TW201718492A - Method for manufacturing 4-(4-formylthiazolyl)piperidine compound - Google Patents

Method for manufacturing 4-(4-formylthiazolyl)piperidine compound Download PDF

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TW201718492A
TW201718492A TW105127908A TW105127908A TW201718492A TW 201718492 A TW201718492 A TW 201718492A TW 105127908 A TW105127908 A TW 105127908A TW 105127908 A TW105127908 A TW 105127908A TW 201718492 A TW201718492 A TW 201718492A
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piperidine
thiazolyl
methyl
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TW105127908A
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TWI747839B (en
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Daisuke Horikoshi
Makoto Bamba
Tsuyoshi Kawano
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Sds Biotech Corp
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

The present invention relates to a method for manufacturing a compound represented by formula [1], to a method for manufacturing a compound represented by formula [5a], and to a compound represented by formula [4] or a salt thereof, a compound represented by formula [5] or a salt thereof, and a compound represented by formula [1] and a salt thereof.

Description

4-(4-甲醯基噻唑基)哌啶化合物之製造方法 Method for producing 4-(4-carbamoylthiazolyl) piperidine compound

本發明係關於4-(4-甲醯基噻唑基)哌啶化合物之製造方法。 The present invention relates to a process for producing a 4-(4-carbamoylthiazolyl) piperidine compound.

至今為止已提出4-噻唑基哌啶衍生物能使用作為殺菌性作物保護劑(例如、專利文獻1~8)。該化合物合成中，身為重要中間體之4-(4-甲醯基噻唑基)哌啶化合物在專利文獻2~8等中已揭示其之製造方法，但使用此方法試圖以工業性製造該化合物之情況，則變得有使用低溫下之有機金屬反應、還原反應或氧化反應等構築醛之必要而造成問題，故從作業效率及經濟性之觀點，則逐漸要求更有效率之該化合物之製造方法。 It has been proposed that a 4-thiazolyl piperidine derivative can be used as a bactericidal crop protectant (for example, Patent Documents 1 to 8). In the synthesis of the compound, a 4-(4-carbamoylthiazolyl)piperidine compound which is an important intermediate is disclosed in Patent Documents 2 to 8 and the like, but it is attempted to industrially manufacture the method using this method. In the case of a compound, there is a problem that it is necessary to construct an aldehyde by using an organometallic reaction, a reduction reaction, or an oxidation reaction at a low temperature. Therefore, from the viewpoint of work efficiency and economy, a more efficient compound is gradually required. Production method.

[先前技術文獻] [Previous Technical Literature] [專利文獻] [Patent Literature]

[專利文獻1]WO2007/014290號公報 [Patent Document 1] WO2007/014290

[專利文獻2]WO2008/013925號公報 [Patent Document 2] WO2008/013925

[專利文獻3]WO2010/066353號公報 [Patent Document 3] WO2010/066353

[專利文獻4]WO2011/076699號公報 [Patent Document 4] WO2011/076699

[專利文獻5]WO2011/146182號公報 [Patent Document 5] WO2011/146182

[專利文獻6]WO2012/020060號公報 [Patent Document 6] WO2012/020060

[專利文獻7]WO2012/025557號公報 [Patent Document 7] WO2012/025557

[專利文獻8]WO2014/118143號公報 [Patent Document 8] WO2014/118143

[專利文獻9]WO2014/075874號公報 [Patent Document 9] WO2014/075874

[專利文獻10]WO2014/075873號公報 [Patent Document 10] WO2014/075873

[專利文獻11]CN104650061 [Patent Document 11] CN104650061

[非專利文獻] [Non-patent literature]

[非專利文獻1]ANDO, N. et al., A novel synthesis of the 2-amino-1H-imidazol-4-carbaldehyde derivatives and its application to the efficient synthesis of 2-aminoimidazole alkaloids, oroidin, hymenidin, dispacamide, monobromodispacamide, and ageladine A, Tetrahedron, 2010, Volume 66, Issue 32, pages 6224-6237 [Non-Patent Document 1] ANDO, N. et al., A novel synthesis of the 2-amino-1H-imidazol-4-carbaldehyde derivatives and its application to the luminous synthesis of 2-aminoimidazole alkaloids, oroidin, hymenidin, dispacamide, Monobromodispacamide, and ageladine A, Tetrahedron, 2010, Volume 66, Issue 32, pages 6224-6237

本發明之目的在於提供一種有效率調製有用作為殺菌性作物保護劑之哌啶衍生物之合成中間體即4-(4-甲醯基噻唑基)哌啶化合物的方法。 It is an object of the present invention to provide a process for efficiently preparing a 4-(4-carbamoylthiazolyl) piperidine compound which is a synthetic intermediate of a piperidine derivative useful as a bactericidal crop protectant.

本發明者的等為了解決前述課題經過精心研討之結 果，發現了有效率地調製式[1]所示之4-(4-甲醯基噻唑基)哌啶化合物之方法，並根據該知識見解而完成本發明。 The inventors of the present invention have carefully studied the knot in order to solve the aforementioned problems. As a result, a method of efficiently modulating a 4-(4-carbamoylthiazolyl)piperidine compound represented by the formula [1] was found, and the present invention was completed based on the knowledge.

本發明包括以下之化合物之製造方法、或化合物或其鹽之揭示。 The present invention includes the production of the following compounds, or the disclosure of the compounds or salts thereof.

(1)一種式[1]所表示之化合物之製造方法，其特徵為包含使式[2]所表示之化合物與式[3]所表示之化合物反應之步驟； {式中，A為選自下述之基， (1) A process for producing a compound represented by the formula [1], which comprises the step of reacting a compound represented by the formula [2] with a compound represented by the formula [3]; In the formula, A is selected from the group consisting of

R1及R2係各自獨立為C1~C4烷基、C1~C4鹵烷基、或鹵素原子；R3、R4、R5、R6及R7係各自獨立為氫原子、鹵素原子、氰基、羥基、胺基、硝基、C1~C6烷基、C2~C6烯基、C2~C6炔基、C1~C6鹵烷基、C2~C6鹵烯基、C2~C6鹵炔基、C1~C6烷氧基、C1~C6鹵烷氧基、C3~C6環烷基、C3~C6鹵環烷基、C4~C10環烷基烷基、C4~C10烷基環烷 基、C5~C10烷基環烷基烷基、C2~C6烷氧基烷基、C1~C6羥基烷基、C1~C6烷硫基、C1~C6鹵烷硫基、C1~C6烷基亞磺醯基、C1~C6鹵烷基亞磺醯基、C1~C6烷基磺醯基、C1~C6鹵烷基磺醯基、C1~C6烷基胺基、C2~C8二烷基胺基、C3~C6環烷基胺基、C2~C6烷基羰基、C2~C6鹵烷基羰基、C2~C6烷氧基羰基、C2~C6鹵烷氧基羰基、C2~C6烷基羰氧基、C2~C6烷基羰硫基、C2~C6烷基胺基羰基、C3~C8(二烷基胺基)羰基、或C3~C6三烷基矽基；R8為氫原子、C1~C4烷基、C1~C4烯基、苄基(在此苄基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、C2~C6烷基羰基、C2~C6鹵烷基羰基、苯基羰基(在此苯基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、C2~C6烷氧基羰基、苄基氧基羰基(在此苄基氧基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、苯基氧基羰基(在此苯基氧基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、三苯基甲基、甲醯基或基-SO2R9；R9為C1~C4烷基、C1~C4鹵烷基或苯基(在此苯基之苯環亦可被選自鹵素原子、C1~C4烷基、C1~C4烷氧基或硝基之1種以上之取代基所取代)} R 1 and R 2 are each independently a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, or a halogen atom; and R 3 , R 4 , R 5 , R 6 and R 7 are each independently a hydrogen atom. , halogen atom, cyano group, hydroxyl group, amine group, nitro group, C 1 -C 6 alkyl group, C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group, C 1 -C 6 haloalkyl group, C 2 ~C 6 haloalkenyl, C 2 ~C 6 haloalkynyl, C 1 ~C 6 alkoxy, C 1 ~C 6 haloalkoxy, C 3 ~C 6 cycloalkyl, C 3 ~C 6 halo a cycloalkyl group, a C 4 -C 10 cycloalkylalkyl group, a C 4 -C 10 alkylcycloalkyl group, a C 5 -C 10 alkylcycloalkylalkyl group, a C 2 -C 6 alkoxyalkyl group, C 1 -C 6 hydroxyalkyl, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfin Sulfhydryl, C 1 ~C 6 alkylsulfonyl, C 1 ~C 6 haloalkylsulfonyl, C 1 -C 6 alkylamino, C 2 -C 8 dialkylamine, C 3 ~ C 6 cycloalkylamino group, C 2 -C 6 alkylcarbonyl group, C 2 -C 6 haloalkylcarbonyl group, C 2 -C 6 alkoxycarbonyl group, C 2 -C 6 haloalkoxycarbonyl group, C 2 ~C 6 alkylcarbonyloxy, C 2 -C 6 alkylcarbonylthio, C 2 -C 6 alkylaminocarbonyl, C 3 -C 8 (dialkylamino)carbonyl, or C 3 ~C 6 trialkyl Sulfhydryl; R 8 is a hydrogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 alkenyl group, a benzyl group (wherein the benzene ring of the benzyl group may also be selected from a halogen atom, a C 1 -C 4 alkyl group) Or a C 1 -C 4 alkoxy group substituted with one or more substituents), a C 2 -C 6 alkylcarbonyl group, a C 2 -C 6 haloalkylcarbonyl group, a phenylcarbonyl group (the phenyl group of the phenylcarbonyl group) The ring may be substituted with one or more substituents selected from a halogen atom, a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group), a C 2 -C 6 alkoxycarbonyl group, or a benzyloxy group. a carbonyl group (wherein the benzene ring of the benzyloxycarbonyl group may be substituted with one or more substituents selected from a halogen atom, a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group), phenyl oxygen a carbonyl group (the phenyl ring of the phenyloxycarbonyl group may be substituted with one or more substituents selected from a halogen atom, a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group), and a triphenyl group. Methyl, decyl or yl-SO 2 R 9 ; R 9 is C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or phenyl (wherein the phenyl ring of the phenyl group may also be selected from Substituted by one or more substituents of a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 alkoxy group or a nitro group)}

{式中，X為鹵素原子或-OR10，R10係各自獨立為C1~C4烷基，L1為鹵素原子等之脫離基}。 In the formula, X is a halogen atom or -OR 10 , and each of R 10 is independently a C 1 -C 4 alkyl group, and L 1 is a leaving group such as a halogen atom.

(2)一種式[1]所表示之化合物之製造方法，其特徵為包含使式[2]所表示之化合物與式[3a]所表示之化合物在鹼之存在下反應，而取得式[4]所表示之化合物之步驟，及，使前述式[4]所表示之化合物在酸或路易斯酸之存在下，較佳在酸之存在下進行反應之步驟； {式中，A係如同(1)中所定義} (2) A method for producing a compound represented by the formula [1], which comprises reacting a compound represented by the formula [2] with a compound represented by the formula [3a] in the presence of a base to obtain a formula [4] a step of expressing the compound, and a step of reacting the compound represented by the above formula [4] in the presence of an acid or a Lewis acid, preferably in the presence of an acid; {where, A is as defined in (1)}

{式中，R10及L1係如同(1)中所定義} {wherein, R 10 and L 1 are as defined in (1)}

(3)一種式[5a]所表示之化合物之製造方法，其特徵為包含使式[2]所表示之化合物與式[3a]所表示之化合物在鹼之存在下反應，而取得式[4]所表示之化合物之步驟，及，使前述式[4]所表示之化合物在酸或路易斯酸之存在下反應之步驟； {式中，A及R10係如同(1)中所定義} (3) A method for producing a compound represented by the formula [5a], which comprises reacting a compound represented by the formula [2] with a compound represented by the formula [3a] in the presence of a base to obtain a formula [4] a step of expressing the compound, and a step of reacting the compound represented by the above formula [4] in the presence of an acid or a Lewis acid; {where, A and R 10 are as defined in (1)}

{式中，L1係如同(1)中所定義} {where L 1 is as defined in (1)}

(4)一種式[1]所表示之化合物之製造方法，其特徵為包含使式[5]所表示之化合物變換成前述式[1]所表示之化合物之步驟； {式中，A係如同(1)中所定義} (4) A method for producing a compound represented by the formula [1], which comprises the step of converting a compound represented by the formula [5] into a compound represented by the above formula [1]; {where, A is as defined in (1)}

{式中，X係如同(1)中所定義}。 In the formula, X is as defined in (1)}.

(5)一種式[1]所表示之化合物之製造方法，其特徵為包含使式[2]所表示之化合物與式[3a]所表示之化合物反 應之步驟； {式中，A為選自下述之基， (5) A process for producing a compound represented by the formula [1], which comprises the step of reacting a compound represented by the formula [2] with a compound represented by the formula [3a]; In the formula, A is selected from the group consisting of

R1及R2係各自獨立為C1~C4烷基、C1~C4鹵烷基、或鹵素原子；R3、R4、R5、R6及R7係各自獨立為氫原子、鹵素原子、氰基、羥基、胺基、硝基、C1~C6烷基、C2~C6烯基、C2~C6炔基、C1~C6鹵烷基、C2~C6鹵烯基、C2~C6鹵炔基、C1~C6烷氧基、C1~C6鹵烷氧基、C3~C6環烷基、C3~C6鹵環烷基、C4~C10環烷基烷基、C4~C10烷基環烷基、C5~C10烷基環烷基烷基、C2~C6烷氧基烷基、C1~C6羥基烷基、C1~C6烷硫基、C1~C6鹵烷硫基、C1~C6烷基亞磺醯基、C1~C6鹵烷基亞磺醯基、C1~C6烷基磺醯基、C1~C6鹵烷基磺醯基、C1~C6烷基胺基、C2~C8二烷基胺基、C3~C6環烷基胺基、C2~C6烷基羰基、C2~C6鹵烷基羰基、C2~C6烷氧基羰基、C2~C6鹵烷氧基羰基、C2~C6烷基羰氧基、C2~C6烷基羰硫基、C2~C6烷基胺基羰基、C3~C8 (二烷基胺基)羰基、或C3~C6三烷基矽基；R8為C1~C4烷基、C1~C4烯基、苄基(在此苄基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、C2~C6烷基羰基、C2~C6鹵烷基羰基、苯基羰基(在此苯基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、C2~C6烷氧基羰基、苄基氧基羰基(在此苄基氧基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、苯基氧基羰基(在此苯基氧基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、三苯基甲基、甲醯基或基-SO2R9；R9為C1~C4烷基、C1~C4鹵烷基或苯基(在此苯基之苯環亦可被選自鹵素原子、C1~C4烷基、C1~C4烷氧基或硝基之1種以上之取代基所取代)} R 1 and R 2 are each independently a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, or a halogen atom; and R 3 , R 4 , R 5 , R 6 and R 7 are each independently a hydrogen atom. , halogen atom, cyano group, hydroxyl group, amine group, nitro group, C 1 -C 6 alkyl group, C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group, C 1 -C 6 haloalkyl group, C 2 ~C 6 haloalkenyl, C 2 ~C 6 haloalkynyl, C 1 ~C 6 alkoxy, C 1 ~C 6 haloalkoxy, C 3 ~C 6 cycloalkyl, C 3 ~C 6 halo a cycloalkyl group, a C 4 -C 10 cycloalkylalkyl group, a C 4 -C 10 alkylcycloalkyl group, a C 5 -C 10 alkylcycloalkylalkyl group, a C 2 -C 6 alkoxyalkyl group, C 1 -C 6 hydroxyalkyl, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfin Sulfhydryl, C 1 ~C 6 alkylsulfonyl, C 1 ~C 6 haloalkylsulfonyl, C 1 -C 6 alkylamino, C 2 -C 8 dialkylamine, C 3 ~ C 6 cycloalkylamino group, C 2 -C 6 alkylcarbonyl group, C 2 -C 6 haloalkylcarbonyl group, C 2 -C 6 alkoxycarbonyl group, C 2 -C 6 haloalkoxycarbonyl group, C 2 ~C 6 alkylcarbonyloxy, C 2 -C 6 alkylcarbonylthio, C 2 -C 6 alkylaminocarbonyl, C 3 -C 8 (dialkylamino)carbonyl, or C 3 ~C 6 trialkyl a mercapto group; R 8 is a C 1 -C 4 alkyl group, a C 1 -C 4 alkenyl group, a benzyl group (wherein the benzene ring of the benzyl group may also be selected from a halogen atom, a C 1 -C 4 alkyl group or a C 1 group) or more of one kind of ~ C 4 alkoxy substituents), C 2 ~ C 6 alkylcarbonyl group, C 2 ~ C 6 haloalkyl carbonyl, phenylcarbonyl group (this phenyl ring of phenylcarbonyl group may Substituted by one or more substituents selected from a halogen atom, a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group), a C 2 -C 6 alkoxycarbonyl group, a benzyloxycarbonyl group (in The benzene ring of the benzyloxycarbonyl group may be substituted with one or more substituents selected from a halogen atom, a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group), a phenyloxycarbonyl group ( The phenyl ring of the phenyloxycarbonyl group may be substituted with one or more substituents selected from a halogen atom, a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group), triphenylmethyl group. , a mercapto group or a group -SO 2 R 9 ; R 9 is a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group or a phenyl group (wherein the phenyl ring of the phenyl group may also be selected from a halogen atom, Substituted by one or more substituents of C 1 -C 4 alkyl, C 1 -C 4 alkoxy or nitro))

{式中，R10係各自獨立為C1~C4烷基，L1為鹵素原子等之脫離基}。 In the formula, R 10 is each independently a C 1 -C 4 alkyl group, and L 1 is a leaving group such as a halogen atom.

(6)一種式[1]所表示之化合物之製造方法，其特徵為包含使式[2]所表示之化合物與式[3a]所表示之化合物在鹼之存在下反應，而取得式[4]所表示之化合物之步驟，及，使前述式[4]所表示之化合物在酸或路易斯酸之存在下，較佳係在酸之存在下反應之步驟； {式中，A係如同(5)中所定義} (6) A process for producing a compound represented by the formula [1], which comprises reacting a compound represented by the formula [2] with a compound represented by the formula [3a] in the presence of a base to obtain a formula [4] a step of expressing the compound, and a step of reacting the compound represented by the above formula [4] in the presence of an acid or a Lewis acid, preferably in the presence of an acid; {where, A is as defined in (5)}

{式中，R10及L1係如同(5)中所定義} {wherein, R 10 and L 1 are as defined in (5)}

(7)一種式[5a]所表示之化合物之製造方法，其特徵 為包含使式[2]所表示之化合物與式[3a]所表示之化合物在鹼之存在下反應，而取得式[4]所表示之化合物之步驟，及，使前述式[4]所表示之化合物在酸或路易斯酸之存在下反應之步驟； {式中，A及R10係如同(5)中所定義} (7) A process for producing a compound represented by the formula [5a], which comprises reacting a compound represented by the formula [2] with a compound represented by the formula [3a] in the presence of a base to obtain a formula [4] a step of expressing the compound, and a step of reacting the compound represented by the above formula [4] in the presence of an acid or a Lewis acid; {where, A and R 10 are as defined in (5)}

{式中，L1係如同(5)中所定義} {where L 1 is as defined in (5)}

(8)一種式[1]所表示之化合物之製造方法，其特徵為包含使式[5a]所表示之化合物在酸或路易斯酸之存在 下，較佳在酸之存在下反應之步驟； {式中，A係如同(5)中所定義} (8) A process for producing a compound represented by the formula [1], which comprises a step of reacting a compound represented by the formula [5a] in the presence of an acid or a Lewis acid, preferably in the presence of an acid; {where, A is as defined in (5)}

{式中，R10係如同(5)中所定義}。 In the formula, R 10 is as defined in (5)}.

(9)一種式[1]所表示之化合物之製造方法，其特徵為包含使式[2]所表示之化合物與式[3]所表示之化合物反應之步驟； {式中，A係如同(5)中所定義} (9) A process for producing a compound represented by the formula [1], which comprises the step of reacting a compound represented by the formula [2] with a compound represented by the formula [3]; {where, A is as defined in (5)}

{式中，X為鹵素原子或-OR10，R10係各自獨立為C1~C4烷基，L1為鹵素原子等之脫離基}。 In the formula, X is a halogen atom or -OR 10 , and each of R 10 is independently a C 1 -C 4 alkyl group, and L 1 is a leaving group such as a halogen atom.

(10)一種式[1]所表示之化合物之製造方法，其特徵為包含使式[5]所表示之化合物變換成前述式[1]所表示之化合物之步驟； {式中，A係如同(5)中所定義} (10) A method for producing a compound represented by the formula [1], which comprises the step of converting a compound represented by the formula [5] into a compound represented by the above formula [1]; {where, A is as defined in (5)}

{式中，X係如同(9)中所定義}。 In the formula, X is as defined in (9)}.

(11)如(1)~(10)中任一項之製造方法，其中R1及R2係各自獨為C1~C4烷基、C1~C4鹵烷基、或鹵素原子，R4、R5及R7為氫原子，R3及R6係各自獨立為氫原子、鹵素原子、C1~C6烷 基或C1~C6鹵烷基，R8為C2~C6烷基羰基、苄基、苯基羰基、C2~C6烷氧基羰基。 (11) The production method according to any one of (1) to (10) wherein R 1 and R 2 are each independently a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, or a halogen atom. R 4 , R 5 and R 7 are each a hydrogen atom, and R 3 and R 6 each independently represent a hydrogen atom, a halogen atom, a C 1 -C 6 alkyl group or a C 1 -C 6 haloalkyl group, and R 8 is C 2 ~. C 6 alkylcarbonyl, benzyl, phenylcarbonyl, C 2 -C 6 alkoxycarbonyl.

(12)如(1)~(11)中任一項之製造方法，其中R1為三氟甲基、二氟甲基、或氯原子，R2為甲基、三氟甲基、二氟甲基、或氯原子，R3及R6係各自獨立為氫原子、氯原子、三氟甲基或甲基，R8為乙醯基、苄基、苯基羰基、甲氧基羰基、乙氧基羰基、1,1-二甲基乙基氧基羰基或2,2-二甲基丙醯基，X為-OR10，R10係各自獨立為甲基或乙基，L1為氯原子或溴原子。 (12) The process according to any one of (1) to (11) wherein R 1 is a trifluoromethyl group, a difluoromethyl group or a chlorine atom, and R 2 is a methyl group, a trifluoromethyl group or a difluoro group. a methyl group or a chlorine atom, each of R 3 and R 6 is independently a hydrogen atom, a chlorine atom, a trifluoromethyl group or a methyl group, and R 8 is an ethyl hydrazino group, a benzyl group, a phenylcarbonyl group, a methoxycarbonyl group, or a Oxycarbonyl, 1,1-dimethylethyloxycarbonyl or 2,2-dimethylpropanyl, X is -OR 10 , R 10 is each independently methyl or ethyl, and L 1 is chlorine Atom or bromine atom.

(13)如(1)~(12)中任一項之製造方法，其中A為A-1，X為-OR10，R10為甲基，L1為溴原子。 (13) (1) to (12) The production method according to any of wherein A is A-1, X is -OR 10, R 10 is a methyl group, L 1 is a bromine atom.

(14)如(1)~(13)中任一項之製造方法，其中A為2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基或2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基。 (14) A process according to any one of (1) to (13) wherein A is 2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetamidine Or 2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl.

(15)如(1)~(12)中任一項之製造方法，其中A為乙醯基、苄基、苯基羰基、甲氧基羰基、乙氧基羰基、1,1-二甲基乙基氧基羰基或2,2-二甲基丙醯基， X為-OR10，R10為甲基，L1為溴原子。 (15) The process according to any one of (1) to (12) wherein A is ethyl benzyl, benzyl, phenylcarbonyl, methoxycarbonyl, ethoxycarbonyl, 1,1-dimethyl Ethyloxycarbonyl or 2,2-dimethylpropanyl, X is -OR 10 , R 10 is a methyl group, and L 1 is a bromine atom.

(16)一種式[4]所表示之化合物或其鹽； {式中，A為選自下述之基， (16) A compound represented by the formula [4] or a salt thereof; In the formula, A is selected from the group consisting of

R1為三氟甲基、二氟甲基、或氯原子，R2為甲基、三氟甲基、二氟甲基、或氯原子，R4、R5及R7為氫原子，R3及R6係各自獨立為氫原子、氯原子、三氟甲基或甲基，R8為乙醯基、苄基、苯基羰基、甲氧基羰基、乙氧基羰基、1,1-二甲基乙基氧基羰基或2,2-二甲基丙醯基，R10係各自獨立為甲基或乙基}。 R 1 is a trifluoromethyl group, a difluoromethyl group or a chlorine atom, R 2 is a methyl group, a trifluoromethyl group, a difluoromethyl group or a chlorine atom, and R 4 , R 5 and R 7 are a hydrogen atom, R 3 and R 6 are each independently a hydrogen atom, a chlorine atom, a trifluoromethyl group or a methyl group, and R 8 is an ethyl hydrazino group, a benzyl group, a phenylcarbonyl group, a methoxycarbonyl group, an ethoxycarbonyl group, and a 1,1- oxycarbonyl-dimethylethyl 2,2-dimethyl propyl group or acyl, R 10 are each independently based} methyl or ethyl.

(17)如(16)之化合物或其鹽，其中A為2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基或2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基， R10為甲基。 (17) A compound of (16) or a salt thereof, wherein A is 2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl or 2-[3 , 5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl, R 10 is methyl.

(18)如(16)之化合物或其鹽，其中A為乙醯基、苄基、苯基羰基、甲氧基羰基、乙氧基羰基、1,1-二甲基乙基氧基羰基或2,2-二甲基丙醯基，R10為甲基。 (18) A compound of (16) or a salt thereof, wherein A is ethyl hydrazino, benzyl, phenylcarbonyl, methoxycarbonyl, ethoxycarbonyl, 1,1-dimethylethyloxycarbonyl or 2,2-dimethylpropanyl, R 10 is methyl.

(19)一種式[5]所表示之化合物或其鹽； {式中，A為選自下述之基， (19) A compound represented by the formula [5] or a salt thereof; In the formula, A is selected from the group consisting of

R1為三氟甲基、二氟甲基、或氯原子，R2為甲基、三氟甲基、二氟甲基、或氯原子，R4、R5及R7為氫原子，R3及R6係各自獨立為氫原子、氯原子、三氟甲基或甲基，R8為乙醯基、苄基、苯基羰基、甲氧基羰基、乙氧基羰基、1,1-二甲基乙基氧基羰基或2,2-二甲基丙醯基，X為氯原子或-OR10，R10係各自獨立為甲基或乙基}。 R 1 is a trifluoromethyl group, a difluoromethyl group or a chlorine atom, R 2 is a methyl group, a trifluoromethyl group, a difluoromethyl group or a chlorine atom, and R 4 , R 5 and R 7 are a hydrogen atom, R 3 and R 6 are each independently a hydrogen atom, a chlorine atom, a trifluoromethyl group or a methyl group, and R 8 is an ethyl hydrazino group, a benzyl group, a phenylcarbonyl group, a methoxycarbonyl group, an ethoxycarbonyl group, and a 1,1- Dimethylethyloxycarbonyl or 2,2-dimethylpropanyl, X is a chlorine atom or -OR 10 , and each of R 10 is independently methyl or ethyl}.

(20)一種式[5a]所表示之化合物或其鹽； {式中，A為選自下述之基， (20) a compound represented by the formula [5a] or a salt thereof; In the formula, A is selected from the group consisting of

R1為三氟甲基、二氟甲基、或氯原子，R2為甲基、三氟甲基、二氟甲基、或氯原子，R4、R5及R7為氫原子，R3及R6係各自獨立為氫原子、氯原子、三氟甲基或甲基，R8為乙醯基、苄基、苯基羰基、甲氧基羰基、乙氧基羰基、1,1-二甲基乙基氧基羰基或2,2-二甲基丙醯基，R10係各自獨立為甲基或乙基}。 R 1 is a trifluoromethyl group, a difluoromethyl group or a chlorine atom, R 2 is a methyl group, a trifluoromethyl group, a difluoromethyl group or a chlorine atom, and R 4 , R 5 and R 7 are a hydrogen atom, R 3 and R 6 are each independently a hydrogen atom, a chlorine atom, a trifluoromethyl group or a methyl group, and R 8 is an ethyl hydrazino group, a benzyl group, a phenylcarbonyl group, a methoxycarbonyl group, an ethoxycarbonyl group, and a 1,1- oxycarbonyl-dimethylethyl 2,2-dimethyl propyl group or acyl, R 10 are each independently based} methyl or ethyl.

(21)如(19)或(20)之化合物或其鹽，其中A為2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基或2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基，X為-OR10，R10為甲基。 (21) A compound of (19) or (20), wherein A is 2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl or 2-[3,5-Bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl, X is -OR 10 and R 10 is methyl.

(22)如(19)或(20)之化合物或其鹽，其中A為 乙醯基、苄基、苯基羰基、甲氧基羰基、乙氧基羰基、1,1-二甲基乙基氧基羰基或2,2-二甲基丙醯基，X為-OR10，R10為甲基。 (22) A compound of (19) or (20) or a salt thereof, wherein A is ethyl benzyl, benzyl, phenylcarbonyl, methoxycarbonyl, ethoxycarbonyl, 1,1-dimethylethyl Oxycarbonyl or 2,2-dimethylpropanyl, X is -OR 10 and R 10 is methyl.

(23)一種式[1]所表示之化合物或其鹽； {式中，A為乙醯基、苄基、苯基羰基、甲氧基羰基、乙氧基羰基或2,2-二甲基丙醯基}。 (23) A compound represented by the formula [1] or a salt thereof; In the formula, A is ethyl benzyl, benzyl, phenylcarbonyl, methoxycarbonyl, ethoxycarbonyl or 2,2-dimethylpropanyl}.

(24)如(23)之化合物或其鹽，其中A為苄基、苯基羰基、甲氧基羰基、乙氧基羰基或2,2-二甲基丙醯基。 (24) A compound of (23) or a salt thereof, wherein A is benzyl, phenylcarbonyl, methoxycarbonyl, ethoxycarbonyl or 2,2-dimethylpropanyl.

(25)一種式[1]所表示之化合物之製造方法，其特徵為包含使式[2]所表示之化合物與1,1,3-三氯丙烷-2-酮在溶劑存在下反應，而取得式[6]所表示之化合物之步驟，及，使前述式[6]所表示之化合物轉換成前述式[1]所表示之化合物之步驟； {式中，A係如同(1)中所定義} (25) A process for producing a compound represented by the formula [1], which comprises reacting a compound represented by the formula [2] with 1,1,3-trichloropropan-2-one in the presence of a solvent, and a step of obtaining a compound represented by the formula [6], and a step of converting the compound represented by the above formula [6] into a compound represented by the above formula [1]; {where, A is as defined in (1)}

(26)一種式[1]所表示之化合物之製造方法，其特徵為包含使式[2]所表示之化合物與1,1,3-三氯丙烷-2-酮在溶劑存在下反應，而取得式[6]所表示之化合物之步驟，及，使前述式[6]所表示之化合物轉換成前述式[1]所表示之化合物之步驟； {式中，A係如同(5)中所定義} (26) A process for producing a compound represented by the formula [1], which comprises reacting a compound represented by the formula [2] with 1,1,3-trichloropropan-2-one in the presence of a solvent, and a step of obtaining a compound represented by the formula [6], and a step of converting the compound represented by the above formula [6] into a compound represented by the above formula [1]; {where, A is as defined in (5)}

(27)如(25)或(26)之製造方法，其中R1及R2係各自獨立為C1~C4烷基、C1~C4鹵烷基、或鹵素原子，R4、R5及R7為氫原子，R3及R6係各自獨立為氫原子、鹵素原子、C1~C6烷基或C1~C6鹵烷基，R8為C2~C6烷基羰基、苄基、苯基羰基、C2~C6烷氧基羰基。 (27) The production method according to (25) or (26), wherein each of R 1 and R 2 is independently a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, or a halogen atom, R 4 , R 5 and R 7 are a hydrogen atom, and each of R 3 and R 6 is independently a hydrogen atom, a halogen atom, a C 1 -C 6 alkyl group or a C 1 -C 6 haloalkyl group, and R 8 is a C 2 -C 6 alkyl group. Carbonyl, benzyl, phenylcarbonyl, C 2 -C 6 alkoxycarbonyl.

(28)如(25)~(27)中任一項之製造方法，其中R1為三氟甲基、二氟甲基、或氯原子，R2為甲基、三氟甲基、二氟甲基、或氯原子，R3及R6係各自獨立為氫原子、氯原子、三氟甲基或甲基，R8為乙醯基、苄基、苯基羰基、甲氧基羰基、乙氧基羰基、1,1-二甲基乙基氧基羰基或2,2-二甲基丙醯基。 (28) The process according to any one of (25) to (27) wherein R 1 is a trifluoromethyl group, a difluoromethyl group or a chlorine atom, and R 2 is a methyl group, a trifluoromethyl group or a difluoro group. a methyl group or a chlorine atom, each of R 3 and R 6 is independently a hydrogen atom, a chlorine atom, a trifluoromethyl group or a methyl group, and R 8 is an ethyl hydrazino group, a benzyl group, a phenylcarbonyl group, a methoxycarbonyl group, or a Oxycarbonyl, 1,1-dimethylethyloxycarbonyl or 2,2-dimethylpropanyl.

(29)如(25)~(28)中任一項之製造方法，其中A為A-1。 The manufacturing method of any one of (25)-(28), wherein A is A-1.

(30)如(25)~(29)中任一項之製造方法，其中A為2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基或2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基。 (30) The process according to any one of (25) to (29) wherein A is 2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetamidine Or 2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl.

(31)如(25)~(28)中任一項之製造方法，其中 A為乙醯基、苄基、苯基羰基、甲氧基羰基、乙氧基羰基、1,1-二甲基乙基氧基羰基或2,2-二甲基丙醯基。 (31) The manufacturing method of any one of (25) to (28), wherein A is ethyl benzyl, benzyl, phenylcarbonyl, methoxycarbonyl, ethoxycarbonyl, 1,1-dimethylethyloxycarbonyl or 2,2-dimethylpropanyl.

(32)一種式[1c]所表示之化合物之製造方法，其特徵為包含使式[2a]所表示之化合物與式[3b]所表示之化合物在酸之存在下反應之步驟； (32) A process for producing a compound represented by the formula [1c], which comprises a step of reacting a compound represented by the formula [2a] with a compound represented by the formula [3b] in the presence of an acid;

{式中，R23係各自獨立為C1~C4烷基，L1為鹵素原子等之脫離基}。 In the formula, R 23 is each independently a C 1 -C 4 alkyl group, and L 1 is a leaving group such as a halogen atom.

(33)一種如(32)之式[1c]所表示之化合物之使用，其使用作為殺菌性作物保護劑之中間體。 (33) Use of a compound represented by the formula [1c] of (32), which is used as an intermediate of a bactericidal crop protectant.

(34)一種式[7]所表示之化合物之製造方法，其特徵為包含使式[1]所表示之化合物與式[8]所表示之化合物反應之步驟，且式[1]之化合物係藉由如前述(1)、(2)、(4)及(25)中任一項之方法所製造者； {式中，A係如同(1)中所定義；R11、R12、R13及R14係各自獨立為氫原子、C1~C6烷基、C3~C6環烷基、C1~C6鹵烷基、C1~C6烷氧基、C1~C6鹵烷氧基、鹵素原子、氰基或羥基，或R11與R12、及R13與R14係各自獨立與彼等所結合之碳原子一同形成羰基(C=O)；X1、X2、X3及X4係各自獨立為氫原子、鹵素原子、氰基、羥基、硝基、甲醯基、巰基、C1~C6烷基、C2~C6烯基、C2~C6炔基、C1~C6鹵烷基、C2~C6鹵烯基、C2~C6鹵炔基、C1~C6烷氧基、C2~C6烯氧基、C2~C6炔氧基、C1~C6鹵烷氧基、C2~C6鹵烯氧基、C2~C6鹵炔氧基、羧基、胺甲醯基、C3~C6環烷基、C3~C8鹵環烷基、C3~C6環烷氧基、C3~C8鹵環烷氧基、C2~C6烷氧基烷基、C4~C10環烷氧基烷基、C2~C6鹵烷氧基烷基、C4~C10鹵環烷氧基烷基、C3~C8烷氧基烷氧基烷基、C2~C6烷氧基烷氧基、C4~C10環烷基烷氧基、C1~C6羥基烷基、C4~C10環烷基烷基、C4~C10烷基環烷基、C6~C14環烷基環烷基、C4~C10鹵環烷基烷基、C6~C14鹵環烷基環烷基、C4~C10鹵烷基環烷 基、C5~C10烷基環烷基烷基、C3~C8環烯基、C3~C8鹵環烯基、-SR15、-S(O)R15、-S(O)2R15、-OS(O)2R15、-(C1~C6烷基)S(O)2R15、C2~C6烷硫基烷基、C2~C6烷基亞磺醯基烷基、C2~C6烷基磺醯基烷基、C2~C6烷基羰基、C2~C6鹵烷基羰基、C4~C8環烷基羰基、C2~C6烷氧基羰基、C2~C6鹵烷氧基羰基、C4~C8環烷氧基羰基、C5~C10環烷基烷氧基羰基、C2~C6烷基羰氧基、C2~C6鹵烷基羰氧基、C4~C8環烷基羰氧基、C2~C6烷氧基羰氧基、C2~C6鹵烷氧基羰氧基、C4~C8環烷氧基羰氧基、C3~C6烷基羰基烷氧基、-NR16R17、C2~C6烷基胺基烷基、C3~C8(二烷基胺基)烷基、C2~C6鹵烷基胺基烷基、C4~C10環烷基胺基烷基、C1~C6烷基磺醯基胺基、C1~C6鹵烷基磺醯基胺基、C2~C6烷基胺基羰基、C3~C10(二烷基胺基)羰基、C4~C8環烷基胺基羰基、C2~C8(N-烷氧基-N-烷基)胺基、C2~C8(二烷基胺基)羥基、C3~C10三烷基胼基、C3~C10三烷基矽基、C4~C10三烷基矽基烷基、C5~C10三烷基矽基炔基、C3~C10三烷基矽氧基、C4~C12三烷基矽基烷基氧基、C5~C12三烷基矽基烷氧基烷基、C5~C12三烷基矽基炔氧基、C2~C6烷基磺醯氧基烷基、C2~C6鹵烷基磺醯氧基烷基、-C(=NOR18)R19、-C(=NR20)R19、C2~C6氰基烷基、苯基、苯氧基或苄基，或X1及X2、X2及X3、以及X3及X4一同地形成可包含氧原子、硫原子、氮原子之C2~C6伸烷基鏈，或與彼等所結合之碳原子一同地形成噻吩環、吡啶環、吡咯環、咪唑環、苯環、萘環、嘧啶環、 呋喃環、吡嗪環、吡唑環或噁唑環；R15係各自獨立為C1~C8烷基、C3~C8環烷基、C1~C6鹵烷基、C3~C8鹵環烷基、C1~C6烷基胺基、苯基或苄基，苯基或苄基亦可至少一個R21所取代；R21係各自獨立為C1~C6烷基、C3~C8環烷基、C1~C6鹵烷基、C1~C6烷氧基、C1~C6鹵烷氧基、C3~C8環烷氧基、C3~C8鹵環烷基、C1~C6烷硫基、C1~C6烷基亞磺醯基、C1~C6烷基磺醯基、C1~C6鹵烷硫基、C1~C6鹵烷基亞磺醯基、C1~C6鹵烷基磺醯基、鹵素原子、氰基或羥基；R16及R17係各自獨立為氫原子、C1~C6烷基、C3~C8環烷基、C1~C6鹵烷基、C3~C8鹵環烷基、C1~C6烷氧基、C2~C8二烷基胺基、C2~C6烷基羰基、C2~C6鹵烷基羰基、C4~C8環烷基羰基、C2~C6烷氧基羰基、C2~C6鹵烷氧基羰基或C3~C10(二烷基胺基)羰基；R18為氫原子、C1~C6烷基、C1~C6鹵烷基或苄基；R19為氫原子、C1~C6烷基、C3~C8環烷基、C1~C6鹵烷基、C3~C8鹵環烷基、C4~C10環烷基烷基、苯基或苄基；R20為C1~C6烷基、C3~C8環烷基、C1~C6鹵烷基、C3~C8鹵環烷基、苯基或苄基} (34) A process for producing a compound represented by the formula [7], which comprises the step of reacting a compound represented by the formula [1] with a compound represented by the formula [8], and the compound of the formula [1] Produced by the method according to any one of the above (1), (2), (4) and (25); In the formula, A is as defined in (1); R 11 , R 12 , R 13 and R 14 are each independently a hydrogen atom, a C 1 -C 6 alkyl group, a C 3 -C 6 cycloalkyl group, C 1 to C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, halogen atom, cyano or hydroxy group, or R 11 and R 12 , and R 13 and R 14 each Independently forming a carbonyl group (C=O) together with the carbon atoms to which they are combined; X 1 , X 2 , X 3 and X 4 are each independently a hydrogen atom, a halogen atom, a cyano group, a hydroxyl group, a nitro group, and a fluorenyl group. , fluorenyl, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 ~C 6 Haloalkynyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyloxy, C 2 -C 6 alkynyloxy, C 1 -C 6 haloalkoxy, C 2 -C 6 haloalkoxy , C 2 ~ C 6 haloalkoxy group, carboxyl group, amine carbenyl group, C 3 ~ C 6 cycloalkyl group, C 3 ~ C 8 halocycloalkyl group, C 3 ~ C 6 cycloalkoxy group, C 3 ~ C 8 halocycloalkoxy, C 2 -C 6 alkoxyalkyl, C 4 -C 10 cycloalkoxyalkyl, C 2 -C 6 haloalkoxyalkyl, C 4 -C 10 halo ring Alkoxyalkyl, C 3 -C 8 alkoxyalkoxyalkyl, C 2 -C 6 alkoxyalkoxy, C 4 -C 10 naphthenic Alkoxy group, C 1 -C 6 hydroxyalkyl group, C 4 -C 10 cycloalkylalkyl group, C 4 -C 10 alkylcycloalkyl group, C 6 -C 14 cycloalkylcycloalkyl group, C 4 ~C 10 halocycloalkylalkyl, C 6 -C 14 halocycloalkylcycloalkyl, C 4 -C 10 haloalkylcycloalkyl, C 5 -C 10 alkylcycloalkylalkyl, C 3 ~C 8 cycloalkenyl, C 3 -C 8 halocycloalkenyl, -SR 15 , -S(O)R 15 , -S(O) 2 R 15 , -OS(O) 2 R 15 , -(C 1 to C 6 alkyl)S(O) 2 R 15 , C 2 to C 6 alkylthioalkyl, C 2 to C 6 alkylsulfinylalkyl, C 2 to C 6 alkylsulfonyl Alkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 haloalkylcarbonyl, C 4 -C 8 cycloalkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 haloalkoxy a carbonyl group, a C 4 -C 8 cycloalkoxycarbonyl group, a C 5 -C 10 cycloalkylalkoxycarbonyl group, a C 2 -C 6 alkylcarbonyloxy group, a C 2 -C 6 haloalkylcarbonyloxy group, C 4 -C 8 cycloalkylcarbonyloxy, C 2 -C 6 alkoxycarbonyloxy, C 2 -C 6 haloalkoxycarbonyloxy, C 4 -C 8 cycloalkoxycarbonyloxy, C 3 -C 6 alkylcarbonylalkoxy, -NR 16 R 17 , C 2 -C 6 alkylaminoalkyl, C 3 -C 8 (dialkylamino)alkyl, C 2 -C 6 haloalkyl aminoalkyl, C 4 ~ C 10 cycloalkyl Alkyl amino group, C 1 ~ C 6 alkyl sulfonic acyl group, C 1 ~ C 6 haloalkyl sulfonic acyl group, C 2 ~ C 6 alkyl amino carbonyl, C 3 ~ C 10 ( Dialkylamino)carbonyl, C 4 ~C 8 cycloalkylaminocarbonyl, C 2 ~C 8 (N-alkoxy-N-alkyl)amine, C 2 ~C 8 (dialkylamine Hydroxy, C 3 ~ C 10 trialkyl fluorenyl, C 3 ~ C 10 trialkyl fluorenyl, C 4 ~ C 10 trialkyl decyl alkyl, C 5 ~ C 10 trialkyl decyl alkyne , C 3 ~ C 10 trialkyl decyloxy, C 4 ~ C 12 trialkyl decylalkyloxy, C 5 ~ C 12 trialkyl decyl alkoxyalkyl, C 5 ~ C 12 Trialkylnonylalkynyloxy, C 2 -C 6 alkylsulfonyloxyalkyl, C 2 -C 6 haloalkylsulfonyloxyalkyl, -C(=NOR 18 )R 19 , -C (=NR 20 )R 19 , C 2 -C 6 cyanoalkyl, phenyl, phenoxy or benzyl, or X 1 and X 2 , X 2 and X 3 , and X 3 and X 4 are formed together A C 2 -C 6 alkyl chain which may contain an oxygen atom, a sulfur atom or a nitrogen atom, or a thiophene ring, a pyridine ring, a pyrrole ring, an imidazole ring, a benzene ring or a naphthalene ring together with the carbon atom to which they are bonded , pyrimidine ring, furan ring, pyrazine ring, pyrazole ring or oxazole ring; R 15 series Each independently is a C 1 -C 8 alkyl group, a C 3 -C 8 cycloalkyl group, a C 1 -C 6 haloalkyl group, a C 3 -C 8 halocycloalkyl group, a C 1 -C 6 alkylamino group, a benzene group. Or a benzyl group, a phenyl group or a benzyl group may also be substituted with at least one R 21 group; each of the R 21 groups is independently a C 1 -C 6 alkyl group, a C 3 -C 8 cycloalkyl group, a C 1 -C 6 haloalkyl group. , C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 3 -C 8 cycloalkoxy, C 3 -C 8 halocycloalkyl, C 1 -C 6 alkylthio, C 1 to C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylthio, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 a haloalkylsulfonyl group, a halogen atom, a cyano group or a hydroxyl group; each of R 16 and R 17 is independently a hydrogen atom, a C 1 -C 6 alkyl group, a C 3 -C 8 cycloalkyl group, a C 1 -C 6 halo group Alkyl, C 3 -C 8 halocycloalkyl, C 1 -C 6 alkoxy, C 2 -C 8 dialkylamino, C 2 -C 6 alkylcarbonyl, C 2 -C 6 haloalkyl a carbonyl group, a C 4 -C 8 cycloalkylcarbonyl group, a C 2 -C 6 alkoxycarbonyl group, a C 2 -C 6 haloalkoxycarbonyl group or a C 3 -C 10 (dialkylamino)carbonyl group; R 18 is a hydrogen atom, a C 1 -C 6 alkyl group, a C 1 -C 6 haloalkyl group or a benzyl group; R 19 is a hydrogen atom, a C 1 -C 6 alkyl group, a C 3 -C 8 cycloalkyl group, C 1 to C 6 haloalkyl, C 3 -C 8 halocycloalkyl, C 4 -C 10 cycloalkylalkyl, phenyl or benzyl; R 20 is C 1 -C 6 alkyl, C 3 ~C 8 -cycloalkyl, C 1 -C 6 haloalkyl, C 3 -C 8 halocycloalkyl, phenyl or benzyl}

