JP2014034539A - Optically active pyrazole amide derivative and pest control agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an optically active pyrazole amide derivative having excellent insecticidal activity at a low dose.SOLUTION: Provided are an optically active pyrazole amide derivative represented by the specified general formula (1) and a pest control agent. [In the formula, Rrepresents a hydrogen atom, a methyl group, an ethyl group, or an R-substituted methyl group; Rrepresents an R-substituted methyl group, or -S(O)R; Rrepresents -OR; Rrepresents -S(O)CH; Rand Reach independently represent a methyl group or an ethyl group; and r represents an integer of 0-2.]

Description

  The present invention relates to an optically active pyrazole amide derivative and a pest control agent characterized by containing them as active ingredients. The pest control agent in the present invention is the field of agriculture and horticulture or the field of livestock and hygiene (internal parasites / external parasites for domestic animals and pets, hygiene pests and unpleasant pests for domestic and commercial use) It means a pest control agent for harmful arthropods such as The agrochemical in the present invention means an insecticide / acaricide, nematicide, herbicide, fungicide, etc. in the field of agriculture and horticulture.

  Patent Document 1 discloses that pyrazole amide derivatives are useful as insecticides. However, the compound of Patent Document 1 has an asymmetric carbon atom on the substituent of the amide structure at the 4-position of pyrazole, and the presence of an optical isomer is expected. There is no disclosure regarding optical isomers.

International Publication No. 2012/061290

  The development of pest control agents for the purpose of controlling various pests such as agricultural and horticultural pests, forest pests, and hygiene pests has progressed, and a wide variety of drugs have been put to practical use to date.

  However, due to the long-term use of such drugs, in recent years, pests have acquired drug resistance, making it difficult to control with existing insecticides and fungicides that have been used. In addition, some of the existing pest control agents have a short residual effect, which increases the number of spraying of the drug, which is a heavy burden on farmers, and is one of the existing pest control agents. Some of them are highly toxic, and the problem of disrupting ecosystems is becoming apparent. Under such circumstances, development of a novel pest control agent not only having high pest control activity but also low toxicity is always expected.

  As a result of intensive studies aimed at solving the above-mentioned problems, the present inventors have found that the optically active (S) -pyrazole amide derivative according to the present invention is more suitable for controlling pests than the other optically active substance and racemate. The present invention has been completed by finding out that it is far superior in terms of activity, influence on non-target organisms, residual effect, soil persistence and the like.

  That is, the present invention relates to the following [1] to [9].

[1]
General formula (1):

[Wherein R ¹ represents a hydrogen atom, a methyl group, an ethyl group or a methyl group optionally substituted with R ³ ;
R ² represents a methyl group optionally substituted with R ⁴ or —S (O) _r R ⁵ ,
R ³ represents -OR ⁶ ;
R ⁴ represents —S (O) _r CH ₃ ,
R ⁵ and R ⁶ each independently represent a methyl group or an ethyl group,
r represents an integer of 0 to 2. ] The optically active pyrazole amide derivative represented by this.

[2]
General formula (1):

[Wherein R ¹ represents a hydrogen atom, a methyl group, an ethyl group or a methyl group optionally substituted with R ³ ;
R ² represents a methyl group optionally substituted with R ⁴ or —S (O) _r R ⁵ ,
R ³ represents -OR ⁶ ;
R ⁴ represents —S (O) _r CH ₃ ,
R ⁵ and R ⁶ each independently represent a methyl group or an ethyl group,
r represents an integer of 0 to 2. ] The optically active pyrazole amide derivative represented by this.

  However, the compounds described below are excluded.

[3]
A pest control agent comprising one or more selected from the optically active pyrazole amide derivatives according to the above [1] to [2] as active ingredients.

[4]
An agrochemical containing one or more selected from the optically active pyrazole amide derivatives according to the above [1] to [2] as active ingredients.

[5]
A mammal or bird internal or ectoparasite control agent comprising one or more selected from the optically active pyrazole amide derivatives described in [1] to [2] as an active ingredient.

[6]
An insecticide or acaricide containing as an active ingredient one or more selected from the optically active pyrazole amide derivatives described in [1] to [2] above.

[7]
A soil treatment agent containing one or more selected from the optically active pyrazole amide derivatives described in [1] to [2] as an active ingredient.

[8]
The soil treatment agent according to the above [7], wherein the soil treatment method is soil irrigation treatment.

[9]
An insecticide for paddy rice containing, as an active ingredient, one or more selected from the optically active pyrazole amide derivatives described in [1] to [2] above.

  The optically active (S) -pyrazole amide derivative of the present invention is more agricultural than the corresponding other optical isomer (R) -pyrazole amide derivative and racemic (RS) -pyrazole amide derivative. It has excellent insecticidal and acaricidal activity against pests, spider mites, mammals, or internal or ectoparasites of birds. Furthermore, it has little adverse effect on non-target organisms such as mammals, fish, crustaceans, and beneficial insects, and has low persistence and a low environmental burden. It also has excellent environmental dynamics such as residual effect and soil persistence, and has a light environmental impact.

  Therefore, the present invention can provide a useful novel pest control agent.

  Among the compounds included in the present invention, those that can be converted into acid addition salts according to a conventional method include, for example, hydrohalic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, and the like. Salts of inorganic acids such as salts, nitric acid, sulfuric acid, phosphoric acid, chloric acid, perchloric acid, salts of sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, Salts of carboxylic acids such as formic acid, acetic acid, propionic acid, trifluoroacetic acid, fumaric acid, tartaric acid, succinic acid, maleic acid, malic acid, succinic acid, benzoic acid, mandelic acid, ascorbic acid, lactic acid, gluconic acid, citric acid, etc. A salt of an amino acid such as glutamic acid or aspartic acid can be used.

  Alternatively, among the compounds included in the present invention, those that can be converted into a metal salt according to a conventional method include, for example, alkali metal salts such as lithium, sodium, and potassium, and alkaline earth metals such as calcium, barium, and magnesium. It can be a salt or a salt of aluminum.

  Next, specific examples of each substituent shown in the present specification are shown below. Here, n- represents normal, i- represents iso, s- represents secondary, and tert- represents tertiary, and Ph represents phenyl.

The notation methyl group optionally substituted by a methyl group, or R ⁴ optionally substituted by R ³ in the present specification, by any R ³ or R ^4, any hydrogen atoms bonded to a carbon atom of the methyl group Represents a substituted methyl group. Accordingly, there can be a minimum of 1 and a maximum of 3 substituents R ³ or R ⁴ . At this time, when there are two or more substituents R ³ or R ⁴ on each methyl group, each R ³ or R ⁴ may be the same as or different from each other.

  The optically active pyrazole amide derivative of the present invention can be produced by optical resolution of the corresponding racemate.

  The racemic pyrazole amide derivative can be produced by the method described in Patent Document 1.

  As the optical resolution method, for example, a method of separating the (R) optical isomer and the (S) optical isomer by using a high performance liquid chromatography column for optical isomer separation can be employed. . Columns for high-performance liquid chromatography for optical isomer separation are generally commercially available. For example, Chiral Pak AD (CHIRAL PAK AD; manufactured and sold by Daicel Chemical Industries, Ltd.) has 1,4-poly-2 as a resolving agent. , 3,6-tri-O-phenylcarbamoyl-β-D-glucoside is packed in silica gel).

  Solvents used in optical resolution include aliphatic hydrocarbons such as hexane and heptane, alcohols such as methanol, ethanol, 1-propanol, 2-propanol and 1-butanol, and halogenated hydrocarbons such as dichloromethane and chloroform. And ethers such as diethyl ether, 1,2-diethoxyethane, diisopropyl ether, tetrahydrofuran or 1,4-dioxane, nitriles such as acetonitrile, acetic acid, water, or a mixed solvent thereof.

  The optically active pyrazole amide derivative of the present invention can also be synthesized according to the method described in the following production method.

  Manufacturing method A

General formula (7) [wherein R ¹ represents the same meaning as described above. ] In general formula (8-1) [wherein R ² represents the same meaning as described above]. And a compound represented by the general formula (9) [wherein R ¹ and R ² represent the same meaning as described above. This invention compound represented by this can be synthesize | combined. In this reaction, the compound represented by the general formula (8-1) can be used in the range of 0.5 to 50 equivalents with respect to 1 equivalent of the compound represented by the general formula (7). If necessary, a base such as potassium carbonate, triethylamine, pyridine, 4- (dimethylamino) pyridine can be used. This reaction may be carried out without solvent, but a solvent may be used, for example, N, N-dimethylformamide, N, N-dimethylacetamide, acetonitrile, dimethyl sulfoxide, 1,3-dimethyl-2- Polar solvents such as imidazolinone, alcohols such as methanol, ethanol, propanol, 2-propanol and ethylene glycol, ethers such as diethyl ether, tetrahydrofuran and diphenyl ether, aromatic hydrocarbons such as benzene, toluene and xylene, methylene chloride , Halogenated hydrocarbons such as chloroform and carbon tetrachloride, and aliphatic hydrocarbons such as pentane and n-hexane. These solvents may be used alone or as a mixture of two or more thereof.

  The reaction temperature can be set to any temperature from −60 ° C. to the reflux temperature of the reaction mixture, and the reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but is usually arbitrary in the range of 5 minutes to 100 hours. Can be set.

  Some of the compounds represented by formula (8-1) are known compounds, and some of them are available as commercial products. Others can be synthesized according to known methods described in the literature.

The compound represented by the general formula (7) is represented by the general formula (8-2) [wherein R ² represents the same meaning as described above. The compound of the present invention represented by the general formula (9) can also be synthesized by reacting the compound represented by formula (9) with a condensing agent. In this reaction, 1 to 4 equivalents of WSC {1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride}, CDI (carbonyldioxychloride) per 1 equivalent of the compound represented by the general formula (8-2). A condensing agent such as imidazole can be used. Moreover, the compound represented by General formula (8-2) can be used in 0.5-50 equivalent with respect to 1 equivalent of compounds represented by General formula (7). If necessary, a base such as potassium carbonate, triethylamine, pyridine, 4- (dimethylamino) pyridine can be used.

  This reaction may be carried out without solvent, but a solvent may be used, for example, N, N-dimethylformamide, N, N-dimethylacetamide, acetonitrile, dimethyl sulfoxide, 1,3-dimethyl-2- Polar solvents such as imidazolinone, alcohols such as methanol, ethanol, propanol, 2-propanol and ethylene glycol, ethers such as diethyl ether, tetrahydrofuran and diphenyl ether, aromatic hydrocarbons such as benzene, toluene and xylene, methylene chloride , Halogenated hydrocarbons such as chloroform and carbon tetrachloride, and aliphatic hydrocarbons such as pentane and n-hexane. These solvents may be used alone or as a mixture of two or more thereof.

  The reaction temperature can be set to any temperature from −60 ° C. to the reflux temperature of the reaction mixture, and the reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but is usually arbitrary in the range of 5 minutes to 100 hours. Can be set.

  Some of the compounds represented by formula (8-2) are known compounds, and some of them are available as commercial products. Others can be easily synthesized according to known methods described in the literature.

  Manufacturing method B

General formula (2-12) [In formula, R < ¹ > and R < ² > represents the same meaning as the above. And a compound represented by the general formula (2-2) [wherein L ₁ is a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, -B (OH) ₂ group or -B (OR ⁵¹ ) ₂ group (formula R ⁵¹ represents a hydrogen atom or C _{1 to} C ₆ alkyl which may be the same or different, or two R ⁵¹ together represent —CH ₂ CH ₂ — or —C (CH ₃ ) ₂ C. (CH ₃ ) ₂ — may be formed). The compound of the present invention represented by the general formula (9) can be obtained by reacting the compound represented by formula (9) in the presence of a catalyst and a base.

  The amount of the compound represented by the general formula (2-2) can be used in the range of 0.8 to 5 equivalents relative to 1 equivalent of the compound represented by the general formula (2-12).

  Some of the compounds represented by the general formula (2-2) used here are known compounds, and some of them are available as commercial products. Others can be easily synthesized according to the methods described in the literature.

  Examples of the catalyst that can be used in this reaction include palladium catalysts such as palladium-carbon, palladium chloride, palladium acetate, bis (triphenylphosphine) palladium dichloride, tetrakis (triphenylphosphine) palladium, or copper metal, copper acetate (I). And copper catalysts such as copper (II) acetate, copper (I) oxide, copper (II) oxide and copper iodide. The usage-amount of a catalyst is 0.001-1.0 equivalent with respect to 1 equivalent of compounds represented by General formula (2-12), Preferably, it is 0.01-0.5 equivalent, More preferably, it is 0.05. It can be used in the range of ~ 0.2 equivalent.

  Examples of the base used include tertiary amine compounds such as pyridine, diisopropylethylamine, and triethylamine, and inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, and sodium bicarbonate. . The usage-amount of a base can be used in the range of 0.1-10.0 equivalent with respect to 1 equivalent of compounds represented by General formula (2-12).

