応に供した。 Reference Production Example 199
Dissolve ethyl 5-hydroxymethylisoxazole-3-carboxylate (0.29 g, 1.7 mmol) in tetrahydrofuran (10 mL) and add 3-fluoro-2-naphthylmethyl bromide (0.48 g, 2.0 mmol) and 18-crown-6 (0.05 g, 0.2 mmol) was added. Sodium hydride (60% oily) (0.14 g, 3.4 mmol) was gradually added at room temperature, stirred at room temperature overnight, diluted hydrochloric acid was added, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in ethanol (4 mL), an aqueous solution in which potassium hydroxide (0.56 g, 10 mmol) was dissolved in water (2 mL) was added at room temperature, and the mixture was stirred at 80 ° C. for 3 hours. Water was added to the reaction mixture and concentrated under reduced pressure. To the concentrate was added tert-butyl methyl ether, and the aqueous layer was separated. Dilute hydrochloric acid was added to the obtained aqueous layer, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

0.48 g of 5- (3-fluoro-2-naphthylmethoxymethyl) isoxazole-3-carboxylic acid represented by This was subjected to the next reaction without purification.

で示される５−（１−フルオロ−２−ナフチルメトキシメチル）イソキサゾール−３−カルボン酸０．５９ｇを得た。このものは精製することなく次の反応に供した。 Reference production example 200
Dissolve ethyl 5-hydroxymethylisoxazole-3-carboxylate (0.72 g, 4.2 mmol) in tetrahydrofuran (25 mL) and add 1-fluoro-2-naphthylmethyl bromide (1.20 g, 5.0 mmol) and 18-crown-6 (0.11 g, 0.4 mmol) was added. Sodium hydride (60% oily) (0.34 g, 8.4 mmol) was gradually added at room temperature, stirred overnight at room temperature, diluted hydrochloric acid was added, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in ethanol (10 mL), an aqueous solution in which potassium hydroxide (1.40 g, 25 mmol) was dissolved in water (5 mL) was added at room temperature, and the mixture was stirred at 80 ° C. for 3 hr. Water was added to the reaction mixture and concentrated under reduced pressure. To the concentrate was added tert-butyl methyl ether, and the aqueous layer was separated. Dilute hydrochloric acid was added to the obtained aqueous layer, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

In this way, 0.59 g of 5- (1-fluoro-2-naphthylmethoxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained. This was subjected to the next reaction without purification.

で示される５−（２，５−ジフルオロベンジルオキシメチル）イソキサゾール−３−カルボン酸１．０８ｇを得た。このものは精製することなく次の反応に供した。 Reference production example 201
Ethyl 5-hydroxymethylisoxazole-3-carboxylate (0.86 g, 5.0 mmol) was dissolved in tetrahydrofuran (25 mL) and 2,5-difluorobenzyl bromide (1.24 g, 6.0 mmol) and 18- Crown-6 (0.13 g, 0.5 mmol) was added. Sodium hydride (60% oily) (0.40 g, 10.0 mmol) was gradually added at room temperature, stirred overnight at room temperature, diluted hydrochloric acid was added, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in ethanol (10 mL), an aqueous solution in which potassium hydroxide (1.40 g, 25 mmol) was dissolved in water (5 mL) was added at room temperature, and the mixture was stirred at 80 ° C. for 3 hr. Water was added to the reaction mixture and concentrated under reduced pressure. To the concentrate was added tert-butyl methyl ether, and the aqueous layer was separated. Dilute hydrochloric acid was added to the obtained aqueous layer, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

1.08 g of 5- (2,5-difluorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by This was subjected to the next reaction without purification.

で示される５−（４−クロロ−２−フルオロベンジルオキシメチル）イソキサゾール−３−カルボン酸２．２９ｇを得た。このものは精製することなく次の反応に供した。 Reference production example 202
Ethyl 5-hydroxymethylisoxazole-3-carboxylate (1.71 g, 10 mmol) was dissolved in tetrahydrofuran (35 mL) and 4-chloro-2-fluorobenzyl bromide (2.68 g, 12 mmol) and 18-crown- 6 (0.26 g, 1 mmol) was added. Sodium hydride (60% oily) (0.80 g, 20 mmol) was gradually added at room temperature, stirred overnight at room temperature, diluted hydrochloric acid was added, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in ethanol (20 mL), an aqueous solution prepared by dissolving potassium hydroxide (2.81 g, 50 mmol) in water (10 mL) was added at room temperature, and the mixture was stirred at 80 ° C. for 3 hours. Water was added to the reaction mixture and concentrated under reduced pressure. To the concentrate was added tert-butyl methyl ether, and the aqueous layer was separated. Dilute hydrochloric acid was added to the obtained aqueous layer, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

Thus, 2.29 g of 5- (4-chloro-2-fluorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained. This was subjected to the next reaction without purification.

で示される５−（３−クロロ−４−フルオロベンジルオキシメチル）イソキサゾール−３−カルボン酸２．５５ｇを得た。このものは精製することなく次の反応に供した。 Reference Production Example 203
In Reference Production Example 202, 3-chloro-4-fluorobenzyl bromide (2.68 g, 12 mmol) was used instead of 4-chloro-2-fluorobenzyl bromide, and the reaction was performed in the same manner.

Thus, 2.55 g of 5- (3-chloro-4-fluorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained. This was subjected to the next reaction without purification.

で示される５−（３，５−ジブロモベンジルオキシメチル）イソキサゾール−３−カルボン酸３．２５ｇを得た。このものは精製することなく次の反応に供した。 Reference production example 204
In Reference Production Example 202, 3,5-dibromobenzyl bromide (3.95 g, 12 mmol) was used instead of 4-chloro-2-fluorobenzyl bromide, and the reaction was carried out in the same manner.

Thus, 3.25 g of 5- (3,5-dibromobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained. This was subjected to the next reaction without purification.

で示される５−（３，４−ジフルオロベンジルオキシメチル）イソキサゾール−３−カルボン酸１．０６ｇを得た。このものは精製することなく次の反応に供した。 Reference production example 205
In Reference Production Example 201, 3,4-difluorobenzyl bromide (1.24 g, 6.0 mmol) was used instead of 2,5-difluorobenzyl bromide, and the reaction was performed in the same manner.

1.06 g of 5- (3,4-difluorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by This was subjected to the next reaction without purification.

で示される５−（２−フルオロベンジルオキシメチル）イソキサゾール−３−カルボン酸１．９８ｇを得た。このものは精製することなく次の反応に供した。 Reference production example 206
In Reference Production Example 201, 2-fluorobenzyl bromide (1.13 g, 6.0 mmol) was used instead of 2,5-difluorobenzyl bromide, and the same reaction was performed.

1.98 g of 5- (2-fluorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained. This was subjected to the next reaction without purification.

で示される５−（２−ブロモベンジルオキシメチル）イソキサゾール−３−カルボン酸１．２１ｇを得た。このものは精製することなく次の反応に供した。 Reference production example 207
In Reference Production Example 201, 2-bromobenzyl bromide (1.50 g, 6.0 mmol) was used instead of 2,5-difluorobenzyl bromide, and a similar reaction was performed.

As a result, 1.21 g of 5- (2-bromobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained. This was subjected to the next reaction without purification.

で示される５−（３，５−ジフルオロベンジルオキシメチル）イソキサゾール−３−カルボン酸１．３８ｇを得た。このものは精製することなく次の反応に供した。 Reference production example 208
Ethyl 5-hydroxymethylisoxazole-3-carboxylate (1.71 g, 10.0 mmol) was dissolved in tetrahydrofuran (50 mL) and 3,5-difluorobenzyl bromide (2.48 g, 12.0 mmol) and 18- Crown-6 (0.26 g, 1.0 mmol) was added. Sodium hydride (60% oily) (0.80 g, 20.0 mmol) was gradually added at room temperature, stirred overnight at room temperature, diluted hydrochloric acid was added, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in ethanol (20 mL), an aqueous solution prepared by dissolving potassium hydroxide (2.81 g, 50 mmol) in water (10 mL) was added at room temperature, and the mixture was stirred at 80 ° C. for 3 hours. Water was added to the reaction mixture and concentrated under reduced pressure. To the concentrate was added tert-butyl methyl ether, and the aqueous layer was separated. Dilute hydrochloric acid was added to the obtained aqueous layer, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

1.38 g of 5- (3,5-difluorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained. This was subjected to the next reaction without purification.

で示される５−（３，４，５−トリフルオロベンジルオキシメチル）イソキサゾール−３−カルボン酸２．２１ｇを得た。このものは精製することなく次の反応に供した。 Reference Production Example 209
In Reference Production Example 208, 3,4,5-trifluorobenzyl bromide (2.70 g, 12.0 mmol) was used instead of 3,5-difluorobenzyl bromide, and a similar reaction was performed.

Thus, 2.21 g of 5- (3,4,5-trifluorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained. This was subjected to the next reaction without purification.

で示される５−（３−クロロ−５−フルオロベンジルオキシメチル）イソキサゾール−３−カルボン酸２．０３ｇを得た。このものは精製することなく次の反応に供した。 Reference production example 210
In Reference Production Example 202, 3-chloro-5-fluorobenzyl bromide (2.68 g, 12 mmol) was used instead of 4-chloro-2-fluorobenzyl bromide, and the reaction was similarly performed.

2.03 g of 5- (3-chloro-5-fluorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained. This was subjected to the next reaction without purification.

で示される５−（２，３，５，６−テトラフルオロベンジルオキシメチル）イソキサゾール−３−カルボン酸０．１９ｇを得た。このものは精製することなく次の反応に供した。 Reference production example 211
In Reference Production Example 208, 2,3,5,6-tetrafluorobenzyl bromide (2.92 g, 12.0 mmol) was used instead of 3,5-difluorobenzyl bromide, and a similar reaction was performed.

0.19 g of 5- (2,3,5,6-tetrafluorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by This was subjected to the next reaction without purification.

で示される５−（２，３，４−トリフルオロベンジルオキシメチル）イソキサゾール−３−カルボン酸１．２１ｇを得た。このものは精製することなく次の反応に供した。 Reference Production Example 212
In Reference Production Example 201, 2,3,4-trifluorobenzyl bromide (1.35 g, 6.0 mmol) was used instead of 2,5-difluorobenzyl bromide, and the same reaction was carried out.

As a result, 1.21 g of 5- (2,3,4-trifluorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained. This was subjected to the next reaction without purification.

で示される５−（３，５−ジメチルベンジルオキシメチル）イソキサゾール−３−カルボン酸１．９３ｇを得た。このものは精製することなく次の反応に供した。 Reference production example 213
In Reference Production Example 202, 3,5-dimethylbenzyl bromide (2.39 g, 12 mmol) was used instead of 4-chloro-2-fluorobenzyl bromide, and the reaction was carried out in the same manner.

1.93 g of 5- (3,5-dimethylbenzyloxymethyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained. This was subjected to the next reaction without purification.

で示される５−（４−ブロモ−３−フルオロベンジルオキシメチル）イソキサゾール−３−カルボン酸２．４１ｇを得た。このものは精製することなく次の反応に供した。 Reference production example 214
In Reference Production Example 202, 4-bromo-3-fluorobenzyl bromide (3.22 g, 12 mmol) was used instead of 4-chloro-2-fluorobenzyl bromide, and the reaction was similarly performed.

Thus, 2.41 g of 5- (4-bromo-3-fluorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained. This was subjected to the next reaction without purification.

で示される５−（４−メチル−２，３，５，６−テトラフルオロベンジルオキシメチル）イソキサゾール−３−カルボン酸０．２９ｇを得た。このものは精製することなく次の反応に供した。 Reference Production Example 215
In Reference Production Example 208, 4-methyl-2,3,5,6-tetrafluorobenzyl bromide (3.08 g, 12.0 mmol) was used instead of 3,5-difluorobenzyl bromide, and the same reaction was carried out. , The following formula

0.29 g of 5- (4-methyl-2,3,5,6-tetrafluorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by This was subjected to the next reaction without purification.

で示される５−（２，３−ジフルオロベンジルオキシメチル）イソキサゾール−３−カルボン酸１．０５ｇを得た。このものは精製することなく次の反応に供した。 Reference Production Example 216
In Reference Production Example 201, 2,3-difluorobenzyl bromide (1.24 g, 6.0 mmol) was used instead of 2,5-difluorobenzyl bromide, and the reaction was carried out in the same manner.

1.05 g of 5- (2,3-difluorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by This was subjected to the next reaction without purification.

で示される５−（２，６−ジフルオロベンジルオキシメチル）イソキサゾール−３−カルボン酸１．０２ｇを得た。このものは精製することなく次の反応に供した。 Reference Production Example 217
In Reference Production Example 201, 2,6-difluorobenzyl bromide (1.24 g, 6.0 mmol) was used instead of 2,5-difluorobenzyl bromide, and the same reaction was carried out.

1.02 g of 5- (2,6-difluorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by This was subjected to the next reaction without purification.

で示される５−（４−クロロ−３−フルオロベンジルオキシメチル）イソキサゾール−３−カルボン酸１．０６ｇを得た。このものは精製することなく次の反応に供した。 Reference Production Example 218
Ethyl 5-hydroxymethylisoxazole-3-carboxylate (1.71 g, 10.0 mmol) was dissolved in N, N-dimethylformamide (50 mL), and 4-chloro-3-fluorobenzyl bromide was added to the resulting solution. (2.79 g, 12.5 mmol) was added. Sodium hydride (60% oily) (0.40 g, 10.0 mmol) was gradually added under cooling in an ice-water bath, and the mixture was stirred at room temperature for 1 hour, diluted hydrochloric acid was added, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in ethanol (20 mL), an aqueous solution prepared by dissolving potassium hydroxide (2.81 g, 50 mmol) in water (10 mL) was added at room temperature, and the mixture was stirred at 80 ° C. for 3 hours. Water was added to the reaction mixture and concentrated under reduced pressure. To the concentrate was added tert-butyl methyl ether, and the aqueous layer was separated. Dilute hydrochloric acid was added to the obtained aqueous layer, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

As a result, 1.06 g of 5- (4-chloro-3-fluorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained. This was subjected to the next reaction without purification.

で示される５−（３−フルオロ−４−メトキシベンジルオキシメチル）イソキサゾール−３−カルボン酸１．９８ｇを得た。このものは精製することなく次の反応に供した。 Reference Production Example 219
In Reference Production Example 202, 3-fluoro-4-methoxybenzyl bromide (3.22 g, 12 mmol) was used instead of 4-chloro-2-fluorobenzyl bromide, and the reaction was similarly performed.

1.98 g of 5- (3-fluoro-4-methoxybenzyloxymethyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained. This was subjected to the next reaction without purification.

で示される５−（２，４−ジフルオロベンジルオキシメチル）イソキサゾール−３−カルボン酸２．０３ｇを得た。このものは精製することなく次の反応に供した。 Reference Production Example 220
In Reference Production Example 202, 2,4-difluorobenzyl bromide (2.48 g, 12 mmol) was used instead of 4-chloro-2-fluorobenzyl bromide, and the reaction was performed in the same manner.

2.03 g of 5- (2,4-difluorobenzyloxymethyl) isoxazole-3-carboxylic acid represented by This was subjected to the next reaction without purification.

で示される５−（５−ベンゾチオフェニルメトキシメチル）イソキサゾール−３−カルボン酸エチル３００ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．８９ （１Ｈ，ｄ），７．８０（１Ｈ，ｓ），７．４８（１Ｈ，ｄ），７．３４（２Ｈ，ｄｄ），６．７１（１Ｈ，ｓ），４．７３（２Ｈ，ｓ），４．６８（２Ｈ，ｄ），４．４５（２Ｈ，ｑ），１．４２（３Ｈ，ｔ） Reference Production Example 221
In Reference Production Example 43, 5-bromomethylbenzothiophene (500 mg, 2.20 mmol) was used instead of 2-chlorobenzyl bromide, and the same reaction was performed.

As a result, 300 mg of ethyl 5- (5-benzothiophenylmethoxymethyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.89 (1H, d), 7.80 (1 H, s), 7.48 (1 H, d), 7.34 (2 H, dd ), 6.71 (1H, s), 4.73 (2H, s), 4.68 (2H, d), 4.45 (2H, q), 1.42 (3H, t)

５−（５−ベンゾチオフェニルメトキシメチル）イソキサゾール−３−カルボン酸２４０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ，δ（ｐｐｍ））：７．８９（１Ｈ，ｄ），７．８１（１Ｈ，ｓ），７．４９（１Ｈ，ｄ），７．３５（２Ｈ，ｄ），６．７６（１Ｈ，ｓ），４．７５（２Ｈ，ｓ），４．７０（２Ｈ，ｓ） Reference Production Example 222
In Reference Production Example 44, instead of ethyl 5- (2-chlorobenzyloxymethyl) isoxazole-3-carboxylate, ethyl 5- (5-benzothiophenylmethoxymethyl) isoxazole-3-carboxylate (300 mg, 0.945 mmol) ) Using the following formula

240 mg of 5- (5-benzothiophenylmethoxymethyl) isoxazole-3-carboxylic acid was obtained.
¹ H-NMR (DMSO-d ₆ , TMS, δ (ppm)): 7.89 (1H, d), 7.81 (1H, s), 7.49 (1H, d), 7.35 (2H , D), 6.76 (1H, s), 4.75 (2H, s), 4.70 (2H, s)

で示される５−（１，３−ベンゾジオキソール−５−イルメチル）イソキサゾール−３−カルボン酸エチル１８０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４０（３Ｈ，ｓ），４．０４（２Ｈ，ｓ），４．４２（２Ｈ，ｑ），５．９６（２Ｈ，ｓ），６．３３（１Ｈ，ｓ），６．７１（１Ｈ，ｄ），６．７２（１Ｈ，ｓ），６．７７（１Ｈ，ｄ） Reference Production Example 223
Ethyl 5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (300 mg, 0.98 mmol), 1,3-benzodioxole-5-boronic acid (281 mg, 1.27 mmol) and potassium carbonate (270 mg, 1.95 mmol) was added to a mixture of toluene (5 mL) and water (1 mL). Under an argon atmosphere, palladium acetate (11 mg, 0.05 mmol) and triphenylphosphine (51 mg, 0.19 mmol) were added, stirred at 90 to 95 ° C. for 4 hours, cooled, poured water, and twice with ethyl acetate. Extracted. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 180 mg of ethyl 5- (1,3-benzodioxol-5-ylmethyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.40 (3H, s), 4.04 (2H, s), 4.42 (2H, q), 5.96 (2H, s) ), 6.33 (1H, s), 6.71 (1H, d), 6.72 (1H, s), 6.77 (1H, d)

で示される５−（１，３−ベンゾジオキソラン−５−イルメチル）イソキサゾール−３−カルボン酸２．００ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．１１（２Ｈ，ｓ），６．００（２Ｈ，ｓ），６．５４（１Ｈ，ｓ），６．７４−６．８０（１Ｈ，ｍ），６．８４−６．９２（２Ｈ，ｍ），１３．９０（１Ｈ，ｂｒ ｓ） Reference Production Example 224
Ethyl 5- (1,3-benzodioxolan-5-ylmethyl) isoxazole-3-carboxylate (2.60 g, 9.45 mmol) was added to a mixture of ethanol (25 mL) and 2 mol / L aqueous sodium hydroxide (12 mL). After adding at 0 ° C. and stirring at room temperature for 16 hours, the mixture was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with a mixture of diethyl ether and petroleum ether to obtain the following formula

2.00 g of 5- (1,3-benzodioxolan-5-ylmethyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 4.11 (2H, s), 6.00 (2H, s), 6.54 (1H, s), 6.74-6. 80 (1H, m), 6.84-6.92 (2H, m), 13.90 (1H, br s)

で示される５−（３，５−ジフルオロベンジル）イソキサゾール−３−カルボン酸エチル１６２ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．４１（３Ｈ，ｔ），４．１２（２Ｈ，ｓ），４．４３（２Ｈ，ｑ），６．４２（１Ｈ，ｓ），６．７２−６．８２（３Ｈ，ｍ） Reference production example 225
5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (300 mg, 0.98 mmol), 3,5-difluorophenylboronic acid (200 mg, 1.27 mmol) and potassium carbonate (269 mg, 1.95 mmol). To a mixture of toluene (5 mL) and water (1 mL). Under an argon atmosphere, palladium acetate (11 mg, 0.05 mmol) and triphenylphosphine (51 mg, 0.19 mmol) were added, and the mixture was stirred at 90 to 95 ° C. for 4 hours, cooled, added with water, and twice with ethyl acetate. Extracted. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

