JPWO2007046440A1 - Herbicidal composition - Google Patents

Abstract

A novel herbicidal composition and herbicidal method are provided. A herbicidal composition comprising a compound (A) represented by: ## STR1 ## and at least one compound selected from Daimlon, dimethylpiperate and esprocarb. A herbicidal method in which the compound (A) and at least one compound selected from Daimlon, dimethylpiperate and esprocarb are applied simultaneously or with a time difference. [Selection figure] None

Description

  The present invention relates to a herbicidal composition and a herbicidal method with reduced phytotoxicity to crops, particularly paddy rice.

Compound (A) is patent-pending as a herbicide for paddy rice, has an extremely low dosage and exhibits an effect on many weeds, and has high safety against paddy rice under normal planting conditions, but extremely shallow planting And under water leakage conditions, it may cause phytotoxicity to paddy rice.
Daimlon, dimepiperate, and esprocarb are compounds that have been put to practical use as herbicides for paddy rice, but the effect of reducing the phytotoxicity of compound (A) on paddy rice has not been reported so far.
Patent Document 1 discloses that pyrazole sulfonylureas having a dioxazine ring bonded to a pyrazole ring have herbicidal activity. However, Patent Document 1 does not specifically disclose pyrazole sulfonylureas such as compound (A) in which a substituent is bonded to a dioxazine ring on a pyrazole ring.
Japanese Unexamined Patent Publication No. 7-118269

  At present, many compounds have been put to practical use as herbicides for paddy rice, but existing drugs do not completely satisfy the requirement of selectively controlling only the target weeds without causing phytotoxicity to paddy rice.

〔式中、Ｒ¹はＣ_1-3アルキル基、Ｃ_1-3ハロアルキル基、Ｃ_1-3アルコキシＣ_1-3アルキル基、フェニル基またはピリジル基を表し、
Ｒ²は水素原子、Ｃ_1-3アルキル基、Ｃ_1-3ハロアルキル基、Ｃ_1-3アルコキシ基またはハロゲン原子を表し、
Ｒ³、Ｒ⁴、Ｒ⁵およびＲ⁶はそれぞれ独立して水素原子、Ｃ_1-3アルキル基またはＣ_1-3ハロアルキル基を表し、但し、Ｒ³、Ｒ⁴、Ｒ⁵およびＲ⁶のうち、少なくともひとつはＣ_1-3アルキル基またはＣ_1-3ハロアルキル基を表すか、又はＲ³とＲ⁴とが一緒になって＝ＣＨ_２を表し、
ＸおよびＹはそれぞれ独立してＣ_1-3アルキル基、Ｃ_1-3ハロアルキル基、Ｃ_1-3アルコキシ基、Ｃ_1-3ハロアルコキシ基、ハロゲン原子またはジ（Ｃ_1-3アルキル）アミノ基を表し、
Ｚは窒素原子またはメチン基を表す。〕で表されるピラゾールスルホニルウレア化合物（Ａ）と、
ダイムロン、ジメピペレート及びエスプロカルブの中から選ばれる少なくとも１種の化合物とを含有する除草剤組成物。
〔２〕前記化合物（Ａ）と、ダイムロン、ジメピペレート及びエスプロカルブの中から選ばれる少なくとも１種の化合物とを含有する水稲用除草剤組成物。
〔３〕前記化合物（Ａ）と、ダイムロン、ジメピペレート及びエスプロカルブの中から選ばれる少なくとも１種の化合物とを同時に、または時間差を設けて施用する除草方法。
〔４〕前記化合物（Ａ）と、ダイムロン、ジメピペレート及びエスプロカルブの中から選ばれる少なくとも１種の化合物とを同時に、または時間差を設けて施用する水田の除草方法。
〔５〕前記化合物（Ａ）と、Ｂ群（但し、Ｂ群は、ピラゾスルフロンエチル（ｐｙｒａｚｏｓｕｌｆｕｒｏｎ−ｅｔｈｙｌ／一般名）、ベンスルフロンメチル（ｂｅｎｓｕｌｆｕｒｏｎ−ｍｅｔｈｙｌ／一般名）、シノスルフロン（ｃｉｎｏｓｕｌｆｕｒｏｎ／一般名）、イマゾスルフロン（ｉｍａｚｏｓｕｌｆｕｒｏｎ／一般名）、アジムスルフロン（ａｚｉｍｓｕｌｆｕｒｏｎ／一般名）、ハロスルフロンメチル（ｈａｌｏｓｕｌｆｕｒｏｎ−ｍｅｔｈｙｌ／一般名）、シクロスルファムロン（ｃｙｃｌｏｓｕｌｆａｍｕｒｏｎ／一般名）、エトキシスルフロン（ｅｔｈｏｘｙｓｕｌｆｕｒｏｎ／一般名）、ピラゾレート（ｐｙｒａｚｏｌａｔｅ／一般名）、ピラゾキシフェン（ｐｙｒａｚｏｘｙｆｅｎ／一般名）、ベンゾフェナップ（ｂｅｎｚｏｆｅｎａｐ／一般名）、ブロモブチド（ｂｒｏｍｏｂｕｔｉｄｅ／一般名）、ナプロアニリド（ｎａｐｒｏａｎｉｌｉｄｅ／一般名）、プレチラクロール（ｐｒｅｔｉｌａｃｈｌｏｒ／一般名）、ブタクロール（ｂｕｔａｃｈｌｏｒ／一般名）、テニルクロール（ｔｈｅｎｙｌｃｈｌｏｒ／一般名）、ＣＮＰ（一般名）、クロメトキシニル（ｃｈｌｏｍｅｔｈｏｘｙｎｉｌ／一般名）、ビフェノックス（ｂｉｆｅｎｏｘ／一般名）、オキサジアゾン（ｏｘａｄｉａｚｏｎ／一般名）、オキサジアルギル（ｏｘａｄｉａｒｇｙｌ／一般名）、ペントキサゾン（ｐｅｎｔｏｘａｚｏｎｅ／一般名）、カフェンストロール（ｃａｆｅｎｓｔｒｏｌｅ／一般名）、オキサジクロメホン（ｏｘａｚｉｃｌｏｍｅｆｏｎｅ／一般名）、インダノファン（ｉｎｄａｎｏｆａｎ／一般名）、ピリミノバックメチル（ｐｙｒｉｍｉｎｏｂａｃ−ｍｅｔｈｙｌ／一般名）、シハロホップブチル（ｃｙｈａｌｏｆｏｐ−ｂｕｔｙｌ／一般名）、フェントラザミド（ｆｅｎｔｒａｚａｍｉｄｅ／一般名）、メフェナセット（ｍｅｆｅｎａｃｅｔ／一般名）、ブテナクロール（ｂｕｔｅｎａｃｈｌｏｒ／一般名）、ジチオピル（ｄｉｔｈｉｏｐｙｌ／一般名）、ベンフレセート（ｂｅｎｆｕｒｅｓａｔｅ／一般名）、ピリブチカルブ（ｐｙｒｉｂｕｔｉｃａｒｂ／一般名）、ベンチオカーブ（ｂｅｎｔｈｉｏｃａｒｂ／一般名）、モリネート（ｍｏｌｉｎａｔｅ／一般名）、ブタミフォス（ｂｕｔａｍｉｆｏｓ／一般名）、キンクロラック（ｑｕｉｎｃｌｏｒａｃ／一般名）、シンメスリン（ｃｉｎｍｅｔｈｙｌｉｎ／一般名）、シメトリン（ｓｉｍｅｔｒｙｎ／一般名）、ベンスリド（ｂｅｎｓｕｌｉｄｅ／一般名）、ジメタメトリン（ｄｉｍｅｔｈａｍｅｔｒｙｎ／一般名）、ＭＣＰＡ（一般名）、ＭＣＰＢ（一般名）、エトベンザニド（ｅｔｏｂｅｎｚａｎｉｄ／一般名）、クミルロン（ｃｕｍｙｌｕｒｏｎ／一般名）、ベンゾビシクロン（ｂｅｎｚｏｂｉｃｙｃｌｏｎ／一般名）、ピリフタリド（ｐｙｒｉｆｔａｌｉｄ／一般名），ビスピリバック（ｂｉｓｐｙｒｉｂａｃ／一般名）、ピラクロニル（ｐｙｒａｃｌｏｎｉｌ／一般名）、アニロホス（ａｎｉｌｏｆｏｓ／一般名）、ＯＫ−７０１（試験名）、ペノキススラム（ｐｅｎｏｘｓｕｌａｍ／一般名）、ＡＶＨ−３０１（試験名）、ＫＵＨ−０２１（試験名）、ＴＨ−５４７（試験名）、ベンタゾン（Ｂｅｎｔａｚｏｎｅ／一般名）、２，４−ＰＡ（一般名）、メタミホップ（一般名）、フルセトスルフロン(ｆｌｕｃｅｔｏｓｕｌｆｕｒｏｎ／一般名)、ＨＯＫ−２０１（一般名）、メソトリオン（ｍｅｓｏｔｒｉｏｎｅ／一般名）、プロパニル（ｐｒｏｐａｎｉｌ／一般名）、キノクラミン（ｑｕｉｎｏｃｌａｍｉｎｅ／一般名）およびクロメプロップ（ｃｌｏｍｅｐｒｏｐ）からなる。）から選ばれる少なくとも１種の化合物を含有することを特徴とする除草剤組成物。
〔６〕前記化合物（Ａ）と、前記Ｂ群から選ばれる少なくとも１種の化合物とを含有する水稲用除草剤組成物。
〔７〕前記化合物（Ａ）と、前記Ｂ群から選ばれる少なくとも１種の化合物とを同時に、または時間差を設けて施用する除草方法。
〔８〕前記化合物（Ａ）と、前記Ｂ群から選ばれる少なくとも１種の化合物とを同時に、または時間差で施用する水田の除草方法。As a result of intensive studies to solve the above problems, the inventors of the present invention have demonstrated that the compound (A) and Daimlone, dimepiperate, or esprocarb have a greater phytotoxicity-reducing effect than expected, and the compound (A) It has been found that mixing with certain herbicides complements each other's herbicidal spectrum without antagonizing each other, thus completing the present invention. That is, the present invention relates to a herbicide composition described in the following [1] and [2] (hereinafter referred to as the present composition), and a herbicidal method described in [3] and [4] (hereinafter referred to as the present method). .).
[1] Formula (1):

[Wherein R ¹ represents a C _1-3 alkyl group, a C _1-3 haloalkyl group, a C _1-3 alkoxy C _1-3 alkyl group, a phenyl group or a pyridyl group,
R ² represents a hydrogen atom, a C _1-3 alkyl group, a C _1-3 haloalkyl group, a C _1-3 alkoxy group or a halogen atom,
R ³ , R ⁴ , R ⁵ and R ⁶ each independently represents a hydrogen atom, a C _1-3 alkyl group or a C _1-3 haloalkyl group, provided that R ³ , R ⁴ , R ⁵ and R ⁶ , At least one represents a C _1-3 alkyl group or a C _1-3 haloalkyl group, or R ³ and R ⁴ together represent ═CH ₂ ,
X and Y are each independently a C _1-3 alkyl group, a C _1-3 haloalkyl group, a C _1-3 alkoxy group, a C _1-3 haloalkoxy group, a halogen atom or a di (C _1-3 alkyl) amino group. Represents
Z represents a nitrogen atom or a methine group. And a pyrazole sulfonylurea compound (A) represented by:
A herbicidal composition containing at least one compound selected from Daimlon, dimethylpiperate, and esprocarb.
[2] A herbicidal composition for paddy rice containing the compound (A) and at least one compound selected from Daimlon, dimethylpiperate, and esprocarb.
[3] A herbicidal method in which the compound (A) and at least one compound selected from Daimlon, dimethylpiperate and esprocarb are applied simultaneously or with a time difference.
[4] A paddy field weeding method, wherein the compound (A) and at least one compound selected from Daimlon, dimethylpiperate and eprocarb are applied simultaneously or with a time difference.
[5] The compound (A), group B (provided that group B is pyrazosulfuron-ethyl / generic name), bensulfuron methyl (bensulfuron-methyl / generic name), sinosulfuron / cynosulfuron / generic name ), Imazosulfuron (generic name), azisulfuron (generic name), halosulfuron methyl (generic name), cyclosulfamuron (generic name), ethoxysulfuron (generic name) ), Pyrazolate (generic name), pyrazoxifene (generic name), benzophenap ( enzofenap / generic name), bromobutide (generic name), naproanilide (generic name / generic name), pretilachlor (general name), butachlor (general name), tenylchlorN (generic name) ), Clomethoxynil (generic name), biphenox (bifenox / generic name), oxadiazone (generic name), oxadialgyl (generic name), pentoxazone (generic name), cfentroro (c / en) Oxadichromemephone (general name), Indano Fan (indanofan / generic name), pyriminobac-methyl / generic name, cyhalohop-butyl (generic name), fentolazamide (fentrazamide / generic name), mefenacet / generic name , Butenachlor (butenachlor / generic name), dithiopyr (dithiopyl / generic name), benfrate (benfurateate / generic name), piributicalb (generic name), benchiocarb (bentocarb / generic name), molinate (Butamifos / generic name), quinchlorac (quincrorac / generic name), cinmesulin (cinm) Ethylin / generic name), cimetrin (simmetryn / generic name), bensulide (bensulide / generic name), dimetamethrin (dimetametrin / generic name), MCPA (generic name), MCPB (generic name), etenzanide / etobanzanid / generic name Cumylron (cumylon / generic name), benzobicyclon (benzobicyclone / generic name), pyriftalide (pyriftalid / generic name), bispyribac (general name), pyraclonil (pyraclonil / generic name), anilofos (generic name) OK-701 (test name), penoxsulam (penoxslam / generic name), AVH-301 (test name), KUH-021 (test name), TH-547 Test name), bentazone (Bentazole / generic name), 2,4-PA (generic name), metamihop (generic name), flucetosulfuron (flucetosulfuron / generic name), HOK-201 (generic name), mesotrione / mesotrione / Common name), propanil (propanil / generic name), quinoclamine (generic name) and chromeprop. A herbicide composition comprising at least one compound selected from
[6] A herbicidal composition for paddy rice containing the compound (A) and at least one compound selected from the group B.
[7] A herbicidal method in which the compound (A) and at least one compound selected from the group B are applied simultaneously or with a time difference.
[8] A method for weeding paddy fields, wherein the compound (A) and at least one compound selected from the group B are applied simultaneously or with a time difference.

  According to the present invention, phytotoxicity to crops, particularly paddy rice, caused by compound (A), which is an active ingredient of a herbicide, is reduced by Daimlon, dimethylpiperate and esprocarb, and the herbicidal effect on various weeds does not decrease. Also, mixtures of compound (A) with certain herbicides complement each other in the herbicidal spectrum without antagonism. For these reasons, the utility in an actual application scene according to the present invention is extremely high.

〔式中、Ｒ¹、Ｒ²、Ｒ³、Ｒ⁴、Ｒ⁵、Ｒ⁶、Ｘ、ＹおよびＺは前記と同様の意味を表す。〕
反応式１は４−（５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール−５−スルホンアミド（２）を塩基存在下または非存在下、２−フェノキシカルボニルアミノピリミジン（またはトリアジン）（３）と反応させて化合物（１）を製造する方法を示す。
本反応において、（３）は（２）に対して通常０．５ないし１０倍モル、好ましくは０．９ないし１．１倍モル使用される。
本反応に使用される塩基としては水酸化ナトリウム、水酸化カリウム、炭酸カリウム、炭酸ナトリウムおよび水素化ナトリウム等の無機塩基類、ピリジン、４−ジメチルアミノピリジン、トリエチルアミン、Ｎ，Ｎ−ジメチルアニリン、１，８−ジアザビシクロ［５．４．０］−７−ウンデセンおよび１，４−ジアザビシクロ［２．２．２］オクタン等の有機塩基類、ｎ−ブチルリチウムおよびｓｅｃ−ブチルリチウム等の有機リチウム類、リチウムジイソプロピルアミドおよびリチウムビス（トリメチルシリル）アミド等の有機リチウムアミド類、並びにナトリウムメトキシド、ナトリウムエトキシドおよびカリウムｔ−ブトキシド等の金属アルコキシド類が挙げられる。塩基は（２）に対して通常０ないし１０倍モル、好ましくは０ないし２倍モル使用される。
本反応は無溶媒でも進行するが、必要に応じて溶媒を使用できる。溶媒は反応に不活性なものであれば特に制限はないが、例えば、ヘキサン、シクロヘキサン、ベンゼンおよびトルエン等の炭化水素類、四塩化炭素、クロロホルムおよび１，２−ジクロロエタン等のハロゲン系炭化水素類、ジエチルエーテル、ジイソプロピルエーテル、ジオキサンおよびテトラヒドロフラン等のエーテル類、アセトン、メチルエチルケトンおよびメチルイソブチルケトン等のケトン類、アセトニトリルおよびプロピオニトリル等のニトリル類、並びにこれらの混合溶媒が挙げられる。
反応温度は通常−９０ないし２００℃、好ましくは０ないし１２０℃である。
反応時間は通常０．０５ないし１００時間、好ましくは０．５ないし１０時間である。In the present specification, the symbol Ph in the formula represents a phenyl group, Me represents a methyl group, and Bu represents a butyl group.
Compound (A) can be produced by the methods shown in the following reaction formulas 1 to 3.
[Reaction Formula 1]

[Wherein, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , X, Y and Z represent the same meaning as described above. ]
Reaction Formula 1 shows that 4- (5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide (2) is added in the presence or absence of a base to 2-phenoxycarbonylaminopyrimidine (or triazine). ) A method for producing compound (1) by reacting with (3) is shown.
In this reaction, (3) is generally used in an amount of 0.5 to 10-fold mol, preferably 0.9 to 1.1-fold mol based on (2).
Bases used in this reaction include inorganic bases such as sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate and sodium hydride, pyridine, 4-dimethylaminopyridine, triethylamine, N, N-dimethylaniline, 1 , 8-diazabicyclo [5.4.0] -7-undecene and 1,4-diazabicyclo [2.2.2] octane and other organic bases, n-butyllithium and sec-butyllithium and other organic lithiums, Examples include organic lithium amides such as lithium diisopropylamide and lithium bis (trimethylsilyl) amide, and metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide. The base is generally used in an amount of 0 to 10 moles, preferably 0 to 2 moles compared to (2).
This reaction proceeds even without solvent, but a solvent can be used if necessary. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, and halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane. , Ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, and mixed solvents thereof.
The reaction temperature is usually -90 to 200 ° C, preferably 0 to 120 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

〔式中、Ｒ¹、Ｒ²、Ｒ³、Ｒ⁴、Ｒ⁵、Ｒ⁶、Ｘ、ＹおよびＺは前記と同様の意味を表す。〕
反応式２は４−（５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール−５−スルホニルカーバメート（４）を塩基存在下または非存在下、２−アミノピリミジン（またはトリアジン）（５）と反応させて化合物（１）を製造する方法を示す。
本反応において、（５）は（４）に対して通常０．５ないし１０倍モル、好ましくは０．９ないし１．１倍モル使用される。
本反応に使用される塩基としては水酸化ナトリウム、水酸化カリウム、炭酸カリウム、炭酸ナトリウムおよび水素化ナトリウム等の無機塩基類、ピリジン、４−ジメチルアミノピリジン、トリエチルアミン、Ｎ，Ｎ−ジメチルアニリン、１，８−ジアザビシクロ［５．４．０］−７−ウンデセンおよび１，４−ジアザビシクロ［２．２．２］オクタン等の有機塩基類、ｎ−ブチルリチウムおよびｓｅｃ−ブチルリチウム等の有機リチウム類、リチウムジイソプロピルアミドおよびリチウムビス（トリメチルシリル）アミド等の有機リチウムアミド類、並びにナトリウムメトキシド、ナトリウムエトキシドおよびカリウムｔ−ブトキシド等の金属アルコキシド類が挙げられる。塩基は（４）に対して通常０ないし１０倍モル、好ましくは０ないし２倍モル使用される。
本反応は無溶媒でも進行するが、必要に応じて溶媒を使用できる。溶媒は反応に不活性なものであれば特に制限はないが、例えば、ヘキサン、シクロヘキサン、ベンゼンおよびトルエン等の炭化水素類、四塩化炭素、クロロホルムおよび１，２−ジクロロエタン等のハロゲン系炭化水素類、ジエチルエーテル、ジイソプロピルエーテル、ジオキサンおよびテトラヒドロフラン等のエーテル類、アセトン、メチルエチルケトンおよびメチルイソブチルケトン等のケトン類、アセトニトリルおよびプロピオニトリル等のニトリル類、並びにこれらの混合溶媒が挙げられる。
反応温度は通常−９０ないし２００℃、好ましくは０ないし１２０℃である。
反応時間は通常０．０５ないし１００時間、好ましくは０．５ないし１０時間である。[Reaction formula 2]

[Wherein, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , X, Y and Z represent the same meaning as described above. ]
Reaction Scheme 2 shows 4- (5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonylcarbamate (4) in the presence or absence of a base, 2-aminopyrimidine (or triazine) ( A method for producing compound (1) by reacting with 5) is shown.
In this reaction, (5) is usually used in an amount of 0.5 to 10-fold mol, preferably 0.9 to 1.1-fold mol based on (4).
Bases used in this reaction include inorganic bases such as sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate and sodium hydride, pyridine, 4-dimethylaminopyridine, triethylamine, N, N-dimethylaniline, 1 , 8-diazabicyclo [5.4.0] -7-undecene and 1,4-diazabicyclo [2.2.2] octane and other organic bases, n-butyllithium and sec-butyllithium and other organic lithiums, Examples include organic lithium amides such as lithium diisopropylamide and lithium bis (trimethylsilyl) amide, and metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide. The base is usually used in an amount of 0 to 10 moles, preferably 0 to 2 moles compared to (4).
This reaction proceeds even without solvent, but a solvent can be used if necessary. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, and halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane. , Ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, and mixed solvents thereof.
The reaction temperature is usually -90 to 200 ° C, preferably 0 to 120 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

〔式中、Ｒ¹、Ｒ²、Ｒ³、Ｒ⁴、Ｒ⁵、Ｒ⁶、Ｘ、ＹおよびＺは前記と同様の意味を表す。〕
反応式３は４−（５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール−５−スルホニルイソシアナート（６）を塩基存在下または非存在下、２−アミノピリミジン（またはトリアジン）（５）と反応させて化合物（１）を製造する方法を示す。
本反応において、（５）は（６）に対して通常０．５ないし１０倍モル、好ましくは０．９ないし１．１倍モル使用される。
本反応に使用される塩基としては水酸化ナトリウム、水酸化カリウム、炭酸カリウム、炭酸ナトリウムおよび水素化ナトリウム等の無機塩基類、ピリジン、４−ジメチルアミノピリジン、トリエチルアミン、Ｎ，Ｎ−ジメチルアニリン、１，８−ジアザビシクロ［５．４．０］−７−ウンデセンおよび１，４−ジアザビシクロ［２．２．２］オクタン等の有機塩基類、ｎ−ブチルリチウムおよびｓｅｃ−ブチルリチウム等の有機リチウム類、リチウムジイソプロピルアミドおよびリチウムビス（トリメチルシリル）アミド等の有機リチウムアミド類、並びにナトリウムメトキシド、ナトリウムエトキシドおよびカリウムｔ−ブトキシド等の金属アルコキシド類が挙げられる。塩基は（３）に対して通常０ないし１０倍モル、好ましくは０ないし２倍モル使用される。
本反応は無溶媒でも進行するが、必要に応じて溶媒を使用できる。溶媒は反応に不活性なものであれば特に制限はないが、例えば、ヘキサン、シクロヘキサン、ベンゼンおよびトルエン等の炭化水素類、四塩化炭素、クロロホルムおよび１，２−ジクロロエタン等のハロゲン系炭化水素類、ジエチルエーテル、ジイソプロピルエーテル、ジオキサンおよびテトラヒドロフラン等のエーテル類、アセトン、メチルエチルケトンおよびメチルイソブチルケトン等のケトン類、アセトニトリルおよびプロピオニトリル等のニトリル類、並びにこれらの混合溶媒が挙げられる。
反応温度は通常−９０ないし２００℃、好ましくは０ないし１２０℃である。
反応時間は通常０．０５ないし１００時間、好ましくは０．５ないし１０時間である。[Reaction Formula 3]

[Wherein, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , X, Y and Z represent the same meaning as described above. ]
Reaction Scheme 3 is a method of preparing 4- (5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonyl isocyanate (6) in the presence or absence of a base, 2-aminopyrimidine (or triazine). A method for producing compound (1) by reacting with (5) is shown.
In this reaction, (5) is usually used in an amount of 0.5 to 10-fold mol, preferably 0.9 to 1.1-fold mol based on (6).
Bases used in this reaction include inorganic bases such as sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate and sodium hydride, pyridine, 4-dimethylaminopyridine, triethylamine, N, N-dimethylaniline, 1 , 8-diazabicyclo [5.4.0] -7-undecene and 1,4-diazabicyclo [2.2.2] octane and other organic bases, n-butyllithium and sec-butyllithium and other organic lithiums, Examples include organic lithium amides such as lithium diisopropylamide and lithium bis (trimethylsilyl) amide, and metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide. The base is generally used in an amount of 0 to 10 moles, preferably 0 to 2 moles compared to (3).
This reaction proceeds even without solvent, but a solvent can be used if necessary. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, and halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane. , Ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, and mixed solvents thereof.
The reaction temperature is usually -90 to 200 ° C, preferably 0 to 120 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

4- (5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide (2) used in the method shown in Reaction Formula 1 can be produced by the method shown in Reaction Formulas 4-6.
Further, 4- (5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonylcarbamate (4) and 4- (5H, 6H-1) used in the methods shown in Reaction Schemes 2 to 3 are used. , 4,2-Dioxazin-3-yl) pyrazole-5-sulfonyl isocyanate (6) is 4- (5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide (2) Can be synthesized with reference to the methods described in JP-A-59-219281 and JP-A-55-13266.

〔式中、Ｒ¹、Ｒ²、Ｒ³、Ｒ⁴、Ｒ⁵およびＲ⁶は前記と同様の意味を表す。〕
反応式４は、５−クロロ−４−（５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（７）を水硫化ナトリウムと反応させて５−メルカプト−４−（５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（８）とし（工程Ａ）、（８）を塩素または次亜塩素酸ナトリウム等の塩素化剤と反応させて４−（５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール−５−スルホニルクロリド（９）とし（工程Ｂ）、（９）をアンモニア水または炭酸アンモニウムと反応させて（工程Ｃ）、４−（５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール−５−スルホンアミド（２）を製造する方法を示す。[Reaction Formula 4]

[Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ represent the same meaning as described above. ]
Reaction scheme 4 is a reaction of 5-chloro-4- (5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (7) with sodium hydrosulfide to give 5-mercapto-4- (5H, 6H). -1,4,2-dioxazin-3-yl) pyrazole (8) (step A), (8) is reacted with a chlorinating agent such as chlorine or sodium hypochlorite to give 4- (5H, 6H- 1,4,2-dioxazin-3-yl) pyrazole-5-sulfonyl chloride (9) (step B), (9) is reacted with aqueous ammonia or ammonium carbonate (step C), 4- (5H, A method for producing 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide (2) is shown.

In the reaction of Step A, sodium hydrosulfide is generally used in an amount of 1.0 to 10 times mol, preferably 2 to 5 times mol, of (7).
This reaction proceeds even without solvent, but a solvent can be used if necessary. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, and halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane. , Ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, N, N-dimethylformamide, N, N-dimethylacetamide And amides such as N-methyl-2-pyrrolidone, sulfur-containing polar solvents such as dimethyl sulfoxide and sulfolane, water, and a mixed solvent thereof.
The reaction temperature is usually -90 to 200 ° C, preferably 0 to 120 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

In the reaction of Step B, chlorine or sodium hypochlorite is usually used in an amount of 1 to 100 times mol, preferably 2 to 10 times mol for (8).
This reaction can use a solvent as needed. The solvent is not particularly limited as long as it is inert to the reaction, and examples thereof include halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane, water, and a mixed solvent thereof.
The reaction temperature is usually -90 to 100 ° C, preferably -10 to 50 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

In the reaction of Step C, ammonia or ammonium carbonate is usually used in an amount of 1.0 to 100-fold mol, preferably 2 to 5-fold mol based on (9).
This reaction proceeds even without solvent, but a solvent can be used if necessary. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, and halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane. , Ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, N, N-dimethylformamide, N, N-dimethylacetamide And amides such as N-methyl-2-pyrrolidone, sulfur-containing polar solvents such as dimethyl sulfoxide and sulfolane, water, and a mixed solvent thereof.
The reaction temperature is usually -90 to 200 ° C, preferably 0 to 100 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

〔式中、Ｒ¹、Ｒ²、Ｒ³、Ｒ⁴、Ｒ⁵およびＲ⁶は前記と同様の意味を表す。〕
反応式５は、５−ベンジルメルカプト−４−（５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（１０）を塩素または次亜塩素酸ナトリウム等の塩素化剤と反応させ、４−（５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール−５−スルホニルクロリド（９）を製造する方法を示す。
本反応において、塩素または次亜塩素酸ナトリウムは（１０）に対して通常１ないし１００倍モル、好ましくは２ないし１０倍モル使用される。
本反応は、必要に応じて溶媒を使用できる。溶媒は反応に不活性なものであれば特に制限はないが、例えば、四塩化炭素、クロロホルムおよび１，２−ジクロロエタン等のハロゲン系炭化水素類、水、並びにこれらの混合溶媒が挙げられる。
反応温度は通常−９０ないし１００℃、好ましくは−１０ないし５０℃である。
反応時間は通常０．０５ないし１００時間、好ましくは０．５ないし１０時間である。[Reaction Formula 5]

[Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ represent the same meaning as described above. ]
Reaction scheme 5 is a reaction of 5-benzylmercapto-4- (5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (10) with a chlorinating agent such as chlorine or sodium hypochlorite, A method for producing 4- (5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonyl chloride (9) will be described.
In this reaction, chlorine or sodium hypochlorite is usually used in an amount of 1 to 100 times mol, preferably 2 to 10 times mol, of (10).
This reaction can use a solvent as needed. The solvent is not particularly limited as long as it is inert to the reaction, and examples thereof include halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane, water, and a mixed solvent thereof.
The reaction temperature is usually -90 to 100 ° C, preferably -10 to 50 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

  (9) can be derived into 4- (5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide (2) by Step C of Reaction Scheme 4. Further, referring to the method described in JP-A-7-118267, (1) can be produced by reacting (9) and (5).