  This reaction can be carried out without solvent, but a solvent may be used. For example, polar solvent such as N, N-dimethylformamide, N, N-dimethylacetamide, acetonitrile, dimethyl sulfoxide, 1,3-dimethyl-2-imidazolinone, water, methanol, ethanol, propanol, 2-propanol, ethylene glycol Alcohols such as diethyl ether, tetrahydrofuran and diphenyl ether, aromatic hydrocarbons such as benzene, toluene and xylene, halogenated hydrocarbons such as methylene chloride, chloroform and carbon tetrachloride, pentane and n-hexane And aliphatic hydrocarbons. These solvents may be used alone or as a mixture of two or more thereof.

  The reaction temperature can be set to any temperature from −60 ° C. to the reflux temperature of the reaction mixture, and the reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but is usually arbitrary in the range of 5 minutes to 100 hours. Can be set.

  Manufacturing method C

3-Chloro-1- (pyridin-3-yl) -1H-pyrazol-4-amine (13) is a compound represented by the general formula (8-1) or a method similar to Production Method A, or By reacting with the compound represented by general formula (8-2), general formula (41) [wherein R ² represents the same meaning as described above. This invention compound represented by this can be obtained.

Subsequently, the compound represented by the general formula (41) is represented by the general formula (5) [wherein R ¹ represents the same meaning as described above, J ^b represents a halogen atom, —OH, —OSO ₂ CH ₃ , —OSO _2. Represents a leaving group such as CF ₃ . The compound of the present invention represented by the general formula (9) can be obtained by reacting with the compound represented by formula (9).

  In this reaction, the compound represented by the general formula (5) can be used in the range of 0.5 to 50 equivalents with respect to 1 equivalent of the compound represented by the general formula (41). If necessary, bases such as hydrochloric acid, sulfuric acid, p-toluenesulfonic acid, etc., potassium carbonate, triethylamine, pyridine, 4- (dimethylamino) pyridine, sodium hydride, sodium hydroxide, potassium hydroxide, or diethylazo Mitsunobu reaction using dicarboxylate and triphenylphosphine or the like can be used.

  This reaction can be carried out without solvent, but a solvent may be used. For example, polar solvent such as N, N-dimethylformamide, N, N-dimethylacetamide, acetonitrile, dimethyl sulfoxide, 1,3-dimethyl-2-imidazolinone, water, methanol, ethanol, propanol, 2-propanol, ethylene glycol Alcohols such as diethyl ether, tetrahydrofuran and diphenyl ether, aromatic hydrocarbons such as benzene, toluene and xylene, halogenated hydrocarbons such as methylene chloride, chloroform and carbon tetrachloride, pentane and n-hexane And aliphatic hydrocarbons. These solvents may be used alone or as a mixture of two or more thereof.

  The reaction temperature can be set to any temperature from −60 ° C. to the reflux temperature of the reaction mixture, and the reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but is usually arbitrary in the range of 5 minutes to 100 hours. Can be set.

  Some of the compounds represented by the general formula (5) are known compounds, and some of them are commercially available. Others can be synthesized according to known methods described in the literature.

  The reaction from production method A to production method C may be carried out in an inert gas atmosphere such as nitrogen or argon if necessary.

  In the reaction from production method A to production method C, the reaction mixture after completion of the reaction is directly concentrated, or dissolved in an organic solvent, concentrated after washing with water, or poured into ice water, followed by normal post-treatment such as concentration after extraction with an organic solvent. The objective compound of the present invention can be obtained. Moreover, when the necessity for purification arises, it can be separated and purified by any purification method such as recrystallization, column chromatograph, thin layer chromatograph, liquid chromatographic fractionation and the like.

  The compound represented by the general formula (7) used in the production method A can be synthesized by, for example, the following reaction formula 1 and reaction formula 2.

  Reaction formula 1

That is, general formula (2-1) [wherein R ⁵⁰ represents a C _{1 to} C ₆ alkyl group. The compound represented by the general formula (2-4) [wherein R ⁵⁰ represents the same meaning as described above. It can be synthesized by a Sandmeyer reaction of a compound represented by Some of the compounds represented by formula (2-4) are known compounds, and some of them are available as commercial products. Others can be synthesized according to known methods described in the literature.

In addition, the compound represented by the general formula (2-1) is represented by the general formula (2-6) [wherein R ⁵⁰ represents the same meaning as described above, and P ¹ represents tertiary butyl, benzyl, 4-methoxybenzyl, acetyl. Represents a protecting group such as methoxymethyl or methylthiomethyl. ] Can be synthesized by deprotection with an acid or base. The compound represented by the general formula (2-6) can be synthesized according to a known method known in the literature, for example, a known method described in Journal of Heterocyclic Chemistry 1987, Vol. 24, page 693. it can.

Next, the compound represented by the general formula (2-1) is converted into a known general formula according to a known method known in the literature, for example, the method described in Journal of Organic Chemistry 2004, 69, 5578. (2-2) [L ₁ is a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, -B (OH) ₂ group or -B (OR ⁵¹ ) ₂ group (wherein R ⁵¹ is a hydrogen atom or the same or different May represent C ₁ -C ₆ alkyl, or two R ⁵¹ together may form —CH ₂ CH ₂ — or —C (CH ₃ ) ₂ C (CH ₃ ) ₂ —. ). ] In the presence of a metal catalyst such as copper and a base, or in the presence of a transition metal catalyst such as palladium and a base, wherein R ⁵⁰ is the above-mentioned Means the same. Can be obtained.

  Furthermore, 3-chloro-1- (pyridin-3-yl) -1H-pyrazole-4 is obtained by subjecting the compound represented by the general formula (2-3) to a hydrolysis reaction according to a known method known in the literature. -Carboxylic acid (2) can be produced.

  Reaction formula 2

3-Chloro-1- (pyridin-3-yl) -1H-pyrazole-4-carboxylic acid (2) is converted to diphenylphosphoryl azide (DPPA) and general formula (3) [wherein R ^6a is C _{1 to} C _6. Represents an alkyl group. ] Is reacted with a compound represented by the general formula (4) [wherein R ^6a represents the same meaning as described above. The compound represented by this can be obtained.

  In this reaction, DPPA can be used in the range of 0.5 to 50 equivalents relative to 1 equivalent of the compound represented by the general formula (2), and the compound represented by the general formula (3) It can be used in the range of 1 equivalent to the amount of solvent with respect to 1 equivalent of the compound represented by (2). If necessary, a base such as potassium carbonate, triethylamine, pyridine, 4- (dimethylamino) pyridine can be used.

  This reaction can be carried out without solvent, but a solvent may be used. For example, polar solvent such as N, N-dimethylformamide, N, N-dimethylacetamide, acetonitrile, dimethyl sulfoxide, 1,3-dimethyl-2-imidazolinone, water, methanol, ethanol, propanol, 2-propanol, ethylene glycol Alcohols such as diethyl ether, tetrahydrofuran and diphenyl ether, aromatic hydrocarbons such as benzene, toluene and xylene, halogenated hydrocarbons such as methylene chloride, chloroform and carbon tetrachloride, pentane and n-hexane And aliphatic hydrocarbons. These solvents may be used alone or as a mixture of two or more thereof.

  The reaction temperature can be set to any temperature from −60 ° C. to the reflux temperature of the reaction mixture, and the reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but is usually arbitrary in the range of 5 minutes to 100 hours. Can be set.

  Some of the compounds represented by the general formula (3) are known compounds, and some of them are commercially available. Others can be synthesized according to known methods described in the literature.

By reacting the compound represented by the general formula (4) with the compound represented by the general formula (5) in the same manner as in the production method C, the general formula (6) [wherein R ¹ and R ^6a Represents the same meaning as described above. The compound represented by this can be obtained.

The compound represented by the general formula (6) synthesized as described above is deprotected with an acid or a base, so that the general formula (7) [wherein R ¹ represents the same meaning as described above. ] Can be synthesized.

  The compound represented by General Formula (2-12) used in Production Method B can be synthesized, for example, as follows.

  Reaction formula 3

That is, by reacting the compound represented by the general formula (2-6) according to a known method known in the literature, the general formula (2-7) [wherein P ¹ has the same meaning as described above]. Represent. The compound represented by this can be manufactured.

Subsequently, from the compound represented by the general formula (2-7), using the same method as the above reaction formula 2, the general formula (2-8) [wherein R ^6a and P ¹ represent the same meaning as described above. ] Can be synthesized.

Next, by reacting the compound represented by the general formula (2-8) and the compound represented by the general formula (5) in the same manner as in the reaction formula 2, the general formula (2-9) [ In the formula, R ¹ , R ^6a and P ¹ represent the same meaning as described above. ] Can be synthesized.

Furthermore, from the compound represented by the general formula (2-9), according to the reaction formula 2, the general formula (2-10) [wherein R ¹ and P ¹ represent the same meaning as described above. The compound represented by general formula (2-11) [wherein R ¹ , R ² and P ¹ represent the same meaning as described above. ] Can be synthesized.

The compound represented by the general formula (2-11) synthesized as described above is deprotected with an acid or a base to give a general formula (2-12) [wherein R ¹ and R ² have the same meaning as described above. Represents. ] Can be synthesized.

  The compound represented by the general formula (7) used in the production method A can be synthesized, for example, as follows.

  Reaction formula 3

Formula (2-13) [wherein R ¹ represents the same meaning as described above. ] Can be synthesized according to a known method described in, for example, International Publication No. 2011/048082.

  A compound represented by the general formula (7) by reacting the compound represented by the general formula (2-13) and the compound represented by the general formula (2-2) in the same manner as in Production Method B. Can be synthesized.

  The compound represented by the general formula (13) used in the production method C can be synthesized, for example, as follows.

  Reaction formula 4

  By reacting 3-chloro-1- (pyridin-3-yl) -1H-pyrazole-4-carboxylic acid (2) with a nitrating agent in the presence of an acid anhydride, 3- (3-chloro-4-nitro -1H-pyrazol-1-yl) pyridine (2-14) can be synthesized.

  3- (3-Chloro-4-nitro-1H-pyrazol-1-yl) pyridine (2-14) is a compound represented by the general formula (3-chloro-4-nitro-1H-pyrazole (2-16)) It can synthesize | combine by making the compound represented by 2-2) react by the method similar to the manufacturing method B.

  3-Chloro-4-nitro-1H-pyrazole (2-16) can be synthesized according to a known method described in, for example, Tetrahedron 2008, 64, 11249.

  Subsequently, 3- (3-chloro-4-nitro-1H-pyrazol-1-yl) pyridine (2-14) was converted to 3-chloro-1- (pyridin-3-yl) by a known nitro group reduction method. ) -1H-pyrazol-4-amine (13) can be synthesized.

  The compound represented by the general formula (8-1) and a part of the compound represented by (8-2) used in the production method A can be prepared by methods known in the literature, such as US Patent Application Publication No. 2005/146823 It can be synthesized according to the method described in the book. Moreover, it can also synthesize | combine according to the method of Reaction formula 5.

  Reaction formula 5

In other words, the general formula (8-3) [is ^{J b} wherein the same meanings as defined above. And a compound represented by formula (8-4) [wherein R ⁵ represents the same meaning as described above. The compound represented by general formula (8-5) [wherein R ⁵ represents the same meaning as described above]. ] Can be synthesized.

  In this reaction, the compound represented by the general formula (8-4) can be used in the range of 0.5 to 50 equivalents relative to 1 equivalent of the compound represented by the general formula (8-3). If necessary, bases such as hydrochloric acid, sulfuric acid, p-toluenesulfonic acid, etc., potassium carbonate, sodium hydrogen carbonate, triethylamine, pyridine, 4- (dimethylamino) pyridine, sodium hydride, sodium hydroxide, potassium hydroxide, etc. Alternatively, Mitsunobu reaction using diethyl azodicarboxylate and triphenylphosphine or the like can be used.

  This reaction can be carried out without solvent, but a solvent may be used. For example, polar solvent such as N, N-dimethylformamide, N, N-dimethylacetamide, acetonitrile, dimethyl sulfoxide, 1,3-dimethyl-2-imidazolinone, water, methanol, ethanol, propanol, 2-propanol, ethylene glycol Alcohols such as diethyl ether, tetrahydrofuran and diphenyl ether, aromatic hydrocarbons such as benzene, toluene and xylene, halogenated hydrocarbons such as methylene chloride, chloroform and carbon tetrachloride, pentane and n-hexane And aliphatic hydrocarbons. These solvents may be used alone or as a mixture of two or more thereof.

  The reaction temperature can be set to any temperature from −60 ° C. to the reflux temperature of the reaction mixture, and the reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but is usually arbitrary in the range of 5 minutes to 100 hours. Can be set.

  Some of the compounds represented by formula (8-3) are known compounds, and some of them are available as commercial products. Others can be synthesized according to known methods described in the literature.

  Some of the compounds represented by formula (8-4) are known compounds, and some of them are available as commercial products. Others can be synthesized according to known methods described in the literature.

Subsequently, the compound represented by the general formula (8-5) is reacted with thionyl chloride, oxalyl chloride and the like according to a known method known in the literature, thereby obtaining the general formula (8-6) [wherein R ⁵ represents the same meaning as described above. ] Can be synthesized.

In addition, the compound represented by the general formula (8-5) is oxidized by using an oxidizing agent such as hydrogen peroxide or metachloroperbenzoic acid according to a known method known in the literature, thereby allowing the general formula (8- 7) [wherein R ⁵ represents the same meaning as described above. ] Can be synthesized.