162 mg of ethyl 5- (3,5-difluorobenzyl) isoxazole-3-carboxylate represented by
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.41 (3H, t), 4.12 (2H, s), 4.43 (2H, q), 6.42 (1H, s) , 6.72-6.82 (3H, m)

で示される５−（３，５−ジフルオロベンジル）イソキサゾール−３−カルボン酸１．５０ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．２８（２Ｈ，ｓ），６．６４（１Ｈ，ｓ），７．０５−７．２０（３Ｈ，ｍ），１３．９５（１Ｈ，ｂｒ ｓ） Reference Production Example 226
Ethyl 5- (3,5-difluorobenzyl) isoxazole-3-carboxylate (2.30 g, 8.61 mmol) was added to a mixture of ethanol (25 mL) and 2 mol / L aqueous sodium hydroxide (12 mL) at 0 ° C., After stirring at room temperature for 16 hours, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with a mixture of diethyl ether and petroleum ether,

1.50 g of 5- (3,5-difluorobenzyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 4.28 (2H, s), 6.64 (1H, s), 7.05-7.20 (3H, m), 13. 95 (1H, br s)

で示される５−（３，４−ジフルオロベンジル）イソキサゾール−３−カルボン酸エチル１５４ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．４０（３Ｈ，ｔ），４．１０（２Ｈ，ｓ），４．４３（２Ｈ，ｑ），６．３７（１Ｈ，ｓ），６．９４−７．１８（３Ｈ，ｍ） Reference Production Example 227
5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (300 mg, 0.98 mmol), 3,4-difluorophenylboronic acid (200 mg, 1.27 mmol) and potassium carbonate (269 mg, 1.95 mmol). To a mixture of toluene (5 mL) and water (1 mL). Under an argon atmosphere, palladium acetate (11 mg, 0.05 mmol) and triphenylphosphine (51 mg, 0.19 mmol) were added, and the mixture was stirred at 90 to 95 ° C. for 4 hours, then cooled, water was added, and ethyl acetate twice. Extracted. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 154 mg of ethyl 5- (3,4-difluorobenzyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.40 (3H, t), 4.10 (2H, s), 4.43 (2H, q), 6.37 (1H, s) , 6.94-7.18 (3H, m)

で示される５−（３，４−ジフルオロベンジル）イソキサゾール−３−カルボン酸１．５６ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．２３（２Ｈ，ｓ），６．６０（１Ｈ，ｓ），７．１２−７．２１（１Ｈ，ｍ），７．３５−７．４５（２Ｈ，ｍ），１３．９５（１Ｈ，ｂｒ ｓ） Reference Production Example 228
Ethyl 5- (3,4-difluorobenzyl) isoxazole-3-carboxylate (2.20 g, 8.23 mmol) was added to a mixture of ethanol (25 mL) and 2 mol / L aqueous sodium hydroxide (12 mL) at 0 ° C., The mixture was stirred at room temperature for 16 hours, diluted with water, and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with a mixture of diethyl ether and petroleum ether to obtain the following formula

Thus, 1.56 g of 5- (3,4-difluorobenzyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 4.23 (2H, s), 6.60 (1H, s), 7.12-7.21 (1H, m), 7. 35-7.45 (2H, m), 13.95 (1H, br s)

で示される５−（３，５−ジクロロベンジル）イソキサゾール−３−カルボン酸エチル１７０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．４１（３Ｈ，ｔ），４．１０（２Ｈ，ｓ），４．４３（２Ｈ，ｑ），６．４２（１Ｈ，ｓ），７．１２−７．１６（２Ｈ，ｍ），７．２９−７．３２（１Ｈ，ｍ） Reference Production Example 229
Ethyl 5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (300 mg, 0.98 mmol), 3,5-dichlorophenylboronic acid (242 mg, 1.27 mmol) and potassium carbonate (269 mg, 1.95 mmol) in toluene To a mixture of (5 mL) and water (1 mL). Under an argon atmosphere, palladium acetate (11 mg, 0.05 mmol) and triphenylphosphine (51 mg, 0.19 mmol) were added, and the mixture was stirred at 90 to 95 ° C. for 4 hours, then cooled and added with water, and twice with ethyl acetate. Extracted. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

170 (mg) of ethyl 5- (3,5-dichlorobenzyl) isoxazole-3-carboxylate
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.41 (3H, t), 4.10 (2H, s), 4.43 (2H, q), 6.42 (1H, s) , 7.12-7.16 (2H, m), 7.29-7.32 (1H, m)

で示される５−（３，５−ジクロロベンジル）イソキサゾール−３−カルボン酸１．７０ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．２７（２Ｈ，ｓ），６．６５（１Ｈ，ｓ），７．４０−７．４４（２Ｈ，ｍ），７．５３−７．５６（１Ｈ，ｍ），１３．９６（１Ｈ，ｂｒ ｓ） Reference production example 230
Ethyl 5- (3,5-dichlorobenzyl) isoxazole-3-carboxylate (2.45 g, 8.20 mmol) was added to a mixture of ethanol (25 mL) and 2 mol / L aqueous sodium hydroxide (12 mL) at 0 ° C., After stirring at room temperature for 16 hours, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with a mixture of diethyl ether and petroleum ether,

1.70 g of 5- (3,5-dichlorobenzyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 4.27 (2H, s), 6.65 (1H, s), 7.40-7.44 (2H, m), 7. 53-7.56 (1H, m), 13.96 (1H, br s)

で示される５−（２−チエニルメチル）イソキサゾール−３−カルボン酸エチル３２ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．４０（３Ｈ，ｔ），４．１６（２Ｈ，ｓ），４．４３（２Ｈ，ｑ），６．３８（１Ｈ，ｓ），６．７５−７．０１（１Ｈ，ｍ），７．１０−７．１４（１Ｈ，ｍ），７．３２（１Ｈ，ｄｄ） Reference Production Example 231
To a toluene solution (4 mL) of ethyl 5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (100 mg, 0.33 mmol) and 2-thienylboronic acid (54 mg, 0.42 mmol), saturated aqueous sodium carbonate solution (1 mL) Was added. Under an argon atmosphere, 1,1′-bis (diphenylphosphino) ferrocene-palladium (II) dichloride (24 mg, 0.03 mmol) was added, stirred at 75 to 80 ° C. for 4 hours, diluted with ethyl acetate, and celite. And filtered. The filtrate was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 32 mg of ethyl 5- (2-thienylmethyl) isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.40 (3H, t), 4.16 (2H, s), 4.43 (2H, q), 6.38 (1H, s) 6.75-7.01 (1H, m), 7.10-7.14 (1H, m), 7.32 (1H, dd)

で示される５−（２−チエニルメチル）イソキサゾール−３−カルボン酸２００ｍｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．４７（２Ｈ，ｓ），６．６１（１Ｈ，ｓ），６．９６−７．０４（２Ｈ，ｍ），７．４１−７．４６（１Ｈ，ｍ），１３．９５（１Ｈ，ｂｒ ｓ） Reference Production Example 232
Ethyl 5- (2-thienylmethyl) isoxazole-3-carboxylate (750 mg, 3.16 mmol) was added to a mixture of ethanol (8 mL) and 2 mol / L aqueous sodium hydroxide solution (4 mL) at 0 ° C., and at room temperature for 16 hours. After stirring, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed twice with a mixture of diethyl ether and petroleum ether

200 mg of 5- (2-thienylmethyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 4.47 (2H, s), 6.61 (1H, s), 6.96-7.04 (2H, m), 7. 41-7.46 (1H, m), 13.95 (1H, br s)

で示される５−（３−チエニルメチル）イソキサゾール−３−カルボン酸エチル５６ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．４０（３Ｈ，ｔ），４．１６（２Ｈ，ｓ），４．４３（２Ｈ，ｑ），６．３４（１Ｈ，ｓ），６．９９（１Ｈ，ｄ），７．１０−７．１３（１Ｈ，ｍ），７．３０−７．３４（１Ｈ，ｍ） Reference Production Example 233
To a toluene solution (4 mL) of ethyl 5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (100 mg, 0.33 mmol) and 3-thienylboronic acid (54 mg, 0.42 mmol), saturated aqueous sodium carbonate solution (1 mL) Was added. Under an argon atmosphere, 1,1′-bis (diphenylphosphino) ferrocene-palladium (II) dichloride (24 mg, 0.03 mmol) was added, stirred at 75 to 80 ° C. for 4 hours, diluted with ethyl acetate, and celite. And filtered. The filtrate was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 56 mg of ethyl 5- (3-thienylmethyl) isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.40 (3H, t), 4.16 (2H, s), 4.43 (2H, q), 6.34 (1H, s) , 6.99 (1H, d), 7.10-7.13 (1H, m), 7.30-7.34 (1H, m)

で示される５−（３−チエニルメチル）イソキサゾール−３−カルボン酸３００ｍｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．２２（２Ｈ，ｓ），６．５６（１Ｈ，ｓ），７．０４−７．０８（１Ｈ，ｍ），７．３４−７．３８（１Ｈ，ｍ），７．５０−７．５６（１Ｈ，ｍ），１３．９０（１Ｈ，ｂｒ ｓ） Reference Production Example 234
Ethyl 5- (3-thienylmethyl) isoxazole-3-carboxylate (900 mg, 3.79 mmol) was added to a mixture of ethanol (9 mL) and 2 mol / L aqueous sodium hydroxide solution (4 mL) at 0 ° C., and at room temperature for 16 hours. After stirring, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed twice with a mixture of diethyl ether and petroleum ether

As a result, 300 mg of 5- (3-thienylmethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 4.22 (2H, s), 6.56 (1H, s), 7.04-7.08 (1H, m), 7. 34-7.38 (1H, m), 7.50-7.56 (1H, m), 13.90 (1H, br s)

で示される５−（２−フラニルメチル）イソキサゾール−３−カルボン酸エチル２１ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．４０（３Ｈ，ｔ），４．１９（２Ｈ，ｓ），４．４３（２Ｈ，ｑ），６．２１（１Ｈ，ｄ），６．３５（１Ｈ，ｄｄ），６．４６（１Ｈ，ｓ），７．３８（１Ｈ，ｄ） Reference Production Example 235
To a toluene solution (4 mL) of ethyl 5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (100 mg, 0.33 mmol) and 2-furanylboronic acid (48 mg, 0.42 mmol) was added a saturated aqueous sodium carbonate solution (1 mL). added. Under an argon atmosphere, 1,1′-bis (diphenylphosphino) ferrocene-palladium (II) dichloride (24 mg, 0.03 mmol) was added, stirred at 75 to 80 ° C. for 4 hours, diluted with ethyl acetate, and celite. And filtered. The filtrate was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

21 mg of ethyl 5- (2-furanylmethyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.40 (3H, t), 4.19 (2H, s), 4.43 (2H, q), 6.21 (1H, d) 6.35 (1H, dd), 6.46 (1H, s), 7.38 (1H, d)

で示される５−（２−フラニルメチル）イソキサゾール−３−カルボン酸１５０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．３２（２Ｈ，ｓ），６．２８−６．３２（１Ｈ，ｍ），６．４１−６．４５（１Ｈ，ｍ），６．６０（１Ｈ，ｓ），７．５８−７．６３（１Ｈ，ｍ），１３．９４（１Ｈ，ｂｒ ｓ） Reference Production Example 236
Ethyl 5- (2-furanylmethyl) isoxazole-3-carboxylate (1.00 g, 4.52 mmol) was added to a mixture of ethanol (10 mL) and 2 mol / L aqueous sodium hydroxide solution (5 mL) at 0 ° C. After stirring for hours, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with a mixture of ethyl acetate and petroleum ether to obtain the following formula:

150 mg of 5- (2-furanylmethyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 4.32 (2H, s), 6.28-6.32 (1H, m), 6.41-6.45 (1H, m ), 6.60 (1H, s), 7.58-7.63 (1H, m), 13.94 (1H, br s)

で示される５−（３−フラニルメチル）イソキサゾール−３−カルボン酸エチル２２ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．４０（３Ｈ，ｔ），３．９７（２Ｈ，ｓ），４．４３（２Ｈ，ｑ），６．３４（１Ｈ，ｓ），６．４０（１Ｈ，ｓ），７．３８（１Ｈ，ｓ），７．４１−７．４２（１Ｈ，ｍ） Reference Production Example 237
To a toluene solution (4 mL) of ethyl 5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (100 mg, 0.33 mmol) and 3-furanylboronic acid (48 mg, 0.42 mmol) was added a saturated aqueous sodium carbonate solution (1 mL). added. Under an argon atmosphere, 1,1′-bis (diphenylphosphino) ferrocene-palladium (II) dichloride (24 mg, 0.03 mmol) was added, stirred at 75 to 80 ° C. for 4 hours, diluted with ethyl acetate, and celite. And filtered. The filtrate was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

22 mg of ethyl 5- (3-furanylmethyl) isoxazole-3-carboxylate represented by
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.40 (3H, t), 3.97 (2H, s), 4.43 (2H, q), 6.34 (1H, s) 6.40 (1H, s), 7.38 (1H, s), 7.41-7.42 (1H, m)

で示される５−（３−フラニルメチル）イソキサゾール−３−カルボン酸５３１ｍｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．０３（１Ｈ，ｓ），６．４５−６．４８（１Ｈ，ｍ），６．５６（１Ｈ，ｓ），７．５８−７．６６（２Ｈ，ｍ），１３．９２（１Ｈ，ｂｒ ｓ） Reference Production Example 238
Ethyl 5- (3-furanylmethyl) isoxazole-3-carboxylate (800 mg, 3.62 mmol) was added to a mixture of ethanol (8 mL) and 2 mol / L aqueous sodium hydroxide solution (4 mL) at 0 ° C. and stirred at room temperature for 16 hours. And then diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with a mixture of ethyl acetate and petroleum ether to obtain the following formula:

531 mg of 5- (3-furanylmethyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 4.03 (1H, s), 6.45-6.48 (1H, m), 6.56 (1H, s), 7. 58-7.66 (2H, m), 13.92 (1H, br s)

で示される５−（３−メトキシベンジル）イソキサゾール−３−カルボン酸エチル２１３ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．３９（３Ｈ，ｔ），３．８０（３Ｈ，ｓ），４．１０（２Ｈ，ｓ），４．４１（２Ｈ，ｑ），６．３５（１Ｈ，ｓ），６．７６−６．８６（３Ｈ，ｍ），７．２３−７．２９（１Ｈ，ｍ） Reference Production Example 239
5- (Diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (300 mg, 0.98 mmol), 3-methoxyphenylboronic acid (193 mg, 1.27 mmol) and potassium carbonate (269 mg, 1.95 mmol) were added to toluene ( 4 mL) and water (1 mL). Under an argon atmosphere, palladium acetate (11 mg, 0.05 mmol) and triphenylphosphine (51 mg, 0.19 mmol) were added, stirred at 90 to 95 ° C. for 4 hours, diluted with ethyl acetate, and filtered through celite. . The filtrate was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 213 mg of ethyl 5- (3-methoxybenzyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.39 (3H, t), 3.80 (3H, s), 4.10 (2H, s), 4.41 (2H, q) 6.35 (1H, s), 6.76-6.86 (3H, m), 7.2-3.29 (1H, m).

で示される５−（３−メトキシベンジル）イソキサゾール−３−カルボン酸１３０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：３．７４（３Ｈ，ｓ），４．１８（２Ｈ，ｓ），６．５７（１Ｈ，ｓ），６．８２−６．９０（３Ｈ，ｍ），７．２６（１Ｈ，ｄｄ），１３．９１（１Ｈ，ｂｒ ｓ） Reference Production Example 240
Ethyl 5- (3-methoxybenzyl) isoxazole-3-carboxylate (200 mg, 0.77 mmol) was added to a mixture of ethanol (2 mL) and 2 mol / L aqueous sodium hydroxide solution (1 mL) at 0 ° C., and 16 hours at room temperature. After stirring, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with petroleum ether

In this way, 130 mg of 5- (3-methoxybenzyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 3.74 (3H, s), 4.18 (2H, s), 6.57 (1H, s), 6.82-6. 90 (3H, m), 7.26 (1H, dd), 13.91 (1H, br s)

で示される５−（３−トリフルオロメトキシベンジル）イソキサゾール−３−カルボン酸エチル２００ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．４０（３Ｈ，ｔ），４．１６（２Ｈ，ｓ），４．４３（２Ｈ，ｑ），６．３８（１Ｈ，ｓ），７．０８−７．２２（３Ｈ，ｍ），７．３４−７．４２（１Ｈ，ｍ） Reference Production Example 241
5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (300 mg, 0.98 mmol), 3-trifluoromethoxyphenylboronic acid (262 mg, 1.27 mmol) and potassium carbonate (269 mg, 1.95 mmol). To a mixture of toluene (4 mL) and water (1 mL). Under an argon atmosphere, palladium acetate (11 mg, 0.05 mmol) and triphenylphosphine (51 mg, 0.19 mmol) were added, stirred at 90 to 95 ° C. for 4 hours, diluted with ethyl acetate, and filtered through celite. . The filtrate was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

200 mg of ethyl 5- (3-trifluoromethoxybenzyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.40 (3H, t), 4.16 (2H, s), 4.43 (2H, q), 6.38 (1H, s) 7.08-7.22 (3H, m), 7.34-7.42 (1H, m)

で示される５−（３−トリフルオロメトキシベンジル）イソキサゾール−３−カルボン酸１．８０ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．３１（２Ｈ，ｓ），６．６１（１Ｈ，ｓ），７．２４−７．３８（３Ｈ，ｍ），７．４５−７．５４（１Ｈ，ｍ），１３．９２（１Ｈ，ｂｒ ｓ） Reference production example 242
Ethyl 5- (3-trifluoromethoxybenzyl) isoxazole-3-carboxylate (2.60 g, 8.44 mmol) was added to a mixture of ethanol (25 mL) and 2 mol / L aqueous sodium hydroxide (12 mL) at 0 ° C., After stirring at room temperature for 16 hours, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with a mixture of diethyl ether and petroleum ether to obtain the following formula

To 1.80 g of 5- (3-trifluoromethoxybenzyl) isoxazole-3-carboxylic acid represented by the following formula.
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 4.31 (2H, s), 6.61 (1H, s), 7.24-7.38 (3H, m), 7. 45-7.54 (1H, m), 13.92 (1H, br s)

で示される５−（４−メトキシベンジル）イソキサゾール−３−カルボン酸エチル１５０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．３９（３Ｈ，ｔ），３．８０（３Ｈ，ｓ），４．０７（２Ｈ，ｓ），４．２１（２Ｈ，ｑ），６．３０（１Ｈ，ｓ），６．８８（ｓＨ，ｄ），７．１７（２Ｈ，ｄ） Reference Production Example 243
Ethyl 5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (300 mg, 0.98 mmol), 4-methoxyphenylboronic acid (193 mg, 1.27 mmol) and potassium carbonate (269 mg, 1.95 mmol) in toluene ( 4 mL) and water (1 mL). Under an argon atmosphere, palladium acetate (11 mg, 0.05 mmol) and triphenylphosphine (51 mg, 0.19 mmol) were added, stirred at 90 to 95 ° C. for 4 hours, diluted with ethyl acetate, and filtered through celite. . The filtrate was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

150 mg of ethyl 5- (4-methoxybenzyl) isoxazole-3-carboxylate
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.39 (3H, t), 3.80 (3H, s), 4.07 (2H, s), 4.21 (2H, q) , 6.30 (1H, s), 6.88 (sH, d), 7.17 (2H, d)

で示される５−（４−メトキシベンジル）イソキサゾール−３−カルボン酸１．５０ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：３．７３（３Ｈ，ｓ），４．１３（２Ｈ，ｓ），６．５１（１Ｈ，ｓ），６．８７−６．９３（２Ｈ，ｍ），７．１９−７．２６（２Ｈ，ｍ），１３．９０（１Ｈ，ｂｒ ｓ） Reference production example 244
Ethyl 5- (4-methoxybenzyl) isoxazole-3-carboxylate (2.40 g, 9.20 mmol) was added to a mixture of ethanol (25 mL) and 2 mol / L aqueous sodium hydroxide solution (12 mL) at 0 ° C. and at room temperature. After stirring for 16 hours, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with a mixture of diethyl ether and petroleum ether to obtain the following formula

To 1.50 g of 5- (4-methoxybenzyl) isoxazole-3-carboxylic acid represented by the following formula.
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 3.73 (3H, s), 4.13 (2H, s), 6.51 (1H, s), 6.87-6. 93 (2H, m), 7.19-7.26 (2H, m), 13.90 (1H, br s)