〔式中、Ｒ¹、Ｒ²、Ｒ³、Ｒ⁴、Ｒ⁵およびＲ⁶は前記と同様の意味を表す。〕
反応式６は、４−（５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（１１）のピラゾール環上５位をｎ−ブチルリチウム（ｎ−ＢｕＬｉ）またはリチウムジイソプロピルアミド（ＬＤＡ）等によりリチオ化後、二酸化硫黄と反応させて４−（５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール−５−スルフィン酸リチウム（１２）とし（工程Ｄ）、（１２）をＮ−クロロコハク酸イミドと反応させて（工程Ｅ）、４−（５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール−５−スルホニルクロリド（９）を製造する方法を示す。[Reaction Formula 6]

[Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ represent the same meaning as described above. ]
In Reaction Scheme 6, 4- (5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (11) is substituted with 5-position of n-butyllithium (n-BuLi) or lithium diisopropylamide (LDA) on the pyrazole ring. ) And the like, and then reacted with sulfur dioxide to give lithium 4- (5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfinate (12) (step D), (12) ) Is reacted with N-chlorosuccinimide (Step E) to produce 4- (5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonyl chloride (9) .

In the reaction of step D 1), n-butyllithium or lithium diisopropylamide is usually used in an amount of 1 to 100-fold mol, preferably 1 to 5-fold mol based on (11).
This reaction proceeds even without solvent, but a solvent can be used if necessary. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, and mixtures thereof A solvent is mentioned.
The reaction temperature is usually -120 to 100 ° C, preferably -78 to 10 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

In the reaction of step D 2), sulfur dioxide is usually used in an amount of 1.0 to 100-fold mol, preferably 1 to 10-fold mol based on (11).
This reaction proceeds even without solvent, but a solvent can be used if necessary. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, and mixtures thereof A solvent is mentioned.
The reaction temperature is usually -120 to 100 ° C, preferably -78 to 10 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

In the reaction of Step E, N-chlorosuccinimide is usually used in an amount of 1.0 to 100-fold mol, preferably 1 to 10-fold mol based on (12).
The solvent used in this reaction is not particularly limited as long as it is inert to the reaction. For example, halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane, water, and mixtures thereof A solvent is mentioned.
The reaction temperature is usually -90 to 100 ° C, preferably -10 to 50 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

  (9) can be derived into 4- (5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide (2) by Step C of Reaction Scheme 4.

〔式中、Ｒ¹、Ｒ²、Ｒ³、Ｒ⁴、Ｒ⁵およびＲ⁶は前記と同様の意味を表し、Ｘ¹はハロゲン原子を表し、Ｌは塩素原子、ベンジルチオ基または水素原子を表す。〕
反応式７は、ピラゾール−４−ヒドロキサム酸（１３）を隣接ジハロゲン化アルキル（１４）と反応させて４−（５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（７）、（１０）または（１１）を製造する方法を示す。
本反応において、（１４）は（１３）に対して通常１．０ないし１００倍モル、好ましくは１ないし５倍モル使用される。
本反応に使用される塩基としては水酸化ナトリウム、水酸化カリウム、炭酸カリウム、炭酸ナトリウム、炭酸水素カリウム、炭酸水素ナトリウムおよび水素化ナトリウム等の無機塩基類、ピリジン、４−ジメチルアミノピリジン、トリエチルアミン、Ｎ，Ｎ−ジメチルアニリン、１，８−ジアザビシクロ［５．４．０］−７−ウンデセンおよび１，４−ジアザビシクロ［２．２．２］オクタン等の有機塩基類、ｎ−ブチルリチウムおよびｓｅｃ−ブチルリチウム等の有機リチウム類、リチウムジイソプロピルアミドおよびリチウムビス（トリメチルシリル）アミド等の有機リチウムアミド類、並びにナトリウムメトキシド、ナトリウムエトキシドおよびカリウムｔ−ブトキシド等の金属アルコキシド類が挙げられる。塩基は（１３）に対して通常０ないし１０倍モル、好ましくは０ないし２倍モル使用される。
本反応は無溶媒でも進行するが、必要に応じて溶媒を使用できる。溶媒は反応に不活性なものであれば特に制限はないが、例えば、ヘキサン、シクロヘキサン、ベンゼンおよびトルエン等の炭化水素類、四塩化炭素、クロロホルムおよび１，２−ジクロロエタン等のハロゲン系炭化水素類、ジエチルエーテル、ジイソプロピルエーテル、ジオキサンおよびテトラヒドロフラン等のエーテル類、アセトン、メチルエチルケトンおよびメチルイソブチルケトン等のケトン類、アセトニトリルおよびプロピオニトリル等のニトリル類、Ｎ，Ｎ−ジメチルホルムアミド、Ｎ，Ｎ−ジメチルアセトアミドおよびＮ−メチル−２−ピロリドン等のアミド類、ジメチルスルホキシドおよびスルホラン等の含硫黄極性溶媒類、水、並びにこれらの混合溶媒が挙げられる。
反応温度は通常−９０ないし２００℃、好ましくは０ないし１００℃である。
反応時間は通常０．０５ないし１００時間、好ましくは０．５ないし１０時間である。5-Chloro-4- (5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (7), 5-benzylmercapto-4- (5H, 6H) used in the methods shown in Reaction Schemes 4 to 6 -1,4,2-dioxazin-3-yl) pyrazole (10) and 4- (5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (11) are represented by the reaction schemes 7 to 15. Can be manufactured.
[Reaction Scheme 7]

[Wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ and R ⁶ represent the same meaning as described above, X ¹ represents a halogen atom, and L represents a chlorine atom, a benzylthio group or a hydrogen atom. . ]
Scheme 7 shows a reaction of pyrazole-4-hydroxamic acid (13) with an adjacent dihalogenated alkyl (14) to give 4- (5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (7), A method for producing (10) or (11) will be described.
In this reaction, (14) is generally used in an amount of 1.0 to 100-fold mol, preferably 1 to 5-fold mol based on (13).
Examples of the base used in this reaction include sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, sodium hydride and other inorganic bases, pyridine, 4-dimethylaminopyridine, triethylamine, Organic bases such as N, N-dimethylaniline, 1,8-diazabicyclo [5.4.0] -7-undecene and 1,4-diazabicyclo [2.2.2] octane, n-butyllithium and sec- Examples thereof include organic lithiums such as butyl lithium, organic lithium amides such as lithium diisopropylamide and lithium bis (trimethylsilyl) amide, and metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide. The base is usually used in an amount of 0 to 10 moles, preferably 0 to 2 moles compared to (13).
This reaction proceeds even without solvent, but a solvent can be used if necessary. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, and halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane. , Ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, N, N-dimethylformamide, N, N-dimethylacetamide And amides such as N-methyl-2-pyrrolidone, sulfur-containing polar solvents such as dimethyl sulfoxide and sulfolane, water, and a mixed solvent thereof.
The reaction temperature is usually -90 to 200 ° C, preferably 0 to 100 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

〔式中、Ｒ¹、Ｒ²、Ｒ³、Ｒ⁴、Ｒ⁵、Ｒ⁶およびＬは前記と同様の意味を表し、Ｘ²はハロゲン原子、Ｃ_1-3アルキルスルホニルオキシ基またはＣ_1-3ハロアルキルスルホニルオキシ基を表す。〕
反応式８は、ピラゾール−４−カルボン酸クロリド（１５）をアルコキシアミン（１６）と反応させてピラゾール−４−ヒドロキサム酸エステル（１７）とし（工程Ｆ）、（１７）を塩基と反応させて（工程Ｇ）、４−（５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（７）、（１０）または（１１）を製造する方法を示す。[Reaction Formula 8]

[Wherein, R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and L represent the same meaning as described above, and X ² represents a halogen atom, a C _1-3 alkylsulfonyloxy group or a C _{1- 3} represents a haloalkylsulfonyloxy group. ]
In Reaction Scheme 8, pyrazole-4-carboxylic acid chloride (15) is reacted with alkoxyamine (16) to give pyrazole-4-hydroxamic acid ester (17) (Step F), and (17) is reacted with a base. (Step G) shows a method for producing 4- (5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (7), (10) or (11).

In the reaction of Step F, (16) is usually used in an amount of 1 to 100-fold mol, preferably 2 to 5-fold mol based on (15).
Examples of the base used in this reaction include sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, sodium hydride and other inorganic bases, pyridine, 4-dimethylaminopyridine, triethylamine, Organic bases such as N, N-dimethylaniline, 1,8-diazabicyclo [5.4.0] -7-undecene and 1,4-diazabicyclo [2.2.2] octane, n-butyllithium and sec- Examples thereof include organic lithiums such as butyl lithium, organic lithium amides such as lithium diisopropylamide and lithium bis (trimethylsilyl) amide, and metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide. The base is generally used in an amount of 0 to 10 moles, preferably 0 to 2 moles compared to (15).
This reaction proceeds even without solvent, but a solvent can be used if necessary. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, and halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane. , Ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, N, N-dimethylformamide, N, N-dimethylacetamide And amides such as N-methyl-2-pyrrolidone, water, and a mixed solvent thereof.
The reaction temperature is usually -90 to 200 ° C, preferably 0 to 100 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

Examples of the base used in the reaction of Step G include inorganic bases such as sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate and sodium hydride, pyridine, 4-dimethylaminopyridine, triethylamine, N, N-dimethyl. Organic bases such as aniline, 1,8-diazabicyclo [5.4.0] -7-undecene and 1,4-diazabicyclo [2.2.2] octane, and organic bases such as n-butyllithium and sec-butyllithium Examples include lithiums, organic lithium amides such as lithium diisopropylamide and lithium bis (trimethylsilyl) amide, and metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide. The base is generally used in an amount of 0 to 10 moles, preferably 0 to 2 moles compared to (17).
This reaction proceeds even without solvent, but a solvent can be used if necessary. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, and halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane. , Ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, N, N-dimethylformamide, N, N-dimethylacetamide And amides such as N-methyl-2-pyrrolidone, water, and a mixed solvent thereof.
The reaction temperature is usually -90 to 200 ° C, preferably 0 to 100 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

〔式中、Ｒ¹、Ｒ²、Ｒ³、Ｒ⁵、Ｒ⁶、Ｘ¹およびＬは前記と同様の意味を表し、Ｒ⁷およびＲ⁸はそれぞれ独立して水素原子またはＣ_1-3アルキル基を表す。〕
反応式９は、ピラゾール−４−カルボン酸クロリド（１５）をアリルオキシアミン（１６ａ）と反応させてピラゾール−４−ヒドロキサム酸エステル（１７ａ）とし（工程Ｈ）、（１７ａ）をハロゲンまたはＮ−ハロゲン化コハク酸イミドと反応させて４−（５−ハロアルキル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（７ａ）、（１０ａ）または（１１ａ）とし（工程Ｉ）、（７ａ）、（１０ａ）または（１１ａ）を還元して(工程Ｊ）、４−（５−アルキル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（７ｂ）、（１０ｂ）または（１１ｂ）を製造する方法を示す。[Reaction Formula 9]

[Wherein R ¹ , R ² , R ³ , R ⁵ , R ⁶ , X ¹ and L represent the same meaning as described above, and R ⁷ and R ⁸ each independently represents a hydrogen atom or C _1-3 alkyl. Represents a group. ]
In Reaction Scheme 9, pyrazole-4-carboxylic acid chloride (15) is reacted with allyloxyamine (16a) to give pyrazole-4-hydroxamic acid ester (17a) (step H), and (17a) is halogenated or N- Reacting with a halogenated succinimide to give 4- (5-haloalkyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (7a), (10a) or (11a) (step I); (7a), (10a) or (11a) is reduced (Step J) to give 4- (5-alkyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (7b), (10b) ) Or (11b) is produced.

In the reaction of Step H, (16a) is usually used in an amount of 1 to 100 times mol, preferably 2 to 5 times mol to (15).
Examples of the base used in this reaction include sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, sodium hydride and other inorganic bases, pyridine, 4-dimethylaminopyridine, triethylamine, Organic bases such as N, N-dimethylaniline, 1,8-diazabicyclo [5.4.0] -7-undecene and 1,4-diazabicyclo [2.2.2] octane, n-butyllithium and sec- Examples thereof include organic lithiums such as butyl lithium, organic lithium amides such as lithium diisopropylamide and lithium bis (trimethylsilyl) amide, and metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide. The base is generally used in an amount of 0 to 10 moles, preferably 0 to 2 moles compared to (15).
This reaction proceeds even without solvent, but a solvent can be used if necessary. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, and halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane. , Ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, N, N-dimethylformamide, N, N-dimethylacetamide And amides such as N-methyl-2-pyrrolidone, water, and a mixed solvent thereof.
The reaction temperature is usually -90 to 200 ° C, preferably 0 to 100 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

In the reaction of Step I, halogen or N-halogenosuccinimide is generally used in an amount of 1 to 100-fold mol, preferably 1 to 5-fold mol based on (17a).
This reaction proceeds even without solvent, but a solvent can be used if necessary. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, and halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane. , Ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, carboxylic acid esters such as methyl acetate or ethyl acetate, methanol , Alcohols such as ethanol or ethylene glycol, amides such as N, N-dimethylformamide, N, N-dimethylacetamide and N-methyl-2-pyrrolidone, water, and mixed solvents thereof It is.
The reaction temperature is usually -90 to 200 ° C, preferably 0 to 100 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

Examples of the reducing agent and the reduction system used in the reaction of Step J include a system using an alkali metal such as metallic sodium / liquid ammonia, metallic lithium / liquid ammonia and metallic sodium / t-butyl alcohol-tetrahydrofuran mixed solvent, zinc / acetic acid and Systems using metallic zinc such as zinc / potassium hydroxide / water, such as triphenyltin hydride, diphenyltin hydride, tri-n-butyltin hydride, di-n-butyltin hydride, triethyltin hydride and trimethyltin hydride Systems using organotin hydrides, systems combining the above organotin compounds and free radical initiators such as azobisisobutyronitrile, systems using silanes such as trichlorosilane, triethylsilane and trimethylsilane, lithium aluminum hydride , Aluminum hydride sodium , Systems using metal hydrogen complex compounds such as sodium bis (2-methoxyethoxy) aluminum hydride, sodium borohydride and sodium cyanoborohydride, systems using borane derivatives such as diborane, trimethylamine-borane and pyridine-borane And catalytic reduction systems such as hydrogen / palladium-carbon and hydrogen / Raney nickel.
The reducing agent is usually used in an amount of 1 to 100 times mol, preferably 1 to 5 times mol for (7a), (10a) or (11a).
This reduction reaction proceeds even without solvent, but a solvent can be used as necessary. The solvent is not particularly limited as long as it is inactive to each of the above reducing systems. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, halogen systems such as carbon tetrachloride, chloroform and 1,2-dichloroethane. Hydrocarbons, ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, carboxylic acid esters such as methyl acetate and ethyl acetate , Alcohols such as methanol, ethanol or ethylene glycol, amides such as N, N-dimethylformamide, N, N-dimethylacetamide and N-methyl-2-pyrrolidone, water, and mixed solutions thereof And the like.
The reaction temperature is usually -90 to 200 ° C, preferably -78 to 100 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

〔式中、Ｒ¹、Ｒ²、Ｒ⁵、Ｒ⁶、Ｒ⁷、Ｒ⁸、Ｘ²およびＬは前記と同様の意味を表す。〕
反応式１０は、４−（５−ハロアルキル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（７ｃ）、（１０ｃ）または（１１ｃ）を塩基存在下または非存在下、脱ハロゲン化水素化して、各々対応する４−（５−アルキリデン−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（７ｄ）、（１０ｄ）または（１１ｄ）とし（工程Ｋ）、（７ｄ）、（１０ｄ）または（１１ｄ）を還元して（工程Ｌ）、各々対応する４−（５−アルキル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（７ｅ）、（１０ｅ）または（１１ｅ）を製造する方法を示す。[Reaction Scheme 10]

[Wherein, R ¹ , R ² , R ⁵ , R ⁶ , R ⁷ , R ⁸ , X ² and L represent the same meaning as described above. ]
Reaction scheme 10 shows the removal of 4- (5-haloalkyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (7c), (10c) or (11c) in the presence or absence of a base. Hydrogenated to the corresponding 4- (5-alkylidene-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (7d), (10d) or (11d) (step K), Reduction of (7d), (10d) or (11d) (Step L), respectively corresponding 4- (5-alkyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (7e) , (10e) or (11e) will be described.

Examples of the base used in the reaction of Step K include inorganic bases such as sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, potassium bicarbonate, sodium bicarbonate and sodium hydride, pyridine, 4-dimethylaminopyridine, Organic bases such as triethylamine, N, N-dimethylaniline, 1,8-diazabicyclo [5.4.0] -7-undecene and 1,4-diazabicyclo [2.2.2] octane, n-butyllithium and Examples include organolithiums such as sec-butyllithium, organolithiums such as lithium diisopropylamide and lithium bis (trimethylsilyl) amide, and metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide. The base is generally used in an amount of 0 to 100-fold mol, preferably 0 to 5-fold mol based on (7c), (10c) or (11c).
This reaction proceeds even without solvent, but a solvent can be used if necessary. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, and halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane. , Ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, N, N-dimethylformamide, N, N-dimethylacetamide And amides such as N-methyl-2-pyrrolidone, water, and a mixed solvent thereof.
The reaction temperature is usually -90 to 200 ° C, preferably 0 to 100 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

Examples of the reducing agent and the reduction system used in the reaction of Step L include systems using alkali metals such as metallic sodium / liquid ammonia, metallic lithium / liquid ammonia and metallic lithium / ethylamine, aluminum-mercury / diethyl ether-water, and aluminum- Systems using metal aluminum such as nickel / sodium hydroxide / water, systems using aluminum hydride compounds such as diisobutylaluminum hydride, and hydrosilanes such as triethylsilane-trifluoroacetic acid and polymethylhydrosiloxane / palladium-carbon System, metallic water such as lithium aluminum hydride, sodium aluminum hydride, sodium bis (2-methoxyethoxy) aluminum hydride, sodium borohydride and sodium cyanoborohydride Systems using complex compounds, systems using borane derivatives such as diborane, trimethylamine-borane and pyridine-borane, hydrazine hydrate / air, hydrazine hydrate / potassium hexacyanoferrate (III) and hydroxylamine-O-sulfonic acid / water System using diimide generated in reaction system such as sodium oxide, heterogeneous catalytic reduction system such as hydrogen / palladium-carbon and hydrogen / Raney nickel, and hydrogen / chlorotris (triphenylphosphine) rhodium (I), hydrogen And homogeneous catalytic reduction systems such as / hydridocarbonyltris (triphenylphosphine) rhodium (I), hydrogen / rhodium acetate (II) and hydrogen / ruthenium acetate (II).
This reduction reaction proceeds even without solvent, but a solvent can be used as necessary. The solvent is not particularly limited as long as it is inactive to each of the above reducing systems. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, halogen systems such as carbon tetrachloride, chloroform and 1,2-dichloroethane. Hydrocarbons, ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, carboxylic acid esters such as methyl acetate and ethyl acetate , Alcohols such as methanol, ethanol or ethylene glycol, amides such as N, N-dimethylformamide, N, N-dimethylacetamide and N-methyl-2-pyrrolidone, water, and mixed solutions thereof And the like.
The reaction temperature is usually -90 to 200 ° C, preferably -78 to 100 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

〔式中、Ｒ¹、Ｒ²、Ｒ³、Ｒ⁵、Ｒ⁶、Ｒ⁷、Ｒ⁸およびＬは前記と同様の意味を表す。〕
反応式１１は、ピラゾール−４−ヒドロキサム酸エステル（１７ａ）または（１７ｂ）を酸（Ｈ＋）と反応させて４−（５−アルキル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（７ｂ）、（１０ｂ）または（１１ｂ）を製造する方法を示す。[Reaction Formula 11]

[Wherein, R ¹ , R ² , R ³ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and L represent the same meaning as described above. ]
Scheme 11 shows the reaction of pyrazole-4-hydroxamic acid ester (17a) or (17b) with acid (H +) to give 4- (5-alkyl-5H, 6H-1,4,2-dioxazin-3-yl. ) Shows a method for producing pyrazole (7b), (10b) or (11b).

Examples of the acid used in this reaction include inorganic acids such as hydrochloric acid, sulfuric acid and phosphoric acid, and organic acids such as acetic acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid and p-toluenesulfonic acid. The acid is generally used in an amount of 0.01 to 100-fold mol, preferably 0.05 to 10-fold mol based on (17a) or (17b).
This reaction proceeds even without solvent, but a solvent can be used if necessary. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, and halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane. , Ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, N, N-dimethylformamide, N, N-dimethylacetamide And amides such as N-methyl-2-pyrrolidone, water, and a mixed solvent thereof.
The reaction temperature is usually -90 to 200 ° C, preferably 0 to 100 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

〔式中、Ｒ³、Ｒ⁵、Ｒ⁶、Ｒ⁷、Ｒ⁸およびＸ²は前記と同様の意味を表す。〕
反応式１２は、ピラゾール−４−ヒドロキサム酸（１３）を塩基存在下または非存在下、ハロゲン化アリル（１８）と反応させて、反応式９および反応式１１で用いられるピラゾール−４−ヒドロキサム酸エステル（１７ａ）を製造する方法を示す。[Reaction Formula 12]

[Wherein R ³ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and X ² represent the same meaning as described above. ]
Scheme 12 shows the reaction of pyrazole-4-hydroxamic acid (13) with allyl halide (18) in the presence or absence of a base to form pyrazole-4-hydroxamic acid used in Scheme 9 and Scheme 11. The method to manufacture ester (17a) is shown.

In this reaction, (18) is generally used in an amount of 1 to 100-fold mol, preferably 1 to 5-fold mol based on (13).
Examples of the base used in this reaction include sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, sodium hydride and other inorganic bases, pyridine, 4-dimethylaminopyridine, triethylamine, Organic bases such as N, N-dimethylaniline, 1,8-diazabicyclo [5.4.0] -7-undecene and 1,4-diazabicyclo [2.2.2] octane, n-butyllithium and sec- Examples thereof include organic lithiums such as butyl lithium, organic lithium amides such as lithium diisopropylamide and lithium bis (trimethylsilyl) amide, and metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide. The base is generally used in an amount of 0 to 100-fold mol, preferably 0 to 5-fold mol based on (13).
This reaction proceeds even without solvent, but a solvent can be used if necessary. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, and halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane. , Ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, N, N-dimethylformamide, N, N-dimethylacetamide And amides such as N-methyl-2-pyrrolidone, water, and a mixed solvent thereof.
The reaction temperature is usually -90 to 200 ° C, preferably 0 to 100 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

〔式中、Ｒ³、Ｒ⁵、Ｒ⁶、Ｒ⁷、Ｒ⁸およびＸ²は前記と同様の意味を表す。〕
反応式１３は、ピラゾール−４−ヒドロキサム酸（１３）を塩基存在下または非存在下、ハロヒドリン（１９）またはオキシラン（２０）と反応させて、反応式１１で用いられるピラゾール−４−ヒドロキサム酸エステル（１７ｂ）を製造する方法を示す。[Reaction Formula 13]

[Wherein R ³ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and X ² represent the same meaning as described above. ]
Scheme 13 shows the reaction of pyrazole-4-hydroxamic acid ester used in Scheme 11 by reacting pyrazole-4-hydroxamic acid (13) with halohydrin (19) or oxirane (20) in the presence or absence of a base. The method to manufacture (17b) is shown.

In this reaction, (19) or (20) is generally used in an amount of 1 to 100-fold mol, preferably 2 to 5-fold mol based on (13).
Examples of the base used in this reaction include sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, sodium hydride and other inorganic bases, pyridine, 4-dimethylaminopyridine, triethylamine, Organic bases such as N, N-dimethylaniline, 1,8-diazabicyclo [5.4.0] -7-undecene and 1,4-diazabicyclo [2.2.2] octane, n-butyllithium and sec- Examples thereof include organic lithiums such as butyl lithium, organic lithium amides such as lithium diisopropylamide and lithium bis (trimethylsilyl) amide, and metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide. The base is generally used in an amount of 0 to 100-fold mol, preferably 0 to 5-fold mol based on (13).
This reaction proceeds even without solvent, but a solvent can be used if necessary. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, and halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane. , Ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, N, N-dimethylformamide, N, N-dimethylacetamide And amides such as N-methyl-2-pyrrolidone, water, and a mixed solvent thereof.
The reaction temperature is usually -90 to 200 ° C, preferably 0 to 100 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

〔式中、Ｒ¹、Ｒ²、Ｒ³、Ｒ⁵、Ｒ⁶、Ｒ⁷、Ｒ⁸およびＬは前記と同様の意味を表す。〕
反応式１４は、ピラゾール−４−ヒドロキサム酸（１３）を塩基存在下または非存在下、エピハロヒドリン（２１）と反応させて、ピラゾール−４−ヒドロキサム酸エステル（１７ｃ）とし（工程Ｌ）、（１７ｃ）を酸または塩基で処理して、４−（５−ヒドロキシアルキル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（７ｆ）、（１０ｆ）または（１１ｆ）とし（工程Ｍ）、次に、（７ｆ）、（１０ｆ）または（１１ｆ）をハロゲン化またはアルキルスルホニル化する（工程Ｎ）ことにより、各々対応する、４−（５−ハロアルキル（またはアルキルスルホニルオキシアルキル）−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（７ｃ）、（１０ｃ）または（１１ｃ）を製造する方法を示す。（７ｃ）、（１０ｃ）または（１１ｃ）は反応式１０で使用される。[Reaction Scheme 14]

[Wherein, R ¹ , R ² , R ³ , R ⁵ , R ⁶ , R ⁷ , R ⁸ and L represent the same meaning as described above. ]
In Reaction Scheme 14, pyrazole-4-hydroxamic acid (13) is reacted with epihalohydrin (21) in the presence or absence of a base to give pyrazole-4-hydroxamic acid ester (17c) (step L), (17c ) With acid or base to give 4- (5-hydroxyalkyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (7f), (10f) or (11f) (Step M ), Then (7f), (10f) or (11f) is halogenated or alkylsulfonylated (Step N) to give the corresponding 4- (5-haloalkyl (or alkylsulfonyloxyalkyl) -5H , 6H-1,4,2-dioxazin-3-yl) pyrazole (7c), (10c) or (11c). (7c), (10c) or (11c) is used in Reaction Scheme 10.