{式中，A係如同(1)中所定義} {where, A is as defined in (1)}

(35)一種式[7]所表示之化合物之製造方法，其特徵為包含使式[5a]所表示之化合物與式[8]所表示之化合物反應之步驟，且式[5a]之化合物係藉由如前述(3)之方法所製造者； {式中，A係如同(1)中所定義，R11、R12、R13、R14、X1、X2、X3及X4係如同(34)中所定義} (35) A process for producing a compound represented by the formula [7], which comprises a step of reacting a compound represented by the formula [5a] with a compound represented by the formula [8], and a compound of the formula [5a] Produced by the method of (3) above; Wherein A is as defined in (1), and R 11 , R 12 , R 13 , R 14 , X 1 , X 2 , X 3 and X 4 are as defined in (34)}

{式中，R10係如同(1)中所定義} {where R 10 is as defined in (1)}

(36)一種式[7]所表示之化合物之製造方法，其特徵為包含使式[1]所表示之化合物與式[8]所表示之化合物反應之步驟，且式[1]之化合物係藉由如前述(5)、(6)、(8)~(10)及(26)中任一項之方法所製造者； {式中，A係如同(5)中所定義；R11、R12、R13及R14係各自獨立為氫原子、C1~C6烷基、C3~C6環烷基、C1~C6鹵烷基、C1~C6烷氧基、C1~C6鹵烷氧基、鹵素原子、氰基或羥基，或R11與R12、及R13與R14係各自獨立與彼等所結合之碳原子一同地形成羰基(C=O)；X1、X2、X3及X4係各自獨立為氫原子、鹵素原子、氰基、羥基、硝基、甲醯基、巰基、C1~C6烷基、C2~C6 烯基、C2~C6炔基、C1~C6鹵烷基、C2~C6鹵烯基、C2~C6鹵炔基、C1~C6烷氧基、C2~C6烯氧基、C2~C6炔氧基、C1~C6鹵烷氧基、C2~C6鹵烯氧基、C2~C6鹵炔氧基、羧基、胺甲醯基、C3~C6環烷基、C3~C8鹵環烷基、C3~C6環烷氧基、C3~C8鹵環烷氧基、C2~C6烷氧基烷基、C4~C10環烷氧基烷基、C2~C6鹵烷氧基烷基、C4~C10鹵環烷氧基烷基、C3~C8烷氧基烷氧基烷基、C2~C6烷氧基烷氧基、C4~C10環烷基烷氧基、C1~C6羥基烷基、C4~C10環烷基烷基、C4~C10烷基環烷基、C6~C14環烷基環烷基、C4~C10鹵環烷基烷基、C6~C14鹵環烷基環烷基、C4~C10鹵烷基環烷基、C5~C10烷基環烷基烷基、C3~C8環烯基、C3~C8鹵環烯基、-SR15、-S(O)R15、-S(O)2R15、-OS(O)2R15、-(C1~C6烷基)S(O)2R15、C2~C6烷硫基烷基、C2~C6烷基亞磺醯基烷基、C2~C6烷基磺醯基烷基、C2~C6烷基羰基、C2~C6鹵烷基羰基、C4~C8環烷基羰基、C2~C6烷氧基羰基、C2~C6鹵烷氧基羰基、C4~C8環烷氧基羰基、C5~C10環烷基烷氧基羰基、C2~C6烷基羰氧基、C2~C6鹵烷基羰氧基、C4~C8環烷基羰氧基、C2~C6烷氧基羰氧基、C2~C6鹵烷氧基羰氧基、C4~C8環烷氧基羰氧基、C3~C6烷基羰基烷氧基、-NR16R17、C2~C6烷基胺基烷基、C3~C8(二烷基胺基)烷基、C2~C6鹵烷基胺基烷基、C4~C10環烷基胺基烷基、C1~C6烷基磺醯基胺基、C1~C6鹵烷基磺醯基胺基、C2~C6烷基胺基羰基、C3~C10(二烷基胺基)羰基、C4~C8環烷基胺基羰基、C2~C8(N-烷氧基-N-烷基)胺 基、C2~C8(二烷基胺基)羥基、C3~C10三烷基胼基、C3~C10三烷基矽基、C4~C10三烷基矽基烷基、C5~C10三烷基矽基炔基、C3~C10三烷基矽氧基、C4~C12三烷基矽基烷基氧基、C5~C12三烷基矽基烷氧基烷基、C5~C12三烷基矽基炔氧基、C2~C6烷基磺醯氧基烷基、C2~C6鹵烷基磺醯氧基烷基、-C(=NOR18)R19、-C(=NR20)R19、C2~C6氰基烷基、苯基、苯氧基或苄基，或X1及X2、X2及X3、以及X3及X4一同地形成可包含氧原子、硫原子、氮原子之C2~C6伸烷基鏈，或與彼等所結合之碳原子一同地形成噻吩環、吡啶環、吡咯環、咪唑環、苯環、萘環、嘧啶環、呋喃環、吡嗪環、吡唑環或噁唑環；R15係各自獨立為C1~C8烷基、C3~C8環烷基、C1~C6鹵烷基、C3~C8鹵環烷基、C1~C6烷基胺基、苯基或苄基，苯基或苄基亦可被至少一個R21所取代；R21係各自獨立為C1~C6烷基、C3~C8環烷基、C1~C6鹵烷基、C1~C6烷氧基、C1~C6鹵烷氧基、C3~C8環烷氧基、C3~C8鹵環烷基、C1~C6烷硫基、C1~C6烷基亞磺醯基、C1~C6烷基磺醯基、C1~C6鹵烷硫基、C1~C6鹵烷基亞磺醯基、C1~C6鹵烷基磺醯基、鹵素原子、氰基或羥基；R16及R17係各自獨立為氫原子、C1~C6烷基、C3~C8環烷基、C1~C6鹵烷基、C3~C8鹵環烷基、C1~C6烷氧基、C2~C8二烷基胺基、C2~C6烷基羰基、C2~C6鹵烷基羰基、C4~C8環烷基羰基、C2~C6烷氧基羰基、C2~C6鹵烷氧基羰基或C3~C10(二烷基胺基)羰基； R18為氫原子、C1~C6烷基、C1~C6鹵烷基或苄基；R19為氫原子、C1~C6烷基、C3~C8環烷基、C1~C6鹵烷基、C3~C8鹵環烷基、C4~C10環烷基烷基、苯基或苄基；R20為C1~C6烷基、C3~C8環烷基、C1~C6鹵烷基、C3~C8鹵環烷基、苯基或苄基} (36) A process for producing a compound represented by the formula [7], which comprises the step of reacting a compound represented by the formula [1] with a compound represented by the formula [8], and the compound of the formula [1] Produced by the method according to any one of the above (5), (6), (8) to (10) and (26); In the formula, A is as defined in (5); R 11 , R 12 , R 13 and R 14 are each independently a hydrogen atom, a C 1 -C 6 alkyl group, a C 3 -C 6 cycloalkyl group, C 1 to C 6 haloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, halogen atom, cyano or hydroxy group, or R 11 and R 12 , and R 13 and R 14 each Forming a carbonyl group (C=O) independently with the carbon atoms to which they are combined; X 1 , X 2 , X 3 and X 4 are each independently a hydrogen atom, a halogen atom, a cyano group, a hydroxyl group, a nitro group, and a hydrazine group. Base, fluorenyl, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 ~C 6 haloalkynyl, C 1 ~C 6 alkoxy, C 2 ~C 6 alkenyloxy, C 2 ~C 6 alkynyloxy, C 1 ~C 6 haloalkoxy, C 2 ~C 6 halooxy Base, C 2 ~ C 6 haloalkoxy group, carboxyl group, amine carbenyl group, C 3 ~ C 6 cycloalkyl group, C 3 ~ C 8 halocycloalkyl group, C 3 ~ C 6 cycloalkoxy group, C 3 ~C 8 halocycloalkoxy, C 2 -C 6 alkoxyalkyl, C 4 -C 10 cycloalkoxyalkyl, C 2 -C 6 haloalkoxyalkyl, C 4 ~C 10 halo Cycloalkoxyalkyl, C 3 -C 8 alkoxyalkoxyalkyl, C 2 -C 6 alkoxyalkoxy, C 4 ~C 10 ring Alkyl alkoxy, C 1 -C 6 hydroxyalkyl, C 4 -C 10 cycloalkylalkyl, C 4 -C 10 alkylcycloalkyl, C 6 -C 14 cycloalkylcycloalkyl, C 4 to C 10 halocycloalkylalkyl, C 6 -C 14 halocycloalkylcycloalkyl, C 4 -C 10 haloalkylcycloalkyl, C 5 -C 10 alkylcycloalkylalkyl, C 3 ~ C 8 cycloalkenyl, C 3 ~ C 8 halocycloalkenyl, -SR 15 , -S(O)R 15 , -S(O) 2 R 15 , -OS(O) 2 R 15 , -( C 1 ~C 6 alkyl)S(O) 2 R 15 , C 2 ~C 6 alkylthioalkyl, C 2 -C 6 alkylsulfinylalkyl, C 2 -C 6 alkylsulfonyl Alkyl group, C 2 -C 6 alkylcarbonyl group, C 2 -C 6 haloalkylcarbonyl group, C 4 -C 8 cycloalkylcarbonyl group, C 2 -C 6 alkoxycarbonyl group, C 2 -C 6 haloalkane Oxycarbonyl, C 4 -C 8 cycloalkoxycarbonyl, C 5 -C 10 cycloalkylalkoxycarbonyl, C 2 -C 6 alkylcarbonyloxy, C 2 -C 6 haloalkylcarbonyloxy , C 4 -C 8 cycloalkylcarbonyloxy, C 2 -C 6 alkoxycarbonyloxy, C 2 -C 6 haloalkoxycarbonyloxy, C 4 -C 8 cycloalkoxycarbonyloxy , C 3 -C 6 alkylcarbonylalkoxy, -NR 16 R 17 , C 2 -C 6 alkylaminoalkyl, C 3 -C 8 (dialkylamino)alkyl, C 2 -C aminoalkyl 6 haloalkyl, C 4 ~ C 10 Alkylamino group, C 1 ~ C 6 alkyl sulfonic acyl group, C 1 ~ C 6 haloalkyl sulfonic acyl group, C 2 ~ C 6 alkyl amino carbonyl, C 3 ~ C 10 (dialkylamino)carbonyl, C 4 -C 8 cycloalkylaminocarbonyl, C 2 -C 8 (N-alkoxy-N-alkyl)amine, C 2 -C 8 (dialkyl Amino)hydroxyl, C 3 -C 10 trialkylsulfonyl, C 3 -C 10 trialkylsulfonyl, C 4 -C 10 trialkyldecylalkyl, C 5 -C 10 trialkylsulfonyl Alkynyl, C 3 -C 10 trialkyldecyloxy, C 4 -C 12 trialkyldecylalkyloxy, C 5 -C 12 trialkyldecyloxyalkyl, C 5 -C 12 trialkylnonylalkynyloxy, C 2 -C 6 alkylsulfonyloxyalkyl, C 2 -C 6 haloalkylsulfonyloxyalkyl, -C(=NOR 18 )R 19 ,- C(=NR 20 )R 19 , C 2 -C 6 cyanoalkyl, phenyl, phenoxy or benzyl, or X 1 and X 2 , X 2 and X 3 , and X 3 and X 4 together Forming a C 2 -C 6 alkyl chain which may contain an oxygen atom, a sulfur atom or a nitrogen atom, or forming a thiophene ring, a pyridine ring, a pyrrole ring, an imidazole ring, a benzene ring or a naphthalene together with the carbon atom to which they are bonded ring, a pyrimidine ring, a furan ring, a pyrazine ring, a pyrazole ring or an oxazole ring; R 15 Are each independently C 1 ~ C 8 alkyl group, C 3 ~ C 8 cycloalkyl, C 1 ~ C 6 haloalkyl, C 3 ~ C 8 halocycloalkyl, C 1 ~ C 6 alkyl group, benzyl Or a benzyl group, a phenyl group or a benzyl group may also be substituted by at least one R 21 ; each of the R 21 groups is independently a C 1 -C 6 alkyl group, a C 3 -C 8 cycloalkyl group, a C 1 -C 6 haloalkyl group. a group, a C 1 -C 6 alkoxy group, a C 1 -C 6 haloalkoxy group, a C 3 -C 8 cycloalkoxy group, a C 3 -C 8 halocycloalkyl group, a C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylthio, C 1 -C 6 haloalkylsulfinyl, C 1 ~C a 6 haloalkylsulfonyl group, a halogen atom, a cyano group or a hydroxyl group; each of R 16 and R 17 is independently a hydrogen atom, a C 1 -C 6 alkyl group, a C 3 -C 8 cycloalkyl group, or a C 1 -C 6 group; Haloalkyl, C 3 -C 8 halocycloalkyl, C 1 -C 6 alkoxy, C 2 -C 8 dialkylamino, C 2 -C 6 alkylcarbonyl, C 2 -C 6 halo a carbonyl group, a C 4 -C 8 cycloalkylcarbonyl group, a C 2 -C 6 alkoxycarbonyl group, a C 2 -C 6 haloalkoxycarbonyl group or a C 3 -C 10 (dialkylamino)carbonyl group; R 18 is a hydrogen atom, C 1 ~ C 6 alkyl group, C 1 ~ C 6 alkyl halide or benzyl; R 19 is a hydrogen atom, C 1 ~ C 6 alkyl group, C 3 ~ C 8 cycloalkyl , C 1 ~ C 6 haloalkyl, C 3 ~ C 8 halocycloalkyl, C 4 ~ C 10 cycloalkyl group, phenyl or benzyl; R 20 is C 1 ~ C 6 alkyl, C 3 ~C 8 cycloalkyl, C 1 ~C 6 haloalkyl, C 3 ~C 8 halocycloalkyl, phenyl or benzyl}

{式中，A係如同(5)中所定義} {where, A is as defined in (5)}

(37)一種式[7]所表示之化合物之製造方法，其特徵為包含使式[5a]所表示之化合物與式[8]所表示之化合物反應之步驟，且式[5a]之化合物係藉由如前述(7)之方法所製造者； {式中，A係如同(5)中所定義；R11、R12、R13、R14、X1、X2、X3及X4係如同(36)中所定義} (37) A process for producing a compound represented by the formula [7], which comprises a step of reacting a compound represented by the formula [5a] with a compound represented by the formula [8], and a compound of the formula [5a] Produced by the method of the above (7); Wherein A is as defined in (5); R 11 , R 12 , R 13 , R 14 , X 1 , X 2 , X 3 and X 4 are as defined in (36)}

{式中，R10係如同(5)中所定義} {where, R 10 is as defined in (5)}

(38)如(34)~(37)中任一項之製造方法，其中R1及R2係各自獨立為C1~C4烷基、C1~C4鹵烷基、或鹵素原子；R4、R5及R7為氫原子；R3及R6係各自獨立為氫原子、鹵素原子、C1~C6烷基或C1~C6鹵烷基，R8為C2~C6烷基羰基、苄基、苯基羰基、C2~C6烷氧 基羰基。 The method of any one of (34) to (37), wherein R 1 and R 2 are each independently a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, or a halogen atom; R 4 , R 5 and R 7 are each a hydrogen atom; and R 3 and R 6 each independently represent a hydrogen atom, a halogen atom, a C 1 -C 6 alkyl group or a C 1 -C 6 haloalkyl group, and R 8 is C 2 ~ C 6 alkylcarbonyl, benzyl, phenylcarbonyl, C 2 -C 6 alkoxycarbonyl.

(39)如(34)~(38)中任一項之製造方法，其中R1為三氟甲基、二氟甲基、或氯原子，R2為甲基、三氟甲基、二氟甲基、或氯原子，R3及R6係各自獨立為氫原子、氯原子、三氟甲基或甲基，R8為乙醯基、苄基、苯基羰基、甲氧基羰基、乙氧基羰基、1,1-二甲基乙基氧基羰基或2,2-二甲基丙醯基，R10係各自獨立為甲基或乙基，L1為氯原子或溴原子。 (39) The process according to any one of (34) to (38) wherein R 1 is a trifluoromethyl group, a difluoromethyl group or a chlorine atom, and R 2 is a methyl group, a trifluoromethyl group or a difluoro group. a methyl group or a chlorine atom, each of R 3 and R 6 is independently a hydrogen atom, a chlorine atom, a trifluoromethyl group or a methyl group, and R 8 is an ethyl hydrazino group, a benzyl group, a phenylcarbonyl group, a methoxycarbonyl group, or a oxycarbonyl group, a 1,1-dimethylethyl group, a carbonyl group or a 2,2-dimethyl propyl acyl, R 10 are each independently based methyl or ethyl, L 1 is a chlorine atom or a bromine atom.

(40)如(34)~(39)中任一項之製造方法，其中A為A-1，R10為甲基，L1為溴原子。 (40) as (34) - (39) The production method according to any of wherein A is A-1, R 10 is a methyl group, L 1 is a bromine atom.

(41)如(34)~(40)中任一項之製造方法，其中A為2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基或2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基。 (41) A process according to any one of (34) to (40) wherein A is 2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetamidine Or 2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl.

(42)如(34)~(39)中任一項之製造方法，其中A為乙醯基、苄基、苯基羰基、甲氧基羰基、乙氧基羰基、1,1-二甲基乙基氧基羰基或2,2-二甲基丙醯基，R10為甲基，L1為溴原子。 The method of any one of (34) to (39), wherein A is an ethyl hydrazino group, a benzyl group, a phenylcarbonyl group, a methoxycarbonyl group, an ethoxycarbonyl group, and a 1,1-dimethyl group. Ethyloxycarbonyl or 2,2-dimethylpropanyl, R 10 is a methyl group, and L 1 is a bromine atom.

(43)如(34)~(37)中任一項之製造方法，其中R11及R13為氫原子， R12及R14係各自獨立為氫原子或甲基；X1、X2、X3及X4係各自獨立為氫原子、鹵素原子、氰基、羥基、硝基、甲醯基、巰基、C1~C6烷基、C2~C6烯基、C2~C6炔基、C3~C6環烷基、C1~C6鹵烷基、C1~C6羥基烷基、C1~C6烷氧基、C1~C6鹵烷氧基、羧基、C2~C6炔氧基、C2~C6烷氧基烷基、-SR15、-S(O)R15、-S(O)2R15、-OS(O)2R15、C2~C6烷硫基烷基、C2~C6烷基羰基、C2~C6烷氧基羰基、C2~C6烷基羰氧基、C2~C6烷氧基羰氧基、-NR16R17、C1~C6烷基磺醯基胺基、C2~C6烷基胺基烷基、-C(=NOR18)R19、C2~C6氰基烷基、苯基、苯氧基或苄基，或X1及X2、X2及X3、以及X3及X4一同地形成可包含氧原子之C2~C6伸烷基鏈，或與彼等所結合之碳原子一同地形成苯環；R15係各自獨立為C1~C8烷基、C3~C6環烷基、C1~C6鹵烷基、或C1~C6烷基胺基；R16及R17係各自獨立為氫原子、C1~C6烷基、C2~C6烷基羰基或C2~C6烷氧基羰基；R18及R19係各自獨立為氫原子或C1~C6烷基；R1及R2係各自獨立為C1~C6烷基、C1~C6鹵烷基、或鹵素原子；R3及R6係各自獨立為氫原子、鹵素原子、C1~C6烷基或C1~C6鹵烷基；R4、R5及R7為氫原子。 The method of any one of (34) to (37), wherein R 11 and R 13 are each a hydrogen atom, and R 12 and R 14 are each independently a hydrogen atom or a methyl group; X 1 , X 2 , Each of X 3 and X 4 is independently a hydrogen atom, a halogen atom, a cyano group, a hydroxyl group, a nitro group, a decyl group, a fluorenyl group, a C 1 -C 6 alkyl group, a C 2 -C 6 alkenyl group, or a C 2 -C 6 group. Alkynyl, C 3 -C 6 cycloalkyl, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxyalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, carboxy , C 2 ~C 6 alkynyloxy, C 2 -C 6 alkoxyalkyl, -SR 15 , -S(O)R 15 , -S(O) 2 R 15 , -OS(O) 2 R 15 , C 2 -C 6 alkylthioalkyl, C 2 -C 6 alkylcarbonyl, C 2 -C 6 alkoxycarbonyl, C 2 -C 6 alkylcarbonyloxy, C 2 -C 6 alkoxy Carbonyloxy, -NR 16 R 17 , C 1 -C 6 alkylsulfonylamino, C 2 -C 6 alkylaminoalkyl, -C(=NOR 18 )R 19 , C 2 ~C 6 a cyanoalkyl group, a phenyl group, a phenoxy group or a benzyl group, or X 1 and X 2 , X 2 and X 3 , and X 3 and X 4 together form a C 2 -C 6 alkylene group which may contain an oxygen atom the binding of the chain, or together with their carbon atoms to form a benzene ring; R 15 are each independently based C 1 ~ C 8 alkyl group, C 3 ~ C 6 Alkyl group, C 1 ~ C 6 haloalkyl, or C 1 ~ C 6 alkyl group; R 16 and R 17 are each independently a hydrogen atom based, C 1 ~ C 6 alkyl group, C 2 ~ C 6 alkyl a carbonyl group or a C 2 -C 6 alkoxycarbonyl group; each of R 18 and R 19 is independently a hydrogen atom or a C 1 -C 6 alkyl group; and R 1 and R 2 are each independently a C 1 -C 6 alkyl group, C a 1 -C 6 haloalkyl group or a halogen atom; each of R 3 and R 6 is independently a hydrogen atom, a halogen atom, a C 1 -C 6 alkyl group or a C 1 -C 6 haloalkyl group; R 4 and R 5 and R 7 is a hydrogen atom.

(44)如(34)~(37)及(43)中任一項之製造方 法，其中R12及R14為氫原子；X1、X2、X3及X4係各自獨立為氫原子、鹵素原子、氰基、羥基、硝基、甲醯基、C1~C4烷基、C1~C4鹵烷基、C1~C4羥基烷基、C1~C4烷氧基、C1~C4鹵烷氧基、-SR15、-S(O)2R15、-OS(O)2R15、C2~C4烷基羰氧基、C2~C4烷氧基羰氧基、或-C(=NOR18)R19；R15係各自獨立為C1~C4烷基、環丙基或C1~C4鹵烷基；R18及R19係各自獨立為氫原子或甲基；R1及R2係各自獨立為C1~C4烷基、C1~C4鹵烷基、或鹵素原子；R3及R6係各自獨立為氫原子、氯原子、甲基或三氟甲基。 The method of any one of (34) to (37), wherein R 12 and R 14 are each a hydrogen atom; and X 1 , X 2 , X 3 and X 4 are each independently a hydrogen atom. , halogen atom, cyano group, hydroxyl group, nitro group, formyl group, C 1 -C 4 alkyl group, C 1 -C 4 haloalkyl group, C 1 -C 4 hydroxyalkyl group, C 1 -C 4 alkoxy group , C 1 -C 4 haloalkoxy, -SR 15 , -S(O) 2 R 15 , -OS(O) 2 R 15 , C 2 -C 4 alkylcarbonyloxy, C 2 -C 4 alkane An oxycarbonyloxy group, or -C(=NOR 18 )R 19 ; R 15 each independently a C 1 -C 4 alkyl group, a cyclopropyl group or a C 1 -C 4 haloalkyl group; R 18 and R 19 systems Each of them is independently a hydrogen atom or a methyl group; R 1 and R 2 are each independently a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, or a halogen atom; and R 3 and R 6 are each independently a hydrogen atom. , chlorine atom, methyl or trifluoromethyl.

(45)如(34)~(37)、(43)及(44)中任一項之製造方法，其中X1、X2、X3及X4係各自獨立為氫原子、硝基、氟原子、甲基、三氟甲基、甲氧基、二氟甲氧基、三氟甲氧基或-OS(O)2R15；R15為甲基；R1為三氟甲基、二氟甲基、或氯原子；R2為甲基、三氟甲基、二氟甲基、或氯原子；R3及R6係各自獨立為氫原子、氯原子、三氟甲基或甲基。 (45) The method of any one of (34) to (37), (43) and (44), wherein each of X 1 , X 2 , X 3 and X 4 is independently a hydrogen atom, a nitro group, or a fluorine atom. Atom, methyl, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy or -OS(O) 2 R 15 ; R 15 is methyl; R 1 is trifluoromethyl, a fluoromethyl group or a chlorine atom; R 2 is a methyl group, a trifluoromethyl group, a difluoromethyl group, or a chlorine atom; and each of R 3 and R 6 is independently a hydrogen atom, a chlorine atom, a trifluoromethyl group or a methyl group. .

(46)如(34)~(37)及(43)~(45)中任一項之製造方法，其中X1、X2、X3、X4之任一個為-OS(O)2R15。 (46) The method of any one of (34) to (37) and (43) to (45), wherein any one of X 1 , X 2 , X 3 , and X 4 is -OS(O) 2 R 15 .

(47)如(34)~(37)及(43)~(46)中任一項之製造方法，其中X1為-OS(O)2R15。 The method of any one of (34) to (37) and (43) to (46), wherein X 1 is -OS(O) 2 R 15 .

(48)如(34)~(37)及(43)~(47)中任一項之製造方法，其中X2及X3為氫原子。 The production method according to any one of (34) to (37), wherein X 2 and X 3 are a hydrogen atom.

(49)如(34)~(37)及(43)~(48)中任一項之製造方法，其中A為A-1。 (49) The method of any one of (34) to (37) and (43) to (48), wherein A is A-1.

(50)如(34)~(37)及(43)~(49)中任一項之製造方法，其中式[7]所表示之化合物為選自4-[4-(1,5-二氫-3H-2,4-苯并二噁呯(Benzodioxepin)-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6,9-二氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7,8-二甲基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7,8-二氯-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙 醯基]哌啶、4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-乙基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氟-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(1,5-二氫-3H-2,4-萘并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-環丙基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡 唑-1-基]乙醯基]哌啶、4-[4-(6-甲基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-溴-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[7-(三氟甲基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6,7,8,9-四氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(1-甲基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-甲基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-丁基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑- 1-基]乙醯基]哌啶、4-[4-(6-丙基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氯-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-溴-9-甲氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-辛基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲氧基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-異丙基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-乙基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑- 1-基]乙醯基]哌啶、4-[4-[6-(1,1,1-三氟丙烷-3-基)磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(1,5,7,8,9-五氫-3H-2,4-茚并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-9-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-羥基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-環丙基羰氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6-(三氟甲基)磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲氧基羰氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑- 1-基]乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氟-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲氧基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-氯-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲基磺醯基胺基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、 4-[4-(6-甲基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-氟-6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲氧基-9-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲基磺醯基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-苯基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6,9-二氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6,9-二氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、 4-[4-(6-羥基甲基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-異丙基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-丁基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6,7,8,9-四氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-苯基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-溴-9-甲氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氯-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-辛基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、 4-[4-[7-(三氟甲基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(1,5,7,8,9-五氫-3H-2,4-茚并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6-(甲氧基亞胺基)甲基-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6-氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、及4-[4-(6,9-二氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶。 (50) The production method according to any one of (34) to (37), wherein the compound represented by the formula [7] is selected from the group consisting of 4-[4-(1,5-di) Hydrogen-3H-2,4-benzodioxin (Benzodioxepin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H- Pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-fluoro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2- Thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6,9- Difluoro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl) -1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(7,8-dimethyl-1,5-dihydro-3H-2,4-benzodioxin Ind-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4 -[4-(7,8-Dichloro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5- Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]B Mercapto] piperidine, 4-[4-(6-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl] 1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-ethylsulfonyloxy) 1,2-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl) -1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-fluoro-9-methylsulfonyloxy-1,5-dihydro-3H-2,4- Benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl] Piperidine, 4-[4-(7-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1- [2-[5-Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(1,5-dihydro-3H-2 , 4-naphthodioxan-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]B Mercapto] piperidine, 4-[4-(7-fluoro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2 -[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-nitro-1,5-dihydro- 3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazole-1- Ethyl Piperidine, 4-[4-(6-cyclopropylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]- 1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyridyl Zin-1-yl]ethinyl]piperidine, 4-[4-(6-methyl-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2- Thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-bromo- 1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)- 1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-[7-(trifluoromethyl)-1,5-dihydro-3H-2,4-benzodioxin- 3-yl]-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[ 4-(6,7,8,9-tetrafluoro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[ 5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(1-methyl-1,5-dihydro-3H- 2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl] Ethyl]piperidine, 4-[4-(6-methyl-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl) -2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(7 -methyl-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoro) Methyl)-1H-pyrazol-1-yl]acetamidine Piperidine, 4-[4-(6-butylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]- 1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazole- 1-yl]ethinyl]piperidine, 4-[4-(6-propylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)- 2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6- Chloro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl) -1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-bromo-9-methoxy-1,5-dihydro-3H-2,4-benzoic) Indole-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-octylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2- [5-Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-methoxy-9-methylsulfonyloxy) 1,2-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl) -1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(7-nitro-1,5-dihydro-3H-2,4-benzodioxin-3- 2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4- (6-isopropylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-A Base -3- (three Fluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(7-ethylsulfonyloxy-1,5-dihydro-3H-2,4-benzene And dioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazole- 1-yl]ethinyl]piperidine, 4-[4-[6-(1,1,1-trifluoropropan-3-yl)sulfonyloxy-1,5-dihydro-3H-2, 4-benzodioxin-3-yl]-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetamidine Piperidine, 4-[4-(1,5,7,8,9-pentahydro-3H-2,4-indolodioxin-3-yl)-2-thiazolyl]-1-[ 2-[5-Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-methylsulfonyloxy-9- Nitro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl) -1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-hydroxy-1,5-dihydro-3H-2,4-benzodioxin-3- 2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4- (6-Cyclopropylcarbonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl -3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-fluoro-1,5-dihydro-3H-2,4-benzene And dioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-[6-(Trifluoromethyl)sulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2-thiazolyl]-1 -[2-[5-methyl- 3-(3-trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-methoxycarbonyloxy-1,5-dihydro-3H-2 , 4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazole- 1-yl]ethinyl]piperidine, 4-[4-(6-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)- 2-thiazolyl]-1-[2-(2,5-dimethylphenyl)ethinyl]piperidine, 4-[4-(6-methylsulfonyloxy-1,5-dihydro -3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl Ethyl]piperidine, 4-[4-(6-fluoro-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl) -2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-A Oxy-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3, 5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(7-chloro-1,5-dihydro-3H-2,4-benzene Dioxan-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidin Pyridine, 4-[4-(6-fluoro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3, 5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-methylsulfonyloxy-1,5-dihydro-3H- 2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]acetamidine base] Acridine, 4-[4-(6-methylsulfonylamino-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1- [2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-Methyl-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]- 1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(7-fluoro-6-methylsulfonate) Oxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl) -1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-methoxy-9-nitro-1,5-dihydro-3H-2,4-benzene Dioxan-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidin Pyridine, 4-[4-(6-methylsulfonyl-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2 -[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-phenylsulfonyloxy-1,5 -dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyridyl Zin-1-yl]ethinyl]piperidine, 4-[4-(7-nitro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2- Thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6,9-difluoro -1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H -pyrazole-1-yl]B Piperidine, 4-[4-(6,9-difluoro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1- [2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-Hydroxymethyl-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5- Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-isopropylsulfonyloxy-1,5-dihydrol -3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl Ethyl]piperidine, 4-[4-(6-butylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazole 1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6,7,8,9 -tetrafluoro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl) -1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-phenyl-1,5-dihydro-3H-2,4-benzodioxin-3- 2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4- (6-Bromo-9-methoxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5 -Bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-chloro-1,5-dihydro-3H-2,4-benzo Diox-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4 -[4-(6-octylsulfonyloxy) Base-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)- 1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-[7-(Trifluoromethyl)-1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2-thiazolyl]-1-[2- [3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(1,5,7,8,9-pentahydro-3H- 2,4-indolodin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetamidine Piperidine, 4-[4-[6-(methoxyimino)methyl-1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2- Thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-methyl) Sulfomethoxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl) Ethyl]piperidine, 4-[4-(6-fluoro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[ 2-(2,5-dichlorophenyl)ethinyl]piperidine and 4-[4-(6,9-difluoro-1,5-dihydro-3H-2,4-benzodioxin Ind-3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl)ethinyl]piperidine.

(51)如(34)~(37)及(43)~(49)中任一項之製造方法，其中式[7]所表示之化合物為選自4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-乙基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氟-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二 噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-環丙基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-丁基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-丙基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-辛基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲氧基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-異丙基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁 呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-乙基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6-(1,1,1-三氟丙烷-3-基)磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-9-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6-(三氟甲基)磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氟-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲氧基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)- 1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-氟-6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-苯基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-異丙基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-丁基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-辛基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、 4-[4-(6,7-二甲基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氯-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-溴-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-異丙基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-丁基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氟-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6-(二甲基胺基磺醯氧基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-碘-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、 4-[4-(6-氯-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6,9-雙(甲基磺醯氧基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(3,5-二甲基-1H-吡唑-1-基)乙醯基]哌啶、4-[4-(6-甲氧基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-氯-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲氧基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(3,5-二氯-1H-吡唑-1-基)乙醯基]哌啶、4-[4-(6-甲氧基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(3,5-二甲基-1H-吡唑-1-基)乙醯基]哌啶、4-[4-(6-氯-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲氧基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、 4-[4-(6-氯-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氯甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氟-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(3,5-二甲基-1H-吡唑-1-基)乙醯基]哌啶、4-[4-(6,7-二甲基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6,7-二甲基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-溴-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-9-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-溴-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、 4-[4-(6-甲基磺醯氧基-9-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-碘-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-碘-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-氟-6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-氟-6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6-(二氟甲氧基)-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、 4-[4-[6,9-雙(甲基磺醯氧基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6,9-雙(甲基磺醯氧基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氟-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氟-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-丁基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-氟-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6-甲氧基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6-甲氧基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯- 3-基)-2-噻唑基]-1-[2-[2,5-雙(三氟甲基)苯基]乙醯基]哌啶、4-[4-(6,7-二甲基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6,7-二甲基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6-溴-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-9-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6-溴-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-9-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-氯-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-碘-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二 噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-氯-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(7-氟-6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(7-氟-6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6-碘-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(7-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、及4-[4-[6,9-雙(甲基磺醯氧基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶。 (51) The production method according to any one of (34) to (37), wherein the compound represented by the formula [7] is selected from the group consisting of 4-[4-(6-methylsulfonate).醯oxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoro) Methyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-ethylsulfonyloxy-1,5-dihydro-3H-2,4-benzoxyl) Dioxan-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine 4-[4-(6-fluoro-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzoic acid Indole-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(7-Methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2- [5-Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-cyclopropylsulfonyloxy-1,5 -dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyridyl Zin-1-yl]ethinyl]piperidine, 4-[4-(6-methyl-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin Ind-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4 -[4-(6-butylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[ 5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-propylsulfonyloxy-1,5-di Hydrogen-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazole- 1-yl]ethinyl]piperidine, 4-[4-(6-octylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)- 2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-( 6-methoxy-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2- [5-Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-isopropylsulfonyloxy-1,5 -dihydro-3H-2,4-benzodioxin Ind-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4 -[4-(7-ethylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[ 5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-[6-(1,1,1-trifluoropropane-3) -yl)sulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2-thiazolyl]-1-[2-[5-methyl-3 -(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-methylsulfonyloxy-9-nitro-1,5-dihydro -3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazole-1 -yl]ethinyl]piperidine, 4-[4-[6-(trifluoromethyl)sulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3- 4-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4- (6-Methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5- Dimethylphenyl)ethinyl]piperidine, 4-[4-(6-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl )-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6- -9-Methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5- Bis(difluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-methoxy-9-methylsulfonyloxy-1,5-di Hydrogen-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)- 1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin- 3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4- (6-Methyl-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2- [3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(7-fluoro-6-methylsulfonyloxy-1, 5-Dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H- Pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-phenylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3- 2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4- (6-isopropylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5 -Bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-butylsulfonyloxy-1,5-dihydro-3H-2 , 4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl Piperidine, 4-[4-(6-octylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazide 1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-methylsulfonyloxy) 1,2-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl)ethenyl Piperidine 4-[4-(6,7-Dimethyl-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazole 1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-chloro-9) -methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3 -(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-bromo-9-methylsulfonyloxy-1,5-dihydro- 3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazole-1- 4-[4-(6-isopropylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2 -thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-butylsulfonate)醯oxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl) -1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-fluoro-9-methylsulfonyloxy-1,5-dihydro-3H-2,4- Benzodioxa-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine 4-[4-[6-(Dimethylaminosulfonyloxy)-1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2-thiazole 1-[2-[5-Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-iodo-9-- Sulfosulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-( Trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-Chloro-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1 -[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-[6,9-bis(methylsulfonate)醯oxy)-1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2-thiazolyl]-1-[2-[5-methyl-3-(three Fluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzene And dioxin-3-yl)-2-thiazolyl]-1-[2-(3,5-dimethyl-1H-pyrazol-1-yl)ethenyl]piperidine, 4-[4 -(6-methoxy-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[ 2-[5-chloro-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-methoxy-9-methylsulfonate) Oxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(3,5-dichloro-1H-pyrazole -1-yl)ethinyl]piperidine, 4-[4-(6-methoxy-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin Ind-3-yl)-2-thiazolyl]-1-[2-(3,5-dimethyl-1H-pyrazol-1-yl)ethenyl]piperidine, 4-[4-(6 -chloro-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3, 5-double (two Methyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-methoxy-9-methylsulfonyloxy-1,5-dihydro-3H- 2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]acetamidine Pipipyridine 4-[4-(6-Chloro-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1 -[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-methylsulfonyloxy-1, 5-Dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(dichloromethyl)-1H-pyrazole -1-yl]ethinyl]piperidine, 4-[4-(6-fluoro-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin- 3-yl)-2-thiazolyl]-1-[2-(3,5-dimethyl-1H-pyrazol-1-yl)ethenyl]piperidine, 4-[4-(6,7 -Dimethyl-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[ 3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6,7-dimethyl-9-methylsulfonyloxy) -1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H -pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-bromo-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzoic acid Ester-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4- [4-(6-Methylsulfonyloxy-9-nitro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1- [2-[3, 5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-bromo-9-methylsulfonyloxy-1,5-di Hydrogen-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazole-1- Ethyl]piperidine, 4-[4-(6-Methylsulfonyloxy-9-nitro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]- 1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-iodo-9-methylsulfonate) Oxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl) -1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-iodo-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzene And dioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(7-fluoro-6-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1 -[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(7-fluoro-6-methylsulfonyloxy) Base-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)- 1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(7-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin- 3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4- (7-Methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5- Bis(trifluoro -1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-[6-(difluoromethoxy)-9-methylsulfonyloxy-1,5-dihydro -3H-2,4-benzodioxin-3-yl]-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazole-1 -yl]ethinyl]piperidine, 4-[4-[6,9-bis(methylsulfonyloxy)-1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2-thiazolyl]- 1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-[6,9-bis(methylsulfonate) Oxy)-1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl) -1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-fluoro-9-methylsulfonyloxy-1,5-dihydro-3H-2,4- Benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(difluoromethyl)-1H-pyrazol-1-yl]ethenyl] Piperidine, 4-[4-(6-fluoro-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl ]-1-[2-(2,5-Dimethylphenyl)ethinyl]piperidine, 4-[4-(6-butylsulfonyloxy-1,5-dihydro-3H-2 , 4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dimethylphenyl)ethinyl]piperidine, 4-[4-(6 -fluoro-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2, 5-dichlorophenyl)ethinyl]piperidine, 4-[4-(6-methoxy-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzo Diox-3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl)ethinyl]piperidine, 4-[4-(6-methoxy-9 - Sulfosulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dimethylbenzene Ethyl)piperidinyl, 4-[4-(6-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin- 3-yl)-2-thiazolyl]-1-[2-[2,5-bis(trifluoromethyl)phenyl]ethinyl]piperidine, 4-[4-(6,7-dimethyl 9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5 -Dimethylphenyl)ethinyl]piperidine, 4-[4-(6,7-dimethyl-9-methylsulfonyloxy-1,5-dihydro-3H-2,4- Benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl)ethinyl]piperidine, 4-[4-(6-bromo-9 -methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dimethyl Phenyl)ethinyl]piperidine, 4-[4-(6-methylsulfonyloxy-9-nitro-1,5-dihydro-3H-2,4-benzodioxin- 3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl)ethinyl]piperidine, 4-[4-(6-bromo-9-methylsulfonyloxy) 1,2-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl)ethenyl Piperidine, 4-[4-(6-methylsulfonyloxy-9-nitro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2- Thiazolyl]-1-[2-(2,5-dimethylphenyl)ethinyl]piperidine, 4-[4-(6-chloro-9-methylsulfonyloxy-1,5- Dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dimethylphenyl)ethenyl Piperidine, 4-[4-(6-iodo-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzoic) Ester-3-yl)-2-thiazolyl]-1-[2-(2,5-dimethylphenyl)ethinyl]piperidine, 4-[4-(6-chloro-9-methyl Sulfosulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl) Ethyl)piperidine, 4-[4-(7-fluoro-6-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl) -2-thiazolyl]-1-[2-(2,5-dimethylphenyl)ethinyl]piperidine, 4-[4-(7-fluoro-6-methylsulfonyloxy-1 ,5-Dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl)ethinyl]piperidine 4-[4-(6-Iodo-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]- 1-[2-(2,5-dichlorophenyl)ethinyl]piperidine, 4-[4-(7-methylsulfonyloxy-1,5-dihydro-3H-2,4- Benzodioxa-3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl)ethinyl]piperidine, and 4-[4-[6,9- Bis(methylsulfonyloxy)-1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2-thiazolyl]-1-[2-(2,5- Dimethylphenyl)ethinyl]piperidine.