で示される５−（４−トリフルオロメトキシベンジル）イソキサゾール−３−カルボン酸エチル１８２ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．４０（３Ｈ，ｔ），４．１５（２Ｈ，ｓ），４．４２（２Ｈ，ｑ），６．３７（１Ｈ，ｓ），７．１７−７．２１（２Ｈ，ｍ），７．２４−７．３２（２Ｈ，ｍ） Reference Production Example 245
5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (300 mg, 0.98 mmol), 4-trifluoromethoxyphenylboronic acid (262 mg, 1.27 mmol) and potassium carbonate (269 mg, 1.95 mmol). To a mixture of toluene (4 mL) and water (1 mL). Under an argon atmosphere, palladium acetate (11 mg, 0.05 mmol) and triphenylphosphine (51 mg, 0.19 mmol) were added, stirred at 90 to 95 ° C. for 4 hours, diluted with ethyl acetate, and filtered through celite. . The filtrate was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 182 mg of ethyl 5- (4-trifluoromethoxybenzyl) isoxazole-3-carboxylate represented by formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.40 (3H, t), 4.15 (2H, s), 4.42 (2H, q), 6.37 (1H, s) 7.17-7.21 (2H, m), 7.24-7.32 (2H, m)

で示される５−（４−トリフルオロメトキシベンジル）イソキサゾール−３−カルボン酸１．７０ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．２８（２Ｈ，ｓ），６．６１（１Ｈ，ｓ），７．３１−７．３８（２Ｈ，ｍ），７．４０−７．４８（２Ｈ，ｍ），１３．９２（１Ｈ，ｂｒ ｓ） Reference Production Example 246
Ethyl 5- (4-trifluoromethoxybenzyl) isoxazole-3-carboxylate (2.60 g, 8.25 mmol) was added to a mixture of ethanol (25 mL) and 2 mol / L aqueous sodium hydroxide (12 mL) at 0 ° C., After stirring at room temperature for 16 hours, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with a mixture of diethyl ether and petroleum ether to obtain the following formula

1.70 g of 5- (4-trifluoromethoxybenzyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 4.28 (2H, s), 6.61 (1H, s), 7.31-7.38 (2H, m), 7. 40-7.48 (2H, m), 13.92 (1H, br s)

で示される５−（４−トリフルオロメチルベンジル）イソキサゾール−３−カルボン酸エチル１６６ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．４０（３Ｈ，ｔ），４．２０（２Ｈ，ｓ），４．４３（２Ｈ，ｑ），６．３８（１Ｈ，ｓ），７．４２−７．６０（４Ｈ，ｍ） Reference Production Example 247
5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (300 mg, 0.98 mmol), 4-trifluoromethylphenylboronic acid (241 mg, 1.27 mmol) and potassium carbonate (269 mg, 1.95 mmol). To a mixture of toluene (4 mL) and water (1 mL). Under an argon atmosphere, palladium acetate (11 mg, 0.05 mmol) and triphenylphosphine (51 mg, 0.19 mmol) were added, stirred at 90 to 95 ° C. for 4 hours, diluted with ethyl acetate, and filtered through celite. . The filtrate was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 166 mg of ethyl 5- (4-trifluoromethylbenzyl) isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.40 (3H, t), 4.20 (2H, s), 4.43 (2H, q), 6.38 (1H, s) , 7.42-7.60 (4H, m)

で示される５−（４−トリフルオロメチルベンジル）イソキサゾール−３−カルボン酸１．７０ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．３６（２Ｈ，ｓ），６．６４（１Ｈ，ｓ），７．５２−７．５８（２Ｈ，ｍ），７．６９−７．７６（２Ｈ，ｍ），１３．９２（１Ｈ，ｂｒ ｓ） Reference Production Example 248
Ethyl 5- (4-trifluoromethylbenzyl) isoxazole-3-carboxylate (2.40 g, 8.02 mmol) was added to a mixture of ethanol (25 mL) and 2 mol / L aqueous sodium hydroxide (12 mL) at 0 ° C. After stirring at room temperature for 16 hours, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with a mixture of diethyl ether and petroleum ether to obtain the following formula

1.70 g of 5- (4-trifluoromethylbenzyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 4.36 (2H, s), 6.64 (1H, s), 7.52 to 7.58 (2H, m), 7. 69-7.76 (2H, m), 13.92 (1H, br s)

で示される５−（２−メトキシベンジル）イソキサゾール−３−カルボン酸エチル１４０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．３９（３Ｈ，ｔ），３．８２（３Ｈ，ｓ），４．１２（２Ｈ，ｓ），４．４１（２Ｈ，ｑ），６．２８（１Ｈ，ｓ），６．８６−６．９６（２Ｈ，ｍ），７．１６−７．２０（１Ｈ，ｍ） Reference Production Example 249
Ethyl 5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (300 mg, 0.98 mmol), 2-methoxyphenylboronic acid (193 mg, 1.27 mmol) and potassium carbonate (269 mg, 1.95 mmol) in toluene ( 4 mL) and water (1 mL). Under an argon atmosphere, palladium acetate (11 mg, 0.05 mmol) and triphenylphosphine (51 mg, 0.19 mmol) were added, stirred at 90 to 95 ° C. for 4 hours, diluted with ethyl acetate, and filtered through celite. . The filtrate was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 140 mg of ethyl 5- (2-methoxybenzyl) isoxazole-3-carboxylate represented by formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.39 (3H, t), 3.82 (3H, s), 4.12 (2H, s), 4.41 (2H, q) , 6.28 (1H, s), 6.86-6.96 (2H, m), 7.16-7.20 (1H, m)

で示される５−（２−メトキシベンジル）イソキサゾール−３−カルボン酸１．４０ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：３．７９（３Ｈ，ｓ），４．１３（２Ｈ，ｓ），６．４１（１Ｈ，ｓ），６．９０−６．９６（１Ｈ，ｍ），７．０１−７．０５（１Ｈ，ｍ），７．１８−７．２４（１Ｈ，ｍ），７．２６−７．３３（１Ｈ，ｍ），１３．９０（１Ｈ，ｂｒ ｓ） Reference production example 250
Ethyl 5- (2-methoxybenzyl) isoxazole-3-carboxylate (2.00 g, 7.66 mmol) was added to a mixture of ethanol (20 mL) and 2 mol / L aqueous sodium hydroxide solution (10 mL) at 0 ° C. and at room temperature. After stirring for 16 hours, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with a mixture of diethyl ether and petroleum ether to obtain the following formula

1.40 g of 5- (2-methoxybenzyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 3.79 (3H, s), 4.13 (2H, s), 6.41 (1H, s), 6.90-6. 96 (1H, m), 7.01-7.05 (1H, m), 7.18-7.24 (1H, m), 7.26-7.33 (1H, m), 13.90 ( 1H, br s)

で示される５−（３−フルオロベンジル）イソキサゾール−３−カルボン酸エチル１５７ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．３９（３Ｈ，ｔ），４．１７（２Ｈ，ｓ），４．４１（２Ｈ，ｑ），６．３７（１Ｈ，ｓ），７．０６−７．１６（２Ｈ，ｍ），７．２２−７．３３（２Ｈ，ｍ） Reference Production Example 251
Ethyl 5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (300 mg, 0.98 mmol), 3-fluorophenylboronic acid (175 mg, 1.27 mmol) and potassium carbonate (269 mg, 1.95 mmol) in toluene ( 4 mL) and water (1 mL). Under an argon atmosphere, palladium acetate (11 mg, 0.05 mmol) and triphenylphosphine (51 mg, 0.19 mmol) were added, stirred at 90 to 95 ° C. for 4 hours, diluted with ethyl acetate, and filtered through celite. . The filtrate was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 157 mg of ethyl 5- (3-fluorobenzyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.39 (3H, t), 4.17 (2H, s), 4.41 (2H, q), 6.37 (1H, s) 7.06-7.16 (2H, m), 7.22-7.33 (2H, m)

で示される５−（３−フルオロベンジル）イソキサゾール−３−カルボン酸１００ｍｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．２５（２Ｈ，ｓ），６．６０（１Ｈ，ｓ），７．０８−７．２２（３Ｈ，ｍ），７．３６−７．４４（１Ｈ，ｍ），１３．９２（１Ｈ，ｂｒ ｓ） Reference production example 252
Ethyl 5- (3-fluorobenzyl) isoxazole-3-carboxylate (150 mg, 0.60 mmol) was added to a mixture of ethanol (2 mL) and 2 mol / L aqueous sodium hydroxide solution (1 mL) at 0 ° C., and at room temperature for 16 hours. After stirring, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with petroleum ether

100 mg of 5- (3-fluorobenzyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 4.25 (2H, s), 6.60 (1H, s), 7.08-7.22 (3H, m), 7. 36-7.44 (1H, m), 13.92 (1H, br s)

で示される５−（４−フルオロベンジル）イソキサゾール−３−カルボン酸エチル１５０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．３９（３Ｈ，ｔ），４．１１（２Ｈ，ｓ），４．４２（２Ｈ，ｑ），６．３３（１Ｈ，ｓ），７．００−７．０７（２Ｈ，ｍ），７．１９−７．２５（２Ｈ，ｍ） Reference production example 253
Ethyl 5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (300 mg, 0.98 mmol), 4-fluorophenylboronic acid (175 mg, 1.27 mmol) and potassium carbonate (269 mg, 1.95 mmol) in toluene ( 4 mL) and water (1 mL). Under an argon atmosphere, palladium acetate (11 mg, 0.05 mmol) and triphenylphosphine (51 mg, 0.19 mmol) were added, stirred at 90 to 95 ° C. for 4 hours, diluted with ethyl acetate, and filtered through celite. . The filtrate was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

150 mg of ethyl 5- (4-fluorobenzyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.39 (3H, t), 4.11 (2H, s), 4.42 (2H, q), 6.33 (1H, s) , 7.00-7.07 (2H, m), 7.19-7.25 (2H, m)

で示される５−（４−フルオロベンジル）イソキサゾール−３−カルボン酸１００ｍｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．２２（２Ｈ，ｓ），６．５６（１Ｈ，ｓ），７．１４−７．２２（２Ｈ，ｍ），７．３２−７．３９（２Ｈ，ｍ），１３．９２（１Ｈ，ｂｒ ｓ） Reference Production Example 254
Ethyl 5- (4-fluorobenzyl) isoxazole-3-carboxylate (150 mg, 0.60 mmol) was added to a mixture of ethanol (2 mL) and 2 mol / L aqueous sodium hydroxide solution (1 mL) at 0 ° C., and at room temperature for 16 hours. After stirring, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with petroleum ether

100 mg of 5- (4-fluorobenzyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 4.22 (2H, s), 6.56 (1H, s), 7.14-7.22 (2H, m), 7. 32-7.39 (2H, m), 13.92 (1H, br s)

で示される５−（２−フルオロベンジル）イソキサゾール−３−カルボン酸エチル１４６ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．４０（３Ｈ，ｔ），４．１３（２Ｈ，ｓ），４．４２（２Ｈ，ｑ），６．３７（１Ｈ，ｓ），６．９４−７．０６（３Ｈ，ｍ），７．２７−７．３６（１Ｈ，ｍ） Reference Production Example 255
Ethyl 5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (300 mg, 0.98 mmol), 2-fluorophenylboronic acid (175 mg, 1.27 mmol) and potassium carbonate (269 mg, 1.95 mmol) in toluene ( 4 mL) and water (1 mL). Under an argon atmosphere, palladium acetate (11 mg, 0.05 mmol) and triphenylphosphine (51 mg, 0.19 mmol) were added, stirred at 90 to 95 ° C. for 4 hours, diluted with ethyl acetate, and filtered through celite. . The filtrate was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 146 mg of ethyl 5- (2-fluorobenzyl) isoxazole-3-carboxylate was obtained.
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.40 (3H, t), 4.13 (2H, s), 4.42 (2H, q), 6.37 (1H, s) 6.94-7.06 (3H, m), 7.27-7.36 (1H, m)

で示される５−（２−フルオロベンジル）イソキサゾール−３−カルボン酸９０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．２６（２Ｈ，ｓ），６．５５（１Ｈ，ｓ），７．１７−７．２７（２Ｈ，ｍ），７．３３−７．４３（２Ｈ，ｍ），１３．９２（１Ｈ，ｂｒ ｓ） Reference production example 256
Ethyl 5- (2-fluorobenzyl) isoxazole-3-carboxylate (140 mg, 0.56 mmol) was added to a mixture of ethanol (2 mL) and 2 mol / L aqueous sodium hydroxide solution (1 mL) at 0 ° C., and at room temperature for 16 hours. After stirring, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with petroleum ether

90 mg of 5- (2-fluorobenzyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 4.26 (2H, s), 6.55 (1H, s), 7.17-7.27 (2H, m), 7. 33-7.43 (2H, m), 13.92 (1H, br s)

で示される５−（３−クロロベンジル）イソキサゾール−３−カルボン酸エチル１１０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．４０（３Ｈ，ｔ），４．１２（２Ｈ，ｓ），４．４２（２Ｈ，ｑ），６．３７（１Ｈ，ｓ），７．１２−７．１６（１Ｈ，ｍ），７．２３−７．３０（３Ｈ，ｍ） Reference Production Example 257
Ethyl 5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (200 mg, 0.65 mmol), 3-chlorophenylboronic acid (132 mg, 0.84 mmol) and potassium carbonate (179 mg, 1.30 mmol) in toluene (4 mL) ) And water (1 mL). Under an argon atmosphere, palladium acetate (7 mg, 0.03 mmol) and triphenylphosphine (34 mg, 0.13 mmol) were added, stirred at 90 to 95 ° C. for 4 hours, diluted with ethyl acetate, and filtered through celite. . The filtrate was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

110 mg of ethyl 5- (3-chlorobenzyl) isoxazole-3-carboxylate represented by
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.40 (3H, t), 4.12 (2H, s), 4.42 (2H, q), 6.37 (1H, s) , 7.12-7.16 (1H, m), 7.23-7.30 (3H, m)

で示される５−（３−クロロベンジル）イソキサゾール−３−カルボン酸７０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．２５（２Ｈ，ｓ），６．６１（１Ｈ，ｓ），７．２６−７．３０（１Ｈ，ｍ），７．３３−７．４２（３Ｈ，ｍ），１３．９２（１Ｈ，ｂｒ ｓ） Reference Production Example 258
Ethyl 5- (3-chlorobenzyl) isoxazole-3-carboxylate (110 mg, 0.41 mmol) was added to a mixture of ethanol (2 mL) and 2 mol / L aqueous sodium hydroxide solution (1 mL) at 0 ° C., and at room temperature for 16 hours. After stirring, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with petroleum ether

70 mg of 5- (3-chlorobenzyl) isoxazole-3-carboxylic acid represented by
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 4.25 (2H, s), 6.61 (1H, s), 7.26-7.30 (1H, m), 7. 33-7.42 (3H, m), 13.92 (1H, br s)

で示される５−（４−クロロベンジル）イソキサゾール−３−カルボン酸エチル１３２ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．４０（３Ｈ，ｔ），４．１１（２Ｈ，ｓ），４．４２（２Ｈ，ｑ），６．３４（１Ｈ，ｓ），７．１９（２Ｈ，ｄ），７．３２（２Ｈ，ｄ） Reference Production Example 259
Ethyl 5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (300 mg, 0.98 mmol), 4-chlorophenylboronic acid (199 mg, 1.27 mmol) and potassium carbonate (269 mg, 1.95 mmol) in toluene (4 mL) ) And water (1 mL). Under an argon atmosphere, palladium acetate (11 mg, 0.05 mmol) and triphenylphosphine (51 mg, 0.19 mmol) were added, stirred at 90 to 95 ° C. for 4 hours, diluted with ethyl acetate, and filtered through celite. . The filtrate was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

132 mg of ethyl 5- (4-chlorobenzyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.40 (3H, t), 4.11 (2H, s), 4.42 (2H, q), 6.34 (1H, s) 7.19 (2H, d), 7.32 (2H, d)

で示される５−（４−クロロベンジル）イソキサゾール−３−カルボン酸１．７０ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．２３（２Ｈ，ｓ），６．５８（１Ｈ，ｓ），７．３０−７．３６（２Ｈ，ｍ），７．３６−７．４４（２Ｈ，ｍ），１３．９０（１Ｈ，ｂｒ ｓ） Reference Production Example 260
Ethyl 5- (4-chlorobenzyl) isoxazole-3-carboxylate (2.60 g, 9.81 mmol) was added to a mixture of ethanol (25 mL) and 2 mol / L aqueous sodium hydroxide solution (12 mL) at 0 ° C. and at room temperature. After stirring for 16 hours, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with petroleum ether

1.70 g of 5- (4-chlorobenzyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
_{^{1 H-NMR (DMSO-d}} 6, TMS) δ (ppm): 4.23 (2H, s), 6.58 (1H, s), 7.30-7.36 (2H, m), 7. 36-7.44 (2H, m), 13.90 (1H, br s)

で示される５−（２−クロロベンジル）イソキサゾール−３−カルボン酸エチル１４０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．３９（３Ｈ，ｔ），４．２３（２Ｈ，ｓ），４．４１（２Ｈ，ｑ），６．３４（１Ｈ，ｓ），７．２２−７．３０（３Ｈ，ｍ），７．３８−７．４５（１Ｈ，ｍ） Reference Production Example 261
Ethyl 5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (300 mg, 0.98 mmol), 2-chlorophenylboronic acid (199 mg, 1.27 mmol) and potassium carbonate (269 mg, 1.95 mmol) in toluene (4 mL) ) And water (1 mL). Under an argon atmosphere, palladium acetate (11 mg, 0.05 mmol) and triphenylphosphine (51 mg, 0.19 mmol) were added, stirred at 90 to 95 ° C. for 4 hours, diluted with ethyl acetate, and filtered through celite. . The filtrate was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 140 mg of ethyl 5- (2-chlorobenzyl) isoxazole-3-carboxylate represented by formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.39 (3H, t), 4.23 (2H, s), 4.41 (2H, q), 6.34 (1H, s) 7.22-7.30 (3H, m), 7.38-7.45 (1H, m)

で示される５−（２−クロロベンジル）イソキサゾール−３−カルボン酸１．９０ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．３２（２Ｈ，ｓ），６．５１（１Ｈ，ｓ），７．３０−７．５２（４Ｈ，ｍ），１３．９６（１Ｈ，ｂｒ ｓ） Reference Production Example 262
Ethyl 5- (2-chlorobenzyl) isoxazole-3-carboxylate (2.70 g, 10.18 mmol) was added to a mixture of ethanol (25 mL) and 2 mol / L aqueous sodium hydroxide solution (12 mL) at 0 ° C. and at room temperature. After stirring for 16 hours, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with a mixture of diethyl ether and petroleum ether to obtain the following formula

1.90 g of 5- (2-chlorobenzyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 4.32 (2H, s), 6.51 (1H, s), 7.30-7.52 (4H, m), 13. 96 (1H, br s)

で示される５−（２，３，４−トリフルオロベンジル）イソキサゾール−３−カルボン酸エチル４０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．４０（３Ｈ，ｔ），４．１６（２Ｈ，ｓ），４．４３（２Ｈ，ｑ），６．４１（１Ｈ，ｓ），６．９４−７．２０（２Ｈ，ｍ） Reference Production Example 263
5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (100 mg, 0.33 mmol), 2,3,4-trifluorophenylboronic acid (75 mg, 0.42 mmol) and potassium carbonate (133 mg,. 65 mmol) was added to a mixture of toluene (4 mL) and water (1 mL). Under an argon atmosphere, palladium acetate (4 mg, 0.02 mmol) and triphenylphosphine (17 mg, 0.07 mmol) were added, stirred at 90 to 95 ° C. for 4 hours, diluted with ethyl acetate, and filtered through celite. . The filtrate was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

40 mg of ethyl 5- (2,3,4-trifluorobenzyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.40 (3H, t), 4.16 (2H, s), 4.43 (2H, q), 6.41 (1H, s) , 6.94-7.20 (2H, m)

で示される５−（２，３，４−トリフルオロベンジル）イソキサゾール−３−カルボン酸１．１０ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．３１（２Ｈ，ｓ），６．６２（１Ｈ，ｓ），７．２３−７．４０（２Ｈ，ｍ），１３．９８（１Ｈ，ｂｒ ｓ） Reference Production Example 264
Ethyl 5- (2,3,4-trifluorobenzyl) isoxazole-3-carboxylate (1.50 g, 5.26 mmol) in a mixture of ethanol (15 mL) and 2 mol / L aqueous sodium hydroxide (7.5 mL). The mixture was added at 0 ° C., stirred at room temperature for 16 hours, diluted with water, and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with a mixture of diethyl ether and petroleum ether to obtain the following formula

1.10 g of 5- (2,3,4-trifluorobenzyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 4.31 (2H, s), 6.62 (1H, s), 7.23-7.40 (2H, m), 13. 98 (1H, br s)