In the reaction of Step L, (21) is generally used in an amount of 1 to 100-fold mol, preferably 1 to 5-fold mol based on (13).
Examples of the base used in this reaction include sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, sodium hydride and other inorganic bases, pyridine, 4-dimethylaminopyridine, triethylamine, Organic bases such as N, N-dimethylaniline, 1,8-diazabicyclo [5.4.0] -7-undecene and 1,4-diazabicyclo [2.2.2] octane, n-butyllithium and sec- Examples thereof include organic lithiums such as butyl lithium, organic lithium amides such as lithium diisopropylamide and lithium bis (trimethylsilyl) amide, and metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide. The base is generally used in an amount of 0 to 100-fold mol, preferably 0 to 5-fold mol based on (13).
This reaction proceeds even without solvent, but a solvent can be used if necessary. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, and halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane. , Ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, N, N-dimethylformamide, N, N-dimethylacetamide And amides such as N-methyl-2-pyrrolidone, water, and a mixed solvent thereof.
The reaction temperature is usually -90 to 200 ° C, preferably 0 to 100 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

Examples of the acid or base used in the reaction of Step M include inorganic acids such as hydrochloric acid, sulfuric acid and phosphoric acid, organic acids such as acetic acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid and p-toluenesulfonic acid, Inorganic bases such as sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, potassium bicarbonate, sodium bicarbonate and sodium hydride, pyridine, 4-dimethylaminopyridine, triethylamine, N, N-dimethylaniline, 1, Organic bases such as 8-diazabicyclo [5.4.0] -7-undecene and 1,4-diazabicyclo [2.2.2] octane, organic lithiums such as n-butyllithium and sec-butyllithium, lithium Diisopropylamide and lithium bis (trimethylsilyl ) Organic lithium amide such as amide, and sodium methoxide, metal alkoxides such as sodium ethoxide and potassium t- butoxide. The acid or base is generally used in an amount of 0 to 100-fold mol, preferably 0 to 5-fold mol based on (17c).
This reaction proceeds even without solvent, but a solvent can be used if necessary. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, and halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane. , Ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, N, N-dimethylformamide, N, N-dimethylacetamide And amides such as N-methyl-2-pyrrolidone, water, and a mixed solvent thereof.
The reaction temperature is usually -90 to 200 ° C, preferably 0 to 100 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

In the reaction of Step N, the halogenating agent or alkylsulfonylating agent is generally used in an amount of 1 to 100-fold mol, preferably 1 to 5-fold mol based on (7f), (10f) or (11f).
Examples of the halogenating agent used in this reaction include hydrogen halide acids such as hydrogen chloride, hydrogen bromide and hydrogen iodide, phosphorus halides such as phosphorus trichloride, phosphorus pentachloride, phosphorus oxychloride and phosphorus tribromide. Systems such as triphenyl phosphonate / benzyl chloride and triphenylphosphine / carbon tetrachloride, sulfonium halides such as methanesulfonyl chloride and p-toluenesulfonyl chloride, and thionyl halides such as thionyl chloride and thionyl bromide. .
Examples of the alkylsulfonylating agent used in this reaction include sulfonium halides such as methanesulfonyl chloride and p-toluenesulfonyl chloride.
This reaction proceeds even without solvent, but a solvent can be used if necessary. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, and halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane. , Ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, N, N-dimethylformamide, N, N-dimethylacetamide And amides such as N-methyl-2-pyrrolidone, water, and a mixed solvent thereof.
The reaction temperature is usually -90 to 200 ° C, preferably 0 to 100 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

反応式１５は、ピラゾール−４−カルボン酸クロリド（１５）を塩基存在下または非存在下、ヒドロキシアミンと反応させて、反応式７、反応式１２ないし１４で用いられるピラゾール−４−ヒドロキサム酸（１３）を製造する方法を示す。[Reaction Scheme 15]

Reaction Scheme 15 is the reaction of pyrazole-4-carboxylic acid chloride (15) with hydroxyamine in the presence or absence of a base to give pyrazole-4-hydroxamic acid ( 13) shows a method of manufacturing.

In this reaction, hydroxylamine is usually used in an amount of 1 to 100 times mol, preferably 1 to 5 times mol, of (15).
Examples of the base used in this reaction include sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, sodium hydride and other inorganic bases, pyridine, 4-dimethylaminopyridine, triethylamine, Organic bases such as N, N-dimethylaniline, 1,8-diazabicyclo [5.4.0] -7-undecene and 1,4-diazabicyclo [2.2.2] octane, n-butyllithium and sec- Examples thereof include organic lithiums such as butyl lithium, organic lithium amides such as lithium diisopropylamide and lithium bis (trimethylsilyl) amide, and metal alkoxides such as sodium methoxide, sodium ethoxide and potassium t-butoxide. The base is generally used in an amount of 0 to 100-fold mol, preferably 0 to 5-fold mol based on (15).
This reaction proceeds even without solvent, but a solvent can be used if necessary. The solvent is not particularly limited as long as it is inert to the reaction. For example, hydrocarbons such as hexane, cyclohexane, benzene and toluene, and halogenated hydrocarbons such as carbon tetrachloride, chloroform and 1,2-dichloroethane. , Ethers such as diethyl ether, diisopropyl ether, dioxane and tetrahydrofuran, ketones such as acetone, methyl ethyl ketone and methyl isobutyl ketone, nitriles such as acetonitrile and propionitrile, N, N-dimethylformamide, N, N-dimethylacetamide And amides such as N-methyl-2-pyrrolidone, water, and a mixed solvent thereof.
The reaction temperature is usually -90 to 200 ° C, preferably 0 to 100 ° C.
The reaction time is usually 0.05 to 100 hours, preferably 0.5 to 10 hours.

  The desired product obtained by the above reaction can be isolated and purified by operations such as filtration, extraction, washing, column chromatography, recrystallization and distillation after completion of the reaction.

  Examples of the synthesis of the compounds will be specifically described below, but the present invention is not limited thereto.

アセトニトリル（８ｍｌ）に３−クロロ−１−メチル−４−（５−メチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール−５−スルホンアミド（０．６４ｇ、２．２ｍｍｏｌ）とＮ−（４，６−ジメトキシピリミジン−２−イル）カルバミン酸フェニル（０．５９ｇ、２．１ｍｍｏｌ）を溶解し、１，８−ジアザビシクロ［５．４．０］−７−ウンデセン（０．３３ｇ、２．２ｍｍｏｌ）を加え、室温で１時間撹拌した。水（８ｍｌ）を加えた後、ジエチルエーテルで抽出した。得られた水層に１２％塩酸を加えてｐＨ１に調整し、ジエチルエーテルで再度抽出した。得られたジエチルエーテル溶液を水および塩化ナトリウム飽和水溶液で順次洗浄後、無水硫酸ナトリウムで乾燥、溶媒留去した。得られた残渣をｎ−ヘキサンで洗浄、乾燥して目的物（０．４０ｇ）を得た。融点１７７−１７９℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．３８（ｄ，Ｊ＝６．６Ｈｚ，３Ｈ），３．６９−３．７２（ｍ，１Ｈ），３．９６（ｓ，６Ｈ），４．１３−４．１８（ｍ，１Ｈ），４．３０（ｓ，３Ｈ），４．４９−４．６３（ｍ，１Ｈ），５．７７（ｓ，１Ｈ），７．６７（ｂｒｓ，１Ｈ），１２．９１（ｂｒｓ，１Ｈ）。[Synthesis Example 1]
N-((4,6-dimethoxypyrimidin-2-yl) aminocarbonyl) -3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) Synthesis of pyrazole-5-sulfonamide (Compound No. 1)

3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide (0.64 g, 2.2 mmol) in acetonitrile (8 ml) ) And phenyl N- (4,6-dimethoxypyrimidin-2-yl) carbamate (0.59 g, 2.1 mmol) were dissolved in 1,8-diazabicyclo [5.4.0] -7-undecene (0 .33 g, 2.2 mmol) was added and stirred at room temperature for 1 hour. Water (8 ml) was added and extracted with diethyl ether. The obtained aqueous layer was adjusted to pH 1 by adding 12% hydrochloric acid and extracted again with diethyl ether. The obtained diethyl ether solution was washed successively with water and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was washed with n-hexane and dried to obtain the desired product (0.40 g). Melting point 177-179 [deg.] C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.38 (d, J = 6.6 Hz, 3H), 3.69-3.72 (m, 1H), 3.96 (s, 6H), 4.13-4.18 (m, 1H), 4.30 (s, 3H), 4.49-4.63 (m, 1H), 5.77 (s, 1H), 7.67. (Brs, 1H), 12.91 (brs, 1H).

原料に３−クロロ−４−（５−ヨードメチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）−１−メチルピラゾール−５−スルホンアミド（０．０９０ｇ、０．２１ｍｍｏｌ）を用い、合成例１と同様にして目的物（０．１０ｇ）を得た。融点９１−９４℃
。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）３．２８−３．４２（ｍ，２Ｈ），３．８９−４．０５（ｍ，７Ｈ），４．０４−４．１２（ｍ，１Ｈ），４．３１（ｓ，３Ｈ），４．５６−４．６０（ｍ，１Ｈ），５．７９（ｓ，１Ｈ），７．４３（ｂｒｓ，１Ｈ），１２．９３（ｓ，１Ｈ）。[Synthesis Example 2]
N-((4,6-dimethoxypyrimidin-2-yl) aminocarbonyl) -3-chloro-4- (5-iodomethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1-methyl Synthesis of pyrazole-5-sulfonamide (Compound No. 2)

3-Chloro-4- (5-iodomethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1-methylpyrazole-5-sulfonamide (0.090 g, 0.21 mmol) was used as a raw material. The target product (0.10 g) was obtained in the same manner as in Synthesis Example 1. Melting point 91-94 ° C
. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 3.28-3.42 (m, 2H), 3.89-4.05 (m, 7H), 4.04-4.12 ( m, 1H), 4.31 (s, 3H), 4.56-4.60 (m, 1H), 5.79 (s, 1H), 7.43 (brs, 1H), 12.93 (s) , 1H).

原料に３−クロロ−４−（５，５−ジメチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）−１−メチルピラゾール−５−スルホンアミド（０．４７ｇ、１．５ｍｍｏｌ）を用い、合成例１と同様にして目的物（０．４２ｇ）を得た。融点１８９−１９１℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．４１（ｓ，６Ｈ），３．７８（ｓ，２Ｈ），３．９７（ｓ，６Ｈ），４．３０（ｓ，３Ｈ），５．７８（ｓ，１Ｈ），７．５８（ｂｒｓ，１Ｈ），１２．９２（ｂｒｓ，１Ｈ）。[Synthesis Example 3]
N-((4,6-dimethoxypyrimidin-2-yl) aminocarbonyl) -3-chloro-4- (5,5-dimethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1 -Synthesis of methylpyrazole-5-sulfonamide (Compound No. 3)

3-Chloro-4- (5,5-dimethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1-methylpyrazole-5-sulfonamide (0.47 g, 1.5 mmol) as raw material Was used in the same manner as in Synthesis Example 1 to obtain the desired product (0.42 g). Melting point 189-191 [deg.] C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.41 (s, 6H), 3.78 (s, 2H), 3.97 (s, 6H), 4.30 (s, 3H ), 5.78 (s, 1H), 7.58 (brs, 1H), 12.92 (brs, 1H).

原料に３−クロロ−４−（５−ヨードメチル−５−メチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）−１−メチルピラゾール−５−スルホンアミド（０．２１ｇ、０．４８ｍｍｏｌ）を用い、合成例１と同様にして目的物（０．１４ｇ）を得た。融点９０−９３℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．５５（ｓ，３Ｈ），３．３０−３．４９（ｍ，２Ｈ），３．８１−３．８４（ｍ，１Ｈ），３．９７（ｓ，６Ｈ），４．２３−４．３０（ｍ，４Ｈ），５．８０（ｓ，１Ｈ），７．２９（ｂｒｓ，１Ｈ），１２．９３（ｓ，１Ｈ）。[Synthesis Example 4]
N-((4,6-dimethoxypyrimidin-2-yl) aminocarbonyl) -3-chloro-4- (5-iodomethyl-5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) Synthesis of -1-methylpyrazole-5-sulfonamide (Compound No. 4)

3-Chloro-4- (5-iodomethyl-5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) -1-methylpyrazole-5-sulfonamide (0.21 g,. 48 mmol), and the target product (0.14 g) was obtained in the same manner as in Synthesis Example 1. Melting point 90-93 ° C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.55 (s, 3H), 3.30-3.49 (m, 2H), 3.81-3.84 (m, 1H) 3.97 (s, 6H), 4.23-4.30 (m, 4H), 5.80 (s, 1H), 7.29 (brs, 1H), 12.93 (s, 1H).

原料に１，３−ジメチル−４−（５−メチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール−５−スルホンアミド（０．０７０ｇ、０．２６ｍｍｏｌ）を用い、合成例１と同様にして目的物（０．０９０ｇ）を得た。融点１８０−１８２℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．３６（ｄ，Ｊ＝６．６Ｈｚ，３Ｈ），２．２９（ｓ，３Ｈ），３．６２−３．６９（ｍ，１Ｈ），３．９７（ｓ，６Ｈ），４．１１−４．１６（ｍ，１Ｈ），４．２７（ｓ，３Ｈ），４．４９−４．５４（ｍ，１Ｈ），５．７８（ｓ，１Ｈ），７．２３（ｂｒｓ，１Ｈ），１２．７４（ｂｒｓ，１Ｈ）。[Synthesis Example 5]
N-((4,6-dimethoxypyrimidin-2-yl) aminocarbonyl) -1,3-dimethyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole- Synthesis of 5-sulfonamide (Compound No. 5)

Using 1,3-dimethyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide (0.070 g, 0.26 mmol) as a raw material In the same manner as in Example 1, the target product (0.090 g) was obtained. Melting point 180-182 ° C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.36 (d, J = 6.6 Hz, 3H), 2.29 (s, 3H), 3.62-3.69 (m, 1H), 3.97 (s, 6H), 4.11-4.16 (m, 1H), 4.27 (s, 3H), 4.49-4.54 (m, 1H), 5.78 (S, 1H), 7.23 (brs, 1H), 12.74 (brs, 1H).

原料に４−（５−ヨードメチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）−１，３−ジメチルピラゾール−５−スルホンアミド（０．５３ｇ、１．３ｍｍｏｌ）を用い、合成例１と同様にして目的物（０．３４ｇ）を得た。融点６６−６９℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）２．３４（ｓ，３Ｈ），３．３６（ｍ，２Ｈ），３．９２−４．１９（ｍ，８Ｈ），４．２３（ｓ，３Ｈ），４．５４−４．５９（ｍ，１Ｈ），５．７８（ｓ，１Ｈ），７．４１（ｂｒｓ，１Ｈ），１２．６４（ｂｒｓ，１Ｈ）。[Synthesis Example 6]
N-((4,6-dimethoxypyrimidin-2-yl) aminocarbonyl) -3-chloro-4- (5-iodomethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1-methyl Synthesis of pyrazole-5-sulfonamide (Compound No. 6)

Synthesis using 4- (5-iodomethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1,3-dimethylpyrazole-5-sulfonamide (0.53 g, 1.3 mmol) as a raw material In the same manner as in Example 1, the desired product (0.34 g) was obtained. Mp 66-69 ° C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 2.34 (s, 3H), 3.36 (m, 2H), 3.92-4.19 (m, 8H), 4.23 (S, 3H), 4.54-4.59 (m, 1H), 5.78 (s, 1H), 7.41 (brs, 1H), 12.64 (brs, 1H).

原料に４−（５，５−ジメチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）−１，３−ジメチルピラゾール−５−スルホンアミド（０．１３ｇ、０．４５ｍｍｏｌ）を用い、合成例１と同様にして目的物（０．１２ｇ）を得た。融点１９９−２０１℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．３９（ｓ，６Ｈ），２．２７（ｓ，３Ｈ），３．７５（ｓ，２Ｈ），３．９７（ｓ，６Ｈ），４．２７（ｓ，３Ｈ），５．７８（ｓ，１Ｈ），７．２２（ｂｒｓ，１Ｈ），１２．７５（ｓ，１Ｈ）。[Synthesis Example 7]
N-((4,6-dimethoxypyrimidin-2-yl) aminocarbonyl) -4- (5,5-dimethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1,3-dimethyl Synthesis of pyrazole-5-sulfonamide (Compound No. 7)

4- (5,5-Dimethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1,3-dimethylpyrazole-5-sulfonamide (0.13 g, 0.45 mmol) was used as a raw material. The target product (0.12 g) was obtained in the same manner as in Synthesis Example 1. Melting point: 199-201 ° C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.39 (s, 6H), 2.27 (s, 3H), 3.75 (s, 2H), 3.97 (s, 6H) ), 4.27 (s, 3H), 5.78 (s, 1H), 7.22 (brs, 1H), 12.75 (s, 1H).

原料に４−（５−ヨードメチル−５−メチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）−１，３−ジメチルピラゾール−５−スルホンアミド（０．０８０ｇ、０．１９ｍｍｏｌ）を用い、合成例１と同様にして目的物（０．０５０ｇ）を得た。融点１３３−１３５℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．６３（ｓ，３Ｈ），２．２９（ｓ，３Ｈ），３．３１−３．４６（ｍ，２Ｈ），３．７８−３．８２（ｍ，１Ｈ），３．９７（ｓ，６Ｈ），４．１７−４．２７（ｍ，４Ｈ），５．７９（ｓ，１Ｈ），７．４０（ｂｒｓ，１Ｈ），１２．７６（ｂｒｓ，１Ｈ）。[Synthesis Example 8]
N-((4,6-dimethoxypyrimidin-2-yl) aminocarbonyl) -4- (5-iodomethyl-5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) -1,3 -Synthesis of dimethylpyrazole-5-sulfonamide (Compound No. 8)

4- (5-Iodomethyl-5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) -1,3-dimethylpyrazole-5-sulfonamide (0.080 g, 0.19 mmol) as a raw material Was used in the same manner as in Synthesis Example 1 to obtain the desired product (0.050 g). Mp 133-135 ° C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.63 (s, 3H), 2.29 (s, 3H), 3.31-3.46 (m, 2H), 3.78 -3.82 (m, 1H), 3.97 (s, 6H), 4.17-4.27 (m, 4H), 5.79 (s, 1H), 7.40 (brs, 1H), 12.76 (brs, 1H).

原料に１，３−ジメチル−４−（６−メチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール−５−スルホンアミド（０．１４ｇ、０．５１ｍｍｏｌ）を用い、合成例１と同様にして目的物（０．１７ｇ）を得た。融点１８７−１８９℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．２８（ｄ，Ｊ＝８．０Ｈｚ，３Ｈ），２．２９（ｓ，３Ｈ），３．９６（ｓ，６Ｈ），３．９９−４．０４（ｍ，２Ｈ），４．２７（ｓ，３Ｈ），４．２９−４．３３（ｍ，１Ｈ），５．７８（ｓ，１Ｈ），７．２６（ｂｒｓ，１Ｈ），１２．７０（ｂｒｓ，１Ｈ）。[Synthesis Example 9]
N-((4,6-dimethoxypyrimidin-2-yl) aminocarbonyl) -1,3-dimethyl-4- (6-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole- Synthesis of 5-sulfonamide (Compound No. 9)

Synthesis using 1,3-dimethyl-4- (6-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide (0.14 g, 0.51 mmol) as a raw material In the same manner as in Example 1, the desired product (0.17 g) was obtained. Melting point 187-189 [deg.] C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.28 (d, J = 8.0 Hz, 3H), 2.29 (s, 3H), 3.96 (s, 6H), 3 .99-4.04 (m, 2H), 4.27 (s, 3H), 4.29-4.33 (m, 1H), 5.78 (s, 1H), 7.26 (brs, 1H) ), 12.70 (brs, 1H).

[Synthesis Example 10]
N-((4,6-dimethoxypyrimidin-2-yl) aminocarbonyl) -3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) Synthesis of Pyrazole-5-sulfonamide (Compound No. 1) (Part 2)
Toluene (100 ml) was added N-methoxycarbonyl-3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide (20. 3 g, 57.5 mmol) and 2-amino-4,6-dimethoxypyrimidine (9.40 g, 60.6 mmol) were added, and the mixture was heated under reflux for 4 hours while distilling off the by-produced methanol under reduced pressure (700 mmHg). did. After 15 ml of toluene was distilled off at the same temperature, it was cooled to room temperature with stirring. The precipitated solid was collected by filtration, washed with toluene, and dried to obtain the desired product (24.1 g). Melting point 177-179 [deg.] C.

[Synthesis Example 11]
N-((4,6-dimethoxypyrimidin-2-yl) aminocarbonyl) -3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) Synthesis of pyrazole-5-sulfonamide (Compound No. 1) (Part 3)
To a solution of 2-amino-4,6-dimethoxypyrimidine (0.46 g, 3.0 mmol) in acetonitrile (3 ml) was added 3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2). -Dioxazin-3-yl) pyrazole-5-sulfonyl isocyanate (1.0 g, 3.1 mmol) in toluene (5 ml) was added and stirred at room temperature for 3 hours. The precipitated solid was collected by filtration, washed with toluene, and dried to obtain the desired product (1.2 g). Melting point 177-179 [deg.] C.

[Synthesis Example 12]
N-((4,6-dimethoxypyrimidin-2-yl) aminocarbonyl) -3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) Synthesis of pyrazole-5-sulfonamide (Compound No. 1) (Part 4)
To a solution of 2-amino-4,6-dimethoxypyrimidine (1.55 g, 10.0 mmol) in acetonitrile (15 ml), pyridine (0.16 g, 2.0 mol) and sodium cyanate (0.72 g, 11 mmol) were added, With stirring at 40 ° C., 3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonyl chloride (3.45 g, 11 0.0 mmol) was added in portions over 1 hour. The mixture was further stirred at 40 ° C. for 1.5 hours. After cooling to room temperature, water (60 ml) was added, the pH was adjusted to 1 with 35% hydrochloric acid, and the precipitated solid was collected by filtration. The obtained solid was washed with methanol and dried to obtain the desired product (4.70 g). Melting point 177-179 [deg.] C.

原料に１−メチル−４−（５−メチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール−５−スルホンアミド（０．２０ｇ、０．７７ｍｍｏｌ）を用い、合成例１と同様にして目的物（０．２５ｇ）を得た。融点１５４−１５７℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．３５（ｄ，Ｊ＝６．３Ｈｚ，３Ｈ），３．５６−３．６４（ｍ，１Ｈ），４．０３−４．１３（ｍ，７Ｈ），４．３４（ｓ，３Ｈ），４．４４−４．５０（ｍ，１Ｈ），５．７８（ｓ，１Ｈ），７．４５（ｂｒｓ，１Ｈ），７．７２（ｓ，１Ｈ），１２．６６Ｈｚ（ｂｒｓ，１Ｈ）。[Synthesis Example 13]
N-((4,6-dimethoxypyrimidin-2-yl) aminocarbonyl) -1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5 Synthesis of sulfonamide (Compound No. 10)

Synthesis Example 1 using 1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide (0.20 g, 0.77 mmol) as a raw material In the same manner as described above, the desired product (0.25 g) was obtained. Melting point 154-157 [deg.] C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.35 (d, J = 6.3 Hz, 3H), 3.56-3.64 (m, 1H), 4.03-4. 13 (m, 7H), 4.34 (s, 3H), 4.44-4.50 (m, 1H), 5.78 (s, 1H), 7.45 (brs, 1H), 7.72 (S, 1H), 12.66 Hz (brs, 1H).

[Synthesis Example 14]
Synthesis of (Compound No. 1) (Part 2)
3-Chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonyl chloride (0.32 g, 1.0 mmol) in acetonitrile (4 ml) ), Sodium cyanate (0.07 g, 1.1 mmol) and 2-amino-4,6-dimethoxypyrimidine (0.16 g, 1.0 mmol) were added, and the mixture was stirred at 40 ° C. for 10 minutes. Pyridine (0.04 g, 0.5 mmol) was added dropwise over 3 minutes and stirred at 40 ° C. for 1 hour. Under ice-cooling, methylene chloride (5 ml) was added, 12% hydrochloric acid was added to adjust to pH 1, and the phases were separated. The aqueous layer was extracted with methylene chloride. The obtained methylene chloride solutions were combined, washed with a saturated aqueous solution of sodium chloride, and then dried over anhydrous sodium sulfate. The solvent was distilled off, and the obtained residue was purified by silica gel column chromatography (developing solution: n-hexane / ethyl acetate = 1/2) to obtain 0.37 g of the desired product. Melting point 177-179 [deg.] C.

アセトニトリル（６ｍｌ）に３−クロロ−１−メチル−４−（５−メチレン−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール−５−スルホンアミド（０．１３ｇ、０．４４ｍｍｏｌ）とＮ−（４，６−ジメトキシピリミジン−２−イル）カルバミン酸フェニル（０．１３ｇ、０．４７ｍｍｏｌ）を溶解し、１，８−ジアザビシクロ［５．４．０］−７−ウンデセン（０．０７ｇ、０．４６ｍｍｏｌ）を加え、室温で１時間撹拌した。減圧下溶媒を留去し、２規定塩酸を加えた後、酢酸エチルで抽出した。得られた酢酸エチル溶液を無水硫酸ナトリウムで乾燥後、減圧下濃縮すると油状物が得られた。この油状物にトルエンとヘキサンの混合溶媒を加え、析出した固体を濾取し、少量のトルエンで洗浄後、減圧乾燥することにより、目的物（０．1０ｇ）を得た。白色固体。融点１６４−１６７℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）３．９５（ｓ，６Ｈ），４．３２（ｓ，３Ｈ），４．３５（ｓ，２Ｈ），４．４２（ｄ，Ｊ＝２．７Ｈｚ、１Ｈ），４．７８（ｄ，Ｊ＝２．７Ｈｚ、１Ｈ），５．８０（ｓ，１Ｈ），７．３２（ｂｒｓ，１Ｈ），１１．９８（ｂｒｓ，１Ｈ）。[Synthesis Example 15]
N-((4,6-dimethoxypyrimidin-2-yl) aminocarbonyl) -3-chloro-1-methyl-4- (5-methylene-5H, 6H-1,4,2-dioxazin-3-yl) Synthesis of pyrazole-5-sulfonamide (Compound No. 21)

3-Chloro-1-methyl-4- (5-methylene-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide (0.13 g, 0.44 mmol) in acetonitrile (6 ml) ) And phenyl N- (4,6-dimethoxypyrimidin-2-yl) carbamate (0.13 g, 0.47 mmol) are dissolved in 1,8-diazabicyclo [5.4.0] -7-undecene (0 0.07 g, 0.46 mmol) was added, and the mixture was stirred at room temperature for 1 hour. The solvent was evaporated under reduced pressure, 2N hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate solution was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain an oil. A mixed solvent of toluene and hexane was added to this oily substance, and the precipitated solid was collected by filtration, washed with a small amount of toluene, and dried under reduced pressure to obtain the desired product (0.10 g). White solid. Melting point 164-167 [deg.] C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 3.95 (s, 6H), 4.32 (s, 3H), 4.35 (s, 2H), 4.42 (d, J = 2.7 Hz, 1H), 4.78 (d, J = 2.7 Hz, 1H), 5.80 (s, 1H), 7.32 (brs, 1H), 11.98 (brs, 1H).

アリルオキシアミン塩酸塩（２．３ｇ、２１ｍｍｏｌ）のテトラヒドロフラン（２０ｍｌ）懸濁液に、０℃でトリエチルアミン（２．９ｇ、２９ｍｍｏｌ）を加え、室温で５分間撹拌後、５−ベンジルチオ−３−クロロ−１−メチルピラゾール−４−カルボン酸クロリド（２．１ｇ、７．０ｍｍｏｌ）のテトラヒドロフラン（１０ｍｌ）溶液を滴下した。室温で１時間撹拌後、水（１００ｍｌ）を加え、酢酸エチルで抽出した。得られた酢酸エチル溶液を塩化ナトリウム飽和水溶液で洗浄、無水硫酸ナトリウムで乾燥、溶媒留去して目的物（２．４ｇ）を得た。油状物質。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）３．４５（ｓ，３Ｈ），４．１１（ｓ，２Ｈ），４．５３（ｄ，Ｊ＝６．３Ｈｚ，２Ｈ），５．３４−５．４５（ｍ，２Ｈ），６．００−６．１３（ｍ，１Ｈ），７．０３−７．０６（ｍ，２Ｈ），７．２４−７．２８（ｍ，３Ｈ），９．１４（ｂｒｓ，１Ｈ）。[Reference Example 1]
(1) Synthesis of (5-benzylthio-3-chloro-1-methylpyrazol-4-yl) -N-allyloxycarboxylic acid amide

To a suspension of allyloxyamine hydrochloride (2.3 g, 21 mmol) in tetrahydrofuran (20 ml) was added triethylamine (2.9 g, 29 mmol) at 0 ° C., and the mixture was stirred at room temperature for 5 minutes, and then 5-benzylthio-3-chloro. A solution of -1-methylpyrazole-4-carboxylic acid chloride (2.1 g, 7.0 mmol) in tetrahydrofuran (10 ml) was added dropwise. After stirring at room temperature for 1 hour, water (100 ml) was added, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate solution was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain the desired product (2.4 g). Oily substance. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 3.45 (s, 3H), 4.11 (s, 2H), 4.53 (d, J = 6.3 Hz, 2H), 5 .34-5.45 (m, 2H), 6.00-6.13 (m, 1H), 7.03-7.06 (m, 2H), 7.24-7.28 (m, 3H) , 9.14 (brs, 1H).

（５−ベンジルチオ−３−クロロ−１−メチルピラゾール−４−イル）−Ｎ−アリルオキシカルボン酸アミド（２．２ｇ、６．５ｍｍｏｌ）のアセトニトリル（７０ｍｌ）溶液に、０℃でヨウ素（５．０ｇ、２０ｍｍｏｌ）を加えた。室温で６時間撹拌後、水（１５０ｍｌ）を加え、酢酸エチルで抽出した。得られた酢酸エチル溶液をチオ硫酸ナトリウム飽和水溶液、炭酸水素ナトリウム飽和水溶液、塩化ナトリウム飽和水溶液および水で順次洗浄後、無水硫酸ナトリウムで乾燥、溶媒留去して目的物（３．０ｇ）を得た。油状物質。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）３．２５（ｓ，３Ｈ），３．３４−３．４２（ｍ，２Ｈ），４．０４−４．１１（ｍ，３Ｈ）４．３２−４．４０（ｍ，１Ｈ），４．５８−４．６５（ｍ，１Ｈ），７．００−７．０８（ｍ，２Ｈ），７．２１−７．２７（ｍ，３Ｈ）。(2) Synthesis of 5-benzylthio-3-chloro-4- (5-iodomethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1-methylpyrazole

To a solution of (5-benzylthio-3-chloro-1-methylpyrazol-4-yl) -N-allyloxycarboxylic acid amide (2.2 g, 6.5 mmol) in acetonitrile (70 ml) at 0 ° C. with iodine (5. 0 g, 20 mmol) was added. After stirring at room temperature for 6 hours, water (150 ml) was added, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate solution was washed successively with saturated aqueous sodium thiosulfate solution, saturated aqueous sodium hydrogen carbonate solution, saturated aqueous sodium chloride solution and water, then dried over anhydrous sodium sulfate and evaporated to give the desired product (3.0 g). It was. Oily substance. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 3.25 (s, 3H), 3.34-3.42 (m, 2H), 4.04-4.11 (m, 3H) 4.32-4.40 (m, 1H), 4.58-4.65 (m, 1H), 7.00-7.08 (m, 2H), 7.21-7.27 (m, 3H) ).

