WO2019009387A1 - Method for producing condensed heterocyclic compound - Google Patents

Method for producing condensed heterocyclic compound Download PDF

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Publication number
WO2019009387A1
WO2019009387A1 PCT/JP2018/025615 JP2018025615W WO2019009387A1 WO 2019009387 A1 WO2019009387 A1 WO 2019009387A1 JP 2018025615 W JP2018025615 W JP 2018025615W WO 2019009387 A1 WO2019009387 A1 WO 2019009387A1
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Prior art keywords
group
halo
general formula
compound represented
alkoxy
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PCT/JP2018/025615
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French (fr)
Japanese (ja)
Inventor
登 阿部
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日本農薬株式会社
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/76—1,3-Oxazoles; Hydrogenated 1,3-oxazoles

Definitions

  • the present invention relates to a process for producing fused heterocyclic compounds useful as insecticides.
  • the fused heterocyclic compound of the present invention is useful as an insecticide, particularly as an agricultural and horticultural insecticide and an animal ectoparasite control agent.
  • a method of performing a cyclization reaction after forming an amide bond which is disclosed in Patent Document 1, etc., is reported.
  • any of the methods as to the method via the CH bond activated transition metal catalyzed cross coupling reaction of a substituted benzoxazole according to the present invention with a 2-position halogen substituted pyridine derivative, There is no disclosure or suggestion.
  • the object of the present invention is to provide a novel and industrially advantageous process for producing fused heterocyclic compounds useful as insecticides.
  • the present inventors have found that cross coupling reactions of substituted benzoxazoles and 2-position halogen substituted pyridine derivatives in the presence of a CH bond activated transition metal catalyst and subsequent reactions
  • the present inventors have completed the present invention by finding a short-step and high-yield production method of a fused heterocyclic compound useful as an insecticide by the reaction. It is industrially advantageous without requiring complicated process control.
  • R 1 is (a1) hydrogen atom; (a2) halogen atom; (a3) (C 1 -C 6 ) alkyl group; (a4) halo (C 1 -C 6 ) alkyl group; (a5) (C 1 -C 6 ) alkoxy group; (a6) halo (C 1 -C 6 ) alkoxy; (a7) halo (C 1 -C 6 ) alkylthio group; (a8) halo (C 1 -C 6 ) alkylsulfinyl group; or (a9) A halo (C 1 -C 6 ) alkylsulfonyl group is shown.
  • R 2 is (b1) hydrogen atom; (b2) halogen atom; (b3) (C 1 -C 6 ) alkyl group; (b4) (C 3 -C 6 ) cycloalkyl group; (b5) (C 1 -C 6 ) alkoxy group; (b6) halo (C 1 -C 6 ) alkyl groups; (b7) halo (C 3 -C 6 ) cycloalkyl group; (b8) halo (C 1 -C 6 ) alkoxy; (b9) halo (C 1 -C 6 ) alkylthio group; (b10) halo (C 1 -C 6 ) alkylsulfinyl group; or (b11) a halo (C 1 -C 6 ) alkylsulfonyl group is shown.
  • n an integer of 1 or 2.
  • R 1 is (a1) hydrogen atom; (a2) halogen atom; (a3) (C 1 -C 6 ) alkyl group; (a4) halo (C 1 -C 6 ) alkyl group; (a5) (C 1 -C 6 ) alkoxy group; (a6) halo (C 1 -C 6 ) alkoxy; (a7) halo (C 1 -C 6 ) alkylthio group; (a8) halo (C 1 -C 6 ) alkylsulfiny
  • R 2 is (b1) hydrogen atom; (b2) halogen atom; (b3) (C 1 -C 6 ) alkyl group; (b4) (C 3 -C 6 ) cycloalkyl group; (b5) (C 1 -C 6 ) alkoxy group; (b6) halo (C 1 -C 6 ) alkyl groups; (b7) halo (C 3 -C 6 ) cycloalkyl group; (b8) halo (C 1 -C 6 ) alkoxy; (b9) halo (C 1 -C 6 ) alkylthio group; (b10) halo (C 1 -C 6 ) alkylsulfinyl group; or (b11) a halo (C 1 -C 6 ) alkylsulfonyl group is shown.