(52)如(34)~(37)及(43)~(49)中任一項之製造方法，其中式[7]所表示之化合物為選自4-[4-(6,7-二甲基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、 4-[4-(6-氯-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-溴-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-異丙基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-丁基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6-(氯甲基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲醯基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6-(2,2-二甲基亞肼基)甲基-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6-(氰基甲基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、 4-[4-(6-苯基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲氧基-9-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(1-甲基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(1,5-二氫-3H-2,4-萘并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-第三丁基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-第三丁基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、 4-[4-[7-(三氟甲基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-溴-9-甲氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲氧基-9-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6,7,8,9-四氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6-(三氟甲氧基)-9-甲氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氟-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(1-甲基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、 4-[4-(1,5-二氫-3H-2,4-萘并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6-(二甲基胺基磺醯氧基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-第三丁基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氯-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6-(二氟甲氧基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6-(羥基亞胺基)甲基-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、 4-[4-[6-(二氟甲基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-溴-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-溴-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6,9-二溴-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-碘-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氯-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6,9-雙(甲基磺醯氧基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氰基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、 4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(3,5-二甲基-1H-吡唑-1-基)乙醯基]哌啶、4-[4-(6-甲氧基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-氯-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲氧基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(3,5-二氯-1H-吡唑-1-基)乙醯基]哌啶、4-[4-(6-氯-9-甲氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-溴-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氯-9-甲氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-溴-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、 4-[4-(6-甲氧基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(3,5-二甲基-1H-吡唑-1-基)乙醯基]哌啶、4-[4-(6-氯-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲氧基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氯-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氯甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氟-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(3,5-二甲基-1H-吡唑-1-基)乙醯基]哌啶、4-[4-(6,7-二甲基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6,7-二甲基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、 4-[4-(6-溴-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-9-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-溴-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-9-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-碘-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-碘-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-氟-6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、 4-[4-(7-氟-6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氟-9-甲氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲氧基-9-甲基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6-(二氟甲氧基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6-(二氟甲氧基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(7-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、 4-[4-(6-甲氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-甲氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氟-9-甲氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6-(二氟甲氧基)-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-乙醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6-(羥基亞胺基)甲基-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6,9-雙(甲基磺醯氧基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6,9-雙(甲基磺醯氧基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、 4-[4-(6-氰基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-[6-(羥基亞胺基)甲基-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氰基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氟-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6-氟-9-羥基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶、4-[4-(6,9-二氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-氟-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-甲氧基-9-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌 啶、4-[4-(7-氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-丁基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(1-甲基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-氟-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6-溴-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(7-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-溴-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6-氯-9-甲氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(7-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6-氯-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、 4-[4-(6-氯-9-甲氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6-溴-9-甲氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-溴-9-甲氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6-甲氧基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6,7,8,9-四氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-甲氧基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6,7,8,9-四氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[2,5-雙(三氟甲基)苯基]乙醯基]哌啶、4-[4-(6,7-二甲基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6,7-二甲基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯 基]哌啶、4-[4-(6-溴-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-9-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6-溴-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6-甲基磺醯氧基-9-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-氯-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-硝基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-碘-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-氯-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二 噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(7-氟-6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(7-氟-6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6-碘-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6-甲氧基-9-甲基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-(6-甲氧基-9-甲基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-[6-(二氟甲氧基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、4-[4-[6-(二氟甲氧基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(7-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6-甲氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、 4-[4-(6-甲氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶、4-[4-(6-氟-9-甲氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶、及4-[4-[6,9-雙(甲基磺醯氧基)-1,5-二氫-3H-2,4-苯并二噁呯-3-基]-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯基]哌啶。 (52) The production method according to any one of (34) to (37), wherein the compound represented by the formula [7] is selected from the group consisting of 4-[4-(6,7-di) Methyl-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5- Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-Chloro-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1 -[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-bromo-9-methylsulfonate)醯oxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoro) Methyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-isopropylsulfonyloxy-1,5-dihydro-3H-2,4-benzene And dioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-butylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2- [3,5-Bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-[6-(chloromethyl)-1,5-dihydro- 3H-2,4-benzodioxin-3-yl]-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazole-1- Benzyl]piperidinyl, 4-[4-(6-methylindolyl-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl] 1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-[6-(2,2- Dimethylindenyl)methyl-1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2-thiazolyl]-1-[2-[5-methyl -3-(trifluoromethyl) -1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-[6-(cyanomethyl)-1,5-dihydro-3H-2,4-benzodioxin Ind-3-yl]-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-phenyl-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5 -Bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-methoxy-9-nitro-1,5-dihydro-3H -2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]B Mercapto] piperidine, 4-[4-(1-methyl-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[ 2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(1,5-dihydro-3H-2,4- Benzodioxa-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine 4-[4-(1,5-Dihydro-3H-2,4-naphthodioxan-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(di) Fluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(7-tert-butyl-1,5-dihydro-3H-2,4-benzoic acid Ester-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4- [4-(7-Tertibutyl-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-A 3-(3-trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(7-fluoro-1,5-dihydro-3H-2,4- Benzodioxa-3-yl)-2-thiazolyl]- 1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-[7-(Trifluoromethyl)-1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2-thiazolyl]-1-[2- [3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-bromo-9-methoxy-1,5-di Hydrogen-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazole-1- Benzyl]piperidinyl, 4-[4-(6-methoxy-9-nitro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)- 2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6,7, 8,9-tetrafluoro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(three Fluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(1,5-dihydro-3H-2,4-benzodioxin-3-yl) -2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-[6-( Trifluoromethoxy)-9-methoxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2-thiazolyl]1-[2-[5- Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-fluoro-9-methylsulfonyloxy-1,5 -dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazole- 1-yl]ethinyl]piperidine, 4-[4-( 1-methyl-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl) -1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(1,5-Dihydro-3H-2,4-naphthodioxan-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoro) Methyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-[6-(dimethylaminosulfonyloxy)-1,5-dihydro-3H-2 , 4-benzodioxin-3-yl]-2-thiazolyl]1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetamidine Piperidine, 4-[4-(7-fluoro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2- [3,5-Bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(7-tert-butyl-1,5-dihydro-3H -2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]B Mercapto] piperidine, 4-[4-(6-chloro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2 -[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-[6-(difluoromethoxy)-1,5- Dihydro-3H-2,4-benzodioxin-3-yl]-2-thiazolyl]1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazole- 1-yl]ethinyl]piperidine, 4-[4-(7-nitro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl ]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-[6-(hydroxyimino) Methyl-1,5-dihydro-3H -2,4-benzodioxin-3-yl]-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl Ethyl]piperidine, 4-[4-[6-(Difluoromethyl)-1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2-thiazolyl]-1-[2- [5-Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(7-bromo-1,5-dihydro-3H- 2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl] Ethyl]piperidine, 4-[4-(7-bromo-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[ 2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6,9-dibromo-1,5-dihydro -3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazole-1 -yl]ethinyl]piperidine, 4-[4-(6-iodo-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3- 2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4- (6-Chloro-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[ 5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-[6,9-bis(methylsulfonyloxy)- 1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)- 1H-pyrazol-1-yl]ethenyl] Acridine, 4-[4-(6-cyano-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5 -methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-Methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2- (3,5-Dimethyl-1H-pyrazol-1-yl)ethinyl]piperidine, 4-[4-(6-methoxy-9-methylsulfonyloxy-1,5- Dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-chloro-3-(trifluoromethyl)-1H-pyrazole- 1-yl]ethinyl]piperidine, 4-[4-(6-methoxy-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin 3-yl)-2-thiazolyl]-1-[2-(3,5-dichloro-1H-pyrazol-1-yl)ethenyl]piperidine, 4-[4-(6-chloro -9-methoxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(three Fluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-bromo-1,5-dihydro-3H-2,4-benzodioxin)- 3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4- (6-chloro-9-methoxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5 -Bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-bromo-1,5-dihydro-3H-2,4-benzo) Diox-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4 -[4-(6-nitro-1,5-two Hydrogen-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazole-1- Ethyl]piperidine, 4-[4-(6-Methoxy-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl] 1-[2-(3,5-dimethyl-1H-pyrazol-1-yl)ethenyl]piperidine, 4-[4-(6-chloro-9-methylsulfonyloxy)- 1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H- Pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-methoxy-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzoxyl) Diox-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4 -[4-(6-chloro-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1- [2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-methylsulfonyloxy-1,5 -dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(dichloromethyl)-1H-pyrazole- 1-yl]ethinyl]piperidine, 4-[4-(6-fluoro-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3 -yl)-2-thiazolyl]-1-[2-(3,5-dimethyl-1H-pyrazol-1-yl)ethenyl]piperidine, 4-[4-(6,7- Dimethyl-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3 , 5-double ( Fluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6,7-dimethyl-9-methylsulfonyloxy-1,5-dihydrol -3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl Ethyl]piperidine, 4-[4-(6-Bromo-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1 -[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-methylsulfonyloxy-9- Nitro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl) -1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-bromo-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzene And dioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-nitro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5 -Bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-methylsulfonyloxy-9-nitro-1,5-di Hydrogen-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazole-1- 4-[4-(6-iodo-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl) )-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6- Iodine-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5 - double (difluorocarbon) -1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(7-fluoro-6-methylsulfonyloxy-1,5-dihydro-3H-2,4- Benzodioxa-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine , 4-[4-(7-fluoro-6-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1 -[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-fluoro-9-methoxy-1 ,5-Dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H -pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-methoxy-9-methyl-1,5-dihydro-3H-2,4-benzodioxin 3-yl)-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4 -(6-methoxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3 -(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-[6-(difluoromethoxy)-1,5-dihydro-3H-2 , 4-benzodioxin-3-yl]-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl Piperidine, 4-[4-[6-(difluoromethoxy)-1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2-thiazolyl]- 1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(7-methylsulfonyloxy-1 ,5-Dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyridyl Zin-1-yl]ethinyl] Acridine, 4-[4-(7-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[ 2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-methoxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3, 5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-methoxy-1,5-dihydro-3H-2,4 -benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidin Acridine, 4-[4-(6-fluoro-9-methoxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1- [2-[3,5-Bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-[6-(difluoromethoxy)-9- Methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2-thiazolyl]-1-[2-[5-methyl-3- (trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-acetoxy-1,5-dihydro-3H-2,4-benzene Dioxan-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidin Acridine, 4-[4-[6-(hydroxyimino)methyl-1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2-thiazolyl]-1 -[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-[6,9-bis(methylsulfonate) -1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl) -1H-pyrazole-1- Ethyl]piperidine, 4-[4-[6,9-bis(methylsulfonyloxy)-1,5-dihydro-3H-2,4-benzodioxin-3-yl ]-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-Cyano-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[3,5 -Bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-[6-(hydroxyimino)methyl-1,5-dihydro-3H -2,4-benzodioxin-3-yl]-2-thiazolyl]-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]B Mercapto] piperidine, 4-[4-(6-cyano-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[ 2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine, 4-[4-(6-fluoro-9-methylsulfonyloxy)- 1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[5-methyl-3-(difluoromethyl)- 1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4-(6-fluoro-9-hydroxy-1,5-dihydro-3H-2,4-benzodioxin-3 -yl)-2-thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine, 4-[4 -(6,9-difluoro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-di Methylphenyl)ethinyl]piperidine, 4-[4-(6-fluoro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl 1-[2-(2,5-Dimethylphenyl)ethinyl]piperidine, 4-[4-(6-fluoro-9-methylsulfonyloxy-1,5-dihydro) -3H-2,4-benzodioxin 3-yl)-2-thiazolyl]-1-[2-(2,5-dimethylphenyl)ethinyl]piperidine, 4-[4-(6-methoxy-9-nitro Base-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dimethylphenyl)acetamidine Base Pyridine, 4-[4-(7-fluoro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2, 5-dimethylphenyl)ethinyl]piperidine, 4-[4-(1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl] 1-[2-(2,5-dimethylphenyl)ethenyl]piperidine, 4-[4-(6-butylsulfonyloxy-1,5-dihydro-3H-2, 4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dimethylphenyl)ethinyl]piperidine, 4-[4-(1- Methyl-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dimethylphenyl) Mercapto] piperidine, 4-[4-(6-fluoro-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2 -thiazolyl]-1-[2-(2,5-dichlorophenyl)ethinyl]piperidine, 4-[4-(6-bromo-1,5-dihydro-3H-2,4- Benzodioxa-3-yl)-2-thiazolyl]-1-[2-(2,5-dimethylphenyl)ethinyl]piperidine, 4-[4-(7-nitro -1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dimethylphenyl)ethenyl Piperidine, 4-[4-(6-bromo-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-( 2,5-Dichlorophenyl)ethinyl]piperidine, 4-[4-(6-chloro-9-methoxy-1,5-dihydro-3H-2,4-benzodioxin -3-yl)-2-thiazolyl ]-1-[2-(2,5-Dimethylphenyl)ethinyl]piperidine, 4-[4-(7-nitro-1,5-dihydro-3H-2,4-benzene And dioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl)ethinyl]piperidine, 4-[4-(6-chloro-1, 5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl)ethinyl]piperidine, 4-[4-(6-chloro-9-methoxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2 -(2,5-dichlorophenyl)ethinyl]piperidine, 4-[4-(6-bromo-9-methoxy-1,5-dihydro-3H-2,4-benzoic acid Ester-3-yl)-2-thiazolyl]-1-[2-(2,5-dimethylphenyl)ethinyl]piperidine, 4-[4-(6-bromo-9-methyl) Oxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl)acetamidine Piperidine, 4-[4-(6-methoxy-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)- 2-thiazolyl]-1-[2-(2,5-dichlorophenyl)ethinyl]piperidine, 4-[4-(6,7,8,9-tetrafluoro-1,5-di Hydrogen-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dimethylphenyl)ethinyl]piperidine, 4- [4-(6-Methoxy-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1 -[2-(2,5-dimethylphenyl)ethinyl]piperidine, 4-[4-(6,7,8,9-tetrafluoro-1,5-dihydro-3H-2, 4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl)ethinyl]piperidine, 4-[4-(6-A Sulfosulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-[2,5-bis(trifluoro) Methyl)phenyl]ethenyl] Pyridine, 4-[4-(6,7-dimethyl-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2 -thiazolyl]-1-[2-(2,5-dimethylphenyl)ethinyl]piperidine, 4-[4-(6,7-dimethyl-9-methylsulfonyloxy) -1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl)acetamidine Piperidine, 4-[4-(6-bromo-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2- Thiazolyl]-1-[2-(2,5-dimethylphenyl)ethinyl]piperidine, 4-[4-(6-methylsulfonyloxy-9-nitro-1,5 -dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl)ethinyl]piperidine, 4 -[4-(6-Bromo-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1- [2-(2,5-Dichlorophenyl)ethinyl]piperidine, 4-[4-(6-nitro-1,5-dihydro-3H-2,4-benzodioxin)- 3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl)ethinyl]piperidine, 4-[4-(6-methylsulfonyloxy-9- Nitro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dimethylphenyl) Mercapto] piperidine, 4-[4-(6-chloro-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2 -thiazolyl]-1-[2-(2,5-dimethylphenyl)ethinyl]piperidine, 4-[4-(6-nitro-1,5-dihydro-3H-2, 4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dimethylphenyl)ethinyl]piperidine, 4-[4-(6- Iodine-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5 -two Phenyl) acetyl] piperidine, 4- [4- (6-chloro-9-methyl-1,5-dihydro-sulfonylurea -3H-2,4- benzodiazepin Ester-3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl)ethinyl]piperidine, 4-[4-(7-fluoro-6-methyl Sulfomethoxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dimethylphenyl) Ethyl)piperidine, 4-[4-(7-fluoro-6-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl) -2-thiazolyl]-1-[2-(2,5-dichlorophenyl)ethinyl]piperidine, 4-[4-(6-iodo-9-methylsulfonyloxy-1, 5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl)ethinyl]piperidine, 4-[4-(6-methoxy-9-methyl-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[ 2-(2,5-dimethylphenyl)ethinyl]piperidine, 4-[4-(6-methoxy-9-methyl-1,5-dihydro-3H-2,4- Benzo diepin-3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl)ethinyl]piperidine, 4-[4-[6-(difluoro Methoxy)-1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2-thiazolyl]-1-[2-(2,5-dimethylphenyl) Ethyl)piperidine, 4-[4-[6-(difluoromethoxy)-1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2- Thiazolyl]-1-[2-(2,5-dichlorophenyl)ethinyl]piperidine, 4-[4-(7-methylsulfonyloxy-1,5-dihydro-3H- 2,4- Benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dichlorophenyl)ethinyl]piperidine, 4-[4-(6-methoxy -1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2,5-dimethylphenyl)ethenyl Piperidine 4-[4-(6-Methoxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1-[2-(2, 5-dichlorophenyl)ethinyl]piperidine, 4-[4-(6-fluoro-9-methoxy-1,5-dihydro-3H-2,4-benzodioxin-3 -yl)-2-thiazolyl]-1-[2-(2,5-dimethylphenyl)ethinyl]piperidine, and 4-[4-[6,9-bis(methylsulfonate) Oxy)-1,5-dihydro-3H-2,4-benzodioxin-3-yl]-2-thiazolyl]-1-[2-(2,5-dimethylphenyl) Ethyl] piperidine.

以下，詳細說明關於本發明。 Hereinafter, the present invention will be described in detail.

式[1]係賦予藉由本發明而能調製之4-(4-甲醯基噻唑基)哌啶化合物之一般定義。上述及下述所示之關於式之基之理想定義係記載如以下。此種定義係適用於式[1]所表示之最終生成物，及，同樣地亦適用於全部之中間體。 The formula [1] imparts a general definition of a 4-(4-carbamoylthiazolyl)piperidine compound which can be prepared by the present invention. The ideal definitions of the bases of the above formulas shown below and below are described below. This definition applies to the final product represented by the formula [1], and the same applies to all the intermediates.

A係較佳為A-1或R8，更佳為A-1。 The A system is preferably A-1 or R 8 , more preferably A-1.

R1及R2係各自獨立較佳為C1~C6烷基、C1~C6鹵烷基、或鹵素原子，更佳為甲基、三氟甲基、二氟甲基、或氯原子。 R 1 and R 2 each independently are preferably a C 1 -C 6 alkyl group, a C 1 -C 6 haloalkyl group, or a halogen atom, more preferably a methyl group, a trifluoromethyl group, a difluoromethyl group or a chlorine group. atom.

R4、R5及R7係較佳為氫原子。 R 4 , R 5 and R 7 are preferably a hydrogen atom.

R3及R6係各自獨立較佳為氫原子、鹵素原子、C1~C6烷基或C1~C6鹵烷基，更佳為氫原子、氯原子、三氟甲基或甲基。 R 3 and R 6 each independently are preferably a hydrogen atom, a halogen atom, a C 1 -C 6 alkyl group or a C 1 -C 6 haloalkyl group, more preferably a hydrogen atom, a chlorine atom, a trifluoromethyl group or a methyl group. .

R8係較佳為C2~C6烷基羰基、苄基、苯基羰基、 C2~C6烷氧基羰基，更佳為乙醯基、苄基、苯基羰基、甲氧基羰基、乙氧基羰基、1,1-二甲基乙基氧基羰基或2,2-二甲基丙醯基。 R 8 is preferably a C 2 -C 6 alkylcarbonyl group, a benzyl group, a phenylcarbonyl group, a C 2 -C 6 alkoxycarbonyl group, more preferably an ethyl fluorenyl group, a benzyl group, a phenylcarbonyl group or a methoxycarbonyl group. Ethoxycarbonyl, 1,1-dimethylethyloxycarbonyl or 2,2-dimethylpropanyl.

R10係各自獨立較佳為甲基或乙基，更佳為甲基。 The R 10 groups are each independently preferably a methyl group or an ethyl group, more preferably a methyl group.

R11、R12、R13及R14係較佳為氫原子或甲基，更佳為氫原子。 R 11 , R 12 , R 13 and R 14 are preferably a hydrogen atom or a methyl group, more preferably a hydrogen atom.

X1、X2、X3及X4係各自獨立較佳為氫原子、鹵素原子、氰基、羥基、硝基、甲醯基、C1~C4烷基、C1~C4鹵烷基、C1~C4羥基烷基、C1~C4烷氧基、C1~C4鹵烷氧基、-SR15、-S(O)2R15、-OS(O)2R15、C2~C4烷基羰氧基、C2~C4烷氧基羰氧基、或-C(=NOR18)R19，更佳為X1、X2、X3及X4之中至少一個為-OS(O)2R15，特佳係為X1-OS(O)2R15，特佳係X2及X3為氫原子，特佳係X4為氫原子、硝基、鹵素原子、甲基、甲氧基、三氟甲基、二氟甲氧基、三氟甲氧基或-OS(O)2R15，最佳係X4為氫原子、硝基、甲基、氟原子或甲氧基。 X 1 , X 2 , X 3 and X 4 are each independently preferably a hydrogen atom, a halogen atom, a cyano group, a hydroxyl group, a nitro group, a decyl group, a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group. Base, C 1 -C 4 hydroxyalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, -SR 15 , -S(O) 2 R 15 , -OS(O) 2 R 15 , C 2 -C 4 alkylcarbonyloxy, C 2 -C 4 alkoxycarbonyloxy, or -C(=NOR 18 )R 19 , more preferably X 1 , X 2 , X 3 and X 4 At least one of them is -OS(O) 2 R 15 , particularly preferably X 1 -OS(O) 2 R 15 , and particularly preferably X 2 and X 3 are hydrogen atoms, and particularly preferred X 4 is a hydrogen atom. Nitro, halogen atom, methyl, methoxy, trifluoromethyl, difluoromethoxy, trifluoromethoxy or -OS(O) 2 R 15 , the most preferred group X 4 is a hydrogen atom, a nitro group , methyl, fluorine atom or methoxy group.

R15係各自獨立較佳為C1~C4烷基、環丙基或C1~C4鹵烷基，更佳為甲基。 The R 15 groups are each independently preferably a C 1 -C 4 alkyl group, a cyclopropyl group or a C 1 -C 4 haloalkyl group, more preferably a methyl group.

R18係較佳為氫原子或C1~C4烷基，更佳為氫原子或甲基。 R 18 is preferably a hydrogen atom or a C 1 -C 4 alkyl group, more preferably a hydrogen atom or a methyl group.

R19係較佳為氫原子或C1~C4烷基，更佳為氫原子或甲基。 R 19 is preferably a hydrogen atom or a C 1 -C 4 alkyl group, more preferably a hydrogen atom or a methyl group.

L1係較佳為氯原子或溴原子，更佳為溴原子。 L 1 is preferably a chlorine atom or a bromine atom, more preferably a bromine atom.

在一般範圍或較佳範圍中，上述所示之基之定義及說 明係因應必要亦能互相組合。即，亦能在個別之範圍與較佳範圍之間予以組合。此等係適用於最終生成物與對應於此之前驅物及中間體之兩者。 In the general scope or preferred range, the definition and description of the above-mentioned basis The Ming system can also be combined with each other as necessary. That is, it is also possible to combine between individual ranges and preferred ranges. These apply to both the final product and the corresponding precursors and intermediates.

較佳之1種態樣為式[1]{式中，A表示2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基}所表示之化合物。 A preferred aspect is the formula [1] wherein A represents 2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl} Compound.

較佳之其他態樣為式[1]{式中，A表示2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基}所表示之化合物。 Preferably, the other aspect is the formula [1] wherein A represents a compound represented by 2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl}.

較佳之其他態樣為式[1]{式中，A表示2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基}所表示之化合物。 A further preferred embodiment is the formula [1] wherein A represents a compound represented by 2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl}.

較佳之其他態樣為式[1]{式中，A表示2-(3,5-二甲基-1H-吡唑-1-基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [1] wherein A represents 2-(3,5-dimethyl-1H-pyrazol-1-yl)ethenyl}.

較佳之其他態樣為式[1]{式中，A表示2-(2,5-二甲基苯基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [1] wherein A represents 2-(2,5-dimethylphenyl)ethenyl}.

較佳之其他態樣為式[1]{式中，A表示2-(2,5-二氯苯基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [1] wherein A represents 2-(2,5-dichlorophenyl)ethenyl}.

較佳之其他態樣為式[1]{式中，A表示2-(2,5-二溴苯基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [1] wherein A represents 2-(2,5-dibromophenyl)ethenyl}.

較佳之其他態樣為式[1]{式中，A表示2-[2,5-雙(三氟甲基)苯基]乙醯基}所表示之化合物。 Preferably, the other aspect is the formula [1] wherein A represents a compound represented by 2-[2,5-bis(trifluoromethyl)phenyl]ethenyl}.

較佳之其他態樣為式[1]{式中，A表示2-(5-溴-2-甲基苯基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [1] wherein A represents 2-(5-bromo-2-methylphenyl)ethenyl}.

較佳之其他態樣為式[1]{式中，A表示2-[2-甲基-5-(三氟甲基)苯基]乙醯基}所表示之化合物。 Preferably, the other aspect is the formula [1] wherein A represents a compound represented by 2-[2-methyl-5-(trifluoromethyl)phenyl]ethenyl}.

較佳之其他態樣為式[1]{式中，A表示2-[2-氟-5- (三氟甲基)苯基]乙醯基}所表示之化合物。 Preferably, the other aspect is the formula [1] {wherein, A represents 2-[2-fluoro-5- A compound represented by (trifluoromethyl)phenyl]ethenyl}.

較佳之其他態樣為式[1]{式中，A表示2-[2-氯-5-(三氟甲基)苯基]乙醯基}所表示之化合物。 Preferably, the other aspect is the formula [1] wherein A represents a compound represented by 2-[2-chloro-5-(trifluoromethyl)phenyl]ethenyl}.

較佳之其他態樣為式[1]{式中，A表示2-[2-溴-5-(三氟甲基)苯基]乙醯基}所表示之化合物。 Preferably, the other aspect is the formula [1] wherein A represents a compound represented by 2-[2-bromo-5-(trifluoromethyl)phenyl]ethenyl}.

較佳之其他態樣為式[1]{式中，A表示乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [1] wherein A represents an ethyl hydrazide.

較佳之其他態樣為式[1]{式中，A表示苄基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [1] wherein A represents a benzyl group.

較佳之其他態樣為式[1]{式中，A表示苯基羰基}所表示之化合物。 The other preferred embodiment is a compound represented by the formula [1] {wherein A represents a phenylcarbonyl group}.

較佳之其他態樣為式[1]{式中，A表示甲氧基羰基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [1] {wherein A represents a methoxycarbonyl group}.

較佳之其他態樣為式[1]{式中，A表示乙氧基羰基}所表示之化合物。 The other preferred embodiment is a compound represented by the formula [1] {wherein A represents an ethoxycarbonyl group}.

較佳之其他態樣為式[1]{式中，A表示1,1-二甲基乙基氧基羰基}所表示之化合物。 The other preferred embodiment is a compound represented by the formula [1] {wherein A represents 1,1-dimethylethyloxycarbonyl}.

較佳之其他態樣為式[1]{式中，A表示2,2-二甲基丙醯基}所表示之化合物。 Other preferred embodiments are those represented by the formula [1] {wherein A represents 2,2-dimethylpropenyl}.

較佳之1種態樣為式[5]{式中，A表示2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基}所表示之化合物。 A preferred aspect is the formula [5] where A represents 2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl} Compound.

較佳之其他態樣為式[5]{式中，A表示2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基}所表示之化合物。 A further preferred embodiment is the formula [5] wherein A represents a compound represented by 2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl}.

較佳之其他態樣為式[5]{式中，A表示2-[3,5-雙(二 氟甲基)-1H-吡唑-1-基]乙醯基}所表示之化合物。 Preferably, the other aspect is the formula [5] {where A represents 2-[3,5-double (two A compound represented by fluoromethyl)-1H-pyrazol-1-yl]ethenyl}.

較佳之其他態樣為式[5]{式中，A表示2-(3,5-二甲基-1H-吡唑-1-基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5] wherein A represents 2-(3,5-dimethyl-1H-pyrazol-1-yl)ethenyl}.

較佳之其他態樣為式[5]{式中，A表示2-(2,5-二甲基苯基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5] wherein A represents 2-(2,5-dimethylphenyl)ethenyl}.

較佳之其他態樣為式[5]{式中，A表示2-(2,5-二氟苯基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5] wherein A represents 2-(2,5-difluorophenyl)ethenyl}.

較佳之其他態樣為式[5]{式中，A表示2-(2,5-二氯苯基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5] wherein A represents 2-(2,5-dichlorophenyl)ethenyl}.

較佳之其他態樣為式[5]{式中，A表示2-(2,5-二溴苯基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5] wherein A represents 2-(2,5-dibromophenyl)ethenyl}.

較佳之其他態樣為式[5]{式中，A表示2-[2,5-雙(三氟甲基)苯基]乙醯基}所表示之化合物。 Preferably, the other aspect is the formula [5] wherein A represents a compound represented by 2-[2,5-bis(trifluoromethyl)phenyl]ethenyl}.

較佳之其他態樣為式[5]{式中，A表示2-(5-溴-2-甲基苯基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5] wherein A represents 2-(5-bromo-2-methylphenyl)ethenyl}.

較佳之其他態樣為式[5]{式中，A表示2-[2-甲基-5-(三氟甲基)苯基]乙醯基}所表示之化合物。 A further preferred embodiment is the formula [5] wherein A represents a compound represented by 2-[2-methyl-5-(trifluoromethyl)phenyl]ethenyl}.

較佳之其他態樣為式[5]{式中，A表示2-[2-氟-5-(三氟甲基)苯基]乙醯基}所表示之化合物。 A further preferred embodiment is the formula [5] wherein A represents a compound represented by 2-[2-fluoro-5-(trifluoromethyl)phenyl]ethenyl}.

較佳之其他態樣為式[5]{式中，A表示2-[2-氯-5-(三氟甲基)苯基]乙醯基}所表示之化合物。 A further preferred embodiment is the formula [5] wherein A represents a compound represented by 2-[2-chloro-5-(trifluoromethyl)phenyl]ethenyl}.

較佳之其他態樣為式[5]{式中，A表示2-[2-溴-5-(三氟甲基)苯基]乙醯基}所表示之化合物。 A further preferred embodiment is the formula [5] wherein A represents a compound represented by 2-[2-bromo-5-(trifluoromethyl)phenyl]ethenyl}.

較佳之其他態樣為式[5]{式中，A表示乙醯基}所表示 之化合物。 Preferably, the other aspect is represented by the formula [5] {wherein, A represents an ethyl group} Compound.

較佳之其他態樣為式[5]{式中，A表示苄基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5] wherein A represents a benzyl group.

較佳之其他態樣為式[5]{式中，A表示苯基羰基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5] wherein A represents a phenylcarbonyl group.

較佳之其他態樣為式[5]{式中，A表示甲氧基羰基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5] wherein A represents a methoxycarbonyl group.

較佳之其他態樣為式[5]{式中，A表示乙氧基羰基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5] wherein A represents an ethoxycarbonyl group.

較佳之其他態樣為式[5]{式中，A表示1,1-二甲基乙基氧基羰基}所表示之化合物。 The other preferred embodiment is a compound represented by the formula [5] wherein A represents 1,1-dimethylethyloxycarbonyl}.

較佳之其他態樣為式[5]{式中，A表示2,2-二甲基丙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5] wherein A represents 2,2-dimethylpropionyl}.

較佳之1種態樣為式[5a]{式中，A表示2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基}所表示之化合物。 A preferred aspect is the formula [5a] wherein A represents 2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl} Compound.

較佳之其他態樣為式[5a]{式中，A表示2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基}所表示之化合物。 A further preferred embodiment is the formula [5a] wherein A represents a compound represented by 2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl}.

較佳之其他態樣為式[5a]{式中，A表示2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基}所表示之化合物。 A further preferred embodiment is the formula [5a] wherein A represents a compound represented by 2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl}.

較佳之其他態樣為式[5a]{式中，A表示2-(3,5-二甲基-1H-吡唑-1-基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5a] wherein A represents 2-(3,5-dimethyl-1H-pyrazol-1-yl)ethenyl}.

較佳之其他態樣為式[5a]{式中，A表示2-(2,5-二甲基苯基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5a] wherein A represents 2-(2,5-dimethylphenyl)ethenyl}.

較佳之其他態樣為式[5a]{式中，A表示2-(2,5-二氟 苯基)乙醯基}所表示之化合物。 Preferably, the other aspect is the formula [5a] {wherein, A represents 2-(2,5-difluoro A compound represented by phenyl)ethenyl}.

較佳之其他態樣為式[5a]{式中，A表示2-(2,5-二氯苯基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5a] wherein A represents 2-(2,5-dichlorophenyl)ethenyl}.

較佳之其他態樣為式[5a]{式中，A表示2-(2,5-二溴苯基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5a] wherein A represents 2-(2,5-dibromophenyl)ethenyl}.

較佳之其他態樣為式[5a]{式中，A表示2-[2,5-雙(三氟甲基)苯基]乙醯基}所表示之化合物。 A further preferred embodiment is the formula [5a] wherein A represents a compound represented by 2-[2,5-bis(trifluoromethyl)phenyl]ethenyl}.

較佳之其他態樣為式[5a]{式中，A表示2-(5-溴-2-甲基苯基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5a] wherein A represents 2-(5-bromo-2-methylphenyl)ethenyl}.

較佳之其他態樣為式[5a]{式中，A表示2-[2-甲基-5-(三氟甲基)苯基]乙醯基}所表示之化合物。 A further preferred embodiment is the formula [5a] wherein A represents a compound represented by 2-[2-methyl-5-(trifluoromethyl)phenyl]ethenyl}.

較佳之其他態樣為式[5a]{式中，A表示2-[2-氟-5-(三氟甲基)苯基]乙醯基}所表示之化合物。 A further preferred embodiment is the formula [5a] wherein A represents a compound represented by 2-[2-fluoro-5-(trifluoromethyl)phenyl]ethenyl}.

較佳之其他態樣為式[5a]{式中，A表示2-[2-氯-5-(三氟甲基)苯基]乙醯基}所表示之化合物。 A further preferred embodiment is the formula [5a] wherein A represents a compound represented by 2-[2-chloro-5-(trifluoromethyl)phenyl]ethenyl}.

較佳之其他態樣為式[5a]{式中，A表示2-[2-溴-5-(三氟甲基)苯基]乙醯基}所表示之化合物。 A further preferred embodiment is the formula [5a] wherein A represents a compound represented by 2-[2-bromo-5-(trifluoromethyl)phenyl]ethenyl}.

較佳之其他態樣為式[5a]{式中，A表示乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5a] wherein A represents an ethyl group.

較佳之其他態樣為式[5a]{式中，A表示苄基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5a] wherein A represents a benzyl group.

較佳之其他態樣為式[5a]{式中，A表示苯基羰基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5a] {wherein A represents a phenylcarbonyl group}.

較佳之其他態樣為式[5a]{式中，A表示甲氧基羰基} 所表示之化合物。 Preferably, the other aspect is the formula [5a] {wherein A represents a methoxycarbonyl group} The compound represented.

較佳之其他態樣為式[5a]{式中，A表示乙氧基羰基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5a] {wherein A represents an ethoxycarbonyl group}.

較佳之其他態樣為式[5a]{式中，A表示1,1-二甲基乙基氧基羰基}所表示之化合物。 The other preferred embodiment is a compound represented by the formula [5a] {wherein A represents 1,1-dimethylethyloxycarbonyl}.

較佳之其他態樣為式[5a]{式中，A表示2,2-二甲基丙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [5a] {wherein A represents 2,2-dimethylpropenyl}.

較佳之1種態樣為式[7]{式中，A表示2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基}所表示之化合物。 A preferred aspect is the formula [7] where A represents 2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl} Compound.

較佳之其他態樣為式[7]{式中，A表示2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基}所表示之化合物。 Preferably, the other aspect is the formula [7] wherein A represents a compound represented by 2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl}.

較佳之其他態樣為式[7]{式中，A表示2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基}所表示之化合物。 Preferably, the other aspect is the formula [7] wherein A represents a compound represented by 2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl}.

較佳之其他態樣為式[7]{式中，A表示2-(3,5-二甲基-1H-吡唑-1-基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [7] wherein A represents 2-(3,5-dimethyl-1H-pyrazol-1-yl)ethenyl}.

較佳之其他態樣為式[7]{式中，A表示2-(2,5-二甲基苯基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [7] wherein A represents 2-(2,5-dimethylphenyl)ethenyl}.

較佳之其他態樣為式[7]{式中，A表示2-(2,5-二氟苯基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [7] wherein A represents 2-(2,5-difluorophenyl)ethenyl}.

較佳之其他態樣為式[7]{式中，A表示2-(2,5-二氯苯基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [7] wherein A represents 2-(2,5-dichlorophenyl)ethenyl}.

較佳之其他態樣為式[7]{式中，A表示2-(2,5-二溴苯基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [7] wherein A represents 2-(2,5-dibromophenyl)ethenyl}.

較佳之其他態樣為式[7]{式中，A表示2-[2,5-雙(三 氟甲基)苯基]乙醯基}所表示之化合物。 Preferably, the other aspect is the formula [7] {where A represents 2-[2,5-double (three A compound represented by fluoromethyl)phenyl]ethenyl}.

較佳之其他態樣為式[7]{式中，A表示2-(5-溴-2-甲基苯基)乙醯基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [7] wherein A represents 2-(5-bromo-2-methylphenyl)ethenyl}.

較佳之其他態樣為式[7]{式中，A表示2-[2-甲基-5-(三氟甲基)苯基]乙醯基}所表示之化合物。 A further preferred embodiment is the formula [7] wherein A represents a compound represented by 2-[2-methyl-5-(trifluoromethyl)phenyl]ethenyl}.

較佳之其他態樣為式[7]{式中，A表示2-[2-氟-5-(三氟甲基)苯基]乙醯基}所表示之化合物。 A further preferred embodiment is the formula [7] wherein A represents a compound represented by 2-[2-fluoro-5-(trifluoromethyl)phenyl]ethenyl}.

較佳之其他態樣為式[7]{式中，A表示2-[2-氯-5-(三氟甲基)苯基]乙醯基}所表示之化合物。 Preferably, the other aspect is the formula [7] wherein A represents a compound represented by 2-[2-chloro-5-(trifluoromethyl)phenyl]ethenyl}.