で示される５−（３，４−ジクロロベンジル）イソキサゾール−３−カルボン酸エチル１８１ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．４０（３Ｈ，ｔ），４．１０（２Ｈ，ｓ），４．４３（２Ｈ，ｑ），６．３９（１Ｈ，ｓ），７．１０（１Ｈ，ｄｄ），７．３５（１Ｈ，ｄ），７．４２（１Ｈ，ｄ） Reference Production Example 265
Ethyl 5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (300 mg, 0.98 mmol), 3,4-dichlorophenylboronic acid (199 mg, 1.27 mmol) and potassium carbonate (269 mg, 1.95 mmol) in toluene To a mixture of (5 mL) and water (1 mL). Under an argon atmosphere, palladium acetate (11 mg, 0.05 mmol) and triphenylphosphine (51 mg, 0.19 mmol) were added, stirred at 90 to 95 ° C. for 4 hours, diluted with ethyl acetate, and filtered through celite. . The filtrate was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 181 mg of ethyl 5- (3,4-dichlorobenzyl) isoxazole-3-carboxylate represented by formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.40 (3H, t), 4.10 (2H, s), 4.43 (2H, q), 6.39 (1H, s) , 7.10 (1H, dd), 7.35 (1H, d), 7.42 (1H, d)

で示される５−（３，４−ジクロロベンジル）イソキサゾール−３−カルボン酸１．８６ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．２６（２Ｈ，ｓ），６．６２（１Ｈ，ｓ），７．３０−７．３４（１Ｈ，ｍ），７．６０−７．６６（２Ｈ，ｍ），１３．９５（１Ｈ，ｂｒ ｓ） Reference Production Example 266
Ethyl 5- (3,4-dichlorobenzyl) isoxazole-3-carboxylate (2.60 g, 8.66 mmol) was added to a mixture of ethanol (25 mL) and 2 mol / L aqueous sodium hydroxide (12 mL) at 0 ° C., After stirring at room temperature for 16 hours, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with a mixture of diethyl ether and petroleum ether to obtain the following formula

1.86 g of 5- (3,4-dichlorobenzyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 4.26 (2H, s), 6.62 (1H, s), 7.30-7.34 (1H, m), 7. 60-7.66 (2H, m), 13.95 (1H, br s)

で示される５−（２−ビフェニルメチル）イソキサゾール−３−カルボン酸エチル４０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．３９（３Ｈ，ｔ），４．０８（２Ｈ，ｓ），４．４１（２Ｈ，ｑ），６．１６（１Ｈ，ｓ），７．２１−７．４２（９Ｈ，ｍ） Reference Production Example 267
Ethyl 5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (100 mg, 0.33 mmol), 2-biphenylboronic acid (77 mg, 0.39 mmol) and potassium carbonate (87 mg, 0.65 mmol) in toluene (4 mL) ) And water (1 mL). Under an argon atmosphere, palladium acetate (4 mg, 0.02 mmol) and triphenylphosphine (17 mg, 0.07 mmol) were added, and the mixture was stirred at 90 to 95 ° C. for 1 hour under microwave irradiation, and then diluted with ethyl acetate. And filtered. The filtrate was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

40 mg of ethyl 5- (2-biphenylmethyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.39 (3H, t), 4.08 (2H, s), 4.41 (2H, q), 6.16 (1H, s) , 7.21-7.42 (9H, m)

で示される５−（２−ビフェニルメチル）イソキサゾール−３−カルボン酸１．３２ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．１５（２Ｈ，ｓ），６．２４（１Ｈ，ｓ），７．２２−７．３２（３Ｈ，ｍ），７．３５−７．４８（６Ｈ，ｍ），１３．９０（１Ｈ，ｂｒ ｓ） Reference Production Example 268
Ethyl 5- (2-biphenylmethyl) isoxazole-3-carboxylate (1.80 g, 5.86 mmol) was added to a mixture of ethanol (20 mL) and 2 mol / L aqueous sodium hydroxide solution (10 mL) at 0 ° C., and at room temperature. After stirring for 16 hours, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with petroleum ether

1.32 g of 5- (2-biphenylmethyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 4.15 (2H, s), 6.24 (1H, s), 7.22-7.32 (3H, m), 7. 35-7.48 (6H, m), 13.90 (1H, br s)

で示される５−（３−ビフェニルメチル）イソキサゾール−３−カルボン酸エチル３０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．３９（３Ｈ，ｔ），４．２０（２Ｈ，ｓ），４．４１（２Ｈ，ｑ），６．３８（１Ｈ，ｓ），７．２１−７．２６（１Ｈ，ｍ），７．３２−７．６０（８Ｈ，ｍ） Reference Production Example 269
Ethyl 5- (diethoxyphosphoryloxymethyl) -isoxazole-3-carboxylate (100 mg, 0.33 mmol), 3-biphenylboronic acid (77 mg, 0.39 mmol) and potassium carbonate (87 mg, 0.65 mmol) in toluene ( 4 mL) and water (1 mL). Under an argon atmosphere, palladium acetate (4 mg, 0.02 mmol) and triphenylphosphine (17 mg, 0.07 mmol) were added, and the mixture was stirred at 90 to 95 ° C. for 1 hour under microwave irradiation. The reaction was diluted with ethyl acetate and filtered through celite. The filtrate was added to water and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

30 mg of ethyl 5- (3-biphenylmethyl) isoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.39 (3H, t), 4.20 (2H, s), 4.41 (2H, q), 6.38 (1H, s) , 7.21-7.26 (1H, m), 7.32-7.60 (8H, m)

で示される５−（３−ビフェニルメチル）イソキサゾール−３−カルボン酸１．１０ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：４．３０（２Ｈ，ｓ），６．６２（１Ｈ，ｓ），７．２８−７．５０（５Ｈ，ｍ），７．５６−７．６８（４Ｈ，ｍ），１３．９２（１Ｈ，ｂｒ ｓ） Reference Production Example 270
Ethyl 5- (3-biphenylmethyl) isoxazole-3-carboxylate (1.50 g, 4.88 mmol) was added to a mixture of ethanol (15 mL) and 2 mol / L aqueous sodium hydroxide solution (7 mL) at 0 ° C. and at room temperature. After stirring for 16 hours, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with petroleum ether

1.10 g of 5- (3-biphenylmethyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 4.30 (2H, s), 6.62 (1H, s), 7.28-7.50 (5H, m), 7. 56-7.68 (4H, m), 13.92 (1H, br s)

で示される５−（３−メチルベンジル）イソキサゾール−３−カルボン酸エチル１２４ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．３９（３Ｈ，ｔ），２．３４（３Ｈ，ｓ），４．０８（２Ｈ，ｓ），４．４１（２Ｈ，ｑ），６．３１（１Ｈ，ｓ），７．０４−７．２２（４Ｈ，ｍ） Reference Production Example 271
Ethyl 5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (300 mg, 0.98 mmol), 3-methylphenylboronic acid (173 mg, 1.27 mmol) and potassium carbonate (269 mg, 1.95 mmol) in toluene ( 4 mL) and water (1 mL). Under an argon atmosphere, palladium acetate (11 mg, 0.05 mmol) and triphenylphosphine (51 mg, 0.19 mmol) were added, and the mixture was stirred at 90 to 95 ° C. for 4 hours, then cooled, water was added, and ethyl acetate twice. Extracted. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 124 mg of ethyl 5- (3-methylbenzyl) isoxazole-3-carboxylate represented by formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.39 (3H, t), 2.34 (3H, s), 4.08 (2H, s), 4.41 (2H, q) , 6.31 (1H, s), 7.04-7.22 (4H, m)

で示される５−（３−メチルベンジル）イソキサゾール−３−カルボン酸１．６６ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：２．２９（３Ｈ，ｓ），４．１６（２Ｈ，ｓ），６．５７（１Ｈ，ｓ），７．０４−７．１４（３Ｈ，ｍ），７．１９−７．２８（１Ｈ，ｍ），１３．９２（１Ｈ，ｂｒ ｓ） Reference Production Example 272
Ethyl 5- (3-methylbenzyl) isoxazole-3-carboxylate (2.20 g, 8.98 mmol) was added to a mixture of ethanol (22 mL) and 2 mol / L aqueous sodium hydroxide solution (11 mL) at 0 ° C. and at room temperature. After stirring for 16 hours, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with petroleum ether

1.66 g of 5- (3-methylbenzyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 2.29 (3H, s), 4.16 (2H, s), 6.57 (1H, s), 7.04-7. 14 (3H, m), 7.19-7.28 (1H, m), 13.92 (1H, br s)

で示される５−（４−メチルベンジル）イソキサゾール−３−カルボン酸エチル１３０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．３９（３Ｈ，ｔ），２．３４（３Ｈ，ｓ），４．０８（２Ｈ，ｓ），４．４１（２Ｈ，ｑ），６．３０（１Ｈ，ｓ），７．０５−７．２０（４Ｈ，ｍ） Reference Production Example 273
Ethyl 5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (300 mg, 0.98 mmol), 4-methylphenylboronic acid (173 mg, 1.27 mmol) and potassium carbonate (269 mg, 1.95 mmol) in toluene ( 4 mL) and water (1 mL). Under an argon atmosphere, palladium acetate (11 mg, 0.05 mmol) and triphenylphosphine (51 mg, 0.19 mmol) were added, and the mixture was stirred at 90 to 95 ° C. for 4 hours, cooled, added with water, and twice with ethyl acetate. Extracted. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

130 mg of ethyl 5- (4-methylbenzyl) isoxazole-3-carboxylate represented by
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.39 (3H, t), 2.34 (3H, s), 4.08 (2H, s), 4.41 (2H, q) 6.30 (1H, s), 7.05-7.20 (4H, m)

で示される５−（４−メチルベンジル）イソキサゾール−３−カルボン酸１．５８ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：２．２８（３Ｈ，ｓ），４．１６（２Ｈ，ｓ），６．５４（１Ｈ，ｓ），７．１２−７．２２（４Ｈ，ｍ），１３．９１（１Ｈ，ｂｒ ｓ） Reference Production Example 274
Ethyl 5- (4-methylbenzyl) isoxazole-3-carboxylate (2.10 g, 8.57 mmol) was added to a mixture of ethanol (20 mL) and 2 mol / L aqueous sodium hydroxide solution (10 mL) at 0 ° C. and at room temperature. After stirring for 16 hours, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with petroleum ether

Thus, 1.58 g of 5- (4-methylbenzyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 2.28 (3H, s), 4.16 (2H, s), 6.54 (1H, s), 7.12-7. 22 (4H, m), 13.91 (1H, br s)

で示される５−（２−メチルベンジル）イソキサゾール−３−カルボン酸エチル１２０ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３，ＴＭＳ）δ（ｐｐｍ）：１．３９（３Ｈ，ｔ），２．２９（３Ｈ，ｓ），４．１１（２Ｈ，ｓ），４．４０（２Ｈ，ｑ），６．２１（１Ｈ，ｓ），７．０８−７．２４（４Ｈ，ｍ） Reference Production Example 275
Ethyl 5- (diethoxyphosphoryloxymethyl) isoxazole-3-carboxylate (300 mg, 0.98 mmol), 2-methylphenylboronic acid (173 mg, 1.27 mmol) and potassium carbonate (269 mg, 1.95 mmol) in toluene ( 4 mL) and water (1 mL). Under an argon atmosphere, palladium acetate (11 mg, 0.05 mmol) and triphenylphosphine (51 mg, 0.19 mmol) were added, and the mixture was stirred at 90 to 95 ° C. for 4 hours, then cooled and added with water, and twice with ethyl acetate. Extracted. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

120 mg of ethyl 5- (2-methylbenzyl) isoxazole-3-carboxylate represented by
¹ H-NMR (CDCl ₃ , TMS) δ (ppm): 1.39 (3H, t), 2.29 (3H, s), 4.11 (2H, s), 4.40 (2H, q) , 6.21 (1H, s), 7.08-7.24 (4H, m)

で示される５−（２−メチルベンジル）イソキサゾール−３−カルボン酸１．４６ｇを得た。
^１Ｈ−ＮＭＲ（ＤＭＳＯ−ｄ_６，ＴＭＳ）δ（ｐｐｍ）：２．２７（３Ｈ，ｓ），４．２０（２Ｈ，ｓ），６．４８（１Ｈ，ｓ），７．１４−７．２４（４Ｈ，ｍ），１３．９１（１Ｈ，ｂｒ ｓ） Reference Production Example 276
Ethyl 5- (2-methylbenzyl) isoxazole-3-carboxylate (2.00 g, 8.16 mmol) was added to a mixture of ethanol (20 mL) and 2 mol / L aqueous sodium hydroxide solution (10 mL) at 0 ° C., and at room temperature. After stirring for 16 hours, it was diluted with water and concentrated under reduced pressure. The concentrate was acidified with 1 mol / L hydrochloric acid at 0 ° C., and extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is washed with petroleum ether

1.46 g of 5- (2-methylbenzyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (DMSO-d ₆ , TMS) δ (ppm): 2.27 (3H, s), 4.20 (2H, s), 6.48 (1H, s), 7.14-7. 24 (4H, m), 13.91 (1H, br s)

で示される１−ブチル−１Ｈ−１，２，３−トリアゾール−４−カルボン酸エチル０．６５ｇ及び、下式

で示される２−ブチル−２Ｈ−１，２，３−トリアゾール−４−カルボン酸エチル０．２４ｇを得た。
１−ブチル−１Ｈ−１，２，３−トリアゾール−４−カルボン酸エチル
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９５（ｔ，３Ｈ），１．３４（ｔｑ，２Ｈ），１．４１（ｔ，３Ｈ），１．９８（ｔｔ，２Ｈ），４．４３（ｑ，２Ｈ），４．５０（ｔ，２Ｈ），８．０４（ｓ，１Ｈ）
２−ブチル−２Ｈ−１，２，３−トリアゾール−４−カルボン酸エチル
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９７（ｔ，３Ｈ），１．３２−１．４４（ｍ，５Ｈ），１．９２（ｔｔ，２Ｈ），４．４０−４．４６（ｍ，４Ｈ），８．０７（ｓ，１Ｈ） Reference Production Example 277
60% sodium hydride (0.29 g, 7.14 mmol) was added to N, N-dimethylformamide and stirred at 50 ° C. To the mixture was slowly added a solution of ethyl 1,2,3-triazole-4-carboxylate (1.00 g, 7.14 mmol) in N, N-dimethylformamide (3 mL) and stirred at 50 ° C. for 1 hour. Bromobutane (1.08 g, 7.85 mmol) was added dropwise, the temperature was raised to 60 ° C., and the mixture was stirred for 3 hours. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.65 g of ethyl 1-butyl-1H-1,2,3-triazole-4-carboxylate represented by the formula:

In this manner, 0.24 g of ethyl 2-butyl-2H-1,2,3-triazole-4-carboxylate represented by the formula:
1-butyl-1H-1,2,3-triazole-4-carboxylate
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.95 (t, 3H), 1.34 (tq, 2H), 1.41 (t, 3H), 1.98 (tt, 2H) ), 4.43 (q, 2H), 4.50 (t, 2H), 8.04 (s, 1H)
2-Butyl-2H-1,2,3-triazole-4-carboxylate ethyl
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.97 (t, 3H), 1.32-1.44 (m, 5H), 1.92 (tt, 2H), 4.40 -4.46 (m, 4H), 8.07 (s, 1H)

で示される１−ブチル−１Ｈ−１，２，３−トリアゾール−４−カルボン酸０．５６ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９４（ｔ，３Ｈ），１．３３（ｔｑ，２Ｈ），１．９８（ｔｔ，２Ｈ），４．５０（ｔ，２Ｈ），８．０７（ｓ，１Ｈ） Reference Production Example 278
Ethyl 1-butyl-1H-1,2,3-triazole-4-carboxylate (0.65 g, 3.30 mmol) was added to ethanol (1 mL), and potassium hydroxide (0.23 g, 4.05 mmol) and Water (7 mL) was added, and the mixture was stirred overnight at room temperature, and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

Thus, 0.56 g of 1-butyl-1H-1,2,3-triazole-4-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.94 (t, 3H), 1.33 (tq, 2H), 1.98 (tt, 2H), 4.50 (t, 2H) ), 8.07 (s, 1H)

で示される２−ブチル−２Ｈ−１，２，３−トリアゾール−４−カルボン酸０．１７ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９８（ｔ，３Ｈ），１．３８（ｔｑ，２Ｈ），１．９５（ｔｔ，２Ｈ），４．４５（ｔ，２Ｈ），８．１５（ｓ，１Ｈ） Reference Production Example 279
Ethyl 2-butyl-2H-1,2,3-triazole-4-carboxylate (0.24 g, 1.22 mmol) was added to ethanol (0.5 mL), and potassium hydroxide (0.08 g, 1.46 mmol) was added. ) And water (3 mL) were added, and the mixture was stirred at room temperature for 4 hours, and then concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

0.17 g of 2-butyl-2H-1,2,3-triazole-4-carboxylic acid represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.98 (t, 3H), 1.38 (tq, 2H), 1.95 (tt, 2H), 4.45 (t, 2H) ), 8.15 (s, 1H)

で示される２，４−ジオキソ−３−メチル−５−フェニルメトキシ−２−ペンタン酸エチル０．６０ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．２３−１．３５（６Ｈ，ｍ），４．０９−４．３９（５Ｈ，ｍ），４．５４（２Ｈ，ｓ），７．２８−７．４３（５Ｈ，ｍ） Reference Production Example 280
1-Phenylmethoxy-2-butanone (1.55 g, 8.70 mmol) and diethyl oxalate (1.53 g, 10.44 mmol) were dissolved in ethanol (17.4 ml), and the temperature was reduced to −10 ° C. or lower under a nitrogen atmosphere. Cooled down. Sodium ethoxide (20% ethanol solution, about 3 g, about 8.70 mmol) was added dropwise to the mixture over 15 minutes, and the mixture was stirred for 1 hour and 45 minutes while gradually warming to room temperature. Neutralized with hydrochloric acid and extracted with methyl-tert-butyl ether. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 0.60 g of ethyl 2,4-dioxo-3-methyl-5-phenylmethoxy-2-pentanoate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.23-1.35 (6H, m), 4.09-4.39 (5H, m), 4.54 (2H, s) , 7.28-7.43 (5H, m)

で示される５−ベンジルオキシメチル−４−メチルイソキサゾール−３−カルボン酸エチル３００ｍｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４３（３Ｈ，ｔ），２．２１（３Ｈ，ｓ），４．４５（２Ｈ，ｑ），４．５６（２Ｈ，ｓ），４．６２（２Ｈ，ｓ），７．２９−７．４１（５Ｈ，ｍ） Reference Production Example 281
Dissolve ethyl 2,4-dioxo-3-methyl-5-benzyloxymethyl-2-pentanoate (800 mg, 2.88 mmol) in ethanol (3 ml) and add hydroxylamine hydrochloride (400 mg, 5.76 mmol). The mixture was heated to reflux for 5 hours under a nitrogen atmosphere. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, diluted with ethyl acetate, and washed successively with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 300 mg of ethyl 5-benzyloxymethyl-4-methylisoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.43 (3H, t), 2.21 (3H, s), 4.45 (2H, q), 4.56 (2H, s) ), 4.62 (2H, s), 7.29-7.41 (5H, m)

で示される５−（５−フェニル−２−チエニルメチルオキシメチル）イソキサゾール−３−カルボン酸エチル０．５２ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４２（ｔ，３Ｈ），４．４５（ｑ，２Ｈ），４．７０（ｓ，２Ｈ），４．７７（ｓ，２Ｈ），６．７１（ｂｒ ｓ，１Ｈ），７．０１（ｄ，１Ｈ），７．１９（ｄ，１Ｈ）， ７．２８−７．３２（１Ｈ，ｍ）， ７．３７−７．４１（２Ｈ，ｍ），７．５８−７．６０（２Ｈ，ｍ） Reference Production Example 282
Ethyl nitroacetate (0.56 g, 4.20 mmol), (5-phenyl-2-thienylmethyl) propargyl ether (0.48 g, 2.10 mmol) and 1,4-diazabicyclo [2.2.2] octane (0 .05 g, 0.42 mmol) was added to chloroform (amylene-added product) (1 mL), heated under reflux for 14 hours, cooled to room temperature, diluted hydrochloric acid was added, and the mixture was extracted twice with ethyl acetate. The organic layer was washed once with saturated multilayered water, then with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.52 g of ethyl 5- (5-phenyl-2-thienylmethyloxymethyl) isoxazole-3-carboxylate represented by
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42 (t, 3H), 4.45 (q, 2H), 4.70 (s, 2H), 4.77 (s, 2H) ), 6.71 (brs, 1H), 7.01 (d, 1H), 7.19 (d, 1H), 7.28-7.32 (1H, m), 7.37-7.41. (2H, m), 7.58-7.60 (2H, m)