  • n an integer of 1 or 2.
  • R 1 is (a1) hydrogen atom; (a2) halogen atom; (a3) (C 1 -C 6 ) alkyl group; (a4) halo (C 1 -C 6 ) alkyl group; (a5) (C 1 -C 6 ) alkoxy group; (a6) halo (C 1 -C 6 ) alkoxy; (a7) halo (C 1 -C 6 ) alkylthio group; (a8) halo (C 1 -C 6 ) alkylsulfinyl group; or (a9) A halo (C 1 -C 6 ) alkylsulfonyl group is shown.
  • R 2 is (b1) hydrogen atom; (b2) halogen atom; (b3) (C 1 -C 6 ) alkyl group; (b4) (C 3 -C 6 ) cycloalkyl group; (b5) (C 1 -C 6 ) alkoxy group; (b6) halo (C 1 -C 6 ) alkyl groups; (b7) halo (C 3 -C 6 ) cycloalkyl group; (b8) halo (C 1 -C 6 ) alkoxy; (b9) halo (C 1 -C 6 ) alkylthio group; (b10) halo (C 1 -C 6 ) alkylsulfinyl group; or (b11) a halo (C 1 -C 6 ) alkylsulfonyl group is shown.
  • n an integer of 1 or 2.
  • a method of producing a compound represented by General formula (2) (Wherein, R 1 and R 2 are as defined above, and Y is a halogen atom; or (C 1 -C 6 ) alkylsulfonyl group).
  • R 1 is (a1) hydrogen atom; (a2) halogen atom; (a3) (C 1 -C 6 ) alkyl group; (a4) halo (C 1 -C 6 ) alkyl group; (a5) (C 1 -C 6 ) alkoxy group; (a6) halo (C 1 -C 6 ) alkoxy; (a7) halo (C 1 -C 6 ) alkylthio group; (a8) halo (C 1 -C 6 ) alkylsulfinyl group; or (a9) A halo (C 1 -C 6 ) alkylsulfonyl group is shown.
  • R 2 is (b1) hydrogen atom; (b2) halogen atom; (b3) (C 1 -C 6 ) alkyl group; (b4) (C 3 -C 6 ) cycloalkyl group; (b5) (C 1 -C 6 ) alkoxy group; (b6) halo (C 1 -C 6 ) alkyl groups; (b7) halo (C 3 -C 6 ) cycloalkyl group; (b8) halo (C 1 -C 6 ) alkoxy; (b9) halo (C 1 -C 6 ) alkylthio group; (b10) halo (C 1 -C 6 ) alkylsulfinyl group; or (b11) a halo (C 1 -C 6 ) alkylsulfonyl group is shown.
  • n an integer of 1 or 2.
  • a method of producing a compound represented by General formula (1-1) (Wherein, R 1 and R 2 are as defined above) A process of performing an oxidation reaction on the compound represented by [5] A reaction between the compound represented by the general formula (4) and the compound represented by the general formula (3), characterized in that the reaction is performed in the presence of a transition metal catalyst,
  • R 1 is (a2) halogen atom; (a4) halo (C 1 -C 6 ) alkyl group; (a6) halo (C 1 -C 6 ) alkoxy; (a7) halo (C 1 -C 6 ) alkylthio group; (a8) halo (C 1 -C 6 ) alkylsulfinyl group; or (a9) halo (C 1 -C 6 ) alkylsulfonyl group, The manufacturing method according to any one of the above [1] to [5
  • R 2 is (b1) hydrogen atom; (b2) halogen atom; (b3) (C 1 -C 6 ) alkyl group; (b4) (C 3 -C 6 ) cycloalkyl group; (b5) (C 1 -C 6 ) alkoxy group; (b6) halo (C 1 -C 6 ) alkyl groups; (b7) halo (C 3 -C 6 ) cycloalkyl group; (b8) halo (C 1 -C 6 ) alkoxy; (b9) halo (C 1 -C 6 ) alkylthio group; (b10) halo (C 1 -C 6 ) alkylsulfinyl group; or (b11) represents a halo (C 1 -C 6 ) alkylsulfonyl group; X represents a halogen atom, Y represents a halogen atom; or (C 1
  • the target compound can be produced efficiently and economically advantageously on an industrial scale.