較佳之其他態樣為式[7]{式中，A表示2-[2-溴-5-(三氟甲基)苯基]乙醯基}所表示之化合物。 Preferably, the other aspect is the formula [7] wherein A represents a compound represented by 2-[2-bromo-5-(trifluoromethyl)phenyl]ethenyl}.

較佳之其他態樣為式[7]{式中，X1、X2、X3及X4之中至少一個為甲基磺醯氧基}所表示之化合物。 A further preferred embodiment is a compound represented by the formula [7], wherein at least one of X 1 , X 2 , X 3 and X 4 is methylsulfonyloxy}.

較佳之其他態樣為式[7]{式中，X1為甲基磺醯氧基，X2、X3及X4表示氫原子}所表示之化合物。 Other preferred embodiments are those represented by the formula [7] wherein X 1 is a methylsulfonyloxy group, and X 2 , X 3 and X 4 represent a hydrogen atom.

較佳之其他態樣為式[7]{式中，X1為甲基磺醯氧基，X2及X3為氫原子，X4表示氟原子}所表示之化合物。 The other preferred embodiment is a compound represented by the formula [7] wherein X 1 is a methylsulfonyloxy group, X 2 and X 3 are a hydrogen atom, and X 4 represents a fluorine atom.

較佳之其他態樣為式[7]{式中，X1為甲基磺醯氧基，X2及X3為氫原子，X4表示甲氧基}所表示之化合物。 Further preferred is a compound represented by the formula [7] wherein X 1 is a methylsulfonyloxy group, X 2 and X 3 are a hydrogen atom, and X 4 represents a methoxy group.

較佳之其他態樣為式[7]{式中，X1為甲基磺醯氧基，X2及X3為氫原子，X4表示氰基}所表示之化合物。 The other preferred embodiment is a compound represented by the formula [7] wherein X 1 is a methylsulfonyloxy group, X 2 and X 3 are a hydrogen atom, and X 4 represents a cyano group.

說明本說明書中記載之用語。 The terms described in this manual are explained.

鹵素原子係指包括氟原子、氯原子、溴原子或碘原子。 The halogen atom means a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

如C1~C6之元素記號與下標之數字所成之標示係代表其後所標示之基之元素數在下標數字所示之範圍內。例如，於此情況下係表示碳數為1~6，且C2~C6之標示係表示碳數為2~6。 The indications of the elements of the symbols C 1 to C 6 and the numbers of the subscripts represent the number of elements of the bases indicated thereafter within the range indicated by the subscript numbers. For example, in this case, the carbon number is 1 to 6, and the C 2 to C 6 is a sign indicating that the carbon number is 2 to 6.

在如C1~C6之元素記號與下標之數字所成之標示之後標示有複合取代基之情況，則表示複合取代基全體之元素數在下標數字所示之範圍內。例如，C4~C8環烷基羰氧基係表示環烷基羰氧基全體之碳數為4~8，且包含環丙基羰基等。又，例如C2~C8氰基烷基係表示氰基烷基全體之碳數為2~8。C2~C8氰基烷基係包含1個或複數之氰基，且包含氰基甲基等。 After the elements such as C 1 ~ C 6 symbol number of the subscript of the label into the label of the composite of substituents, the substituent group represents a composite of all the number of elements within the scope of the standard shown in the following figures. For example, a C 4 -C 8 cycloalkylcarbonyloxy group means that the total number of carbon atoms of the cycloalkylcarbonyloxy group is 4 to 8, and a cyclopropylcarbonyl group or the like is contained. Further, for example, a C 2 -C 8 cyanoalkyl group means that the total number of carbon atoms of the cyanoalkyl group is 2 to 8. The C 2 -C 8 cyanoalkyl group contains one or a plurality of cyano groups and contains a cyanomethyl group or the like.

烷基並無特別限定，意指碳數為1~8，較佳係碳數為1~6之直鏈或分枝鏈狀之烷基，可舉出例如甲基、乙基、n-丙基、異丁基、n-丁基、sec-丁基、異丁基、tert-丁基、n-戊基、1-甲基丁基、2-甲基丁基、3-甲基丁基、1-乙基丙基、1,1-二甲基丙基、1,2-二甲基丙基、新戊基、n-己基、1-甲基戊基、2-甲基戊基、3-甲基戊基、4-甲基戊基、1-乙基丁基、2-乙基丁基、1,1-二甲基丁基、1,2-二甲基丁基、1,3-二甲基丁基、2,2-二甲基丁基、2,3-二甲基丁基、3,3-二甲基丁基、1,1,2-三甲基丙基、1,2,2-三甲基丙基、1-乙基-1-甲基丙基、1-乙基-2-甲基丙基等之基。此定義在未另行定義之情況下，亦適用於作為鹵烷基、烷硫基、烷基羧基、烷基磺醯氧基等之作為複合取代基之一部之烷基。例如，在如烷基環烷基在末端包含烷基之複合 取代基之情況，環烷基之該部分亦可被相同亦可為相異之烷基所獨立單取代或多取代。其他基例如在末端具有烯基、烷氧基、羥基、鹵素原子等之複合取代基亦進行相同解釋。 The alkyl group is not particularly limited, and means a straight or branched chain alkyl group having a carbon number of 1 to 8, preferably a carbon number of 1 to 6, and examples thereof include a methyl group, an ethyl group, and an n-propyl group. Base, isobutyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl , 1-ethylpropyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, neopentyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1, 3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1,1,2-trimethylpropyl, A group such as 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl or the like. This definition also applies to an alkyl group which is a part of a complex substituent, such as a haloalkyl group, an alkylthio group, an alkylcarboxy group, an alkylsulfonyloxy group, etc., unless otherwise defined. For example, in the case where an alkylcycloalkyl group contains an alkyl group at the end In the case of a substituent, the moiety of the cycloalkyl group may be independently mono- or polysubstituted by the same or different alkyl groups. Other groups such as a complex substituent having an alkenyl group, an alkoxy group, a hydroxyl group, a halogen atom or the like at the terminal are also explained the same.

環烷基在未特別限定時，意指具有碳數3~8，較佳為具有碳數3~6之分枝鏈之環烷基，可舉出例如環丙基、1-甲基環丙基、2-甲基環丙基、環丁基、環戊基、環己基、4,4-二甲基環己基等之基。此定義在未另行定義之情況，亦可適用於例如鹵環烷基等之做為複合取代基之一部分之環烷基。 The cycloalkyl group means a cycloalkyl group having a carbon number of 3 to 8, preferably a branched chain having 3 to 6 carbon atoms, and examples thereof include a cyclopropyl group and a 1-methylcyclopropane group. a group such as 2-methylcyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 4,4-dimethylcyclohexyl or the like. This definition is also applicable to, for example, a cycloalkyl group such as a halocycloalkyl group as a part of a composite substituent, unless otherwise defined.

環烯基在未特別限定時，意指具有碳數3~8，較佳為具有碳數3~6之分枝鏈之環烯基，可舉出例如環丙烯基、1-甲基環丙烯基、環丁烯基、環戊烯基、環己烯基等之基。此定義在未另行定義之情況，亦適用於例如鹵環烯基等之作為複合取代基之一部分之環烯基。 When the cycloalkenyl group is not particularly limited, it means a cycloalkenyl group having a carbon number of 3 to 8, preferably a branched chain having 3 to 6 carbon atoms, and examples thereof include a cyclopropenyl group and a 1-methylcyclopropene group. a group such as a cyclobutenyl group, a cyclopentenyl group, a cyclohexenyl group or the like. This definition is also applicable to a cycloalkenyl group as a part of a complex substituent such as a halocycloalkenyl group, unless otherwise defined.

環烷氧基在未特別時，意指具有碳數3~8，較佳為具有碳數3~6之分枝鏈之環烷氧基，可舉出例如環丙氧基、1-甲基環丙氧基、環丁氧基、環戊氧基、環己氧基等之基。此定義在未另行定義之情況，亦適用於例如鹵環烷氧基等之作為複合取代基之一部分之環烷氧基。 The cycloalkoxy group means a cycloalkoxy group having a carbon number of 3 to 8, preferably a branched chain having 3 to 6 carbon atoms, and examples thereof include a cyclopropoxy group and a 1-methyl group. A group of a cyclopropoxy group, a cyclobutoxy group, a cyclopentyloxy group, a cyclohexyloxy group or the like. This definition is also applicable, for example, to a cycloalkyloxy group as a part of a complex substituent such as a halocycloalkoxy group, unless otherwise defined.

「鹵‧‧‧」(例如，「鹵烷基」)中之「鹵」之用語係包括氟原子、氯原子、溴原子及碘原子。「鹵」之接頭語所表示之鹵取代係包括單取代或多取代，較佳係包括單取代、二取代及三取代。 The term "halogen" in "halo‧" (for example, "haloalkyl") includes a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. The halogen substitution represented by the term "halo" includes mono- or poly-substitution, and preferably includes mono-, di-, and tri-substitution.

鹵烷基在未特別限定時，意指碳數1~6之直鏈或分枝鏈狀之烷基，且此等基中之氫原子之一部分或全部被鹵素原子所取代之基，可舉出例如氟甲基、氯甲基、溴甲基、碘甲基、二氟甲基、二氯甲基、二溴甲基、二碘甲基、三氟甲基、三氯甲基、三溴甲基、三碘甲基、1-氯乙基、1-溴乙基、2-三氟乙基、3-氯丙基、3-溴丙基、4-氯丁基、4-溴丁基、4-三氟丁基、5-氯戊基、6-氯己基等之基。此定義在未另行定義之情況，亦適用於例如鹵烷基羰基等之作為複合取代基之一部分之鹵烷基。 The haloalkyl group means a straight-chain or branched-chain alkyl group having 1 to 6 carbon atoms, and a group in which one or all of the hydrogen atoms in the group is substituted by a halogen atom, For example, fluoromethyl, chloromethyl, bromomethyl, iodomethyl, difluoromethyl, dichloromethyl, dibromomethyl, diiodomethyl, trifluoromethyl, trichloromethyl, tribromo Methyl, triiodomethyl, 1-chloroethyl, 1-bromoethyl, 2-trifluoroethyl, 3-chloropropyl, 3-bromopropyl, 4-chlorobutyl, 4-bromobutyl a group of 4-trifluorobutyl, 5-chloropentyl, 6-chlorohexyl or the like. This definition also applies to a haloalkyl group which is a part of a composite substituent such as a haloalkylcarbonyl group, unless otherwise defined.

烯基在未特別限定時，意指碳數2~6之直鏈或分枝鏈狀之烯基，可舉出例如乙烯基、1-丙烯基、2-丙烯基、異丙烯基、3-丁烯基、1,3-丁二烯基、4-戊烯基、5-己烯基等之基。此定義在未另行定義之情況，亦適用於例如鹵烯基等之作為複合取代基之一部分之烯基。 When the alkenyl group is not particularly limited, it means a linear or branched chain alkenyl group having 2 to 6 carbon atoms, and examples thereof include a vinyl group, a 1-propenyl group, a 2-propenyl group, an isopropenyl group, and 3 A group such as a butenyl group, a 1,3-butadienyl group, a 4-pentenyl group, a 5-hexenyl group or the like. This definition is also applicable to, for example, an alkenyl group which is a part of a complex substituent, such as a haloalkenyl group, unless otherwise defined.

炔基在未特別限定時，意指碳數2~6之直鏈或分枝鏈狀之炔基，可舉出例如乙炔基、1-丙炔基、2-丙炔基、3-丁炔基、1-甲基-3-丙炔基、4-戊炔基、5-己炔基等之基。此定義在未另行定義之情況，亦適用於例如鹵炔基等之作為複合取代基之一部分之炔基。 The alkynyl group means a straight-chain or branched-chain alkynyl group having 2 to 6 carbon atoms, and examples thereof include an ethynyl group, a 1-propynyl group, a 2-propynyl group, and a 3-butyne group. a group of a group, a 1-methyl-3-propynyl group, a 4-pentynyl group, a 5-hexynyl group or the like. This definition also applies to alkynyl groups which are part of a complex substituent such as a haloalkyn group, unless otherwise defined.

烷氧基在未特別限定時，意指碳數1~6之直鏈或分枝鏈狀之烷氧基，可舉出例如甲氧基、乙氧基、丙氧基、異丙氧基、丁氧基、異丁氧基、sec-丁氧基、tert-丁氧基、戊氧基、己氧基等之基。此定義在未另行定義之情況，亦適用於例如鹵烷氧基、烷氧基羰基等之作為複合取代基之 一部分之烷氧基。 The alkoxy group means a straight-chain or branched-chain alkoxy group having 1 to 6 carbon atoms, and examples thereof include a methoxy group, an ethoxy group, a propoxy group, and an isopropoxy group. A group such as butoxy group, isobutoxy group, sec-butoxy group, tert-butoxy group, pentyloxy group, hexyloxy group or the like. This definition is also applicable to, for example, a haloalkoxy group, an alkoxycarbonyl group or the like as a composite substituent, unless otherwise defined. Part of the alkoxy group.

鹵烷氧基在未特別限定時，意指被1個以上，較佳係被1~10個鹵素原子所取代之碳數1~6之直鏈或分枝鏈狀之烷氧基，可舉出例如氟甲氧基、氯甲氧基、溴甲氧基、碘甲氧基、二氟甲氧基、二氯甲氧基、二溴甲氧基、二碘甲氧基、三氟甲氧基、三氯甲氧基、三溴甲氧基、三碘甲氧基、1-氯乙氧基、1-溴乙氧基、2-三氟乙氧基、3-氯丙氧基、3-溴丙氧基、4-氯丁氧基、4-溴丁氧基、4-三氟丁氧基、5-氯戊氧基、6-氯己氧基等之基。此定義在未另行定義之情況，亦適用於例如鹵烷氧基羰基等之作為複合取代基之一部分之鹵烷氧基。 The haloalkoxy group means a straight or branched chain alkoxy group having 1 to 6 carbon atoms which is substituted by one or more, preferably 1 to 10, halogen atoms, unless otherwise specified. For example, fluoromethoxy, chloromethoxy, bromomethoxy, iodomethoxy, difluoromethoxy, dichloromethoxy, dibromomethoxy, diiodomethoxy, trifluoromethoxy , trichloromethoxy, tribromomethoxy, triiodomethoxy, 1-chloroethoxy, 1-bromoethoxy, 2-trifluoroethoxy, 3-chloropropoxy, 3 a group of -bromopropoxy, 4-chlorobutoxy, 4-bromobutoxy, 4-trifluorobutoxy, 5-chloropentyloxy, 6-chlorohexyloxy and the like. This definition also applies to a haloalkoxy group which is a part of a complex substituent such as a haloalkoxycarbonyl group, unless otherwise defined.

烷硫基在特別限定時，意指烷基部分係指上述碳數1~6之(烷基)-S-基，可舉出例如甲硫基、乙硫基、n-丙硫基、異丙硫基等之基。此定義在未另行定義之情況，亦適用於例如鹵烷硫基等之作為複合取代基之一部分之烷硫基。 When the alkylthio group is specifically limited, it means that the alkyl moiety means the above-mentioned (alkyl)-S- group having 1 to 6 carbon atoms, and examples thereof include a methylthio group, an ethylthio group, an n-propylthio group, and an iso group. The base of propylthio group. This definition is also applicable to, for example, alkanethio group as a part of a complex substituent such as a haloalkylthio group, unless otherwise defined.

烷基亞磺醯基在未特別限定時，意指烷基部分係上述所指之碳數1~6之(烷基)-SO-基，可舉出例如甲基亞磺醯基、乙基亞磺醯基、n-丙基亞磺醯基、異丙基亞磺醯基等之基。此定義在未另行定義之情況，亦適用於例如鹵烷基亞磺醯基等之作為複合取代基之一部分之烷基亞磺醯基。 The alkylsulfinyl group is not particularly limited, and means that the alkyl moiety is the above-mentioned (alkyl)-SO- group having 1 to 6 carbon atoms, and examples thereof include methylsulfinyl group and ethyl group. A group such as a sulfinyl group, an n-propylsulfinyl group, or an isopropylsulfinyl group. This definition is also applicable, for example, to an alkylsulfinyl group as a part of a complex substituent such as a haloalkylsulfinyl group, unless otherwise defined.

烷基磺醯基在未特別限定時，意指烷基部分為上述所指之碳數1~6之(烷基)-SO2-基，可舉出例如甲基磺醯 基、乙基磺醯基、n-丙基磺醯基、異丙基磺醯基等之基。此定義在未另行定義之情況，亦適用於例如鹵烷基磺醯基等之作為複合取代基之一部分之烷基磺醯基。 The alkylsulfonyl group is not particularly limited, and means that the alkyl moiety is the above-mentioned (alkyl)-SO 2 - group having 1 to 6 carbon atoms, and examples thereof include methylsulfonyl group and ethylsulfonate. A group of a mercapto group, an n-propylsulfonyl group, an isopropylsulfonyl group or the like. This definition is also applicable, for example, to alkylsulfonyl as a part of a complex substituent, such as a haloalkylsulfonyl group, unless otherwise defined.

羥基烷基係意指被1~5個羥基所取代之碳原子數1~6之直鏈狀或分枝狀之烷基，可舉出例如羥基甲基、羥基乙基、羥基丙基或羥基異丙基等。 The hydroxyalkyl group means a linear or branched alkyl group having 1 to 6 carbon atoms which is substituted by 1 to 5 hydroxyl groups, and examples thereof include a hydroxymethyl group, a hydroxyethyl group, a hydroxypropyl group or a hydroxyl group. Isopropyl and the like.

烷基磺醯氧基在未特別限定時，意指烷基部分係上述所指之碳數1~6之(烷基)-S(O)2O-基，可舉出例如甲基磺醯氧基、乙基磺醯氧基、n-丙基磺醯氧基、異丙基磺醯氧基等之基。此定義在未另行定義之情況，亦適用於例如鹵烷基磺醯氧基等之作為複合取代基之一部分之烷基磺醯氧基。 The alkylsulfonyloxy group is not particularly limited, and means that the alkyl moiety is the above-mentioned (alkyl)-S(O) 2 O- group having 1 to 6 carbon atoms, and examples thereof include methylsulfonium. A group such as an oxy group, an ethylsulfonyloxy group, an n-propylsulfonyloxy group, or an isopropylsulfonyloxy group. This definition is also applicable, for example, to an alkylsulfonyloxy group as a part of a complex substituent, such as a haloalkylsulfonyloxy group, unless otherwise defined.

烷基羰基在未特別限定時，意指烷基部分係上述所指之(烷基)-C(=O)-基，可舉出例如甲醯基、乙醯基、丙醯基、丁醯基、三甲基乙醯基等之基。此定義在未另行定義之情況，亦適用於例如鹵烷基羰基等之作為複合取代基之一部分之烷基羰基。 The alkylcarbonyl group is not particularly limited, and means that the alkyl moiety is the above-mentioned (alkyl)-C(=O)- group, and examples thereof include a methyl group, an ethyl group, a propyl group, a butyl group, and a butyl group. A group such as trimethylethenyl. This definition also applies to an alkylcarbonyl group as a part of a complex substituent such as a haloalkylcarbonyl group, unless otherwise defined.

烷基羰氧基在未特別限定時，意指烷基部分係上述所指之(烷基)-C(=O)O-基，可舉出例如甲基羰氧基、乙基羰氧基、丙基羰氧基等之基。此定義在未另行定義之情況，亦適用於例如鹵烷基羰氧基等之作為複合取代基之一部分之烷基羰氧基。 When the alkylcarbonyloxy group is not particularly limited, it means that the alkyl moiety is the above-mentioned (alkyl)-C(=O)O- group, and examples thereof include a methylcarbonyloxy group and an ethylcarbonyloxy group. a group such as a propylcarbonyloxy group. This definition is also applicable, for example, to an alkylcarbonyloxy group as a part of a complex substituent such as a haloalkylcarbonyloxy group, unless otherwise defined.

本發明在反應中所使用之酸在未特別敘及之情況，意指在反應系統中放出質子之布氏酸，可例示如鹽酸、氫溴 酸、硫酸等之無機酸、乙酸、三氟乙酸、p-甲苯磺酸、三氟甲烷磺酸等之有機酸。本發明在反應中所使用之路易斯酸係意指出氫離子以外在反應系統中機能作為電子對受體之化合物，可例示例如氯化鋅、氯化鋁、氯化錫、三氯化硼、三氟化硼、三氟甲烷磺酸三甲基矽基等。 The acid used in the reaction of the present invention, unless otherwise specified, means a protonic acid which releases protons in the reaction system, and examples thereof include hydrochloric acid and hydrobromine. An organic acid such as an acid, a sulfuric acid or the like, an acetic acid, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid or trifluoromethanesulfonic acid. The Lewis acid used in the reaction of the present invention is intended to mean a compound which functions as a electron pair acceptor in the reaction system other than hydrogen ions, and examples thereof include zinc chloride, aluminum chloride, tin chloride, boron trichloride, and the like. Boron fluoride, trimethylsulfonium trifluoromethanesulfonate, and the like.

本發明在反應中使用之鹼在未特別敘及之情況，意指在反應系統中接受質子之化合物，或在反應系統中機能作為電子對提供體之化合物，可例示如三乙基胺、吡啶、4-二甲基胺基吡啶、N,N-二甲基苯胺、1,8-二吖[5,4,0]-7-十一烯等之有機胺類；碳酸鈉、碳酸鉀、碳酸鎂、碳酸鈣等之金屬碳酸鹽類；碳酸氫鈉、碳酸氫鉀等之金屬碳酸氫鹽類；乙酸鈉、乙酸鉀、乙酸鈣、乙酸鎂等之金屬乙酸鹽類所代表之羧酸金屬鹽類；甲氧基化鈉、乙氧基化鈉、第三丁氧基化鈉、甲氧基化鉀、第三丁氧基化鉀等之金屬烷氧化物；氫氧化鈉、氫氧化鉀、氫氧化鈣、氫氧化鎂等之金屬氫氧化物；氫化鋰、氫化鈉、氫化鈣等之金屬氫化物等。 The base used in the reaction in the present invention means a compound which accepts a proton in a reaction system, or a compound which functions as an electron pair donor in a reaction system, and may be exemplified as triethylamine or pyridine, unless otherwise specified. , 4-dimethylaminopyridine, N,N-dimethylaniline, organic amines such as 1,8-dioxa[5,4,0]-7-undecene; sodium carbonate, potassium carbonate, a metal carbonate such as magnesium carbonate or calcium carbonate; a metal hydrogencarbonate such as sodium hydrogencarbonate or potassium hydrogencarbonate; a metal carboxylate represented by a metal acetate such as sodium acetate, potassium acetate, calcium acetate or magnesium acetate. Salt; metal alkoxides such as sodium methoxylate, sodium ethoxylate, sodium third potassium oxylate, potassium methoxylate, potassium third potassium oxylate; sodium hydroxide, potassium hydroxide a metal hydroxide such as calcium hydroxide or magnesium hydroxide; a metal hydride such as lithium hydride, sodium hydride or calcium hydride.

本發明中，式[3]所表示之化合物中之脫離基L1在未特別敘及之情況，意指異屬鍵裂解(Heterolysis bond cleavage)中持有電子對而脫離之化學基，可例示如氟原子、氯原子、溴原子或碘原子之鹵素原子、甲烷磺醯氧基、三氟甲烷磺醯氧基等之烷基磺醯氧基、苯磺醯氧基、p-甲苯磺醯氧基等之芳基磺醯氧基、硝酸酯基、磷酸酯基等之無機酸酯基。 In the present invention, the cleavage group L 1 in the compound represented by the formula [3] means a chemical group which has an electron pair and is detached in a Heterolysis bond cleavage, unless otherwise specified, and can be exemplified An alkylsulfonyloxy group such as a fluorine atom, a chlorine atom, a bromine atom or a halogen atom of an iodine atom, a methanesulfonyloxy group, a trifluoromethanesulfonyloxy group, a benzenesulfonyloxy group, or a p-toluenesulfonyloxy group An inorganic acid ester group such as an arylsulfonyloxy group, a nitrate ester group or a phosphate group.

本說明書之表中之下述之標記係如下述所示，分別表示其所該當之基。 The following symbols in the tables of the present specification are as follows, and indicate the basis thereof.

例如，Me係表示甲基，Et係表示乙基，n-Pr係表示n-丙基，i-Pr係表示異丙基，c-Pr係表示環丙基，n-Bu係表示n-丁基，t-Bu係表示tert-丁基，Ph係表示苯基。 For example, Me represents methyl, Et represents ethyl, n-Pr represents n-propyl, i-Pr represents isopropyl, c-Pr represents cyclopropyl, and n-Bu represents n-butyl. The base, t-Bu represents tert-butyl, and Ph represents phenyl.

式[1]所示之化合物之代表性製造方法係例示如以下，但並非係受到此等方法所限定者。 Representative production methods of the compounds represented by the formula [1] are exemplified below, but are not limited by the methods.

<製造方法1> <Manufacturing method 1>

式[1]所示之化合物係可藉由由如下述例示之反應式所構成之方法進行製造。 The compound represented by the formula [1] can be produced by a method consisting of a reaction formula as exemplified below.

(式中，A為選自(1)中定義之A-1、A-2及A-3之基，R1~R7係如同(1)中所定義，R8為C1~C4烷基、C1~C4烯基、苄基(在此苄基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、 C2~C6烷基羰基、C2~C6鹵烷基羰基、苯基羰基(在此苯基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、C2~C6烷氧基羰基、苄基氧基羰基(在此苄基氧基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、苯基氧基羰基(在此苯基氧基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、三苯基甲基、甲醯基或基-SO2R9，R9係如同(1)中所定義，R10及L1係分別如同(1)中所定義)。 (wherein A is a group selected from the group consisting of A-1, A-2 and A-3 defined in (1), R 1 to R 7 are as defined in (1), and R 8 is C 1 to C 4 An alkyl group, a C 1 -C 4 alkenyl group, or a benzyl group (the benzene ring of the benzyl group may be one or more selected from the group consisting of a halogen atom, a C 1 -C 4 alkyl group, or a C 1 -C 4 alkoxy group). Substituted by a substituent), a C 2 -C 6 alkylcarbonyl group, a C 2 -C 6 haloalkylcarbonyl group, a phenylcarbonyl group (wherein the phenyl ring of the phenylcarbonyl group may also be selected from a halogen atom, C 1 to C 4 a substituent of one or more of an alkyl group or a C 1 -C 4 alkoxy group), a C 2 -C 6 alkoxycarbonyl group, or a benzyloxycarbonyl group (the benzene ring of the benzyloxycarbonyl group may also be used) Substituted by one or more substituents selected from a halogen atom, a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group), a phenyloxycarbonyl group (the phenyl ring of the phenyloxycarbonyl group is also It may be substituted with one or more substituents selected from a halogen atom, a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group), a triphenylmethyl group, a decyl group or a group -SO 2 R 9 R 9 is as defined in (1), and R 10 and L 1 are as defined in (1), respectively.

藉由使式[2](依據WO2008/013925之記載而能製造)所表示之化合物與式[3a]所表示之化合物在溶劑中反應，而可製造式[1]所表示之化合物。 The compound represented by the formula [1] can be produced by reacting a compound represented by the formula [2] (manufactured according to the description of WO 2008/013925) with a compound represented by the formula [3a] in a solvent.

在此使用之式[3a]之化合物之使用量，相對於式[2]之化合物1莫耳，適宜選自1.0~10莫耳之範圍即可，較佳為1.0~1.5莫耳。 The compound used in the formula [3a] used herein is preferably selected from the range of 1.0 to 10 moles, preferably 1.0 to 1.5 moles, based on the mole of the compound 1 of the formula [2].

作為本步驟可使用之溶劑，只要係不阻礙本反應進行者即可，可使用例如乙腈等之腈類；二乙基醚、二異丙基醚、四氫呋喃、二噁烷、單甘醇二甲醚、二甘醇二甲醚等之醚類；乙酸甲酯、乙酸乙酯、乙酸丁酯等之烴類；二氯甲烷、二氯乙烷、氯仿、四氯化碳、四氯乙烷等之鹵化烴類；苯、氯苯、硝基苯、甲苯等之芳香族烴類；N,N-二甲基甲醯胺、N,N-二甲基乙醯胺等之醯胺類；1,3-二甲基-2-咪唑啉酮等之咪唑啉酮類；二甲亞碸等之硫化合物類等， 並且亦可使用此等之混合溶劑。 As the solvent which can be used in this step, as long as it does not inhibit the progress of the reaction, a nitrile such as acetonitrile or the like; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane or monoglycol can be used. An ether such as ether or diglyme; a hydrocarbon such as methyl acetate, ethyl acetate or butyl acetate; dichloromethane, dichloroethane, chloroform, carbon tetrachloride, tetrachloroethane, etc. Halogenated hydrocarbons; aromatic hydrocarbons such as benzene, chlorobenzene, nitrobenzene, toluene; amides such as N,N-dimethylformamide, N,N-dimethylacetamide; , imidazolinones such as 3-dimethyl-2-imidazolidinone; sulfur compounds such as dimethyl hydrazine; It is also possible to use such a mixed solvent.

相對於式[2]之化合物1莫耳，溶劑之使用量係適宜選自0.01~100L之範圍即可，較佳為0.1~10L。 The solvent is preferably used in an amount of from 0.01 to 100 L, preferably from 0.1 to 10 L, based on the compound of the formula [2].

反應溫度係選自從-20℃至所使用之惰性溶劑之沸點區域範圍即可，較佳係宜在0℃~100℃之範圍內進行。 The reaction temperature is selected from the range of from -20 ° C to the boiling point range of the inert solvent to be used, and is preferably carried out in the range of from 0 ° C to 100 ° C.

反應時間係根據反應溫度、反應基質、反應量等而相異，但通常為10分~48小時。 The reaction time varies depending on the reaction temperature, the reaction substrate, the reaction amount, etc., but is usually from 10 minutes to 48 hours.

反應之目的物即式[1]之化合物在反應結束後亦可藉由常規方法從反應系統中採取，因應必要藉由管柱層析法、再結晶等之操作而進行純化。 The object of the reaction, that is, the compound of the formula [1] can also be taken from the reaction system by a conventional method after completion of the reaction, and purification is carried out by an operation such as column chromatography or recrystallization.

<製造方法2> <Manufacturing method 2>

式[1]所示之化合物係亦可藉由由下述例示之反應式所構成之方法進行製造。 The compound represented by the formula [1] can also be produced by a method comprising the reaction formula exemplified below.

(式中，A為選自(1)中所定義之A-1、A-2及A-3之基，R1~R7係如同(1)中所定義，R8為C1~C4烷基、C1~C4烯基、苄基(在此苄基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取 代)、C2~C6烷基羰基、C2~C6鹵烷基羰基、苯基羰基(在此苯基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、C2~C6烷氧基羰基、苄基氧基羰基(在此苄基氧基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、苯基氧基羰基(在此苯基氧基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、三苯基甲基、甲醯基或基-SO2R9，R9係如同(1)中所定義，R10及L1係分別如同(1)中所定義)。 (wherein A is a group selected from A-1, A-2 and A-3 as defined in (1), R 1 to R 7 are as defined in (1), and R 8 is C 1 to C a tetraalkyl group, a C 1 -C 4 alkenyl group, or a benzyl group (the benzene ring of the benzyl group may be one or more selected from the group consisting of a halogen atom, a C 1 -C 4 alkyl group, or a C 1 -C 4 alkoxy group). Substituted by a substituent), a C 2 -C 6 alkylcarbonyl group, a C 2 -C 6 haloalkylcarbonyl group, a phenylcarbonyl group (wherein the phenyl ring of the phenylcarbonyl group may also be selected from a halogen atom, C 1 -C Substituted with one or more substituents of a 4- alkyl or C 1 -C 4 alkoxy group), a C 2 -C 6 alkoxycarbonyl group, a benzyloxycarbonyl group (wherein the benzene ring of the benzyloxycarbonyl group is also It may be substituted by one or more substituents selected from a halogen atom, a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group), a phenyloxycarbonyl group (the phenyl ring of the phenyloxycarbonyl group here) It may be substituted with one or more substituents selected from a halogen atom, a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group), a triphenylmethyl group, a decyl group or a yl-SO 2 R group. 9 , R 9 is as defined in (1), and R 10 and L 1 are as defined in (1), respectively.

(步驟1) (step 1)

式[4]之化合物係可藉由使式[2]所表示之化合物與式[3a]所表示之化合物在鹼之存在下溶劑中進行反應而製造。 The compound of the formula [4] can be produced by reacting a compound represented by the formula [2] with a compound represented by the formula [3a] in a solvent in the presence of a base.

相對於式[2]之化合物1莫耳，本步驟中使用之式[3a]之化合物之使用量係適宜選自1.0~10莫耳之範圍即可，較佳為1.0~1.5莫耳。 The compound of the formula [3a] used in the present step is preferably used in an amount selected from the range of 1.0 to 10 mol, preferably 1.0 to 1.5 mol, based on the compound 1 mol of the formula [2].

作為本步驟中可使用之鹼，可舉出例如三乙基胺、吡啶、4-二甲基胺基吡啶、N,N-二甲基苯胺、1,8-二吖[5,4,0]-7-十一烯等之有機胺類；碳酸鈉、碳酸鉀、碳酸鎂、碳酸鈣等之金屬碳酸鹽類；碳酸氫鈉、碳酸氫鉀等之金屬碳酸氫鹽類；乙酸鈉、乙酸鉀、乙酸鈣、乙酸鎂等之金屬乙酸鹽類所代表之羧酸金屬鹽類；甲氧基化鈉、乙氧 基化鈉、第三丁氧基化鈉、甲氧基化鉀、第三丁氧基化鉀等之金屬烷氧化物；氫氧化鈉、氫氧化鉀、氫氧化鈣、氫氧化鎂等之金屬氫氧化物；氫化鋰、氫化鈉、氫化鈣等之金屬氫化物等。 The base which can be used in this step includes, for example, triethylamine, pyridine, 4-dimethylaminopyridine, N,N-dimethylaniline, 1,8-dioxi[5,4,0. An organic amine such as -7-undecene; a metal carbonate such as sodium carbonate, potassium carbonate, magnesium carbonate or calcium carbonate; a metal hydrogencarbonate such as sodium hydrogencarbonate or potassium hydrogencarbonate; sodium acetate or acetic acid; a metal carboxylate represented by a metal acetate such as potassium, calcium acetate or magnesium acetate; sodium methoxylate or ethoxylate a metal alkoxide such as sodium hydride, sodium third potassium oxylate, potassium methoxylate or potassium third potassium oxylate; metal such as sodium hydroxide, potassium hydroxide, calcium hydroxide or magnesium hydroxide a hydroxide; a metal hydride such as lithium hydride, sodium hydride or calcium hydride.

相對於式[2]之化合物1莫耳，本反應中使用之鹼之使用量係適宜選自1.0~10莫耳之範圍即可，較佳為1.0~3.0莫耳。 The amount of the base used in the reaction is suitably selected from the range of 1.0 to 10 moles, preferably 1.0 to 3.0 moles, relative to the compound 1 mole of the formula [2].

作為本步驟中可使用之溶劑，可舉出如與在製造方法1中所說明之相同者。 The solvent which can be used in this step is the same as that described in the production method 1.

又，相對於式[2]之化合物1莫耳，溶劑之使用量係適宜選自0.01~100L之範圍即可，較佳為0.1~10L。 Further, the amount of the solvent used is preferably in the range of 0.01 to 100 L, preferably 0.1 to 10 L, based on the compound 1 of the formula [2].

反應溫度係選自從-20℃至所使用之惰性溶劑之沸點區域範圍即可，較佳係宜在0℃~100℃之範圍內進行。 The reaction temperature is selected from the range of from -20 ° C to the boiling point range of the inert solvent to be used, and is preferably carried out in the range of from 0 ° C to 100 ° C.

反應時間係根據反應溫度、反應基質、反應量等而相異，但通常為10分~48小時。 The reaction time varies depending on the reaction temperature, the reaction substrate, the reaction amount, etc., but is usually from 10 minutes to 48 hours.

藉由本步驟所得之式[4]之化合物可不經過單獨分離而使用於下個步驟，但因應必要亦可藉由管柱層析法、再結晶等之操作進行純化。 The compound of the formula [4] obtained by this step can be used in the next step without separate separation, but may be purified by an operation such as column chromatography or recrystallization, if necessary.

(步驟2) (Step 2)

式[1]之化合物係可藉由使式[4]所表示之化合物在溶劑存在下/非存在下，酸或路易斯酸之存在下，較佳係酸之存在下進行反應而製造。 The compound of the formula [1] can be produced by reacting a compound represented by the formula [4] in the presence or absence of a solvent, in the presence of an acid or a Lewis acid, preferably in the presence of an acid.

作為本步驟中可使用之酸，可舉出例如鹽酸、氫溴 酸、硫酸等之無機酸、乙酸、三氟乙酸、p-甲苯磺酸、三氟甲烷磺酸等之有機酸等。 As the acid which can be used in this step, for example, hydrochloric acid or hydrobromine can be mentioned. An inorganic acid such as an acid or a sulfuric acid, an organic acid such as acetic acid, trifluoroacetic acid, p-toluenesulfonic acid or trifluoromethanesulfonic acid.

作為本步驟中可使用之路易斯酸，可舉出例如氯化鋅、氯化鋁、氯化錫、三氯化硼、三氟化硼、三氟甲烷磺酸三甲基矽基等。 The Lewis acid which can be used in this step may, for example, be zinc chloride, aluminum chloride, tin chloride, boron trichloride, boron trifluoride or trimethylsulfonium trifluoromethanesulfonate.

相對於式[4]之化合物1莫耳，酸或路易斯酸之使用量係適宜選自0.01~100莫耳之範圍即可，較佳為0.1~10莫耳。 The amount of the compound 1 used in the formula [4], the acid or the Lewis acid is preferably selected from the range of 0.01 to 100 moles, preferably 0.1 to 10 moles.

作為本步驟中可使用之溶劑，可舉出與在製造方法1中所說明之相同者。 The solvent which can be used in this step is the same as that described in the production method 1.

又，相對於式[4]之化合物1莫耳，溶劑之使用量係適宜選自0.01~100L之範圍即可，較佳為0~10L。 Further, the solvent is preferably used in an amount of from 0.01 to 100 L, preferably from 0 to 10 L, based on the compound 1 of the formula [4].

反應溫度係選自從-20℃至所使用之惰性溶劑之沸點區域範圍即可，較佳係宜在0℃~100℃之範圍內進行。 The reaction temperature is selected from the range of from -20 ° C to the boiling point range of the inert solvent to be used, and is preferably carried out in the range of from 0 ° C to 100 ° C.

反應時間係根據反應溫度、反應基質、反應量等而相異，但通常為10分~48小時。 The reaction time varies depending on the reaction temperature, the reaction substrate, the reaction amount, etc., but is usually from 10 minutes to 48 hours.

反應之目的物即式[1]之化合物在反應結束後亦可藉由常規方法從反應系統中採取，因應必要藉由管柱層析法、再結晶等之操作而進行純化。 The object of the reaction, that is, the compound of the formula [1] can also be taken from the reaction system by a conventional method after completion of the reaction, and purification is carried out by an operation such as column chromatography or recrystallization.

<製造方法3> <Manufacturing method 3>

式[1]所示之化合物係亦可藉由由下述例示之反應式所構成之方法進行製造。 The compound represented by the formula [1] can also be produced by a method comprising the reaction formula exemplified below.

(式中，A為選自(1)中所定義之A-1、A-2及A-3之基，R1~R7係如同(1)中所定義，R8為C1~C4烷基、C1~C4烯基、苄基(在此苄基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、C2~C6烷基羰基、C2~C6鹵烷基羰基、苯基羰基(在此苯基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、C2~C6烷氧基羰基、苄基氧基羰基(在此苄基氧基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、苯基氧基羰基(在此苯基氧基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、三苯基甲基、甲醯基或基-SO2R9，R9係如同(1)中所定義，R10係如同(1)中所定義)。 (wherein A is a group selected from A-1, A-2 and A-3 as defined in (1), R 1 to R 7 are as defined in (1), and R 8 is C 1 to C a tetraalkyl group, a C 1 -C 4 alkenyl group, or a benzyl group (the benzene ring of the benzyl group may be one or more selected from the group consisting of a halogen atom, a C 1 -C 4 alkyl group, or a C 1 -C 4 alkoxy group). Substituted by a substituent), a C 2 -C 6 alkylcarbonyl group, a C 2 -C 6 haloalkylcarbonyl group, a phenylcarbonyl group (wherein the phenyl ring of the phenylcarbonyl group may also be selected from a halogen atom, C 1 -C Substituted with one or more substituents of a 4- alkyl or C 1 -C 4 alkoxy group), a C 2 -C 6 alkoxycarbonyl group, a benzyloxycarbonyl group (wherein the benzene ring of the benzyloxycarbonyl group is also It may be substituted by one or more substituents selected from a halogen atom, a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group), a phenyloxycarbonyl group (the phenyl ring of the phenyloxycarbonyl group here) It may be substituted with one or more substituents selected from a halogen atom, a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group), a triphenylmethyl group, a decyl group or a yl-SO 2 R group. 9 , R 9 is as defined in (1), R 10 is as defined in (1).

(步驟1) (step 1)

式[5a]之化合物係可藉由使式[4]所表示之化合物在酸或路易斯酸之存在下於溶劑中進行反應而製造。 The compound of the formula [5a] can be produced by reacting a compound represented by the formula [4] in a solvent in the presence of an acid or a Lewis acid.

作為本步驟中可使用之酸及路易斯酸，可舉出與在製造方法2步驟2中所說明之相同者。 The acid and Lewis acid which can be used in this step are the same as those described in the second step of the production method 2.

相對於式[4]之化合物1莫耳，酸或路易斯酸之使用量係適宜選自0.01~10莫耳之範圍即可，較佳為0.1~3.0莫耳。 The amount of the compound 1 molar, the acid or the Lewis acid used in the formula [4] is suitably selected from the range of 0.01 to 10 moles, preferably 0.1 to 3.0 moles.

作為本步驟中可使用之溶劑，可舉出與在製造方法1中所說明之相同者。 The solvent which can be used in this step is the same as that described in the production method 1.

又，相對於式[4]之化合物1莫耳，溶劑之使用量係適宜選自0.01~100L之範圍即可，較佳為0~10L。 Further, the solvent is preferably used in an amount of from 0.01 to 100 L, preferably from 0 to 10 L, based on the compound 1 of the formula [4].

反應溫度係選自從-20℃至所使用之惰性溶劑之沸點區域範圍即可，較佳係宜在0℃~100℃之範圍內進行。 The reaction temperature is selected from the range of from -20 ° C to the boiling point range of the inert solvent to be used, and is preferably carried out in the range of from 0 ° C to 100 ° C.