で示される５−（５−フェニル−２−チエニルメチルオキシメチル）イソキサゾール−３−カルボン酸０．６８ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：４．７１（ｓ，２Ｈ），４．７８（ｓ，２Ｈ），６．７７（ｓ，１Ｈ），７．０２（ｄ，１Ｈ），７．２０（ｄ，１Ｈ）， ７．２８−７．３２（１Ｈ，ｍ）， ７．３７−７．４１（２Ｈ，ｍ），７．５８−７．６０（２Ｈ，ｍ） Reference Production Example 283
Ethyl 5- (5-phenyl-2-thienylmethyloxymethyl) isoxazole-3-carboxylate (0.82 g, 2.51 mmol) was added to ethanol (4 mL) and potassium hydroxide (0.17 g, 3.01 mmol). And water (6.5 mL) were added, and the mixture was stirred overnight at room temperature and concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

As a result, 0.68 g of 5- (5-phenyl-2-thienylmethyloxymethyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 4.71 (s, 2H), 4.78 (s, 2H), 6.77 (s, 1H), 7.02 (d, 1H) ), 7.20 (d, 1H), 7.28-7.32 (1H, m), 7.37-7.41 (2H, m), 7.58-7.60 (2H, m)

で示される５−（５，６，７，８−テトラヒドロナフタレン−２−イル）オキシメチルイソキサゾール−３−カルボン酸エチル０．６９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４２（３Ｈ，ｔ），１．７６−１．７９（４Ｈ，ｍ），２．７２（４Ｈ，ｂｒ），４．４４（２Ｈ，ｑ），５．１７（２Ｈ，ｓ），６．６５（１Ｈ，ｄ），６．６９−６．７１（１Ｈ，ｍ），６．７４（１Ｈ，ｂｒ ｓ），６．９９（１Ｈ，ｄ） Reference Production Example 284
Under a nitrogen atmosphere, ethyl 5-hydroxymethylisoxazole-3-carboxylate (1.73 g, 10.1 mmol), triphenylphosphine (2.65 g, 10.1 mmol) and 5,6,7,8-tetrahydro- 2-Naphthol (1.50 g, 10.1 mmol) was added to dry tetrahydrofuran (30 ml). A toluene solution of diisopropyl azodicarboxylate (40%, 5.63 g, 11.1 mmol) was added dropwise to the mixture, stirred overnight at room temperature, added to dilute hydrochloric acid, extracted with ethyl acetate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 0.69 g of ethyl 5- (5,6,7,8-tetrahydronaphthalen-2-yl) oxymethylisoxazole-3-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.42 (3H, t), 1.76-1.79 (4H, m), 2.72 (4H, br), 4.44 (2H, q), 5.17 (2H, s), 6.65 (1H, d), 6.69-6.71 (1H, m), 6.74 (1H, br s), 6.99. (1H, d)

で示される５−（５，６，７，８−テトラヒドロナフタレン−２−イル）オキシメチルイソキサゾール−３−カルボン酸０．５９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．７６−１．７９（４Ｈ，ｍ），２．７２（４Ｈ，ｂｒ），５．１９（２Ｈ，ｓ），６．６６（１Ｈ，ｄ），６．６９−６．７２（１Ｈ，ｍ），６．７９（１Ｈ，ｂｒ ｓ），６．９９（１Ｈ，ｄ） Reference Production Example 285
Ethyl 5- (5,6,7,8-tetrahydronaphthalen-2-yl) oxymethylisoxazole-3-carboxylate (0.69 g, 2.29 mmol) was added to ethanol (3.5 mL) and hydroxylated. Potassium (0.15 g, 2.75 mmol) and water (5.5 mL) were added, and the mixture was stirred at room temperature for 8 hr and concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

In this way, 0.59 g of 5- (5,6,7,8-tetrahydronaphthalen-2-yl) oxymethylisoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.76-1.79 (4H, m), 2.72 (4H, br), 5.19 (2H, s), 6.66 (1H, d), 6.69-6.72 (1H, m), 6.79 (1H, br s), 6.99 (1H, d)

で示される５−（３−ブロモプロピル）イソキサゾール−３−カルボン酸エチル２．１３ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４０（３Ｈ，ｔ），１．８２−１．８５（２Ｈ，m），３．０１（２Ｈ，t），３．４１−３．４４（２Ｈ，m），４．４１（２H，q），６．４７（１Ｈ，ｓ） Reference Production Example 286
Ethyl 5- (3-hydroxypropyl) isoxazole-3-carboxylate (6.37 g, 32 mmol) and carbon tetrabromide (15.90 g, 48 mmol) were added to tetrahydrofuran (200 ml). Triphenylphosphine (8.39 g, 48 mmol) was added to the mixture over 30 minutes, stirred at room temperature for 18 hours, and the solvent was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

2.13 g of ethyl 5- (3-bromopropyl) isoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.40 (3H, t), 1.82-1.85 (2H, m), 3.01 (2H, t), 3.41 -3.44 (2H, m), 4.41 (2H, q), 6.47 (1H, s)

で示される３−ベンジルオキシメチルイソキサゾール−５−カルボン酸エチル１．２１ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：１．４０（３Ｈ，ｔ），４．４３（２Ｈ，ｑ），４．５６（２Ｈ，ｓ），４．６５（２Ｈ，ｓ），７．００（１Ｈ，ｓ），７．２５−７．３８（５Ｈ，ｍ） Reference Production Example 287
Benzyloxynitroethane (1.81 g, 10 mmol), ethyl propiolate (0.98 g, 10 mmol) and 4- (dimethylamino) pyridine (0.30 g, 2.5 mmol) were added to dry tetrahydrofuran (26 mL). Di-tert-butyl carbonate (3.82 g, 17.5 mmol) was added to the mixture, stirred at room temperature for 24 hours, then stirred at 50 degrees for 5 hours, cooled to room temperature, added water, and extracted twice with ethyl acetate. did. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 1.21 g of ethyl 3-benzyloxymethylisoxazole-5-carboxylate represented by the formula:
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 1.40 (3H, t), 4.43 (2H, q), 4.56 (2H, s), 4.65 (2H, s) ), 7.00 (1H, s), 7.25-7.38 (5H, m)

で示される５−ベンジルオキシメチルイソキサゾール−３−カルボン酸０．４９ｇを得た。
^１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．２５−７．３８（５Ｈ，ｍ），７．１２（１Ｈ，ｄ），４．６８（２Ｈ，ｓ），４．５８（２Ｈ，ｓ） Reference Production Example 288
Ethyl 3-benzyloxymethylisoxazole-5-carboxylate (1.21 g, 4.6 mmol) was added to ethanol (30 mL), and potassium hydroxide (0.78 g, 13.9 mmol) and water (10 mL) were added. After that, the mixture was stirred overnight at room temperature and concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and then crystallized with a mixture of t-butyl methyl ether and hexane.

As a result, 0.49 g of 5-benzyloxymethylisoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.25-7.38 (5H, m), 7.12 (1H, d), 4.68 (2H, s), 4.58 (2H, s)

で示される５−（２−メトキシベンジルオキシメチル）イソキサゾール−３−カルボン酸１．１５ｇを得た。
^１Ｈ−ＮＭＲ（CDCｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．２８−７．３５（ｍ，２Ｈ），６．８７−６．９７（ｍ，２Ｈ），６．７４（ｓ，１Ｈ），４．７１（ｓ，２Ｈ），４．６５（ｓ，２Ｈ）．３．８３（ｓ，３Ｈ） Reference Production Example 293
Under a nitrogen atmosphere, ethyl 5-hydroxymethylisoxazole-3-carboxylate (0.86 g, 5.0 mmol) was added to dry tetrahydrofuran (25 ml) and cooled to 0 ° C. 60% sodium hydride (0.40 g, 10.0 mmol) was added to the mixture, and the mixture was further stirred for 30 minutes, 2-methoxybenzyl chloride (0.94 g, 6.0 mmol) was added, and the mixture was warmed to room temperature and heated for 16 hours. After stirring, the mixture was poured into a saturated aqueous ammonium chloride solution and extracted twice with ethyl acetate. The organic layer was washed with water and saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. Ethanol (25 mL) was added to the residue, 2N sodium hydroxide (15 mL) was added, and the mixture was stirred at room temperature for 16 hr and concentrated under reduced pressure. Dilute hydrochloric acid was added to the reaction mixture, the mixture was cooled to 0 ° C., and the precipitated solid was filtered. The solid is dried under reduced pressure.

1.15 g of 5- (2-methoxybenzyloxymethyl) isoxazole-3-carboxylic acid represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.28-7.35 (m, 2H), 6.87-6.97 (m, 2H), 6.74 (s, 1H) 4.71 (s, 2H), 4.65 (s, 2H). 3.83 (s, 3H)

で示される５−（２−メチルベンジルオキシメチル）イソキサゾール−３−カルボン酸１．１５ｇを得た。
^１Ｈ−ＮＭＲ（CDCｌ_３、ＴＭＳ、δ（ｐｐｍ））：７．１７−７．３０（ｍ，４Ｈ），６．７１（ｓ，１Ｈ），４．６７（ｓ，２Ｈ），４．６２（ｓ，２Ｈ）．２．３１（ｓ，３Ｈ） Reference Production Example 294
Under a nitrogen atmosphere, ethyl 5-hydroxymethylisoxazole-3-carboxylate (0.86 g, 5.0 mmol) was added to dry tetrahydrofuran (25 ml) and cooled to 0 ° C. To the mixture, 60% sodium hydride (0.40 g, 10.0 mmol) was added, and the mixture was further stirred for 30 minutes, 2-methylbenzyl bromide (1.1 g, 6.0 mmol) was added, and the mixture was warmed to room temperature and stirred for 16 hours. After stirring, the mixture was poured into a saturated aqueous ammonium chloride solution and extracted twice with ethyl acetate. The organic layer was washed with water and saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. Ethanol (25 mL) was added to the residue, 2N sodium hydroxide (15 mL) was added, and the mixture was stirred at room temperature for 16 hr and concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, cooled to 0 ° C., and the precipitated solid was filtered. The solid is dried under reduced pressure.

1.15 g of 5- (2-methylbenzyloxymethyl) isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 7.17-7.30 (m, 4H), 6.71 (s, 1H), 4.67 (s, 2H), 4.62 (S, 2H). 2.31 (s, 3H)

で示される５−プロパルギルオキシメチルイソキサゾール−３−カルボン酸エチル３．３３ｇを得た。
^１Ｈ−ＮＭＲ（CDCｌ_３、ＴＭＳ、δ（ｐｐｍ））：６．７１（ｓ，１Ｈ），４．７４（ｓ，２Ｈ），４．４３（２Ｈ，ｑ），４．２４（ｄ，２Ｈ）．２．５２（ｔ，１Ｈ），４．１４（ｔ，３Ｈ） Reference production example 295
Under a nitrogen atmosphere, ethyl 5-hydroxymethylisoxazole-3-carboxylate (5.14 g, 30.0 mmol) was added to dry N, N-dimethylformamide (60 ml) and cooled to 0 ° C. 60% sodium hydride (1.32 g, 33.0 mmol) was added to the mixture, and the mixture was further stirred for 30 minutes, propargyl bromide (3.92 g, 33.0 mmol) was added, and the mixture was warmed to room temperature and stirred for 16 hours. The mixture was poured into a saturated aqueous ammonium chloride solution and extracted twice with ethyl acetate. The organic layer was washed with water and saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

In this manner, 3.33 g of ethyl 5-propargyloxymethylisoxazole-3-carboxylate represented by the following formula was obtained.
¹ H-NMR (CDCl ₃ , TMS, δ (ppm)): 6.71 (s, 1H), 4.74 (s, 2H), 4.43 (2H, q), 4.24 (d, 2H) ). 2.52 (t, 1H), 4.14 (t, 3H)

で示される５−プロパルギルオキシメチルイソキサゾール−３−カルボン酸２．８８ｇを得た。 Reference Production Example 296
Ethyl 5-propargyloxymethylisoxazole-3-carboxylate (3.33 g, 15.9 mmol) is added to ethanol (30 mL), lithium hydroxide (0.77 g, 31.8 mmol) and water (30 mL) are added. After that, the mixture was stirred overnight at room temperature and concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

As a result, 2.88 g of 5-propargyloxymethylisoxazole-3-carboxylic acid represented by the following formula was obtained.

で示される２−ブチル−２Ｈ−テトラゾール−５−カルボン酸エチル０．５９ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９８（ｔ，３Ｈ），１．３８（ｔｑ，２Ｈ），１．４９（ｔ，３Ｈ），１．９３（ｔｔ，２Ｈ），４．５４（ｑ，２Ｈ），４．７５（ｔ，２Ｈ） Reference Production Example 297
1H-tetrazole-5-carboxylic acid ethyl sodium salt (1.00 g, 6.09 mmol) was added to dimethylformamide (10 mL), and the mixture was stirred at 50 ° C. 1-Bromobutane (0.92 g, 6.70 mmol) was added dropwise to the mixture, and then the mixture was heated to 60 ° C. and stirred for 4 hours. After cooling to room temperature, tap water was added and extracted twice with ethyl acetate. The organic layer was washed with saturated brine and then concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

As a result, 0.59 g of ethyl 2-butyl-2H-tetrazole-5-carboxylate represented by the formula:
1H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.98 (t, 3H), 1.38 (tq, 2H), 1.49 (t, 3H), 1.93 (tt, 2H) , 4.54 (q, 2H), 4.75 (t, 2H)

で示される２−ブチル−２Ｈ−テトラゾール−５−カルボン酸０．３９ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９９（ｔ，３Ｈ），１．３９（ｔｑ，２Ｈ），２．０８（ｔｔ，２Ｈ），４．７５（ｔ，２Ｈ） Reference Production Example 298
Ethyl 2-butyl-2H-tetrazole-5-carboxylate (0.59 g, 2.98 mmol) was added to ethanol (1 mL), and potassium hydroxide (0.20 g, 3.58 mmol) and water (7 mL) were added. Thereafter, the mixture was stirred at room temperature for 2 hours. Then, it concentrated under pressure reduction. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

As a result, 0.39 g of 2-butyl-2H-tetrazole-5-carboxylic acid represented by the formula (1) was obtained.
1H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.99 (t, 3H), 1.39 (tq, 2H), 2.08 (tt, 2H), 4.75 (t, 2H)

で示される５−ブチル−１，２，４−オキサジアゾール−３−カルボン酸エチル３．６９ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９６（３Ｈ，ｔ），１．４０−１．５０（５Ｈ，ｍ），１．８１−１．８９（２Ｈ，ｍ），２．９８（２Ｈ，ｔ），４．５１（２Ｈ，ｑ） Reference Production Example 299
Ethyl 2-amino-2-hydroxyiminoacetate (4.62 g, 35 mmol) and diisopropylethylamine (7.24 g, 56 mmol) were added to chloroform (amylene-added product) (100 mL). Valeryl chloride (4.22 g, 35 mmol) was added to the mixture at −30 to −20 ° C., and the mixture was stirred at room temperature for 24 hours. Thereafter, ice water was added to the reaction mixture, and extracted three times with chloroform. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in pyridine (120 mL), stirred for 20 hours under reflux with heating, and concentrated under reduced pressure. The concentrate was dissolved in ethyl acetate, and the organic layer was washed 3 times with water, then with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

3.69 g of ethyl 5-butyl-1,2,4-oxadiazole-3-carboxylate represented by the formula:
1H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.96 (3H, t), 1.40-1.50 (5H, m), 1.81-1.89 (2H, m), 2.98 (2H, t), 4.51 (2H, q)

で示される５−ブチル−１，２，４−オキサジアゾール−３−カルボン酸１．８１ｇを得た。このものは精製することなく次反応に供した。 Reference production example 300
Potassium hydroxide (1.12 g, 20 mmol) and water (3 mL) were added to ethanol (27 mL), and the mixture was stirred at room temperature for 10 minutes. After adding ethyl 5-butyl-1,2,4-oxadiazole-3-carboxylate (1.98 g, 10 mmol) to the mixture at room temperature, the mixture was stirred overnight at room temperature and concentrated under reduced pressure. After the concentrate was dissolved in water, the aqueous layer was washed with tert-butyl-methyl ether, diluted hydrochloric acid was added to the aqueous layer, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

Thus, 1.81 g of 5-butyl-1,2,4-oxadiazole-3-carboxylic acid represented by the following formula was obtained. This was subjected to the next reaction without purification.

で示される３−ブチル−１，２，４−オキサジアゾール−５−カルボン酸エチル７．８４ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９５（３Ｈ，ｔ），１．３５−１．４３（２Ｈ，ｍ），１．４７（３Ｈ，ｔ），１．７３−１．８２（２Ｈ，ｍ），２．８４（２Ｈ，ｔ），４．５３（２Ｈ，ｑ） Reference production example 301
N-hydroxy-pentaneamidine (6.39 g, 55 mmol) and pyridine (13.05 g, 165 mmol) were added to chloroform (amylene-added product) (55 mL), and then ethyl chloroglyoxylate ( 11.26 g, 83 mmol) was added. After stirring at 0 ° C. for 30 minutes, the mixture was stirred overnight at room temperature, water was added, and the mixture was extracted with chloroform. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

In this manner, 7.84 g of ethyl 3-butyl-1,2,4-oxadiazole-5-carboxylate represented by the formula:
1H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.95 (3H, t), 1.35 to 1.43 (2H, m), 1.47 (3H, t), 1.73- 1.82 (2H, m), 2.84 (2H, t), 4.53 (2H, q)

で示される２−ブチル−オキサゾール−４−カルボン酸エチル０．１９ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９３（３Ｈ，ｔ），１．３３−１．４３（５Ｈ，ｍ），１．７２−１．８１（２Ｈ，ｍ），２．８２（２Ｈ，ｔ），４．３９（２Ｈ，ｑ），８．１４（１Ｈ，ｓ） Reference Production Example 302
Palladium acetate (28 mg, 0.13 mmol), (2-biphenyl) dicyclohexylphosphine (88 mg, 0.25 mmol), cesium carbonate (1.63 g, 5.0 mmol) were added to tetrahydrofuran (7 mL). To the mixture, ethyl oxazole-4-carboxylate (0.35 g, 2.5 mmol) and 1-bromobutane (0.69 g, 5.0 mmol) were added at room temperature, and the reaction vessel was replaced with nitrogen, and then 110 ° C. For 18 hours. Water was added to the reaction mixture, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

0.19 g of ethyl 2-butyl-oxazole-4-carboxylate represented by
1H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.93 (3H, t), 1.33-1.43 (5H, m), 1.72-1.81 (2H, m), 2.82 (2H, t), 4.39 (2H, q), 8.14 (1H, s)

で示される２−ブチル−オキサゾール−４−カルボン酸０．１０ｇを得た。このものは精製することなく次反応に供した。 Reference Production Example 303
Ethyl 2-butyl-oxazole-4-carboxylate (0.19 g, 1.0 mmol) was added to ethanol (2.7 mL). To the mixture were added potassium hydroxide (0.11 g, 1.9 mmol) and water (0.3 mL) at room temperature, and the mixture was stirred overnight at room temperature and concentrated under reduced pressure. After the concentrate was dissolved in water, the aqueous layer was washed with tert-butyl-methyl ether, diluted hydrochloric acid was added to the aqueous layer, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

0.10 g of 2-butyl-oxazole-4-carboxylic acid represented by This was subjected to the next reaction without purification.

で示される５−ブチル−オキサゾール−２−カルボン酸エチル１．９０ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：０．９４（３Ｈ，ｔ），１．３４−１．４６（５Ｈ，ｍ），１．６４−１．７３（２Ｈ，ｍ），２．７４（２Ｈ，ｔ），４．４６（２Ｈ，ｑ），６．９６（１Ｈ，ｓ） Reference production example 304
1-Amino-2-hexanone hydrochloride (1.66 g, 11 mmol) was added to chloroform (amylene-added product) (22 mL). To the mixture, ethyl chloroglyoxylate (1.50 g, 11 mmol) and diisopropylethylamine (3.62 g, 28 mmol) were added at 0 ° C., and the mixture was stirred at 0 ° C. for 30 minutes, then stirred at room temperature overnight, and water was added. And extracted three times with chloroform. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The concentrate was dissolved in toluene (24 mL), phosphoryl chloride (5.52 g, 36 mmol) was added, and the mixture was stirred with heating under reflux for 15 hours. A saturated aqueous sodium hydrogen carbonate solution was slowly added, and then the organic layer was saturated with sodium hydrogen carbonate. Washed twice with aqueous solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography.