５−ベンジルチオ−３−クロロ−４−（５−ヨードメチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）−１−メチルピラゾール（２．９ｇ、６．３ｍｍｏｌ）のジメチルスルホキシド（４０ｍｌ）溶液に、水素化ホウ素ナトリウム（０．４７ｇ、１２ｍｍｏｌ）を加えた。６０℃で０．５時間撹拌後、６％塩酸（２００ｍｌ）を加え、酢酸エチルで抽出した。得られた酢酸エチル溶液を塩化ナトリウム飽和水溶液および水で順次洗浄後、無水硫酸ナトリウムで乾燥、溶媒留去して目的物（２．０ｇ）を得た。油状物質。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．４４（ｄ，Ｊ＝６．６Ｈｚ，３Ｈ），３．２４（ｓ，３Ｈ），３．７４−３．８５（ｍ，１Ｈ），４．０４（ｓ，２Ｈ），４．２２−４．２９（ｍ，１Ｈ），４．５６−４．６５（ｍ，１Ｈ），６．９７−７．０６（ｍ，２Ｈ），７．１９−７．２１（ｍ，３Ｈ）。(3) Synthesis of 5-benzylthio-3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole

5-Benzylthio-3-chloro-4- (5-iodomethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1-methylpyrazole (2.9 g, 6.3 mmol) in dimethyl sulfoxide (40 ml) ) To the solution was added sodium borohydride (0.47 g, 12 mmol). After stirring at 60 ° C. for 0.5 hour, 6% hydrochloric acid (200 ml) was added, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate solution was washed successively with a saturated aqueous sodium chloride solution and water, dried over anhydrous sodium sulfate, and evaporated to give the desired product (2.0 g). Oily substance. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.44 (d, J = 6.6 Hz, 3H), 3.24 (s, 3H), 3.74-3.85 (m, 1H), 4.04 (s, 2H), 4.22-4.29 (m, 1H), 4.56-4.65 (m, 1H), 6.97-7.06 (m, 2H) , 7.19-7.21 (m, 3H).

５−ベンジルチオ−３−クロロ−１−メチル−４−（５−メチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（１．９ｇ、５．６ｍｍｏｌ）の塩化メチレン（３０ｍｌ）溶液に、水（３０ｍｌ）と３５％塩酸（２．３ｇ、２２ｍｍｏｌ）を加え、激しく撹拌しながら８％次亜塩素酸ナトリウム水溶液（２０．５ｇ、２２．０ｍｍｏｌ）を５℃にて加え、０．５時間撹拌した。窒素を導入して過剰の塩素を追い出した後、水（５０ｍｌ）を加え、塩化メチレンで抽出した。得られた塩化メチレン溶液を減圧下濃縮後、残渣をテトラヒドロフラン（８ｍｌ）に溶解し、０℃にて２８％アンモニア水（５ｍｌ）を加え、室温で０．２５時間撹拌した。水（２０ｍｌ）を加え、ジエチルエーテルで抽出し、ジエチルエーテル層を廃棄した。得られた水層に３５％塩酸を加えて、ｐＨ１に調整後、再びジエチルエーテルで抽出した。得られたジエチルエーテル溶液を塩化ナトリウム飽和水溶液で洗浄後、無水硫酸ナトリウムで乾燥、溶媒留去して目的物（０．６４ｇ）を得た。融点１２０−１２２℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．４３（ｄ，Ｊ＝６．３Ｈｚ，３Ｈ），３．７４−３．８０（ｍ，１Ｈ），４．１３（ｓ，３Ｈ），４．２１−４．２６（ｍ，１Ｈ），４．５７−４．６７（ｍ，１Ｈ），６．１２（ｂｒｓ，２Ｈ）。(4) Synthesis of 3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide (Part 1)

5-Benzylthio-3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (1.9 g, 5.6 mmol) in methylene chloride (30 ml) ) To the solution, water (30 ml) and 35% hydrochloric acid (2.3 g, 22 mmol) were added, and 8% aqueous sodium hypochlorite solution (20.5 g, 22.0 mmol) was added at 5 ° C. with vigorous stirring. Stir for 0.5 hour. Nitrogen was introduced to drive off excess chlorine, water (50 ml) was added, and the mixture was extracted with methylene chloride. The obtained methylene chloride solution was concentrated under reduced pressure, the residue was dissolved in tetrahydrofuran (8 ml), 28% aqueous ammonia (5 ml) was added at 0 ° C., and the mixture was stirred at room temperature for 0.25 hr. Water (20 ml) was added and extracted with diethyl ether, and the diethyl ether layer was discarded. The obtained aqueous layer was adjusted to pH 1 by adding 35% hydrochloric acid, and extracted again with diethyl ether. The obtained diethyl ether solution was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain the desired product (0.64 g). Melting point 120-122 ° C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.43 (d, J = 6.3 Hz, 3H), 3.74-3.80 (m, 1H), 4.13 (s, 3H), 4.21-4.26 (m, 1H), 4.57-4.67 (m, 1H), 6.12 (brs, 2H).

原料に５−ベンジルチオ−３−クロロ−４−（５−ヨードメチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）−１−メチルピラゾール（０．２４ｇ、０．５２ｍｍｏｌ）を用い、参考例１の（４）と同様にして目的物（０．０９０ｇ）を得た。固体。[Reference Example 2]
Synthesis of 3-chloro-4- (5-iodomethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1-methylpyrazole-5-sulfonamide

5-Benzylthio-3-chloro-4- (5-iodomethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1-methylpyrazole (0.24 g, 0.52 mmol) was used as a raw material, The target product (0.090 g) was obtained in the same manner as in Reference Example 1 (4). solid.

原料に２−メチル−２−プロペニルオキシアミン塩酸塩（１．２ｇ、９．７ｍｍｏｌ）を用い、参考例１の（１）と同様にして目的物（１．８ｇ）を得た。油状物質。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．８８（ｓ，３Ｈ），３．３６（ｓ，３Ｈ），４．１１（ｓ，２Ｈ），４．４５（ｓ，２Ｈ），５．０８（ｄ，Ｊ＝９．９Ｈｚ，２Ｈ），７．０１−７．０６（ｍ，２Ｈ），７．２２−７．２８（ｍ，３Ｈ），９．１５（ｂｒｓ，１Ｈ）。[Reference Example 3]
(1) Synthesis of (5-benzylthio-3-chloro-1-methylpyrazol-4-yl) -N- (2-methyl-2-propenyloxy) carboxylic acid amide

Using 2-methyl-2-propenyloxyamine hydrochloride (1.2 g, 9.7 mmol) as a raw material, the target product (1.8 g) was obtained in the same manner as (1) of Reference Example 1. Oily substance. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.88 (s, 3H), 3.36 (s, 3H), 4.11 (s, 2H), 4.45 (s, 2H) ), 5.08 (d, J = 9.9 Hz, 2H), 7.01-7.06 (m, 2H), 7.22-7.28 (m, 3H), 9.15 (brs, 1H) ).

原料に（５−ベンジルチオ−３−クロロ−１−メチルピラゾール−４−イル）−Ｎ−（２−メチル−２−プロペニルオキシ）カルボン酸アミド（１．７ｇ、４．８ｍｍｏｌ）を用い、参考例１の（２）と同様にして目的物（２．３ｇ）を得た。油状物質。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．６１（ｓ，３Ｈ），３．２３（ｓ，３Ｈ），３．３９−３．５５（ｍ，２Ｈ），３．９１−３．９５（ｍ，１Ｈ），４．１１（ｓ，２Ｈ），４．２５−４．２９（ｍ，１Ｈ），６．９８−７．０６（ｍ，２Ｈ），７．２１−７．２８（ｍ，３Ｈ）。(2) Synthesis of 5-benzylthio-3-chloro-4- (5-iodomethyl-5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) -1-methylpyrazole

A reference example using (5-benzylthio-3-chloro-1-methylpyrazol-4-yl) -N- (2-methyl-2-propenyloxy) carboxylic acid amide (1.7 g, 4.8 mmol) as a raw material The target product (2.3 g) was obtained in the same manner as in (2) of 1. Oily substance. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.61 (s, 3H), 3.23 (s, 3H), 3.39-3.55 (m, 2H), 3.91 -3.95 (m, 1H), 4.11 (s, 2H), 4.25-4.29 (m, 1H), 6.98-7.06 (m, 2H), 7.21-7 .28 (m, 3H).

原料に（５−ベンジルチオ−３−クロロ−４−（５−ヨードメチル−５−メチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）−１−メチルピラゾール（１．７ｇ、３．６ｍｍｏｌ）を用い、参考例１の（３）と同様にして目的物（１．３ｇ）を得た。油状物質。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．４８（ｓ，６Ｈ），３．２３（ｓ，３Ｈ），３．８８（ｓ，２Ｈ），４．０５（ｓ，２Ｈ），６．９９−７．０６（ｍ，２Ｈ），７．２１−７．２８（ｍ，３Ｈ）。(3) Synthesis of 5-benzylthio-3-chloro-1-methyl-4- (5,5-dimethyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole

(5-Benzylthio-3-chloro-4- (5-iodomethyl-5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) -1-methylpyrazole (1.7 g, 3. 6 mmol), and the target product (1.3 g) was obtained in the same manner as (3) in Reference Example 1. Oily substance Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.48 ( s, 6H), 3.23 (s, 3H), 3.88 (s, 2H), 4.05 (s, 2H), 6.99-7.06 (m, 2H), 7.21-7 .28 (m, 3H).

原料に５−ベンジルチオ−３−クロロ−１−メチル−４−（５，５−ジメチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（１．２ｇ、３．４ｍｍｏｌ）を用い、参考例１の（４）と同様にして目的物（０．４７ｇ）を得た。固体。(4) Synthesis of 3-chloro-1-methyl-4- (5,5-dimethyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide

5-Benzylthio-3-chloro-1-methyl-4- (5,5-dimethyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (1.2 g, 3.4 mmol) was used as a raw material. In the same manner as in (4) of Reference Example 1, the desired product (0.47 g) was obtained. solid.

原料に５−ベンジルチオ−３−クロロ−４−（５−ヨードメチル−５−メチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）−１−メチルピラゾール（０．５０ｇ、１．０ｍｍｏｌ）を用い、参考例１の（４）と同様にして目的物（０．２１ｇ）を得た。固体。[Reference Example 4]
Synthesis of 3-chloro-4- (5-iodomethyl-5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) -1-methylpyrazole-5-sulfonamide

5-Benzylthio-3-chloro-4- (5-iodomethyl-5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) -1-methylpyrazole (0.50 g, 1.0 mmol) as a raw material ) Was used in the same manner as (4) in Reference Example 1 to obtain the desired product (0.21 g). solid.

原料に５−ベンジルチオ−１，３−ジメチルピラゾール−４−カルボン酸クロリド（１．６ｇ、５．７ｍｍｏｌ）を用い、参考例１の（１）と同様にして目的物（１．５ｇ）を得た。油状物質。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）２．５０（ｓ，３Ｈ），３．３４（ｓ，３Ｈ），３．９２（ｓ，２Ｈ），４．４８−４．５１（ｍ，２Ｈ），５．３２−５．４３（ｍ，２Ｈ），６．０２−６．１１（ｍ，１Ｈ），６．９６−７．００（ｍ，２Ｈ），７．２３−７．３０（ｍ，３Ｈ），９．７７（ｓ，１Ｈ）。[Reference Example 5]
(1) Synthesis of (5-benzylthio-1,3-dimethylpyrazol-4-yl) -N-allyloxycarboxylic acid amide

Using 5-benzylthio-1,3-dimethylpyrazole-4-carboxylic acid chloride (1.6 g, 5.7 mmol) as a raw material, the target product (1.5 g) was obtained in the same manner as (1) in Reference Example 1. It was. Oily substance. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 2.50 (s, 3H), 3.34 (s, 3H), 3.92 (s, 2H), 4.48-4.51 (M, 2H), 5.32-5.43 (m, 2H), 6.02-6.11 (m, 1H), 6.96-7.00 (m, 2H), 7.23-7 .30 (m, 3H), 9.77 (s, 1H).

原料に（５−ベンジルチオ−１，３−ジメチルピラゾール−４−イル）−Ｎ−アリルオキシカルボン酸アミド（０．９２ｇ、２．９ｍｍｏｌ）を用い、参考例１の（２）と同様にして目的物（０．７４ｇ）を得た。融点７９−８１℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）２．３７（ｓ，３Ｈ），３．２９（ｓ，３Ｈ），３．３６−３．４０（ｍ，２Ｈ），３．９７−４．０４（ｍ，３Ｈ），４．２９−４．３４（ｍ，１Ｈ），４．５３−４．６０（ｍ，１Ｈ），７．００−７．０６（ｍ，２Ｈ），７．２０−７．２８（ｍ，３Ｈ）。(2) Synthesis of 5-benzylthio-4- (5-iodomethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1,3-dimethylpyrazole

(5-Benzylthio-1,3-dimethylpyrazol-4-yl) -N-allyloxycarboxylic acid amide (0.92 g, 2.9 mmol) was used as a starting material in the same manner as (2) of Reference Example 1 Product (0.74 g) was obtained. Melting point 79-81 ° C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 2.37 (s, 3H), 3.29 (s, 3H), 3.36-3.40 (m, 2H), 3.97 -4.04 (m, 3H), 4.29-4.34 (m, 1H), 4.53-4.60 (m, 1H), 7.00-7.06 (m, 2H), 7 20-7.28 (m, 3H).

原料に５−ベンジルチオ−４−（５−ヨードメチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）−１，３−ジメチルピラゾール（０．７１ｇ、１．６ｍｍｏｌ）を用い、参考例１の（３）と同様にして目的物（０．１９ｇ）を得た。油状物質。(3) Synthesis of 5-benzylthio-1,3-dimethyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole

5-Benzylthio-4- (5-iodomethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1,3-dimethylpyrazole (0.71 g, 1.6 mmol) was used as a raw material, and Reference Example The target product (0.19 g) was obtained in the same manner as in 1 (3). Oily substance.

原料に５−ベンジルチオ−１，３−ジメチル−４−（５−メチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（０．１９ｇ、０．６ｍｍｏｌ）を用い、参考例１の（４）と同様にして目的物（０．０７０ｇ）を得た。固体。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．４２（ｓ，３Ｈ），２．３３（ｓ，３Ｈ），３．７１−３．７８（ｍ，１Ｈ），４．１０（ｓ，３Ｈ），４．２１−４．２５（ｍ，１Ｈ），４．６０（ｍ，１Ｈ），６．１５（ｓ，２Ｈ）。(4) Synthesis of 1,3-dimethyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide

Reference example using 5-benzylthio-1,3-dimethyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (0.19 g, 0.6 mmol) as a raw material The target product (0.070 g) was obtained in the same manner as (1) (4). solid. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.42 (s, 3H), 2.33 (s, 3H), 3.71-3.78 (m, 1H), 4.10 (S, 3H), 4.21-4.25 (m, 1H), 4.60 (m, 1H), 6.15 (s, 2H).

原料に５−ベンジルチオ−４−（５−ヨードメチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）−１，３−ジメチルピラゾール（０．７０ｇ、１．６ｍｍｏｌ）を用い、参考例１の（４）と同様にして目的物（０．５３ｇ）を得た。固体。[Reference Example 6]
Synthesis of 4- (5-iodomethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1,3-dimethylpyrazole-5-sulfonamide

5-Benzylthio-4- (5-iodomethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1,3-dimethylpyrazole (0.70 g, 1.6 mmol) was used as a raw material, and a reference example The target product (0.53 g) was obtained in the same manner as in (1) (4). solid.

原料に５−ベンジルチオ−１，３−ジメチルピラゾール−４−カルボン酸クロリド（１．１０ｇ、３．９ｍｍｏｌ）と２−メチル−２−プロペニルオキシアミン塩酸塩（１．３０ｇ、１０．５ｍｍｏｌ）を用い、参考例１の（１）と同様にして目的物（１．１５ｇ）を得た。油状物質。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．８９（ｓ，３Ｈ），２．５１（ｓ，３Ｈ），３．３３（ｓ，３Ｈ），３．９１（ｓ，２Ｈ），４．４２（ｓ，２Ｈ），５．０６（ｄ，Ｊ＝１１．３Ｈｚ，２Ｈ），６．９５−７．０１（ｍ，２Ｈ），７．２４−７．２９（ｍ，３Ｈ），９．７７（ｂｒｓ，１Ｈ）。[Reference Example 7]
(1) Synthesis of (5-benzylthio-1,3-dimethylpyrazol-4-yl) -N- (2-methyl-2-propenyloxy) carboxylic acid amide

5-Benzylthio-1,3-dimethylpyrazole-4-carboxylic acid chloride (1.10 g, 3.9 mmol) and 2-methyl-2-propenyloxyamine hydrochloride (1.30 g, 10.5 mmol) were used as raw materials. In the same manner as in (1) of Reference Example 1, the desired product (1.15 g) was obtained. Oily substance. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.89 (s, 3H), 2.51 (s, 3H), 3.33 (s, 3H), 3.91 (s, 2H) ), 4.42 (s, 2H), 5.06 (d, J = 11.3 Hz, 2H), 6.95-7.01 (m, 2H), 7.24-7.29 (m, 3H) ), 9.77 (brs, 1H).

原料に（５−ベンジルチオ−１，３−ジメチルピラゾール−４−イル）−Ｎ−（２−メチル−２−プロペニルオキシ）カルボン酸アミド（０．６０ｇ、１．８ｍｍｏｌ）を用い、参考例１の（２）と同様にして目的物（０．７８ｇ）を得た。油状物質。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）１．６０（ｓ，３Ｈ），２．３７（ｓ，３Ｈ），３．２７（ｓ，３Ｈ），３．３９−３．５２（ｍ，２Ｈ），３．８８−３．９３（ｍ，１Ｈ），４．００（ｓ，２Ｈ），４．１９−４．２４（ｍ，１Ｈ），７．００−７．０５（ｍ，２Ｈ），７．２０−７．２４（ｍ，３Ｈ）。(2) Synthesis of 5-benzylthio-4- (5-iodomethyl-5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) -1,3-dimethylpyrazole

(5-Benzylthio-1,3-dimethylpyrazol-4-yl) -N- (2-methyl-2-propenyloxy) carboxylic acid amide (0.60 g, 1.8 mmol) was used as a raw material. The target product (0.78 g) was obtained in the same manner as (2). Oily substance. Proton nuclear magnetic resonance chemical shift value δ (ppm) 1.60 (s, 3H), 2.37 (s, 3H), 3.27 (s, 3H), 3.39-3.52 (m, 2H) 3.88-3.93 (m, 1H), 4.00 (s, 2H), 4.19-4.24 (m, 1H), 7.00-7.05 (m, 2H), 7 20-7.24 (m, 3H).

原料に５−ベンジルチオ−４−（５−ヨードメチル−５−メチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）−１，３−ジメチルピラゾール（０．５４ｇ、１．２ｍｍｏｌ）を用い、参考例１の（３）と同様にして目的物（０．３８ｇ）を得た。油状物質。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）１．４７（ｓ，６Ｈ），２．３４（ｓ，３Ｈ），３．２６（ｓ，３Ｈ），３．８６（ｓ，２Ｈ），４．００（ｓ，２Ｈ），６．９８−７．０５（ｍ，２Ｈ），７．２１−７．２５（ｍ，３Ｈ）。(3) Synthesis of 5-benzylthio-1,3-dimethyl-4- (5,5-dimethyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole

5-Benzylthio-4- (5-iodomethyl-5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) -1,3-dimethylpyrazole (0.54 g, 1.2 mmol) was used as a raw material. In the same manner as in (3) of Reference Example 1, the desired product (0.38 g) was obtained. Oily substance. Proton nuclear magnetic resonance chemical shift value δ (ppm) 1.47 (s, 6H), 2.34 (s, 3H), 3.26 (s, 3H), 3.86 (s, 2H), 4.00 (S, 2H), 6.98-7.05 (m, 2H), 7.21-7.25 (m, 3H).

原料に５−ベンジルチオ−１，３−ジメチル−４−（５，５−ジメチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（０．３４ｇ、１．０ｍｍｏｌ）を用い、参考例１の（４）と同様にして目的物（０．１３ｇ）を得た。固体。(4) Synthesis of 1,3-dimethyl-4- (5,5-dimethyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide

Using 5-benzylthio-1,3-dimethyl-4- (5,5-dimethyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (0.34 g, 1.0 mmol) as a raw material, The target product (0.13 g) was obtained in the same manner as in Reference Example 1 (4). solid.

原料に５−ベンジルチオ−４−（５−ヨードメチル−５−メチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）−１，３−ジメチルピラゾール（０．２０ｇ、０．４４ｍｍｏｌ）を用い、参考例１の（４）と同様にして目的物（０．０８０ｇ）を得た。固体。[Reference Example 8]
Synthesis of 4- (5-iodomethyl-5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) -1,3-dimethylpyrazole-5-sulfonamide

5-Benzylthio-4- (5-iodomethyl-5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) -1,3-dimethylpyrazole (0.20 g, 0.44 mmol) was used as a raw material. In the same manner as in (4) of Reference Example 1, the desired product (0.080 g) was obtained. solid.

５−ベンジルチオ−３−クロロ−１−メチルピラゾール−４−カルボン酸（１．０ｇ、３．８ｍｍｏｌ）の塩化メチレン（２０ｍｌ）溶液に、２−アミノオキシプロパン酸エチル（０．５８ｇ、４．４ｍｍｏｌ）とＮ−エチル−Ｎ’−（３−ジメチルアミノプロピル）カルボジイミド塩酸塩（０．８３ｇ、４．３ｍｍｏｌ）を加え、室温で１２時間撹拌した。減圧下、溶媒留去後、水（５０ｍｌ）を加え、酢酸エチルで抽出した。得られた酢酸エチル溶液を塩化ナトリウム飽和水溶液で洗浄、無水硫酸ナトリウムで乾燥、溶媒留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（展開液：ｎ−ヘキサン／酢酸エチル＝１／１）で精製し、目的物０．８８ｇを得た。油状物質。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．３０（ｔ，Ｊ＝８Ｈｚ，３Ｈ），１．５７（ｄ，Ｊ＝１０Ｈｚ，３Ｈ），２．４７（ｓ，３Ｈ）），３．２８（ｓ，３Ｈ），３．４０（ｑ，Ｊ＝８Ｈｚ，２Ｈ），４．１８−４．３２（ｍ，２Ｈ），４．６２−４．７１（ｍ，１Ｈ），６．９１−７．０７（ｍ，２Ｈ），７．１５−７．３１（ｍ，３Ｈ），１０．４０（ｓ，１Ｈ）。[Reference Example 9]
(1) Synthesis of ethyl 2- (1,3-dimethyl-5-benzylthiopyrazol-4-yl) carbonylaminooxy) propanoate

To a solution of 5-benzylthio-3-chloro-1-methylpyrazole-4-carboxylic acid (1.0 g, 3.8 mmol) in methylene chloride (20 ml) was added ethyl 2-aminooxypropanoate (0.58 g, 4.4 mmol). ) And N-ethyl-N ′-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.83 g, 4.3 mmol) were added, and the mixture was stirred at room temperature for 12 hours. After evaporating the solvent under reduced pressure, water (50 ml) was added, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate solution was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography (developing solution: n-hexane / ethyl acetate = 1/1) to obtain 0.88 g of the desired product. Oily substance. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.30 (t, J = 8 Hz, 3H), 1.57 (d, J = 10 Hz, 3H), 2.47 (s, 3H) ), 3.28 (s, 3H), 3.40 (q, J = 8 Hz, 2H), 4.18-4.32 (m, 2H), 4.62-4.71 (m, 1H), 6.91-7.07 (m, 2H), 7.15-7.31 (m, 3H), 10.40 (s, 1H).

水素化リチウムアルミニウム（０．０９０ｇ、２．４ｍｍｏｌ）のジエチルエーテル（２０ｍｌ）懸濁液に、撹拌下、５℃で、２−（１，３−ジメチル−５−ベンジルチオピラゾール−４−イル）カルボニルアミノオキシ）プロパン酸エチル（０．８８ｇ、２．３ｍｍｏｌ）のジエチルエーテル（５ｍｌ）溶液を滴下した。同温度で２．５時間撹拌後、反応液を氷水（２０ｍｌ）にあけ、１０％塩酸を加えてｐＨ１に調整し、酢酸エチルで抽出した。酢酸エチル溶液を水洗、無水硫酸ナトリウムで乾燥、溶媒留去して目的物（０．７０ｇ）を得た。油状物質。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．２９（ｄ，Ｊ＝８Ｈｚ，３Ｈ），２．７４（ｓ，３Ｈ），３．２６−３．５０（ｍ，１Ｈ），３．４２（ｓ，３Ｈ），３．５９−３．７２（ｍ，１Ｈ），３．９４（ｓ，２Ｈ），３．９６−４．０３（ｍ，１Ｈ），４．７２（ｂｒｓ，１Ｈ），６．９１−７．０２（ｍ，２Ｈ），７．２０−７．３２（ｍ，３Ｈ），９．６０（ｂｒｓ，１Ｈ）。(2) Synthesis of (1,3-dimethyl-5-benzylthiopyrazol-4-yl) -N- (2-hydroxyisopropoxy) carboxylic acid amide

To a suspension of lithium aluminum hydride (0.090 g, 2.4 mmol) in diethyl ether (20 ml) with stirring at 5 ° C., 2- (1,3-dimethyl-5-benzylthiopyrazol-4-yl) A solution of ethyl carbonylaminooxy) propanoate (0.88 g, 2.3 mmol) in diethyl ether (5 ml) was added dropwise. After stirring at the same temperature for 2.5 hours, the reaction solution was poured into ice water (20 ml), adjusted to pH 1 by adding 10% hydrochloric acid, and extracted with ethyl acetate. The ethyl acetate solution was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain the desired product (0.70 g). Oily substance. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.29 (d, J = 8 Hz, 3H), 2.74 (s, 3H), 3.26-3.50 (m, 1H) 3.42 (s, 3H), 3.59-3.72 (m, 1H), 3.94 (s, 2H), 3.96-4.03 (m, 1H), 4.72 (brs) , 1H), 6.91-7.02 (m, 2H), 7.20-7.32 (m, 3H), 9.60 (brs, 1H).

（１，３−ジメチル−５−ベンジルチオピラゾール−４−イル）−Ｎ−（２−ヒドロキシイソプロポキシ）カルボン酸アミド（０．７０ｇ、２．１ｍｍｏｌ）の塩化メチレン（５ｍｌ）溶液に、塩化チオニル（０．３４ｍｌ、４．６ｍｍｏｌ）を加え、１．５時間還流後、溶媒留去した。得られた残渣をＮ，Ｎ−ジメチルホルムアミド（１０ｍｌ）に溶解し、５℃にて、５５％水素化ナトリウム（０．１０ｇ、２．３ｍｍｏｌ）を加え、さらに同温度で１時間撹拌した。水（２０ｍｌ）を加え、酢酸エチルで抽出し、得られた酢酸エチル溶液を塩化ナトリウム飽和水溶液で洗浄後、無水硫酸ナトリウムで乾燥、溶媒留去した。得られた残渣をシリカゲル薄層クロマトグラフィー（展開液：ｎ−ヘキサン／酢酸エチル＝１／１）で精製して目的物（０．３２ｇ）を得た。固体。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．３７（ｄ，Ｊ＝８Ｈｚ，３Ｈ），２．３３（ｓ，３Ｈ），３．２８（ｓ，３Ｈ），３．９５−４．０５（ｍ，２Ｈ），４．０８−４．１３（ｍ，１Ｈ），４．４４−４．５１（ｍ，１Ｈ），６．９９−７．０６（ｍ，２Ｈ），７．０９−７．１５（ｍ，３Ｈ）。(3) Synthesis of 5-benzylthio-1,3-dimethyl-4- (6-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole

To a solution of (1,3-dimethyl-5-benzylthiopyrazol-4-yl) -N- (2-hydroxyisopropoxy) carboxylic acid amide (0.70 g, 2.1 mmol) in methylene chloride (5 ml) was added thionyl chloride. (0.34 ml, 4.6 mmol) was added and the solvent was distilled off after refluxing for 1.5 hours. The obtained residue was dissolved in N, N-dimethylformamide (10 ml), 55% sodium hydride (0.10 g, 2.3 mmol) was added at 5 ° C., and the mixture was further stirred at the same temperature for 1 hour. Water (20 ml) was added, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate solution was washed with a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel thin layer chromatography (developing solution: n-hexane / ethyl acetate = 1/1) to obtain the desired product (0.32 g). solid. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.37 (d, J = 8 Hz, 3H), 2.33 (s, 3H), 3.28 (s, 3H), 3.95 -4.05 (m, 2H), 4.08-4.13 (m, 1H), 4.44-4.51 (m, 1H), 699-7.06 (m, 2H), 7 .09-7.15 (m, 3H).