反應時間係根據反應溫度、反應基質、反應量等而相異，但通常為10分~48小時。 The reaction time varies depending on the reaction temperature, the reaction substrate, the reaction amount, etc., but is usually from 10 minutes to 48 hours.

藉由本步驟所得之式[5a]之化合物可不經過單獨分離而使用於下個步驟，但因應必要亦可藉由管柱層析法、再結晶等之操作進行純化。 The compound of the formula [5a] obtained by this step can be used in the next step without isolation alone, but may be purified by an operation such as column chromatography or recrystallization, if necessary.

(步驟2) (Step 2)

式[1]之化合物係可藉由使式[5a]所表示之化合物在酸或路易斯酸之存在下，較佳在酸之存在下於溶劑中進行反應而製造。 The compound of the formula [1] can be produced by reacting a compound represented by the formula [5a] in the presence of an acid or a Lewis acid, preferably in the presence of an acid in a solvent.

作為本步驟中可使用之酸及路易斯酸，可舉出與在製造方法2步驟2中所說明之相同者。 The acid and Lewis acid which can be used in this step are the same as those described in the second step of the production method 2.

相對於式[5a]之化合物1莫耳，酸或路易斯酸之使用量係適宜選自0.01~10莫耳之範圍即可，較佳為0.1~3.0莫耳。 The amount of the acid or Lewis acid to be used is preferably from 0.01 to 10 moles, preferably from 0.1 to 3.0 moles, per mole of the compound 1 of the formula [5a].

作為本步驟中可使用之溶劑，可舉出與在製造方法1中所說明之相同者。 The solvent which can be used in this step is the same as that described in the production method 1.

又，相對於式[5a]之化合物1莫耳，溶劑之使用量係適宜選自0.01~100L之範圍即可，較佳為0~10L。 Further, the amount of the solvent used is preferably in the range of 0.01 to 100 L, preferably 0 to 10 L, based on the compound 1 of the formula [5a].

反應溫度係選自從-20℃至所使用之惰性溶劑之沸點區域範圍即可，較佳係宜在0℃~100℃之範圍內進行。 The reaction temperature is selected from the range of from -20 ° C to the boiling point range of the inert solvent to be used, and is preferably carried out in the range of from 0 ° C to 100 ° C.

反應時間係根據反應溫度、反應基質、反應量等而相異，但通常為10分~48小時。 The reaction time varies depending on the reaction temperature, the reaction substrate, the reaction amount, etc., but is usually from 10 minutes to 48 hours.

反應之目的物即式[1]之化合物在反應結束後亦可藉由常規方法從反應系統中採取，因應必要藉由管柱層析法、再結晶等之操作而進行純化。 The object of the reaction, that is, the compound of the formula [1] can also be taken from the reaction system by a conventional method after completion of the reaction, and purification is carried out by an operation such as column chromatography or recrystallization.

<製造方法4> <Manufacturing method 4>

式[1]所示之化合物係亦可藉由由下述例示之反應式所構成之方法進行製造。 The compound represented by the formula [1] can also be produced by a method comprising the reaction formula exemplified below.

(式中，A為選自(1)中所定義之A-1、A-2及A-3之基，R1~R7係如同(1)中所定義，R8為C1~C4烷基、C1~C4烯基、苄基(在此苄基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、C2~C6烷基羰基、C2~C6鹵烷基羰基、苯基羰基(在此苯基羰基之苯環亦可被選自鹵素原子、C1~C4烷基 或C1~C4烷氧基之1種以上之取代基所取代)、C2~C6烷氧基羰基、苄基氧基羰基(在此苄基氧基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、苯基氧基羰基(在此苯基氧基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、三苯基甲基、甲醯基或基-SO2R9，R9係如同(1)中所定義)。 (wherein A is a group selected from A-1, A-2 and A-3 as defined in (1), R 1 to R 7 are as defined in (1), and R 8 is C 1 to C a tetraalkyl group, a C 1 -C 4 alkenyl group, or a benzyl group (the benzene ring of the benzyl group may be one or more selected from the group consisting of a halogen atom, a C 1 -C 4 alkyl group, or a C 1 -C 4 alkoxy group). Substituted by a substituent), a C 2 -C 6 alkylcarbonyl group, a C 2 -C 6 haloalkylcarbonyl group, a phenylcarbonyl group (wherein the phenyl ring of the phenylcarbonyl group may also be selected from a halogen atom, C 1 -C Substituted with one or more substituents of a 4- alkyl or C 1 -C 4 alkoxy group), a C 2 -C 6 alkoxycarbonyl group, a benzyloxycarbonyl group (wherein the benzene ring of the benzyloxycarbonyl group is also It may be substituted by one or more substituents selected from a halogen atom, a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group), a phenyloxycarbonyl group (the phenyl ring of the phenyloxycarbonyl group here) It may be substituted with one or more substituents selected from a halogen atom, a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group), a triphenylmethyl group, a decyl group or a yl-SO 2 R group. 9 , R 9 is as defined in (1).

(步驟1) (step 1)

式[6]之化合物係可藉由使式[2]所表示之化合物與1,1,3-三氯丙烷-2-酮在溶劑中進行反應而製造。本反應中因應必要亦可添加相間轉移觸媒。 The compound of the formula [6] can be produced by reacting a compound represented by the formula [2] with 1,1,3-trichloropropan-2-one in a solvent. In this reaction, an interphase transfer catalyst may also be added as necessary.

相對於式[2]之化合物1莫耳，1,1,3-三氯丙烷-2-酮之使用量係適宜選自1.0~5.0莫耳之範圍即可，較佳為1.0~1.5莫耳。 With respect to the compound 1 of the formula [2], the amount of 1,1,3-trichloropropan-2-one used is suitably selected from the range of 1.0 to 5.0 moles, preferably 1.0 to 1.5 moles. .

作為本步驟中可使用之相間轉移觸媒，可舉出如氟化四丁基銨、氯化苄基三乙基銨、氯化四乙基銨、溴化四甲基銨、溴化四丁基銨、碘化四丁基銨、氫氧化四丁基銨等之銨鹽；氯化苄基三苯基鏻、溴化四甲基鏻、碘化四苯基鏻、四丁基銨四氟硼酸鹽等之鏻鹽；15-冠-5-醚、15-冠5-醚18-冠6-醚等之冠醚等。 Examples of the interphase transfer catalyst which can be used in this step include tetrabutylammonium fluoride, benzyltriethylammonium chloride, tetraethylammonium chloride, tetramethylammonium bromide, and tetrabutyl bromide. Ammonium salt of ammonium amide, tetrabutylammonium iodide, tetrabutylammonium hydroxide, etc.; benzyltriphenylphosphonium chloride, tetramethylphosphonium bromide, tetraphenylphosphonium iodide, tetrabutylammonium tetrafluoro a cerium salt such as a borate; a crown ether such as 15-crown-5-ether or 15-crown 5-ether 18-crown 6-ether.

相對於式[2]之化合物1莫耳，相間轉移觸媒之使用量係適宜選自0~1.5莫耳之範圍即可，較佳為0~0.1莫耳。 The amount of the phase transfer catalyst used is preferably selected from the range of 0 to 1.5 moles, preferably 0 to 0.1 moles, relative to the compound 1 mole of the formula [2].

作為本步驟中可使用之溶劑，可舉出與在製造方法1中所說明之相同者。 The solvent which can be used in this step is the same as that described in the production method 1.

又，相對於式[2]之化合物1莫耳，溶劑之使用量係適宜選自0.01~100L之範圍即可，較佳為0~10L。 Further, the amount of the solvent used is preferably in the range of 0.01 to 100 L, preferably 0 to 10 L, based on the compound 1 of the formula [2].

反應溫度係選自從-20℃至所使用之惰性溶劑之沸點區域範圍即可，較佳係宜在0℃~100℃之範圍內進行。 The reaction temperature is selected from the range of from -20 ° C to the boiling point range of the inert solvent to be used, and is preferably carried out in the range of from 0 ° C to 100 ° C.

反應時間係根據反應溫度、反應基質、反應量等而相異，但通常為10分~48小時。 The reaction time varies depending on the reaction temperature, the reaction substrate, the reaction amount, etc., but is usually from 10 minutes to 48 hours.

藉由本步驟所得之式[6]之化合物可不經過單獨分離而使用於下個步驟，但因應必要亦可藉由管柱層析法、再結晶等之操作進行純化。 The compound of the formula [6] obtained by this step can be used in the next step without separate separation, but may be purified by an operation such as column chromatography or recrystallization, if necessary.

(步驟2) (Step 2)

式[1]之化合物係可藉由使式[6]所表示之化合物在酸或鹼之存在下於水中進行反應而製造。 The compound of the formula [1] can be produced by reacting a compound represented by the formula [6] in water in the presence of an acid or a base.

作為本步驟中可使用之酸，可舉出與在製造方法2步驟2中所說明之相同者。 The acid which can be used in this step is the same as that described in the second step of the production method 2.

相對於式[6]之化合物1莫耳，酸之使用量係適宜選自0.1~50莫耳之範圍即可，較佳為1.0~10莫耳。 The amount of the acid to be used is suitably selected from the range of 0.1 to 50 moles, preferably 1.0 to 10 moles, relative to the compound 1 of the formula [6].

作為本步驟中可使用之鹼，可舉出與在製造方法2步驟1中所說明之相同者。 The base which can be used in this step is the same as that described in the first step of the production method 2.

相對於式[2]之化合物1莫耳，本反應中使用之鹼之使用量係適宜選自1.0~10莫耳之範圍即可，較佳為1.0~2.0莫耳。 The amount of the base used in the reaction is suitably selected from the range of 1.0 to 10 moles, preferably 1.0 to 2.0 moles, relative to the compound 1 mole of the formula [2].

相對於式[6]之化合物1莫耳，水之使用量係適宜選自0.01~100L之範圍即可，較佳為0~10L。 The amount of water used is preferably selected from the range of 0.01 to 100 L, preferably 0 to 10 L, based on the compound 1 of the formula [6].

反應溫度係選自水之沸點區域之範圍即可，較佳宜在20℃~100℃之範圍內進行。 The reaction temperature may be selected from the range of the boiling point region of water, and is preferably carried out in the range of from 20 ° C to 100 ° C.

反應時間係根據反應溫度、反應基質、反應量等而相異，但通常為10分~48小時。 The reaction time varies depending on the reaction temperature, the reaction substrate, the reaction amount, etc., but is usually from 10 minutes to 48 hours.

反應之目的物即式[1]之化合物在反應結束後亦可藉由常規方法從反應系統中採取，因應必要藉由管柱層析法、再結晶等之操作而進行純化。 The object of the reaction, that is, the compound of the formula [1] can also be taken from the reaction system by a conventional method after completion of the reaction, and purification is carried out by an operation such as column chromatography or recrystallization.

並且，以本製造方法取得之式[1b](A為A-2或A-3之化合物)之化合物藉由適當脫保護條件而進行脫保護後，藉由使用既知方法而能轉換成殺菌性作物保護劑之中間體即式[1a](A為A-1之化合物)之化合物(請參照例如WO2008/013925號公報第79頁第8~26行)。關於保護基之方法，若係化學合成領域之業界人士即為顯而易知(例如參照T.W.Greene及P.G.Wuts著，Protective Groups in Organic Synthesis、第4版；Wiley：New York、2007)。 Further, the compound of the formula [1b] (A is a compound of A-2 or A-3) obtained by the present production method can be converted into bactericidal property by using a known method after deprotection by an appropriate deprotection condition. The intermediate of the crop protection agent is a compound of the formula [1a] (A is a compound of A-1) (refer to, for example, WO2008/013925, page 79, lines 8 to 26). The method of protecting the group is apparent to those skilled in the art of chemical synthesis (for example, see T. W. Greene and P. G. Wuts, Protective Groups in Organic Synthesis, 4th edition; Wiley: New York, 2007).

<製造方法5> <Manufacturing method 5>

式[1c]所示之化合物係可藉由由下述例示之反應式所構成知方法而製造。 The compound represented by the formula [1c] can be produced by a known method comprising the reaction formula exemplified below.

(式中，R23及L1係分別如同(32)中所定義)。 (wherein R 23 and L 1 are as defined in (32), respectively).

藉由使式[2a](能依據WO2015/189115號公報之記載等而製造)所表示之化合物與式[3b]所表示之化合物在酸之存在下於溶劑中進行反應，而可製造式[1c]所表示之化合物。 The compound represented by the formula [2a] (manufactured according to the description of WO2015/189115, etc.) and the compound represented by the formula [3b] are reacted in a solvent in the presence of an acid to produce a formula [ 1c] the compound represented.

在此使用之式[3b]之化合物之使用量係相對於式[2a]之化合物1莫耳而言，適宜選自1.0-10莫耳之範圍即可，較佳為1.0-1.5莫耳。 The compound of the formula [3b] used herein is used in an amount suitably selected from the range of 1.0 to 10 moles, preferably 1.0 to 1.5 moles, relative to the compound 1 mole of the formula [2a].

作為本步驟中可使用之溶劑，只要不阻礙本反應進行者即可，可使用例如甲醇、乙醇、1-丙醇、2-丙醇、2-甲基-2-丙醇等之醇類、乙腈等之腈類；二乙基醚、二異丙基醚、四氫呋喃、二噁烷、單甘醇二甲醚、二甘醇二甲醚等之醚類；二氯甲烷、二氯乙烷、氯仿、四氯化碳、四氯乙烷等之鹵化烴類；苯、氯苯、硝基苯、甲苯等之芳香族烴類；N,N-二甲基甲醯胺、N,N-二甲基乙醯胺等之醯胺類；1,3-二甲基-2-咪唑啉酮等之咪唑啉酮類；二甲亞碸等之硫化合物類等，並亦可使用此等之混合溶劑，較佳為甲醇、乙醇或2-丙醇。 As the solvent which can be used in this step, as long as the reaction is not inhibited, an alcohol such as methanol, ethanol, 1-propanol, 2-propanol or 2-methyl-2-propanol can be used. a nitrile such as acetonitrile; an ether such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, monoglyme, diglyme or the like; dichloromethane, dichloroethane, Halogenated hydrocarbons such as chloroform, carbon tetrachloride, tetrachloroethane; aromatic hydrocarbons such as benzene, chlorobenzene, nitrobenzene, toluene; N,N-dimethylformamide, N,N-di a guanamine such as methyl acetamide; an imidazolinone such as 1,3-dimethyl-2-imidazolidinone; a sulfur compound such as dimethyl hydrazine; and the like The solvent is preferably methanol, ethanol or 2-propanol.

作為本步驟中可使用之酸，可舉出例如鹽酸、氫溴 酸、硫酸等之無機酸、乙酸、三氟乙酸、p-甲苯磺酸、三氟甲烷磺酸等之有機酸等，較佳為鹽酸。 As the acid which can be used in this step, for example, hydrochloric acid or hydrobromine can be mentioned. An inorganic acid such as an acid or a sulfuric acid, an organic acid such as acetic acid, trifluoroacetic acid, p-toluenesulfonic acid or trifluoromethanesulfonic acid, or the like is preferably hydrochloric acid.

相對於式[2a]之化合物1莫耳，酸之使用量係適宜選自0.01~5莫耳之範圍即可，較佳為1.0~2.0莫耳。 The amount of the acid to be used is suitably selected from the range of 0.01 to 5 moles, preferably 1.0 to 2.0 moles, relative to the compound 1 of the formula [2a].

相對於式[2a]之化合物1莫耳，溶劑之使用量係適宜選自0.01~100L之範圍即可，較佳為0.1~10L。 The solvent is preferably used in an amount of from 0.01 to 100 L, preferably from 0.1 to 10 L, based on the compound of the formula [2a].

反應溫度係選自從-20℃至所使用之惰性溶劑之沸點區域範圍即可，較佳係宜在0℃~100℃之範圍內進行。 The reaction temperature is selected from the range of from -20 ° C to the boiling point range of the inert solvent to be used, and is preferably carried out in the range of from 0 ° C to 100 ° C.

反應時間係根據反應溫度、反應基質、反應量等而相異，但通常為10分~48小時。 The reaction time varies depending on the reaction temperature, the reaction substrate, the reaction amount, etc., but is usually from 10 minutes to 48 hours.

反應之目的物即式[1c]之化合物在反應結束後亦可藉由常規方法從反應系統中採取，因應必要藉由管柱層析法、再結晶等之操作而進行純化。亦或，藉由先前技術內之周知基本方法，式[1c]之胺亦能單獨分離作為酸鹽。 The object of the reaction, that is, the compound of the formula [1c] can also be taken from the reaction system by a conventional method after completion of the reaction, and purification is carried out by an operation such as column chromatography or recrystallization. Alternatively, the amine of formula [1c] can also be isolated separately as the acid salt by the well-known basic method in the prior art.

並且，以本製造方法取得之式[1c]之化合物藉由使用既知方法即可轉換成殺菌性作物保護劑之中間體即式[1a]之化合物(請參照例如WO2008/013925號公報第79頁第8~26行)。 Further, the compound of the formula [1c] obtained by the above production method can be converted into a compound of the formula [1a] which is an intermediate of a bactericidal crop protection agent by using a known method (refer to, for example, WO2008/013925, page 79). Lines 8~26).

(式中，R1及R2係各自獨立為甲基、二氟甲基或三氟甲基)。 (wherein R 1 and R 2 are each independently a methyl group, a difluoromethyl group or a trifluoromethyl group).

<製造方法6> <Manufacturing Method 6>

式[7]所示之本發明化合物係可藉由由下述例示之反應式所構成之方法而製造。 The compound of the present invention represented by the formula [7] can be produced by a method consisting of the reaction formula exemplified below.

(式中，A為選自(1)中所定義之A-1、A-2及A-3之基，R1~R7係如同(1)中所定義，R8為C1~C4烷基、C1~C4烯基、苄基(在此苄基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、C2~C6烷基羰基、C2~C6鹵烷基羰基、苯基羰基(在此苯基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、C2~C6烷氧基羰基、苄基氧基羰基(在此苄基氧基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、苯基氧基羰基(在此苯基氧基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、三苯基甲基、甲醯基或基-SO2R9，R9係如同(1)中所定義，R11、R12、R13、R14、 X1、X2、X3、及X4係分別如同(34)中所定義)。 (wherein A is a group selected from A-1, A-2 and A-3 as defined in (1), R 1 to R 7 are as defined in (1), and R 8 is C 1 to C a tetraalkyl group, a C 1 -C 4 alkenyl group, or a benzyl group (the benzene ring of the benzyl group may be one or more selected from the group consisting of a halogen atom, a C 1 -C 4 alkyl group, or a C 1 -C 4 alkoxy group). Substituted by a substituent), a C 2 -C 6 alkylcarbonyl group, a C 2 -C 6 haloalkylcarbonyl group, a phenylcarbonyl group (wherein the phenyl ring of the phenylcarbonyl group may also be selected from a halogen atom, C 1 -C Substituted with one or more substituents of a 4- alkyl or C 1 -C 4 alkoxy group), a C 2 -C 6 alkoxycarbonyl group, a benzyloxycarbonyl group (wherein the benzene ring of the benzyloxycarbonyl group is also It may be substituted by one or more substituents selected from a halogen atom, a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group), a phenyloxycarbonyl group (the phenyl ring of the phenyloxycarbonyl group here) It may be substituted with one or more substituents selected from a halogen atom, a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group), a triphenylmethyl group, a decyl group or a yl-SO 2 R group. 9 , R 9 is as defined in (1), and R 11 , R 12 , R 13 , R 14 , X 1 , X 2 , X 3 , and X 4 are as defined in (34), respectively.

藉由使式[1]所表示之化合物與式[8]所表示之化合物在溶劑中、酸或路易斯酸之存在下，較佳在酸之存在下進行反應，而可製造式[7]所表示之本發明化合物。 The compound of the formula [7] can be produced by reacting a compound represented by the formula [1] with a compound represented by the formula [8] in the presence of a solvent, an acid or a Lewis acid, preferably in the presence of an acid. A compound of the invention is represented.

在此使用之式[8]之化合物之使用量係相對於式[1]之化合物1莫耳而言，適宜選自1.0~10莫耳之範圍即可，較佳為1.0~3.0莫耳。 The compound of the formula [8] used herein is preferably used in an amount selected from the range of 1.0 to 10 moles, preferably 1.0 to 3.0 moles, relative to the mole of the compound 1 of the formula [1].

作為本步驟中可使用之酸，可舉出例如鹽酸、氫溴酸、硫酸等之無機酸、乙酸、三氟乙酸、p-甲苯磺酸、三氟甲烷磺酸等之有機酸等。 The acid which can be used in this step may, for example, be an inorganic acid such as hydrochloric acid, hydrobromic acid or sulfuric acid, or an organic acid such as acetic acid, trifluoroacetic acid, p-toluenesulfonic acid or trifluoromethanesulfonic acid.

作為本步驟中可使用之路易斯酸，可舉出例如氯化鋅、氯化鋁、氯化錫、三氯化硼、三氟化硼、三氟甲烷磺酸三甲基矽基等。 The Lewis acid which can be used in this step may, for example, be zinc chloride, aluminum chloride, tin chloride, boron trichloride, boron trifluoride or trimethylsulfonium trifluoromethanesulfonate.

相對於式[1]之化合物1莫耳，酸或路易斯酸之使用量係適宜選自0.01~5莫耳之範圍即可，較佳為0.1~1.0莫耳。 The amount of the compound 1 molar, the acid or the Lewis acid used in the formula [1] is suitably selected from the range of 0.01 to 5 moles, preferably 0.1 to 1.0 mole.

作為本步驟中可使用之溶劑，只要係不阻礙本反應進行者即可，可使用例如乙腈等之腈類；二乙基醚、二異丙基醚、四氫呋喃、二噁烷、單甘醇二甲醚、二甘醇二甲醚等之醚類；二氯甲烷、二氯乙烷、氯仿、四氯化碳、四氯乙烷等之鹵化烴類；苯、氯苯、硝基苯、甲苯等之芳香族烴類；N,N-二甲基甲醯胺、N,N-二甲基乙醯胺等之醯胺類；1,3-二甲基-2-咪唑啉酮等之咪唑啉酮類；二甲亞碸等之硫化合物類等，並且亦可使用此等混合溶劑。 As the solvent which can be used in this step, as long as it does not inhibit the progress of the reaction, a nitrile such as acetonitrile or the like; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane or monoglycol can be used. An ether such as methyl ether or diglyme; a halogenated hydrocarbon such as dichloromethane, dichloroethane, chloroform, carbon tetrachloride or tetrachloroethane; benzene, chlorobenzene, nitrobenzene, toluene And other aromatic hydrocarbons; amides such as N,N-dimethylformamide, N,N-dimethylacetamide; imidazoles such as 1,3-dimethyl-2-imidazolidinone Sulphones, sulfur compounds such as dimethyl hydrazine, and the like, and such mixed solvents can also be used.

相對於式[1]之化合物1莫耳，溶劑之使用量係適宜選自0.01~100L之範圍即可，較佳為0.1~10L。 The solvent is preferably used in an amount of from 0.01 to 100 L, preferably from 0.1 to 10 L, based on the compound of the formula [1].

反應溫度係選自-20℃至所使用之惰性溶劑之沸點區域範圍即可，較佳係宜在0℃~150℃之範圍下進行。 The reaction temperature is selected from the range of -20 ° C to the boiling point range of the inert solvent to be used, and it is preferably carried out at a temperature ranging from 0 ° C to 150 ° C.

反應時間係根據反應溫度、反應基質、反應量等而相異，但通常為10分~48小時。 The reaction time varies depending on the reaction temperature, the reaction substrate, the reaction amount, etc., but is usually from 10 minutes to 48 hours.

反應之目的物即式[7]之化合物在反應結束後亦可藉由常規方法從反應系統中採取，因應必要藉由管柱層析法、再結晶等之操作而進行純化。 The object of the reaction, that is, the compound of the formula [7] can also be taken from the reaction system by a conventional method after completion of the reaction, and purification is carried out by an operation such as column chromatography or recrystallization.

<製造方法7> <Manufacturing method 7>

式[7]所示之本發明化合物係藉由由下述例示之反應式所構成之方法而製造。 The compound of the present invention represented by the formula [7] is produced by a method consisting of the following reaction schemes.

(式中，A係選自(1)中所定義之A-1、A-2及A-3之基，R1~R7係如同(1)中所定義，R8為C1~C4烷基、C1~C4烯基、苄基(在此苄基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取 代)、C2~C6烷基羰基、C2~C6鹵烷基羰基、苯基羰基(在此苯基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、C2~C6烷氧基羰基、苄基氧基羰基(在此苄基氧基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、苯基氧基羰基(在此苯基氧基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、三苯基甲基、甲醯基或基-SO2R9，R9係如同(1)中所定義，R10係如同(1)中所定義，R11、R12、R13、R14、X1、X2、X3、及X4係分別如同(34)中所定義)。 (wherein A is selected from the group consisting of A-1, A-2 and A-3 as defined in (1), R 1 to R 7 are as defined in (1), and R 8 is C 1 to C a tetraalkyl group, a C 1 -C 4 alkenyl group, or a benzyl group (the benzene ring of the benzyl group may be one or more selected from the group consisting of a halogen atom, a C 1 -C 4 alkyl group, or a C 1 -C 4 alkoxy group). Substituted by a substituent), a C 2 -C 6 alkylcarbonyl group, a C 2 -C 6 haloalkylcarbonyl group, a phenylcarbonyl group (wherein the phenyl ring of the phenylcarbonyl group may also be selected from a halogen atom, C 1 -C Substituted with one or more substituents of a 4- alkyl or C 1 -C 4 alkoxy group), a C 2 -C 6 alkoxycarbonyl group, a benzyloxycarbonyl group (wherein the benzene ring of the benzyloxycarbonyl group is also It may be substituted by one or more substituents selected from a halogen atom, a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group), a phenyloxycarbonyl group (the phenyl ring of the phenyloxycarbonyl group here) It may be substituted with one or more substituents selected from a halogen atom, a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group), a triphenylmethyl group, a decyl group or a yl-SO 2 R group. 9 , R 9 is as defined in (1), R 10 is as defined in (1), R 11 , R 12 , R 13 , R 14 , X 1 , X 2 , X 3 , and X 4 are respectively As defined in (34).

藉由使式[5a]所表示之化合物與式[8]所表示之化合物在溶劑中、酸或路易斯酸之存在下進行反應，而可製造式[7]所表示之本發明化合物。 The compound of the present invention represented by the formula [7] can be produced by reacting a compound represented by the formula [5a] with a compound represented by the formula [8] in a solvent, an acid or a Lewis acid.

在此使用之式[8]之化合物之使用量係相對於式[5a]之化合物1莫耳而言，適宜選自1.0~10莫耳之範圍即可，較佳為1.0~3.0莫耳。 The compound of the formula [8] used herein is preferably used in an amount selected from the range of 1.0 to 10 moles, preferably 1.0 to 3.0 moles, relative to the mole of the compound 1 of the formula [5a].

作為本步驟中可使用之酸，可舉出例如鹽酸、氫溴酸、硫酸等之無機酸、乙酸、三氟乙酸、p-甲苯磺酸、三氟甲烷磺酸等之有機酸等。 The acid which can be used in this step may, for example, be an inorganic acid such as hydrochloric acid, hydrobromic acid or sulfuric acid, or an organic acid such as acetic acid, trifluoroacetic acid, p-toluenesulfonic acid or trifluoromethanesulfonic acid.

作為本步驟中可使用之路易斯酸，可舉出例如氯化鋅、氯化鋁、氯化錫、三氯化硼、三氟化硼、三氟甲烷磺酸三甲基矽基等。 The Lewis acid which can be used in this step may, for example, be zinc chloride, aluminum chloride, tin chloride, boron trichloride, boron trifluoride or trimethylsulfonium trifluoromethanesulfonate.

相對於式[5a]之化合物1莫耳，酸或路易斯酸之使用 量係適宜選自0.01~5莫耳之範圍即可，較佳為0.1~1.0莫耳。 Use of compound 1 molar, acid or Lewis acid relative to formula [5a] The amount is suitably selected from the range of 0.01 to 5 moles, preferably 0.1 to 1.0 moles.

作為本步驟中可使用之溶劑，只要係不阻礙本反應進行者即可，可使用例如乙腈等之腈類；二乙基醚、二異丙基醚、四氫呋喃、二噁烷、單甘醇二甲醚、二甘醇二甲醚等之醚類；二氯甲烷、二氯乙烷、氯仿、四氯化碳、四氯乙烷等之鹵化烴類；苯、氯苯、硝基苯、甲苯等之芳香族烴類；N,N-二甲基甲醯胺、N,N-二甲基乙醯胺等之醯胺類；1,3-二甲基-2-咪唑啉酮等之咪唑啉酮類；二甲亞碸等之硫化合物類等，並且亦可使用此等之混合溶劑。 As the solvent which can be used in this step, as long as it does not inhibit the progress of the reaction, a nitrile such as acetonitrile or the like; diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane or monoglycol can be used. An ether such as methyl ether or diglyme; a halogenated hydrocarbon such as dichloromethane, dichloroethane, chloroform, carbon tetrachloride or tetrachloroethane; benzene, chlorobenzene, nitrobenzene, toluene And other aromatic hydrocarbons; amides such as N,N-dimethylformamide, N,N-dimethylacetamide; imidazoles such as 1,3-dimethyl-2-imidazolidinone A ketone compound, a sulfur compound such as dimethyl hydrazine, or the like, and a mixed solvent of these may also be used.

相對於式[5a]之化合物1莫耳，溶劑之使用量係適宜選自0.01~100L之範圍即可，較佳為0.1~10L。 The solvent is preferably used in an amount selected from the range of 0.01 to 100 L, preferably 0.1 to 10 L, based on the compound 1 molar of the formula [5a].

反應溫度係選自-20℃至所使用之惰性溶劑之沸點區域範圍即可，較佳係宜在0℃~150℃之範圍下進行。 The reaction temperature is selected from the range of -20 ° C to the boiling point range of the inert solvent to be used, and it is preferably carried out at a temperature ranging from 0 ° C to 150 ° C.

反應時間係根據反應溫度、反應基質、反應量等而相異，但通常為10分~48小時。 The reaction time varies depending on the reaction temperature, the reaction substrate, the reaction amount, etc., but is usually from 10 minutes to 48 hours.

反應之目的物即式[7]之化合物在反應結束後亦可藉由常規方法從反應系統中採取，因應必要藉由管柱層析法、再結晶等之操作而進行純化。 The object of the reaction, that is, the compound of the formula [7] can also be taken from the reaction system by a conventional method after completion of the reaction, and purification is carried out by an operation such as column chromatography or recrystallization.

<中間體製造方法1> <Intermediate Manufacturing Method 1>

(式中，X1、X2、X3、X4係分別如同(34)中所定義)。 (wherein X 1 , X 2 , X 3 , and X 4 are as defined in (34), respectively).

式[8a]之化合物係可藉由使式[70]之化合物在溶劑中使用還原劑進行還原而製造。 The compound of the formula [8a] can be produced by reducing a compound of the formula [70] using a reducing agent in a solvent.

作為本步驟中可使用之還原劑，可舉出如氫化鋁鋰、氫化二異丁基鋁、硼烷等。 The reducing agent which can be used in this step may, for example, be lithium aluminum hydride, diisobutylaluminum hydride or borane.

相對於式[70]之化合物1莫耳，還原劑之使用量係適宜選自1.0~10莫耳之範圍即可，較佳為2.0~5.0莫耳。 The amount of the reducing agent to be used is suitably selected from the range of 1.0 to 10 moles, preferably 2.0 to 5.0 moles, relative to the compound 1 mole of the formula [70].

作為本步驟中可使用之溶劑，可舉出與在製造方法1中所說明之相同者。 The solvent which can be used in this step is the same as that described in the production method 1.

相對於式[70]之化合物1莫耳，溶劑之使用量係適宜選自0.01~100L之範圍即可，較佳為0.1~10L。 The solvent is preferably used in an amount of from 0.01 to 100 L, preferably from 0.1 to 10 L, based on the compound of the formula [70].

反應溫度係選自從-20℃至所使用之惰性溶劑之沸點區域範圍即可，較佳係宜在0℃~100℃之範圍內進行。 The reaction temperature is selected from the range of from -20 ° C to the boiling point range of the inert solvent to be used, and is preferably carried out in the range of from 0 ° C to 100 ° C.

反應時間係根據反應溫度、反應基質、反應量等而相異，但通常為10分~48小時。 The reaction time varies depending on the reaction temperature, the reaction substrate, the reaction amount, etc., but is usually from 10 minutes to 48 hours.

反應之目的物即式[8a]之化合物在反應結束後亦可藉由常規方法從反應系統中採取，因應必要藉由管柱層析法、再結晶等之操作而進行純化。 The object of the reaction, that is, the compound of the formula [8a] can also be taken from the reaction system by a conventional method after completion of the reaction, and purification is carried out by an operation such as column chromatography or recrystallization.

<中間體製造方法2> <Intermediate Manufacturing Method 2>

(式中，X1、X2、X3、X4係分別如同(34)中所定義，R22表示氫原子或C1~C4烷基)。 (wherein, X 1 , X 2 , X 3 and X 4 are each as defined in (34), and R 22 represents a hydrogen atom or a C 1 to C 4 alkyl group).

又，式[8a]之化合物係亦可藉由使式[71]之化合物在溶劑中使用還原劑進行還原而製造。 Further, the compound of the formula [8a] can also be produced by reducing a compound of the formula [71] with a reducing agent in a solvent.

作為本步驟中可使用之還原劑，可舉出與在中間體製造方法1中所說明之相同者。 The reducing agent which can be used in this step is the same as that described in the intermediate production method 1.

相對於式[71]之化合物1莫耳，還原劑之使用量係適宜選自1.0~10莫耳之範圍即可，較佳為2.0~5.0莫耳。 The amount of the reducing agent to be used is suitably selected from the range of 1.0 to 10 moles, preferably 2.0 to 5.0 moles, relative to the compound 1 mole of the formula [71].

作為本步驟中可使用之溶劑，可舉出與在製造方法1中所說明之相同者。 The solvent which can be used in this step is the same as that described in the production method 1.

相對於式[71]之化合物1莫耳，溶劑之使用量係適宜選自0.01~100L之範圍即可，較佳為0.1~10L。 The solvent is preferably used in an amount selected from the range of 0.01 to 100 L, preferably 0.1 to 10 L, based on the compound 1 molar of the formula [71].

反應溫度係選自從-20℃至所使用之惰性溶劑之沸點區域範圍即可，較佳係宜在0℃~100℃之範圍內進行。 The reaction temperature is selected from the range of from -20 ° C to the boiling point range of the inert solvent to be used, and is preferably carried out in the range of from 0 ° C to 100 ° C.

反應時間係根據反應溫度、反應基質、反應量等而相異，但通常為10分~48小時。 The reaction time varies depending on the reaction temperature, the reaction substrate, the reaction amount, etc., but is usually from 10 minutes to 48 hours.

反應之目的物即式[8a]之化合物在反應結束後亦可藉由常規方法從反應系統中採取，因應必要藉由管柱層析法、再結晶等之操作而進行純化。 The object of the reaction, that is, the compound of the formula [8a] can also be taken from the reaction system by a conventional method after completion of the reaction, and purification is carried out by an operation such as column chromatography or recrystallization.

<中間體製造方法3> <Intermediate Manufacturing Method 3>

(式中，R11、R12、X1、X2、X3及X4係分別如同(34)中所定義)。 (wherein R 11 , R 12 , X 1 , X 2 , X 3 and X 4 are as defined in (34), respectively).

式[8b]之化合物係可藉由使式[72]之化合物在溶劑中使用還原劑進行還原而製造。 The compound of the formula [8b] can be produced by reducing a compound of the formula [72] with a reducing agent in a solvent.

作為本步驟中可使用之還原劑，可舉出與在中間體製造方法1中所說明之相同者。 The reducing agent which can be used in this step is the same as that described in the intermediate production method 1.

相對於式[72]之化合物1莫耳，還原劑之使用量係適宜選自1.0~10莫耳之範圍即可，較佳為1.0~3.0莫耳。 The reducing agent is preferably used in an amount selected from the range of 1.0 to 10 moles, preferably 1.0 to 3.0 moles, relative to the compound 1 mole of the formula [72].

作為本步驟中可使用之溶劑，可舉出與在製造方法1中所說明之相同者。 The solvent which can be used in this step is the same as that described in the production method 1.

相對於式[72]之化合物1莫耳，溶劑之使用量係適宜選自0.01~100L之範圍即可，較佳為0.1~10L。 The solvent is preferably used in an amount selected from the range of 0.01 to 100 L, preferably 0.1 to 10 L, based on the compound 1 molar of the formula [72].

反應溫度係選自從-20℃至所使用之惰性溶劑之沸點區域範圍即可，較佳係宜在0℃~100℃之範圍內進行。 The reaction temperature is selected from the range of from -20 ° C to the boiling point range of the inert solvent to be used, and is preferably carried out in the range of from 0 ° C to 100 ° C.

反應時間係根據反應溫度、反應基質、反應量等而相異，但通常為10分~48小時。 The reaction time varies depending on the reaction temperature, the reaction substrate, the reaction amount, etc., but is usually from 10 minutes to 48 hours.

反應之目的物即式[8b]之化合物在反應結束後亦可藉由常規方法從反應系統中採取，因應必要藉由管柱層析 法、再結晶等之操作而進行純化。 The object of the reaction, that is, the compound of the formula [8b] can also be taken from the reaction system by a conventional method after completion of the reaction, if necessary by column chromatography Purification is carried out by an operation such as a method or recrystallization.

可預想到調製式[1]、式[1c]、式[4]、式[5]、式[5a]或式[7]之化合物用之上述幾種試藥及反應條件會有不適合存在於中間體上之特定官能基的情況。於此等之例中，藉由在合成中導入保護/脫保護之手法或官能基之相互轉換，即可取得所欲之生成物。保護基之使用與選項則係對於化學合成領域之業界人士為顯而易知者(參照例如T.W.Greene及P.G.Wuts著、Protective Groups in Organic Synthesis、第4版；Wiley：New York、2007)。業界人士應會體認到根據情況不同，如各別反應流程中所說明，在導入特定試藥後，為了完成式[1]、式[1c]、式[4]、式[5]、式[5a]或式[7]之化合物之合成，而會有可能必須追加實施未說明知常規方法之合成步驟。業界人士應會體認到在為了調製式[1]、式[1c]、式[4]、式[5]、式[5a]或式[7]之化合物所提案之特定順序所示之以外之順序，會有可能必須實施上述反應流程所例示之步驟之組合。 It is expected that the above-mentioned several reagents and reaction conditions for the compound of the formula [1], the formula [1c], the formula [4], the formula [5], the formula [5a] or the formula [7] may be unsuitable for existence. The case of a particular functional group on an intermediate. In such an example, a desired product can be obtained by introducing a protection/deprotection method or a mutual conversion of a functional group in the synthesis. The use and options of protecting groups are well known to those skilled in the chemical synthesis arts (see, for example, T. W. Greene and P. G. Wuts, Protective Groups in Organic Synthesis, 4th edition; Wiley: New York, 2007). The industry should recognize that, depending on the situation, as indicated in the individual reaction procedures, after the introduction of a specific reagent, in order to complete the formula [1], formula [1c], formula [4], formula [5], [5a] or the synthesis of the compound of the formula [7], and it may be necessary to additionally carry out a synthesis step which is not described in the conventional method. Those skilled in the art will recognize that in addition to the specific order suggested for the compounds of formula [1], formula [1c], formula [4], formula [5], formula [5a] or formula [7] In the order of the steps, it may be necessary to implement a combination of the steps exemplified in the above reaction scheme.

[實施例] [Examples]

以下例舉實施例，具體地說明本發明，即使不更加詳細，只要係業界人士即能將本發明利用致最大限度。因此，以下之實施例單僅係解釋成例示性者，而並非係限制本發明揭示內容者。以下之例中之步驟係說明全體合成展開中之各步驟之操作順序者，各步驟之起始原料在其他例或步驟中並不一定必須要藉由已記載操作順序之特定調製 之實施進行調製。 The present invention will be specifically described below by way of examples, and the present invention can be utilized to the fullest extent as long as it is not described in detail. Therefore, the following examples are merely illustrative, and are not intended to limit the invention. The steps in the following examples are illustrative of the sequence of operations of the various steps in the overall synthesis, and the starting materials for each step do not necessarily have to be specifically modulated by the stated sequence of operations in other examples or steps. The implementation is modulated.

尚且，以下之說明中「%」表示重量百分率，「份」表示重量份。 In the following description, "%" means weight percentage, and "part" means parts by weight.

[實施例1]4-(4-甲醯基-2-噻唑基)-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶之調製 [Example 1] 4-(4-Mexyl-2-thiazolyl)-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]B Modulation of sulfhydryl] piperidine

使1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶-4-硫代甲醯胺(990mg)(WO2008/013925號公報記載之化合物)溶解於N,N-二甲基甲醯胺(15mL)，冰冷下添加3-溴-1,1-二甲氧基丙烷-2-酮(710mg)(WO2003/008282號公報記載之化合物)在室溫下攪拌一晚。對反應液添加水，使用乙酸乙酯進行萃取。以水及飽和食鹽水洗淨有機層，以無水硫酸鈉進行乾燥，過濾分離無機物後，減壓下餾除溶劑。藉由使用由快速自動純化裝置(biotage AB公司製/IsoleraTM)所成之矽膠快速層析法(Silica gel flash chromatography)(乙酸乙酯-己烷：50%-100%下析出)純化殘渣，而取得標題化合物作為黃色非晶狀固體(650mg，收率56%)。 1-[2-[5-Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine-4-thiocarbamide (990 mg) (WO2008/ The compound described in 013925 was dissolved in N,N-dimethylformamide (15 mL), and 3-bromo-1,1-dimethoxypropan-2-one (710 mg) was added under ice cooling (WO2003/008282) The compound described in the publication was stirred at room temperature for one night. Water was added to the reaction liquid, and extraction was performed using ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the organic matter was separated by filtration, and the solvent was evaporated under reduced pressure. Purification by flash by using an automatic device (manufactured by Biotage AB / Isolera TM) as to the silica gel flash chromatography (Silica gel flash chromatography) (ethyl acetate - hexane: 50% -100% for the precipitation) The residue was purified The title compound was obtained as a yellow amorphous solid (650 mg, yield: 56%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.75~1.85(m,2H)、2.16~2.28(m,2H)、2.37(s,3H)、2.93(t,1H)、3.28~3.38(m,2H)、4.10(d,1H)、4.59(d,1H)、5.00(m,2H)、6.34(s,1H)、8.11(s,1H)、10.00(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.75~1.85 (m, 2H), 2.16~2.28 (m, 2H), 2.37 (s, 3H), 2.93 (t, 1H), 3.28~ 3.38 (m, 2H), 4.10 (d, 1H), 4.59 (d, 1H), 5.00 (m, 2H), 6.34 (s, 1H), 8.11 (s, 1H), 10.00 (s, 1H).