Further, by reacting the compound represented by the general formula (8-7) with thionyl chloride, oxalyl chloride, etc. according to a known method known in the literature, the general formula (8-8) [in the formula, R ⁵ represents the same meaning as described above. ] Can be synthesized.

The compounds of the present invention are stored in warehouses, so-called agricultural pests that harm agricultural and horticultural crops and trees, so-called livestock pests that parasitize livestock and poultry, so-called sanitary pests that cause various adverse effects in the human living environment such as houses. It is possible to effectively control insects such as so-called stored grain pests that harm cereals and the like, and pests such as mites, crustaceans, molluscs, and nematodes that occur and harm in similar situations at low concentrations.

  Specific examples of insects, mites, crustaceans, molluscs and nematodes that can be controlled using the compounds of the present invention include the following organisms, but the present invention is not limited to these. is not.

  Adoxophyes honmai, Adoxophyes orana faciata, Archips breviplicanus, Archips fuscocupreanus, Grapholita molesta, Chama magnan Leguminivora glycinivorella), Matsumuraeses phaseoli, Pandemis heparana, Bucculatrix pyrivorella, Lyonetia clerkella, Lyonetia prunifal ringoniella), mandarin leaf moth (Phyllocnistis citrella), green moth (Acrolepiopsis sapporensis), wild moth (Acrolepiopsis suzukiella), black moth (Plutella xylostella), oyster leaf moth (Stathmopoda masinissa), cystogram tria ora gossypiella), peach sinker moth (Carposina sasakii), codling moth (Cydla pomonella), green moth (Chilo suppressalis), corn borer (Cnaphalocrocis medinalis), peach moth (Conogethes punctiferalis), cotton moth (Dia) (Etiella zinckenella), Glyphodes pyloalis, Hellula undalis, Ostrinia furnacalis, Ostrinia scapulalis, European corn borer (Ostrinia nubilaliseter, Pesta pal) ), White-tailed butterfly (Pieris brassicae), white-tailed butterfly (Pieris rapae crucivora), mugwort (Ascotis selenaria), soy bean looper (Pseudoplusia includens), chadokuga (Euproctis pseudoconspersa), maimaiga (Lymantria disparia), thymeina ), White-spotted starfish (Hyphantria cunea), white-spotted starfish (Lemyra imparilis), Akebiko-no-ha (Adris tyrannus), red-footed butterfly (Aedia leucomelas), red-footed squirrel (Agrotis ipsilon), red-tailed squirrel (Agrotis segetum) Uwaba (Ctenoplusia agnata), Helicoverpa armigera, Tobacco moth (Helicoverpa assulta), Cotton ball worm (Helicoverpa zea), Tobacco bad worm (Heliothis virescens), Mamestra brassicae, Mythimna naa ), Southern army worm (Spodoptera eridania), Spodoptera exigua, Fall army worm (Spodoptera frugiperda), Cotton leaf worm (Spodoptera littoralis), Spodoptera litura, Spodoptera litura, Spodoptera era ), Leeb Berry Moss (Endopiza viteana), tomato horn worm (Manduca quinquemaculata), tobacco horn worm (Manduca sexta) lepidopteran insects such as.

  Thrips thrips (Frankliniella intonsa), Citrus thrips (Frankliniella occidentalis), Croton thrips (Prithia thrips) Moths in total.

  Spotted beetle (Dolycoris baccarum), sea turtle (Eurydema rugosum), bark beetle (Eysarcoris aeneus), horseshoe beetle (Eysarcoris lewisi), white-headed beetle (Eysarcoris ventralis), subtilus , Nezara antennata, Nezara viridula, Piezodorus hybneri, Plautia crossota, Scotinophora lurida, tiger C Stink bug (Leptocorisa chinensis), Hoso-heli beetle (Riptortus clavatus), Red-headed beetle (Rhopalus msculatus), Cavelerius saccharivorus, Toba hemipterus cus, Togo hemipterus (Stephanitis pyrioides), Kuroto Bikasumi turtle (Halticus insularis), Turned plant bug (Lygus lineolaris), Nagamu sika turtle (Stenodema sibiricum), Akasika sika turtle (Stenotus rubrovittatus), Rice moss turtle (Trigonotylus caelestialium), ical Arisbori dia Green leafhopper (Balclutha saltuella), butterfly leafhopper (Epiacanthus stramineus), potato leaf hopper (Empoasca fabae), oyster leafhopper (Empoasca nipponica), Chanomidorimempei (Empoasca onukii), omenosaka ), Leafhopper leafhopper (Macrosteles striifrons), leafhopper leafhopper (Nephotettix cinctinceps), cotton-free hopper (Psuedatomoscelis seriatus), leafhopper (Laodelphax striatella), leafhopper (Nilaparvata lugens) Psylla pyrisuga, Aleurocanthus spiniferus, Silver leaf whitefly (Bemisia argentifolii), Tobacco whitefly (Bemisia tabaci), Citrus whitefly (Dialeurodes citri), Onsitsuna whitefly (trialeurous grape rum, Trialeurodes vapor Cotton Aphid (Aphis gossypii), Snowy Aphid (Aphis spiraecola), Peach Aphid (Myzus persicae), Komikan Aphid (Toxoptera aurantii), Alaska Scale Aphid (Drosicha corpulenta), Iceria scale P solani), citrus scale insect (Planococcus citri), stag beetle scale (Planococcus kuraunhiae), stag beetle scale (Pseudococcus comstocki), horn beetle (Ceroplastes ceriferus), ruby rotum (Ceroplastes rubens), red scallop Nymphalidae (Comstockaspis perniciosa), tea scale (Fiorinia theae), chanomarine scale insect (Pseudaonidia paeoniae), stag beetle (Pseudaulacaspis pentagona), scallop scale (Pseudaulacaspis prunicola), euglena (Unaspis yanonensis), Hemiptera (Cimex lectularius) and other Hemiptera insects.

  Douganebubui (Anomala cuprea), Japanese common squirrel (Anomala rufocuprea), Core ohanamuri (Gametis jucunda), Nagachakogane (Heptophylla picea), Japanese beetle (Popillia japonica), Colorado potato beetle (Lepinotarsa decemlineata) White-footed beetle (Melanotus tamsuyensis), Tobacco beetle (Lasioderma serricorne), Himetaketakekisui (Epuraea domina), Green beetle (Epilachna varivestis), Nijuya-hoshi-tento (Epilachna vigintioctopunctata), T. Tribolium castaneum, Anoplophora malasiaca, Monochamus alternatus, Psacothea hilaris, Xylotrechus pyrrhoderus, callosobruchus, Callosobruchus Western Root beetle (Chaetocnema concinna), Southern corn root worm (Diabrotica undecimpunctata), Western corn root worm (Diabrotica virgifera), Northern corn root worm (Diabrotica barberi), Inedro beetle (Oulema oryzae), Phyllotreta nastriatum, Phyllotreta striol Tobet beetle (Psylliodes angusticollis), peach weevil (Rhynchites heros), aphid weevil (Cylas formicarius), cotton weevil (Anthonomus grandis), weevil (Echinocnemus squameus), weevil (Euscepes postfasciatus) Rice weevil (Lissohoptrus oryzophilus), horned weevil (Otiorhynchus sulcatus), granary weevil (Sitophilus granarius), hornet weevil (Sitophilus zeamais), bark weevil (Sphenophorus venatus vestitus moth) erus fuscipes).

  Soybean flies (Asphondylia yushimai), mud wings (Sitodiplosis mosellana), fruit flies (Bactrocera cucurbitae), citrus fruit flies (Bactrocera dorsalis), citrus fruit flies (Ceratitis capitata), rice moth flies Leafhopper (Agromyza oryzae), Leafworm (Chromatomyia horticola), Eggplant leaffly (Liriomyza bryoniae), Leafhopper (Liriomyza chinensis), Tomato leaffly (Liriomyza sativae), Beanworm (Liriomyza trifoli), Liriomyza trifoli (Pegomya cunicularia), apple haggot (Rhagoletis pomonella), hessian fly (Mayetiola destructor), housefly (Musca domestica), barn fly (Stomoxys calcitrans), sheep flies (Melophagus ovinus), bullflies (Hypoderma bovisma), , Sheep flies (Oestrus ovis), tsetse flies (Glossina palpalis, Glossina morsitans), black-headed ayu (Prosimulium yezoensis), bullfly (Tabanus trigonus), giant fly (Telmatoscopus albipunctatus), nipponen sip (Leptocons) Diptera, such as Aedes aegypti, Aedes albopicutus, Anopheles hyracanus sinesis.

  Bumblebee (Apethymus kuri), Bumblebee (Athalia rosae), Bumblebee (Arge pagana), Bumblebee (Neodiprion sertifer), Bumblebee (Dryocosmus kuriphilus), Gantai (Eciton burchelli, Eciton schmitus), Eciton burchelli, Eciton schmitus Hymenoptera insects such as mandarina, bulldog ant (Myrmecia spp.), fire ant (Solenopsis spp.), pharaoh ant (Monomorium pharaonis).

  Straight-legged insects such as Teleogryllus emma, Gryllotalpa orientalis, Locusta migratoria, Oxya yezoensis, Schistocerca gregaria and others.

  Coleoptera insects such as Onychiurus folsomi, Onychiurus sibiricus and Bourletiella hortensis.

  Reticulate insects such as black cockroach (Periplaneta fuliginosa), cockroach (Periplaneta japonica), German cockroach (Blattella germanica).

  Termite insects such as termites (Coptotermes formosanus), Yamato termites (Reticulitermes speratus), Taiwan termites (Odontotermes formosanus).

  Coleoptera insects such as cat fleas (Ctenocephalidae felis), dog fleas (Ctenocephalides canis), chicken fleas (Echidnophaga gallinacea), human fleas (Pulex irritans), keops rat fleas (Xenopsylla cheopis) and the like.

  White-headed insects such as chicken lice (Menacanthus stramineus) and bovine lice (Bovicola bovis).

  Louse insects such as cattle lice (Haematopinus eurysternus), pig lice (Haematopinus suis), cattle white lice (Linognathus vituli), horned lice (Solenopotes capillatus) and the like.

  Dust mites such as cyclamen dust mite (Phytonemus pallidus), chano dust mite (Polyphagotarsonemus latus), and Sudabuto dust mite (Tarsonemus bilobatus).

  Spider mites such as cabbage mite (Penthaleus erythrocephalus) and wheat mite (Penthaleus major).

  Spider mites such as rice spider mite (Oligonychus shinkajii), citrus spider mite (Panonychus citri), blue spider mite (Panonychus mori), apple spider mite (Panonychus ulmi), Kanzawa spider mite (Tetranychus kanzawai), spider mite (Tetranychus urticae), etc.

  Chinese cabbage mite (Acaphylla theavagrans), tulip rust mite (Aceria tulipae), tomato rust mite (Aculops lycopersici), citrus red mite (Aculops pelekassi), apple rust mite (Aculus schlechtendali), black rust mite (Eriophyes chitrastrostrum) ) Etc.

  Acarids such as Robin tick (Rhizoglyphus robini), Tyrophagus putrescentiae, and Tyrophagus similis.

  Bee mites such as honeybee mite (Varroa jacobsoni).

  Tick tick (Boophilus microplus), Rhipicephalus sanguineus, Tick tick (Haemaphysalis longicornis), Tick tick (Haemophysalis flava), Tick tick (Haemophysalis campanulata), Tick tick (Ixo tus tick) Tick such as Amblyomma spp.), Dermacentor spp.

  Crawling ticks, such as the crayfish tick (Cheyletiella yasguri) and the cat crawfish tick (Cheyletiella blakei).

  Acne mites, such as Inodex canis and Demodex cati.

  Cucumber mites such as sheep cucumber mites (Psoroptes ovis).

  Spider mites, such as Sarcoptes scabiei, Notoedres cati, and Knemidocoptes spp.

  Crustacea such as Armadillidium vulgare.

  Gastropods such as Pomacea canaliculata, African mussel (Achatina fulica), Slug (Meghimatium bilineatum), Chaukoura slug (Limax Valentiana), Uskawamai (Acusta despecta sieboldiana), Mishamai mai (Euhadra peliomphala).

  Southern nematode nematode (Prathylenchus coffeae), Kitane-negususa nematode (Prathylenchus penetrans), Kurume rushes nematode (Prathylenchus vulnus), potato cyst nematode (Globodera rostochiensis), soybean cyst nematode (Heterodera lypter Nematodes such as root-knot nematodes (Meloidogyne incognita), rice-spotted nematodes (Aphelenchoides besseyi), and pine wood nematodes (Bursaphelenchus xylophilus).

  In addition, specific examples of endoparasites such as livestock, poultry, and pet animals that can be controlled using the compounds of the present invention include the following organisms, but the present invention is not limited to these. .

Haemonchus, Trichostrongylus, Ostertagia, Nematodirus, Cooperia, Ascaris, Bunostomum, Esphagostomum Genus (Oesophagostomum), Chabertia, Trichuris, Strongylus, Trichonema, Dictyocaulus, Capillaria, Heterakis ), Toxocara, Ascaridia, Oxyuris, Ancylostoma, Uncinaria, Toxacaris, Parascaris, and other nematodes ,
Filariidae nematodes such as Wuchereria, Blueia, Onchoceca, Dirofilaria and Loa.