原料に５−ベンジルチオ−１，３−ジメチル−４−（６−メチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（０．３２ｇ、１．０ｍｍｏｌ）を用い、参考例１の（４）と同様にして目的物（０．１４ｇ）を得た。固体。(4) Synthesis of 1,3-dimethyl-4- (6-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide

Reference example using 5-benzylthio-1,3-dimethyl-4- (6-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (0.32 g, 1.0 mmol) as a raw material The target product (0.14 g) was obtained in the same manner as in (4) of 1. solid.

ヒドロキシルアミン塩酸塩（１０６．９ｇ、１．５３８ｍｏｌ）の水（２００ｍｌ）溶液に、５ないし１５℃にて８５％水酸化カリウム（１０１．５ｇ、１．５３８ｍｏｌ）の水（２００ｍｌ）溶液を加え、室温で５分間撹拌した。次に、３ないし８℃にて３，５−ジクロロ−１−メチルピラゾール−４−カルボン酸クロリド（１００．０ｇ、０．５１２８ｍｏｌ）のテトラヒドロフラン（１７０ｍｌ）溶液を２時間で滴下した。さらに５℃で０．５時間撹拌後、３５％塩酸を加えｐＨ３ないし４に調整した。析出した固体を濾取、水洗、乾燥して目的物（９４．９ｇ）を得た。融点２００−２０２℃（分解）。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ジメチルスルホキシド−ｄ₆中）３．７９（ｓ，３Ｈ），９．２４（ｂｒｓ，１Ｈ），１０．８３（ｂｒｓ，１Ｈ）。[Reference Example 10]
(1) Synthesis of 3,5-dichloro-1-methylpyrazole-4-carbohydroxamic acid

To a solution of hydroxylamine hydrochloride (106.9 g, 1.538 mol) in water (200 ml) at 85 ° C. was added 85% potassium hydroxide (101.5 g, 1.538 mol) in water (200 ml), Stir at room temperature for 5 minutes. Next, a solution of 3,5-dichloro-1-methylpyrazole-4-carboxylic acid chloride (100.0 g, 0.5128 mol) in tetrahydrofuran (170 ml) was added dropwise at 3 to 8 ° C. over 2 hours. Further, after stirring at 5 ° C. for 0.5 hour, 35% hydrochloric acid was added to adjust to pH 3-4. The precipitated solid was collected by filtration, washed with water and dried to obtain the desired product (94.9 g). Melting point 200-202 ° C. (decomposition). Proton nuclear magnetic resonance chemical shift value δ (ppm) (in dimethyl sulfoxide-d ₆ ) 3.79 (s, 3H), 9.24 (brs, 1H), 10.83 (brs, 1H).

炭酸カリウム（１５．８ｇ、１１４ｍｍｏｌ）の水（６０ｍｌ）溶液に、３，５−ジクロロ−１−メチルピラゾール−４−カルボヒドロキサム酸（２０．０ｇ、９５．２ｍｍｏｌ）と臭化アリル（１３．８ｇ、１１４ｍｍｏｌ）のトルエン（６０ｍｌ）溶液を加え、５０℃にて３時間撹拌した。室温まで冷却後、３５％塩酸を加えてｐＨ１に調整し、析出した固体を濾取、水およびトルエンで順次洗浄後、乾燥して目的物（１７．２ｇ）を得た。融点９６−９７℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）３．８４（ｓ，３Ｈ），４．５１（ｄ，Ｊ＝６．３Ｈｚ，２Ｈ），５．３０−５．４６（ｍ，２Ｈ），５．９４−６．１３（ｍ，１Ｈ），８．８０（ｂｒｓ，１Ｈ）。(2) Synthesis of N-allyloxy-3,5-dichloro-1-methylpyrazole-4-carboxylic acid amide

To a solution of potassium carbonate (15.8 g, 114 mmol) in water (60 ml) was added 3,5-dichloro-1-methylpyrazole-4-carbohydroxamic acid (20.0 g, 95.2 mmol) and allyl bromide (13.8 g). 114 mmol) in toluene (60 ml) was added and stirred at 50 ° C. for 3 hours. After cooling to room temperature, 35% hydrochloric acid was added to adjust to pH 1, and the precipitated solid was collected by filtration, washed successively with water and toluene, and dried to obtain the desired product (17.2 g). Mp 96-97 ° C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 3.84 (s, 3H), 4.51 (d, J = 6.3 Hz, 2H), 5.30-5.46 (m, 2H), 5.94-6.13 (m, 1H), 8.80 (brs, 1H).

Ｎ−アリルオキシ−３，５−ジクロロ−１−メチルピラゾール−４−カルボン酸アミド（４０．０ｇ、１６０ｍｍｏｌ）のアセトニトリル（２００ｍｌ）溶液に、ヨウ素（１２２ｇ、４８１ｍｍｏｌ）を加え、室温にて４．５時間撹拌した。チオ硫酸ナトリウム飽和水溶液（１５０ｍｌ）を加え、酢酸エチルで抽出し、得られた酢酸エチル溶液を炭酸水素ナトリウム飽和水溶液、塩化ナトリウム飽和水溶液および水で順次洗浄後、無水硫酸ナトリウムで乾燥、溶媒留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（溶離液：ｎ−ヘキサン／酢酸エチル＝５／２）で精製して目的物（５４．０ｇ）を得た。油状物質。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）３．３７（ｄ，Ｊ＝６．９Ｈｚ，２Ｈ），３．８３（ｓ，３Ｈ），３．９９−４．０６（ｍ，１Ｈ），４．３２−４．３８（ｍ，１Ｈ），４．５４−４．６２（ｍ，１Ｈ）。(3) Synthesis of 3,5-dichloro-4- (5-iodomethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1-methylpyrazole

To a solution of N-allyloxy-3,5-dichloro-1-methylpyrazole-4-carboxylic acid amide (40.0 g, 160 mmol) in acetonitrile (200 ml) was added iodine (122 g, 481 mmol), and 4.5 at room temperature. Stir for hours. A saturated aqueous sodium thiosulfate solution (150 ml) was added, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate solution was washed successively with a saturated aqueous sodium hydrogen carbonate solution, a saturated aqueous sodium chloride solution and water, then dried over anhydrous sodium sulfate, and the solvent was distilled off. did. The obtained residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 5/2) to obtain the desired product (54.0 g). Oily substance. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 3.37 (d, J = 6.9 Hz, 2H), 3.83 (s, 3H), 3.99-4.06 (m, 1H), 4.32-4.38 (m, 1H), 4.54-4.62 (m, 1H).

水素化ホウ素ナトリウム（０．３０ｇ、７．９ｍｍｏｌ）のＮ，Ｎ−ジメチルホルムアミド（１５ｍｌ）溶液に、３，５−ジクロロ−４−（５−ヨードメチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）−１−メチルピラゾール（２．０ｇ、５．３ｍｍｏｌ）を加え、６０℃で０．５時間撹拌した。室温まで冷却後、水（１０ｍｌ）を加え、さらに３５％塩酸を加えてｐＨ１に調整し、酢酸エチルで抽出した。得られた酢酸エチル溶液を炭酸水素ナトリウム飽和水溶液、塩化ナトリウム飽和水溶液および水で順次洗浄後、無水硫酸ナトリウムで乾燥、溶媒留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（溶離液：ｎ−ヘキサン／酢酸エチル＝５／２）で精製して目的物（１．１ｇ）を得た。融点５０−５１℃、沸点１４２℃／０．３ｍｍＨｇ。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．４１（ｄ，Ｊ＝６．３Ｈｚ，３Ｈ），３．６９−３．７６（ｍ，１Ｈ），３．８２（ｓ，３Ｈ），４．２０−４．２６（ｍ，１Ｈ），４．５２−４．６１（ｍ，１Ｈ）。(4) Synthesis of 3,5-dichloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (Part 1)

To a solution of sodium borohydride (0.30 g, 7.9 mmol) in N, N-dimethylformamide (15 ml) was added 3,5-dichloro-4- (5-iodomethyl-5H, 6H-1,4,2-dioxazine. -3-yl) -1-methylpyrazole (2.0 g, 5.3 mmol) was added and stirred at 60 ° C. for 0.5 hour. After cooling to room temperature, water (10 ml) was added, and further 35% hydrochloric acid was added to adjust to pH 1, followed by extraction with ethyl acetate. The obtained ethyl acetate solution was washed successively with a saturated aqueous solution of sodium hydrogen carbonate, a saturated aqueous solution of sodium chloride and water, then dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 5/2) to obtain the desired product (1.1 g). Melting point 50-51 ° C., boiling point 142 ° C./0.3 mmHg. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.41 (d, J = 6.3 Hz, 3H), 3.69-3.76 (m, 1H), 3.82 (s, 3H), 4.20-4.26 (m, 1H), 4.52-4.61 (m, 1H).

７０％水硫化ナトリウム（４．３ｇ、５４ｍｍｏｌ）のＮ，Ｎ−ジメチルホルムアミド（３８ｍｌ）懸濁液に、３，５−ジクロロ−１−メチル−４−（５−メチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（３．８ｇ、１５ｍｍｏｌ）を加え、８０℃で５．５時間撹拌した。室温まで冷却後、水（５０ｍｌ）を加え、不溶物を濾別した。ろ液に３５％塩酸を加えてｐＨ１に調整し、析出した固体を濾取、水洗、乾燥して目的物（２．５５ｇ）を得た。融点６０−６４℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．４８（ｄ，Ｊ＝６．３Ｈｚ，３Ｈ），３．７５（ｓ，３Ｈ），３．７９−３．８５（ｍ，１Ｈ），４．２８−４．３２（ｍ，１Ｈ），４．６４−４．７４（ｍ，１Ｈ）。(5) Synthesis of 3-chloro-5-mercapto-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole

To a suspension of 70% sodium hydrosulfide (4.3 g, 54 mmol) in N, N-dimethylformamide (38 ml) was added 3,5-dichloro-1-methyl-4- (5-methyl-5H, 6H-1, 4,2-Dioxazin-3-yl) pyrazole (3.8 g, 15 mmol) was added and stirred at 80 ° C. for 5.5 hours. After cooling to room temperature, water (50 ml) was added and the insoluble material was filtered off. The filtrate was adjusted to pH 1 by adding 35% hydrochloric acid, and the precipitated solid was collected by filtration, washed with water and dried to obtain the desired product (2.55 g). Melting point 60-64 ° C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.48 (d, J = 6.3 Hz, 3H), 3.75 (s, 3H), 3.79-3.85 (m, 1H), 4.28-4.32 (m, 1H), 4.64-4.74 (m, 1H).

３−クロロ−５−メルカプト−１−メチル−４−（５−メチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（２．５ｇ、１０ｍｍｏｌ）の１，２−ジクロロエタン（５０ｍｌ）溶液に水（２０ｍｌ）を加え、氷冷下、激しく撹拌しながら塩素（２．１ｇ、３０ｍｍｏｌ）を導入した。この間反応温度は２０℃まで上昇した。窒素を導入して過剰の塩素を除去した後、１，２−ジクロロエタン層を分離した。得られた１，２−ジクロロエタン溶液を亜硫酸水素ナトリウム飽和水溶液、水で順次洗浄後、無水硫酸ナトリウムで乾燥、溶媒留去し、目的物（３．１ｇ）を得た。融点６３−６８℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．４１（ｄ，Ｊ＝６．３Ｈｚ，３Ｈ），３．７５−３．８１（ｍ，１Ｈ），４．２０（ｓ，３Ｈ），４．２３−４．２８（ｍ，１Ｈ），４．５４−４．６４（ｍ，１Ｈ）。(6) Synthesis of 3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonyl chloride

3-chloro-5-mercapto-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (2.5 g, 10 mmol) in 1,2-dichloroethane ( 50 ml) Water (20 ml) was added to the solution, and chlorine (2.1 g, 30 mmol) was introduced with vigorous stirring under ice cooling. During this time, the reaction temperature rose to 20 ° C. After introducing nitrogen to remove excess chlorine, the 1,2-dichloroethane layer was separated. The obtained 1,2-dichloroethane solution was washed successively with a saturated aqueous solution of sodium hydrogen sulfite and water, dried over anhydrous sodium sulfate, and evaporated to give the desired product (3.1 g). Melting point 63-68 ° C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.41 (d, J = 6.3 Hz, 3H), 3.75-3.81 (m, 1H), 4.20 (s, 3H), 4.23-4.28 (m, 1H), 4.54-4.64 (m, 1H).

(7) Synthesis of 3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide (Part 2)
1,2 of 3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonyl chloride (3.1 g, 9.9 mmol) -To a dichloroethane (30 ml) solution, 28% aqueous ammonia (1.5 g, 24.7 mmol) was added dropwise with ice-cooling and vigorous stirring. After stirring at room temperature for 0.5 hour, water (20 ml) and 35% hydrochloric acid (5.2 g, 50 mmol) were added, and the mixture was extracted with 1,2-dichloroethane. The obtained 1,2-dichloroethane solution was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain the desired product (2.8 g). Melting point 120-122 ° C.

３−クロロ−１−メチル−４−（５−メチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール−５−スルホンアミド（３．０ｇ、１０ｍｍｏｌ）のアセトニトリル（１５ｍｌ）溶液に、無水炭酸カリウム（１．８ｇ、１３ｍｍｏｌ）とクロロギ酸メチル（０．９６ｇ、１０ｍｍｏｌ）を加え、１時間加熱還流した。減圧下、溶媒留去して得られた残渣を水（２０ｍｌ）に溶解し、不要物を濾別後、１，２−ジクロロエタンで抽出した。得られた水層に３５％塩酸を加え、ｐＨ１に調整し、析出した固体を濾取、水洗、乾燥し、目的物（２．４ｇ）を得た。融点１３３−１３４℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．４３（ｄ，Ｊ＝６．６Ｈｚ，３Ｈ），３．７２（ｓ，３Ｈ），３．７４−３．８１（ｍ，１Ｈ），４．２１−４．３０（ｍ，１Ｈ），４．２５（ｓ，３Ｈ），４．５６−４．６６（ｍ，１Ｈ），８．８３（ｂｒｓ，１Ｈ）。(8) Synthesis of N-methoxycarbonyl-3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide

A solution of 3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide (3.0 g, 10 mmol) in acetonitrile (15 ml) To the mixture, anhydrous potassium carbonate (1.8 g, 13 mmol) and methyl chloroformate (0.96 g, 10 mmol) were added, and the mixture was heated to reflux for 1 hour. The residue obtained by distilling off the solvent under reduced pressure was dissolved in water (20 ml), and unnecessary substances were filtered off and extracted with 1,2-dichloroethane. 35% hydrochloric acid was added to the obtained aqueous layer to adjust to pH 1, and the precipitated solid was collected by filtration, washed with water and dried to obtain the desired product (2.4 g). Mp 133-134 ° C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.43 (d, J = 6.6 Hz, 3H), 3.72 (s, 3H), 3.74-3.81 (m, 1H), 4.21-4.30 (m, 1H), 4.25 (s, 3H), 4.56-4.66 (m, 1H), 8.83 (brs, 1H).

３，５−ジクロロ−４−（５−ヨードメチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）−１−メチルピラゾール（１．５ｇ、４．０ｍｍｏｌ）のテトラヒドロフラン（１０ｍｌ）溶液に、カリウムｔ−ブトキシド（０．５２ｇ、４．６ｍｍｏｌ）を加え、室温で０．２５時間撹拌した。飽和塩化アンモニウム水溶液（２０ｍｌ）を加え、酢酸エチルで抽出した。得られた酢酸エチル溶液を水および塩化ナトリウム飽和水溶液で順次洗浄後、無水硫酸ナトリウムで乾燥、溶媒留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（溶離液：ｎ−ヘキサン／酢酸エチル＝１／１）で精製して目的物（０．８８ｇ）を得た。融点６８−７０℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）３．８４（ｓ，３Ｈ），４．４２（ｓ，２Ｈ），４．４５（ｄ，Ｊ＝１．８Ｈｚ，１Ｈ），４．８５（ｄ，Ｊ＝１．８Ｈｚ，１Ｈ）。[Reference Example 11]
(1) Synthesis of 3,5-dichloro-1-methyl-4- (5-methylene-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole

To a solution of 3,5-dichloro-4- (5-iodomethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1-methylpyrazole (1.5 g, 4.0 mmol) in tetrahydrofuran (10 ml) , Potassium t-butoxide (0.52 g, 4.6 mmol) was added, and the mixture was stirred at room temperature for 0.25 hour. Saturated aqueous ammonium chloride solution (20 ml) was added, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate solution was washed successively with water and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and evaporated. The obtained residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 1/1) to obtain the desired product (0.88 g). Melting point 68-70 ° C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 3.84 (s, 3H), 4.42 (s, 2H), 4.45 (d, J = 1.8 Hz, 1H), 4 .85 (d, J = 1.8 Hz, 1H).

(2) Synthesis of 3,5-dichloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (Part 2)

  To a solution of 3,5-dichloro-1-methyl-4- (5-methylene-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (2.8 g, 11 mmol) in ethyl acetate (56 ml), 5% Palladium-carbon (0.56 g) was added, and the mixture was stirred at room temperature for 17 hours under an atmosphere of hydrogen (1 atm). 5% Palladium-carbon (0.05 g) was added, the mixture was further stirred for 1 hour under the above conditions, and the catalyst was filtered off. The solvent was distilled off from the filtrate, and the resulting residue was purified by alumina column chromatography (eluent: chloroform) to obtain the desired product (2.6 g). Mp 50-51 ° C.

[Reference Example 12]
Synthesis of 3,5-dichloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (Part 3)

  A solution of N-allyloxy-3,5-dichloro-1-methylpyrazole-4-carboxylic acid amide (0.50 g, 2.0 mmol) in toluene (5 ml) was added to trifluoromethanesulfonic acid (0.10 g, 1.0 mmol). And refluxed for 20 hours. The obtained toluene solution was washed successively with a saturated aqueous potassium carbonate solution and water, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 1/1) to obtain the desired product (0.08 g). Mp 50-51 ° C.

３−クロロ−１−メチル−４−（５−メチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール−５−スルホンアミド（５．３１ｇ、１８．０ｍｍｏｌ）の１，２−ジクロロエタン（３０ｍｌ）溶液に、無水炭酸カリウム（３．７６ｇ、２７．０ｍｍｏｌ）とｎ−ブチルイソシアナート（２．１４ｇ、２１．６ｍｍｏｌ）を加え、１時間加熱還流した。室温まで冷却後、水（２５ｍｌ）を加え、激しく撹拌した。有機層を分離し、得られた水層に３５％塩酸を加え、ｐＨ１に調整し、１，２−ジクロロエタンで抽出した。得られた１，２−ジクロロエタン溶液を水洗後、無水硫酸ナトリウムで乾燥、溶媒留去した。得られた残渣に少量のジイソプロピルエーテルを加え、析出した固体を濾取、水洗、乾燥し、目的物（３．５３ｇ）を得た。融点１３０−１３３℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）０．８９（ｔ，Ｊ＝７．２Ｈｚ，３Ｈ），１．２０−１．５０（ｍ，７Ｈ），３．１０−３．１９（ｍ，２Ｈ），３．３６−３．８３（ｍ，１Ｈ），４．１６（ｓ，３Ｈ），４．１５−４．２９（ｍ，１Ｈ），４．５６−４．６７（ｍ，１Ｈ），６．５６（ｔ，１Ｈ），９．５０−９．９２（ｂｒｓ，１Ｈ）。[Reference Example 13]
(1) N- (n-butylaminocarbonyl) -3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide Synthesis of

1,2 of 3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide (5.31 g, 18.0 mmol) -Anhydrous potassium carbonate (3.76 g, 27.0 mmol) and n-butyl isocyanate (2.14 g, 21.6 mmol) were added to a dichloroethane (30 ml) solution, and the mixture was heated to reflux for 1 hour. After cooling to room temperature, water (25 ml) was added and stirred vigorously. The organic layer was separated, 35% hydrochloric acid was added to the obtained aqueous layer to adjust to pH 1, and the mixture was extracted with 1,2-dichloroethane. The obtained 1,2-dichloroethane solution was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off. A small amount of diisopropyl ether was added to the obtained residue, and the precipitated solid was collected by filtration, washed with water and dried to obtain the desired product (3.53 g). Mp 130-133 ° C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 0.89 (t, J = 7.2 Hz, 3H), 1.20-1.50 (m, 7H), 3.10-3. 19 (m, 2H), 3.36-3.83 (m, 1H), 4.16 (s, 3H), 4.15-4.29 (m, 1H), 4.56-4.67 ( m, 1H), 6.56 (t, 1H), 9.50-9.92 (brs, 1H).

トルエン（１５ｍｌ）にＮ−（ｎ−ブチルアミノカルボニル）−３−クロロ−１−メチル−４−（５−メチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール−５−スルホンアミド（５．０ｇ、１３ｍｍｏｌ）、ビストリクロロメチルカーボネート（９．４ｇ，３２ｍｍｏｌ）およびトリエチルアミン（０．１ｍｌ）を加え、８時間加熱還流した。溶媒留去して目的物（４．０ｇ）を得た。油状物質。(2) Synthesis of 3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonyl isocyanate

Toluene (15 ml) with N- (n-butylaminocarbonyl) -3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5- Sulfonamide (5.0 g, 13 mmol), bistrichloromethyl carbonate (9.4 g, 32 mmol) and triethylamine (0.1 ml) were added, and the mixture was heated to reflux for 8 hours. The solvent was distilled off to obtain the desired product (4.0 g). Oily substance.

３−クロロ−５−メルカプト−１−メチル−４−（５−メチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（１．０ｇ、４．０ｍｍｏｌ）のＮ，Ｎ−ジメチルホルムアミド（１０ｍｌ）溶液に、室温で撹拌しながら、３．５時間にわたり空気を吹き込んだ。析出した固体を濾取、水洗、乾燥して目的物（０．４９ｇ）を得た。融点１６５−１６７℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．３６（ｄ，Ｊ＝６．３Ｈｚ，３Ｈ），３．４９−３．６４（ｍ，１Ｈ），３．８９（ｓ，３Ｈ），４．０４−４．１８（ｍ，１Ｈ），４．３２−４．４８（ｍ，１Ｈ）。[Reference Example 14]
(1) Synthesis of bis (3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazol-5-yl) disulfide

3-chloro-5-mercapto-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (1.0 g, 4.0 mmol) N, N- Air was bubbled through the dimethylformamide (10 ml) solution for 3.5 hours with stirring at room temperature. The precipitated solid was collected by filtration, washed with water, and dried to obtain the desired product (0.49 g). Melting point 165-167 [deg.] C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.36 (d, J = 6.3 Hz, 3H), 3.49-3.64 (m, 1H), 3.89 (s, 3H), 4.04-4.18 (m, 1H), 4.32-4.48 (m, 1H).

(2) Synthesis of 3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonyl chloride (part 2)
Of bis (3-chloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazol-5-yl) disulfide (2.5 g, 5.1 mmol) Water (20 ml) was added to a 1,2-dichloroethane (50 ml) solution, and chlorine (2.1 g, 30 mmol) was introduced with vigorous stirring under ice cooling. During this time, the reaction temperature rose to 20 ° C. After introducing nitrogen to remove excess chlorine, the 1,2-dichloroethane layer was separated. The obtained 1,2-dichloroethane solution was washed successively with a saturated aqueous solution of sodium hydrogen sulfite and water, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain the desired product (3.0 g). Melting point 63-68 ° C.

[Reference Example 15]
Synthesis of 3,5-dichloro-4- (5-iodomethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1-methylpyrazole (part 2)
To a solution of N-allyloxy-3,5-dichloro-1-methylpyrazole-4-carboxylic acid amide (0.50 g, 2.0 mmol) in acetonitrile (5 ml) was added N-iodosuccinimide (0.67 g, 3.0 mmol). ) And stirred at room temperature for 15 hours. A saturated aqueous solution of sodium hydrogen sulfite (10 ml) was added, and the mixture was extracted with ethyl acetate. The resulting ethyl acetate solution was washed successively with a saturated aqueous solution of sodium bicarbonate, a saturated aqueous solution of sodium chloride and water, then dried over anhydrous sodium sulfate, and the solvent was distilled off. did. The obtained residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 3/1) to obtain the desired product (0.60 g). Oily substance.

Ｎ−アリルオキシ−３，５−ジクロロ−１−メチルピラゾール−４−カルボン酸アミド（２０．０ｇ、８０．０ｍｍｏｌ）のアセトニトリル（２００ｍｌ）溶液に、Ｎ−ブロモコハク酸イミド（１７．１ｇ、９６．０ｍｍｏｌ）を加え、室温にて１時間撹拌した。亜硫酸水素ナトリウム飽和水溶液（１００ｍｌ）を加え、アセトニトリルを留去した。次に、酢酸エチルで抽出し、得られた酢酸エチル溶液を水および塩化ナトリウム飽和水溶液で順次洗浄後、無水硫酸ナトリウムで乾燥、溶媒留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（溶離液：ｎ−ヘキサン／酢酸エチル＝３／１）で精製して目的物（１８．４ｇ）を得た。融点５３−５４℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）３．５７−３．６１（ｄ，Ｊ＝６．９Ｈｚ，２Ｈ），３．８３（ｓ，３Ｈ），４．０６−４．１１（ｍ，１Ｈ），４．２９−４．３３（ｍ，１Ｈ），４．６５−４．７２（ｍ，１Ｈ）。[Reference Example 16]
(1) Synthesis of 4- (5-bromomethyl-5H, 6H-1,4,2-dioxazin-3-yl) -3,5-dichloro-1-methylpyrazole

To a solution of N-allyloxy-3,5-dichloro-1-methylpyrazole-4-carboxylic acid amide (20.0 g, 80.0 mmol) in acetonitrile (200 ml) was added N-bromosuccinimide (17.1 g, 96.0 mmol). ) And stirred at room temperature for 1 hour. A saturated aqueous solution of sodium hydrogen sulfite (100 ml) was added, and acetonitrile was distilled off. Next, the mixture was extracted with ethyl acetate, and the resulting ethyl acetate solution was washed successively with water and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 3/1) to obtain the desired product (18.4 g). Mp 53-54 ° C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 3.57-3.61 (d, J = 6.9 Hz, 2H), 3.83 (s, 3H), 4.06-4. 11 (m, 1H), 4.29-4.33 (m, 1H), 4.65-4.72 (m, 1H).

(2) Synthesis of 3,5-dichloro-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (Part 3)
4- (5-Bromomethyl-5H, 6H-1,4,2-dioxazin-3-yl) -3,5-dichloro-1-methylpyrazole (0.50 g, 1.5 mmol) in N-methyl-2- Sodium borohydride (0.11 g, 3.0 mmol) was added to the pyrrolidone (5 ml) solution, and the mixture was stirred at 60 ° C. for 1 hour. After cooling to room temperature, water (5 ml) was added, and further 35% hydrochloric acid was added to adjust to pH 1, followed by extraction with ethyl acetate. The obtained ethyl acetate solution was washed successively with a saturated aqueous solution of sodium hydrogen carbonate, a saturated aqueous solution of sodium chloride and water, then dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 5/2) to obtain the desired product (0.31 g). Mp 50-51 ° C.

５−ベンジルチオ−１−メチルピラゾール−４−カルボン酸（１５．９ｇ、６４．０ｍｍｏｌ）のトルエン（１００ｍｌ）懸濁液に、塩化チオニル（１１．４ｇ、９５．８ｍｍｏｌ）とＮ，Ｎ−ジメチルホルムアミド（０．１ｇ）を加え、４時間、加熱還流した。溶媒留去して得られた残渣をテトラヒドロフラン（４０ｍｌ）に溶解した。
別途、ヒドロキシルアミン塩酸塩（１３．３ｇ、１９１ｍｍｏｌ）の水（４０ｍｌ）溶液に、５ないし１５℃にて８５％水酸化カリウム（１２．６ｇ、１９１ｍｍｏｌ）の水（４０ｍｌ）溶液を加え、室温で１５分間撹拌した。次に、３ないし１５℃にて、上記テトラヒドロフラン溶液を０．２５時間で滴下した。さらに３℃で１．５時間撹拌後、３５％塩酸（２０ｍｌ）を加え、ｐＨ３ないし４に調整し、酢酸エチルで抽出した。得られた酢酸エチル溶液を水洗後、無水硫酸ナトリウムで乾燥し、溶媒留去して得られた残渣をシリカゲルカラムクロマトグラフィー（溶離液：ｎ−ヘキサン／酢酸エチル＝１／１）で精製して目的物（１０．３ｇ）を得た。樹脂状物質。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）３．４２（ｓ，３Ｈ），３．９５（ｓ，２Ｈ），６．９３−７．０１（ｍ，２Ｈ），７．２０−７．２８（ｍ，３Ｈ），８．０４（ｓ，１Ｈ），９．７６（ｂｒｓ，１Ｈ）。[Reference Example 17]
(1) Synthesis of 5-benzylthio-1-methylpyrazole-4-carbohydroxamic acid

To a suspension of 5-benzylthio-1-methylpyrazole-4-carboxylic acid (15.9 g, 64.0 mmol) in toluene (100 ml) was added thionyl chloride (11.4 g, 95.8 mmol) and N, N-dimethylformamide. (0.1 g) was added and heated to reflux for 4 hours. The residue obtained by distilling off the solvent was dissolved in tetrahydrofuran (40 ml).
Separately, a solution of hydroxylamine hydrochloride (13.3 g, 191 mmol) in water (40 ml) was added with a solution of 85% potassium hydroxide (12.6 g, 191 mmol) in water (40 ml) at 5 to 15 ° C. at room temperature. Stir for 15 minutes. Next, the tetrahydrofuran solution was added dropwise at 3 to 15 ° C. over 0.25 hours. After further stirring at 3 ° C. for 1.5 hours, 35% hydrochloric acid (20 ml) was added to adjust the pH to 3 to 4, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate solution was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off. The resulting residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 1/1). The target product (10.3 g) was obtained. Resinous material. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 3.42 (s, 3H), 3.95 (s, 2H), 6.93-7.01 (m, 2H), 7.20 -7.28 (m, 3H), 8.04 (s, 1H), 9.76 (brs, 1H).