[實施例2]4-(4-甲醯基-2-噻唑基)-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶之調製 [Example 2] 4-(4-Mexyl-2-thiazolyl)-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]B Modulation of sulfhydryl] piperidine 步驟1：3,3-二甲氧基-2-氧代丙烷-1-基1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶-4-碳醯亞胺硫化酸酯之調製 Step 1: 3,3-Dimethoxy-2-oxopropan-1-yl 1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl] Preparation of acetamido] piperidine-4-carboquinone sulfonate

使1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶-4-硫代甲醯胺(1.0g)溶解於乙酸乙酯(50mL)，添加3-溴-1,1-二甲氧基丙烷-2-酮(770mg)與乙酸鈉(500mg)，在室溫下攪拌一晚。對反應液添加水，使用乙酸乙酯進行萃取。以水及飽和食鹽水洗淨有機層，以無水硫酸鈉進行乾燥，過濾分離無機物後，減壓下餾除溶劑。藉由使用快速自動純化裝置(biotage AB公司製/IsoleraTM)所成之矽膠快速層析法(乙酸乙酯-己烷：50%-100%下析出)純化殘渣，而取得目的生成物作為無色非晶狀固體(1.2g，收率89%)。 Dissolving 1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine-4-thioformamide (1.0 g) in Ethyl acetate (50 mL) was added 3-bromo-1,1-dimethoxypropan-2-one (770 mg) and sodium acetate (500 mg) and stirred at room temperature overnight. Water was added to the reaction liquid, and extraction was performed using ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the organic matter was separated by filtration, and the solvent was evaporated under reduced pressure. By using fast automatic purification apparatus (Biotage AB Corporation / Isolera TM) as to the silica gel flash chromatography (ethyl acetate - hexane: 50% -100% for the precipitation) to give the residue, and obtaining the target product as a colorless Amorphous solid (1.2 g, yield 89%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.67~1.71(m,2H)、1.98~2.04(m,2H)、2.29(s,3H)、2.76~2.87(m,2H)、2.87(m,1H)、3.20(s,3H)、3.51(s,3H)、3.55(m,1H)、3.56(d,1H)、3.95(d,1H)、4.38(s,1H)、4.40~4.50(m,1H)、4.96(m,2H)、6.32(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.67 to 1.71 (m, 2H), 1.98 to 2.04 (m, 2H), 2.29 (s, 3H), 2.76 to 2.87 (m, 2H), 2.87 (m, 1H), 3.20 (s, 3H), 3.51 (s, 3H), 3.55 (m, 1H), 3.56 (d, 1H), 3.95 (d, 1H), 4.38 (s, 1H), 4.40 ~4.50 (m, 1H), 4.96 (m, 2H), 6.32 (s, 1H).

步驟2：4-(4-甲醯基-2-噻唑基)-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶之調製 Step 2: 4-(4-Mexyl-2-thiazolyl)-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl Modulation of piperidine

使上述實施例2之步驟1中取得之生成物(250mg)溶解於乙酸(5mL)，在70℃下攪拌4小時。在減壓下餾除乙酸，對殘渣添加水，使用乙酸乙酯進行萃取。以水及飽和食鹽水洗淨有機層，以無水硫酸鈉進行乾燥，過濾分離無機物後，減壓下餾除溶劑。藉由使用快速自動純化裝置(biotage AB公司製/IsoleraTM)所成之矽膠快速層析法(乙酸乙酯-己烷：50%-100%下析出)純化殘渣，而取得標題化合物作為無色非晶狀固體(192mg，收率90%)。 The product (250 mg) obtained in the above step 1 of Example 2 was dissolved in acetic acid (5 mL), and stirred at 70 ° C for 4 hours. The acetic acid was distilled off under reduced pressure, water was added to the residue, and ethyl acetate was used for extraction. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the organic matter was separated by filtration, and the solvent was evaporated under reduced pressure. By using fast automatic purification apparatus (Biotage AB Corporation / Isolera TM) as to the silica gel flash chromatography (ethyl acetate - hexane: 50% -100% for the precipitation) to give the residue, and obtaining the title compound as a colorless Crystalline solid (192 mg, yield 90%).

[實施例3]4-(4-甲醯基-2-噻唑基)-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶之調製 [Example 3] 4-(4-Mexyl-2-thiazolyl)-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]B Modulation of sulfhydryl] piperidine 步驟1：4-(4-二甲氧基甲基-2-噻唑基)-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶之調製 Step 1: 4-(4-Dimethoxymethyl-2-thiazolyl)-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl] Modulation of ethyl hydrazine

使上述實施例2之步驟1中取得之生成物(338mg)溶解於甲醇(10mL)，添加氯化鋅(76mg)在70℃下攪拌5.5小時。濃縮反應液後，對殘渣添加水，使用乙酸乙酯進行萃取，以水及飽和食鹽水洗淨有機層，以無水硫酸鈉進行乾燥，過濾分離無機物後，減壓下餾除溶劑。藉由使用快速自動純化裝置(biotage AB公司製/IsoleraTM)所成之矽膠快速層析法(乙酸乙酯-己烷：50%-100%下析出)純化殘渣，而取得目的生成物作為無色非晶狀固體(160mg，收率49%)。 The product (338 mg) obtained in the above step 1 of Example 2 was dissolved in methanol (10 mL), and zinc chloride (76 mg) was added and stirred at 70 ° C for 5.5 hours. After the reaction liquid was concentrated, water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and then filtered and then evaporated. By using fast automatic purification apparatus (Biotage AB Corporation / Isolera TM) as to the silica gel flash chromatography (ethyl acetate - hexane: 50% -100% for the precipitation) to give the residue, and obtaining the target product as a colorless Amorphous solid (160 mg, yield 49%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.70~1.83(m,2H)、2.15~2.28(m,2H)、2.32(s,3H)、2.85(t,1H )、3.24~3.36(m,2H)、3.38(s,6H)、4.03(d,1H)、4.98(m,2H)、5.50(s,1H)、6.33(s,1H)、7.30(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.70~1.83 (m, 2H), 2.15~2.28 (m, 2H), 2.32 (s, 3H), 2.85 (t, 1H), 3.24~ 3.36 (m, 2H), 3.38 (s, 6H), 4.03 (d, 1H), 4.98 (m, 2H), 5.50 (s, 1H), 6.33 (s, 1H), 7.30 (s, 1H).

步驟2：4-(4-甲醯基-2-噻唑基)-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶之調製 Step 2: 4-(4-Mexyl-2-thiazolyl)-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl Modulation of piperidine

使藉由上述實施例3之步驟1所得之生成物(690mg)溶解於丙酮(10mL)及水(1mL)，添加p-甲苯磺酸一水合物(0.3g)，在室溫下攪拌2小時。濃縮反應液，對殘渣添加水，使用乙酸乙酯進行萃取。以水及飽和食鹽水洗淨有機層，以無水硫酸鈉進行乾燥，過濾分離無機物後，藉由在減壓下餾除溶劑，而取得標題化合物作為無色非晶狀固體(607mg，收率99%)。 The product (690 mg) obtained in the first step of the above Example 3 was dissolved in acetone (10 mL) and water (1 mL), and p-toluenesulfonic acid monohydrate (0.3 g) was added thereto, and stirred at room temperature for 2 hours. . The reaction solution was concentrated, water was added to the residue, and ethyl acetate was used for extraction. The organic layer was washed with water and a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate, and then filtered, and the solvent was evaporated to give the title compound as a colorless amorphous solid (607 mg, yield: 99%) ).

[實施例4]1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 4] 1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]-4-(4-methylindenyl-2-thiazolyl) Modulation of piperidine

使1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶-4-硫代甲醯胺(與實施例1之1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶-4-硫代甲醯胺同樣方法進行合成)(90mg)溶解於N,N-二甲基甲醯胺(5mL)，冰冷下添加3-溴-1,1-二甲氧基丙烷-2-酮(76mg)，藉由與實施例1之調製同樣地使其反應，進行純化，而取得標題化合物作為黃色非晶狀固體(53mg，收率51%)。 1-[2-[3,5-Bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine-4-thiocarbamamine (with 1 in Example 1) [2-[5-Methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine-4-thioformamide was synthesized in the same manner) (90 mg) dissolved N-N-dimethylformamide (5 mL) was added, and 3-bromo-1,1-dimethoxypropan-2-one (76 mg) was added under ice-cooling, The reaction was purified to give the title compound as a yellow amorphous solid (53 mg, yield 51%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.78~1.95(m,2H)、2.26(dd,2H)、2.94(t,1H)、3.32~3.39(m,2H)、3.94(d,1H)、4.59(d,1H)、5.16(m,2H)、6.53~7.02(m,3H)、8.11(s,1H)、10.01(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.78 to 1.95 (m, 2H), 2.26 (dd, 2H), 2.94 (t, 1H), 3.32 to 3.39 (m, 2H), 3.94 ( d, 1H), 4.59 (d, 1H), 5.16 (m, 2H), 6.53 to 7.02 (m, 3H), 8.11 (s, 1H), 10.01 (s, 1H).

[實施例5]1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 5] 1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]-4-(4-methylindenyl-2-thiazolyl) Modulation of piperidine 步驟1：3,3-二甲氧基-2-氧代丙烷-1-基1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶-4-碳醯亞胺硫化酸酯(carboimidethioate)之調製 Step 1: 3,3-Dimethoxy-2-oxopropan-1-yl 1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetamidine Modulation of carbodiimidethioate

使1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶-4-硫代甲醯胺(790mg)溶解於乙酸乙酯(10mL)，添加3-溴-1,1-二甲氧基丙烷-2-酮(570mg)與乙酸鈉(360mg)，藉由與實施例2步驟1之調製同樣地使其反應，而取得目的生成物作為黃色油狀物(800mg，收率100%)。 Dissolving 1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine-4-thioformamide (790 mg) in ethyl acetate (10 mL), 3-bromo-1,1-dimethoxypropan-2-one (570 mg) and sodium acetate (360 mg) were added, and the reaction was carried out in the same manner as in the preparation of the step 1 of Example 2. The desired product was obtained as a yellow oil (yield: 800 mg, yield: 100%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.66~1.74(m,2H)、1.98~2.13(m,2H)、2.75~2.94(m,2H)、3.17~3.27(m,3H)、3.53(s,3H)、3.57(s,3H)、3.82(d,1H)、4.39(s,1H)、4.40~4.49(m,1H)、5.11(s,2H)、6.52~7.00(m,3H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.66~1.74 (m, 2H), 1.98~2.13 (m, 2H), 2.75~2.94 (m, 2H), 3.17~3.27 (m, 3H) ), 3.53 (s, 3H), 3.57 (s, 3H), 3.82 (d, 1H), 4.39 (s, 1H), 4.40 to 4.49 (m, 1H), 5.11 (s, 2H), 6.52 to 7.00 ( m, 3H).

步驟2：4-(4-甲醯基-2-噻唑基)-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶之調製 Step 2: 4-(4-Mexyl-2-thiazolyl)-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperider Pyridine modulation

使上述實施例5之步驟1中取得之生成物(800mg)溶解於乙酸(11mL)，藉由與實施例2之步驟2之調製同樣地使其反應，進行純化，而取得標題化合物作為黃色非晶狀固體(900mg，收率100%)。 The product obtained in the first step of Example 5 (800 mg) was dissolved in acetic acid (11 mL), and the mixture was reacted in the same manner as in the second step of Example 2, and purified to obtain the title compound as a yellow non. Crystalline solid (900 mg, yield 100%).

[實施例6]1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 6] 1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]-4-(4-methylindenyl-2-thiazolyl) Modulation of piperidine 步驟1：1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]-4-(4-二甲氧基甲基-2-噻唑基)哌啶之調製 Step 1:1-[2-[3,5-Bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]-4-(4-dimethoxymethyl-2-thiazole Modulation of piperidine

使上述實施例5之步驟1中取得之生成物(190mg)溶解於甲醇(10mL)，添加氯化鋅(27mg)，藉由與實施例3之步驟1之調製同樣地使其反應，進行純化，而取得目的生成物作為黃色油狀物(89mg，收率50%)。 The product (190 mg) obtained in the first step of the above-mentioned Example 5 was dissolved in methanol (10 mL), and zinc chloride (27 mg) was added thereto, and the mixture was reacted in the same manner as in the first step of Example 3 to carry out purification. The title product was obtained as a yellow oil (yield: 89 mg, yield 50%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.67~1.83(m,2H)、2.32(d,1H)、2.52(d,1H)、2.86(t,1H)、3.33~3.45(m,2H)、3.53(s,3H)、3.55(s,3H)、3.98(d,1H)、4.73(d,1H)、5.18(m,2H)、5.83(s,1H)、6.55~7.02(m,3H)、7.48(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.67~1.83 (m, 2H), 2.32 (d, 1H), 2.52 (d, 1H), 2.86 (t, 1H), 3.33 to 3.45 ( m, 2H), 3.53 (s, 3H), 3.55 (s, 3H), 3.98 (d, 1H), 4.73 (d, 1H), 5.18 (m, 2H), 5.83 (s, 1H), 6.55 to 7.02 (m, 3H), 7.48 (s, 1H).

步驟2：1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]-4-(4-甲醯基-2-噻唑基)哌啶之調製 Step 2: 1-[2-[3,5-Bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]-4-(4-methylindol-2-thiazolyl)piperidin Pyridine modulation

使上述實施例6之步驟1中取得之生成物(210mg)溶解於丙酮(10mL)及水(1mL)，添加p-甲苯磺酸一水合物(0.3g)，藉由與實施例3之步驟2之調製同樣地 使其反應，而取得標題化合物作為黃色非晶狀固體(193mg，收率100%)。 The product (210 mg) obtained in the above step 1 of Example 6 was dissolved in acetone (10 mL) and water (1 mL), and p-toluenesulfonic acid monohydrate (0.3 g) was added thereto, and the procedure of Example 3 was carried out. Modulation of 2 The title compound was obtained as a yellow amorphous solid (193 mg, yield: 100%).

[實施例7]1-(1,1-二甲基乙基氧基羰基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 7] Preparation of 1-(1,1-dimethylethyloxycarbonyl)-4-(4-methylindenyl-2-thiazolyl)piperidine

使1-(1,1-二甲基乙基氧基羰基)哌啶-4-硫代甲醯胺(370mg)溶解於N,N-二甲基甲醯胺(15mL)，冰冷下添加3-溴-1,1-二甲氧基丙烷-2-酮(450mg)，藉由與實施例1之調製同樣地使其反應，進行純化，而取得標題化合物作為黃色固體(310mg，收率70%)。 1-(1,1-Dimethylethyloxycarbonyl)piperidine-4-thioformamide (370 mg) was dissolved in N,N-dimethylformamide (15 mL). -Bromo-1,1-dimethoxypropan-2-one (450 mg) was reacted in the same manner as in the preparation of Example 1 to give the title compound as a yellow solid (310 mg, yield 70 %).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.48(s,9H)、1.73~1.82(m,2H)、2.12(d,2H)、2.90(t,2H)、3.19~3.25(m,1H)、4.22(m,2H)、8.09(s,1H)、10.00(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.48 (s, 9H), 1.73 to 1.82 (m, 2H), 2.12 (d, 2H), 2.90 (t, 2H), 3.19 to 3.25 ( m, 1H), 4.22 (m, 2H), 8.09 (s, 1H), 10.00 (s, 1H).

[實施例8]1-(1,1-二甲基乙基氧基羰基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 8] Preparation of 1-(1,1-dimethylethyloxycarbonyl)-4-(4-methylindenyl-2-thiazolyl)piperidine 步驟1：3,3-二甲氧基-2-氧代丙烷-1-基1-(1,1-二甲基乙基氧基羰基)哌啶-4-碳醯亞胺硫化酸酯之調製 Step 1: 3,3-Dimethoxy-2-oxopropan-1-yl 1-(1,1-dimethylethyloxycarbonyl)piperidine-4-carbenium imide sulfate modulation

使1-(1,1-二甲基乙基氧基羰基)哌啶-4-硫代甲醯胺(266mg)溶解於乙酸乙酯(8mL)，添加3-溴-1,1-二甲氧基丙烷-2-酮(280mg)與乙酸鈉(180mg)，藉由使實施例2之步驟1之調製同樣地使其反應，而取得目的生成物作為黃色油狀物(390mg，收率100%)。 1-(1,1-Dimethylethyloxycarbonyl)piperidine-4-thioformamide (266 mg) was dissolved in ethyl acetate (8 mL), 3-bromo-1,1-dimethyl The oxypropan-2-one (280 mg) and sodium acetate (180 mg) were reacted in the same manner as in the step 1 of Example 2 to obtain the objective product as a yellow oil (390 mg, yield 100). %).

步驟2：1-(1,1-二甲基乙基氧基羰基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 Step 2: Preparation of 1-(1,1-dimethylethyloxycarbonyl)-4-(4-methylindolyl-2-thiazolyl)piperidine

使上述實施例8之步驟1中取得之生成物(1.47g)溶解於乙酸(10mL)，藉由與實施例2之步驟2之調製同樣地使其反應，進行純化，而取得標題化合物作為黃色固體(450mg，收率37%)。 The product obtained in the first step of Example 8 (1.47 g) was dissolved in acetic acid (10 mL), and the mixture was reacted in the same manner as in the step 2 of Example 2 to obtain the title compound as a yellow compound. Solid (450 mg, yield 37%).

[實施例9]1-(1,1-二甲基乙基氧基羰基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 9] Preparation of 1-(1,1-dimethylethyloxycarbonyl)-4-(4-methylindenyl-2-thiazolyl)piperidine 步驟1：4-(4-二甲氧基甲基-2-噻唑基)-1-(1,1-二甲基乙基氧基羰基)哌啶之調製 Step 1: Preparation of 4-(4-dimethoxymethyl-2-thiazolyl)-1-(1,1-dimethylethyloxycarbonyl)piperidine

使3,3-二甲氧基-2-氧代丙烷-1-基1-(1,1-二甲基乙基氧基羰基)哌啶-4-碳醯亞胺硫化酸酯(320mg)溶解於甲醇(10mL)，添加氯化鋅(74mg)，藉由與實施例3之步驟1之調製同樣地使其反應，進行純化，而取得目的生成物作為黃色油狀物(280mg，收率76%)。 3,3-Dimethoxy-2-oxopropan-1-yl 1-(1,1-dimethylethyloxycarbonyl)piperidine-4-carbenium imide sulfate (320 mg) After dissolving in methanol (10 mL), zinc chloride (74 mg) was added, and the reaction was carried out in the same manner as in the step 1 of Example 3, and the product was obtained as a yellow oil (280 mg, yield 76%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.47(s,9H)、1.72(m,2H)、2.08(m,2H)、2.85(m,2H)、3.20(m,1H)、3.37(s,6H)、4.14(m,1H)、5.50(s,1H)、7.27(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.47 (s, 9H), 1.72 (m, 2H), 2.08 (m, 2H), 2.85 (m, 2H), 3.20 (m, 1H) , 3.37 (s, 6H), 4.14 (m, 1H), 5.50 (s, 1H), 7.27 (s, 1H).

步驟2：1-(1,1-二甲基乙基氧基羰基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 Step 2: Preparation of 1-(1,1-dimethylethyloxycarbonyl)-4-(4-methylindolyl-2-thiazolyl)piperidine

使上述實施例9之步驟1中取得之生成物(230mg)溶解於丙酮(10mL)，添加p-甲苯磺酸一水合物(30mg)，藉由實施例3之步驟2之調製同樣地使其反應，而取得標題化合物作為黃色非晶狀固體(175mg，收率88%)。 The product (230 mg) obtained in the first step of the above-mentioned Example 9 was dissolved in acetone (10 mL), and p-toluenesulfonic acid monohydrate (30 mg) was added thereto, and the same procedure as in the second step of Example 3 was used. The title compound was obtained as a yellow amorphous solid (175 mg, yield: 88%).

[實施例10]1-苄基氧基羰基-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 10] Preparation of 1-benzyloxycarbonyl-4-(4-methylindenyl-2-thiazolyl)piperidine

使1-苄基氧基羰基哌啶-4-硫代甲醯胺(0.9g)溶解於N,丙酮(16mL)，冰冷下添加3-溴-1,1-二甲氧基丙烷-2-酮(0.99g)加熱迴流2小時。濃縮反應液後，對殘渣添加水，使用二氯甲烷進行萃取。以水及飽和食鹽水洗淨有機層，以無水硫酸鈉進行乾燥，過濾分離無機物後，減壓下餾除溶劑。藉由使用快速自動純化裝置(biotage AB公司製/IsoleraTM)所成之矽膠快速層析法(乙酸乙酯-己烷：30%-80%下析出)純化殘渣，而取得標題化合物作為黃色油狀物(0.88mg，收率83%)。 1-Benzyloxycarbonylpiperidine-4-thioformamide (0.9 g) was dissolved in N, acetone (16 mL), and 3-bromo-1,1-dimethoxypropane-2- was added under ice cooling. The ketone (0.99 g) was heated to reflux for 2 hours. After concentrating the reaction mixture, water was added to the residue, and extraction was carried out using dichloromethane. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the organic matter was separated by filtration, and the solvent was evaporated under reduced pressure. By using fast automatic purification apparatus (Biotage AB Corporation / Isolera TM) as to the silica gel flash chromatography (ethyl acetate - hexane: 30% -80% for the precipitation) to give the residue, and the acquired title compound as a yellow oil (0.88 mg, yield 83%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.73~1.87(m,2H)、2.10~2.21(m,2H)、2.99(t,1H)、3.18~3.29(m,2H)、4.29(m,2H)、5.15(s,2H)、7.29~7.36(m,6H)、8.09(s,1H)、10.00(s,1H) 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.73 to 1.87 (m, 2H), 2.10 to 2.21 (m, 2H), 2.99 (t, 1H), 3.18 to 3.29 (m, 2H), 4.29 (m, 2H), 5.15 (s, 2H), 7.29 ~ 7.36 (m, 6H), 8.09 (s, 1H), 10.00 (s, 1H)

[實施例11]1-(苯基羰基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 11] Preparation of 1-(phenylcarbonyl)-4-(4-methylindenyl-2-thiazolyl)piperidine 步驟1：3,3-二甲氧基-2-氧代丙烷-1-基1-(苯基羰基)哌啶-4-碳醯亞胺硫化酸酯之調製 Step 1: Preparation of 3,3-dimethoxy-2-oxopropan-1-yl 1-(phenylcarbonyl)piperidine-4-carbenium imide sulfate

使1-(苯基羰基)哌啶-4-硫代甲醯胺(190mg)溶解於乙酸乙酯(10mL)，添加3-溴-1,1-二甲氧基丙烷-2-酮(195mg)與乙酸鈉(126mg)，藉由與實施例2之步驟1之調製同樣地使其反應，而取得目的生成物作為黃色油狀物(280mg，收率100%)。 1-(Phenylcarbonyl)piperidine-4-thioformamide (190 mg) was dissolved in ethyl acetate (10 mL) and 3-bromo-1,1-dimethoxypropan-2-one (195 mg) And sodium acetate (126 mg) was reacted in the same manner as in the preparation of the step 1 of Example 2 to obtain a desired product as a yellow oil (280 mg, yield: 100%).

步驟2：1-(苯基羰基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 Step 2: Preparation of 1-(phenylcarbonyl)-4-(4-carbamimido-2-thiazolyl)piperidine

使藉由上述實施例11之步驟1所得之生成物(460mg)溶解於乙酸(10mL)，藉由與實施例2之步驟2之調製同樣地使其反應，進行純化，而取得標題化合物作為黃色非晶狀固體(220mg，收率58%)。 The product (460 mg) obtained in the step 1 of the above-mentioned Example 11 was dissolved in acetic acid (10 mL), and was reacted in the same manner as in the step 2 of Example 2 to carry out purification to obtain the title compound as yellow. Amorphous solid (220 mg, yield 58%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.88(m,2H)、2.18(m,1H)、3.08(m,2H)、3.35(m,1H)、3.90(brs,1H)、4.80(brs,1H)、7.42(s,5H)、8.11(s,1H)、10.00(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.88 (m, 2H), 2.18 (m, 1H), 3.08 (m, 2H), 3.35 (m, 1H), 3.90 (brs, 1H) 4.80 (brs, 1H), 7.42 (s, 5H), 8.11 (s, 1H), 10.00 (s, 1H).

[實施例12]1-(苯基羰基)-4-(4-二甲氧基甲基-2-噻唑基)哌啶之調製 [Example 12] Preparation of 1-(phenylcarbonyl)-4-(4-dimethoxymethyl-2-thiazolyl)piperidine

使上述實施例11之步驟1中取得之生成物(280mg)溶解於甲醇(10mL)，添加氯化鋅(52mg)，藉由與實施例3之步驟1之調製同樣地使其 反應，進行純化，而取得標題化合物作為黃色油狀物(100mg，收率38%)。 The product (280 mg) obtained in the above step 11 of Example 11 was dissolved in methanol (10 mL), and zinc chloride (52 mg) was added thereto, and the same procedure as in the step 1 of Example 3 was used. The reaction was purified to give the title compound as a yellow oil (100 mg, yield 38%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.88(m,3H)、2.18(m,2H)、2.93(m,2H)、3.41(s,6H)、3.85(m,1H)、4.84(m,1H)、5.58(s,1H)、7.33(s,1H)、7.41(s,5H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.88 (m, 3H), 2.18 (m, 2H), 2.93 (m, 2H), 3.41 (s, 6H), 3.85 (m, 1H) 4.84 (m, 1H), 5.58 (s, 1H), 7.33 (s, 1H), 7.41 (s, 5H).

[實施例13]1-乙醯基-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 13] Preparation of 1-ethenyl-4-(4-methylindenyl-2-thiazolyl)piperidine

使1-乙醯基哌啶-4-硫代甲醯胺(430mg)(WO2014/075874號公報記載之化合物)溶解於丙酮(24mL)，冰冷下添加3-溴-1,1-二甲氧基丙烷-2-酮(700mg)，藉由與實施例10之調製同樣地使其反應，進行純化，而取得標題化合物作為黃色非晶狀固體(300mg，收率55%)。 1-Ethylpiperidine-4-thioformamide (430 mg) (the compound described in WO2014/075874) was dissolved in acetone (24 mL), and 3-bromo-1,1-dimethoxy was added under ice cooling. The propane-2-one (700 mg) was reacted in the same manner as in the preparation of Example 10, and the title compound was obtained as a yellow amorphous solid (300 mg, yield 55%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.75~1.86(m,2H)、2.13(s,3H)、2.20(m,2H)、2.76(t,1H)、3.21~3.34(m,2H)、3.95(d,1H)、4.70(d,1H)、8.10(s,1H)、10.00(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.75 to 1.86 (m, 2H), 2.13 (s, 3H), 2.20 (m, 2H), 2.76 (t, 1H), 3.21 to 3.34 ( m, 2H), 3.95 (d, 1H), 4.70 (d, 1H), 8.10 (s, 1H), 10.00 (s, 1H).

[實施例14]1-(2,2-二甲基丙醯基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 14] Preparation of 1-(2,2-dimethylpropionyl)-4-(4-methylindenyl-2-thiazolyl)piperidine

使1-(2,2-二甲基丙醯基)哌啶-4-硫代甲醯胺(470mg)溶解於N,N-二甲基甲醯胺(20mL)，冰冷下 添加3-溴-1,1-二甲氧基丙烷-2-酮(590mg)，藉由與實施例1之調製同樣地使其反應，進行純化，而取得標題化合物作為黃色油狀物(390mg，收率70%)。 Dissolve 1-(2,2-dimethylpropionyl)piperidine-4-thioformamide (470 mg) in N,N-dimethylformamide (20 mL), ice cold 3-Bromo-1,1-dimethoxypropan-2-one (590 mg) was added, and the mixture was reacted in the same manner as in Example 1 to give the title compound as a yellow oil (390 mg) , yield 70%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.31(s,9H)、1.75~1.89(m,2H)、2.10(d,2H)、3.00(t,2H)、3.29~3.39(m,1H)、4.52(d,2H)、8.10(s,1H)、10.00(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.31 (s, 9H), 1.75 to 1.89 (m, 2H), 2.10 (d, 2H), 3.00 (t, 2H), 3.29 to 3.39 ( m, 1H), 4.52 (d, 2H), 8.10 (s, 1H), 10.00 (s, 1H).

[實施例15]1-(2,2-二甲基丙醯基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 15] Preparation of 1-(2,2-dimethylpropionyl)-4-(4-methylindenyl-2-thiazolyl)piperidine 步驟1：3,3-二甲氧基-2-氧代丙烷-1-基1-(2,2-二甲基丙醯基)哌啶-4-碳醯亞胺硫化酸酯之調製 Step 1: Preparation of 3,3-dimethoxy-2-oxopropan-1-yl 1-(2,2-dimethylpropionyl)piperidine-4-carbenium imide sulfonate

使1-(2,2-二甲基丙醯基)哌啶-4-硫代甲醯胺(0.91g)溶解於乙酸乙酯(20mL)，添加3-溴-1,1-二甲氧基丙烷-2-酮(1.0g)與乙酸鈉(0.66g)，藉由與實施例2之步驟1之調製同樣地使其反應，進行純化，而取得目的生成物作為黃色油狀物(0.67g，收率49%)。 1-(2,2-Dimethylpropionyl)piperidine-4-thioformamide (0.91 g) was dissolved in ethyl acetate (20 mL) and 3-bromo-1,1-dimethoxy The propane-2-one (1.0 g) and sodium acetate (0.66 g) were reacted in the same manner as in the first step of Example 2, and purified to obtain the desired product as a yellow oil (0.67). g, yield 49%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.28(s,9H)、1.64~1.74(m,2H)、1.99(d,2H)、2.75~2.82(m,1H)、2.91(t,2H)、3.17(m,2H)、3.52(s,3H)、3.56(s,3H)、4.38(s,1H)、4.40(d,2H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.28 (s, 9H), 1.64 to 1.74 (m, 2H), 1.99 (d, 2H), 2.75 to 2.82 (m, 1H), 2.91 ( t, 2H), 3.17 (m, 2H), 3.52 (s, 3H), 3.56 (s, 3H), 4.38 (s, 1H), 4.40 (d, 2H).

步驟2：1-(2,2-二甲基丙醯基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 Step 2: Preparation of 1-(2,2-dimethylpropionyl)-4-(4-methylindolyl-2-thiazolyl)piperidine

使上述實施例15之步驟1中取得之生成物(320mg)溶解於乙酸(10mL)，藉由與實施例2步驟2之調製同樣地使其反應，進行純化，而取得標題化合物作為黃色油狀物(200mg，收率77%)。 The product (320 mg) obtained in the first step of the above-mentioned Example 15 was dissolved in acetic acid (10 mL), and was reacted in the same manner as in the second step of Example 2 to carry out purification to obtain the title compound as a yellow oil. (200 mg, yield 77%).

[實施例16]1-(2,2-二甲基丙醯基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 16] Preparation of 1-(2,2-dimethylpropionyl)-4-(4-methylindenyl-2-thiazolyl)piperidine

使1-(2,2-二甲基丙醯基)-4-(4-二甲氧基甲基-2-噻唑基)哌啶(176mg)溶解於丙酮(10mL)及水(1mL)，添加p-甲苯磺酸一水合物(0.1g)，藉由與實施例3步驟2之調製同樣地使其反應，而取得標題化合物作為黃色油狀物(150mg，收率99%)。 1-(2,2-Dimethylpropenyl)-4-(4-dimethoxymethyl-2-thiazolyl)piperidine (176 mg) was dissolved in acetone (10 mL) and water (1 mL). The p-toluenesulfonic acid monohydrate (0.1 g) was added, and the title compound was obtained as a yellow oil (150 mg, yield 99%).

[實施例17]1-(甲氧基羰基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 17] Preparation of 1-(methoxycarbonyl)-4-(4-methylindenyl-2-thiazolyl)piperidine 步驟1：3,3-二甲氧基-2-氧代丙烷-1-基1-(甲氧基羰基)哌啶-4-碳醯亞胺硫化酸酯之調製 Step 1: Preparation of 3,3-dimethoxy-2-oxopropan-1-yl 1-(methoxycarbonyl)piperidine-4-carbenium imide sulfonate

使1-(甲氧基羰基)哌啶-4-硫代甲醯胺(1.07g)溶解於乙酸乙酯(25mL)，添加3-溴-1,1-二甲氧基丙烷-2-酮(1.36g)與乙酸鈉(0.87g)，藉由與實施例2之步驟1之調製同樣地使其反應，而取得目的生成物作為黃色油狀物(1.58g，收率93%)。 1-(Methoxycarbonyl)piperidine-4-thioformamide (1.07 g) was dissolved in ethyl acetate (25 mL) and 3-bromo-1,1-dimethoxypropan-2-one was added. (1.36 g) and sodium acetate (0.87 g) were reacted in the same manner as in the step 1 of Example 2 to obtain the objective product as a yellow oil (1.58 g, yield 93%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.59~1.72(m,2H)、1.94(d,2H)、2.66~2.74(m,1H)、2.86(t,2H )、3.47(m,2H)、3.51(s,3H)、3.56(s,3H)、3.69(s,3H)、4.06~4.21(m,2H)、4.39(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.59~1.72 (m, 2H), 1.94 (d, 2H), 2.66~2.74 (m, 1H), 2.86 (t, 2H), 3.47 ( m, 2H), 3.51 (s, 3H), 3.56 (s, 3H), 3.69 (s, 3H), 4.06 to 4.21 (m, 2H), 4.39 (s, 1H).

步驟2：1-(甲氧基羰基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 Step 2: Preparation of 1-(methoxycarbonyl)-4-(4-methylindolyl-2-thiazolyl)piperidine

使上述實施例17之步驟1中取得之生成物(1.58g)溶解於乙酸(10mL)，藉由與實施例2之步驟2之調製同樣地使其反應，進行純化，而取得標題化合物作為黃色油狀物(0.48g，收率38%)。 The product obtained in the first step of the above-mentioned Example 17 (1.58 g) was dissolved in acetic acid (10 mL), and the mixture was reacted in the same manner as in the second step of Example 2, and purified to give the title compound as yellow. Oil (0.48 g, yield 38%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.76~1.83(m,2H)、2.15(d,2H)、2.96(t,2H)、3.21~3.27(m,1H)、3.72(s,3H)、4.26(m,1H)、8.09(s,1H)、10.00(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.76~1.83 (m, 2H), 2.15 (d, 2H), 2.96 (t, 2H), 3.21 to 3.27 (m, 1H), 3.72 ( s, 3H), 4.26 (m, 1H), 8.09 (s, 1H), 10.00 (s, 1H).

[實施例18]1-(乙氧基羰基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 18] Preparation of 1-(ethoxycarbonyl)-4-(4-methylindenyl-2-thiazolyl)piperidine

使1-(乙氧基羰基)哌啶-4-硫代甲醯胺(0.87g)溶解於N,N-二甲基甲醯胺(20mL)，冰冷下添加3-溴-1,1-二甲氧基丙烷-2-酮(1.18g)，藉由與實施例1之調製同樣地使其反應，而取得標題化合物作為黃色油狀物(0.51g，收率48%)。 1-(Ethoxycarbonyl)piperidine-4-thioformamide (0.87 g) was dissolved in N,N-dimethylformamide (20 mL), and 3-bromo-1,1- Dimethoxypropan-2-one (1.18 g) was reacted in the same manner as in the preparation of Example 1 to give the title compound as a yellow oil (0.51 g, yield: 48%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.28(s,3H)、1.73~1.84(m,2H)、2.15(d,2H)、2.95(t,2H)、3.21~3.27(m,1H)、4.15(q,2H)、4.27(d,2H)、8.09 (s,1H)、10.00(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.28 (s, 3H), 1.73 to 1.84 (m, 2H), 2.15 (d, 2H), 2.95 (t, 2H), 3.21 to 3.27 ( m, 1H), 4.15 (q, 2H), 4.27 (d, 2H), 8.09 (s, 1H), 10.00 (s, 1H).

[實施例19]1-(乙氧基羰基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 19] Preparation of 1-(ethoxycarbonyl)-4-(4-methylindenyl-2-thiazolyl)piperidine 步驟1：3,3-二甲氧基-2-氧代丙烷-1-基1-(乙氧基羰基)哌啶-4-碳醯亞胺硫化酸酯之調製 Step 1: Preparation of 3,3-dimethoxy-2-oxopropan-1-yl 1-(ethoxycarbonyl)piperidine-4-carbenium imide sulfonate

使1-(乙氧基羰基)哌啶-4-硫代甲醯胺(1.97g)溶解於乙酸乙酯(30mL)，添加3-溴-1,1-二甲氧基丙烷-2-酮(2.33g)與乙酸鈉(1.49g)，藉由與實施例2之步驟1之調製同樣地使其反應，進行純化，而取得目的生成物作為黃色油狀物(3.1g，收率100%)。 1-(Ethoxycarbonyl)piperidine-4-thioformamide (1.97 g) was dissolved in ethyl acetate (30 mL) and 3-bromo-1,1-dimethoxypropan-2-one was added. (2.33 g) and sodium acetate (1.49 g) were reacted in the same manner as in the step 1 of Example 2, and purified to obtain the objective product as a yellow oil (3.1 g, yield 100%) ).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.26(t,3H)、1.59~1.71(m,2H)、1.93(d,2H)、2.67~2.76(m,1H)、2.86(t,2H)、3.45(m,2H)、3.52(s,3H)、3.56(s,3H)、3.69(s,3H)、4.09~4.22(m,4H)、4.39(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.26 (t, 3H), 1.59 to 1.71 (m, 2H), 1.93 (d, 2H), 2.67 to 2.76 (m, 1H), 2.86 ( t, 2H), 3.45 (m, 2H), 3.52 (s, 3H), 3.56 (s, 3H), 3.69 (s, 3H), 4.09 to 4.22 (m, 4H), 4.39 (s, 1H).

步驟2：1-(乙氧基羰基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 Step 2: Preparation of 1-(ethoxycarbonyl)-4-(4-methylindolyl-2-thiazolyl)piperidine

使上述實施例19之步驟1中取得之生成物(3.1g)溶解於乙酸(18mL)，藉由與實施例2之步驟2之調製同樣地使其反應，進行純化，而取得標題化合物作為黃色油狀物(1.08g，收率44%)。 The product (3.1 g) obtained in the first step of the above-mentioned Example 19 was dissolved in acetic acid (18 mL), and the mixture was reacted in the same manner as in the second step of Example 2, and purified to give the title compound as yellow. Oil (1.08 g, yield 44%).

[實施例20]1-(乙氧基羰基)-4-(4-二甲氧基甲基-2-噻唑基)哌啶之調製 [Example 20] Preparation of 1-(ethoxycarbonyl)-4-(4-dimethoxymethyl-2-thiazolyl)piperidine

使上述實施例19之步驟1中取得之生成物(0.53g)溶解於甲醇(16mL)，添加氯化鋅(110mg)，藉由與實施例3之步驟1之調製同樣地使其反應，進行純化，而取得標題化合物作為黃色油狀物(180mg，收率36%)。 The product (0.53 g) obtained in the first step of the above-mentioned Example 19 was dissolved in methanol (16 mL), and zinc chloride (110 mg) was added thereto, and the mixture was reacted in the same manner as in the first step of Example 3 to carry out a reaction. The title compound was obtained as a yellow oil (180 mg, yield 36%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.26(t,3H)、1.67~1.78(m,2H)、211(d,2H)、2.91(t,2H)、3.17~3.24(m,1H)、3.37(s,6H)、4.15(q,2H)、4.24(m,1H)、5.50(s,1H)、7.28(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.26 (t, 3H), 1.67 to 1.78 (m, 2H), 211 (d, 2H), 2.91 (t, 2H), 3.17 to 3.24 ( m, 1H), 3.37 (s, 6H), 4.15 (q, 2H), 4.24 (m, 1H), 5.50 (s, 1H), 7.28 (s, 1H).

[實施例21]1-(2,2-二甲基丙醯基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 21] Preparation of 1-(2,2-dimethylpropionyl)-4-(4-methylindenyl-2-thiazolyl)piperidine 步驟1：1-(2,2-二甲基丙醯基)-4-(4-二氯甲基-2-噻唑基)哌啶之調製 Step 1:1-(2,2-Dimethylpropionyl)-4-(4-dichloromethyl-2-thiazolyl)piperidine

使1-(2,2-二甲基丙醯基)哌啶-4-硫代甲醯胺(400mg)與溴化四丁基銨(58mg)溶解於乙酸乙酯(7mL)，添加1,1,3-三氯丙烷-2-酮(80%，389mg)，在80℃下攪拌4小時。其後返回室溫，對反應液添加水，使用乙酸乙酯進行萃取。以飽和食鹽水洗淨有機層，以無水硫酸鎂進行乾燥，過濾分離無機物後，減壓下餾除溶劑。藉由使用快速自動純化裝置(biotage AB公司製/IsoleraTM)所成之矽膠快速層析法(乙酸乙酯-己烷：0%-100%下析出)純化殘渣，而取得目的生成物作為茶色油 狀物(250mg，收率43%)。 1-(2,2-Dimethylpropionyl)piperidine-4-thioformamide (400 mg) and tetrabutylammonium bromide (58 mg) were dissolved in ethyl acetate (7 mL). 1,3-Trichloropropan-2-one (80%, 389 mg) was stirred at 80 ° C for 4 hours. Thereafter, the mixture was returned to room temperature, and water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. By using fast automatic purification apparatus (Biotage AB Corporation / Isolera TM) as to the silica gel flash chromatography (ethyl acetate - hexanes: 0% -100% for the precipitation) to give the residue, to obtain the target product as a brown and Oil (250 mg, yield 43%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.30(s,9H)、1.69~1.79(m,2H)、2.18(d,2H)、2.97(t,2H)、3.24~3.32(m,1H)、4.50(d,2H)、6.81(s,1H)、7.48(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.30 (s, 9H), 1.69 to 1.79 (m, 2H), 2.18 (d, 2H), 2.97 (t, 2H), 3.24 to 3.32 ( m, 1H), 4.50 (d, 2H), 6.81 (s, 1H), 7.48 (s, 1H).