  Dracunculidae nematodes, such as the genus Deacunculus.

  Dogworms (Dipylidium caninum), caterpillars (Taenia taeniaeformis), rodents (Taenia solium), striped tapeworms (Taenia saginata), contracted tapeworms (Hymenolepis diminuta), Beneden tapeworms (Moniezia benedeni), Tapeworms such as Diphyllobothrium latum, Manson cleftworm (Diphyllobothrium erinacei), Echinococcus granulosus, Echinococcus multilocularis.

  Fasciola hepatica (F. gigantica), Westermann lung fluke (Paragonimus westermanii), hypertrophic fluke (Fasciolopsic bruski), pancreatic fluke (Eurytrema pancreaticum, E. coelomaticum), liver fluke (Clonorchis sinensis), Schistosoma Schistosoma japonicum), Schistosoma haematobium, Schistosoma mansoni, etc.

  Eimeria tenella, Eimeria acervulina, Eimeria brunetti, Eimeria maxima, Eimeria necatrix, Eimeria bovis, Eimeria bovis Eimeria spp., Such as Eimeria ovinoidalis.

  Trypanosomsa cruzi, Leishmania spp., Plasmodium spp., Babesis spp., Trichomonadidae spp., Histomanas spp., Giardia (Giardia spp.), Toxoplasma spp., Entamoeba histolytica, Theileria spp.

  Furthermore, the compound of the present invention is also effective against pests that have developed resistance to existing insecticides such as organophosphorus compounds, carbamate compounds, and pyrethroid compounds.

  That is, the compound of the present invention is composed of the order of mucous eyes (Coleoptera), reticulates (Roaches), straight moths (Grasshoppers), termites, common moths (Thrips), hemimorphs (stink bugs and leafhoppers). Eyes), Lepidoptera (Lepidoptera), Coleoptera (Coleoptera), Hymenoptera (Hymenoptera), Diptera (Flyidae), Islamic (Flea), Liceid, and other insects, ticks In addition, pests belonging to gastropods and nematodes can be effectively controlled at low concentrations. On the other hand, the compounds of the present invention are extremely useful with little adverse effect on mammals, fish, crustaceans and beneficial insects (beneficial insects such as bees and bumblebees, natural enemies such as honeybees, wasps, mistletoe flies, mosquitoes, and mites). Has features.

  When using the compound of the present invention, it is usually mixed with a suitable solid carrier or liquid carrier, and if desired, a surfactant, penetrant, spreading agent, thickener, antifreezing agent, binder, anti-caking agent , Disintegrating agents, antifoaming agents, preservatives and anti-degradation agents, etc., and soluble concentrate, emulsion (emulsifiable concentrate), wettable powder, water-soluble powder, granular water Water dispersible granule, water soluble granule, suspension concentrate, concentrated emulsion, suspoemulsion, microemulsion, dustable powder ), Granule tablets, and emulsifiable gels, and can be put to practical use. Further, from the viewpoint of labor saving and safety improvement, the preparations of any of the above dosage forms can be provided by being enclosed in a water-soluble package such as a water-soluble capsule and a bag of a water-soluble film.

  Examples of the solid carrier include quartz, calcite, gypsum, dolomite, chalk, kaolinite, pyrophyllite, sericite, halosite, metahalosite, kibushi clay, glazed clay, porcelain stone, siegrite, and allophane. Natural minerals such as shirasu, kira, talc, bentonite, activated clay, acid clay, pumice, attapulgite, zeolite and diatomaceous earth, for example, calcined clay, perlite, shirasu balloon, vermiculite, attapulgus clay and calcined diatomaceous earth Baked products such as magnesium carbonate, calcium carbonate, sodium carbonate, sodium bicarbonate, ammonium sulfate, sodium sulfate, magnesium sulfate, diammonium hydrogen phosphate, ammonium dihydrogen phosphate and potassium chloride, such as glucose, fructose , And Sugars such as sugar and lactose, polysaccharides such as starch, powdered cellulose and dextrin, organic materials such as urea, urea derivatives, benzoic acid and benzoic acid salts, such as wood flour, cork flour, corn cobs, walnut shells and Examples include plants such as tobacco stalks, fly ash, white carbon (for example, hydrous synthetic silica, anhydrous synthetic silica, hydrous synthetic silicate, etc.) and fertilizers.

Examples of the liquid carrier include xylene, alkyl (C ₉ or C ₁₀ etc.) benzene, phenyl xylyl ethane and alkyl (C ₁ or C ₃ etc.) naphthalene and other aromatic hydrocarbons, machine oil, normal paraffin, isoparaffin and Aliphatic hydrocarbons such as naphthene, mixtures of aromatic and aliphatic hydrocarbons such as kerosene, alcohols such as ethanol, isopropanol, cyclohexanol, phenoxyethanol and benzyl alcohol, ethylene glycol, propylene glycol, diethylene glycol, hexylene glycol , Polyhydric alcohols such as polyethylene glycol and polypropylene glycol, propyl cellosolve, butyl cellosolve, phenyl cellosolve, propylene glycol monomethyl ether, propylene glycol Ethers such as ethyl monoethyl ether, propylene glycol monopropyl ether, propylene glycol monobutyl ether and propylene glycol monophenyl ether, ketones such as acetophenone, cyclohexanone and γ-butyrolactone, fatty acid methyl esters, dialkyl esters of succinic acid, dialkyl esters of glutamic acid, adipine esters such as dialkyl ester and dialkyl phthalate esters, N- alkyl (C _1, C ₈ or C _12, etc.) acid amide pyrrolidone, soybean oil, linseed oil, rapeseed oil, coconut oil, such as cottonseed oil and castor oil Examples include fats and oils, dimethyl sulfoxide 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 (mono or di) phenyl ether, polyoxyethylene (mono, di or tri) styryl phenyl ether, polyoxyethylene polyoxypropylene block copolymer, polyoxyethylene Ethylene fatty acid (mono or di) ester, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, castor oil ethylene oxide adduct, acetylene glycol, acetylene alcohol, ethylene oxide adduct of acetylene glycol, ethylene oxide adduct of acetylene alcohol and alkyl Nonionic surfactants such as glycosides, alkyl sulfate esters, alkylbenzene sulfonates, lignin sulfonates, alkyls Rufosuccinate, naphthalene sulfonate, alkyl naphthalene sulfonate, salt of formalin condensate of naphthalene sulfonic acid, salt of formalin condensate of alkyl naphthalene sulfonic acid, polyoxyethylene alkyl ether sulfate or phosphate ester salt, polyoxyethylene (Mono or di) alkyl phenyl ether sulfate or phosphate ester salt, polyoxyethylene (mono, di or tri) styryl phenyl ether sulfate or phosphate ester salt, polycarboxylate (eg polyacrylate, polymaleate and maleate) Copolymer of acid and olefin, etc.) and anionic surfactants such as polystyrene sulfonate, cationic surfactants such as alkylamine salts and alkyl quaternary ammonium salts, and amphoteric interfaces such as amino acid type and betaine type Sexual agents, silicone-based surfactants and fluorinated surfactants.

  The content of these surfactants is not particularly limited, but is usually preferably in the range of 0.05 to 20 parts by weight with respect to 100 parts by weight of the preparation of the present invention. These surfactants may be used alone or in combination of two or more.

  The application amount of the compound of the present invention varies depending on the application scene, application time, application method, cultivated crops, etc., but generally 0.005 to 50 kg per hectare (ha) is appropriate as the amount of active ingredient.

  On the other hand, when using the compound of the present invention for the control of the ectoparasites of mammals and birds as domestic animals and pets, an effective amount of the compound of the present invention is administered orally together with injection additives (intramuscular, Parenteral administration such as subcutaneous, intravenous, intraperitoneal; transdermal administration such as immersion, spraying, bathing, washing, pouring-on and spotting-on and dusting; nasal administration Can be administered. The compounds of the present invention can also be administered by molded products using strips, plates, bands, collars, ear marks, limb bands, labeling devices and the like. In administration, the compound of the present invention can be in any dosage form suitable for the administration route.

  Arbitrary forms to be prepared include solid preparations such as powders, granules, wettable powders, pellets, tablets, large pills, capsules, molded products containing active compounds; injection solutions, oral solutions, skin Liquid preparations used above or in body cavities; solution preparations such as Pour-on agents, spot-on agents, flowable agents and emulsions; semi-solid preparations such as ointments and gels.

  The solid preparation can be used mainly for oral administration or diluted with water for transdermal administration or environmental treatment. Solid preparations can be prepared by adding the active compound, if necessary, with adjuncts, mixing with appropriate excipients, and converting to the desired shape. Suitable excipients include, for example, inorganic substances such as carbonates, bicarbonates, phosphates, aluminum oxides, silicas, clays, and organic substances such as sugars, cellulose, crushed grains, and starches.

  Injection solutions can be administered intravenously, intramuscularly and subcutaneously. Injection solutions dissolve the active compound in a suitable solvent and, if necessary, solubilizers, acids, bases, buffer salts, antioxidants. And can be prepared by adding additives such as protective agents. Suitable solvents include water, ethanol, butanol, benzyl alcohol, glycerin, propylene glycol, polyethylene glycol, N-methylpyrrolidone and mixtures thereof, physiologically acceptable vegetable oils, synthetic oils suitable for injection, and the like. Examples of solubilizers include polyvinylpyrrolidone, polyoxyethylated castor oil, and polyoxyethylated sorbitan ester. Protecting agents include benzyl alcohol, trichlorobutanol, p-hydroxybenzoic acid ester and n-butanol.

  Oral solutions can be administered directly or diluted. It can be prepared in the same manner as an injectable solution.

  Flowables, emulsions, etc. can be administered directly or diluted transdermally or by environmental treatment.

  Solutions used on the skin can be administered by dripping, spreading, rubbing, spraying, spraying or applying by dipping (immersion, bathing or washing). These solutions can be prepared in the same manner as injection solutions.

  Pour-on and spot-on agents can be dripped or sprayed onto a limited area of the skin, so that the active compound can be immersed in the skin and act systemically . Drops and drop preparations can be prepared by dissolving, suspending or emulsifying the active ingredient in suitable skin-compatible solvents or solvent mixtures. If necessary, auxiliary agents such as surfactants, colorants, absorption promoting substances, antioxidants, light stabilizers and adhesives may be added.

  Suitable solvents include water, alkanol, glycol, polyethylene glycol, polypropylene glycol, glycerin, benzyl alcohol, phenylethanol, phenoxyethanol, ethyl acetate, butyl acetate, benzyl benzoate, dipropylene glycol monomethyl ether, diethylene glycol monobutyl ether, acetone, Methyl ethyl ketone, aromatic and / or aliphatic hydrocarbons, vegetable or synthetic oil, DMF, liquid paraffin, light liquid paraffin, silicone, dimethylacetamide, N-methylpyrrolidone or 2,2-dimethyl-4-oxy-methylene-1, 3-dioxolane is mentioned. Absorption enhancers include DMSO, isopropyl myristate, dipropylene glycol pelargonate, silicone oil, aliphatic esters, triglycerides and fatty alcohols. Antioxidants include sulfites, metabisulfites, ascorbic acid, butylhydroxytoluene, butylhydroxyanisole and tocopherol.

  The emulsion can be administered orally, transdermally or as an injection. In emulsions, active ingredients are dissolved in a hydrophobic phase or a hydrophilic phase, and this is further added with a suitable emulsifier, and if necessary, a colorant, an absorption promoting substance, a protective agent, an antioxidant, a light-shielding agent, a thickening substance, etc. Can be prepared by homogenizing with other phase solvents together with other auxiliary agents.

  As hydrophobic phase (oil), paraffin oil, silicone oil, sesame oil, almond oil, castor oil, synthetic triglyceride, ethyl stearate, di-n-butyryl adipate, hexyl laurate, dipropylene glycol pelargonate, branched chain Of a short fatty acid having a chain length and a saturated fatty acid having a chain length of C16 to C18, isopropyl myristate, isopropyl palmitate, capryl / caprate of a saturated fatty alcohol having a chain length of C12 to C18, isopropyl stearate, oleyl oleate Decyl oleate, ethyl oleate, ethyl lactate, waxy fatty acid ester, dibutyl phthalate, diisopropyl adipate, isotridecyl alcohol, 2-octyldodecanol, cetyl stearyl alcohol, oleyl alcohol It is.

  Examples of the hydrophilic phase include water, propylene glycol, glycerin, and sorbitol.

  Emulsifiers include nonionic interfaces such as polyoxyethylated castor oil, polyoxyethylated sorbitan monoolefin acid, sorbitan monostearate, glyceryl monostearate, polyoxyethyl stearate, alkylphenol polyglycol ether, etc. Activators; amphoteric surfactants such as disodium N-lauryl-β-iminodipropionate and lecithin; anions such as sodium lauryl sulfate, fatty alcohol sulfate ether, monoethanolamine salt of mono / dialkyl polyglycol orthophosphate Surfactants; cationic surfactants such as cetyltrimethylammonium chloride.