1.90 g of ethyl 5-butyl-oxazole-2-carboxylate represented by formula (1) was obtained.
1H-NMR (CDCl ₃ , TMS, δ (ppm)): 0.94 (3H, t), 1.34-1.46 (5H, m), 1.64-1.73 (2H, m), 2.74 (2H, t), 4.46 (2H, q), 6.96 (1H, s)

で示される５−（３−ブロモプロピル）−イソキサゾール−３−カルボン酸１．７０ｇを得た。
１Ｈ−ＮＭＲ（ＣＤＣｌ_３、ＴＭＳ、δ（ｐｐｍ））：２．２９（ｔｔ，２Ｈ），３．０５（ｔ，２Ｈ），３．４６（ｔ，２Ｈ），６．５４（ｓ，１Ｈ） Reference production example 305
Ethyl 5- (3-bromopropyl) -isoxazole-3-carboxylate (2.10 g, 7.9 mmol) was added to ethanol (6 mL), potassium hydroxide (0.54 g, 9.60 mmol) and water (10 mL). Was added, and the mixture was stirred overnight at room temperature and concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, and the mixture was extracted twice with chloroform. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure.

1.70 g of 5- (3-bromopropyl) -isoxazole-3-carboxylic acid represented by the formula (1) was obtained.
1H-NMR (CDCl ₃ , TMS, δ (ppm)): 2.29 (tt, 2H), 3.05 (t, 2H), 3.46 (t, 2H), 6.54 (s, 1H)

で示される４−クロロ−５−（２−ナフチルメチルオキシメチル）−１−メチル−１Ｈ−ピラゾール−３−カルボン酸０．７２ｇを得た。
^１Ｈ−ＮＭＲ（CDCｌ３、ＴＭＳ、δ（ｐｐｍ））：７．７７−７．８５（ｍ，４Ｈ），７．４６−７．５１（ｍ，３Ｈ），４．６７（ｓ，２Ｈ），４．６１（ｓ，２Ｈ）．３．９７（ｓ，３Ｈ） Reference Production Example 306
Under a nitrogen atmosphere, 2-naphthalenemethanol (2.62 g, 10.0 mmol) was added to dry tetrahydrofuran (25 ml) and cooled to 0 ° C. Sodium hydride (0.80 g, 20.0 mmol) was added to the mixture, and the mixture was further stirred for 30 minutes, and then ethyl 4-chloro-5-chloromethyl-1-methyl-1H-pyrazole-3-carboxylate (2.57 g). , 10.9 mmol) was added, and the mixture was warmed to room temperature and stirred for 48 hours. The reaction mixture was poured into dilute hydrochloric acid and extracted twice with ethyl acetate. The organic layer was washed with water and saturated brine, dried over sodium sulfate, and concentrated under reduced pressure. Ethanol (50 mL) and water (10 mL) were added to the residue, potassium hydroxide (3.06 g, 54.5 mmol) was added, and the mixture was stirred at room temperature for 12 hr and concentrated under reduced pressure. Dilute hydrochloric acid was added to the concentrate, cooled to 0 ° C., and the precipitated solid was filtered. The solid is dried under reduced pressure.

In this way, 0.72 g of 4-chloro-5- (2-naphthylmethyloxymethyl) -1-methyl-1H-pyrazole-3-carboxylic acid represented by the formula (1) was obtained.
¹ H-NMR (CDC13, TMS, δ (ppm)): 7.77-7.85 (m, 4H), 7.46-7.51 (m, 3H), 4.67 (s, 2H), 4.61 (s, 2H). 3.97 (s, 3H)

Next, specific examples of the compound of the present invention are shown below.

〔式中、Ｑ^１は下記群（Ｑ−１）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-1)

[Wherein Q ¹ represents any group selected from the following group (Q-1)].

〔式中、Ｑ^１は下記群（Ｑ−１）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-2)

[Wherein Q ¹ represents any group selected from the following group (Q-1)].

〔式中、Ｑ^１は下記群（Ｑ−１）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-3)

[Wherein Q ¹ represents any group selected from the following group (Q-1)].

〔式中、Ｑ^１は下記群（Ｑ−１）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-4)

[Wherein Q ¹ represents any group selected from the following group (Q-1)].

〔式中、Ｑ^１は下記群（Ｑ−１）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-5)

[Wherein Q ¹ represents any group selected from the following group (Q-1)].

〔式中、Ｑ^１は下記群（Ｑ−１）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-6)

[Wherein Q ¹ represents any group selected from the following group (Q-1)].

〔式中、Ｑ^１は下記群（Ｑ−１）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-7)

[Wherein Q ¹ represents any group selected from the following group (Q-1)].

〔式中、Ｑ^１は下記群（Ｑ−１）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-8)

[Wherein Q ¹ represents any group selected from the following group (Q-1)].

〔式中、Ｑ^１は下記群（Ｑ−１）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-9)

[Wherein Q ¹ represents any group selected from the following group (Q-1)].

〔式中、Ｑ^１は下記群（Ｑ−１）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-10)

[Wherein Q ¹ represents any group selected from the following group (Q-1)].

〔式中、Ｑ^１は下記群（Ｑ−１）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-11)

[Wherein Q ¹ represents any group selected from the following group (Q-1)].

〔式中、Ｑ^１は下記群（Ｑ−１）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-12)

[Wherein Q ¹ represents any group selected from the following group (Q-1)].

(Group Q-1)
Ethyl group, propyl group, butyl group, pentyl group, 2,2,2-trifluoroethyl group, 3,3,3-trifluoropropyl group, 4,4,4-trifluorobutyl group, 5,5,5 -Trifluoropentyl group, phenyl group, benzyl group, 2-phenylethyl group, 3-phenylpropyl group, 4-phenylbutyl group, 2-fluorophenyl group, 2-fluorobenzyl group, 2- (2-fluorophenyl) Ethyl group, 3- (2-fluorophenyl) propyl group, 4- (2-fluorophenyl) butyl group, 3-fluorophenyl group, 3-fluorobenzyl group, 2- (3-fluorophenyl) ethyl group, 3- (3-fluorophenyl) propyl group, 4- (3-fluorophenyl) butyl group, 4-fluorophenyl group, 4-fluorobenzyl group, 2- (4-fluoropheny group) E) ethyl group, 3- (4-fluorophenyl) propyl group, 4- (4-fluorophenyl) butyl group, 2-chlorophenyl group, 2-chlorobenzyl group, 2- (2-chlorophenyl) ethyl group, 3- (2-chlorophenyl) propyl group, 4- (2-chlorophenyl) butyl group, 3-chlorophenyl group, 3-chlorobenzyl group, 2- (3-chlorophenyl) ethyl group, 3- (3-chlorophenyl) propyl group, 4 -(3-chlorophenyl) butyl group, 4-chlorophenyl group, 4-chlorobenzyl group, 2- (4-chlorophenyl) ethyl group, 3- (4-chlorophenyl) propyl group, 4- (4-chlorophenyl) butyl group, 2-bromophenyl group, 2-bromobenzyl group, 2- (2-bromophenyl) ethyl group, 3- (2-bromophenyl) propyl group, 4- (2-bromophenyl) butyl group, 3-bromophenyl group, 3-bromobenzyl group, 2- (3-bromophenyl) ethyl group, 3- (3-bromophenyl) propyl group, 4- (3- Bromophenyl) butyl group, 4-bromophenyl group, 4-bromobenzyl group, 2- (4-bromophenyl) ethyl group, 3- (4-bromophenyl) propyl group, 4- (4-bromophenyl) butyl group , 3-bromo-5-fluorophenyl group, 3-bromo-5-fluorobenzyl group, 2- (3-bromo-5-fluorophenyl) ethyl group, 3- (3-bromo-5-fluorophenyl) propyl group 4- (3-bromo-5-fluorophenyl) butyl group, 2-trifluoromethylphenyl group, 2-trifluoromethylbenzyl group, 2- (2-trifluoromethylphenyl) ethyl group, -(2-trifluoromethylphenyl) propyl group, 4- (2-trifluoromethylphenyl) butyl group, 3-trifluoromethylphenyl group, 3-trifluoromethylbenzyl group, 2- (3-trifluoromethylphenyl) ) Ethyl group, 3- (3-trifluoromethylphenyl) propyl group, 4- (3-trifluoromethylphenyl) butyl group, 4-trifluoromethylphenyl group, 4-trifluoromethylbenzyl group, 2- (4 -Trifluoromethylphenyl) ethyl group, 3- (4-trifluoromethylphenyl) propyl group, 4- (4-trifluoromethylphenyl) butyl group, 2-trifluoromethoxyphenyl group, 2-trifluoromethoxybenzyl group 2- (2-trifluoromethoxyphenyl) ethyl group, 3- (2-trifluoromethyl) Toxiphenyl) propyl group, 4- (2-trifluoromethoxyphenyl) butyl group, 3-trifluoromethoxyphenyl group, 3-trifluoromethoxybenzyl group, 2- (3-trifluoromethoxyphenyl) ethyl group, 3- (3-trifluoromethoxyphenyl) propyl group, 4- (3-trifluoromethoxyphenyl) butyl group, 4-trifluoromethoxyphenyl group, 4-trifluoromethoxybenzyl group, 2- (4-trifluoromethoxyphenyl) Ethyl group, 3- (4-trifluoromethoxyphenyl) propyl group, 4- (4-trifluoromethoxyphenyl) butyl group, 2-trifluoromethylsulfanylphenyl group, 2-trifluoromethylsulfanylbenzyl group, 2- ( 2-trifluoromethylsulfanylphenyl) Group, 3- (2-trifluoromethylsulfanylphenyl) propyl group, 4- (2-trifluoromethylsulfanylphenyl) butyl group, 3-trifluoromethylsulfanylphenyl group, 3-trifluoromethylsulfanylbenzyl group, 2 -(3-trifluoromethylsulfanylphenyl) ethyl group, 3- (3-trifluoromethylsulfanylphenyl) propyl group, 4- (3-trifluoromethylsulfanylphenyl) butyl group, 4-trifluoromethylsulfanylphenyl group, 4-trifluoromethylsulfanylbenzyl group, 2- (4-trifluoromethylsulfanylphenyl) ethyl group, 3- (4-trifluoromethylsulfanylphenyl) propyl group, 4- (4-trifluoromethylsulfanylphenyl) butyl Tyl group, 1-naphthyl group, 1-naphthylmethyl group, 2- (1-naphthyl) ethyl group, 3- (1-naphthyl) propyl group, 4- (1-naphthyl) butyl group, 2-naphthyl group, 2 -Naphthylmethyl group, 2- (2-naphthyl) ethyl group, 3- (2-naphthyl) propyl group, 8-fluoro-2-naphthyl group, (8-fluoro-2-naphthyl) methyl group, 2- (8 -Fluoro-2-naphthyl) ethyl group, 3- (8-fluoro-2-naphthyl) propyl group, 8-chloro-2-naphthyl group, (8-chloro-2-naphthyl) methyl group, 2- (8- Chloro-2-naphthyl) ethyl group, 3- (8-chloro-2-naphthyl) propyl group, 8-bromo-2-naphthyl group, (8-bromo-2-naphthyl) methyl group, 2- (8-bromo) 2-naphthyl) ethyl group, 3- (8-bromo-2- Naphthyl) propyl group

〔式中、Ｑ^２は下記群（Ｑ−２）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-13)

[Wherein Q ² represents any group selected from the following group (Q-2)].

〔式中、Ｑ^２は下記群（Ｑ−２）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-14)

[Wherein Q ² represents any group selected from the following group (Q-2)].

〔式中、Ｑ^２は下記群（Ｑ−２）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-15)

[Wherein Q ² represents any group selected from the following group (Q-2)].

〔式中、Ｑ^２は下記群（Ｑ−２）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-16)

[Wherein Q ² represents any group selected from the following group (Q-2)].

〔式中、Ｑ^２は下記群（Ｑ−２）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-17)

[Wherein Q ² represents any group selected from the following group (Q-2)].

〔式中、Ｑ^２は下記群（Ｑ−２）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-18)

[Wherein Q ² represents any group selected from the following group (Q-2)].

〔式中、Ｑ^２は下記群（Ｑ−２）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-19)

[Wherein Q ² represents any group selected from the following group (Q-2)].

〔式中、Ｑ^２は下記群（Ｑ−２）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-20)

[Wherein Q ² represents any group selected from the following group (Q-2)].

〔式中、Ｑ^２は下記群（Ｑ−２）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-21)

[Wherein Q ² represents any group selected from the following group (Q-2)].

〔式中、Ｑ^２は下記群（Ｑ−２）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-22)

[Wherein Q ² represents any group selected from the following group (Q-2)].

〔式中、Ｑ^２は下記群（Ｑ−２）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-23)

[Wherein Q ² represents any group selected from the following group (Q-2)].

〔式中、Ｑ^２は下記群（Ｑ−２）より選ばれるいずれかの基を表す〕で示されるアミド化合物。 Formula (Y-24)

[Wherein Q ² represents any group selected from the following group (Q-2)].

(Group Q-2)
Ethyl group, propyl group, butyl group, 2,2,2-trifluoroethyl group, 3,3,3-trifluoropropyl group, 4,4,4-trifluorobutyl group, phenyl group, benzyl group, 2- Phenylethyl group, 3-phenylpropyl group, 2-fluorophenyl group, 2-fluorobenzyl group, 2- (2-fluorophenyl) ethyl group, 3- (2-fluorophenyl) propyl group, 3-fluorophenyl group, 3-fluorobenzyl group, 2- (3-fluorophenyl) ethyl group, 3- (3-fluorophenyl) propyl group, 4-fluorophenyl group, 4-fluorobenzyl group, 2- (4-fluorophenyl) ethyl group 3- (4-fluorophenyl) propyl group, 2-chlorophenyl group, 2-chlorobenzyl group, 2- (2-chlorophenyl) ethyl group, 3- (2- (Rophenyl) propyl group, 3-chlorophenyl group, 3-chlorobenzyl group, 2- (3-chlorophenyl) ethyl group, 3- (3-chlorophenyl) propyl group, 4-chlorophenyl group, 4-chlorobenzyl group, 2- ( 4-chlorophenyl) ethyl group, 3- (4-chlorophenyl) propyl group, 2-bromophenyl group, 2-bromobenzyl group, 2- (2-bromophenyl) ethyl group, 3- (2-bromophenyl) propyl group 3-bromophenyl group, 3-bromobenzyl group, 2- (3-bromophenyl) ethyl group, 3- (3-bromophenyl) propyl group, 4-bromophenyl group, 4-bromobenzyl group, 2- ( 4-bromophenyl) ethyl group, 3- (4-bromophenyl) propyl group, 3-bromo-5-fluorophenyl group, 3-bromo-5-fluoroben Dil group, 2- (3-bromo-5-fluorophenyl) ethyl group, 3- (3-bromo-5-fluorophenyl) propyl group, 2-trifluoromethylphenyl group, 2-trifluoromethylbenzyl group, 2 -(2-trifluoromethylphenyl) ethyl group, 3- (2-trifluoromethylphenyl) propyl group, 3-trifluoromethylphenyl group, 3-trifluoromethylbenzyl group, 2- (3-trifluoromethylphenyl) ) Ethyl group, 3- (3-trifluoromethylphenyl) propyl group, 4-trifluoromethylphenyl group, 4-trifluoromethylbenzyl group, 2- (4-trifluoromethylphenyl) ethyl group, 3- (4 -Trifluoromethylphenyl) propyl group, 2-trifluoromethoxyphenyl group, 2-trifluoromethoxybenzyl 2- (2-trifluoromethoxyphenyl) ethyl group, 3- (2-trifluoromethoxyphenyl) propyl group, 3-trifluoromethoxyphenyl group, 3-trifluoromethoxybenzyl group, 2- (3-trifluoro Methoxyphenyl) ethyl group, 3- (3-trifluoromethoxyphenyl) propyl group, 4-trifluoromethoxyphenyl group, 4-trifluoromethoxybenzyl group, 2- (4-trifluoromethoxyphenyl) ethyl group, 3- (4-trifluoromethoxyphenyl) propyl group, 2-trifluoromethylsulfanylphenyl group, 2-trifluoromethylsulfanylbenzyl group, 2- (2-trifluoromethylsulfanylphenyl) ethyl group, 3- (2-trifluoro Methylsulfanylphenyl) propyl group, 3- Trifluoromethylsulfanylphenyl group, 3-trifluoromethylsulfanylbenzyl group, 2- (3-trifluoromethylsulfanylphenyl) ethyl group, 3- (3-trifluoromethylsulfanylphenyl) propyl group, 4-trifluoromethylsulfanyl Phenyl group, 4-trifluoromethylsulfanylbenzyl group, 2- (4-trifluoromethylsulfanylphenyl) ethyl group, 3- (4-trifluoromethylsulfanylphenyl) propyl group, 1-naphthyl group, 1-naphthylmethyl group 2- (1-naphthyl) ethyl group, 3- (1-naphthyl) propyl group, 2-naphthyl group, 2-naphthylmethyl group, 2- (2-naphthyl) ethyl group, 3- (2-naphthyl) propyl group Group, 8-fluoro-2-naphthyl group, (8-fluoro-2-naphthyl group) L) methyl group, 2- (8-fluoro-2-naphthyl) ethyl group, 3- (8-fluoro-2-naphthyl) propyl group, 8-chloro-2-naphthyl group, (8-chloro-2-naphthyl) ) Methyl group, 2- (8-chloro-2-naphthyl) ethyl group, 3- (8-chloro-2-naphthyl) propyl group, 8-bromo-2-naphthyl group, (8-bromo-2-naphthyl) Methyl group, 2- (8-bromo-2-naphthyl) ethyl group, 3- (8-bromo-2-naphthyl) propyl group

Next, formulation examples are shown. In addition, a part shows a weight part.
Formulation Example 1
20 parts of any one of the compounds of the present invention described in Production Examples 1 to 325 are dissolved in 65 parts of xylene, 15 parts of Solpol 3005X (Toho Chemical Registration) is added, and the mixture is stirred well to obtain an emulsion.

Formulation Example 2
Solpol 3005X5 part is added to 40 parts of any one of the compounds of the present invention described in Production Examples 1 to 325, and mixed well to mix 32 parts of Carplex # 80 (synthetic hydrous silicon oxide, Shionogi Pharmaceutical). Add 23 parts of mesh diatomaceous earth and stir and mix with a juice mixer to obtain a wettable powder.

Formulation Example 3
1.5 parts of any one of the compounds of the present invention described in Production Examples 1 to 325 and 1 part of Toxeal GUN (synthetic hydrous silicon oxide, manufactured by Tokuyama Co., Ltd.), RIAX 85A (sodium lignin sulfonate, manufactured by Westvacochemicals) 2 parts, 30 parts of bentonite Fuji (Bentonite, manufactured by Hojun Co., Ltd.) and 65.5 parts of Katsuyama A clay (Kaolin clay, manufactured by Katsumiyama Mining Co., Ltd.) are thoroughly pulverized and mixed. Granulate with a granulator and dry to obtain 1.5% granules.

Formulation Example 4
10 parts of any one of the compounds of the present invention described in Production Examples 1 to 325, 10 parts of phenylxylylethane, and 0.5 parts of Sumidur L-75 (tolylene diisocyanate, manufactured by Sumitomo Bayer Urethane Co., Ltd.) Thereafter, it is added to 20 parts of a 10% aqueous solution of gum arabic and stirred with a homomixer to obtain an emulsion having an average particle size of 20 μm. 2 parts of ethylene glycol is added thereto, and the mixture is further stirred in a warm bath at 60 ° C. for 24 hours to obtain a microcapsule slurry. On the other hand, 0.2 parts of xanthan gum and 1.0 part of bee gum R (aluminum magnesium silicate, manufactured by Sanyo Kasei) are dispersed in 56.3 parts of ion-exchanged water to obtain a thickener solution. 42.5 parts of the microcapsule slurry and 57.5 parts of the thickener solution are mixed to obtain a microcapsule.

Formulation Example 5
After mixing 10 parts of any one of the compounds of the present invention described in Production Examples 1 to 325 and 10 parts of phenylxylylethane, it is added to 20 parts of a 10% aqueous solution of polyethylene glycol and stirred with a homomixer. An emulsion having an average particle size of 3 μm is obtained. On the other hand, 0.2 parts of xanthan gum and 1.0 part of bee gum R (aluminum magnesium silicate, manufactured by Sanyo Chemical Industries) are dispersed in 58.8 parts of ion-exchanged water to obtain a thickener solution. 40 parts of the emulsion solution and 60 parts of the thickener solution are mixed to obtain a flowable agent.