步驟2：1-(2,2-二甲基丙醯基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 Step 2: Preparation of 1-(2,2-dimethylpropionyl)-4-(4-methylindolyl-2-thiazolyl)piperidine

使上述實施例21之步驟1中取得之生成物(250mg)與純化水(1mL)溶解於乙酸(4mL)，在80℃下加熱4小時。冷卻至室溫後，減壓下餾除溶劑。藉由使用快速自動純化裝置(biotage AB公司製/IsoleraTM)所成之矽膠快速層析法(乙酸乙酯-己烷：0%-100%下析出)純化殘渣，而取得標題化合物作為米黃色固體(140mg，收率67%)。 The product (250 mg) obtained in the above step 1 of Example 21 and purified water (1 mL) were dissolved in acetic acid (4 mL), and heated at 80 ° C for 4 hours. After cooling to room temperature, the solvent was evaporated under reduced pressure. By using fast automatic purification apparatus (Biotage AB Corporation / Isolera TM) as to the silica gel flash chromatography (ethyl acetate - hexanes: 0% -100% for the precipitation) to give the residue, and the acquired title compound as a beige Solid (140 mg, yield 67%).

[實施例22]1-乙醯基-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 22] Preparation of 1-ethenyl-4-(4-methylindenyl-2-thiazolyl)piperidine 步驟1：1-乙醯基-4-(4-二氯甲基-2-噻唑基)哌啶之調製 Step 1:1:1 Preparation of ethionyl-4-(4-dichloromethyl-2-thiazolyl)piperidine

使1-乙醯基哌啶-4-硫代甲醯胺(260mg)與溴化四丁基銨(45mg)溶解於乙酸乙酯(7mL)，添加1,1,3-三氯丙烷-2-酮(80%，309mg)，在80℃下攪拌4小時。其後返回室溫，對反應液添加水，使用乙酸乙酯進行萃取。以飽和食鹽水洗淨有機層，以無水硫酸鎂進行乾燥，過濾分 離無機物後，減壓下餾除溶劑。藉由使用快速自動純化裝置(biotage AB公司製/IsoleraTM)所成之矽膠快速層析法(乙酸乙酯-己烷：0%-100%、甲醇-乙酸乙酯：0%-20%下析出)純化殘渣，而取得目的生成物作為茶色油狀物(130mg，收率32%)。 1-Ethylpiperidine-4-thioformamide (260 mg) and tetrabutylammonium bromide (45 mg) were dissolved in ethyl acetate (7 mL), and 1,1,3-trichloropropane-2 was added. Ketone (80%, 309 mg), stirred at 80 ° C for 4 hours. Thereafter, the mixture was returned to room temperature, and water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. By using fast automatic purification apparatus (Biotage AB Corporation / Isolera TM) as to the silica gel flash chromatography (ethyl acetate - hexanes: 0% -100% methanol - ethyl acetate: 0% -20% lower The residue was purified, and the title compound was obtained as a brown oil (130 mg, yield 32%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.76~1.84(m,2H)、2.12(s,3H)、2.10~2.23(m,2H)、2.76(m,2H)、3.18~3.30(m,2H)、3.92(d、1H)、4.68(d,2H)、6.80(s,1H)、7.48(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.76~1.84 (m, 2H), 2.12 (s, 3H), 2.10~2.23 (m, 2H), 2.76 (m, 2H), 3.18~ 3.30 (m, 2H), 3.92 (d, 1H), 4.68 (d, 2H), 6.80 (s, 1H), 7.48 (s, 1H).

步驟2：1-乙醯基-4-(4-甲醯基-2-噻唑基)哌啶之調製 Step 2: Preparation of 1-Ethyl-4-(4-methylindenyl-2-thiazolyl)piperidine

使上述實施例22之步驟1中取得之生成物(130mg)與純化水(1mL)溶解於乙酸(4mL)，80℃下加熱4小時。冷卻至室溫後，減壓下餾除溶劑。藉由使用快速自動純化裝置(biotage AB公司製/IsoleraTM)所成之矽膠快速層析法(乙酸乙酯-己烷：0%-100%、甲醇-乙酸乙酯：0%-20%下析出)純化殘渣，而取得標題化合物作為茶色非晶狀固體(105mg，收率100%)。 The product (130 mg) obtained in the step 1 of the above Example 22 and purified water (1 mL) were dissolved in acetic acid (4 mL), and heated at 80 ° C for 4 hours. After cooling to room temperature, the solvent was evaporated under reduced pressure. By using fast automatic purification apparatus (Biotage AB Corporation / Isolera TM) as to the silica gel flash chromatography (ethyl acetate - hexanes: 0% -100% methanol - ethyl acetate: 0% -20% lower The residue was purified to give the title compound as a pale brown solid (105 mg, yield 100%).

[實施例23]4-(4-甲醯基-2-噻唑基)-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶之調製 [Example 23] 4-(4-Mexyl-2-thiazolyl)-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]B Modulation of sulfhydryl] piperidine 步驟1：4-(4-二氯甲基-2-噻唑基)-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶之調製 Step 1: 4-(4-Dichloromethyl-2-thiazolyl)-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetamidine Modulation of piperidine

使1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯 基]哌啶-4-硫代甲醯胺(5.0g)與硫酸氫四丁基銨(250mg)溶解於乙酸乙酯(20mL)，添加1,1,3-三氯丙烷-2-酮(80%，3.34g)，在80℃下攪拌3小時。其後返回室溫，對反應液添加水，使用乙酸乙酯進行萃取。以無水硫酸鈉乾燥有機層，過濾分離無機物後，減壓下餾除溶劑。從甲醇-水15%使殘渣進行再結晶，而取得目的生成物作為淡黃色非晶狀固體(5.20g，收率79%)。 1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetamidine Basepiperidin-4-thioformamide (5.0 g) and tetrabutylammonium hydrogen sulfate (250 mg) were dissolved in ethyl acetate (20 mL), and 1,1,3-trichloropropan-2-one was added ( 80%, 3.34 g), stirred at 80 ° C for 3 hours. Thereafter, the mixture was returned to room temperature, and water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the organic matter was separated by filtration. The residue was recrystallized from methanol-water (15%) to obtain the objective product as a pale yellow amorphous solid (5.20 g, yield: 79%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.74~1.80(m,2H)、2.21(t、2H)、2.32(s,3H)、2.85~2.92(m,2H)、3.27~3.32(m,2H)、4.04(d,1H)、5.00(m、2H)、6.34(s,1H)、6.81(s,1H)、7.50(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.74~1.80 (m, 2H), 2.21 (t, 2H), 2.32 (s, 3H), 2.85~2.92 (m, 2H), 3.27~ 3.32 (m, 2H), 4.04 (d, 1H), 5.00 (m, 2H), 6.34 (s, 1H), 6.81 (s, 1H), 7.50 (s, 1H).

步驟2：4-(4-甲醯基-2-噻唑基)-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶之調製 Step 2: 4-(4-Mexyl-2-thiazolyl)-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl Modulation of piperidine

使上述實施例23之步驟1中取得之生成物(3.0g)與純化水(2mL)溶解於乙酸(8mL)，在100℃下加熱1.5小時。冷卻至室溫後，減壓下餾除溶劑。對殘渣添加水，以乙酸乙酯進行萃取。以硫酸鈉乾燥有機層後，過濾分離去除無機物，減壓下餾除溶劑。藉由使殘渣溶解於甲醇並在減壓下餾除溶劑，而取得標題化合物作為黃色液體(2.64g，收率99%)。 The product obtained in the first step of Example 23 (3.0 g) and purified water (2 mL) were dissolved in acetic acid (8 mL) and heated at 100 ° C for 1.5 hours. After cooling to room temperature, the solvent was evaporated under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate. After drying the organic layer with sodium sulfate, the inorganic substance was separated by filtration, and the solvent was evaporated under reduced pressure. The title compound was obtained as a yellow liquid (2.64 g, yield 99%) by dissolving the residue in methanol and distilling solvent under reduced pressure.

[實施例24]1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 24] 1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]-4-(4-methylindenyl-2-thiazolyl) Modulation of piperidine 步驟1：1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]-4-(4-二氯甲基-2-噻唑基)哌啶之調製 Step 1: 1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]-4-(4-dichloromethyl-2-thiazolyl) Modulation of piperidine

使1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶-4-硫代甲醯胺(2.0g)與硫酸氫四丁基銨(97mg)溶解於乙酸乙酯(10mL)，添加1,1,3-三氯丙烷-2-酮(80%，1.27g)，在80℃下攪拌4.5小時。其後返回室溫，對反應液添加水，使用乙酸乙酯進行萃取。以無水硫酸鈉乾燥有機層，過濾分離無機物後，減壓下餾除溶劑。藉由使用快速自動純化裝置(biotage AB公司製/IsoleraTM)所成之矽膠快速層析法(乙酸乙酯-己烷：20%-50%下析出)純化殘渣，而取得目的生成物作為淡黃色非晶狀固體(1.7g，收率65%)。 1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine-4-thioformamide (2.0 g) with hydrogen sulfate The butylammonium (97 mg) was dissolved in ethyl acetate (10 mL), and 1,1,3-trichloropropan-2-one (80%, 1.27 g) was added, and the mixture was stirred at 80 ° C for 4.5 hours. Thereafter, the mixture was returned to room temperature, and water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the organic matter was separated by filtration. By using fast automatic purification apparatus (Biotage AB Corporation / Isolera TM) as to the silica gel flash chromatography (ethyl acetate - hexane: 20% -50% for the precipitation) to give the residue, and obtaining the target product as a pale Yellow amorphous solid (1.7 g, yield 65%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.74~1.86(m,2H)、2.20(d、2H)、2.28(d,2H)、2.92(t,1H)、3.32(m,2H)、3.92(d,1H)、4.57(d,1H)、5.14(m、2H)、6.52~7.02(m,4H)、7.50(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.74~1.86 (m, 2H), 2.20 (d, 2H), 2.28 (d, 2H), 2.92 (t, 1H), 3.32 (m, 2H), 3.92 (d, 1H), 4.57 (d, 1H), 5.14 (m, 2H), 6.52 to 7.02 (m, 4H), 7.50 (s, 1H).

步驟2：1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]-4-(4-甲醯基-2-噻唑基)哌啶之調製 Step 2: 1-[2-[3,5-Bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]-4-(4-methylindol-2-thiazolyl)piperidin Pyridine modulation

使上述實施例24之步驟1中取得之生成物(350mg)與純化水(0.75mL)溶解於乙酸(2.25mL)，在80℃下加熱2.5小時。冷卻至室溫後，減壓下餾除溶劑。對殘渣添加水，使用乙酸乙酯萃取2次。以硫酸鈉乾燥有機層後，過濾分離去除無機物，在減壓下餾除溶劑， 而取得標題化合物作為淡黃色非晶狀固體(276mg、90%)。 The product obtained in the first step of Example 24 (350 mg) and purified water (0.75 mL) were dissolved in acetic acid (2.25 mL), and heated at 80 ° C for 2.5 hours. After cooling to room temperature, the solvent was evaporated under reduced pressure. Water was added to the residue, and extracted twice with ethyl acetate. After drying the organic layer with sodium sulfate, the inorganic matter was removed by filtration, and the solvent was distilled off under reduced pressure. The title compound was obtained as a pale yellow amorphous solid (276 mg, 90%).

[實施例25]1-(苯基羰基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 25] Preparation of 1-(phenylcarbonyl)-4-(4-methylindenyl-2-thiazolyl)piperidine 步驟1：1-(苯基羰基)-4-(4-二氯甲基-2-噻唑基)哌啶之調製 Step 1:1-(Phenylcarbonyl)-4-(4-dichloromethyl-2-thiazolyl)piperidine

使1-(苯基羰基)哌啶-4-硫代甲醯胺(410mg)與溴化四丁基銨(27mg)溶解與乙酸乙酯(10mL)，添加1,1,3-三氯丙烷-2-酮(80%，366mg)，在80℃下攪拌3.5小時。其後返回室溫，對反應液添加水，使用乙酸乙酯萃取2次。以無水硫酸鈉乾燥有機層，過濾分離無機物後，減壓下餾除溶劑。藉由使用快速自動純化裝置(biotage AB公司製/IsoleraTM)所成之矽膠快速層析法(乙酸乙酯-己烷：20%-50%下析出)純化殘渣，而取得目的生成物作為無色固體(365mg，收率62%)。 1-(Phenylcarbonyl)piperidine-4-thioformamide (410 mg) and tetrabutylammonium bromide (27 mg) were dissolved in ethyl acetate (10 mL), and 1,1,3-trichloropropane was added. 2-ketone (80%, 366 mg) was stirred at 80 ° C for 3.5 hours. Thereafter, the mixture was returned to room temperature, water was added to the reaction mixture, and extracted twice with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the organic matter was separated by filtration. By using fast automatic purification apparatus (Biotage AB Corporation / Isolera TM) as to the silica gel flash chromatography (ethyl acetate - hexane: 20% -50% for the precipitation) to give the residue, and obtaining the target product as a colorless Solid (365 mg, yield 62%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.82(br s,2H)、2.17(br s、2H)、3.08(br d,2H)、3.31(m,1H)、3.89(br s,1H)、4.79(br s,1H)、6.81(s,1H)、7.42(s,5H)、7.49(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.82 (br s, 2H), 2.17 (br s, 2H), 3.08 (br d, 2H), 3.31 (m, 1H), 3.89 (br) s, 1H), 4.79 (br s, 1H), 6.81 (s, 1H), 7.42 (s, 5H), 7.49 (s, 1H).

步驟2：1-(苯基羰基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 Step 2: Preparation of 1-(phenylcarbonyl)-4-(4-carbamimido-2-thiazolyl)piperidine

使上述實施例25之步驟1中取得之生成物 (365mg)與純化水(0.5mL)溶解於乙酸(2mL)，在80℃下加熱2.5小時。冷卻至室溫後，減壓下餾除溶劑。對殘渣添加水，使用乙酸乙酯萃取2次。以硫酸鈉乾燥有機層後，過濾分離去除無機物，減壓下餾除溶劑。藉此而取得標題化合物作為黃色非晶狀固體(286mg、90%)。 The product obtained in the first step of the above Example 25 was obtained. (365 mg) and purified water (0.5 mL) were dissolved in acetic acid (2 mL) and heated at 80 ° C for 2.5 hours. After cooling to room temperature, the solvent was evaporated under reduced pressure. Water was added to the residue, and extracted twice with ethyl acetate. After drying the organic layer with sodium sulfate, the inorganic substance was separated by filtration, and the solvent was evaporated under reduced pressure. The title compound was obtained as a yellow amorphous solid (286 mg, 90%).

[實施例26]1-(1,1-二甲基乙基氧基羰基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 26] Preparation of 1-(1,1-dimethylethyloxycarbonyl)-4-(4-methylindenyl-2-thiazolyl)piperidine 步驟1：1-(1,1-二甲基乙基氧基羰基)-4-(4-二氯甲基-2-噻唑基)哌啶之調製 Step 1:1-(1,1-Dimethylethyloxycarbonyl)-4-(4-dichloromethyl-2-thiazolyl)piperidine

使1-(1,1-二甲基乙基氧基羰基)哌啶-4-硫代甲醯胺(1.0g)溶解於2-丁酮(30mL)，添加1,1,3-三氯丙烷-2-酮(80%，830mg)，在80℃下攪拌7小時。其後返回室溫，對反應液添加水，使用乙酸乙酯進行萃取。以無水硫酸鈉乾燥有機層，過濾分離無機物後，減壓下餾除溶劑。藉由使用快速自動純化裝置(biotage AB公司製/IsoleraTM)所成之矽膠快速層析法(乙酸乙酯-己烷：10%-25%下析出)純化殘渣，而取得目的生成物作為淡黃色非晶狀固體(780mg，收率54%)。 1-(1,1-Dimethylethyloxycarbonyl)piperidine-4-thioformamide (1.0 g) was dissolved in 2-butanone (30 mL), and 1,1,3-trichlorobenzene was added. Propane-2-one (80%, 830 mg) was stirred at 80 ° C for 7 hours. Thereafter, the mixture was returned to room temperature, and water was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the organic matter was separated by filtration. By using fast automatic purification apparatus (Biotage AB Corporation / Isolera TM) as to the silica gel flash chromatography (ethyl acetate - hexane: 10% -25% for the precipitation) to give the residue, and obtaining the target product as a pale Yellow amorphous solid (780 mg, yield 54%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.47(s,9H)、1.69~1.74(m,2H)、2.11(d,2H)、2.87(t,2H)、3.18(m,1H)、4.32(br s,1H)、6.81(s,1H)、7.47(s,1H)。 1 H-NMR (CDCl 3 / TMS δ (ppm) value): 1.47 (s, 9H) , 1.69 ~ 1.74 (m, 2H), 2.11 (d, 2H), 2.87 (t, 2H), 3.18 (m, 1H), 4.32 (br s, 1H), 6.81 (s, 1H), 7.47 (s, 1H).

步驟2：1-(1,1-二甲基乙基氧基羰基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 Step 2: Preparation of 1-(1,1-dimethylethyloxycarbonyl)-4-(4-methylindolyl-2-thiazolyl)piperidine

使上述實施例26之步驟1中取得之生成物(780mg)、碳酸氫鈉(2.0g)及純化水(10mL)溶解於甲醇(10mL)，在60℃下加熱2小時。冷卻至室溫後，減壓下餾除溶劑。對殘渣添加水，以乙酸乙酯進行萃取。以飽和食鹽水洗淨有機層，以硫酸鈉進行乾燥後，過濾分離去除無機物，減壓下餾除溶劑。藉由使用快速自動純化裝置(biotage AB公司製/IsoleraTM)所成之矽膠快速層析法(乙酸乙酯-己烷：20%-30%下析出)純化殘渣，而取得標題化合物作為黃色非晶狀固體(340mg、78%)。 The product (780 mg), sodium hydrogencarbonate (2.0 g) and purified water (10 mL) obtained in the step 1 of the above Example 26 were dissolved in methanol (10 mL) and heated at 60 ° C for 2 hours. After cooling to room temperature, the solvent was evaporated under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. By using fast automatic purification apparatus (Biotage AB Corporation / Isolera TM) as to the silica gel flash chromatography (ethyl acetate - hexane: precipitation at 20% -30%) to give the residue, the title compound as a yellow acquired non Crystalline solid (340 mg, 78%).

[實施例27]1-(甲氧基羰基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 [Example 27] Preparation of 1-(methoxycarbonyl)-4-(4-methylindenyl-2-thiazolyl)piperidine 步驟1：1-(甲氧基羰基)-4-(4-二氯甲基-2-噻唑基)哌啶之調製 Step 1:1-(Methoxycarbonyl)-4-(4-dichloromethyl-2-thiazolyl)piperidine

使1-(甲氧基羰基)哌啶-4-硫代甲醯胺(1.0g)溶解於乙酸乙酯(10mL)與溴化四丁基銨(158mg)，添加1,1,3-三氯丙烷-2-酮(95%，878mg)，在80℃下攪拌4小時。其後返回室溫，對反應液添加水，使用乙酸乙酯萃取2次。以無水硫酸鎂乾燥有機層，過濾分離無機物後，減壓下餾除溶劑。藉由使用快速自動純化裝置(biotage AB公司製/IsoleraTM)所成之矽膠快速層析法(乙酸乙酯-己烷：0%-100%下析出)純化殘渣，而取得目的生成物作 為橙色油狀物(1.42g，收率93%)。 1-(Methoxycarbonyl)piperidine-4-thioformamide (1.0 g) was dissolved in ethyl acetate (10 mL) and tetrabutylammonium bromide (158 mg). Chloropropan-2-one (95%, 878 mg) was stirred at 80 ° C for 4 hours. Thereafter, the mixture was returned to room temperature, water was added to the reaction mixture, and extracted twice with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and the organic matter was separated by filtration. By using fast automatic purification apparatus (Biotage AB Corporation / Isolera TM) as to the silica gel flash chromatography (ethyl acetate - hexanes: 0% -100% for the precipitation) to give the residue, and obtaining the target product as an orange Oil (1.42 g, yield 93%).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.68~1.79(m,2H)、2.13(d,2H)、2.94(t,2H)、3.20(m,1H)、3.71(s,3H)、4.24(br s,1H)、6.81(s,1H)、7.48(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.68~1.79 (m, 2H), 2.13 (d, 2H), 2.94 (t, 2H), 3.20 (m, 1H), 3.71 (s, 3H), 4.24 (br s, 1H), 6.81 (s, 1H), 7.48 (s, 1H).

步驟2：1-(甲氧基羰基)-4-(4-甲醯基-2-噻唑基)哌啶之調製 Step 2: Preparation of 1-(methoxycarbonyl)-4-(4-methylindolyl-2-thiazolyl)piperidine

使上述實施例27之步驟1中取得之生成物(1.42g)與純化水(1mL)溶解於乙酸(4mL)，80℃下加熱4小時。冷卻至室溫後，減壓下餾除溶劑。藉由使用快速自動純化裝置(biotage AB公司製/IsoleraTM)所成之矽膠快速層析法(乙酸乙酯-己烷：0%-100%下析出)純化殘渣化，而取得標題化合物作為黃色油狀物(0.7g，收率60%)。 The product obtained in the first step of the above Example 27 (1.42 g) and purified water (1 mL) were dissolved in acetic acid (4 mL), and heated at 80 ° C for 4 hours. After cooling to room temperature, the solvent was evaporated under reduced pressure. By using fast automatic purification apparatus (Biotage AB Corporation / Isolera TM) as to the silica gel flash chromatography (ethyl acetate - hexanes: 0% -100% for the precipitation) of the residue was purified, to obtain the title compound as a yellow and Oil (0.7 g, yield 60%).

[實施例28]4-(4-甲醯基-2-噻唑基)哌啶鹽酸鹽之調製 [Example 28] Preparation of 4-(4-methylindenyl-2-thiazolyl)piperidine hydrochloride

使哌啶-4-硫代甲醯胺(403mg)溶解於乙醇(8.4mL)，添加37%濃鹽酸(253mg)與3-溴-1,1-二甲氧基丙烷-2-酮(500mg)，在70℃下攪拌6小時。使反應液冷卻至室溫後，添加水(1mL)並在室溫下再攪拌一晚。藉由在減壓下餾除溶劑，而取得包含標題化合物之粗生成物(890mg)。此粗生成物未經純化而使用於下個步驟。 Piperidine-4-thioformamide (403 mg) was dissolved in ethanol (8.4 mL), 37% concentrated hydrochloric acid (253 mg) and 3-bromo-1,1-dimethoxypropan-2-one (500 mg) ), stirring at 70 ° C for 6 hours. After the reaction solution was cooled to room temperature, water (1 mL) was added and stirred at room temperature overnight. The crude product (890 mg) containing the title compound was obtained. This crude product was used in the next step without purification.

1H-NMR(DMSO-d6/TMS δ(ppm)值)：1.94~2.04(m,2H)、2.21(d,2H)、2.98~3.07(m,2H)、3.33(d,2H)、3.38~3.47(m,1H)、8.68(s,1H)、9.13(brs,1H)、9.28(brs,1H)、9.90(s,1H)。 1 H-NMR (DMSO-d 6 /TMS δ (ppm) value): 1.94~2.04 (m, 2H), 2.21 (d, 2H), 2.98~3.07 (m, 2H), 3.33 (d, 2H), 3.38~3.47(m,1H), 8.68(s,1H), 9.13(brs,1H), 9.28(brs,1H), 9.90(s,1H).

[實施例29]4-(4-甲醯基-2-噻唑基)-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶之調製 [Example 29] 4-(4-Mexyl-2-thiazolyl)-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]B Modulation of sulfhydryl] piperidine

使實施例28中取得之粗生成物溶解於二氯甲烷(8.4mL)，添加1-{5-甲基-3-(三氟甲基)-1H-吡唑-1-基}-乙酸(580mg)與1-(3-二甲基胺基丙基)-3-乙基碳二醯亞胺鹽酸鹽(534mg)，在室溫下攪拌一晚。對反應液添加水，使用二氯甲烷進行萃取。以飽和食鹽水洗淨有機層，以無水硫酸鈉進行乾燥，過濾分離無機物後，減壓下餾除溶劑。藉由使用快速自動純化裝置(biotage AB公司製/IsoleraTM)所成之矽膠快速層析法(乙酸乙酯-己烷：0%-100%下析出)純化殘渣，而取得標題化合物(240mg)。 The crude product obtained in Example 28 was dissolved in dichloromethane (8.4 mL), and 1-{5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl}-acetic acid was added ( 580 mg) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (534 mg) were stirred at room temperature overnight. Water was added to the reaction liquid, and extraction was carried out using dichloromethane. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. By using fast automatic purification apparatus (Biotage AB Corporation / Isolera TM) as to the silica gel flash chromatography (ethyl acetate - hexanes: 0% -100% for the precipitation) to give the residue, and obtaining the title compound (240 mg of) .

1H-NMR(CDCl3/TMS δ(ppm)值)：1.75~1.85(m,2H)、2.16~2.28(m,2H)、2.37(s,3H)、2.93(t,1H)、3.28~3.38(m,2H)、4.10(d,1H)、4.59(d,1H)、5.00(m,2H)、6.34(s,1H)、8.11(s,1H)、10.00(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.75~1.85 (m, 2H), 2.16~2.28 (m, 2H), 2.37 (s, 3H), 2.93 (t, 1H), 3.28~ 3.38 (m, 2H), 4.10 (d, 1H), 4.59 (d, 1H), 5.00 (m, 2H), 6.34 (s, 1H), 8.11 (s, 1H), 10.00 (s, 1H).

[實施例30]4-(4-甲醯基-2-噻唑基)-1-[2-[3,5-雙(二氟 甲基)-1H-吡唑-1-基]乙醯基]哌啶之調製 [Example 30] 4-(4-Mexyl-2-thiazolyl)-1-[2-[3,5-bis(difluoro) Modulation of methyl)-1H-pyrazol-1-yl]ethenyl]piperidine

使實施例28中取得之粗生成物溶解於二氯甲烷(8.4mL)，添加1-{3,5-雙(二氟甲基)-1H-吡唑-1-基}-乙酸(631mg)與1-(3-二甲基胺基丙基)-3-乙基碳二醯亞胺鹽酸鹽(534mg)，藉由與實施例2之調製同樣地使其反應，進行純化，而取得標題化合物(230mg)。 The crude product obtained in Example 28 was dissolved in dichloromethane (8.4 mL), and 1-{3,5-bis(difluoromethyl)-1H-pyrazol-1-yl}-acetic acid (631 mg) was added. And 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (534 mg) was reacted in the same manner as in the preparation of Example 2, and purified. The title compound (230 mg).

1H-NMR(CDCl3/TMS δ(ppm)值)：1.78~1.95(m,2H)、2.26(dd,2H)、2.94(t,1H)、3.32~3.39(m,2H)、3.94(d,1H)、4.59(d,1H)、5.16(m,2H)、6.53~7.02(m,3H)、8.11(s,1H)、10.01(s,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 1.78 to 1.95 (m, 2H), 2.26 (dd, 2H), 2.94 (t, 1H), 3.32 to 3.39 (m, 2H), 3.94 ( d, 1H), 4.59 (d, 1H), 5.16 (m, 2H), 6.53 to 7.02 (m, 3H), 8.11 (s, 1H), 10.01 (s, 1H).

[實施例31]4-[4-(6,9-二氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶(化合物1-3)之調製 [Example 31] 4-[4-(6,9-difluoro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1- Preparation of [2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine (Compound 1-3)

使實施例1中取得之生成物(210mg)、3,6-二氟-1,2-苯二甲醇(210mg)及p-甲苯磺酸一水合物(11mg)溶解於甲苯(15mL)，使用狄恩史塔克(Dean-Stark)裝置加熱迴流1小時。使反應液冷卻至室溫後，以乙酸乙酯進行稀釋，以水及飽和食鹽水進行洗淨。以無水硫酸鈉乾燥有機層，過濾分離無機物後，減壓下餾除溶劑。藉由使用快速自動純化裝置(biotage AB公司製/IsoleraTM)所成之矽膠快速層析法(乙酸乙酯-己烷：40%-100%下析出)純化殘渣，而取得標題化合物作為白色非晶狀固體(245mg，收率83%)。對取得之非晶狀固體添加甲醇， 加熱迴流下使其溶解後，藉由在室溫下静置而取得白色結晶(融點151℃)。 The product (210 mg) obtained in Example 1, 3,6-difluoro-1,2-benzenedimethanol (210 mg), and p-toluenesulfonic acid monohydrate (11 mg) were dissolved in toluene (15 mL), and used. The Dean-Stark apparatus was heated to reflux for 1 hour. After cooling the reaction solution to room temperature, it was diluted with ethyl acetate, and washed with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate, and the organic matter was separated by filtration. By using fast automatic purification apparatus (Biotage AB Corporation / Isolera TM) as to the silica gel flash chromatography (ethyl acetate - hexane: 40% -100% for the precipitation) to give the residue to obtain the title compound as a white and non- Crystalline solid (245 mg, yield 83%). Methanol was added to the obtained amorphous solid, and the mixture was dissolved under reflux with heating, and then allowed to stand at room temperature to obtain white crystals (melting point: 151 ° C).

[實施例32]4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶(化合物1-6)之調製 [Example 32] 4-[4-(6-Methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]- Preparation of 1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine (Compound 1-6)

使實施例1中取得之生成物(200mg)、3-甲基磺醯氧基-1,2-苯二甲醇(121mg)及p-甲苯磺酸一水合物(20mg)溶解於甲苯(20mL)，藉由與化合物1-3之調製中之反應同樣地使其反應，進行純化，而取得標題化合物作為白色非晶狀固體(298mg，收率96%)。 The product obtained in Example 1 (200 mg), 3-methylsulfonyloxy-1,2-benzenedimethanol (121 mg) and p-toluenesulfonic acid monohydrate (20 mg) were dissolved in toluene (20 mL). The title compound was obtained as a white amorphous solid (298 mg, yield: 96%).

[實施例33]4-[4-(6-氟-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶(化合物1-8)之調製 [Example 33] 4-[4-(6-fluoro-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2- Modulation of thiazolyl]-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine (Compound 1-8)

使實施例1中取得之生成物(220mg)、3-氟-6-甲基磺醯氧基-1,2-苯二甲醇(150mg)及p-甲苯磺酸一水合物(20mg)溶解於甲苯(15mL)，藉由與化合物1-3之調製中之反應同樣地使其反應，進行純化，而取得標題化合物作為白色非晶狀固體(297mg，收率84%)。 The product obtained in Example 1 (220 mg), 3-fluoro-6-methylsulfonyloxy-1,2-benzenedimethanol (150 mg) and p-toluenesulfonic acid monohydrate (20 mg) were dissolved in Toluene (15 mL) was reacted in the same manner as in the preparation of Compound 1-3, and the title compound was obtained as white amorphous solid (297 mg, yield: 84%).

[實施例34]4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶(化合物1-38)之調製 [Example 34] 4-[4-(6-Methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]- Preparation of 1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine (Compound 1-38)

使實施例4中取得之生成物(202mg)、3-甲基磺醯氧基-1,2-苯二甲醇(232mg)及p-甲苯磺酸一水合物(5mg)溶解於甲苯(15mL)，藉由與化合物1-3之調製中之反應同樣地使其反應，進行純化，而取得標題化合物作為白色非晶狀固體(164mg，收率53%)。 The product obtained in Example 4 (202 mg), 3-methylsulfonyloxy-1,2-benzenedimethanol (232 mg) and p-toluenesulfonic acid monohydrate (5 mg) were dissolved in toluene (15 mL). The title compound was obtained as a white amorphous solid (164 mg, yield 53%) by the reaction of the reaction in the preparation of the compound 1-3.

[實施例35]4-[4-(6-甲氧基-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶(化合物1-39)之調製 [Example 35] 4-[4-(6-Methoxy-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)- Preparation of 2-thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine (Compound 1-39)

使實施例4中取得之生成物(202mg)、3-甲氧基-6-甲基磺醯氧基-1,2-苯二甲醇(232mg)及p-甲苯磺酸一水合物(5mg)溶解於甲苯(15mL)，藉由與化合物1-3之調製中之反應同樣地使其反應，進行純化，而取得標題化合物作為白色非晶狀固體(268mg，收率75%)。 The product obtained in Example 4 (202 mg), 3-methoxy-6-methylsulfonyloxy-1,2-benzenedimethanol (232 mg) and p-toluenesulfonic acid monohydrate (5 mg). The title compound was obtained as a white amorphous solid (268 mg, yield: 75%), which was dissolved in toluene (15 mL).

[實施例36]4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶(化合物1-42)之調製 [Example 36] 4-[4-(6-Methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]- Modulation of 1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine (Compound 1-42)

使4-(4-甲醯基-2-噻唑基)-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶(200mg)(與實施例1之4-(4-甲醯基-2-噻唑基)-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶相同之方法進行合成)、3-甲基磺醯氧基-1,2-苯二甲醇(109mg)及p-甲苯磺酸一水合物(5mg)溶解於甲苯(100mL)，藉由與化合物1-3之 調製中之反應同樣地使其反應，進行純化，而取得標題化合物作為白色非晶狀固體(96mg，收率31%)。 4-(4-Methylmethyl-2-thiazolyl)-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine 200 mg) (with 4-(4-carbamimido-2-thiazolyl)-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazole-1-) Synthesis of 3-methylsulfonyloxy-1,2-benzenedimethanol (109 mg) and p-toluenesulfonic acid monohydrate (5 mg) in toluene (synthesis) 100mL), with compound 1-3 The reaction in the preparation was reacted in the same manner, and the title compound was obtained as a white amorphous solid (96 mg, yield 31%).

[實施例37]4-[4-(6,9-二氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶(化合物1-50)之調製 [Example 37] 4-[4-(6,9-difluoro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1- Preparation of [2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine (Compound 1-50)

使4-(4-甲醯基-2-噻唑基)-1-[2-[3,5-雙(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶(200mg)、3,6-二氟-1,2-苯二甲醇(82mg)及p-甲苯磺酸一水合物(5mg)溶解於甲苯(100mL)，藉由與化合物1-3之調製中之反應同樣地使其反應，進行純化，而取得標題化合物作為白色非晶狀固體(183mg，收率53%)。 4-(4-Methylmethyl-2-thiazolyl)-1-[2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine 200 mg), 3,6-difluoro-1,2-benzenedimethanol (82 mg) and p-toluenesulfonic acid monohydrate (5 mg) were dissolved in toluene (100 mL) by compounding with compound 1-3 The reaction was carried out in the same manner and purified to give the title compound as white solid (183 mg, yield 53%).

[實施例38]4-[4-(6-氟-9-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基]哌啶(化合物1-62)之調製 [Example 38] 4-[4-(6-fluoro-9-methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2- Modulation of thiazolyl]-1-[2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine (Compound 1-62)

藉由使實施例4中取得之生成物(202mg)、3-氟-6-甲基磺醯氧基-1,2-苯二甲醇(250mg)及p-甲苯磺酸一水合物(5mg)溶解於甲苯(15mL)，藉由與化合物1-3之調製中之反應同樣地使其反應，進行純化，而取得標題化合物作為白色非晶狀固體(105mg，收率33%)。 The product obtained in Example 4 (202 mg), 3-fluoro-6-methylsulfonyloxy-1,2-benzenedimethanol (250 mg) and p-toluenesulfonic acid monohydrate (5 mg). The title compound was obtained as a white amorphous solid (105 mg, yield 33%), which was dissolved in toluene (15 mL).

[實施例39]4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二甲基苯基)乙醯 基]哌啶(化合物2-1)之調製 [Example 39] 4-[4-(6-Methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]- 1-[2-(2,5-dimethylphenyl)acetamidine Modulation of piperidine (Compound 2-1)

使4-(4-甲醯基-2-噻唑基)-1-[2-(2,5-二甲基苯基)乙醯基]哌啶(與實施例1之4-(4-甲醯基-2-噻唑基)-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶相同之方法進行合成)(200mg)、3-甲基磺醯氧基-1,2-苯二甲醇(142mg)及p-甲苯磺酸一水合物(20mg)溶解於甲苯(15mL)，藉由與化合物1-3之調製中之反應同樣地使其反應，進行純化，而取得標題化合物作為白色非晶狀固體(206mg，收率64%)。 4-(4-Mercapto-2-thiazolyl)-1-[2-(2,5-dimethylphenyl)ethenyl]piperidine (with 4-(4-A) of Example 1 Synthesis of fluorenyl-2-thiazolyl)-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine by the same method) (200 mg), 3-methylsulfonyloxy-1,2-benzenedimethanol (142 mg) and p-toluenesulfonic acid monohydrate (20 mg) were dissolved in toluene (15 mL) by compound 1-3 The reaction in the preparation was reacted in the same manner, and the title compound was obtained as a white amorphous solid (206 mg, yield: 64%).

[實施例40]4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶(化合物2-2)之調製 [Example 40] 4-[4-(6-Methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]- Preparation of 1-[2-(2,5-dichlorophenyl)ethinyl]piperidine (Compound 2-2)

使4-(4-甲醯基-2-噻唑基)-1-[2-(2,5-二氯苯基)乙醯基]哌啶(與實施例1之4-(4-甲醯基-2-噻唑基)-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶相同之方法進行合成)(191mg)、3-甲基磺醯氧基-1,2-苯二甲醇(232mg)及p-甲苯磺酸一水合物(5mg)溶解於甲苯(15mL)，藉由與化合物1-3之調製中之反應同樣地使其反應，進行純化，而取得標題化合物作為白色非晶狀固體(267mg，收率72%)。 4-(4-Mercapto-2-thiazolyl)-1-[2-(2,5-dichlorophenyl)ethenyl]piperidine (with 4-(4-carbazide of Example 1) Synthesis of benzyl-2-thiazolyl)-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl]piperidine by the same method) 191 mg), 3-methylsulfonyloxy-1,2-benzenedimethanol (232 mg) and p-toluenesulfonic acid monohydrate (5 mg) were dissolved in toluene (15 mL), prepared by compound 1-3 The reaction was carried out in the same manner, and the title compound was obtained as white amorphous solid (267 mg, yield: 72%).

[實施例41]4-[4-(6,9-二氟-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-(2,5-二氯苯基)乙醯基]哌啶(化 合物2-4)之調製 [Example 41] 4-[4-(6,9-difluoro-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]-1- [2-(2,5-dichlorophenyl)ethinyl]piperidine Modulation of compound 2-4)

使4-(4-甲醯基-2-噻唑基)-1-[2-(2,5-二氯苯基)乙醯基]哌啶(191mg)、3,6-二氟-1,2-苯二甲醇(174mg)及p-甲苯磺酸一水合物(5mg)溶解於甲苯(15mL)，藉由與化合物1-3之調製中之反應同樣地使其反應，進行純化，而取得標題化合物作為白色非晶狀固體(231mg，收率86%)。 4-(4-Methylmethyl-2-thiazolyl)-1-[2-(2,5-dichlorophenyl)ethinyl]piperidine (191 mg), 3,6-difluoro-1, 2-Benzyldiethanol (174 mg) and p-toluenesulfonic acid monohydrate (5 mg) were dissolved in toluene (15 mL), and the mixture was reacted in the same manner as in the preparation of the compound 1-3, and purified. The title compound was obtained as a white amorphous solid (231 mg, yield 86%).

[實施例42]4-[4-(6-甲基磺醯氧基-1,5-二氫-3H-2,4-苯并二噁呯-3-基)-2-噻唑基]-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶(化合物1-6)之調製 [Example 42] 4-[4-(6-Methylsulfonyloxy-1,5-dihydro-3H-2,4-benzodioxin-3-yl)-2-thiazolyl]- Preparation of 1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethinyl]piperidine (Compound 1-6)

使4-(4-二甲氧基甲基-2-噻唑基)-1-[2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基]哌啶(實施例3之步驟1中取得之生成物)(150mg)、3-甲基磺醯氧基-1,2-苯二甲醇(81mg)、及三氟化硼二乙基醚錯合物(100mg)溶解於二氯甲烷(10mL)，在室溫下攪拌一晚。反應結束後，添加飽和碳酸氫鈉水，以乙酸乙酯進行萃取。以飽和食鹽水洗淨有機層，以無水硫酸鈉進行乾燥。過濾分離無機物後，減壓下餾除溶劑，藉由與化合物1-3之調製同樣地進行純化，而取得標題化合物作為白色非晶狀固體(200mg，收率96%)。 4-(4-Dimethoxymethyl-2-thiazolyl)-1-[2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetamidine a piperidine (product obtained in the first step of Example 3) (150 mg), 3-methylsulfonyloxy-1,2-benzenedimethanol (81 mg), and boron trifluoride diethyl ether The complex (100 mg) was dissolved in dichloromethane (10 mL) and stirred at room temperature overnight. After completion of the reaction, saturated sodium hydrogencarbonate water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. After the inorganic material was separated by filtration, the solvent was evaporated to dryness crystals, crystals crystals crystals crystals crystals

以下之實施例43~46展示上述實施例31~42中使用之製造出發物質之製造例。 The following Examples 43 to 46 show production examples of the manufactured starting materials used in the above Examples 31 to 42.

[實施例43]3,6-二氟-1,2-苯二甲醇之調製 [Example 43] Modulation of 3,6-difluoro-1,2-benzenedimethanol

冰冷下，依順序使氫化鋁鋰(870mg)與3,6-二氟酞酸酐溶解於四氫呋喃27mL，加熱迴流反應液2小時。使反應液冷卻至室溫後，冰冷下添加水，在室溫下攪拌1小時。藉由使用矽藻土過濾溶液，減壓下餾除溶劑，而取得標題化合物作為白色固體(640mg，收率68%)。 Under ice cooling, lithium aluminum hydride (870 mg) and 3,6-difluorophthalic anhydride were dissolved in tetrahydrofuran (27 mL) in that order, and the reaction mixture was heated to reflux for 2 hr. After cooling the reaction solution to room temperature, water was added thereto under ice cooling, and the mixture was stirred at room temperature for 1 hour. The solution was filtered through EtOAc (EtOAc)EtOAc.

1H-NMR(CDCl3/TMS δ(ppm)值)：2.89(brs,2H)、4.84(s,4H)、7.03(dd,2H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 2.89 (brs, 2H), 4.84 (s, 4H), 7.03 (dd, 2H).