  Other adjuvants include carboxymethyl cellulose, methyl cellulose, polyacrylate, alginate, gelatin, gum arabic, polyvinyl pyrrolidone, polyvinyl alcohol, methyl vinyl ether, a copolymer of maleic anhydride, polyethylene glycol, wax, colloidal silica.

  Semi-solid preparations can be administered by application on the skin or spreading or introduction into body cavities. Gels can be prepared by adding sufficient thickener to a solution prepared as described above for an injectable solution to produce a clear material having an ointment-like consistency.

  Next, formulation examples of the preparation when using the compound of the present invention are shown. However, the formulation examples of the present invention are not limited to these. In the following formulation examples, “parts” means parts by weight.

[Wettable powder]
Compound of the present invention 0.1 to 80 parts Solid carrier 5 to 98.9 parts Surfactant 1 to 10 parts Others 0 to 5 parts Other examples include anti-caking agents and decomposition inhibitors.

〔emulsion〕
Compound 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]
Compound of the present invention 0.1 to 70 parts Liquid carrier 15 to 98.89 parts Surfactant 1 to 12 parts Others 0.01 to 30 parts Others include, for example, antifreezing agents and thickeners.

[Granule wettable powder]
Compound 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.

[Liquid]
Compound 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]
Compound 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]
Compound 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.

  Next, although the formulation example which uses this invention compound as an active ingredient is shown more concretely, this invention is not limited to these.

  In the following formulation examples, “parts” means parts by weight.

[Formulation Example 1] wettable powder Compound No.1-001 20 parts pyrophyllite 74 parts Solpol 5039 4 parts (mixture of nonionic surfactant and anionic surfactant: Toho Chemical Co., Ltd.) Product 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 Compound of the present invention No.1-001 5 parts Xylene 75 parts N-methylpyrrolidone 15 parts Solpol 2680 5 parts (mixture of nonionic surfactant and anionic surfactant: Toho Chemical Industry (Product name)
The above is uniformly mixed to obtain an emulsion.

[Formulation Example 3] Suspension Agent Compound No.1-001 25 parts Agrisol S-710 10 parts (Nonionic Surfactant: Kao Corporation trade name)
LUNOX 1000C 0.5 part (anionic surfactant: Toho Chemical Industries, 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 4] Granule wettable powder Compound No.1-001 of the present invention 75 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 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 No. 1-001 of the present invention 5 parts Bentonite 50 parts Talc 45 parts After uniformly mixing and pulverizing the above, a small amount of water is added and mixed with stirring, and granulated with an extrusion granulator. And dried into granules.

[Formulation Example 6] Powder Compound of the present invention No.1-001 3 parts Carplex # 80D 0.5 part (Synthetic hydrous silicic acid: Shionogi Pharmaceutical Co., Ltd. trade name)
Kaolinite 95 parts Diisopropyl phosphate 1.5 parts The above is uniformly mixed and ground to obtain a powder.

  In use, the above preparation is diluted 1 to 10000 times with water or sprayed directly without dilution.

[Formulation Example 7] wettable powder preparation Compound No. 1-001 of the present invention 25 parts sodium diisobutylnaphthalenesulfonate 1 part calcium n-dodecylbenzenesulfonate 10 parts alkylaryl polyglycol ether 12 parts naphthalenesulfonic acid formalin condensate Sodium salt 3 parts Emulsion type silicone 1 part Silicon dioxide 3 parts Kaolin 45 parts [Formulation Example 8] Water-soluble thickener preparation Compound No.1-001 20 parts Polyoxyethylene lauryl ether 3 parts Sodium dioctyl sulfosuccinate 3. 5 parts dimethyl sulfoxide 37 parts 2-propanol 36.5 parts [Formulation Example 9] Solution for spraying the present compound No.1-001 2 parts dimethyl sulfoxide 10 parts 2-propanol 35 parts acetone 53 parts [Formulation Example 10] transdermal Solution for administration The present compound No.1-001 5 Parts hexylene glycol 50 parts isopropanol 45 parts [Formulation Example 11] Solution for transdermal administration Compound No. 1-001 5 parts propylene glycol monomethyl ether 50 parts Dipropylene glycol 45 parts [Formulation example 12] transdermal administration (instillation) ) Solution for the Invention Compound No.1-001 2 parts Light Liquid Paraffin 98 parts [Formulation Example 13] Solution for the transdermal administration (drip) Compound No.1-001 2 parts Light Liquid Paraffin 58 parts Olive Oil 30 parts ODO -H 9 parts Shin-Etsu Silicone 1 part In addition, when the compound of the present invention is used as an agrochemical, other types of herbicides, various insecticides, acaricides, nematicides, You may mix and apply with a disinfectant, a plant growth regulator, a synergist, a fertilizer, a soil conditioner, etc.

  In particular, when mixed with other pesticides or plant hormones, the cost can be reduced by reducing the amount of applied medicine, the insecticidal spectrum can be expanded by the synergistic action of the mixed drugs, and higher pest control effects can be expected. At this time, a combination with a plurality of known agricultural chemicals is also possible. Examples of the type of agricultural chemical used in combination with the compound of the present invention include compounds described in The Pesticide Manual 15th edition, 2009, and the like. Specific examples of common names are as follows, but the general names are not necessarily limited to these.

  Bactericides: acibenzolar-S-methyl, acylaminobenzamide, acypetacs, aldimorph, ametoctradin, amisulbrom, amobam, ampropyl Phos (ampropyfos), anilazine, azaconazole, azithiram, azoxystrobin, barium polysulfide, benalaxyl, benalaxyl-M, benodaril (Benodanil), benomyl, benquinox, bentaluron, benthiavalicarb, benthiazole, benzamacril, benzamorf, bethoxazine, Binapacryl Biphenyl, bitertanol, blasticidin-S, bixafen, bordeaux mixture, boscalid, bromoconazole, bupirimate, buthiobate (Buthiobate), calcium polysulfide, calcium polysulfide, captafol, captan, carpropamid, carbamorph, carbendazim, carboxin (Carboxin), carvone, cheshunt mixture, chinomethionat, clobenthiazone, chloraniformethane, chloranil, chlorfenazol, Chloroneb (c hloroneb), chloropicrin, chlorothalonil, chlorquinox, chlozolinate, climbazole, clotrimazole, copper acetate, basic copper carbonate (copper carbonate, basic), cupric hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper sulfate, basic sulfuric acid Copper sulfate, basic, copper zinc chromate, cufraneb, cuprobam, cyazofamid, cyclafuramid, cycloheximide, cyflufenamid, Simoxanil, cypendazole, cyproconazole (cyp) roconazol), cyprodinil, cyprofuram, dazomet, debacarb, decaentin, dehydroacetic acid, dichlorfluanid, dichlone, Dichlorophen, dichlozoline, diclobutrazol, diclocymet, diclomedine, dicloran, etc.

  Bactericides (continued): diethofencarb, difenoconazole, diflumetorim, dimethirimol, dimethomorph, dimoxystrobin, diniconazole-M, diniconazole-M, diniconazole-M M), dinobuton, dinocap, dinocap-4, dinocap-6, dinoton, dinosulfon, dinoterbon, diphenylamine ), Dipyrithione, ditalimfos, dithianon, dodemorph, dodine, drazoxolon, edifenphos, epoxiconazole, etaconazole, etaconazole Xham (ethaboxam), etem, etirimol, ethoxyquin, etridianol, famoxadone, fenarimol, febuconazole, fenamidone, phenaminosulf ), Fenapanil, fendazosulam, fenfuram, fenhexamid, fenitropan, fenoxanil, fenpiclonil, fenpropidin, fenpyrazamine (fenpyrazamine), fenpropimorph, fentin, ferbam, ferimzone, fluazinam, fludioxonil, flumetover, flumorph, full Fluopicolide, fluopyram, fluoroimide, fluotrimazole, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, fluthianyl (fluoxanil) flutianil), flutolanil, flutriafol, fluxapyroxad, folpet, fosetyl-aluminium, fuberidazole, fluralaxyl, flametopyr ( furametpyr), furcarbanil, furconazole, fluconazole-cis, furmecyclox, furphanate, furyonate, glyodin, griseofulvin, guazachi (Guazatine), halacrinate, hexachlorobenzene, hexaconazole, hexylthiofos, hydroxyquinoline sulfate, hymexazol, imazalil, Imibenconazole, iminoctadine, ipconazole, iprobenfos, iprodione, iprovalicarb, isoprothiolane, isovaledione, etc.

  Fungicide (continued): kasugamycin, kresoxim-methyl, mancopper, mancozeb, mandipropamid, maneb, mebenil, mecarbinzid , Mepanipyrim, mepronil, metalaxyl, metalaxyl-M, metam, metazoxolon, metconazole, metasulfocarb, metoxasulfocarb, metoxafloxam ), Methyl isothiocyanate, metiram, metinominostrobin, metrafenone, metsulfovax, milneb, microbutanil, microzoline (myclozo) lin), nabam, natamycin, nickel bis (dimethyldithiocarbamate), nitrostyrene, nitrothal-isopropyl, nuarimol, OH (OCH), octhilinone, offurace, orysastrobin, oxadixyl, oxine copper, oxycarboxin, oxpoconazole fumarate , Pefurzoate, penconazole, penflufen, penencycuron, penthiopyrad, o-phenylphenol, phosdiphen, phthalide, picoxis Robin (picoxystrobin), piperalin (piperalin), polycarbamate (polycarbamate), polyoxins (polyoxins), polyoxorim (polyoxorim), potassium azide (potassium hydrogen carbonate) (potassium hydrogen carbonate), proquinazid (proquinazid) probenazole), prochloraz, procymidone, propamocarb hydrochloride, propiconazole, propineb, prothiocarb, prothioconazole, pyracarbolid, Pyraclostrobin, pyrazophos, pyridinitril, pyrifenox, pyrimethanil, pyriofenone, pyroculone (pyroq) uilon, pyroxychlor, pyroxyfur, quinomethionate, quinoxyfen, quintozene, quinacetol-sulfate, quinazamid, quinazaazole, quinconazole rabenzazole).

  Fungicide (continued): sodium azide, sodium hydrogen carbonate, sodium hypochlorite, sulfur, spiroxamine, salicylanilide, silthiofam (Silthiofam), simeconazole, tebuconazole, tecnazene, tecoram, tetraconazole, thiabendazole, thiadifluor, thicyofen, thifluzamide thifluzamide, thiochlorfenphim, thiophanate, thiophanate-methyl, thioquinox, thiram, thiadinyl, tioxymid, tolcrophos-me Tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triamiphos, triarimol, triazoxide, triazbutil, tributyltin oxide ), Trichlamide, tricyclazole, tridemorph, trifloxystrobin, triflumizole, triforine, triticonazole, validamycin, validamycin Examples include valifenalate, vinclozolin, zarilamide, zinc sulfate, zineb, ziram, zoxamide and shiitake mycelium extract.

  Bactericides: benzalkonium chloride, bithionol, bronopol, cresol, formaldehyde, nitrapyrin, oxolinic acid, oxyterracycline , Streptomycin and tecloftalam.

  Nematicides: aldoxycarb, cadusafos, DCP, DBCH, dichlofenthion, DSP (DSP), etoprophos, fenamiphos, fensulfothion, fluene Sulfone (fluensulfone), fosthiazate (fosthiazate), fosthietan (fosthietan), imisiafos (imicyafos), isamidofos (isamidofos), isazofos (isazofos), oxamyl (oxamyl) and thionazin (thionazin) and the like.

  Acaricide: acequinocyl, acrinathrin, amitraz, BCI-033 (test name), bifenazate, bromopropylate, chinomethionat, chlorobezilate , Clofentezine, cyenopyrafen, cyflumetofen, cyhexatine, dicofol, dienochlor, denochlor (DNOC), etoxazole, quinazaquin (fenaza) Fenbutatin oxide, fenothiocarb, fenpropathrin, fenpyroximate, fluacrypyrim, halfenprox (halfenpro) x), hexythiazox, milbemectin, propargite, pyridaben, pyrimidifen, S-1870 (test name), spirodiclofen, spiromesifen ( spyromesifen), NNI-0711 (test name), CL900187 (test name) and tebufenpyrad.

  Insecticides: abamectin, acephate, acetamipirid, alanamicarb, aldicarb, allethrin, azamethiphos, azinphos-methyl, bacillus tubulin Bacillus thuringiensis, bendiocarb, benfluthrin, benfuracarb, bensultap, bifenthrin, bioallethrin, bioresmethrin, bistrifluron, tris Buprofezin, butocarboxim, carbaryl, carbofuran, carbosulfan, cartap, chlorantraniliprole, Chlorethxyfos, chlorfenapyr, chlorfenvinphos, chlorfluazuron, chlormephos, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, chromafenozide Clothianidin, cyantraniliprole, cycloprothrin, cyflumetofen, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin cyhalothrin), cypermethrin, alpha-cypermethrin, beta-cypermethrin, zeta-cypermethrin, cyromazine, Deltamethrin, diacloden, diafenthiuron, diazinon, dichlorvos, diflubenzuron, dimethylvinphos, dinotefuran, diofenolan, diofenolan Disulfoton, dimethoate, emamectin-benzoate, empenthrin, endosulfan, alpha-endosulfan, EP-N, EPN, esfenvalerate, etiophencarb (Ethiofencarb), ethiprole, etofenprox, etrimfos, fenitrothion, fenobucarb, fenobucarb Fenoxycarb, fenpropathrin, fenthion, fenvalerate, fipronil, flonicamid, flubendiamide, flucythrinate, flufenerim , Flufenoxuron, flufenprox, flumethrin, fluvalinate, tau-fluvalinate, fonophos, formetanate, formotaion ( formothion), furathiocarb, flufiprole, flupyradifurone, flometoquin and the like.