  • Halo means "halogen atom” and represents a chlorine atom, a bromine atom, an iodine atom or a fluorine atom.
  • the "(C 1 -C 6 ) alkyl group” is, for example, methyl group, ethyl group, normal propyl group, isopropyl group, normal butyl group, isobutyl group, secondary butyl group, tertiary butyl group, normal pentyl group, isopentyl group Tertiary pentyl group, neopentyl group, 2,3-dimethylpropyl group, 1-ethylpropyl group, 1-methylbutyl group, 2-methylbutyl group, normal hexyl group, isohexyl group, 2-hexyl group, 3-hexyl group, Indicates a linear or branched alkyl group having 1 to 6 carbon atoms, such as 2-methylp
  • the “(C 3 -C 6 ) cycloalkyl group” is a cyclic alkyl group having 3 to 6 carbon atoms, such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, etc., and “(C 1 ⁇ As C 6 ) alkoxy group ”, for example, methoxy group, ethoxy group, normal propoxy group, isopropoxy group, normal butoxy group, secondary butoxy group, tertiary butoxy group, normal pentyloxy group, isopentyloxy group, tertiary Pentyloxy group, neopentyloxy group, 2,3-dimethylpropyloxy group, 1-ethylpropyloxy group, 1-methylbutyloxy group, normal hexyloxy group, isohexyloxy group, 1,1,2-trimethylpropyl group A linear or branched chain having 1 to 6 carbon atoms, such as an
  • Examples of “(C 1 -C 6 ) alkylthio group” include methylthio group, ethylthio group, normal propylthio group, isopropylthio group, normal butylthio group, secondary butylthio group, tertiary butylthio group, normal pentylthio group.
  • Examples of “(C 1 -C 6 ) alkylsulfinyl group” include methylsulfinyl group, ethylsulfinyl group, normal propylsulfinyl group, isopropylsulfinyl group, normal butylsulfinyl group, secondary butylsulfinyl group, tertiary butylsulfinyl group, Normal pentyl sulfinyl group, isopentyl sulfinyl group, tertiary pentyl sulfinyl group, neopentyl sulfinyl group, 2,3-dimethylpropyl sulfinyl group, 1-ethylpropylsulfinyl group, 1-methylbutylsulfinyl group, normal hexylsulfinyl group, iso Indicates a linear or branched C 1-6 alkyls
  • Examples of the “(C 1 -C 6 ) alkylsulfonyl group” include a methylsulfonyl group, an ethylsulfonyl group, a normal propylsulfonyl group, an isopropylsulfonyl group, a normal butylsulfonyl group, a secondary butylsulfonyl group, and a tertiary butylsulfonyl group, Normal pentyl sulfonyl group, isopentyl sulfonyl group, tertiary pentyl sulfonyl group, neopentyl sulfonyl group, 2,3-dimethylpropyl sulfonyl group, 1-ethylpropyl sulfonyl group, 1-methyl butyl sulfonyl group, normal hexyl sulfonyl group, iso
  • halogen atoms may be substituted at substitutable positions of “(C 1 -C 6 ) alkylsulfonyl group” and “(C 3 -C 6 ) cycloalkyl group”, and halogens are substituted When the number of atoms is 2 or more, the halogen atoms may be the same or different.
  • Halo (C 1 -C 6 ) alkyl group “halo (C 1 -C 6 ) alkoxy group”, “halo (C 1 -C 6 ) alkylthio group”, “halo (C 1 -C 6 )” respectively It is referred to as “alkylsulfinyl group”, “halo (C 1 -C 6 ) alkylsulfonyl group”, and “halo (C 3 -C 6 ) cycloalkyl group”.