[實施例44]3-甲基磺醯氧基-1,2-苯二甲醇之調製 [Example 44] Preparation of 3-methylsulfonyloxy-1,2-benzenedimethanol

使3-甲基磺醯氧基酞酸酐(2.2g)(WO2004/000796號公報記載之化合物)溶解於四氫呋喃(60mL)，添加硼烷四氫呋喃錯合物(0.9M四氫呋喃溶液、50mL)，在60℃下攪拌6小時。反應結束後，冰冷下添加甲醇，減壓下餾除溶劑。以乙酸乙酯稀釋殘渣，以1N鹽酸、飽和食鹽水進行洗淨。以無水硫酸鈉乾燥有機層，過濾分離無機物後，減壓下餾除溶劑。藉由使用快速自動純化裝置(biotage AB公司製/IsoleraTM)所成之矽膠快速層析法(乙酸乙酯-己烷：30%-100%下析出)純化殘渣，而取得3-甲基磺醯氧基-1,2-苯二甲醇作為白色固體(1.36g，收率64%)。 3-methylsulfonyloxyphthalic anhydride (2.2 g) (the compound described in WO2004/000796) was dissolved in tetrahydrofuran (60 mL), and borane tetrahydrofuran complex (0.9 M tetrahydrofuran solution, 50 mL) was added thereto at 60 Stir at ° C for 6 hours. After completion of the reaction, methanol was added under ice cooling, and the solvent was evaporated under reduced pressure. The residue was diluted with ethyl acetate and washed with 1N hydrochloric acid and brine. The organic layer was dried over anhydrous sodium sulfate, and the organic matter was separated by filtration. By using fast automatic purification apparatus (Biotage AB Corporation / Isolera TM) as to the silica gel flash chromatography (ethyl acetate - hexane: 30% -100% for the precipitation) The residue was purified acquired 3-sulfonamide The decyloxy-1,2-benzenedimethanol was used as a white solid (1.36 g, yield: 64%).

1H-NMR(DMSO-d6/TMS δ(ppm)值)：3.42(s,3H)、4.57(d,2H)、4.70(d,2H)、4.98(t,1H)、5.27(t,1H)、7.25(d,1H)、7.36(t,1H)、7.46(d,1H)。 1 H-NMR (DMSO-d6/TMS δ (ppm) value): 3.42 (s, 3H), 4.57 (d, 2H), 4.70 (d, 2H), 4.98 (t, 1H), 5.27 (t, 1H) ), 7.25 (d, 1H), 7.36 (t, 1H), 7.46 (d, 1H).

[實施例45]3-氟-6-甲基磺醯氧基-1,2-苯二甲醇之調製 [Example 45] Preparation of 3-fluoro-6-methylsulfonyloxy-1,2-benzenedimethanol 步驟1：5-氟-2-甲基磺醯氧基酞內酯之調製 Step 1: Preparation of 5-fluoro-2-methylsulfonyloxylactone

使5-氟-2-羥基酞內酯(200mg)(WO2003/076424號公報記載之化合物)溶解於N,N-二甲基甲醯胺(10mL)，添加甲基磺醯基氯化物(150mg)與三乙基胺(133mg)，在室溫下攪拌1晚。以乙酸乙酯稀釋反應液，以飽和食鹽水進行洗淨。以無水硫酸鈉乾燥有機層，過濾分離無機物後，減壓下餾除溶劑，而取得5-氟-2-甲基磺醯氧基酞內酯作為白色固體(290mg，收率100%)。 5-fluoro-2-hydroxylactone (200 mg) (the compound described in WO2003/076424) was dissolved in N,N-dimethylformamide (10 mL), and methylsulfonyl chloride (150 mg) was added. With triethylamine (133 mg), stir at room temperature for 1 night. The reaction solution was diluted with ethyl acetate and washed with brine. The organic layer was dried over anhydrous sodium sulfate, and the organic matter was separated by filtration. The solvent was evaporated under reduced pressure to give 5-fluoro-2-methylsulfonyloxylactone as a white solid (290 mg, yield 100%).

步驟2：3-氟-6-甲基磺醯氧基-1,2-苯二甲醇之調製 Step 2: Preparation of 3-fluoro-6-methylsulfonyloxy-1,2-benzenedimethanol

使5-氟-2-甲基磺醯氧基酞內酯(290mg)溶解於四氫呋喃(10mL)，添加氫化鋁鋰(45mg)，在室溫下攪拌30分。冰冷下，對反應液添加1N鹽酸，在室溫下攪拌1小時。使用二氯甲烷萃取反應液，以飽和食鹽水進行洗淨。以無水硫酸鈉乾燥有機層，過濾分離無機物後，減壓下餾除溶劑，而取得3-氟-6-甲基磺醯氧基-1,2-苯二甲醇作為白色固體(290mg，收率100%)。 5-Fluoro-2-methylsulfonyloxylactone (290 mg) was dissolved in tetrahydrofuran (10 mL), and lithium aluminum hydride (45 mg) was added thereto, and the mixture was stirred at room temperature for 30 minutes. Under ice cooling, 1N hydrochloric acid was added to the reaction mixture, and the mixture was stirred at room temperature for 1 hour. The reaction solution was extracted with dichloromethane and washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate, and the organic matter was separated by filtration, and the solvent was evaporated under reduced pressure to give 3-fluoro-6-methylsulfonyloxy-1,2-benzenedimethanol as a white solid (290 mg, yield 100%).

1H-NMR(CDCl3/TMS δ(ppm)值)：3.28(s,3H)、3.45(brs,2H)、4.84(s,4H)、7.11(dd,1H)、7.25~7.28(m,1H)。 1 H-NMR (CDCl 3 /TMS δ (ppm) value): 3.28 (s, 3H), 3.45 (brs, 2H), 4.84 (s, 4H), 7.11 (dd, 1H), 7.25 to 7.28 (m, 1H).

[實施例46]3-甲氧基-6-甲基磺醯氧基-1,2-苯二甲醇之調製 [Example 46] Preparation of 3-methoxy-6-methylsulfonyloxy-1,2-benzenedimethanol 步驟1：2,3-雙(甲氧基羰基)-1-甲氧基-4-甲基磺醯氧基苯之調製 Step 1: Preparation of 2,3-bis(methoxycarbonyl)-1-methoxy-4-methylsulfonyloxybenzene

使2,3-雙(甲氧基羰基)-4-甲氧基酚(2.0g)(Synthetic Communication,43(2),260-267；2013記載之化合物)溶解於四氫呋喃(30mL)，添加甲基磺醯基氯化物(1.05g)與三乙基胺(1.01g)，在室溫下攪拌1小時。對反應液添加水，以乙酸乙酯進行萃取後，以飽和食鹽水進行洗淨。以無水硫酸鈉乾燥有機層，過濾分離無機物後，減壓下餾除溶劑，而取得2,3-雙(甲氧基羰基)-1-甲氧基-4-甲基磺醯氧基苯作為白色固體(2.5g，收率100%)。 2,3-bis(methoxycarbonyl)-4-methoxyphenol (2.0 g) (Synthetic Communication, 43(2), 260-267; 2013 compound) was dissolved in tetrahydrofuran (30 mL), and added The sulfonyl chloride (1.05 g) and triethylamine (1.01 g) were stirred at room temperature for 1 hour. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate, and then washed with brine. The organic layer was dried over anhydrous sodium sulfate, and the inorganic substance was separated by filtration. The solvent was evaporated under reduced pressure to give 2,3-bis(methoxycarbonyl)-1-methoxy-4-methylsulfonyloxybenzene as White solid (2.5 g, yield 100%).

步驟2：3-甲氧基-6-甲基磺醯氧基-1,2-苯二甲醇之調製 Step 2: Preparation of 3-methoxy-6-methylsulfonyloxy-1,2-benzenedimethanol

使2,3-雙(甲氧基羰基)-1-甲氧基-4-甲基磺醯氧基苯(2.5g)溶解於四氫呋喃(30mL)，冰冷下添加氫化鋁鋰(620mg)，冰冷下攪拌1小時。冰冷下，對反應液添加1N鹽酸，在室溫下攪拌1小時。使用乙酸乙酯萃取反應液，以飽和食鹽水進行洗淨。以無水硫酸鈉乾燥有機層，過濾分離無機物後，減壓下餾除溶劑。藉由使用快速自動純化裝置(biotage AB公司製/IsoleraTM)所成之矽膠快速層析法(乙酸乙酯-己烷：30%-100%下析出)純化殘渣，而取得3-甲氧基-6-甲基磺醯氧基-1,2-苯二甲醇作為 白色固體(906mg，收率42%)。 2,3-Bis(methoxycarbonyl)-1-methoxy-4-methylsulfonyloxybenzene (2.5 g) was dissolved in tetrahydrofuran (30 mL), and lithium aluminum hydride (620 mg) was added under ice cooling, ice-cooled Stir under 1 hour. Under ice cooling, 1N hydrochloric acid was added to the reaction mixture, and the mixture was stirred at room temperature for 1 hour. The reaction solution was extracted with ethyl acetate and washed with brine. The organic layer was dried over anhydrous sodium sulfate, and the organic matter was separated by filtration. By using fast automatic purification apparatus (Biotage AB Corporation / Isolera TM) as to the silica gel flash chromatography (ethyl acetate - hexane: 30% -100% for the precipitation) Purification of the residue and 3-methoxy group to obtain -6-Methylsulfonyloxy-1,2-benzenedimethanol as a white solid (906 mg, yield 42%).

1H-NMR(DMSO-d6/TMS δ(ppm)值)：3.39(s,3H)、3.81(s,3H)、4.62~4.64(m,4H)、4.84(t,1H)、5.06(t,1H)、7.03(d,1H)、7.28(d,1H)。 1 H-NMR (DMSO-d6/TMS δ (ppm) value): 3.39 (s, 3H), 3.81 (s, 3H), 4.62 to 4.64 (m, 4H), 4.84 (t, 1H), 5.06 (t , 1H), 7.03 (d, 1H), 7.28 (d, 1H).

藉由同樣之製造法，合成出[表1]至[表6]所示之化合物。 The compounds shown in [Table 1] to [Table 6] were synthesized by the same production method.

將上述實施例取得之化合物及以同樣方法所製造之[表1]至[表6]所示之化合物之1H-NMR數據(CDCl3/TMS δ(ppm)值)展示於[表7]至[表19]。 The compound of the above embodiments of obtaining and being fabricated in the same manner [Table 1] to [Table 6] As shown in the 1 H-NMR data of the compound (CDCl 3 / TMS δ (ppm ) value) are shown in [Table 7] To [Table 19].

其次，記述本發明化合物之使用實施例。 Next, the use examples of the compounds of the present invention are described.

(1)製劑化之實施操作順序 (1) Operational sequence of preparation <製劑例1>水合劑 <Formulation Example 1>Hydrating agent

將本發明化合物10份與月桂基硫酸鈉2份、木質素磺酸鈉4份、白碳20份及白土64份進行混合，予以粉碎而取得10%水合劑。 10 parts of the compound of the present invention were mixed with 2 parts of sodium lauryl sulfate, 4 parts of sodium lignin sulfonate, 20 parts of white carbon and 64 parts of white clay, and pulverized to obtain a 10% hydrating agent.

<製劑例2>流動性劑 <Formulation Example 2> Fluidity agent

添加本發明化合物10份、聚氧乙烯烯丙基苯基醚硫酸酯4份、聚氧乙烯烷基醚5份、丙二醇5份、矽系消泡劑0.2份、鈉蒙脫土0.8份、水50份進行混合，使用Dyno-mill研磨機施以濕式粉碎而取得粉碎懸浮液。 10 parts of the compound of the present invention, 4 parts of polyoxyethylene allyl phenyl ether sulfate, 5 parts of polyoxyethylene alkyl ether, 5 parts of propylene glycol, 0.2 parts of an antifoaming agent, 0.8 parts of sodium montmorillonite, and water 50 parts of the mixture were mixed, and the pulverized suspension was obtained by wet pulverization using a Dyno-mill mill.

對粉碎懸浮液75份添加各別包含0.2份、0.1份之黃 原膠、2-苯并異噻唑啉-3-酮之黃原膠溶液10份及水15份後，進行混合而得到10%水性懸濁狀農藥組成物。 Adding to each of the 75 parts of the pulverized suspension, 0.2 parts, 0.1 parts of yellow After 10 parts of the xanthan gum solution of the original gum and 2-benzisothiazolin-3-one and 15 parts of water, the mixture was mixed to obtain a 10% aqueous suspension pesticide composition.

<製劑例3>乳劑 <Formulation Example 3> Emulsion

將本發明化合物10份、十二基苯磺酸鈣2份、乙氧基化菎麻油15份與芳香族烴混合物73份進行混合使其溶解而得到均質之10%可乳化油狀液體。 10 parts of the compound of the present invention, 2 parts of calcium dodecylbenzenesulfonate, 15 parts of ethoxylated castor oil and 73 parts of an aromatic hydrocarbon mixture were mixed and dissolved to obtain a homogeneous 10% emulsifiable oily liquid.

<製劑例4>顆粒水合劑 <Formulation Example 4> Particulate hydrating agent

添加本發明化合物10份、木質素磺酸鈉20份、萘磺酸縮合物之鈉鹽10份、烷基苯磺酸鈉3份、矽系泡消劑0.5份、矽藻土5份、硫酸銨10份、滑石10份、白土份31.5份，進行充分攪混合且進行粉碎而取得粉碎物。因應必要對粉碎物添加適當量之水並以造粒機進行造粒，乾燥後進行篩析而取得10%水合性細粒。 Adding 10 parts of the compound of the present invention, 20 parts of sodium lignin sulfonate, 10 parts of sodium salt of a naphthalenesulfonic acid condensate, 3 parts of sodium alkylbenzenesulfonate, 0.5 part of bismuth-based deodorant, 5 parts of diatomaceous earth, sulfuric acid 10 parts of ammonium, 10 parts of talc, and 31.5 parts of white clay were thoroughly stirred and pulverized to obtain a ground product. It is necessary to add an appropriate amount of water to the pulverized material and granulate it by a granulator, and after drying, it is sieved to obtain 10% hydration fine particles.

<製劑例5>乳化劑 <Formulation Example 5> Emulsifier

添加本發明化合物10份、芳香族烴混合物15份、十二基苯磺酸鈣2份、聚氧乙烯蓖麻油20份、丙二醇4份使其溶解而取得混合液。對水49份添加混合液並使用均質機進行混合而得到均質之10%乳濁液體。 10 parts of the compound of the present invention, 15 parts of an aromatic hydrocarbon mixture, 2 parts of calcium dodecylbenzenesulfonate, 20 parts of polyoxyethylene castor oil, and 4 parts of propylene glycol were added and dissolved to obtain a mixed liquid. A mixed liquid was added to 49 parts of water and mixed using a homogenizer to obtain a homogeneous 10% emulsion liquid.

<製劑例6>粒劑 <Formulation Example 6> Granules

添加本發明化合物10份、聚羧酸型陰離子界面活性 劑3份、二辛基磺基琥珀酸鈉0.2份、糊精2份、皂土鈉15份、碳酸鈣69.8份並進行均勻混合後，加入適當量之水進行混練，以籃型造粒機進行擠壓予以造粒，乾燥後進行篩析而取得10%細粒。 Adding 10 parts of the compound of the invention, polycarboxylate type anionic interface activity 3 parts, 0.2 parts of sodium dioctylsulfosuccinate, 2 parts of dextrin, 15 parts of sodium bentonite, 69.8 parts of calcium carbonate and uniformly mixed, and then added with an appropriate amount of water for kneading to a basket granulator The mixture was granulated by extrusion, dried, and sieved to obtain 10% fine particles.

<製劑例7>微乳化劑 <Formulation Example 7> Microemulsifier

混合本發明化合物10份與脂肪酸二甲基醯胺12份、環己酮10份、乙氧基化芳基酚15份，添加乙氧基化醇10份及水43份，在加溫下攪拌數分鐘，而取得安定之10%水溶性液體。 Mix 10 parts of the compound of the present invention with 12 parts of fatty acid dimethyl decylamine, 10 parts of cyclohexanone, 15 parts of ethoxylated aryl phenol, add 10 parts of ethoxylated alcohol and 43 parts of water, and stir under heating. A few minutes, and obtain a stable 10% water-soluble liquid.

(2)試驗懸浮液之調製之實施操作順序 (2) Operation sequence of preparation of test suspension

根據製劑例1所作成之10%水合劑以調製成1/5000濃度之Teen20水溶液進行稀釋，而將式[1]所示之化合物調整成4ppm濃度。又，試驗4中將式[1]所示之化合物調製成1000ppm之濃度。 The 10% hydrating agent prepared according to Formulation Example 1 was diluted with a Toen 20 aqueous solution prepared at a concentration of 1/5000, and the compound represented by the formula [1] was adjusted to a concentration of 4 ppm. Further, in Test 4, the compound represented by the formula [1] was prepared to have a concentration of 1000 ppm.

(3)對於植物病害之防除效果之評價試驗操作順序 (3) Evaluation of the control effect of plant diseases <試驗1 對於番茄疫病之防除效果試驗> <Test 1 Test on the control effect of tomato blight>

對於5葉期之番茄(品種：雷吉娜(regina)，以每1苗散布試驗懸浮液20ml。散布1日後，噴霧接種調製成1.0×105個/ml濃度之馬鈴薯晚疫黴(Phytophthora infestans)之遊走孢子懸浮液，在調節至22℃之濕室中培養16小時。其後，在室內促使其發病，調查從接種到4 日後葉片上產生之病斑面積率，使用以下之式算出防除價。 For the 5-leaf stage tomato (variety: regina), 20 ml of the test suspension was spread per 1 seedling. After 1 day of spreading, spray inoculation into 1.0 × 10 5 /ml concentration of Phytophthora infestans The spore suspension was cultured for 16 hours in a humid chamber adjusted to 22 ° C. Thereafter, the disease was induced indoors, and the area ratio of the lesions generated on the leaves from the inoculation to the 4th day was investigated, and the following formula was used to calculate the control. price.

防除價之算出式：防除價值={1-已散布試驗藥劑之葉片之發病面積率/無處理之發病面積率}×100 The calculation formula of the price control: the value of the control = {1 - the area ratio of the diseased leaves of the test agent / the area ratio of the disease without treatment} × 100

<試驗2 對於黃瓜露菌病之防除效果試驗> <Test 2 Test on the control effect of cucumber debride disease>

對於2葉期之黃瓜(品種：相模半白(Cucumis sativus))，以每1苗散布試驗懸浮液20ml。散布1日後，噴霧接種調製成1.0×104個/ml濃度之古巴假單軸黴(Pseudoperonospora cubensis)之遊走孢子囊懸浮液，在調節至22℃之濕室中培養16小時。其後，在室內促使其發病，調查從接種到5日後葉片上產生之病斑面積率，使用以下之式算出防除價。 For the cucumber at the 2-leaf stage (variety: Cucumis sativus), 20 ml of the test suspension was spread per 1 seedling. One day after the dispersion, a suspension of the sporozoites of Pseudomonas osporium cubes (Pseudoperonospora cubensis) at a concentration of 1.0 × 10 4 /ml was spray-inoculated, and cultured for 16 hours in a humid chamber adjusted to 22 °C. Thereafter, the disease was promoted indoors, and the area ratio of the lesions generated on the leaves from the inoculation to the 5th day was investigated, and the control price was calculated using the following formula.

防除價之算出式：防除價值={1-已散布試驗藥劑之葉片之發病面積率/無處理之發病面積率}×100 The calculation formula of the price control: the value of the control = {1 - the area ratio of the diseased leaves of the test agent / the area ratio of the disease without treatment} × 100

<試驗3 對於葡萄露菌病之防除效果試驗> <Test 3 Test on the control effect of grape bacillus disease>

對於葡萄(品種：Neo Muscat)實生，已每1苗散布試驗懸浮液20ml散布。散布1日後，噴霧接種調製成1.0×104個/ml濃度之葡萄生單軸黴(Plasmopara viticola)之遊走孢子囊懸浮液，在調節至22℃之濕室中培養16小時。其後，在室內促使其發病，調查從接種到5日後葉片 上產生之病斑面積率，使用以下之式算出防除價。 For the grape (variety: Neo Muscat), 20 ml of the test suspension was spread per 1 seedling. One day after the dissemination, a suspension of the spore sac of Plasmopara viticola at a concentration of 1.0 × 10 4 /ml was spray-inoculated, and cultured for 16 hours in a humid chamber adjusted to 22 °C. Thereafter, the disease was promoted indoors, and the area ratio of the lesions generated on the leaves from the inoculation to the 5th day was investigated, and the control price was calculated using the following formula.

防除價之算出式：防除價值={1-已散布試驗藥劑之葉片之發病面積率/無處理之發病面積率}×100 The calculation formula of the price control: the value of the control = {1 - the area ratio of the diseased leaves of the test agent / the area ratio of the disease without treatment} × 100

<試驗4 對於腐霉(Pythium)菌造成之水稻苗立枯病之防除效果試驗(土壤灌注)> <Experiment 4 Test on control effect of rice seedling blight caused by Pythium bacteria (soil perfusion)>

對以常綠草(bentgrass)種子培養基所培養之禾生腐黴(Pythium graminicola)之菌叢添加蒸餾水，以混合器進行攪拌，以使成為菌5g之方式對土壤1kg進行混合，而調製成污染土。 Distilled water was added to the flora of Pythium graminicola cultured in a seed culture medium of bentgrass, and stirred by a mixer to mix 1 kg of soil in a manner of 5 g of bacteria to prepare contaminated soil. .

在1空格為31×31mm2之空格盤(cell tray)中填充污染土各20ml，在每1空格中撥種已催芽之水稻谷種(品種：越光)3粒，加入5ml之覆土，灌注處理試驗懸浮液2.5ml，在調節成28℃之濕室中培養72小時，進行出芽處理。其後，在5℃之低溫室內促使其2天發病，其後，在25℃之溫室內持續患病14天。 Filling polluted soil each 20ml in a space of 31 × 31mm blank disc 2 of the (cell tray), the per box dialed species have germination of water rice seed (variety: Koshihikari) 3, was added casing 5ml of perfusion 2.5 ml of the test suspension was treated, and cultured in a humid chamber adjusted to 28 ° C for 72 hours to carry out budding treatment. Thereafter, it was caused to cause disease for 2 days in a low temperature chamber at 5 ° C, and thereafter, it was continued for 14 days in a greenhouse at 25 ° C.

沖洗土壤，計算測量枯死株、抑制生育株、健全株，依據下述之式算出發病度。 The soil was washed, and the dead plants, the growth-restricted plants, and the healthy plants were counted, and the degree of disease was calculated according to the following formula.

發病度=[Σ(個別程度之發病株數×發病指數)/(已調査之株×3)]×100 Incidence = [Σ (number of cases of individual degree × incidence index) / (plant investigated × 3)] × 100

[發病指數] [incidence index]

0：健全株 0: Healthy strain

1：抑制生育株 1: Inhibition of fertility

3：枯死株 3: dead strain

又，從所算出之發病度使用以下之式算出防除價。 Moreover, the control price was calculated from the calculated disease degree using the following formula.

防除價之算出式：防除價值={1-已散布試驗藥劑之區之發病度/無處理區之發病度}×100 The calculation formula of the price control: the value of the control = {1 - the degree of disease in the area where the test agent has been spread / the degree of disease in the no treatment area} × 100

(4)對於植物病害<試驗1>至<試驗4>之防除效果之評價試驗結果 (4) Evaluation results of the control effects of plant diseases <Test 1> to <Test 4>

實施試驗1之結果，以下所示之化合物展現防除價80以上：No.1-1~1-149、2-1~2-11、2-13~2-17、2-19~2-21、2-23~2-26、2-29、2-31~2-36、2-38~2-50。 As a result of carrying out the test 1, the compounds shown below exhibited a defense price of 80 or more: No. 1-1 to 1-149, 2-1 to 2-11, 2-13 to 2-17, 2-19 to 2-21 2-23~2-26, 2-29, 2-31~2-36, 2-38~2-50.

實施試驗2之結果，以下所示之化合物展現防除價80以上：No.1-1~1-68、1-71~1-149、2-1~2-45、2-47~2-50。 As a result of carrying out the test 2, the compounds shown below exhibited a defense price of 80 or more: No. 1-1 to 1-68, 1-71 to 1-149, 2-1 to 2-45, 2-47 to 2-50. .

實施試驗3之結果，以下所示之化合物展現防除價80以上：No.1-1~1-143、1-145~1-149、2-1~2-50。 As a result of carrying out the test 3, the compounds shown below exhibited a defense price of 80 or more: No. 1-1 to 1-143, 1-145 to 1-149, and 2-1 to 2-50.

使用數個化合物實施試驗4之結果，化合物皆展現防除價90以上。以下表示其化合物No.：No.1-3、1-6、1-10、1-11、1-15、1-21~1-23、1-32~1-34、1-36、1-40、1-44、1-45、1-47、1-49~1-51、1- 57、1-61、1-62、1-69、1-70、1-72、1-78、1-79、1-84、1-90、1-91、1-95~1-97、1-100、1-107、1-111、1-113、1-117、1-121、1-126、1-128~1-130、1-137、1-141、1-144、2-1、2-2、2-4、2-6、2-9、2-11、2-12、2-15~2-17、2-19、2-20、2-26~2-28、2-36、2-40~2-42、2-45、2-49。 As a result of carrying out the test 4 using several compounds, the compounds exhibited a defense price of 90 or more. The following shows the compound No.: No. 1-3, 1-6, 1-10, 1-1-1, 1-15, 1-21 to 1-23, 1-32 to 1-34, 1-36, 1 -40, 1-44, 1-45, 1-47, 1-49~1-51, 1- 57, 1-61, 1-62, 1-69, 1-70, 1-72, 1-78, 1-79, 1-84, 1-90, 1-91, 1-95~1-97, 1-100, 1-107, 1-111, 1-113, 1-117, 1-121, 1-126, 1-128~1-130, 1-137, 1-141, 1-144, 2- 1, 2, 2-4, 2-6, 2-9, 2-11, 2-12, 2-15~2-17, 2-19, 2-20, 2-26~2-28, 2-36, 2-40~2-42, 2-45, 2-49.

Claims (18)

一種式[1]所表示之化合物之製造方法，其特徵為包含使式[2]所表示之化合物與式[3]所表示之化合物反應之步驟； {式中，A為選自下述之基， R1及R2係各自獨立為C1~C4烷基、C1~C4鹵烷基、或鹵素原子；R3、R4、R5、R6及R7係各自獨立為氫原子、鹵素原子、氰基、羥基、胺基、硝基、C1~C6烷基、C2~C6烯基、C2~C6炔基、C1~C6鹵烷基、C2~C6鹵烯基、C2~C6鹵炔基、C1~C6烷氧基、C1~C6鹵烷氧基、C3~C6環烷基、C3~C6鹵環烷基、C4~C10環烷基烷基、C4~C10烷基環烷基、C5~C10烷基環烷基烷基、C2~C6烷氧基烷基、C1~C6羥基烷基、C1~C6烷硫基、C1~C6鹵烷硫基、C1~C6烷基亞磺醯基、C1~C6鹵烷基亞磺醯基、C1~C6烷基磺醯基、C1~C6鹵烷基磺醯基、C1~C6烷基胺基、C2~C8二烷基胺 基、C3~C6環烷基胺基、C2~C6烷基羰基、C2~C6鹵烷基羰基、C2~C6烷氧基羰基、C2~C6鹵烷氧基羰基、C2~C6烷基羰氧基、C2~C6烷基羰硫基(alkylcarbonylthio)、C2~C6烷基胺基羰基、C3~C8(二烷基胺基)羰基、或C3~C6三烷基矽基；R8為氫原子、C1~C4烷基、C1~C4烯基、苄基(在此苄基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、C2~C6烷基羰基、C2~C6鹵烷基羰基、苯基羰基(在此苯基羰基之苯環亦可被選自由鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、C2~C6烷氧基羰基、苄基氧基羰基(在此苄基氧基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、苯基氧基羰基(在此苯基氧基羰基之苯環亦可被選自鹵素原子、C1~C4烷基或C1~C4烷氧基之1種以上之取代基所取代)、三苯基甲基、甲醯基或基-SO2R9；R9為C1~C4烷基、C1~C4鹵烷基或苯基(在此苯基之苯環亦可被選自鹵素原子、C1~C4烷基、C1~C4烷氧基或硝基之1種以上之取代基所取代)} {式中，X為鹵素原子或-OR10，R10係各自獨立為C1~C4烷基，L1為鹵素原子等之脫離基}。 A process for producing a compound represented by the formula [1], which comprises the step of reacting a compound represented by the formula [2] with a compound represented by the formula [3]; In the formula, A is selected from the group consisting of R 1 and R 2 are each independently a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, or a halogen atom; and R 3 , R 4 , R 5 , R 6 and R 7 are each independently a hydrogen atom. , halogen atom, cyano group, hydroxyl group, amine group, nitro group, C 1 -C 6 alkyl group, C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group, C 1 -C 6 haloalkyl group, C 2 ~C 6 haloalkenyl, C 2 ~C 6 haloalkynyl, C 1 ~C 6 alkoxy, C 1 ~C 6 haloalkoxy, C 3 ~C 6 cycloalkyl, C 3 ~C 6 halo a cycloalkyl group, a C 4 -C 10 cycloalkylalkyl group, a C 4 -C 10 alkylcycloalkyl group, a C 5 -C 10 alkylcycloalkylalkyl group, a C 2 -C 6 alkoxyalkyl group, C 1 -C 6 hydroxyalkyl, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfin Sulfhydryl, C 1 ~C 6 alkylsulfonyl, C 1 ~C 6 haloalkylsulfonyl, C 1 -C 6 alkylamino, C 2 -C 8 dialkylamine, C 3 ~ C 6 cycloalkylamino group, C 2 -C 6 alkylcarbonyl group, C 2 -C 6 haloalkylcarbonyl group, C 2 -C 6 alkoxycarbonyl group, C 2 -C 6 haloalkoxycarbonyl group, C 2 ~ C 6 alkylcarbonyloxy, C 2 ~ C 6 alkyl-carbonyl group (alkylcarbonylthio), C 2 ~ C 6 alkyl amino carbonyl, C 3 ~ C 8 (dialkylamino) carbonyl group, C 3 ~ C 6 trialkyl silicon based; R 8 is a hydrogen atom, C 1 ~ C 4 alkyl, C 1 ~ C 4 alkenyl group, a benzyl group (this phenyl ring of benzyl group may also be selected from halogen atoms a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group substituted with at least one substituent), a C 2 -C 6 alkylcarbonyl group, a C 2 -C 6 haloalkylcarbonyl group, a phenylcarbonyl group (The phenyl ring of the phenylcarbonyl group may be substituted with one or more substituents selected from a halogen atom, a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group), a C 2 -C 6 alkane. An oxycarbonyl group or a benzyloxycarbonyl group (wherein the benzene ring of the benzyloxycarbonyl group may be substituted with one or more selected from the group consisting of a halogen atom, a C 1 -C 4 alkyl group or a C 1 -C 4 alkoxy group) a phenyloxycarbonyl group (the phenyl ring of the phenyloxycarbonyl group may be one or more selected from the group consisting of a halogen atom, a C 1 -C 4 alkyl group, or a C 1 -C 4 alkoxy group). Substituted by a substituent), triphenylmethyl, decyl or yl-SO 2 R 9 ; R 9 is C 1 -C 4 alkyl, C 1 -C 4 haloalkyl or phenyl (here phenyl The benzene ring may be substituted with one or more substituents selected from a halogen atom, a C 1 -C 4 alkyl group, a C 1 -C 4 alkoxy group or a nitro group)} In the formula, X is a halogen atom or -OR 10 , and each of R 10 is independently a C 1 -C 4 alkyl group, and L 1 is a leaving group such as a halogen atom. 一種式[1]所表示之化合物之製造方法，其特徵為包含使式[2]所表示之化合物與式[3a]所表示之化合物在鹼之存在下反應，而取得式[4]所表示之化合物之步驟，及，使前述式[4]所表示之化合物在酸或路易斯酸之存在下反應之步驟； {式中，A係如同請求項1中之所定義} {式中，R10及L1係如同請求項1中所定義} A method for producing a compound represented by the formula [1], which comprises reacting a compound represented by the formula [2] with a compound represented by the formula [3a] in the presence of a base, and obtaining the formula [4] a step of a compound, and a step of reacting the compound represented by the above formula [4] in the presence of an acid or a Lewis acid; {where A is as defined in request 1} {where R 10 and L 1 are as defined in claim 1} 一種式[5a]所表示之化合物之製造方法，其特徵為包含使式[2]所表示之化合物與式[3a]所表示之化合物在鹼之存在下反應，而取得式[4]所表示之化合物之步驟，及，使前述式[4]所表示之化合物在酸或路易斯酸之存在下反應之步驟； {式中，A及R10係如同請求項1中所定義} {式中，L1係如請求項1中所定義} A method for producing a compound represented by the formula [5a], which comprises reacting a compound represented by the formula [2] with a compound represented by the formula [3a] in the presence of a base, and obtaining the formula [4] a step of a compound, and a step of reacting the compound represented by the above formula [4] in the presence of an acid or a Lewis acid; {where, A and R 10 are as defined in claim 1} {where L 1 is as defined in claim 1} 一種式[1]所表示之化合物之製造方法，其特徵包含使式[5]所表示之化合物變換成前述式[1]所表示之化合物之步驟； {式中，A係如請求項1中所定義} {式中，X係如請求項1中所定義}。 A method for producing a compound represented by the formula [1], which comprises the step of converting a compound represented by the formula [5] into a compound represented by the above formula [1]; {where, A is as defined in request 1} In the formula, X is as defined in claim 1. 如請求項1~4中任一項之製造方法，其中R1及R2係各自獨立為C1~C4烷基、C1~C4鹵烷基、 或鹵素原子，R4、R5及R7為氫原子，R3及R6係各自獨立為氫原子、鹵素原子、C1~C6烷基或C1~C6鹵烷基，R8為C2~C6烷基羰基、苄基、苯基羰基、C2~C6烷氧基羰基。 The method of any one of claims 1 to 4, wherein R 1 and R 2 are each independently a C 1 -C 4 alkyl group, a C 1 -C 4 haloalkyl group, or a halogen atom, R 4 , R 5 And R 7 is a hydrogen atom, and each of R 3 and R 6 is independently a hydrogen atom, a halogen atom, a C 1 -C 6 alkyl group or a C 1 -C 6 haloalkyl group, and R 8 is a C 2 -C 6 alkylcarbonyl group. , benzyl, phenylcarbonyl, C 2 -C 6 alkoxycarbonyl. 如請求項1~5中任一項之製造方法，其中R1為三氟甲基、二氟甲基、或氯原子，R2為甲基、三氟甲基、二氟甲基或氯原子，R3及R6係各自獨立為氫原子、氯原子、三氟甲基或甲基，R8為乙醯基、苄基、苯基羰基、甲氧基羰基、乙氧基羰基、1,1-二甲基乙基氧基羰基或2,2-二甲基丙醯基，X為-OR10，R10係各自獨立為甲基或乙基，L1為氯原子或溴原子。 The process according to any one of claims 1 to 5, wherein R 1 is a trifluoromethyl group, a difluoromethyl group or a chlorine atom, and R 2 is a methyl group, a trifluoromethyl group, a difluoromethyl group or a chlorine atom. R 3 and R 6 are each independently a hydrogen atom, a chlorine atom, a trifluoromethyl group or a methyl group, and R 8 is an ethyl hydrazino group, a benzyl group, a phenylcarbonyl group, a methoxycarbonyl group, an ethoxycarbonyl group, and 1, 1-dimethylethyloxycarbonyl or 2,2-dimethylpropanyl, X is -OR 10 , each of R 10 is independently methyl or ethyl, and L 1 is a chlorine atom or a bromine atom. 如請求項1~6中任一項之製造方法，其中A為A-1，X為-OR10，R10為甲基，L1為溴原子。 The production method according to any one of claims 1 to 6, wherein A is A-1, X is -OR 10 , R 10 is a methyl group, and L 1 is a bromine atom. 如請求項1~7中任一項之製造方法，其中A為2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基或2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基。 The production method according to any one of claims 1 to 7, wherein A is 2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl or 2-[ 3,5-Bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl. 如請求項1~6中任一項之製造方法，其中A為乙醯基、苄基、苯基羰基、甲氧基羰基、乙氧基羰基、1,1-二甲基乙基氧基羰基或2,2-二甲基丙醯基，X為-OR10，R10為甲基，L1為溴原子。 The process according to any one of claims 1 to 6, wherein A is ethyl benzyl, benzyl, phenylcarbonyl, methoxycarbonyl, ethoxycarbonyl, 1,1-dimethylethyloxycarbonyl Or 2,2-dimethylpropanyl, X is -OR 10 , R 10 is a methyl group, and L 1 is a bromine atom. 一種式[4]所表示之化合物或其鹽； {式中，A為選自下述之基， R1為三氟甲基、二氟甲基、或氯原子，R2為甲基、三氟甲基、二氟甲基、或氯原子，R4、R5及R7為氫原子，R3及R6係各自獨立為氫原子、氯原子、三氟甲基或甲基，R8為乙醯基、苄基、苯基羰基、甲氧基羰基、乙氧基羰基、1,1-二甲基乙基氧基羰基或2,2-二甲基丙醯基，R10係各自獨立為甲基或乙基}。 a compound represented by the formula [4] or a salt thereof; In the formula, A is selected from the group consisting of R 1 is a trifluoromethyl group, a difluoromethyl group or a chlorine atom, R 2 is a methyl group, a trifluoromethyl group, a difluoromethyl group or a chlorine atom, and R 4 , R 5 and R 7 are a hydrogen atom, R 3 and R 6 are each independently a hydrogen atom, a chlorine atom, a trifluoromethyl group or a methyl group, and R 8 is an ethyl hydrazino group, a benzyl group, a phenylcarbonyl group, a methoxycarbonyl group, an ethoxycarbonyl group, and a 1,1- oxycarbonyl-dimethylethyl 2,2-dimethyl propyl group or acyl, R 10 are each independently based} methyl or ethyl. 如請求項10之化合物或其鹽，其中A為2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基或2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基，R10為甲基。 The compound of claim 10 or a salt thereof, wherein A is 2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl or 2-[3,5- Bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl, R 10 is methyl. 如請求項10之化合物或其鹽，其中A為乙醯基、苄基、苯基羰基、甲氧基羰基、乙氧基羰基、1,1-二甲基乙基氧基羰基或2,2-二甲基丙醯基，R10為甲基。 The compound of claim 10 or a salt thereof, wherein A is ethyl hydrazino, benzyl, phenylcarbonyl, methoxycarbonyl, ethoxycarbonyl, 1,1-dimethylethyloxycarbonyl or 2,2 - dimethylpropanyl, R 10 is methyl. 一種式[5]所表示之化合物或其鹽； {式中，A為選自下述之基， R1為三氟甲基、二氟甲基、或氯原子，R2為甲基、三氟甲基、二氟甲基、或氯原子，R4、R5及R7為氫原子，R3及R6係各自獨立為氫原子、氯原子、三氟甲基或甲基，R8為乙醯基、苄基、苯基羰基、甲氧基羰基、乙氧基羰基、1,1-二甲基乙基氧基羰基或2,2-二甲基丙醯基， X為氯原子或-OR10，R10係各自獨立為甲基或乙基}。 a compound represented by the formula [5] or a salt thereof; In the formula, A is selected from the group consisting of R 1 is a trifluoromethyl group, a difluoromethyl group or a chlorine atom, R 2 is a methyl group, a trifluoromethyl group, a difluoromethyl group or a chlorine atom, and R 4 , R 5 and R 7 are a hydrogen atom, R 3 and R 6 are each independently a hydrogen atom, a chlorine atom, a trifluoromethyl group or a methyl group, and R 8 is an ethyl hydrazino group, a benzyl group, a phenylcarbonyl group, a methoxycarbonyl group, an ethoxycarbonyl group, and a 1,1- Dimethylethyloxycarbonyl or 2,2-dimethylpropanyl, X is a chlorine atom or -OR 10 , and each of R 10 is independently methyl or ethyl}. 如請求項13之化合物或其鹽，其中A為2-[5-甲基-3-(三氟甲基)-1H-吡唑-1-基]乙醯基或2-[3,5-雙(二氟甲基)-1H-吡唑-1-基]乙醯基，X為甲氧基。 The compound of claim 13 or a salt thereof, wherein A is 2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethenyl or 2-[3,5- Bis(difluoromethyl)-1H-pyrazol-1-yl]ethenyl, X is methoxy. 如請求項13之化合物或其鹽，其中A為乙醯基、苄基、苯基羰基、甲氧基羰基、乙氧基羰基、1,1-二甲基乙基氧基羰基或2,2-二甲基丙醯基，X為甲氧基。 The compound of claim 13 or a salt thereof, wherein A is ethyl hydrazino, benzyl, phenylcarbonyl, methoxycarbonyl, ethoxycarbonyl, 1,1-dimethylethyloxycarbonyl or 2,2 - dimethylpropanyl, X is methoxy. 一種式[1]所表示之化合物或其鹽； {式中，A為乙醯基、苄基、苯基羰基、甲氧基羰基、乙氧基羰基或2,2-二甲基丙醯基}。 a compound represented by the formula [1] or a salt thereof; In the formula, A is ethyl benzyl, benzyl, phenylcarbonyl, methoxycarbonyl, ethoxycarbonyl or 2,2-dimethylpropanyl}. 如請求項16之化合物或其鹽，其中A為苄基、苯基羰基、甲氧基羰基、乙氧基羰基或2,2-二甲基丙醯基。 The compound of claim 16 or a salt thereof, wherein A is benzyl, phenylcarbonyl, methoxycarbonyl, ethoxycarbonyl or 2,2-dimethylpropanyl. 一種式[1]所表示之化合物之製造方法，其特徵為包含使式[2]所表示之化合物與1,1,3-三氯丙烷-2-酮在溶劑存在下反應，而取得式[6]所表示之化合物之步驟，及，使前述式[6]所表示之化合物變換成前述式[1]所表示 之化合物之步驟； {式中，A係如請求項1中所定義} A process for producing a compound represented by the formula [1], which comprises reacting a compound represented by the formula [2] with 1,1,3-trichloropropan-2-one in the presence of a solvent to obtain a formula [ 6) a step of converting the compound represented by the above formula [6] into a compound represented by the above formula [1]; {where, A is as defined in request 1}
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