炭酸カリウム（１．３ｇ、９．４ｍｍｏｌ）の水（１０ｍｌ）溶液に、５−ベンジルチオ−１−メチルピラゾール−４−カルボヒドロキサム酸（２．０ｇ、７．６ｍｍｏｌ）と臭化アリル（１．１ｇ、９．１ｍｍｏｌ）のトルエン（１０ｍｌ）溶液を加え、５０℃にて４時間撹拌した。室温まで冷却後、３５％塩酸を加えてｐＨ１に調整し、酢酸エチルで抽出した。得られた酢酸エチル溶液を水洗後、無水硫酸ナトリウムで乾燥し、溶媒留去して目的物（１．９ｇ）を得た。油状物質。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）３．４２（ｓ，３Ｈ），３．９５（ｓ，２Ｈ），４．４９（ｄ，Ｊ＝６．３Ｈｚ，２Ｈ），５．３３−５．４３（ｍ，２Ｈ），６．００−６．１６（ｍ，１Ｈ），６．９３−７．００（ｍ，２Ｈ），７．２１−７．３０（ｍ，３Ｈ），８．０６（ｓ，１Ｈ），９．６８（ｂｒｓ，１Ｈ）。(2) Synthesis of N-allyloxy-5-benzylthio-1-methylpyrazole-4-carboxylic acid amide

To a solution of potassium carbonate (1.3 g, 9.4 mmol) in water (10 ml) was added 5-benzylthio-1-methylpyrazole-4-carbohydroxamic acid (2.0 g, 7.6 mmol) and allyl bromide (1.1 g). , 9.1 mmol) in toluene (10 ml) was added and stirred at 50 ° C. for 4 hours. After cooling to room temperature, 35% hydrochloric acid was added to adjust to pH 1, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate solution was washed with water, dried over anhydrous sodium sulfate, and the solvent was distilled off to obtain the desired product (1.9 g). Oily substance. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 3.42 (s, 3H), 3.95 (s, 2H), 4.49 (d, J = 6.3 Hz, 2H), 5 .33-5.43 (m, 2H), 6.00-6.16 (m, 1H), 6.93-7.00 (m, 2H), 7.21-7.30 (m, 3H) , 8.06 (s, 1H), 9.68 (brs, 1H).

Ｎ−アリルオキシ−５−ベンジルチオ−１−メチルピラゾール−４−カルボン酸アミド（１．８ｇ、５．９ｍｍｏｌ）のアセトニトリル（１０ｍｌ）溶液に、ヨウ素（４．５ｇ、１８ｍｍｏｌ）を加え、室温にて８時間撹拌した。チオ硫酸ナトリウム飽和水溶液（３０ｍｌ）を加え、酢酸エチルで抽出した。得られた酢酸エチル溶液を炭酸水素ナトリウム飽和水溶液、塩化ナトリウム飽和水溶液および水で順次洗浄後、無水硫酸ナトリウムで乾燥、溶媒留去した。得られた残渣をシリカゲルカラムクロマトグラフィー（溶離液：ｎ−ヘキサン／酢酸エチル＝３／１）で精製して目的物（１．７ｇ）を得た。樹脂状物質。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）３．３６−３．４２（ｍ，５Ｈ），３．９８−４．０５（ｍ，３Ｈ），４．３１−４．３８（ｍ，１Ｈ），４．５４−４．５９（ｍ，１Ｈ），６．９７−７．０２（ｍ，２Ｈ），７．２０−７．２４（ｍ，３Ｈ），７．７９（ｓ，１Ｈ）。(3) Synthesis of 5-benzylthio-4- (5-iodomethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1-methylpyrazole

To a solution of N-allyloxy-5-benzylthio-1-methylpyrazole-4-carboxylic acid amide (1.8 g, 5.9 mmol) in acetonitrile (10 ml) was added iodine (4.5 g, 18 mmol), and 8 at room temperature. Stir for hours. A saturated aqueous sodium thiosulfate solution (30 ml) was added, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate solution was washed successively with a saturated aqueous solution of sodium hydrogen carbonate, a saturated aqueous solution of sodium chloride and water, then dried over anhydrous sodium sulfate, and the solvent was distilled off. The obtained residue was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 3/1) to obtain the desired product (1.7 g). Resinous material. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 3.36-3.42 (m, 5H), 3.98-4.05 (m, 3H), 4.31-4.38 ( m, 1H), 4.54-4.59 (m, 1H), 6.97-7.02 (m, 2H), 7.20-7.24 (m, 3H), 7.79 (s, 1H).

５−ベンジルチオ−４−（５−ヨードメチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）−１−メチルピラゾール（１．６ｇ、３．７ｍｍｏｌ）のＮ，Ｎ−ジメチルホルムアミド（８ｍｌ）溶液に、５０℃にて、水素化ホウ素ナトリウム（０．２１ｇ、５．６ｍｍｏｌ）のＮ，Ｎ−ジメチルホルムアミド（５ｍｌ）溶液を０．３時間かけて滴下し、さらに、５０℃で１時間撹拌した。室温まで冷却後、水（２０ｍｌ）を加え、さらに３５％塩酸を加えてｐＨ１に調整し、酢酸エチルで抽出した。得られた酢酸エチル溶液を６％塩酸および水で順次洗浄後、無水硫酸ナトリウムで乾燥、溶媒留去して目的物（１．１ｇ）を得た。樹脂状物質。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．４３（ｄ，Ｊ＝６．３Ｈｚ，３Ｈ），３．３６（ｓ，３Ｈ），３．６９−３．７７（ｍ，１Ｈ），４．０４（ｑ，Ｊ＝１２．６Ｈｚ，２Ｈ），４．２１−４．２７（ｍ，１Ｈ），４．５５−４．６１（ｍ，１Ｈ），６．９８−７．０３（ｍ，２Ｈ），７．１９−７．２４（ｍ，３Ｈ），７．７６（ｓ，１Ｈ）。(4) Synthesis of 5-benzylthio-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole

5-Benzylthio-4- (5-iodomethyl-5H, 6H-1,4,2-dioxazin-3-yl) -1-methylpyrazole (1.6 g, 3.7 mmol) in N, N-dimethylformamide (8 ml) ) A solution of sodium borohydride (0.21 g, 5.6 mmol) in N, N-dimethylformamide (5 ml) was added dropwise to the solution over 0.3 hours, and further at 50 ° C. for 1 hour. Stir. After cooling to room temperature, water (20 ml) was added, and further 35% hydrochloric acid was added to adjust to pH 1, followed by extraction with ethyl acetate. The obtained ethyl acetate solution was washed successively with 6% hydrochloric acid and water, dried over anhydrous sodium sulfate, and evaporated to give the desired product (1.1 g). Resinous material. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.43 (d, J = 6.3 Hz, 3H), 3.36 (s, 3H), 3.69-3.77 (m, 1H), 4.04 (q, J = 12.6 Hz, 2H), 4.21-4.27 (m, 1H), 4.55-4.61 (m, 1H), 6.98-7. 03 (m, 2H), 7.19-7.24 (m, 3H), 7.76 (s, 1H).

５−ベンジルチオ−１−メチル−４−（５−メチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール（１．１ｇ、３．５ｍｍｏｌ）の１，２−ジクロロエタン（１０ｍｌ）溶液に、水（１０ｍｌ）と３５％塩酸（０．１ｇ）を加え、激しく撹拌しながら塩素（２．５ｇ、３５ｍｍｏｌ）を５℃にて導入した。この間、反応液は１９℃まで発熱した。窒素を導入して過剰の塩素を追い出した後、水（２０ｍｌ）を加え、１，２−ジクロロエタンで抽出した。得られた１，２−ジクロロエタン溶液を減圧下８ｍｌまで濃縮した。この溶液を、別途用意した２８％アンモニア水（１ｍｌ）を加えた１，２−ジクロロエタン（８ｍｌ）溶液に、５℃にて、激しく撹拌しながら滴下し、さらに、室温で０．５時間撹拌した。３５％塩酸を加えて、ｐＨ１に調整後、１，２−ジクロロエタンで抽出した。得られた１，２−ジクロロエタン溶液を無水硫酸ナトリウムで乾燥後、溶媒留去して得られた残渣をトルエンで再結晶して目的物（０．４３ｇ）を得た。融点９７−９９℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．４３（ｄ，Ｊ＝６．３Ｈｚ，３Ｈ），３．７０−３．７７（ｍ，１Ｈ），４．１９−４．２６（ｍ，４Ｈ），４．５５−４．６２（ｍ，１Ｈ），６．４９（ｂｒｓ，２Ｈ），７．７５（ｓ，１Ｈ）。(5) Synthesis of 1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide

5-Benzylthio-1-methyl-4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole (1.1 g, 3.5 mmol) in 1,2-dichloroethane (10 ml) Water (10 ml) and 35% hydrochloric acid (0.1 g) were added to the solution, and chlorine (2.5 g, 35 mmol) was introduced at 5 ° C. with vigorous stirring. During this time, the reaction solution exothermed to 19 ° C. Nitrogen was introduced to drive off excess chlorine, water (20 ml) was added, and the mixture was extracted with 1,2-dichloroethane. The resulting 1,2-dichloroethane solution was concentrated to 8 ml under reduced pressure. This solution was added dropwise to a 1,2-dichloroethane (8 ml) solution added with 28% aqueous ammonia (1 ml) separately prepared at 5 ° C. with vigorous stirring, and further stirred at room temperature for 0.5 hours. . 35% hydrochloric acid was added to adjust the pH to 1, followed by extraction with 1,2-dichloroethane. The obtained 1,2-dichloroethane solution was dried over anhydrous sodium sulfate, the solvent was distilled off, and the resulting residue was recrystallized from toluene to obtain the desired product (0.43 g). Mp 97-99 ° C. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.43 (d, J = 6.3 Hz, 3H), 3.70-3.77 (m, 1H), 4.19-4. 26 (m, 4H), 4.55-4.62 (m, 1H), 6.49 (brs, 2H), 7.75 (s, 1H).

原料に５−ベンジルチオ−１−（ピリジル−２−イル）ピラゾール−４−カルボン酸クロリド（３．６３ｇ、１１．０ｍｍｏｌ）を用い、参考例１と同様にして目的物（０．４５ｇ）を得た。樹脂状物質。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ₃中）１．４３（ｄ，Ｊ＝６．３Ｈｚ，３Ｈ），３．７７−３．８３（ｍ，１Ｈ），４．２２−４．２６（ｍ，１Ｈ），４．５８−４．６３（ｍ，１Ｈ），６．４１（ｂｒｓ，２Ｈ），７．４２−７．４４（ｍ，１Ｈ），７．７８−７．８０（ｍ，１Ｈ），７．８７（ｓ，１Ｈ）７．９３−７．９８（ｍ，１Ｈ），８．４８−８．５０（ｍ，１Ｈ）。[Reference Example 18]
Synthesis of 4- (5-methyl-5H, 6H-1,4,2-dioxazin-3-yl) -1- (pyridyl-2-yl) pyrazole-5-sulfonamide

5-Benzylthio-1- (pyridyl-2-yl) pyrazole-4-carboxylic acid chloride (3.63 g, 11.0 mmol) was used as a raw material in the same manner as in Reference Example 1 to obtain the desired product (0.45 g). It was. Resinous material. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl ₃ ) 1.43 (d, J = 6.3 Hz, 3H), 3.77-3.83 (m, 1H), 4.22-4. 26 (m, 1H), 4.58-4.63 (m, 1H), 6.41 (brs, 2H), 7.42-7.44 (m, 1H), 7.78-7.80 ( m, 1H), 7.87 (s, 1H) 7.93-7.98 (m, 1H), 8.48-8.50 (m, 1H).

３−クロロ−１−メチル−４−（５−ヨードメチル−５Ｈ，６Ｈ−１，４，２−ジオキサジン−３−イル）ピラゾール−５−スルホンアミド（０．５５ｇ、１．３ｍｍｏｌ）を１，２−ジメトキシエタン（１０ｍｌ）に溶解し氷冷下撹拌した。次いで２８％ナトリウムメトキシドのメタノール溶液（０．６ｇ、３．１ｍｍｏｌ）を０℃でゆっくり加えた後、１時間撹拌した。２規定塩酸を加え反応を停止し、酢酸エチルで抽出した。酢酸エチル層を水および塩化ナトリウム飽和水溶液で順次洗浄後、無水硫酸ナトリウムで乾燥、溶媒留去したところ油状物が得られた。得られた油状物をシリカゲルカラムクロマトグラフィー（溶離液；ｎ−ヘキサン／酢酸エチル＝１／１）で精製し、目的物（０．３６ｇ）を得た。無色固体。融点１１６−１１９℃。プロトン核磁気共鳴ケミカルシフト値δ（ｐｐｍ）（ＣＤＣｌ3中）４．１５（ｓ，３Ｈ），４．５２（ｓ，２Ｈ），４．５３（ｄ，Ｊ＝２．８Ｈｚ，１Ｈ）、４．９３（ｄ，Ｊ＝２．８Ｈｚ，１Ｈ）６．０３（ｂｒｓ，２Ｈ）。[Reference Example 19]
Synthesis of 3-chloro-1-methyl-4- (5-methylene-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide

3-chloro-1-methyl-4- (5-iodomethyl-5H, 6H-1,4,2-dioxazin-3-yl) pyrazole-5-sulfonamide (0.55 g, 1.3 mmol) -Dissolved in dimethoxyethane (10 ml) and stirred under ice cooling. Subsequently, 28% sodium methoxide in methanol (0.6 g, 3.1 mmol) was slowly added at 0 ° C., followed by stirring for 1 hour. 2N hydrochloric acid was added to stop the reaction, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed successively with water and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and evaporated to give an oil. The obtained oil was purified by silica gel column chromatography (eluent: n-hexane / ethyl acetate = 1/1) to obtain the desired product (0.36 g). Colorless solid. Mp 116-119 ° C. 3. Proton nuclear magnetic resonance chemical shift value δ (ppm) (in CDCl 3) 4.15 (s, 3H), 4.52 (s, 2H), 4.53 (d, J = 2.8 Hz, 1H) 93 (d, J = 2.8 Hz, 1H) 6.03 (brs, 2H).

  The structural formulas and physical properties of the compound (A) synthesized by using the same method as in the synthesis examples and reference examples are shown in Table 1 together with the compounds described in the synthesis examples and reference examples.

  As a combination of the compound (A) and at least one compound selected from dimrone, dimepiperate and esprocarb to be applied at the same time, compound 1 / daimlone, compound 1 / dimepiperate, compound 1 / esprocarb, compound 2 / Daimlon, Compound 2 / Dimepiperate, Compound 2 / Esprocarb, Compound 3 / Dimron, Compound 3 / Dimepiperate, Compound 3 / Esprocarb, Compound 4 / Dimron, Compound 4 / Dimepiperate, Compound 4 / Esprocarb, Compound 5 / Dimron, Compound 5 / Dimepiperate, Compound 5 / Esprocarb, Compound 6 / Dimron, Compound 6 / Dimepiperate, Compound 6 / Esprocarb, Compound 7 / Dimron, Compound 7 / Dimepiperate, Compound 7 / Esprocarb, Compound / Daimuron, Compound 8 / Dimepiperate, Compound 8 / Esprocarb, Compound 9 / Dimron, Compound 9 / Dimepiperate, Compound 9 / Esprocarb, Compound 10 / Dimron, Compound 10 / Dimepiperate, Compound 10 / Esprocarb, Compound 11 / Dimron, Compound 11 / Dipipiperate, Compound 11 / Esprocarb, Compound 12 / Dimron, Compound 12 / Dimepiperate, Compound 12 / Esprocarb, Compound 13 / Dimron, Compound 13 / Dipipiperate, Compound 13 / Esprocarb, Compound 14 / Dimron, Compound 14 / Dimepiperate, Compound 14 / Esprocarb, Compound 15 / Dimron, Compound 15 / Dimepiperate, Compound 15 / Esprocarb, Compound 16 / Dimron, Compound 16 / Dimepipe , Compound 16 / Esprocarb, Compound 17 / Dimron, Compound 17 / Dimepiperate, Compound 17 / Esprocarb, Compound 18 / Dimron, Compound 18 / Dimepiperate, Compound 18 / Esprocarb, Compound 19 / Dimron, Compound 19 / Dimepiperate, Compound 19 / Esprocarb, Compound 20 / Dimron, Compound 20 / Dimepiperate, Compound 20 / Esprocarb, Compound 21 / Dimron, Compound 21 / Dimepiperate, Compound 21 / Esprocarb. In addition to the compound (A) and herbicides that can be applied at the same time, in addition to at least one compound selected from diemron, dimethylpiperate and esprocarb, the compounds described in Table 2 can be mentioned as the compounds of Group B. Furthermore, when simultaneously applying the compound (A) and at least one compound selected from Daimlon, dimethylpiperate and esprocarb, the compounds shown in Table 2 can also be applied simultaneously.

In the present invention, in application, each compound may be applied individually or as a mixed composition. When each is applied individually, it may be applied at the same time or may be processed separately as long as they are close in time, and both cases are included in the method of the present invention.

Specific combinations with the compounds listed in Table 2 that can be applied simultaneously with Compound (A) are shown in Table 3.