Formulation Example 6
5 parts of any one of the compounds of the present invention described in Production Examples 1 to 325 are mixed with 3 parts of Carplex # 80 (synthetic hydrous hydrous powder, Shionogi Pharmaceutical) and PAP (monoisopropyl phosphate and diisopropyl phosphate). 3) and 91.7 parts of talc (300 mesh) are added and stirred and mixed with a juice mixer to obtain a powder.

Formulation Example 7
0.1 part of any one of the compounds of the present invention described in Production Examples 1 to 325 is dissolved in 10 parts of isopropyl alcohol, and this is mixed with 89.9 parts of deodorized kerosene to obtain an oil agent.

Formulation Example 8
One part of any one of the compounds of the present invention described in Production Examples 1 to 325, 5 parts of dichloromethane, and 34 parts of deodorized kerosene are mixed and dissolved, filled into an aerosol container, attached to a valve part, and then passed through the valve part. 60 parts of propellant (liquefied petroleum gas) is pressurized and filled to obtain an oily aerosol.

Formulation Example 9
0.6 parts of any one of the compounds of the present invention described in Production Examples 1 to 325, 5 parts of xylene, 3.4 parts of deodorized kerosene and 1 part of Atmos 300 (emulsifier, registered trademark of Atlas Chemical Co., Ltd.) were mixed and dissolved. One and 50 parts of water are filled into an aerosol container, and 40 parts of a propellant (liquefied petroleum gas) is pressurized and filled through a valve part to obtain an aqueous aerosol.

Formulation Example 10
0.3 g of any one of the compounds of the present invention described in Production Examples 1 to 325 was dissolved in 20 ml of acetone, and this was mixed with an incense base material (tab powder: powdered flour: wood flour = 4: 3: 3 ratio) After mixing uniformly with 99.7 g, 100 ml of water is added, and the kneaded mixture is molded and dried to obtain an insecticidal incense.

Formulation Example 11
Acetone is added to and dissolved in 0.8 g of any one of the compounds of the present invention described in Production Examples 1 to 325 and 0.4 g of piperonyl butoxide to make a total of 10 ml. 0.5 ml of this solution was impregnated uniformly into a 2.5 cm × 1.5 cm, 0.3 cm-thick base material for an electric insecticidal mat (a mixture of cotton linter and pulp filled with a plate). Get an electric insecticidal matting agent.

Formulation Example 12
3 parts of any one of the compounds of the present invention described in Production Examples 1 to 325 was dissolved in 97 parts of deodorized kerosene to obtain a liquid, which was placed in a vinyl chloride container so that the upper part could be heated with a heater. By inserting a liquid core (inorganic powder hardened with a binder and sintered), a part to be used in a liquid absorption core type heat transpiration apparatus is obtained.

Formulation Example 13
100 mg of any one of the compounds of the present invention described in Production Examples 1 to 325 is dissolved in an appropriate amount of acetone, impregnated into a 4.0 cm × 4.0 cm, 1.2 cm thick porous ceramic plate, Get smoke agent.

Formulation Example 14
100 μg of any one of the compounds of the present invention described in Production Examples 1 to 325 is dissolved in an appropriate amount of acetone and uniformly applied to a filter paper having a size of 2 cm × 2 cm and a thickness of 0.3 mm, and then the acetone is air-dried. Obtain a room temperature volatilizer.

Formulation Example 15
10 parts of any one of the compounds of the present invention described in Production Examples 1 to 325, 35 parts of white carbon containing 50 parts of polyoxyethylene alkyl ether sulfate ammonium salt and 55 parts of water are mixed and finely pulverized by a wet pulverization method. By doing so, a formulation is obtained.

Next, the harmful arthropod controlling effect of the compound of the present invention is shown as a test example.

Test example 1
The compound of the present invention (10), (11), (12), (13), (14), (15), (19), (20), (21), (22), obtained by Formulation Example 7 (23), (25), (26), (27), (28), (29), (30), (31), (32), (33), (34), (36), (37 ), (38), (43), (63), (64), (65), (113), (114), (118), (119), (131), (139), (140), Formulations (141), (143), (146), (149), (158), (240), (290), (332), (334) and (337) were prepared with an active ingredient concentration of 2.0. The test drug solution was prepared by diluting with isopropyl alcohol / deodorized kerosene = 1/9 mixture so as to be% w / v.
10 German cockroaches (5 males and 5 females) are placed in a test container with a buttered inner wall (diameter 8.75 cm, height 7.5 cm, bottom 16 mesh wire mesh) and the container is used for testing. It was installed at the bottom of the chamber (bottom: 46 cm × 46 cm, height: 70 cm). From a height of 60 cm above the upper surface of the container, 1.5 ml of a test drug solution was sprayed using a spray gun (a spraying pressure of 0.42 kg / cm ² ). The container was removed from the test chamber 30 seconds after spraying, and the number of insects knocked down after 2 minutes, 5 minutes, and 15 minutes was counted to determine the knockdown rate. The knockdown rate was calculated by the following formula.
Knockdown rate (%) = (number of knockdown insects / number of test insects) × 100
As a result, the compounds (10), (11), (12), (13), (14), (15), (19), (20), (21), (22), (23), (25), (26), (27), (28), (29), (30), (31), (32), (33), (34), (36), (37), (38 ), (43), (63), (64), (65), (113), (114), (118), (119), (131), (139), (140), (141), In the treatment of (143), (146), (149), (158), (240), (290), (332), (334) and (337), the test insect knockdown rate within 15 minutes Was 80% or more.

Test example 2
The present compound (66), (67), (68), (69), (70), (72), (73), (74), (75), (76), obtained by Formulation Example 7 (77), (78), (79), (80), (82), (83), (84), (85), (88), (89), (90), (91), (92 ), (93), (94), (97), (98), (99), (100), (103), (104), (105), (106), (109), (110), (111), (112), (120), (121), (122), (124), (132), (133), (134), (149), (165), (169), (170 ), (172), (174), (175), (176), (177), (178), (180), (184), (186), (1) 0), (194), (195), (196), (198), (200), (204), (210), (211), (213), (217), (221), (226) , (228), (230), (234), (235), (239), (240), (246), (252), (253), (255), (257), (258), ( 260), (261), (263), (264), (265), (266), (267), (268), (270), (274), (276), (277), (278) , (282), (286), (290), (294), (298), (305), (306), (309), (312), (313), (314), (317), ( 318), (319), (321), (322), (324), (325) The preparations of (327), (328), (329), (332), (334), (336) and (338) were prepared using isopropyl alcohol / deodorant so that the active ingredient concentration was 0.1% w / v. It diluted with kerosene = 1/9 liquid mixture, and prepared the chemical | medical solution for a test.
10 German cockroaches (5 males and 5 females) are placed in a test container with a buttered inner wall (diameter 8.75 cm, height 7.5 cm, bottom 16 mesh wire mesh) and the container is used for testing. It was installed at the bottom of the chamber (bottom: 46 cm × 46 cm, height: 70 cm). From a height of 60 cm above the upper surface of the container, 1.5 ml of a test drug solution was sprayed using a spray gun (a spraying pressure of 0.42 kg / cm ² ). The container was removed from the test chamber 30 seconds after spraying, and the number of insects knocked down after 2 minutes, 5 minutes, and 15 minutes was counted to determine the knockdown rate. The knockdown rate was calculated by the following formula.
Knockdown rate (%) = (number of knockdown insects / number of test insects) × 100
As a result, the present compound (66), (67), (68), (69), (70), (72), (73), (74), (75) obtained by the present compound formulation example 7 ), (76), (77), (78), (79), (80), (82), (83), (84), (85), (88), (89), (90), (91), (92), (93), (94), (97), (98), (99), (100), (103), (104), (105), (106), (109 ), (110), (111), (112), (120), (121), (122), (124), (132), (133), (134), (149), (165) , (169), (170), (172), (174), (175), (176), (177), (178), (180), (1 4), (186), (190), (194), (195), (196), (198), (200), (204), (210), (211), (213), (217) , (221), (226), (228), (230), (234), (235), (239), (240), (246), (252), (253), (255), ( 257), (258), (260), (261), (263), (264), (265), (266), (267), (268), (270), (274), (276) , (277), (278), (282), (286), (290), (294), (298), (305), (306), (309), (312), (313), ( 314), (317), (318), (319), (321), (322) In the treatment of (324), (325), (327), (328), (329), (332), (334), (336) and (338), the test insect knockdown rate within 15 minutes Was 80% or more.

Test example 3
The compound of the present invention (11), (13), (14), (15), (20), (21), (22), (26), (27), (30), obtained by Formulation Example 7 (33), (34), (36), (63), (64), (65), (113), (118), (119), (120), (131), (132), (139) ), (140), (141), (143), (146), (150), (158), (159), (160), (169), (176), (213), (235), The preparations (240), (242), (264), (290), (332) and (334) were prepared by adding isopropyl alcohol / deodorized kerosene to an active ingredient concentration of 2.0% w / v = 1 / It diluted with 9 liquid mixture and prepared the chemical | medical solution for a test.
Ten adult house flies (5 males and 5 females) were released in a polyethylene cup (bottom diameter: 10.6 cm) and covered with 16 mesh nylon goose. The polyethylene cup was placed at the bottom of a test chamber (bottom: 46 cm × 46 cm, height: 70 cm). From the height of 30 cm above the upper surface of the polyethylene cup, 0.5 ml of the test drug solution was sprayed using a spray gun (spray pressure 0.9 kg / cm ² ). Immediately after spraying, the cup was removed from the test chamber, and the number of insects knocked down after 2, 5 and 15 minutes was counted to determine the knockdown rate. The knockdown rate was calculated by the following formula.
Knockdown rate (%) = (number of knockdown insects / number of test insects) × 100
As a result, the compounds (11), (13), (14), (15), (20), (21), (22), (26), (27), (30), (33), (34), (36), (63), (64), (65), (113), (118), (119), (120), (131), (132), (139), (140 ), (141), (143), (146), (150), (158), (159), (160), (169), (176), (213), (235), (240), In the treatments (242), (264), (290), (332) and (334), the knockdown rate of the test insects within 15 minutes was 80% or more.

Test example 4
The compound of the present invention (11), (12), (13), (14), (15), (18), (20), (21), (22), (23), obtained by Formulation Example 7 (25), (26), (27), (28), (29), (30), (31), (32), (33), (34), (35), (36), (37 ), (38), (40), (43), (47), (48), (63), (64), (65), (66), (67), (68), (69), (70), (71), (72), (73), (74), (75), (76), (77), (78), (79), (80), (81), (82 ), (83), (84), (85), (88), (89), (90), (91), (92), (93), (94), (95), (96), (97), (98), (99), ( 00), (103), (104), (105), (106), (107), (108), (109), (110), (111), (112), (113), (114) , (117), (118), (119), (120), (121), (122), (123), (124), (125), (131), (132), (133), ( 134), (135), (136), (137), (138), (139), (140), (141), (143), (145), (146), (147), (148) , (149), (150), (158), (159), (160), (161), (162), (163), (169), (171), (170), (172), ( 174), (175), (176), (177), (178), (179) , (180), (181), (182), (183), (184), (185), (186), (187), (188), (189), (190), (191), ( 192), (193), (194), (195), (196), (197), (198), (199), (200), (201), (202), (203), (204) , (209), (210), (211), (213), (217), (221), (226), (227), (228), (229), (230), (231), ( 232), (233), (234), (235), (236), (237), (238), (239), (240), (240), (241), (242), (244) , (245), (246), (247), (248), (249), (2 50), (251), (252), (253), (254), (255), (256), (257), (258), (259), (260), (261), (262) , (263), (264), (265), (266), (267), (268), (269), (270), (271), (272), (273), (274), ( 275), (276), (277), (278), (282), (286), (290), (294), (295), (296), (297), (298), (299) , (300), (305), (306), (307), (308), (309), (312), (313), (314), (315), (316), (317), ( 318), (319), (320), (321), (322), (323) Formulations (324), (325), (327), (328), (329), (332), (333), (334), (335), (336), (337), and (338) The test drug solution was prepared by diluting with an isopropyl alcohol / deodorized kerosene = 1/9 mixture so that the active ingredient concentration was 0.1% w / v.
Ten adult oyster mosquitoes were released in a polyethylene cup (bottom diameter 10.6 cm) and covered with 16 mesh nylon goose. The polyethylene cup was placed at the bottom of a test chamber (bottom: 46 cm × 46 cm, height: 70 cm). From the height of 30 cm above the upper surface of the polyethylene cup, 0.5 ml of the test drug solution was sprayed using a spray gun (spray pressure 0.4 kg / cm ² ). Immediately after spraying, the cup was removed from the test chamber, and the number of insects knocked down after 2, 5 and 15 minutes was counted to determine the knockdown rate. The knockdown rate was calculated by the following formula.
Knockdown rate (%) = (number of knockdown insects / number of test insects) × 100
As a result, the compounds (11), (12), (13), (14), (15), (18), (20), (21), (22), (23), (25), (26), (27), (28), (29), (30), (31), (32), (33), (34), (35), (36), (37), (38 ), (40), (43), (47), (48), (63), (64), (65), (66), (67), (68), (69), (70), (71), (72), (73), (74), (75), (76), (77), (78), (79), (80), (81), (82), (83 ), (84), (85), (88), (89), (90), (91), (92), (93), (94), (95), (96), (97), (98), (99), (100), ( 03), (104), (105), (106), (107), (108), (109), (110), (111), (112), (113), (114), (117) , (118), (119), (120), (121), (122), (123), (124), (125), (131), (132), (133), (134), ( 135), (136), (137), (138), (139), (140), (141), (143), (145), (146), (147), (148), (149) , (150), (158), (159), (160), (161), (162), (163), (169), (171), (170), (172), (174), ( 175), (176), (177), (178), (179), (180 , (181), (182), (183), (184), (185), (186), (187), (188), (189), (190), (191), (192), ( 193), (194), (195), (196), (197), (198), (199), (200), (201), (202), (203), (204), (209) , (210), (211), (213), (217), (221), (226), (227), (228), (229), (230), (231), (232), ( 233), (234), (235), (236), (237), (238), (239), (240), (240), (241), (242), (244), (245) , (246), (247), (248), (249), (250), (2 51), (252), (253), (254), (255), (256), (257), (258), (259), (260), (261), (262), (263) , (264), (265), (266), (267), (268), (269), (270), (271), (272), (273), (274), (275), ( 276), (277), (278), (282), (286), (290), (294), (295), (296), (297), (298), (299), (300) , (305), (306), (307), (308), (309), (312), (313), (314), (315), (316), (317), (318), ( 319), (320), (321), (322), (323), (324) Within 15 minutes in the processing of (325), (327), (328), (329), (332), (333), (334), (335), (336), (337) and (338) The test insect knockdown rate was 80% or more.

Test Example 5
The compound of the present invention (9), (22), (26), (34), (54), (66), (67), (68), (69), (72), obtained by Formulation Example 15 (76), (79), (82), (84), (90), (100), (105), (121), (132), (150), (176), (195), (200 ), (234), (246), (252), (260), (264), (266), (267), (268), (270), (271), (274), (275), (278), (282), (286), (290), (294), (299), (305), (306), (308), (309), (313), (314), (315) ), (319), (321), (322), (324), (325), (333) and (335) Effective ingredient concentration of diluted with water so that 500 ppm, to prepare a test solution.
A filter paper of the same size was laid on the bottom of a polyethylene cup having a diameter of 5.5 cm, 0.7 ml of the test chemical solution was dropped onto the filter paper, and 30 mg of sucrose was uniformly added as a bait. Ten female fly (Muscadomestica) females were released into the polyethylene cup and capped. After 24 hours, the life-and-death of the house fly was investigated to determine the death rate. The death rate was calculated by the following formula.
Death rate (%) = (Number of dead insects / number of test insects) × 100
As a result, the compounds (9), (22), (26), (34), (54), (66), (67), (68), (69), (72), (76), (79), (82), (84), (90), (100), (105), (121), (132), (150), (176), (195), (200), (234 ), (246), (252), (260), (264), (266), (267), (268), (270), (271), (274), (275), (278), (282), (286), (290), (294), (299), (305), (306), (308), (309), (313), (314), (315), (319) ), (321), (322), (324), (325), (333) and (335) It showed a 90 percent or more.

Test Example 6
The compound (39), (63), (71), (72), (92), (93), (95), (106), (150), (171) of the present invention compound obtained in Formulation Example 15 (170), (181), (182), (183), (187), (188), (189), (190), (191), (192), (200), (201), (201 ), (234), (246), (290) and (299) were diluted with water so that the active ingredient concentration was 500 ppm to prepare a test drug solution.
20 test larvae of Culexpipisparlens were released in a solution obtained by adding 0.7 ml of the above medicinal solution for test to 100 ml of ion-exchanged water (active ingredient concentration: 3.5 ppm). Asked. The death rate was calculated by the following formula.
Death rate (%) = (Number of dead insects / number of test insects) × 100
As a result, the compounds (39), (63), (71), (72), (92), (93), (95), (106), (150), (171), (170), (181), (182), (183), (187), (188), (189), (190), (191), (192), (200), (201), (234), (246) ), (290) and (299) showed a death rate of 90% or more.

Test Example 7
The present compound (20), (21), (39), (63), (70), (73), (76), (77), (78), (91), obtained by Formulation Example 15 (92), (93), (95), (96), (105), (106), (119), (146), (150), (167), (171), (170), (181) ), (182), (183), (187), (188), (189), (190), (191), (192), (198), (199), (200), (201), Each formulation of (252), (258), (260), (282), (315) and (332) was diluted with water so that the active ingredient concentration was 500 ppm to prepare a test drug solution.
0.7 ml of the test chemical solution was added to 100 ml of ion-exchanged water (active ingredient concentration: 3.5 ppm). Twenty dead larvae of Culexpipisparlens were released into the liquid, and the viability was investigated 8 days later to determine the mortality rate. The death rate was calculated by the following formula.
Death rate (%) = (Number of dead insects / number of test insects) × 100
As a result, the present compounds (20), (21), (39), (63), (70), (73), (76), (77), (78), (91), (92), (93), (95), (96), (105), (106), (119), (146), (150), (167), (171), (170), (181), (182) ), (183), (187), (188), (189), (190), (191), (192), (198), (199), (200), (201), (252), In the treatments (258), (260), (282), (315) and (332), the death rate was 90% or more.

Test Example 8
Of the compounds (65), (73), (81), (94), (119), (129), (131), (144), (153) and (154) of the present invention obtained in Formulation Example 15. Each formulation was diluted with water so that the active ingredient concentration was 500 ppm to prepare a test spray solution. On the other hand, a cucumber was planted in a polyethylene cup and allowed to grow until the first true leaf developed, and about 20 cotton aphids were infested there. One day later, the test spray solution was sprayed onto the cucumber at a rate of 20 ml / cup. Six days after spraying, the number of cotton aphids was investigated, and the control value was determined by the following formula.
Control value (%) = {1− (Cb × Tai) / (Cai × Tb)} × 100
In addition, the character in a formula represents the following meaning.
Cb: number of insects before treatment in the untreated group Cai: number of insects when observed in the untreated group Tb: number of insects before treatment of the treated group Tai: number of insects during observation of the treated group As a result, the compound of the present invention (65 ), (73), (81), (94), (119), (129), (131), (144), (153) and (154) showed a control value of 90% or more.

Test Example 9
The compound of the present invention (3), (9), (18), (30), (31), (33), (34), (36), (43), (51), obtained by Formulation Example 15 Formulations (52), (54), (57), (58), (90), (105), (106), (129), (142), (154), (194) and (204) A test treatment solution was prepared by diluting with water so that the active ingredient concentration was 500 ppm.
On the other hand, cucumbers were planted in a polyethylene cup having a plurality of small holes in the bottom and allowed to grow until the first true leaf developed. A cup with cucumber planted in a plastic cup containing 5 ml of the test treatment solution was placed so that the soil in the cup was in contact with the treatment solution. Five days later, about 20 cotton aphids were infested, and the number of cotton aphids was investigated 7 days after the insect was applied, and the control value was determined by the following formula.
Control value (%) = {1− (Cb × Tai) / (Cai × Tb)} × 100
In addition, the character in a formula represents the following meaning.
Cb: number of insects before treatment in the untreated group Cai: number of insects when observed in the untreated group Tb: number of insects before treatment of the treated group Tai: number of insects during observation of the treated group As a result, the compound of the present invention (3 ), (9), (18), (30), (31), (33), (34), (36), (43), (51), (52), (54), (57), (58), (90), (105), (106), (129), (142), (154), (194) and (204) the treatment section of the test treatment solution has a control value of 90% or more. Indicated.