  Insecticides (continued): halofenozide, hexaflumuron, hydramethylnon, imidacloprid, isofenphos, indoxacarb, isoprocarb, isoxathion ), Lepimectin, lufenuron, malathion, meperfluthrin, metaflumizone, metalaldehyde, methamidophos, methidathion, methidathion, methacrifos (methacrifos) ), Metalcarb, methomyl, metoprene, methoxychlor, methoxyfenozide, methyl bromide , Monocrotophos, muscalure, nitenpyram, novaluron, noviflumuron, omethoate, oxamyl, oxydemeton-methyl, oxydemeton-methyl (oxydemeton-methyl) oxydeprofos, parathion, parathion-methyl, pentachlorophenol (PCP), permethrin, phenothrin, phenthoate, phoxim, phorate ), Phosalone, phosmet, phosphamidon, pirimicarb, pirimiphos-methyl, profenofos, prothiofos, propaphos, prototri Protrifenbute, pyrometrozine, pyraclofos, pyrethrins, pyridalalyl, pyrifluquinazon, pyriprole, pyrafluprole, proxy, pyrifiprofen, py Resmethrin, rotenone, SI-0405 (study name), sulprofos, silafluofen, spinetram, spinosad, spirotetramat, sulfoxaflor ), Sulfotep, SYJ-159 (test name), tebfenozide, teflubenzuron, tefluthorin, terbufos, tetrachlorvinphos, tetrame Trimethrin, dT-80-phthalthrin, d-tetramethrin, tetramethylfluthrin, thiacloprid, thiocyclam, thiodicarb, thiamethoxam, thiophanox ( thiofanox, thiometon, tolfenpyrad, tralomethrin, trichlorfon, triazuron, triflumuron, vamidomion and ME-5343 (test name).

  Hereinafter, the present invention will be described in more detail by specifically describing synthesis examples and test examples of the compounds of the present invention as examples, but the present invention is not limited thereto.

  The medium pressure preparative liquid chromatography described in the synthesis example used an intermediate pressure preparative apparatus (Yamazen Co., Ltd.);

[Synthesis example]
Synthesis example 1
(S)-(−)-N- {3-Chloro-1- (pyridin-3-yl) -1H-pyrazol-4-yl} -2- (ethylthio) propanamide (present compound 1-004) Manufacturing process 1
Production of (S) -2- (ethylthio) propanoic acid To a solution of 10 g of (R) -2-bromopropionic acid in 100 ml of toluene was added 3.46 g of sodium carbonate, and the mixture was stirred at 50 ° C. for 2 hours. After completion of the reaction, the solvent was distilled off under reduced pressure, and the resulting solid was washed with 50 ml of ethyl acetate. To a solution of the solid obtained after washing and 200 ml of tetrahydrofuran was added 6.6 g of sodium ethyl mercaptan at 0 ° C., and the mixture was stirred at room temperature for 3 days. After completion of the reaction, 100 ml of ethyl acetate was added and extracted with 200 ml of water. The obtained aqueous layer was adjusted to pH 3 with 10% aqueous hydrochloric acid solution, extracted with 300 ml of ethyl acetate, dehydrated and dried over saturated brine and then anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 7.3 g of the desired product as a pale yellow oil.
¹ H NMR (CDCl ₃ , Me ₄ Si, 300 MHz) δ 3.44 (q, J = 7.2 Hz, 1H), 2.80-2.60 (m, 2H), 1.47 (d, J = 7 .2 Hz, 3H), 1.28 (t, J = 7.5 Hz, 3H) (a proton peak corresponding to COOH was not detected)
Process 2
Preparation of (S)-(−)-N- {3-Chloro-1- (pyridin-3-yl) -1H-pyrazol-4-yl} -2- (ethylthio) propanamide (S) -2- ( 7.4 g of oxalyl chloride and then 0.3 ml of N, N-dimethylformamide were added to a solution of 7.2 g of ethylthio) propanoic acid in 20 ml of dichloromethane and stirred at room temperature for 1 hour. After completion of the stirring, the solvent of the reaction solution was distilled off under reduced pressure, and 20 ml of dichloromethane was added to the obtained residue. This solution was added dropwise at 0 ° C. to a solution of 8.7 g of 3-chloro-1- (pyridin-3-yl) -1H-pyrazol-4-amine and 5.3 g of pyridine, prepared separately, at 0 ° C. At rt overnight. After completion of the reaction, 100 ml of water and 150 ml of ethyl acetate were added, and insoluble matters were removed by Celite filtration. The organic layer was taken out by a liquid separation operation, dehydrated and dried over saturated brine and then anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the resulting solid was washed with ethyl acetate to obtain 4.75 g of the desired product as a pale yellow solid. The filtrate was evaporated under reduced pressure, and the resulting residue was eluted with n-hexane-ethyl acetate [7: 3 to 3: 7 (volume ratio, the same applies hereinafter) gradient]. Purification by preparative liquid chromatography gave 7.2 g of the desired product as a pale yellow solid.
Melting point: 115-116 ° C
Specific rotation: [α] _D ^23.6 -47.9 ° (CHCl ₃ , c = 0.518)
The retention time of the target product thus obtained was measured using high performance liquid chromatography having an optically active column according to the optically active substance separation conditions described later. Retention time 11.9 min {(R)-(+)-N- {3-Chloro-1- (pyridin-3-yl) -1H-pyrazol-4-yl} -2- (ethylthio) propanamide (percent area Ratio 10.3%)} and retention time 16.7 min {(S)-(−)-N- {3-chloro-1- (pyridin-3-yl) -1H-pyrazol-4-yl} -2- The fraction corresponding to the peak of (ethylthio) propanamide (percentage area ratio 89.7%, 80% ee)} was detected.

Synthesis example 2
(S)-(−)-N- {3-Chloro-1- (pyridin-3-yl) -1H-pyrazol-4-yl} -2- (ethylthio) -N- (methoxymethyl) propanamide (present Preparation of Inventive Compound 1-005) (S)-(−)-N- {3-Chloro-1- (pyridin-3-yl) -1H-pyrazol-4-yl} -2- (ethylthio) propanamide ( 80% ee) 4.5 g tetrahydrofuran solution 150 ml was cooled to 0 ° C. and 60 wt% sodium hydride (dispersed in mineral oil) 0.88 g was added. After stirring at 0 ° C. for 15 minutes, 1.87 g of chloromethyl methyl ether was added and stirred at room temperature for 1 hour. After completion of the reaction, the reaction solution was cooled to 0 ° C., and 75 ml of a saturated aqueous ammonium chloride solution was added. Extraction was performed with 200 ml of chloroform, and the obtained organic layer was washed with 50 ml of water, and then dehydrated and dried with saturated brine and then anhydrous sodium sulfate. After distilling off the solvent, 5.5 g of the resulting residue was purified using high performance preparative liquid chromatography.

  For high performance liquid chromatography, Shimadzu Corporation 10AVP system was used.

Oven temperature: 40 ° C
Mobile phase: acetonitrile 7 ml / min, water 4 ml / min
Column: GL Science Inertsil-ODS3 (inner diameter 20 mm, length 250 mm, particle diameter 5 μm),
Measurement wavelength: 254 nm
5.5 g of the above product was dissolved in 25 ml of acetonitrile, and this solution was divided into 1.0 ml and subjected to separation work 25 times in total using high performance liquid chromatography under the conditions described above, with a retention time of 10.2 min. The fraction corresponding to the peak of was collected. After the solvent of the collected fraction was distilled off under reduced pressure, 3.6 g of a yellow oily substance was obtained. The same operation was performed again, and 6.4 g of a yellow oily substance was separated from the isomer using high performance liquid chromatography having an optically active column according to the optically active substance separation conditions described later. 0.5 g was obtained as white crystals (99% ee).
Melting point: 62-63 ° C
[Reference example]
Reference example 1
Production of 3-chloro-1- (pyridin-3-yl) -1H-pyrazol-4-amine (Part 1)
To a solution of 10.7 g of 3-chloro-1H-pyrazol-4-amine in 70 ml of toluene, 12.7 g of 3-bromopyridine, 2.65 g of copper iodide (monovalent), 28.9 g of potassium carbonate, and trans-N, N′-dimethylcyclohexane-1,2-diamine (3.96 g) and dimethyl sulfoxide (20 ml) were sequentially added. After completion of the addition, the inside of the reaction vessel was replaced with nitrogen gas, followed by stirring at 100 ° C. for 2 hours. After completion of the reaction, the solid precipitated in the reaction mixture was filtered off. To the obtained filtrate, 100 ml of ethyl acetate was added, washed with 50 ml of a 7% aqueous ammonia solution and then with saturated saline, and then dehydrated and dried over anhydrous sodium sulfate. After evaporating the solvent under reduced pressure, the obtained solid was washed with diisopropyl ether to obtain 8.52 g of the desired product as a brown solid.
Melting point: 139-143 ° C
Reference example 2
Production of 3-chloro-1- (pyridin-3-yl) -1H-pyrazol-4-amine (Part 2)
Process 1
Preparation of ethyl 3-chloro-1H-pyrazole-4-carboxylate To 9.71 g of ethyl 1-tert-butyl-5-chloro-1H-pyrazole-4-carboxylate was added 30 ml of concentrated hydrochloric acid under ice cooling. And stirred at room temperature overnight. After completion of the stirring, 10 ml of concentrated hydrochloric acid was added to the reaction mixture, and stirring was continued for a whole day and night. After completion of the reaction, the reaction mixture was cooled to 0 ° C., neutralized with an aqueous sodium hydroxide solution, and extracted with 100 ml of ethyl acetate. The obtained organic layer was dehydrated and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained solid was washed with n-hexane to obtain 6.28 g of the desired product as a white solid.
¹ H NMR (CDCl ₃ , Me ₄ Si, 300 MHz) δ 11.2 (brs, 1H), 8.10 (s, 1H), 4.33 (q, J = 7.2 Hz, 2H), 1.36 ( t, J = 7.2 Hz, 3H)
Process 2
Preparation of ethyl 3-chloro-1- (pyridin-3-yl) -1H-pyrazole-4-carboxylate 10.2 g of ethyl 3-chloro-1H-pyrazole-4-carboxylate in 150 ml of N, N-dimethylformamide To this, 15.6 g of 3-iodopyridine, 2.23 g of copper iodide (monovalent) and 33.0 g of cesium carbonate were sequentially added. After completion of the addition, the inside of the reaction vessel was replaced with nitrogen gas, followed by stirring at 130 ° C. for 5 hours. After completion of the reaction, the reaction mixture was allowed to cool to room temperature and 100 ml of 1N aqueous sodium hydroxide solution was added. Impurities in the reaction mixture were removed by Celite filtration under reduced pressure, and the obtained filtrate was extracted with 100 ml of ethyl acetate. The obtained organic layer was washed and dried in the order of saturated brine and then anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by medium pressure preparative liquid chromatography eluting with n-hexane-ethyl acetate (1: 1 gradient) to obtain 7.56 g of the desired product as a white solid.
Melting point: 90-93 ° C.

Process 3
Preparation of 3-chloro-1- (pyridin-3-yl) -1H-pyrazole-4-carboxylic acid 16.75 g of ethyl 3-chloro-1- (pyridin-3-yl) -1H-pyrazole-4-carboxylate Was dissolved in 130 ml of ethanol, 5.6 g of potassium hydroxide and 130 ml of water were sequentially added, and the mixture was stirred overnight at room temperature. After completion of the reaction, 2N hydrochloric acid aqueous solution was added to adjust the pH of the reaction mixture to 4, and the precipitated solid was taken out by filtration and washed with water. The taken solid was added to 200 ml of toluene and dehydrated using a Dean-Stark tube under reflux of toluene. After completion of dehydration, the solid in toluene was removed by filtration to obtain 14.5 g of the desired product as a light pink solid.
Melting point: 275-282 ° C.