[Table 3]
――――――――――――――――――――――――――――――――――
Examples of combinations of compounds that can be applied simultaneously
――――――――――――――――――――――――――――――――――
Compound 1 / Pyrazosulfuron ethyl, Compound 1 / Bensulfuron methyl, Compound 1 / Sinosulfuron, Compound 1 / Imazosulfuron, Compound 1 / Azimusulfuron, Compound 1 / Halosulfuron methyl, Compound 1 / Cyclosulfamuron, Compound 1 / Ethoxy Sulfuron, Compound 1 / Pyrazolate, Compound 1 / Pyrazoxifene, Compound 1 / Benzophenap, Compound 1 / Bromobutide, Compound 1 / Naproanilide, Compound 1 / Pretilachlor, Compound 1 / Butachlor, Compound 1 / Tenylchlor, Compound 1 / CNP, Compound 1 / Clomethoxynil, Compound 1 / Bifenox, Compound 1 / Oxadiazone, Compound 1 / Oxadialgyl, Compound 1 / Pentoxazone, Compound 1 / Caffentrol, Compound 1 / Oxadichromone, Compound 1 / indanophan, compound 1 / pyriminobacmethyl, compound 1 / cyhalohop butyl, compound 1 / fentrazamide, compound 1 / mefenacet, compound 1 / butenachlor, compound 1 / dithiopyr, compound 1 / benfresate, compound 1 / pyributycarb Compound 1 / Benio curve, Compound 1 / Molinate, Compound 1 / Buta mifos, Compound 1 / quinclolac, Compound 1 / Symmethrin, Compound 1 / Cymethrin, Compound 1 / Benzulide, Compound 1 / Dimetamethrin, Compound 1 / MCPA, Compound 1 / MCPB Compound 1 / Etobenzanide, Compound 1 / cumyluron, Compound 1 / benzobicyclone, Compound 1 / Pyriphthalide, Compound 1 / Bispyribac, Compound 1 / Pyraclonil, Compound 1 / Anilophos, Compound 1 / OK-701, Compound 1 / Penoxthram, Compound 1 / AVH-301, Compound 1 / KUH-021, Compound 1 / TH-547, Compound 1 / Bentazone, Compound 1 / 2,4-PA, Compound 1 / Metamihop, Compound 1 / Full Cetosulfuron, compound 1 / HOK-201, compound 1 / mesotrione, compound 1 / propanyl, compound 1 / quinoclamin, compound 1 / chromepprop,
Compound 2 / Pyrazosulfuron ethyl, Compound 2 / Bensulfuron methyl, Compound 2 / Sinosulfuron, Compound 2 / Imasosulfuron, Compound 2 / Azylsulfuron, Compound 2 / Halosulfuron methyl, Compound 2 / Cyclosulfamlone, Compound 2 / Ethoxy Sulfuron, Compound 2 / Pyrazolate, Compound 2 / Pyrazoxifene, Compound 2 / Benzofenap, Compound 2 / Bromobutide, Compound 2 / Naproanilide, Compound 2 / Pretilachlor, Compound 2 / Butachlor, Compound 2 / Tenylchlor, Compound 2 / CNP, Compound 2 / Clomethoxynil, Compound 2 / Bifenox, Compound 2 / Oxadiazone, Compound 2 / Oxadiargyl, Compound 2 / Pentoxazone, Compound 2 / Cafentrol, Compound 2 / Oxadiclomephone, Compound 2 / Indanophan, Compound 2 / Pyriminobacmethyl, Compound 2 / Cyhalohop Butyl, Compound 2 / Fentrazamide, Compound 2 / Mefenacet, Compound 2 / Butenachlor, Compound 2 / Dithiopyr, Compound 2 / Benfrecetate, Compound 2 / Pyributicarb Compound 2 / Bencho curve, Compound 2 / Molinate, Compound 2 / Butamifoss, Compound 2 / Quinclorac, Compound 2 / Symmethrin, Compound 2 / Simetrin, Compound 2 / Benzulide, Compound 2 / Dimetamethrin, Compound 2 / MCPA, Compound 2 / MCPB Compound 2 / Etobenzanide, Compound 2 / cumyluron, Compound 2 / benzobicyclone, Compound 2 / pyriphthalide, Compound 2 / bispyribac, Compound 2 / pyracuronyl, Compound 2 / anilophos, Compound 2 / OK-701, Compound 2 / Penox slam, Compound 2 / AVH-301, Compound 2 / KUH-021, Compound 2 / TH-547, Compound 2 / Bentazone, Compound 2 / 2,4-PA, Compound 2 / Metamihop, Compound 2 / Full Cetosulfuron, compound 2 / HOK-201, compound 2 / mesotrione, compound 2 / propanyl, compound 2 / quinoclamin, compound 2 / clomeprop,
Compound 3 / pyrazolsulfuron ethyl, compound 3 / bensulfuron methyl, compound 3 / sinosulfuron, compound 3 / imazosulfuron, compound 3 / azimsulfuron, compound 3 / halosulfuron methyl, compound 3 / cyclosulfamlone, compound 3 / ethoxy Sulfuron, Compound 3 / Pyrazolate, Compound 3 / Pyrazoxifene, Compound 3 / Benzofenap, Compound 3 / Bromobutide, Compound 3 / Naproanilide, Compound 3 / Pretilachlor, Compound 3 / Butachlor, Compound 3 / Tenylchlor, Compound 3 / CNP, Compound 3 / Clomethoxynil, Compound 3 / Bifenox, Compound 3 / Oxadiazone, Compound 3 / Oxadiargyl, Compound 3 / Pentoxazone, Compound 3 / Cafentrol, Compound 3 / Oxadiclomephone, Compound 3 / Indanophan, Compound 3 / Pyriminobacmethyl, Compound 3 / Cyhalohop butyl, Compound 3 / Fentrazamide, Compound 3 / Mefenacet, Compound 3 / Butenachlor, Compound 3 / Dithiopyr, Compound 3 / Benfrecetate, Compound 3 / Pyributicarb Compound 3 / Bencho curve, Compound 3 / Molinate, Compound 3 / Buta mifos, Compound 3 / Quinclorac, Compound 3 / Symmethrin, Compound 3 / Cymethrin, Compound 3 / Benzulide, Compound 3 / Dimetamethrin, Compound 3 / MCPA, Compound 3 / MCPB Compound 3 / Etobenzanide, Compound 3 / cumyluron, Compound 3 / benzobicyclone, Compound 3 / pyriphthalide, Compound 3 / bispyribac, Compound 3 / pyracuronyl, Compound 3 / anilophos, Compound 3 / OK-701, Compound 3 / Penox slam, Compound 3 / AVH-301, Compound 3 / KUH-021, Compound 3 / TH-547, Compound 3 / Bentazone, Compound 3 / 2,4-PA, Compound 3 / Metamihop, Compound 3 / Full Cetosulfuron, compound 3 / HOK-201, compound 3 / mesotrione, compound 3 / propanyl, compound 3 / quinoclamin, compound 3 / chromeprop,
Compound 4 / Pyrazosulfuron ethyl, Compound 4 / Bensulfuron methyl, Compound 4 / Sinosulfuron, Compound 4 / Imasosulfuron, Compound 4 / Azylsulfuron, Compound 4 / Halosulfuron methyl, Compound 4 / Cyclosulfamlone, Compound 4 / Ethoxy Sulfuron, Compound 4 / Pyrazolate, Compound 4 / Pyrazoxifene, Compound 4 / Benzofenap, Compound 4 / Bromobutide, Compound 4 / Naproanilide, Compound 4 / Pretilachlor, Compound 4 / Butachlor, Compound 4 / Tenylchlor, Compound 4 / CNP, Compound 4 / Clomethoxynil, Compound 4 / Bifenox, Compound 4 / Oxadiazone, Compound 4 / Oxadiargyl, Compound 4 / Pentoxazone, Compound 4 / Cafenstrol, Compound 4 / Oxadiclomephone, Compound 4 / Indanophan, Compound 4 / Pyriminobacmethyl, Compound 4 / Cyhalohop butyl, Compound 4 / Fentrazamide, Compound 4 / Mefenacet, Compound 4 / Butenachlor, Compound 4 / Dithiopyr, Compound 4 / Benfrecetate, Compound 4 / Pyributicarb Compound 4 / Bencho curve, Compound 4 / Molinate, Compound 4 / Buta mifos, Compound 4 / Quincrolack, Compound 4 / Symmethrin, Compound 4 / Cymethrin, Compound 4 / Benzulide, Compound 4 / Dimetamethrin, Compound 4 / MCPA, Compound 4 / MCPB Compound 4 / Etobenzanide, Compound 4 / cumyluron, Compound 4 / Benzobicyclone, Compound 4 / Pyriphthalide, Compound 4 / Bispyribac, Compound 4 / Pyraclonil, Compound 4 / Anilophos, Compound 4 / OK-701, Compound 4 / Penox slam, Compound 4 / AVH-301, Compound 4 / KUH-021, Compound 4 / TH-547, Compound 4 / Bentazone, Compound 4 / 2,4-PA, Compound 4 / Metamihop, Compound 4 / Full Cetosulfuron, compound 4 / HOK-201, compound 4 / mesotrione, compound 4 / propanyl, compound 4 / quinoclamin, compound 4 / chromeprop,
Compound 5 / Pyrazosulfuron ethyl, Compound 5 / Bensulfuron methyl, Compound 5 / Sinosulfuron, Compound 5 / Imasosulfuron, Compound 5 / Azylsulfuron, Compound 5 / Halosulfuron methyl, Compound 5 / Cyclosulfamlone, Compound 5 / Ethoxy Sulfuron, Compound 5 / Pyrazolate, Compound 5 / Pyrazoxifene, Compound 5 / Benzofenap, Compound 5 / Bromobutide, Compound 5 / Naproanilide, Compound 5 / Pretilachlor, Compound 5 / Butachlor, Compound 5 / Tenylchlor, Compound 5 / CNP, Compound 5 / Clomethoxynil, Compound 5 / Bifenox, Compound 5 / Oxadiazone, Compound 5 / Oxadialgyl, Compound 5 / Pentoxazone, Compound 5 / Cafentrol, Compound 5 / Oxadiclomephone, Compound 5 / Indanophan, Compound 5 / Pyriminobacmethyl, Compound 5 / Cyhalohop butyl, Compound 5 / Fentrazamide, Compound 5 / Mefenacet, Compound 5 / Butenachlor, Compound 5 / Dithiopyr, Compound 5 / Benfrecetate, Compound 5 / Pyributicarb Compound 5 / Bencho curve, Compound 5 / Molinate, Compound 5 / Buta mifos, Compound 5 / Quinclorac, Compound 5 / Symmethrin, Compound 5 / Cymethrin, Compound 5 / Benzulide, Compound 5 / Dimetamethrin, Compound 5 / MCPA, Compound 5 / MCPB , Compound 5 / Etobenzanide, Compound 5 / cumyluron, Compound 5 / Benzobicyclone, Compound 5 / Pyriphthalide, Compound 5 / Bispyribac, Compound 5 / Pyraclonil, Compound 5 / Anilophos, Compound 5 / OK-701, Compound 5 / Penox slam, Compound 5 / AVH-301, Compound 5 / KUH-021, Compound 5 / TH-547, Compound 5 / Bentazone, Compound 5 / 2,4-PA, Compound 5 / Metamihop, Compound 5 / Full Cetosulfuron, compound 5 / HOK-201, compound 5 / mesotrione, compound 5 / propanyl, compound 5 / quinoclamin, compound 5 / clomeprop,
Compound 6 / Pyrazosulfuron ethyl, Compound 6 / Bensulfuron methyl, Compound 6 / Sinosulfuron, Compound 6 / Imasosulfuron, Compound 6 / Azylsulfuron, Compound 6 / Halosulfuron methyl, Compound 6 / Cyclosulfamlone, Compound 6 / Ethoxy Sulfuron, Compound 6 / Pyrazolate, Compound 6 / Pyrazoxifene, Compound 6 / Benzofenap, Compound 6 / Bromobutide, Compound 6 / Naproanilide, Compound 6 / Pretilachlor, Compound 6 / Butachlor, Compound 6 / Tenylchlor, Compound 6 / CNP, Compound 6 / Clomethoxynil, Compound 6 / Bifenox, Compound 6 / Oxadiazone, Compound 6 / Oxadiargyl, Compound 6 / Pentoxazone, Compound 6 / Caffentrol, Compound 6 / Oxadiclomephone, Compound 6 / Indanophan, Compound 6 / Pyriminobacmethyl, Compound 6 / Cyhalohop butyl, Compound 6 / Fentrazamide, Compound 6 / Mefenacet, Compound 6 / Butenachlor, Compound 6 / Dithiopyr, Compound 6 / Benfrecetate, Compound 6 / Pyributicarb Compound 6 / Bencho curve, Compound 6 / Molinate, Compound 6 / Butamifoss, Compound 6 / Quinchlorac, Compound 6 / Symmethrin, Compound 6 / Cymethrin, Compound 6 / Benzulide, Compound 6 / Dimetamethrin, Compound 6 / MCPA, Compound 6 / MCPB , Compound 6 / Etobenzanide, Compound 6 / cumyluron, Compound 6 / Benzobicyclone, Compound 6 / Pyriphthalide, Compound 6 / Bispyribac, Compound 6 / Pyraclonil, Compound 6 / Anilophos, Compound 6 / OK-701, Compound 6 / penox slam, Compound 6 / AVH-301, Compound 6 / KUH-021, Compound 6 / TH-547, Compound 6 / Bentazone, Compound 6 / 2,4-PA, Compound 6 / Metamihop, Compound 6 / Full Cetosulfuron, compound 6 / HOK-201, compound 6 / mesotrione, compound 6 / propanyl, compound 6 / quinoclamin, compound 6 / clomeprop,
Compound 7 / Pyrazosulfuron ethyl, Compound 7 / Bensulfuron methyl, Compound 7 / Cinosulfuron, Compound 7 / Imasosulfuron, Compound 7 / Azylsulfuron, Compound 7 / Halosulfuron methyl, Compound 7 / Cyclosulfamlone, Compound 7 / Ethoxy Sulfuron, Compound 7 / Pyrazolate, Compound 7 / Pyrazoxifene, Compound 7 / Benzofenap, Compound 7 / Bromobutide, Compound 7 / Naproanilide, Compound 7 / Pretilachlor, Compound 7 / Butachlor, Compound 7 / Tenylchlor, Compound 7 / CNP, Compound 7 / Clomethoxynil, Compound 7 / Bifenox, Compound 7 / Oxadiazone, Compound 7 / Oxadiargyl, Compound 7 / Pentoxazone, Compound 7 / Caffentrol, Compound 7 / Oxadichromene, Compound 7 / Indanophan, Compound 7 / Pyriminobacmethyl, Compound 7 / Cyhalohop butyl, Compound 7 / Fentrazamide, Compound 7 / Mefenacet, Compound 7 / Butenachlor, Compound 7 / Dithiopyr, Compound 7 / Benfrecetate, Compound 7 / Pyributicarb Compound 7 / Bencho curve, Compound 7 / Molinate, Compound 7 / Buta mifos, Compound 7 / Quinclorac, Compound 7 / Symmethrin, Compound 7 / Cymethrin, Compound 7 / Benzulide, Compound 7 / Dimetamethrin, Compound 7 / MCPA, Compound 7 / MCPB , Compound 7 / Etobenzanide, Compound 7 / cumyluron, Compound 7 / Benzobicyclone, Compound 7 / Pyriphthalide, Compound 7 / Bispyribac, Compound 7 / Pyraclonil, Compound 7 / Anilophos, Compound 7 / OK-701, Compound 7 / Penox slam, Compound 7 / AVH-301, Compound 7 / KUH-021, Compound 7 / TH-547, Compound 7 / Bentazone, Compound 7 / 2,4-PA, Compound 7 / Metamihop, Compound 7 / Full Cetosulfuron, compound 7 / HOK-201, compound 7 / mesotrione, compound 7 / propanyl, compound 7 / quinoclamine, compound 7 / clomeprop,
Compound 8 / Pyrazosulfuron ethyl, Compound 8 / Bensulfuron methyl, Compound 8 / Sinosulfuron, Compound 8 / Imasosulfuron, Compound 8 / Azylsulfuron, Compound 8 / Halosulfuron methyl, Compound 8 / Cyclosulfamlone, Compound 8 / Ethoxy Sulfuron, Compound 8 / Pyrazolate, Compound 8 / Pyrazoxifene, Compound 8 / Benzofenap, Compound 8 / Bromobutide, Compound 8 / Naproanilide, Compound 8 / Pretilachlor, Compound 8 / Butachlor, Compound 8 / Tenylchlor, Compound 8 / CNP, Compound 8 / Clomethoxynil, Compound 8 / Bifenox, Compound 8 / Oxadiazone, Compound 8 / Oxadialgyl, Compound 8 / Pentoxazone, Compound 8 / Caffentrol, Compound 8 / Oxadiclomephone, Compound 8 / Indanophan, Compound 8 / Pyriminobacmethyl, Compound 8 / Cyhalohopbutyl, Compound 8 / Fentrazamide, Compound 8 / Mefenacet, Compound 8 / Butenachlor, Compound 8 / Dithiopyr, Compound 8 / Benfrecetate, Compound 8 / Pyributicarb Compound 8 / Bencho curve, Compound 8 / Molinate, Compound 8 / Butamifoss, Compound 8 / Quinclorac, Compound 8 / Symmethrin, Compound 8 / Cymethrin, Compound 8 / Benzulide, Compound 8 / Dimetamethrin, Compound 8 / MCPA, Compound 8 / MCPB , Compound 8 / Etobenzanide, Compound 8 / cumyluron, Compound 8 / Benzobicyclone, Compound 8 / Pyriphthalide, Compound 8 / Bispyribac, Compound 8 / Pyraclonil, Compound 8 / Anilophos, Compound 8 / OK-701, Compound 8 / Penox slam, Compound 8 / AVH-301, Compound 8 / KUH-021, Compound 8 / TH-547, Compound 8 / Bentazone, Compound 8 / 2,4-PA, Compound 8 / Metamihop, Compound 8 / Full Cetosulfuron, compound 8 / HOK-201, compound 8 / mesotrione, compound 8 / propanyl, compound 8 / quinoclamin, compound 8 / clomeprop,
Compound 9 / Pyrazosulfuron ethyl, Compound 9 / Bensulfuron methyl, Compound 9 / Sinosulfuron, Compound 9 / Imasosulfuron, Compound 9 / Azylsulfuron, Compound 9 / Halosulfuron methyl, Compound 9 / Cyclosulfamlone, Compound 9 / Ethoxy Sulfuron, Compound 9 / Pyrazolate, Compound 9 / Pyrazoxifene, Compound 9 / Benzophenap, Compound 9 / Bromobutide, Compound 9 / Naproanilide, Compound 9 / Pretilachlor, Compound 9 / Butachlor, Compound 9 / Tenylchlor, Compound 9 / CNP, Compound 9 / Clomethoxynil, Compound 9 / Bifenox, Compound 9 / Oxadiazone, Compound 9 / Oxadiargyl, Compound 9 / Pentoxazone, Compound 9 / Caffentrol, Compound 9 / Oxadiclomephone, Compound 9 / Indanophan, Compound 9 / Pyriminobacmethyl, Compound 9 / Cyhalohop butyl, Compound 9 / Fentrazamide, Compound 9 / Mefenacet, Compound 9 / Butenachlor, Compound 9 / Dithiopyr, Compound 9 / Benfrecetate, Compound 9 / Pyributicarb Compound 9 / Bencho curve, Compound 9 / Molinate, Compound 9 / Butamifoss, Compound 9 / Quinclorac, Compound 9 / Symmethrin, Compound 9 / Cymethrin, Compound 9 / Benzulide, Compound 9 / Dimetamethrin, Compound 9 / MCPA, Compound 9 / MCPB , Compound 9 / Etobenzanide, Compound 9 / cumyluron, Compound 9 / Benzobicyclone, Compound 9 / Pyriphthalide, Compound 9 / Bispyribac, Compound 9 / Pyraclonil, Compound 9 / Anilophos, Compound 9 / OK-701, Compound 9 / penox slam, Compound 9 / AVH-301, Compound 9 / KUH-021, Compound 9 / TH-547, Compound 9 / Bentazone, Compound 9 / 2,4-PA, Compound 9 / Metamihop, Compound 9 / Full Cetosulfuron, compound 9 / HOK-201, compound 9 / mesotrione, compound 9 / propanyl, compound 9 / quinoclamin, compound 9 / clomeprop,
Compound 10 / Pyrazosulfuron ethyl, Compound 10 / Bensulfuron methyl, Compound 10 / Sinosulfuron, Compound 10 / Imasosulfuron, Compound 10 / Azimsulfuron, Compound 10 / Halosulfuron methyl, Compound 10 / Cyclosulfamlone, Compound 10 / Ethoxy Sulfuron, Compound 10 / Pyrazolate, Compound 10 / Pyrazoxifene, Compound 10 / Benzofenap, Compound 10 / Bromobutide, Compound 10 / Naproanilide, Compound 10 / Pretilachlor, Compound 10 / Butachlor, Compound 10 / Tenylchlor, Compound 10 / CNP, Compound 10 / Clomethoxynil, Compound 10 / Bifenox, Compound 10 / Oxadiazone, Compound 10 / Oxadialgyl, Compound 10 / Pentoxazone, Compound 10 / Kafen Trol, Compound 10 / Oxadiclomephone, Compound 10 / Indanophan, Compound 10 / Pyriminobacmethyl, Compound 10 / Cyhalohopbutyl, Compound 10 / Fentrazamide, Compound 10 / Mefenacet, Compound 10 / Butenachlor, Compound 10 / Dithiopyr, Compound 10 / Benfresate, compound 10 / pyributycarb, compound 10 / bencho curve, compound 10 / molinate, compound 10 / butamifos, compound 10 / quinclolac, compound 10 / simmesrin, compound 10 / cymetrin, compound 10 / benthlide, compound 10 / dimetamethrin, compound 10 / MCPA, compound 10 / MCPB, compound 10 / ethobenzanide, compound 10 / cumyluron, compound 10 / benzobicyclone, compound 10 / pyriphthalide, Product 10 / bispyribac, compound 10 / pyracuronyl, compound 10 / anilophos, compound 10 / OK-701, compound 10 / penoxsulam, compound 10 / AVH-301, compound 10 / KUH-021, compound 10 / TH-547, compound 10 / Bentazone, Compound 10 / 2,4-PA, Compound 10 / Metamihop, Compound 10 / Furcetosulfuron, Compound 10 / HOK-201, Compound 10 / Mesotrione, Compound 10 / propanyl, Compound 10 / Quinoclamine, Compound 10 / Chromprop ,
Compound 11 / Pyrazosulfuron ethyl, Compound 11 / Bensulfuron methyl, Compound 11 / Sinosulfuron, Compound 11 / Imasosulfuron, Compound 11 / Azylsulfuron, Compound 11 / Halosulfuron methyl, Compound 11 / Cyclosulfamlone, Compound 11 / Ethoxy Sulfuron, Compound 11 / Pyrazolate, Compound 11 / Pyrazoxifene, Compound 11 / Benzofenap, Compound 11 / Bromobutide, Compound 11 / Naproanilide, Compound 11 / Pretilachlor, Compound 11 / Butachlor, Compound 11 / Tenylchlor, Compound 11 / CNP, Compound 11 / Clomethoxynil, Compound 11 / Bifenox, Compound 11 / Oxadiazone, Compound 11 / Oxadiargyl, Compound 11 / Pentoxazone, Compound 11 / Kafen Trol, Compound 11 / Oxadiclomephone, Compound 11 / Indanophan, Compound 11 / Pyriminobacmethyl, Compound 11 / Cyhalohopbutyl, Compound 11 / Fentrazamide, Compound 11 / Mefenacet, Compound 11 / Butenachlor, Compound 11 / Dithiopyr, Compound 11 / Benfresate, compound 11 / pyributycarb, compound 11 / bencho curve, compound 11 / molinate, compound 11 / butamifos, compound 11 / quinclolac, compound 11 / simmesrin, compound 11 / cymetrin, compound 11 / benthlide, compound 11 / dimetamethrin, compound 11 / MCPA, Compound 11 / MCPB, Compound 11 / Etobenzanide, Compound 11 / cumyluron, Compound 11 / Benzobicyclone, Compound 11 / Pyriphthalide Compound 11 / bispyribac, compound 11 / pyracuronyl, compound 11 / anilophos, compound 11 / OK-701, compound 11 / penoxsulam, compound 11 / AVH-301, compound 11 / KUH-021, compound 11 / TH-547, compound 11 / Bentazone, Compound 11 / 2,4-PA, Compound 11 / Metamihop, Compound 11 / Furcetosulfuron, Compound 11 / HOK-201, Compound 11 / Mesotrione, Compound 11 / Propanyl, Compound 11 / Quinoclamine, Compound 11 / Chromprop ,
Compound 12 / Pyrazosulfuron ethyl, Compound 12 / Bensulfuron methyl, Compound 12 / Cinosulfuron, Compound 12 / Imasosulfuron, Compound 12 / Azylsulfuron, Compound 12 / Halosulfuron methyl, Compound 12 / Cyclosulfamlone, Compound 12 / Ethoxy Sulfuron, Compound 12 / Pyrazolate, Compound 12 / Pyrazoxifene, Compound 12 / Benzofenap, Compound 12 / Bromobutide, Compound 12 / Naproanilide, Compound 12 / Pretilachlor, Compound 12 / Butachlor, Compound 12 / Tenylchlor, Compound 12 / CNP, Compound 12 / Clomethoxynil, Compound 12 / Bifenox, Compound 12 / Oxadiazone, Compound 12 / Oxadiargyl, Compound 12 / Pentoxazone, Compound 12 / Kafen Trol, Compound 12 / oxadichromemephone, Compound 12 / Indanophan, Compound 12 / Pyriminobacmethyl, Compound 12 / Cyhalohopbutyl, Compound 12 / Fentrazamide, Compound 12 / Mefenacet, Compound 12 / Butenachlor, Compound 12 / Dithiopyr, Compound 12 / Benfresate, compound 12 / pyributycarb, compound 12 / bencho curve, compound 12 / molinate, compound 12 / butamifos, compound 12 / quinclolac, compound 12 / simmesrin, compound 12 / cymetrin, compound 12 / benthlide, compound 12 / dimetamethrin, compound 12 / MCPA, Compound 12 / MCPB, Compound 12 / Etobenzanide, Compound 12 / cumyluron, Compound 12 / Benzobicyclone, Compound 12 / Pyriphthalide Product 12 / bispyribac, compound 12 / pyracuronyl, compound 12 / anilophos, compound 12 / OK-701, compound 12 / penoxsulam, compound 12 / AVH-301, compound 12 / KUH-021, compound 12 / TH-547, compound 12 / Bentazone, Compound 12 / 2,4-PA, Compound 12 / Metamihop, Compound 12 / Furcetosulfuron, Compound 12 / HOK-201, Compound 12 / Mesotrione, Compound 12 / propanyl, Compound 12 / Quinoclamine, Compound 12 / Chromprop ,
Compound 13 / Pyrazosulfuron ethyl, Compound 13 / Bensulfuron methyl, Compound 13 / Sinosulfuron, Compound 13 / Imasosulfuron, Compound 13 / Azimsulfuron, Compound 13 / Halosulfuron methyl, Compound 13 / Cyclosulfamlone, Compound 13 / Ethoxy Sulfuron, Compound 13 / Pyrazolate, Compound 13 / Pyrazoxifene, Compound 13 / Benzofenap, Compound 13 / Bromobutide, Compound 13 / Naproanilide, Compound 13 / Pretilachlor, Compound 13 / Butachlor, Compound 13 / Tenylchlor, Compound 13 / CNP, Compound 13 / Clomethoxynil, Compound 13 / Bifenox, Compound 13 / Oxadiazone, Compound 13 / Oxadiargyl, Compound 13 / Pentoxazone, Compound 13 / Kafen Trol, Compound 13 / Oxadiclomephone, Compound 13 / Indanophan, Compound 13 / Pyriminobacmethyl, Compound 13 / Cyhalohopbutyl, Compound 13 / Fentrazamide, Compound 13 / Mefenacet, Compound 13 / Butenachlor, Compound 13 / Dithiopyr, Compound 13 / Benfresate, compound 13 / pyributicarb, compound 13 / bencho curve, compound 13 / molinate, compound 13 / butamifos, compound 13 / quinclolac, compound 13 / simmesrin, compound 13 / cymetrin, compound 13 / benthlide, compound 13 / dimetamethrin, compound 13 / MCPA, Compound 13 / MCPB, Compound 13 / Etobenzanide, Compound 13 / cumyluron, Compound 13 / Benzobicyclone, Compound 13 / Pyriphthalide, Product 13 / bispyribac, compound 13 / pyracuronyl, compound 13 / anilophos, compound 13 / OK-701, compound 13 / penoxsulam, compound 13 / AVH-301, compound 13 / KUH-021, compound 13 / TH-547, compound 13 / Bentazone, Compound 13 / 2,4-PA, Compound 13 / Metamihop, Compound 13 / Furcetosulfuron, Compound 13 / HOK-201, Compound 13 / Mesotrione, Compound 13 / Propanyl, Compound 13 / Quinoclamine, Compound 13 / Chromprop , Compound 14 / Pyrazosulfuron ethyl, Compound 14 / Bensulfuron methyl, Compound 14 / Cinosulfuron, Compound 14 / Imasosulfuron, Compound 14 / Azimsulfuron, Compound 14 / Halosulfuron methyl, Compound 14 / Cyclosulfur Hamron, compound 14 / ethoxysulfuron, compound 14 / pyrazolate, compound 14 / pyrazoxifene, compound 14 / benzophenap, compound 14 / bromobutide, compound 14 / naproanilide, compound 14 / pretilachlor, compound 14 / butachlor, compound 14 / tenyl chlor , Compound 14 / CNP, Compound 14 / Clomethoxynil, Compound 14 / Bifenox, Compound 14 / Oxadiazone, Compound 14 / Oxadialgyl, Compound 14 / Pentoxazone, Compound 14 / Kafenthrol, Compound 14 / Oxadichromene, Compound 14 / Indanophane, Compound 14 / Pyri Minobacmethyl, Compound 14 / Cyhalohop Butyl, Compound 14 / Fentrazamide, Compound 14 / Mefenacet, Compound 14 / Butenac Compound 14 / dithiopyr, compound 14 / benfresate, compound 14 / pyributicalbub, compound 14 / benchocarb, compound 14 / molinate, compound 14 / butamifos, compound 14 / quinclolac, compound 14 / simmesrin, compound 14 / cymetrin, compound 14 / Benzuride, Compound 14 / Dimetamethrin, Compound 14 / MCPA, Compound 14 / MCPB, Compound 14 / Etobenzanide, Compound 14 / Cumilron, Compound 14 / Benzobicyclone, Compound 14 / Pyriphthalide, Compound 14 / Bispyrivac, Compound 14 / Pyraclonil , Compound 14 / anilophos, Compound 14 / OK-701, Compound 14 / Penoxsulam, Compound 14 / AVH-301, Compound 14 / KUH-021, Compound 14 / TH-547, Compound 14 / Bentazone, Compound 14 / 2,4-PA, Compound 14 / Metamihop, Compound 14 / Furcetosulfuron, Compound 14 / HOK-201, Compound 14 / Mesotrione, Compound 14 / Propanyl, Compound 14 / Quinoclamine, Compound 14 / Chrome prop,
Compound 15 / Pyrazosulfuron ethyl, Compound 15 / Bensulfuron methyl, Compound 15 / Cinosulfuron, Compound 15 / Imasosulfuron, Compound 15 / Azylsulfuron, Compound 15 / Halosulfuron methyl, Compound 15 / Cyclosulfamlone, Compound 15 / Ethoxy Sulfuron, Compound 15 / Pyrazolate, Compound 15 / Pyrazoxifene, Compound 15 / Benzofenap, Compound 15 / Bromobutide, Compound 15 / Naproanilide, Compound 15 / Pretilachlor, Compound 15 / Butachlor, Compound 15 / Tenylchlor, Compound 15 / CNP, Compound 15 / Clomethoxynil, Compound 15 / Bifenox, Compound 15 / Oxadiazone, Compound 15 / Oxadiargyl, Compound 15 / Pentoxazone, Compound 15 / Kafen Trol, Compound 15 / oxadichromemephone, Compound 15 / Indanophan, Compound 15 / Pyriminobacmethyl, Compound 15 / Cyhalohopbutyl, Compound 15 / Fentrazamide, Compound 15 / Mefenacet, Compound 15 / Butenachlor, Compound 15 / Dithiopyr, Compound 15 / Benfresate, compound 15 / pyributicarb, compound 15 / bencho curve, compound 15 / molinate, compound 15 / butamifos, compound 15 / quinclolac, compound 15 / cinmesrin, compound 15 / cymetrin, compound 15 / benthlide, compound 15 / dimetamethrin, compound 15 / MCPA, Compound 15 / MCPB, Compound 15 / Etobenzanide, Compound 15 / cumyluron, Compound 15 / Benzobicyclone, Compound 15 / Pyriphthalide Compound 15 / bispyribac, compound 15 / pyracuronyl, compound 15 / anilophos, compound 15 / OK-701, compound 15 / penoxsulam, compound 15 / AVH-301, compound 15 / KUH-021, compound 15 / TH-547, compound 15 / Bentazone, Compound 15 / 2,4-PA, Compound 15 / Metamihop, Compound 15 / Furcetosulfuron, Compound 15 / HOK-201, Compound 15 / Mesotrione, Compound 15 / Propanyl, Compound 15 / Quinoclamine, Compound 15 / Chromprop ,
Compound 16 / Pyrazosulfuron ethyl, Compound 16 / Bensulfuron methyl, Compound 16 / Cinosulfuron, Compound 16 / Imasosulfuron, Compound 16 / Azimsulfuron, Compound 16 / Halosulfuron methyl, Compound 16 / Cyclosulfamlone, Compound 16 / Ethoxy Sulfuron, Compound 16 / Pyrazolate, Compound 16 / Pyrazoxifene, Compound 16 / Benzofenap, Compound 16 / Bromobutide, Compound 16 / Naproanilide, Compound 16 / Pretilachlor, Compound 16 / Butachlor, Compound 16 / Tenylchlor, Compound 16 / CNP, Compound 16 / Clomethoxynil, Compound 16 / Bifenox, Compound 16 / Oxadiazone, Compound 16 / Oxadiargyl, Compound 16 / Pentoxazone, Compound 16 / Kafen Trol, Compound 16 / Oxadiclomephone, Compound 16 / Indanophan, Compound 16 / Pyriminobacmethyl, Compound 16 / Cyhalohopbutyl, Compound 16 / Fentrazamide, Compound 16 / Mefenacet, Compound 16 / Butenachlor, Compound 16 / Dithiopyr, Compound 16 / Benfresate, compound 16 / pyributicarb, compound 16 / bencho curve, compound 16 / molinate, compound 16 / butamifos, compound 16 / quinclolac, compound 16 / simmesrin, compound 16 / cymetrin, compound 16 / benthlide, compound 16 / dimetamethrin, compound 16 / MCPA, Compound 16 / MCPB, Compound 16 / Etobenzanide, Compound 16 / cumyluron, Compound 16 / Benzobicyclone, Compound 16 / Pyriphthalide Compound 16 / Bispyribac, Compound 16 / Pyraclonil, Compound 16 / Anilophos, Compound 16 / OK-701, Compound 16 / Penoxsulam, Compound 16 / AVH-301, Compound 16 / KUH-021, Compound 16 / TH-547, Compound 16 / Bentazone, Compound 16 / 2,4-PA, Compound 16 / Metamihop, Compound 16 / Furcetosulfuron, Compound 16 / HOK-201, Compound 16 / Mesotrione, Compound 16 / propanyl, Compound 16 / Quinoclamine, Compound 16 / Chromprop ,
Compound 17 / Pyrazosulfuron ethyl, Compound 17 / Bensulfuron methyl, Compound 17 / Sinosulfuron, Compound 17 / Imasosulfuron, Compound 17 / Azimsulfuron, Compound 17 / Halosulfuron methyl, Compound 17 / Cyclosulfamlone, Compound 17 / Ethoxy Sulfuron, Compound 17 / Pyrazolate, Compound 17 / Pyrazoxifene, Compound 17 / Benzofenap, Compound 17 / Bromobutide, Compound 17 / Naproanilide, Compound 17 / Pretilachlor, Compound 17 / Butachlor, Compound 17 / Tenylchlor, Compound 17 / CNP, Compound 17 / Clomethoxynil, Compound 17 / Bifenox, Compound 17 / Oxadiazone, Compound 17 / Oxadiargyl, Compound 17 / Pentoxazone, Compound 17 / Kafen Trol, Compound 17 / Oxadichromene, Compound 17 / Indanophan, Compound 17 / Pyriminobacmethyl, Compound 17 / Cyhalohopbutyl, Compound 17 / Fentrazamide, Compound 17 / Mefenacet, Compound 17 / Butenachlor, Compound 17 / Dithiopyr, Compound 17 / Benfresate, compound 17 / pyributicarb, compound 17 / bencho curve, compound 17 / molinate, compound 17 / butamifos, compound 17 / quinclolac, compound 17 / simmesrin, compound 17 / cymetrin, compound 17 / benthlide, compound 17 / dimetamethrin, compound 17 / MCPA, Compound 17 / MCPB, Compound 17 / Etobenzanide, Compound 17 / cumyluron, Compound 17 / Benzobicyclone, Compound 17 / Pyriphthalide, Compound 17 / bispyribac, compound 17 / pyracuronyl, compound 17 / anilophos, compound 17 / OK-701, compound 17 / penoxsulam, compound 17 / AVH-301, compound 17 / KUH-021, compound 17 / TH-547, compound 17 / Bentazone, Compound 17 / 2,4-PA, Compound 17 / Metamihop, Compound 17 / Furcetosulfuron, Compound 17 / HOK-201, Compound 17 / Mesotrione, Compound 17 / propanyl, Compound 17 / Quinoclamine, Compound 17 / Cromepprop ,
Compound 18 / Pyrazosulfuron ethyl, Compound 18 / Bensulfuron methyl, Compound 18 / Cinosulfuron, Compound 18 / Imasosulfuron, Compound 18 / Azimsulfuron, Compound 18 / Halosulfuron methyl, Compound 18 / Cyclosulfamlone, Compound 18 / Ethoxy Sulfuron, Compound 18 / Pyrazolate, Compound 18 / Pyrazoxifene, Compound 18 / Benzofenap, Compound 18 / Bromobutide, Compound 18 / Naproanilide, Compound 18 / Pretilachlor, Compound 18 / Butachlor, Compound 18 / Tenylchlor, Compound 18 / CNP, Compound 18 / Clomethoxynil, Compound 18 / Bifenox, Compound 18 / Oxadiazone, Compound 18 / Oxadialgyl, Compound 18 / Pentoxazone, Compound 18 / Kafen Trol, Compound 18 / Oxadiclomephone, Compound 18 / Indanophan, Compound 18 / Pyriminobacmethyl, Compound 18 / Cyhalohopbutyl, Compound 18 / Fentrazamide, Compound 18 / Mefenacet, Compound 18 / Butenachlor, Compound 18 / Dithiopyr, Compound 18 / Benfresate, compound 18 / pyributicarb, compound 18 / bencho curve, compound 18 / molinate, compound 18 / butamifos, compound 18 / quinclolac, compound 18 / simmesrin, compound 18 / cymetrin, compound 18 / benthlide, compound 18 / dimetamethrin, compound 18 / MCPA, Compound 18 / MCPB, Compound 18 / Etobenzanide, Compound 18 / cumyluron, Compound 18 / Benzobicyclone, Compound 18 / Pyriphthalide Product 18 / bispyribac, compound 18 / pyracuronyl, compound 18 / anilophos, compound 18 / OK-701, compound 18 / penoxsulam, compound 18 / AVH-301, compound 18 / KUH-021, compound 18 / TH-547, compound 18 / Bentazone, Compound 18 / 2,4-PA, Compound 18 / Metamihop, Compound 18 / Furcetosulfuron, Compound 18 / HOK-201, Compound 18 / Mesotrione, Compound 18 / Propanyl, Compound 18 / Quinoclamine, Compound 18 / Chromprop ,
Compound 19 / Pyrazosulfuron ethyl, Compound 19 / Bensulfuron methyl, Compound 19 / Sinosulfuron, Compound 19 / Imasosulfuron, Compound 19 / Azylsulfuron, Compound 19 / Halosulfuron methyl, Compound 19 / Cyclosulfamlone, Compound 19 / Ethoxy Sulfuron, Compound 19 / Pyrazolate, Compound 19 / Pyrazoxifene, Compound 19 / Benzofenap, Compound 19 / Bromobutide, Compound 19 / Naproanilide, Compound 19 / Pretilachlor, Compound 19 / Butachlor, Compound 19 / Tenylchlor, Compound 19 / CNP, Compound 19 / Clomethoxynil, Compound 19 / Bifenox, Compound 19 / Oxadiazone, Compound 19 / Oxadiargyl, Compound 19 / Pentoxazone, Compound 19 / Kafen Trol, compound 19 / oxadichromemephone, compound 19 / indanophan, compound 19 / pyriminobacmethyl, compound 19 / cyhalohop butyl, compound 19 / fentrazamide, compound 19 / mefenacet, compound 19 / butenachlor, compound 19 / dithiopyr, compound 19 / Benfresate, compound 19 / pyributicalbub, compound 19 / bencho curve, compound 19 / molinate, compound 19 / butamifos, compound 19 / quinclolac, compound 19 / simmesrin, compound 19 / cymetrin, compound 19 / benthlide, compound 19 / dimetamethrin, compound 19 / MCPA, Compound 19 / MCPB, Compound 19 / Etobenzanide, Compound 19 / cumyluron, Compound 19 / Benzobicyclone, Compound 19 / Pyriphthalide, Compound 19 / bispyribac, compound 19 / pyracuronyl, compound 19 / anilophos, compound 19 / OK-701, compound 19 / penoxsulam, compound 19 / AVH-301, compound 19 / KUH-021, compound 19 / TH-547, compound 19 / Bentazone, Compound 19 / 2,4-PA, Compound 19 / Metamihop, Compound 19 / Furcetosulfuron, Compound 19 / HOK-201, Compound 19 / Mesotrione, Compound 19 / Propanyl, Compound 19 / Quinoclamine, Compound 19 / Cromepprop ,
Compound 20 / Pyrazosulfuron ethyl, Compound 20 / Bensulfuron methyl, Compound 20 / Cinosulfuron, Compound 20 / Imasosulfuron, Compound 20 / Azimusulfuron, Compound 20 / Halosulfuron methyl, Compound 20 / Cyclosulfamlone, Compound 20 / Ethoxy Sulfuron, Compound 20 / Pyrazolate, Compound 20 / Pyrazoxifene, Compound 20 / Benzofenap, Compound 20 / Bromobutide, Compound 20 / Naproanilide, Compound 20 / Pretilachlor, Compound 20 / Butachlor, Compound 20 / Tenylchlor, Compound 20 / CNP, Compound 20 / Clomethoxynil, Compound 20 / Bifenox, Compound 20 / Oxadiazone, Compound 20 / Oxadiargyl, Compound 20 / Pentoxazone, Compound 20 / Kafen Trol, Compound 20 / Oxadiclomephone, Compound 20 / Indanophan, Compound 20 / Pyriminobacmethyl, Compound 20 / Cyhalohopbutyl, Compound 20 / Fentrazamide, Compound 20 / Mefenacet, Compound 20 / Butenachlor, Compound 20 / Dithiopyr, Compound 20 / Benfresate, compound 20 / pyributicarb, compound 20 / bencho curve, compound 20 / molinate, compound 20 / butamifos, compound 20 / quinclolac, compound 20 / cinmesrin, compound 20 / cymetrin, compound 20 / benthlide, compound 20 / dimetamethrin, compound 20 / MCPA, Compound 20 / MCPB, Compound / 20 / Etobenzanide, Compound 20 / cumyluron, Compound 20 / Benzobicyclone, Compound 20 / Pyriphthalide, Compound 20 / bispyribac, compound 20 / pyracuronyl, compound 20 / anilophos, compound 20 / OK-701, compound 20 / penoxsulam, compound 20 / AVH-301, compound 20 / KUH-021, compound 20 / TH-547, compound 20 / Bentazone, Compound 20 / 2,4-PA, Compound 20 / Metamihop, Compound 20 / Frucetosulfuron, Compound 20 / HOK-201, Compound 20 / Mesotrione, Compound 20 / Propanyl, Compound 20 / Quinoclamine, Compound 20 / Chrome prop
Compound 21 / Pyrazosulfuron ethyl, Compound 21 / Bensulfuron methyl, Compound 21 / Cinosulfuron, Compound 21 / Imasosulfuron, Compound 21 / Azimsulfuron, Compound 21 / Halosulfuron methyl, Compound 21 / Cyclosulfamlone, Compound 21 / Ethoxy Sulfuron, Compound 21 / Pyrazolate, Compound 21 / Pyrazoxifene, Compound 21 / Benzofenap, Compound 21 / Bromobutide, Compound 21 / Naproanilide, Compound 21 / Pretilachlor, Compound 21 / Butachlor, Compound 21 / Tenylchlor, Compound 21 / CNP, Compound 21 / Clomethoxynil, Compound 21 / Bifenox, Compound 21 / Oxadiazone, Compound 21 / Oxadiargyl, Compound 21 / Pentoxazone, Compound 21 / Kafen Trol, Compound 21 / Oxadiclomephone, Compound 21 / Indanophan, Compound 21 / Pyriminobacmethyl, Compound 21 / Cyhalohopbutyl, Compound 21 / Fentrazamide, Compound 21 / Mefenacet, Compound 21 / Butenachlor, Compound 21 / Dithiopyr, Compound 21 / Benfresate, compound 21 / pyributycarb, compound 21 / bencho curve, compound 21 / molinate, compound 21 / butamifos, compound 21 / quinclolac, compound 21 / simmesrin, compound 21 / cymetrin, compound 21 / benthlide, compound 21 / dimetamethrin, compound 21 / MCPA, compound 21 / MCPB, compound 21 / ethobenzanide, compound 21 / cumyluron, compound 21 / benzobicyclone, compound 21 / pyriphthalide, Compound 21 / Bispyribac, Compound 21 / Pyraclonil, Compound 21 / Anilophos, Compound 21 / OK-701, Compound 21 / Penoxsulam, Compound 21 / AVH-301, Compound 21 / KUH-021, Compound 21 / TH-547, Compound 21 / Bentazone, Compound 21 / 2,4-PA, Compound 21 / Metamihop, Compound 21 / Furcetosulfuron, Compound 21 / HOK-201, Compound 21 / Mesotrione, Compound 21 / Propanyl, Compound 21 / Quinoclamine, Compound 21 / Chromprop
―――――――――――――――――――――――――――――――――