Test Example 10
The present compound (13), (15), (23), (39), (65), (69), (70), (71), (72), (73), obtained from Formulation Example 15 (76), (79), (81), (83), (91), (92), (93), (94), (97), (98), (100), (103), (104 ), (105), (106), (118), (119), (150), (171), (170), (188), (190), (191), (201), (234), The preparations (246), (258), (272), (290), (294), (306), (313) and (318) are diluted with water so that the active ingredient concentration is 500 ppm, and used for the test. A spray solution was prepared.
On the other hand, cabbage was planted in a polyethylene cup and allowed to grow until the third or fourth true leaf developed. The test spray solution was sprayed onto the cabbage at a rate of 20 ml / cup.
After the chemical solution sprayed on the cabbage was dried, 10 third-instar larvae of Pterellaxylostella were parasitized, and the number of P. elegans was investigated after 5 days, and the control value was determined according to the following criteria.
Control value (%) = {1− (Cb × Tai) / (Cai × Tb)} × 100
In addition, the character in a formula represents the following meaning.
Cb: number of insects before treatment in the untreated group Cai: number of insects when observed in the untreated group Tb: number of insects before treatment of the treated group Tai: number of insects during observation of the treated group As a result, the compound of the present invention (13 ), (15), (23), (39), (65), (69), (70), (71), (72), (73), (76), (79), (81), (83), (91), (92), (93), (94), (97), (98), (100), (103), (104), (105), (106), (118 ), (119), (150), (171), (170), (188), (190), (191), (201), (234), (246), (258), (272), The treatment group of the test treatment liquids (290), (294), (306), (313) and (318) showed a control value of 90% or more.

Test Example 11
The present compound (20), (65), (69), (72), (73), (76), (77), (79), (81), (105), obtained from Formulation Example 15 (106), (112), (171), (183), (190), (191), (196), (197), (198), (200), (201), (234), (246) ), (258), (260), (272), (290), (306), (315), (318), (321) and (325) with water so that the active ingredient concentration is 500 ppm. The test spray solution was prepared by diluting with
On the other hand, cabbage was planted in a polyethylene cup and allowed to grow until the third or fourth true leaf developed. The test spray solution was sprayed onto the cabbage at a rate of 20 ml / cup. After the chemical solution sprayed on the cabbage was dried, 10 fourth-instar larvae of Spodoptera were infested. Four days later, the number of surviving insects of Spodoptera litura on the cabbage leaf was examined, and the control value was determined by the following formula.
Control value (%) = {1− (Cb × Tai) / (Cai × Tb)} × 100
In addition, the character in a formula represents the following meaning.
Cb: number of insects before treatment in the untreated group Cai: number of insects when observed in the untreated group Tb: number of insects before treatment of the treated group Tai: number of insects during observation of the treated group As a result, the compound of the present invention (20 ), (65), (69), (72), (73), (76), (77), (79), (81), (105), (106), (112), (171), (183), (190), (191), (196), (197), (198), (200), (201), (234), (246), (258), (260), (272) ), (290), (306), (315), (318), (321) and (325) showed a control value of 80% or more.

Test Example 12
Compound of the Present Invention Obtained by Formulation Example 15 Formulations of the present compounds (39), (65), (73), (122), (150), (171), (170), (183) and (234) Was diluted with water so that the active ingredient concentration would be 500 ppm, and a test spray solution was prepared.
On the other hand, apple seedlings planted in plastic cups (28 days after sowing, tree height of about 15 cm) were each sprayed with 20 ml of the above test spray solution. After air-drying the chemicals sprayed on the apples to dryness, about 30 Apple 1-year-old larvae (Adoxophysoranafasciata) were released. Seven days after spraying, the number of surviving insects on the apple seedlings was examined, and the control value was determined by the following formula.
Control value (%) = {1− (Cb × Tai) / (Cai × Tb)} × 100
In addition, the character in a formula represents the following meaning.
Cb: number of insects before treatment in the untreated group Cai: number of insects when observed in the untreated group Tb: number of insects before treatment of the treated group Tai: number of insects during observation of the treated group As a result, the compound of the present invention (39 ), (65), (73), (122), (150), (171), (170), (183) and (234) showed a control value of 100%.

The compound of the present invention has a controlling effect on harmful arthropods and is useful as an active ingredient of a harmful arthropod controlling agent.

Claims (21)

Formula (I)

[Where,
A represents the following formula (III-a), (III-b) or (III-d)

Represents a group represented by
A ¹ represents an oxygen atom, D ¹ represents an atom or group selected from group D, r represents 0 or 1, p represents 0, 1, or 2, q represents 0 or 1 , R ¹ and R ² are the same or different and each represents a C1-C4 alkyl group which may have one or more halogen atoms, or a hydrogen atom,
n represents 0, 1, or 2 ;
Formula (II)

Represents a 5-membered aromatic ring,
Z represents a nitrogen atom or a carbon atom,
When Z represents a nitrogen atom, a combination of X ¹ , X ² and X ^{3 is} a combination where X ¹ is CR ⁵ , X ² is a nitrogen atom and X ³ is a nitrogen atom; or X ¹ Represents a combination in which CR ⁵ is, X ² is CR ⁵ and X ³ is a nitrogen atom ,
When Z represents a carbon atom, the combination of X ¹ , X ² and X ^{3 is} a combination where X ¹ is CR ⁵ , X ² is NR ⁶ and X ³ is a nitrogen atom; X ¹ is CR ^{A combination} in which X ² is a nitrogen atom and X ³ is NR ⁶ ; a combination in which X ¹ is a nitrogen atom, X ² is a nitrogen atom and X ³ is an oxygen atom; X ¹ is nitrogen A combination in which X ² is an oxygen atom and X ³ is a nitrogen atom; a combination in which X ¹ is a sulfur atom, X ² is a nitrogen atom, and X ³ is CR ⁵ ; or X ¹ Represents a combination of CR ⁵ , X ² is a nitrogen atom, and X ³ is an oxygen atom ,
R ^{5 s} are the same or different and are each a halogen atom, a cyano group, a formyl group, a carboxyl group, a C1-C4 alkoxycarbonyl group optionally having one or more halogen atoms, a carbamoyl group, —OR ⁷ and a halogen atom. A C1-C3 hydrocarbon group which may have one or more atoms or groups selected from the group consisting of:
R ⁶ represents a methyl group or a hydrogen atom, R ⁷ represents —C (═S) SR ⁸ or a hydrogen atom, and R ⁸ represents a C1-C3 hydrocarbon group optionally having one or more halogen atoms. Represents
R ³ and R ⁴ are the same or different and each have one or more atoms or groups selected from C1-C4 alkyl groups, halogen atoms, and group B, which may have one or more halogen atoms. Represents a phenyl group or a hydrogen atom,
Y represents a single bond, an oxygen atom, or a sulfur atom, and when Y is a single bond, m represents 0;
When Y is an oxygen atom or a sulfur atom , m represents 0, 1, 2, 3, 4, 5, 6 or 7,
When Y is a single bond, Q represents a C1-C8 chain hydrocarbon group having one or more atoms or groups selected from group F, or a C3-C8 chain hydrocarbon group,
When Y is an oxygen atom, Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group G;
Or one group selected from group A,
When Y is a sulfur atom, Q is a C1-C8 chain hydrocarbon group optionally having one or more atoms or groups selected from group I;
Or one group selected from group J.
Group A: C3-C8 cycloalkyl group optionally having one or more atoms or groups selected from Group B , optionally having one or more atoms or groups selected from Group B1, 2,3,4-tetrahydronaphthyl group, phenyl group optionally having one or more atoms or groups selected from group B, one or more atoms or groups selected from group B A good naphthyl group , a quinolyl group optionally having one or more atoms or groups selected from group B, a furyl group optionally having one or more atoms or groups selected from group B, group B A thienyl group optionally having one or more atoms or groups selected from, a benzofuranyl group optionally having one or more atoms or groups selected from group B, and one selected from group B With more atoms or groups The group consisting of which may be benzothienyl.
Group B: C1-C4 alkyl group optionally having one or more halogen atoms, C1-C4 alkyl group having one or more benzyloxy groups, having one or more halogen atoms C1-C4 alkoxy group which may have one, C1-C4 alkylthio group which may have one or more halogen atoms, C1-C4 alkylsulfinyl group which may have one or more halogen atoms, one C1-C4 alkylsulfonyl group optionally having one or more halogen atoms, C1-C4 alkoxycarbonyl group optionally having one or more halogen atoms, one or more atoms or groups selected from group E A vinyl group which may have, an ethynyl group which may have an atom or group selected from group E, a phenyl group, a phenoxy group, a cyano group, a nitro group, a carboxyl group Hydroxyl group, -CONR ¹² R ¹³ groups, the group consisting of methoxymethyl group and a halogen atom.
R ¹² and R ¹³ are the same or different and each represents a C1-C4 alkyl group which may have one or more halogen atoms, or a hydrogen atom.
Group D: a group consisting of a C1-C4 alkyl group optionally having one or more halogen atoms, a C1-C4 alkoxy group optionally having one or more halogen atoms, and a halogen atom.
Group E: A group consisting of a C1-C4 alkyl group optionally having one or more halogen atoms and a halogen atom.
Group F : a phenyl group which may have one or more atoms or groups selected from group B , a naphthyl group which may have one or more atoms or groups selected from group B, from group B one or more atoms or thienyl group which may have a group, and may have one or more atoms or groups selected from the group B 1,3-benzodioxolyl group or al selected A group.
Group G: a C3-C8 cycloalkyl group optionally having one or more atoms or groups selected from Group B , optionally having one or more atoms or groups selected from Group B1, 2,3,4-tetrahydronaphthyl group, phenyl group optionally having one or more atoms or groups selected from group B, one or more atoms or groups selected from group B A good naphthyl group , a quinolyl group optionally having one or more atoms or groups selected from group B, a furyl group optionally having one or more atoms or groups selected from group B, group B One or more thienyl groups optionally having one or more atoms or groups selected from, a benzofuranyl group optionally having one or more atoms or groups selected from group B, or one or more selected from group B Having an atom or group of Good benzothienyl group may have one or more atoms or groups selected from the group B 1,3-benzodioxolyl group, and a halogen atom or Ranaru group.
Group I: a group consisting of a phenyl group optionally having one or more atoms or groups selected from Group B, and a naphthyl group optionally having one or more atoms or groups selected from Group B .
Group J: a group consisting of a phenyl group optionally having one or more atoms or groups selected from Group B, and a naphthyl group optionally having one or more atoms or groups selected from Group B . ]
A harmful arthropod control agent comprising the amide compound represented by the above and an inert carrier. R ⁵ is the same or different and each is a halogen atom, a cyano group, a methyl group or a hydrogen atom, and R ³ and R ⁴ are the same or different and may have one or more halogen atoms. When it is a C4 alkyl group, a halogen atom, or a hydrogen atom, and Y is an oxygen atom or a sulfur atom , m is 0, 1, 2, 3, or 4 ;
Group B has a C1-C4 alkyl group which may have one or more halogen atoms, a C1-C4 alkoxy group which may have one or more halogen atoms, and one or more halogen atoms A C1-C4 alkylthio group optionally having one or more halogen atoms, a C1-C4 alkylsulfinyl group optionally having one or more halogen atoms, a C1-C4 alkylsulfonyl group optionally having one or more halogen atoms, A C1-C4 alkoxycarbonyl group optionally having one or more halogen atoms, a vinyl group optionally having one or more atoms or groups selected from group E, an atom or group selected from group E An ethynyl group, cyano group, nitro group, carboxyl group, hydroxyl group, -CONR ¹² R ¹³ group, methoxymethyl group and halogen atom which may have A harmful arthropod control agent comprising the amide compound according to claim 1 and an inert carrier. A harmful arthropod control agent comprising the amide compound according to claim 1 or 2 and an inert carrier , wherein A is a group represented by the formula (III-a) or (III-b ) . A represents the following formula (III-c)

[Wherein, p represents 0, 1, or 2. A harmful arthropod control agent comprising the amide compound according to claim 1 or 2 and an inert carrier. n is 1, The harmful arthropod control agent containing the amide compound as described in any one of Claims 1-4 , and an inert support | carrier. Y is an oxygen atom or a sulfur atom, m is 1, The harmful arthropod control agent containing the amide compound and inert carrier as described in any one of Claims 1-5. Y is an oxygen atom, The harmful arthropod control agent containing the amide compound as described in any one of Claims 1-5, and an inert support | carrier. Y is a single bond, The harmful arthropod control agent containing the amide compound as described in any one of Claims 1-5, and an inert support | carrier. Y is an oxygen atom and Q is a C1-C8 chain hydrocarbon group having one group selected from group G. The amide compound according to any one of claims 1 to 5 and an inert carrier. A harmful arthropod control agent. Z is a carbon atom, X ¹ is CR ^5, an X ² is a nitrogen atom, contain a claim 1-9 amide compound according to any one claim and an inert carrier, which is X ³ is an oxygen atom A harmful arthropod control agent. Claim 1-10 method for controlling noxious arthropods applying an effective amount to the locus of the arthropod pests or harmful arthropod A bromide compound of any one claim. Formula (I-s)

[Where,
A represents the following formula (III-a), (III-b) or (III-d)

Represents a group represented by
A ¹ represents an oxygen atom, D ¹ represents an atom or group selected from group D, r represents 0 or 1, p represents 0, 1, or 2, q represents 0 or 1,
R ¹ and R ² are the same or different and each represents a C1-C4 alkyl group optionally having one or more halogen atoms, or a hydrogen atom,
n represents 0, 1, or 2;
R ⁵ is selected from the group consisting of a halogen atom, a cyano group, a formyl group, a carboxyl group, a C1-C4 alkoxycarbonyl group optionally having one or more halogen atoms, a carbamoyl group, —OR ^7, and a halogen atom. Represents a C1-C3 hydrocarbon group which may have one or more atoms or groups, or a hydrogen atom;
R ⁷ represents —C (═S) SR ⁸ or a hydrogen atom, R ⁸ represents a C1-C3 hydrocarbon group optionally having one or more halogen atoms,
R ³ and R ⁴ are the same or different and each have one or more atoms or groups selected from C1-C4 alkyl groups, halogen atoms, and group B, which may have one or more halogen atoms. Represents a phenyl group or a hydrogen atom,
Y represents a single bond, an oxygen atom, or a sulfur atom.
When Y is a single bond, m represents 0;
When Y is an oxygen atom or a sulfur atom, m represents 0, 1, 2, 3, 4, 5, 6 or 7.
Group A: C3-C8 cycloalkyl group optionally having one or more atoms or groups selected from Group B, optionally having one or more atoms or groups selected from Group B1, 2,3,4-tetrahydronaphthyl group, phenyl group optionally having one or more atoms or groups selected from group B, one or more atoms or groups selected from group B A good naphthyl group, a quinolyl group optionally having one or more atoms or groups selected from group B, a furyl group optionally having one or more atoms or groups selected from group B, group B A thienyl group optionally having one or more atoms or groups selected from, a benzofuranyl group optionally having one or more atoms or groups selected from group B, and one selected from group B With more atoms or groups The group consisting of which may be benzothienyl.
Group B: C1-C4 alkyl group optionally having one or more halogen atoms, C1-C4 alkyl group having one or more benzyloxy groups, having one or more halogen atoms C1-C4 alkoxy group which may have one, C1-C4 alkylthio group which may have one or more halogen atoms, C1-C4 alkylsulfinyl group which may have one or more halogen atoms, one C1-C4 alkylsulfonyl group optionally having one or more halogen atoms, C1-C4 alkoxycarbonyl group optionally having one or more halogen atoms, one or more atoms or groups selected from group E A vinyl group which may have, an ethynyl group which may have an atom or group selected from group E, a phenyl group, a phenoxy group, a cyano group, a nitro group, a carboxyl group Hydroxyl group, -CONR ¹² R ¹³ groups, the group consisting of methoxymethyl group and a halogen atom.
R ¹² and R ¹³ are the same or different and each represents a C1-C4 alkyl group which may have one or more halogen atoms, or a hydrogen atom.
Group D: a group consisting of a C1-C4 alkyl group optionally having one or more halogen atoms, a C1-C4 alkoxy group optionally having one or more halogen atoms, and a halogen atom.
Group E: A group consisting of a C1-C4 alkyl group optionally having one or more halogen atoms and a halogen atom.
Group F: phenyl group optionally having one or more atoms or groups selected from group B, naphthyl group optionally having one or more atoms or groups selected from group B, from group B It consists of a thienyl group optionally having one or more atoms or groups selected, and a 1,3-benzodioxolyl group optionally having one or more atoms or groups selected from group B. group.
Group G: a C3-C8 cycloalkyl group optionally having one or more atoms or groups selected from Group B, optionally having one or more atoms or groups selected from Group B1, 2,3,4-tetrahydronaphthyl group, phenyl group optionally having one or more atoms or groups selected from group B, one or more atoms or groups selected from group B A good naphthyl group, a quinolyl group optionally having one or more atoms or groups selected from group B, a furyl group optionally having one or more atoms or groups selected from group B, group B One or more thienyl groups optionally having one or more atoms or groups selected from, a benzofuranyl group optionally having one or more atoms or groups selected from group B, or one or more selected from group B Having an atom or group of Good benzothienyl group, one or more atoms or groups may have a 1,3-benzodioxolyl group selected from the group B, and the group consisting of halogen atoms.
Group I: a group consisting of a phenyl group optionally having one or more atoms or groups selected from Group B, and a naphthyl group optionally having one or more atoms or groups selected from Group B .
Group J: a group consisting of a phenyl group optionally having one or more atoms or groups selected from Group B, and a naphthyl group optionally having one or more atoms or groups selected from Group B .
When Y is a single bond, Q represents a C1-C8 chain hydrocarbon group having one or more atoms or groups selected from group F;
When Y is an oxygen atom and m is 0, 2, 3, 4, 5, 6 or 7 , Q may have one or more atoms or groups selected from Group G. C1-C8 Represents a chain hydrocarbon group or one group selected from group A;
When Y is an oxygen atom and m is 1, Q is a C1-C8 chain hydrocarbon group which may have one or more atoms or groups selected from Group G, or Group H to display the one group,
When Y is a sulfur atom, Q represents a C1-C8 chain hydrocarbon group which may have one or more atoms or groups selected from group I, or one group selected from group J. Table be.
Group H: C3-C8 cycloalkyl group optionally having one or more atoms or groups selected from Group B , Furyl group optionally having one or more atoms or groups selected from Group B Selected from group B, thienyl group optionally having one or more atoms or groups selected from group B, benzofuranyl group optionally having one or more atoms or groups selected from group B, and group B A group consisting of a benzothienyl group optionally having one or more atoms or groups.
] The amide compound shown by this. R ⁵ is a halogen atom, a cyano group, a methyl group or a hydrogen atom,
R ³ and R ⁴ are the same or different and each is a C1-C4 alkyl group optionally having one or more halogen atoms, a halogen atom, or a hydrogen atom,
When Y is an oxygen atom or a sulfur atom , m is 0, 1, 2, 3 or 4, and the group B may have one or more halogen atoms, a C1-C4 alkyl group, C1-C4 alkoxy group optionally having one or more halogen atoms, C1-C4 alkylthio group optionally having one or more halogen atoms, optionally having one or more halogen atoms A C1-C4 alkylsulfinyl group, a C1-C4 alkylsulfonyl group optionally having one or more halogen atoms, a C1-C4 alkoxycarbonyl group optionally having one or more halogen atoms, from Group E A vinyl group optionally having one or more atoms or groups selected, an ethynyl group optionally having an atom or group selected from group E, a cyano group, a nitro group, a carboxyl group, a hydroxyl group; Le group, -CONR ¹² R ¹³ group, according to claim 1 2 amide compound wherein the group consisting of methoxymethyl group and a halogen atom. A is the formula (III-a) or (III-b) is a group represented by the claims 1 2 or 1 3 amide compound according. A represents the following formula (III-c)

[Wherein, p represents 0, 1, or 2. ]
Claim 1 2 or 1 3 The amide compound according in a group represented. The amide compound according to any one of claims 12 to 15 , wherein n is 1. Y is an oxygen atom or a sulfur atom, according to claim 1 2-16 amide compound of any one claim m is 1. Y is claim 1 2-16 amide compound of any one claim is an oxygen atom. The amide compound according to any one of claims 12 to 16 , wherein Y is a single bond. Y is an oxygen atom, Q is claim 1 2-16 amide compound of any one claim is a C1-C8 chain hydrocarbon group having one group selected from the group G. Y is an oxygen atom, Q is claim 1 2-16 amide compound of any one claim is a methyl group having one group selected from the group G.