Process 4
Production of 3- (3-chloro-4-nitro-1H-pyrazol-1-yl) pyridine 1.72 ml of acetic anhydride was added dropwise at a temperature of 40 ° C. or lower to a solution of concentrated hydrochloric acid 9 ml and fuming nitric acid 3.1 ml. After completion of dropping, the mixture was stirred at room temperature for 30 minutes and then heated to 60 ° C. To this solution, 5 g of 3-chloro-1- (pyridin-3-yl) -1H-pyrazole-4-carboxylic acid was added in 5 portions while maintaining the temperature at 60 ° C. Stir for 2 hours. After completion of the reaction, the reaction mixture was poured into ice water and neutralized with 1N aqueous sodium hydroxide solution. The precipitated solid was filtered, washed with water, and dried to obtain 4.2 g of the desired product as a pale yellow solid.
Melting point: 139-140 ° C
Process 5
Preparation of 3-chloro-1- (pyridin-3-yl) -1H-pyrazol-4-amine 3- (3-chloro-4-nitro-1H-pyrazol-1-yl) pyridine 4 g of ethyl acetate 20 ml, acetic acid 10 ml of water and 10 ml of water were heated to 65 ° C., and 2.5 g of reduced iron was added little by little. After completion of the addition, the mixture was stirred at 70 ° C. for 2 hours. After completion of the reaction, the reaction solution was allowed to cool to room temperature, 50 ml of water was added, and the pH was adjusted to 10 with sodium bicarbonate. Insoluble matters in the reaction solution were removed by filtration, and the organic layer of the filtrate was taken out by liquid separation. The obtained organic layer was dehydrated and dried in the order of saturated brine and then anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained solid was washed with diisopropyl ether to obtain 2.6 g of the desired product as a light purple solid.
Melting point: 142-144 ° C
Reference example 3
Preparation of N- {3-chloro-1- (pyridin-3-yl) -1H-pyrazol-4-yl} -2- (ethylthio) -N- (methoxymethyl) propanamide (racemic compound No. 1-005) body)
Process 1
Preparation of N- {3-chloro-1- (pyridin-3-yl) -1H-pyrazol-4-yl} -2- (ethylthio) propanamide To a solution of 2.5 g of 2- (ethylthio) propanoic acid in 5 ml of dichloromethane , 2.1 g of oxalyl chloride, and then 10 mg of N, N-dimethylformamide were added in this order, and the mixture was stirred at room temperature for 1 hour. After completion of the stirring, the solvent of the reaction solution was distilled off under reduced pressure, and 5 ml of dichloromethane was added to the resulting residue. This solution was added dropwise to a separately prepared solution of 2.5 g of 3-chloro-1- (pyridin-3-yl) -1H-pyrazol-4-amine and 1.5 g of pyridine in 20 ml of dichloromethane and stirred at room temperature for 40 minutes. did. After completion of the reaction, 15 ml of water was added to the reaction mixture and extracted with chloroform (20 ml × 2). The obtained organic layer was washed and dried in the order of saturated brine and then anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained solid was washed with diisopropyl ether to obtain 3.66 g of the desired product as a white solid.
Melting point: 104-105 ° C
Process 2
Preparation of N- {3-chloro-1- (pyridin-3-yl) -1H-pyrazol-4-yl} -2- (ethylthio) -N- (methoxymethyl) propanamide N- {3-Chloro-1 -(Pyridin-3-yl) -1H-pyrazol-4-yl} -2- (ethylthio) propanamide in 30 ml of tetrahydrofuran solution at 0 ° C., 60 wt% sodium hydride (dispersed in mineral oil) 0.23 g was added and stirred for 10 minutes. While maintaining 0 ° C., 0.48 g of chloromethyl methyl ether was added to the reaction solution, and then stirred at room temperature for 1 hour. After completion of the reaction, 15 ml of saturated aqueous ammonium chloride solution was added, and the mixture was extracted with chloroform (30 ml × 3). The obtained organic layer was washed and dried in the order of saturated brine and then anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by medium pressure preparative liquid chromatography eluting with n-hexane-ethyl acetate (9: 1 to 1: 1 gradient), and then again chloroform: methanol (99: 1 to 9). The product was purified by medium pressure preparative liquid chromatography eluting with a gradient of 1 to obtain 380 mg of the target product as a white solid.
Melting point: 68-69 ° C
Reference example 4
Preparation of ethyl 3-chloro-1H-pyrazole-4-carboxylate 1 g of ethyl 3-amino-1H-pyrazole-4-carboxylate was added to a solution of concentrated hydrochloric acid 2.2 ml, acetic acid 2.2 ml and phosphoric acid 1.3 ml. Add and cool to -5 ° C. A diazonium salt solution was prepared by adding dropwise a solution of 0.49 g of sodium nitrite to 1 ml of water while maintaining the temperature at -5 ° C. Separately, 6.4 ml of concentrated hydrochloric acid was cooled to 0 ° C., a solution of 0.73 g of sodium bisulfite in 1.5 ml of water was added dropwise while maintaining 0 ° C., and 0.16 g of copper sulfate pentahydrate was added. To this solution, the previously prepared diazonium salt solution and a solution of 0.73 g of sodium hydrogen sulfite in 1.5 ml of water were simultaneously added dropwise while maintaining 0 ° C. After completion of dropping, the mixture was stirred for 10 minutes, and the reaction solution was poured into ice water and then neutralized with an aqueous potassium hydroxide solution. Extraction was performed with chloroform (20 ml × 3), and the obtained organic layer was dehydrated and dried over saturated brine and then anhydrous sodium sulfate. After the solvent was distilled off, the resulting residue was purified by medium pressure preparative liquid chromatography eluting with n-hexane-ethyl acetate (gradient 5: 1 to 1: 2) to obtain 426 mg of the desired product in white. Obtained as a solid.
¹ H NMR (CDCl ₃ , Me ₄ Si, 300 MHz) δ 11.2 (brs, 1H), 8.10 (s, 1H), 4.33 (q, J = 7.2 Hz, 2H), 1.36 ( t, J = 7.2 Hz, 3H)
Reference Example 5
Preparation of (S) -N- (3-chloro-1H-pyrazol-4-yl) -2-methyl-3- (methylthio) propanamide 3-chloro-1H-pyrazol-4-amine 500 mg, (S)- To a solution of 627 mg of 2-methyl-3- (methylthio) propanoic acid and 979 mg of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride in 10.6 ml of N, N-dimethylformamide, 689 mg of 1-hydroxybenzotriazole is added. The mixture was added and stirred at room temperature for 1 hour. After completion of the reaction, 10 ml of a saturated aqueous sodium hydrogen carbonate solution was added, and the mixture was extracted with 10 ml of ethyl acetate. The obtained organic layer was washed with water, dehydrated and dried with saturated brine and then anhydrous sodium sulfate. After the solvent was distilled off, the resulting residue was purified by medium pressure preparative liquid chromatography eluting with n-hexane-ethyl acetate (4: 1 to 1: 5 gradient) to obtain 105 mg of the desired product {95.5 % ee, [α] _D ^23.4 -31.00 ° (CHCl _3, c = 0.100)} was obtained as a light pink solid.
Melting point: 92-93 ° C
Reference Example 6
Preparation of (S) -N- (3-Chloro-1H-pyrazol-4-yl) -2-methyl-3- (methylsulfinyl) propanamide (S) -N- (3-Chloro-1H-pyrazole-4 -Il) -2-methyl-3- (methylthio) propanamide To a solution of 100 mg of acetic acid in 0.86 ml was added 73 mg of 30 wt% aqueous hydrogen peroxide at room temperature and stirred for 5 hours. After completion of the reaction, 2 ml of a saturated aqueous sodium thiosulfate solution was added to the reaction solution, and a saturated aqueous sodium hydrogen carbonate solution was further added to adjust the pH to 7. Extraction was performed with 3 ml × 3 of ethyl acetate, and the obtained organic layer was dehydrated and dried over anhydrous sodium sulfate. After the solvent was distilled off, the obtained residue was purified by medium pressure preparative liquid chromatography eluting with chloroform-methanol 9: 1 to obtain 90 mg of the desired product {96% ee, [α] _D ^23.3. -61.00 ° (CHCl _3, c = 0.100)} was obtained as a white solid.
Melting point: 140-141 ° C
Reference Example 7
Preparation of (S) -N- (3-chloro-1H-pyrazol-4-yl) -2-methyl-3- (methylsulfonyl) propanamide (S) -N- (3-chloro-1H-pyrazole-4 -Il) -2-Methyl-3- (methylthio) propanamide To a solution of 100 mg of acetic acid in 0.86 ml, 30% by weight of aqueous hydrogen peroxide 145 mg and sodium tungstate dihydrate 8 mg were sequentially added at room temperature. Stir for 5 hours. After completion of the reaction, 2 ml of a saturated aqueous sodium thiosulfate solution was added to the reaction mixture, and a saturated aqueous sodium hydrogen carbonate solution was further added to adjust the pH to 7. Extraction was performed with 3 ml × 3 of ethyl acetate, and the obtained organic layer was dehydrated and dried over anhydrous sodium sulfate. After the solvent was distilled off, the obtained residue was purified by medium pressure preparative liquid chromatography eluting with n-hexane-ethyl acetate (gradient 9: 1 to 0:10) to obtain 82 mg of the desired product { 94.9% ee, [α] _D ^23.3 -54.00 ° (CHCl _3, c = 0.100)} was obtained as a white solid.
Melting point: 152-153 ° C
This invention compound can be manufactured according to the said manufacturing method and an Example. Although the example of this invention compound manufactured like the synthesis examples 1-2 is shown in Table 1, and those physical-property values are shown in Table 2, this invention is not limited only to these.

  In addition, “* 1” represents a resinous form, and “* 2” represents a resinous form having the same structure but a mixture of two isomers. If the isomer ratio is known, the ratio is listed in Table 2. “M.p,” represents a melting point.

The symbols in Table 2 have the following meanings.
s: singlet, d: doublet, t: triplet, q: quartet, m: multiplet, brs: broad peak.
[Table 1]

―――――――――――――――――――――――――――――――――――――――
No. R ¹ R ² mp (℃)
Configuration Optical purity Specific rotation ――――――――――――――――――――――――――――――――――――――――
1-001 CH ₂ CH ₃ S (O) CH ₂ CH ₃ * 2 (~ 3: 1)
(S)-(-) [α] _D ^23.0 -18.18 ° (CHCl ₃ , c = 0.100)
1-002 CH ₂ CH ₃ S (O) ₂ CH ₂ CH ₃ * 1
(S)-(+) 72.1% ee [α] _D ^23.0 + 4.21 ° (CHCl ₃ , c = 0.095)
1-003 H SCH ₃ 136-137
(S)-(-) 89.6% ee [α] _D ^23.0 -45.70 ° (CHCl ₃ , c = 0.498)
1-004 H SCH ₂ CH ₃ 137-138
(S)-(-) 89.6% ee [α] _D ^23.4 -44.35 ° (CHCl ₃ , c = 0.506)
1-005 CH ₂ OCH ₃ SCH ₂ CH ₃ 62-63
(S)-(-) 99% ee [α] _D ^23.4 -30.00 ° (CHCl ₃ , c = 0.510)
1-006 CH ₂ OCH ₃ SCH ₃ 76-78
(S)-(-) 90.1% ee [α] _D ^22.8 -19.21 ° (CHCl ₃ , c = 0.100)
1-007 CH ₂ OCH ₂ CH ₃ CH ₂ SCH ₃ * 1
(S)-(-) 94.9% ee [α] _D ^23.8 -24.31 ° (CHCl ₃ , c = 0.547)
1-008 CH ₂ OCH ₂ CH ₃ SCH ₃ 79-81
(S)-(-) 93.5% ee [α] _D ^22.9 -11.97 ° (CHCl ₃ , c = 0.211)
1-009 CH ₃ SCH ₂ CH ₃ 73-74
(S)-(+) 99% ee [α] _D ^24.2 + 20.00 ° (CHCl ₃ , c = 0.495)
1-010 CH ₃ S (O) ₂ CH ₂ CH ₃ 132-133
(S)-(+) 99% ee [α] _D ^24.3 + 11.15 ° (CHCl ₃ , c = 0.323)
1-011 CH ₂ OCH ₂ CH ₃ SCH ₂ CH ₃ * 1
(S)-(-) 99% ee [α] _D ^24.0 -23.21 ° (CHCl ₃ , c = 0.293)
1-012 CH ₃ S (O) CH ₂ CH ₃ * 2
(S)-(-) [α] _D ^23.8 -13.03 ° (CHCl ₃ , c = 0.261)
1-013 CH ₂ OCH ₃ CH ₂ SCH ₃ * 1
(S)-(-) 99% ee [α] _D ^23.8 -34.55 ° (CHCl ₃ , c = 0.110)
1-014 CH ₃ SCH ₃ 121-122
(S)-(+) 99% ee [α] _D ^23.5 + 30.14 ° (CHCl ₃ , c = 0.492)
―――――――――――――――――――――――――――――――――――――――
[Table 2]
――――――――――――――――――――――――――――――――――
No.
Proton nuclear magnetic resonance chemical shift value (in CDCl ₃ ): σ (ppm)
――――――――――――――――――――――――――――――――――
1-001;
(Isomer ratio 3) 9.00-8.96 (m, 1H), 8.64-8.65 (m, 1H), 8.18-8.10 (m, 1H), 8.04-7 .98 (m, 1H), 7.48-7.40 (m, 1H), 4.05-3.55 (m, 3H) 2.90-2.70 (m, 2H), 1.50- 1.15 (m, 9H)
(Isomer ratio 1) 9.00-8.96 (m, 1H), 8.64-8.65 (m, 1H), 8.18-8.10 (m, 1H), 8.04-7 .98 (m, 1H), 7.48-7.40 (m, 1H), 4.05-3.55 (m, 3H) 2.60-2.45 (m, 2H), 1.50- 1.15 (m, 9H)
1-002;
8.98 (d, J = 2.7 Hz, 1H), 8.62 (dd, J = 4.8, 1.5 Hz, 1H), 8.20 (s, 1H), 8.01 (ddd, J = 8.7, 2.7, 1.5 Hz, 1H), 7.45 (dd, J = 8.7, 4.8 Hz, 1H), 4.05-3.90 (m, 2H), 3. 65-3.45 (m, 1H), 3.45-3.25 (m, 1H), 3.20-3.05 (m, 1H), 1.64 (d, J = 7.2 Hz, 3H ), 1.38 (t, J = 7.5 Hz, 3H), 1.20 (t, J = 7.2 Hz, 3H)
1-007;
8.94 (d, J = 2.4 Hz, 1H), 8.61 (d, J = 4.8 Hz, 1H), 8.15-7.95 (m, 2H), 7.45 (dd, J = 8.1, 4.8 Hz, 1H), 5.70-5.15 (m, 1H), 4.90-4.45 (m, 1H), 3.85-3.65 (m, 2H) , 3.00-2.75 (m, 2H), 2.48 (dd, J = 12.3, 4.8 Hz, 1H), 2.01 (s, 3H), 1.25 (t, J = 7.2 Hz, 3H), 1.20 (d, J = 6.6 Hz, 3H)
1-011;
8.95 (d, J = 2.7 Hz, 1H), 8.62 (dd, J = 4.8, 1.5 Hz, 1H), 8.10 (s, 1H), 8.03 (ddd, J = 8.4, 2.7, 1.5 Hz, 1H), 7.45 (dd, J = 8.4, 4.8 Hz, 1H), 5.70-5.20 (m, 1H), 4. 80-4.40 (m, 1H), 3.75-3.65 (m, 2H), 3.45-3.30 (m, 1H), 2.70-2.50 (m, 2H), 1.49 (d, J = 6.9 Hz, 3H), 1.25 (t, J = 6.9 Hz, 3H), 1.16 (t, J = 7.5 Hz, 3H)
1-012;
8.96 (d, J = 2.7 Hz, 1H), 8.64-8.60 (m, 1H), 8.21-8.20 (m, 1H), 8.03-7.96 (m , 1H), 7.47-7.40 (m, 1H), 3.98 (q, J = 6.9 Hz, 1H), 3.31 (s, 3H), 2, 86-2.50 (m , 2H), 1.4-1.27 (m, 6H)
1-013;
8.96 (d, J = 2.7 Hz, 1H), 8.62 (dd, J = 4.8, 1.2 Hz, 1H), 8.06-8.01 (m, 2H), 7.45 (dd, J = 8.4, 4.8 Hz, 1H), 5.70-5.10 (m, 1H), 4.90-4.30 (m, 1H), 3.48 (s, 3H) 2.99-1.70 (m, 2H), 2.49 (dd, J = 12.6, 4.8 Hz, 1H), 2.01 (s, 3H), 1.21 (d, J = (6.3Hz, 3H)
――――――――――――――――――――――――――――――――――
The proton nuclear magnetic resonance chemical shift values in Table 2 were measured at 300 MHz using Me ₄ Si (tetramethylsilane) as a reference material.