In the present invention, at least one compound selected from Daimlon, dimethylpiperate and esprocarb is usually applied in an amount of 0.001 to 100 parts by weight, preferably 0.01 to 30 parts by weight per 1 part by weight of the compound (A).
The application rate of compound (A) is usually 1 g-10 kg / ha, preferably 10 g-1 kg / ha. The application rate of at least one compound selected from Daimlon, Dimepiperate and Esprocarb is usually 1 g-10 kg / ha, preferably 10 g-3 kg / ha.
The composition of the present invention is usually mixed with a suitable solid carrier or liquid carrier, and if necessary, a surfactant, penetrant, spreading agent, thickener, antifreeze agent, binder, anti-caking agent, disintegrant. , Antifoaming agent, preservative, anti-decomposition agent, etc., and added to liquid concentrate, emulsion concentrate, wettable powder, water soluble powder, granule wettable powder (wet powder powder) water dispersible granule, water soluble granule, suspension (concentrated emulsion), emulsion (suspoemulsion), microphone Emulsion (microemulsion), dusts (dustable powder), can be put into practical use in granules (granule) and gels (gel) like any dosage form of the formulation. In addition, from the viewpoint of labor saving and safety improvement, a preparation of any of the above dosage forms can be enclosed in a water-soluble package. If necessary, it can be used in combination with a plurality of other herbicides, insecticides, fungicides, plant growth regulators, fertilizers and the like during preparation or spraying.
Examples of solid carriers include quartz, kaolinite, pyrophyllite, sericite, talc, bentonite, acid clay, attapulgite, zeolite, and diatomaceous earth, and other inorganic minerals such as calcium carbonate, ammonium sulfate, sodium sulfate, and potassium chloride. Examples include salts, synthetic silicic acid and synthetic silicates.
Examples of the liquid carrier include alcohols such as ethylene glycol, propylene glycol and isopropanol, aromatic hydrocarbons such as xylene, alkylbenzene and alkylnaphthalene, ethers such as butyl cellosolve, ketones such as cyclohexanone, and esters such as γ-butyrolactone. And acid amides such as N-methylpyrrolidone and N-octylpyrrolidone, vegetable oils such as soybean oil, rapeseed oil, cottonseed oil and castor oil, and water.
These solid and liquid carriers may be used alone or in combination of two or more.
Examples of the surfactant include polyoxyethylene alkyl ether, polyoxyethylene alkyl aryl ether, polyoxyethylene styryl phenyl ether, polyoxyethylene polyoxypropylene block copolymer, polyoxyethylene fatty acid ester, sorbitan fatty acid ester and polyoxyethylene sorbitan. Nonionic surfactant such as fatty acid ester, alkyl sulfate, alkylbenzene sulfonate, lignin sulfonate, alkyl sulfosuccinate, naphthalene sulfonate, alkyl naphthalene sulfonate, salt of formalin condensate of naphthalene sulfonate, Salt of formalin condensate of alkylnaphthalenesulfonic acid, polyoxyethylene alkylaryl ether sulfate and phosphate, polyoxyethylenes Anionic surfactants such as rylphenyl ether sulfate and phosphate, polycarboxylate and polystyrene sulfonate, cationic surfactants such as alkylamine salt and alkyl quaternary ammonium salt, and amphoteric types such as amino acid type and betaine type Surfactant is mentioned.
Although content of these surfactants is not specifically limited, The range of 0.05-20 mass parts is desirable normally with respect to 100 mass parts of preparations of this invention. These surfactants may be used alone or in combination of two or more.
At this time, a plurality of other herbicides, insecticides, fungicides, plant growth regulators, fertilizers and the like can be used in combination. In particular, by blending one or more other herbicides, it becomes possible to broaden the herbicidal spectrum, and the effects of the present invention can be made more stable.

Next, formulation examples of preparations when using the composition of the present invention are shown. However, the formulation examples of the present invention are not limited to these. In the following formulation examples, “part” means part by mass.
[Wettable powder]
Composition of the present invention 0.1-80 parts solid carrier 5-98.9 parts Surfactant 1-10 parts Others 0-5 parts Others include, for example, anti-caking agents and decomposition inhibitors.
[Emulsible concentrate]
Composition of the present invention 0.1-30 parts Liquid carrier 45-95 parts Surfactant 4.9-15 parts Others 0-10 parts Others include, for example, spreading agents, decomposition inhibitors and the like.
[Suspension concentrate]
Composition of the present invention 0.1-70 parts Liquid carrier 15-98.89 parts Surfactant 1-12 parts Others 0.01-30 parts Others include, for example, antifreezing agents, thickeners and the like.
[Water dispersible granule]
Composition of the present invention 0.1 to 90 parts Solid carrier 0 to 98.9 parts Surfactant 1 to 20 parts Others 0 to 10 parts Others include, for example, binders and decomposition inhibitors.
[Solution concentrate]
Composition of the present invention 0.01 to 70 parts Liquid carrier 20 to 99.99 parts Others 0 to 10 parts Other examples include antifreezing agents and spreading agents.
[Granule]
Composition of the present invention 0.01 to 80 parts Solid carrier 10 to 99.99 parts Others 0 to 10 parts Others include, for example, binders, decomposition inhibitors and the like.
[Dust Powder]
The composition of the present invention 0.01 to 30 parts Solid support 65 to 99.99 parts Others 0 to 5 parts Other examples include a drift inhibitor and a decomposition inhibitor.
At the time of use, the above-mentioned preparation is diluted with water 1 to 10000 times or without being diluted, and sprayed so that the active ingredient is 0.001 to 50 kg, preferably 0.01 to 10 kg per hectare (ha). .

Formulation Examples Next, specific examples of agrochemical formulations containing the compound as an active ingredient are shown, but the invention is not limited thereto. In the following formulation examples, “part” means part by mass.
[Formulation 1] wettable powder
Compound (A) 10 parts Daimlon 10 parts Pyrophyllite 74 parts Solpol 5039 4 parts (mixture of nonionic surfactant and anionic surfactant: Toho Chemical Industries, Ltd. trade name)
Carplex # 80D 2 parts (Synthetic hydrous silicic acid: Shionogi & Co., Ltd. trade name)
The above is uniformly mixed and ground to obtain a wettable powder.

[Formulation Example 2] Milk (emulsible concentrate)
Compound (A) 2 parts Daimlon 3 parts xylene 75 parts N-methylpyrrolidone 15 parts Solpol 2680 5 parts (mixture of nonionic surfactant and anionic surfactant: Toho Chemical Co., Ltd. trade name)
The above is uniformly mixed to obtain an emulsion.

[Composition Example 3] Suspension concentrate
Compound (A) 15 parts Daimlon 10 parts Agrisol S-710 10 parts (Nonionic surfactant: trade name of Kao Corporation)
Lnox 1000C 0.5 part (anionic surfactant: Toho Chemical Co., Ltd. trade name)
Xanthan gum 0.2 parts Water 64.3 parts After uniformly mixing the above, wet pulverize to make a suspension.

[Formulation Example 4] Granule wettable powder (water dispersible granule)
Compound (A) 25 parts Daimlon 50 parts Hytenol NE-15 5 parts (anionic surfactant: trade name of Daiichi Kogyo Seiyaku Co., Ltd.)
Vanillex N 10 parts (anionic surfactant: Nippon Paper Industries Co., Ltd. trade name)
Carplex # 80D 10 parts (Synthetic hydrous silicic acid: Shionogi Pharmaceutical Co., Ltd. trade name)
After uniformly mixing and pulverizing the above, a small amount of water is added, stirred and mixed, granulated with an extrusion granulator, and dried to obtain a granulated wettable powder.

[Formulation Example 5] Granule
Compound (A) 3 parts Daimlon 2 parts Bentonite 50 parts Talc 45 parts After uniformly mixing and pulverizing the above, a small amount of water is added, stirred and mixed, granulated with an extrusion granulator, dried and granulated. To do.

[Composition Example 6] dust (powder powder)
Compound (A) 1 part Daimlon 2 parts Carplex # 80D 0.5 part (synthetic hydrous silicic acid: Shionogi & Co., Ltd. trade name)
Kaolinite 95 parts Diisopropyl phosphate 1.5 parts or more uniformly mixed and pulverized to obtain a powder.

[Formulation Example 7] wettable powder
Compound (A) 10 parts dimethylpiperate 10 parts pyrophyllite 74 parts Solpol 5039 4 parts (mixture of nonionic surfactant and anionic surfactant: Toho Chemical Industries, Ltd. trade name)
Carplex # 80D 2 parts (Synthetic hydrous silicic acid: Shionogi & Co., Ltd. trade name)
The above is uniformly mixed and ground to obtain a wettable powder.

[Formulation Example 8] Milk (emulsible concentrate)
Compound (A) 2 parts dimethylpiperate 3 parts xylene 75 parts N-methylpyrrolidone 15 parts Solpol 2680 5 parts (mixture of nonionic surfactant and anionic surfactant: Toho Chemical Co., Ltd. trade name)
The above is uniformly mixed to obtain an emulsion.

[Formulation Example 9] Suspension concentrate
Compound (A) 15 parts Dimepiperate 10 parts Agrisol S-710 10 parts (Nonionic surfactant: trade name of Kao Corporation)
Lnox 1000C 0.5 part (anionic surfactant: Toho Chemical Co., Ltd. trade name)
Xanthan gum 0.2 parts Water 64.3 parts After uniformly mixing the above, wet pulverize to make a suspension.

[Composition Example 10] Granular wettable powder (water dispersible granule)
Compound (A) 25 parts Dimepiperate 50 parts Hytenol NE-15 5 parts (anionic surfactant: trade name of Daiichi Kogyo Seiyaku Co., Ltd.)
Vanillex N 10 parts (anionic surfactant: Nippon Paper Industries Co., Ltd. trade name)
Carplex # 80D 40 parts (Synthetic hydrous silicic acid: Shionogi Pharmaceutical Co., Ltd. trade name)
After uniformly mixing and pulverizing the above, a small amount of water is added, stirred and mixed, granulated with an extrusion granulator, and dried to obtain a granulated wettable powder.

[Formulation Example 11] Granule
Compound (A) 3 parts dimethylpiperate 2 parts bentonite 50 parts talc 45 parts After uniformly mixing and pulverizing the above, a small amount of water is added, stirred and mixed, granulated with an extrusion granulator, dried and granulated. To do.

[Composition Example 12] Dust (dustable powder)
Compound (A) 1 part dimethylpiperate 2 parts Carplex # 80D 0.5 part (synthetic hydrous silicic acid: Shionogi Pharmaceutical Co., Ltd. trade name)
Kaolinite 95 parts Diisopropyl phosphate 1.5 parts or more uniformly mixed and pulverized to obtain a powder.

[Formulation 13] wettable powder
Compound (A) 10 parts Esprocarb 10 parts pyrophyllite 74 parts Solpol 5039 4 parts (mixture of nonionic surfactant and anionic surfactant: Toho Chemical Industries, Ltd. trade name)
Carplex # 80D 2 parts (Synthetic hydrous silicic acid: Shionogi & Co., Ltd. trade name)
The above is uniformly mixed and ground to obtain a wettable powder.

[Formulation 14] dairy (emulsible concentrate)
Compound (A) 2 parts Esprocarb 3 parts xylene 75 parts N-methylpyrrolidone 15 parts Solpol 2680 5 parts (mixture of nonionic surfactant and anionic surfactant: Toho Chemical Co., Ltd. trade name)
The above is uniformly mixed to obtain an emulsion.

[Formulation Example 15] Suspension concentrate
Compound (A) 15 parts Esprocarb 10 parts Agrisol S-710 10 parts (Nonionic surfactant: Kao Corporation trade name)
Lnox 1000C 0.5 part (anionic surfactant: Toho Chemical Co., Ltd. trade name)
Xanthan gum 0.2 parts Water 64.3 parts After uniformly mixing the above, wet pulverize to make a suspension.

[Composition Example 16] Granule wettable powder (water dispersible granule)
Compound (A) 25 parts Esprocarb 50 parts Hytenol NE-15 5 parts (anionic surfactant: Daiichi Kogyo Seiyaku Co., Ltd., trade name)
Vanillex N 10 parts (anionic surfactant: Nippon Paper Industries Co., Ltd. trade name)
Carplex # 80D 40 parts (Synthetic hydrous silicic acid: Shionogi Pharmaceutical Co., Ltd. trade name)
After uniformly mixing and pulverizing the above, a small amount of water is added, stirred and mixed, granulated with an extrusion granulator, and dried to obtain a granulated wettable powder.

[Formulation Example 17] Granule
Compound (A) 3 parts Esprocarb 2 parts Bentonite 50 parts Talc 45 parts After uniformly mixing and pulverizing the above, a small amount of water is added, stirred and mixed, granulated with an extrusion granulator, dried and granulated. To do.

[Formulation Example 18] dust powder (dustable powder)
Compound (A) 1 part Esprocarb 2 parts Carplex # 80D 0.5 part (synthetic hydrous silicic acid: Shionogi & Co., Ltd. trade name)
Kaolinite 95 parts Diisopropyl phosphate 1.5 parts or more uniformly mixed and pulverized to obtain a powder.

The usefulness of the composition of the present invention as a herbicide will be specifically described in the following test examples.
The phytotoxicity reduction effect or the herbicidal effect of each test example was investigated according to the following criteria.

Judgment criteria 5 ... 90% or more of herbicide rate (almost completely dead)
4 ... Herbicidal rate 70% or more and less than 90% 3 ... Herbicidal rate 40% or more and less than 70% 2 ... Herbicidal rate 20% or more and less than 40% 1 ... Herbicidal rate 5% or more and less than 20% 0. ..Harvicide rate 5% or less (almost no effect)

[Test Example 1] Chemical damage test under water leakage condition After alluvial soil was put into a 1 / 10,000 are plastic pot with a hole in the bottom, water was added and mixed to make a 4 cm flood condition. A 2.5-leaf rice seedling was transplanted into the pot, and a suspension of a predetermined concentration of the reagent was dropped using a wettable powder prepared according to the formulation example on the 9th day after transplanting. The water leakage operation was performed by placing a pot in a plastic vat and draining the water in the vat, and water leakage of 2 cm / day was applied for 3 consecutive days after the chemical treatment. On the 28th day after the drug treatment, the phytotoxicity to rice was investigated according to the above criteria. As a result, all of the compound (A) + Dimron, the compound (A) + dimethylpiperate, and the compound (A) + esprocarb showed a phytotoxicity-reducing effect on rice compared to the case of the compound (A) alone.

[Test Example 2] Phylogenetic test under standing seedlings and water leakage conditions The standing seedling conditions were as follows: alluvial soil was put into a 1/10000 are plastic pot, and then mixed with water to make a 4 cm flood condition. A 2.5-leaf rice seedling was fixed to the paddy with the roots exposed in the pot. On the other hand, the water leakage conditions were the same as in Test Example 1, and transplanted rice seedlings at the 2.5 leaf stage. Under both conditions, a suspension of a predetermined concentration of the reagent reagent was dropped using a wettable powder prepared according to the formulation example on the sixth day after transplantation. On the 24th day after the drug treatment, the phytotoxicity to rice was investigated according to the above criteria. As a result, all of the compound (A) + Dimron, the compound (A) + dimethylpiperate, and the compound (A) + esprocarb showed a phytotoxicity-reducing effect on rice compared to the case of the compound (A) alone.

[Test Example 3] Herbicidal effect test by pretreatment of weed generation under flooded conditions After alluvial soil was put into a 1/10000 are plastic pot, water was added and mixed to make a 4 cm flooded condition. The seeds of Novier, Inuhotarui, Konagi, Staghorna, and Azena were sown, and a suspension of a predetermined concentration of the reagent was dropped using a wettable powder prepared according to the formulation example on the second day after sowing. On the 38th day after the drug treatment, the herbicidal effect on various weeds was investigated according to the above criteria. As a result, the compound (A) + Dimron, the compound (A) + dimethylpiperate, and the compound (A) + esprocarb did not show a decrease in herbicidal effect compared to the case of the compound (A) alone.

[Test Example 4] Herbicidal effect test by post-weed treatment in submerged conditions After placing alluvial soil in a 1 / 10,000 are plastic pot, seeded with dog firefly seeds, covered with paddy topsoil, nobies, kogi , Seeds of Kakashigusa and Azena were sown, and water was added to make a 4 cm submerged condition. On the 14th day after sowing, a suspension of a predetermined concentration of the reagent was dropped using a wettable powder prepared according to the formulation example. On the 38th day after the drug treatment, the herbicidal effect on various weeds was investigated according to the above criteria. As a result, the compound (A) + Dimron, the compound (A) + dimethylpiperate, and the compound (A) + esprocarb did not show a decrease in herbicidal effect compared to the case of the compound (A) alone.

[Test Example 5] Chemical damage test under rice seedling conditions After alluvial soil was put into a 1/10000 are plastic pot, water was added and mixed to make a 4 cm flood condition. A 2.5-leaf rice seedling was fixed to the paddy with the roots exposed in the pot. On the sixth day of transplantation, a suspension having a predetermined concentration of the reagent reagent was dropped using a wettable powder prepared according to the formulation example. On the 24th day after the drug treatment, the phytotoxicity to rice was investigated according to the above criteria. The results are shown in Table 4.

[Test Example 6] Herbicidal effect test by treatment after generation of Azegaya under flooded conditions After alluvial soil was put into a 1/10000 are plastic pot, Azegaya seeds were sown and grown in a greenhouse. After growing for 20 days, water was added so that the water depth was 2 cm, and a suspension having a predetermined concentration of the reagent was dropped using a wettable powder prepared according to the formulation example. On the 20th day after the drug treatment, the herbicidal effect against Azegaya was investigated according to the above criteria. The results are shown in Table 5.

[Test Example 7] Herbicidal effect test by treatment after generation of nobies in flooded conditions After placing alluvial soil in a 1/10000 are plastic pot, seeds of nobies were sown and grown in a greenhouse. After growing for 14 days, water was added so that the flooding depth was 4 cm, and the suspension of a predetermined concentration of the reagent was dripped using the wettable powder prepared according to the formulation example the next day. On the 21st day after the drug treatment, the herbicidal effect against nobies was investigated according to the above criteria. The results are shown in Table 5.

[Test Example 8] Herbicidal effect test by pre-treatment of firefly firefly under submerged conditions After alluvial soil was put into a 1/10000 are plastic pot, water was added and mixed to obtain a submerged condition of 4 cm. The pot was seeded with Inuta firefly seeds (Honjo City, Akita Prefecture), and a suspension of a predetermined concentration of the reagent was dropped using a wettable powder prepared according to the formulation example on the first day of sowing. On the 21st day after the drug treatment, the herbicidal effect against nobies was investigated according to the above criteria. The results are shown in Table 5.

[Test Example 9] Herbicidal effect test by foliar treatment After alluvial soil was put into a 1/10000 are plastic pot, water was added and mixed to make a 4 cm flood condition. Nobies seeds were sown in the pot, and a pods were placed and grown in a greenhouse. After growing for 14 days, the surface water was extracted, and the wettable powder prepared according to the formulation example was diluted with water to a predetermined dosage, and uniformly treated with a small spray on the foliage. On the 21st day after drug treatment, the herbicidal effect on both plants was investigated according to the above criteria. The results are shown in Table 6.

  As is clear from the above results, the composition of the present invention is useful, for example, as a herbicide for paddy fields.

Claims (8)

Formula (1):

[Wherein R ¹ represents a C _1-3 alkyl group, a C _1-3 haloalkyl group, a C _1-3 alkoxy C _1-3 alkyl group, a phenyl group or a pyridyl group,
R ² represents a hydrogen atom, a C _1-3 alkyl group, a C _1-3 haloalkyl group, a C _1-3 alkoxy group or a halogen atom,
R ³ , R ⁴ , R ⁵ and R ⁶ each independently represents a hydrogen atom, a C _1-3 alkyl group or a C _1-3 haloalkyl group, provided that R ³ , R ⁴ , R ⁵ and R ⁶ , At least one represents a C _1-3 alkyl group or a C _1-3 haloalkyl group, or R ³ and R ⁴ together represent ═CH ₂ ,
X and Y are each independently a C _1-3 alkyl group, a C _1-3 haloalkyl group, a C _1-3 alkoxy group, a C _1-3 haloalkoxy group, a halogen atom or a di (C _1-3 alkyl) amino group. Represents
Z represents a nitrogen atom or a methine group. And a pyrazole sulfonylurea compound (A) represented by:
A herbicidal composition containing at least one compound selected from Daimlon, dimethylpiperate, and esprocarb. A herbicide composition for paddy rice containing the compound (A) and at least one compound selected from Daimlon, dimethylpiperate, and esprocarb. A herbicidal method in which the compound (A) and at least one compound selected from Daimlon, dimethylpiperate and esprocarb are applied simultaneously or with a time difference. A paddy field weeding method comprising applying the compound (A) and at least one compound selected from Daimlon, dimethylpiperate and esprocarb simultaneously or with a time difference. The compound (A), group B (provided that group B is pyrazosulfuron-ethyl / generic name), bensulfuron methyl (bensulfuron-methyl / generic name), sinosulfuron (cynosulfuron / generic name), imazosulfuron (Imazosulfuron / generic name), azisulfuron (generic name), halosulfuron methyl (halosulfuron-methyl / generic name), cyclosulfamuron / generic name, ethoxysulfuron / generic name, ethoxysulfuron / generic name (Pyrazolate / generic name), pyrazoxifene (pyrazoxyphen / generic name), benzophenap (ben offenap / generic name), bromobutide (generic name), naproanilide (generic name / generic name), pretilachlor (general name), butachlor (general name), tenylchlor (general name), C name ), Clomethoxynil (generic name), biphenox (bifenox / generic name), oxadiazone (generic name), oxadialgyl (generic name), pentoxazone (generic name), cfentroro (c / en) Oxadichromemephone (generic name), indanophan indanofan / generic name, pyriminobac-methyl / generic name, cyhalofop-butyl / generic name, fentolazamide / genfenacet / generic name, butenachlor butenachlor / generic name), dithiopyr (dithiopyl / generic name), benfrecetate (benfuresate / generic name), pilibutycarb (pyributicarb / generic name), bencho curve (bentiocarb / generic name), molinate (molinate / genotype / butafos) (Generic name), quinchlorac (quinclorac / generic name), cinmethrin (cinmeth) ylin / generic name), cimetrin (simetryn / generic name), bensulide (bensulide / generic name), dimetamethrin (dimamemetrin / generic name), MCPA (generic name), MCPB (generic name), etobenzanid / generic name Cumyluron (cumylon / generic name), benzobicyclon (benzobicyclone / generic name), pyriftalide (pyriftalid / generic name), bispyribac (bispyribac / generic name), pyraclonil (pyraclonil / generic name), anilofos (generic name) OK-701 (test name), penox slum (penoxslam / generic name), AVH-301 (test name), KUH-021 (test name), TH-547 (test) ), Bentazone (Bentazone / generic name), 2,4-PA (generic name), metamihop (generic name), flucetosulfuron (generic name), HOK-201 (generic name), mesotrione (generic name) ), Propanil (generic name), quinoclamine (generic name) and chromeprop. A herbicide composition comprising at least one compound selected from: A herbicide composition for paddy rice containing the compound (A) and at least one compound selected from the group B. A herbicidal method in which the compound (A) and at least one compound selected from the group B are applied simultaneously or with a time difference. A method for weeding paddy fields, wherein the compound (A) and at least one compound selected from the group B are applied simultaneously or with a time difference.