A part of the optically active form of the compound of the present invention was separated into the optically active form using high performance liquid chromatography having an optically active column. The method will be described in detail, but the present invention is not limited to these.
1, Separation of optically active substance High performance liquid chromatography was made by Shimadzu Corporation; 10AVP system was used.

  The optically active substance was separated according to the conditions described below.

Flow rate: 6.0 ml / min Oven temperature: 40 ° C
Mobile phase: n-hexane: ethanol = 7: 3 (volume ratio)
Column: Daicel CHIRALPAK AD-H (inner diameter 20 mm, length 250 mm, particle diameter 5 μm),
Measurement wavelength: 254 nm
N- {3-chloro-1- (pyridin-3-yl) -1H-pyrazol-4-yl} -2- (ethylthio) -N- (methoxymethyl) propanamide (800 mg) was added to n-hexane: ethanol = This was dissolved in 8 ml of a 7: 3 (volume ratio) mixed solvent, this solution was divided into 0.3 ml, and the separation was performed 25 times in total using high performance liquid chromatography under the conditions described above. Fractions corresponding to a peak of .4 min and a retention time of 26.7 min were each collected. After the solvent of each fraction was distilled off under reduced pressure, 340 mg of a white solid {[α] _D ^23.4 -30.00 ° (CHCl ₃ , c = 0.510) was obtained from the fraction having a retention time of 18.4 min. }, 300 mg of a white solid {[α] _D ^23.4 + 31.07 ° (CHCl ₃ , c = 0.544)} was obtained from the fraction having a retention time of 26.7 min.
2. Determination of Optical Purity Further, the optical purity of the obtained object was measured using high performance liquid chromatography having an optically active column.

  For high performance liquid chromatography, JASCO Corporation; LC-2000 system was used.

  The measurement was performed according to the conditions described below.

Flow rate: 0.6 ml / min Oven temperature: 30 ° C
Mobile phase: n-hexane: ethanol = 75: 25 (volume ratio)
Column: Daicel CHIRALPAK AD-3 (inner diameter 0.1 mm, length 250 mm, particle diameter 5 μm),
Measurement wavelength: 254 nm
As a result,
<1> Retention time 3.06 min [340 mg of white solid {[α] _D ^23.4 -30.00 ° (CHCl ₃ , c = 0.510)} obtained from the fraction having the retention time 18.4 min in 1 above]] 99.9% (99% ee) and
<2> Retention time 4.75 min [300 mg of white solid {[α] _D ^23.4 + 31.07 ° (CHCl ₃ , c = 0.544)} obtained from the fraction with retention time 26.7 min in 1 above] 99.3% A fraction corresponding to the peak at (98.7% ee) was detected.

The peak corresponding to <1> is (S)-(−)-N- {3-chloro-1- (pyridin-3-yl) -1H-pyrazol-4-yl}-prepared in Synthesis Example 2. It coincided with the peak of 2- (ethylthio) -N- (methoxymethyl) propanamide.
Therefore, the peak corresponding to <2> is (R)-(+)-N- {3-chloro-1- (pyridin-3-yl) -1H-pyrazol-4-yl} -2- (ethylthio)- It was determined as the peak of N- (methoxymethyl) propanamide.
[Test example]
Next, the usefulness of the compound of the present invention as a pest control agent will be specifically described in the following test examples, but the present invention is not limited to these.
Test Example 1 Insecticidal test against brown planthopper A 10% emulsion of the compound of the present invention (depending on the compound, 10% wettable powder) was diluted with water containing a spreading agent to prepare a chemical solution having a concentration of 500 ppm. Rice leaf sheaths are immersed in this chemical solution for about 10 seconds, air-dried and placed in a test tube, and 5 second-instar larvae of Nilaparvata lugens are released per test tube, covered with a sponge and 25 Housed in a constant temperature room. The number of dead insects after 6 days was investigated, and the death rate (%) (number of dead insects ÷ number of test insects × 100) was calculated. In addition, the test was performed by 2 continuous systems.

As a result, among the compounds tested, the following compounds showed a death rate of 90% or more.
The present compound: 1-001 to 1-014
Test Example 2 Insecticidal test for silver leaf whitefly A moist filter paper was laid on a styrene cup having an inner diameter of 7 cm, and a green leaf cut into 3 cm was placed thereon. A 10% emulsion of a compound of the present invention (depending on the compound, 10% wettable powder) is diluted with water containing a spreading agent to prepare a chemical solution with a concentration of 500 ppm, and the chemical solution is prepared using a rotary spray tower. 2.5 ml was sprayed per styrene cup (2.5 mg / cm 2). After the leaves were air-dried, adults of silver leaf whiteflies (Bemisia argentifolii) were released, covered, and housed in a thermostatic chamber at 25 ° C. The number of dead insects after 5 days was investigated, and the dead insect rate was calculated from the same calculation formula as in Test Example 1. In addition, the test was performed by 2 continuous systems.

As a result, among the compounds tested, the following compounds showed a death rate of 90% or more.
The present compound: 1-001 to 1-014
Test Example 3 Insecticidal test against peach aphid A moist absorbent cotton is laid on a glass petri dish with an inner diameter of 3 cm, and a kanran leaf cut out to the same diameter is placed thereon, and four mosquito aphids (Myzus persicae) adults are released. did. One day later, a 10% emulsion of the compound of the present invention (depending on the compound, 10% wettable powder was tested) was diluted with water containing a spreading agent to prepare a chemical solution with a concentration of 500 ppm, and then in a rotary spray tower. The chemical solution was sprayed (2.5 mg / cm ² ), covered, and stored in a constant temperature room at 25 ° C. The number of dead insects after 6 days was investigated, and the death rate was calculated from the same calculation formula as in Test Example 1. In addition, the test was performed by 2 continuous systems.

As a result, among the compounds tested, the following compounds showed a death rate of 90% or more.
The present compound: 1-001 to 1-014
Test Example 4 Insecticidal test for cotton aphids Wet cotton wool with a 3 cm inner diameter petri dish and a cucumber leaf cut out to the same diameter were placed on it, and four cotton aphids (Aphis gossypii) adults were released. One day later, a 10% emulsion of the compound of the present invention (depending on the compound, 10% wettable powder was tested) was diluted with water containing a spreading agent to prepare a chemical solution with a concentration of 100 ppm. The chemical solution was sprayed (2.5 mg / cm ² ), covered, and stored in a constant temperature room at 25 ° C. The number of dead insects after 6 days was investigated, and the death rate was calculated from the same calculation formula as in Test Example 1. In addition, the test was performed by 2 continuous systems.

As a result, among the compounds tested, the following compounds showed a death rate of 90% or more.
The present compound: 1-001 to 1-014
Test Example 5 Soil irrigation treatment test for peach aphid A 10% emulsion of the compound of the present invention was diluted with tap water to prepare a chemical solution having a concentration of 100 ppm. 10 ml of the chemical solution was irrigated to the stock soil portion of the plastic cup planted cabbage seedling (2.5 true leaf stage) and left in the greenhouse. One day after the irrigation treatment, 20 mosquitoes / strain of adult peach aphid (Myzus persicae) were released and then left in the greenhouse. The number of surviving insects 6 days after the release was examined, and a control value was calculated from the following formula.
Control value (%) = {1- (Cb × Tai) / (Cai × Tb)} × 100
The characters in the formula represent the following:
Cb: number of insects before treatment in the untreated group Cai: number of live insects at the time of final survey in the untreated group Tb: number of insects before treatment in the treated group Tai: number of live insects at the time of final survey in the treated group Among the compounds tested, the following compounds showed a control value of 90% or more.
The present compound: 1-005 to 1-014
Test Example 6 Residual effect test on peach aphid 1-005 and no. A 1-005 racemic 10% emulsion was diluted with tap water to prepare a chemical solution having a concentration of 10 ppm. 30 ml of a chemical solution was sprayed on a pot planted cabbage (5 leaf stage) infested with a peach aphid (Myzus persicae) and left in a greenhouse.

  The number of parasites was counted 3, 7, 14, 20, 28, and 35 days after the spraying treatment, and adult females of peach aphid were released at 30 heads / strain after each survey.

As a result, the present compound no. No. 1-005 showed a control effect until 35 days later. The racemic form 1-005 showed a control effect only after 20 days.
―――――――――――――――――――――――――――――――――――――――
Days after acid treatment 0 days 3 days 7 days 14 days 20 days 28 days 35 days
Number of parasites ――――――――――――――――――――――――――――――――――――――――
1-005 117 2 4 1 1 12 8
1-005 Racemic 115 2 0 0 13 60 105
―――――――――――――――――――――――――――――――――――――――

  The novel pyrazole derivative in the present invention exhibits excellent pest control activity, particularly insecticidal / miticidal activity, and is extremely useful with little adverse effect on non-target organisms such as mammals, fish and beneficial insects. A compound.

Claims (8)

Formula (1):

[Wherein R ¹ represents a hydrogen atom, a methyl group, an ethyl group or a methyl group optionally substituted with R ³ ;
R ² represents a methyl group optionally substituted with R ⁴ or —S (O) _r R ⁵ ,
R ³ represents -OR ⁶ ;
R ⁴ represents —S (O) _r CH ₃ ,
R ⁵ and R ⁶ each independently represent a methyl group or an ethyl group,
r represents an integer of 0 to 2. ] The optically active pyrazole amide derivative represented by this.   A pest control agent comprising one or more selected from the optically active pyrazole amide derivatives according to claim 1 as an active ingredient.   An agrochemical containing one or more selected from the optically active pyrazole amide derivatives according to claim 1 as an active ingredient.   A mammal or avian internal or ectoparasite control agent comprising one or more selected from the optically active pyrazole amide derivatives according to claim 1 as an active ingredient.   An insecticide or acaricide containing one or more selected from the optically active pyrazole amide derivatives according to claim 1 as an active ingredient.   A soil treatment agent containing one or more selected from the optically active pyrazole amide derivatives according to claim 1 as an active ingredient.   The soil treatment agent according to claim 6, wherein the soil treatment method is soil irrigation treatment.   An insecticide for paddy rice containing one or more selected from the optically active pyrazole amide derivatives according to claim 1 as an active ingredient.