  • (C 1 -C 6 ) “(C 1 -C 3 )” and the like indicate the range of carbon atoms in various substituents, and in the case of “(C 1 -C 6 ) alkyl group”, for example Represents a linear or branched alkyl group having 1 to 6 carbon atoms, and in the case of “(C 1 -C 3 ) alkyl group”, a linear or branched alkyl group having 1 to 3 carbon atoms Indicates
  • the compounds represented by the general formulas (1), (1-1), (2) and (3) (4) included in the production method of the present invention have one or more asymmetric groups in their structural formulae. There may be a center, and there may be two or more optical isomers and diastereomers, and the production method of the present invention includes all of each optical isomer and a mixture containing them in any ratio. It is
  • R 1 is (a2) halogen atom; (a4) halo (C 1 -C 6 ) alkyl group; (a6) halo (C 1 -C 6 ) alkoxy; (a7) halo (C 1 -C 6 ) alkylthio group; (a8) halo (C 1 -C 6 ) alkylsulfinyl group; or (a9) halo (C 1 -C 6 ) alkylsulfonyl group, More preferably, (a2) halogen atom; (a4) halo (C 1 -C 6 ) alkyl group; (a7) halo (C 1 -C 6 ) alkylthio group; (a8) halo (C 1 -C 6 ) alkylsulfinyl group; or (a9) A halo (C 1 -C 6 ) alkylsulfonyl group.
  • R 2 is (b2) halogen atom; (b3) (C 1 -C 6 ) alkyl group; (b4) (C 3 -C 6 ) cycloalkyl group; (b6) halo (C 1 -C 6 ) alkyl groups; (b8) halo (C 1 -C 6 ) alkoxy group; or (b9) a halo (C 1 -C 6 ) alkylthio group, More preferably, (b4) (C 3 -C 6 ) cycloalkyl group.
  • the compound represented by General formula (1) can be manufactured by the manufacturing method of following process [a] thru
  • Process [a] The process of manufacturing the compound represented by General formula (2) by making the compound represented by General formula (4), and the compound represented by General formula (3) react.
  • Step [b] A step of producing a compound represented by the general formula (1-1) by reacting the compound represented by the general formula (2) with ethanethiol or a salt thereof and the like.
  • Step [c] A step of producing a compound represented by the general formula (1) by oxidizing the compound represented by the general formula (1-1).
  • the compound represented by the general formula (2) is generally a compound represented by the general formula (4) and a compound represented by the general formula (3), a transition metal catalyst and It can be produced by reacting in an inert solvent in the presence of a base. This reaction may be carried out according to known methods or methods known per se.
  • palladium compounds such as available zero-valent or divalent palladium metals and salts (including complexes) thereof can be used, and may be supported on activated carbon or the like .
  • palladium (0) / carbon palladium (II) acetate, palladium (II) trifluoroacetate, palladium (II) chloride, bis (triphenyl phosphine) palladium (II) chloride, tetrakis (triphenyl phosphine) palladium ( 0), [1,1′-bis (diphenylphosphino) ferrocene] palladium dichloride, [1,1′-bis (diphenylphosphino) propane] palladium dichloride, [1,1′-bis (diphenylphosphino) butane] ] Palladiumdichloride, bis (dibenzylideneacetone) palladium, tris (dibenzylideneacetone) palladium, tri
  • phosphine ligands examples include triphenylphosphine (PPh 3 ), methyl diphenylphosphine (Ph 2 PCH 3 ), triflyl phosphine (P (2-furyl) 3 ), and triphenylphosphine (P (2-furyl) 3 ).
  • the amount of the ligand used may be appropriately selected usually from the range of 0.001 mol% to 20 mol% with respect to the compound represented by the general formula (4).
  • hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide
  • lithium carbonate lithium hydrogen carbonate, sodium hydrogen carbonate, sodium hydrogen carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, potassium hydrogen carbonate
  • Carbonates such as cesium, acetates such as lithium acetate, sodium acetate and potassium acetate, phosphates such as trisodium phosphate and tripotassium phosphate, sodium methoxide, sodium ethoxide, lithium tertiary butoxide, sodium tartha Metal oxides such as leavetoxide and potassium tert-butoxide, metal hydrides such as sodium hydride and potassium hydride, pyridine, picoline, lutidine, triethylamine, tributylamine, diisopropylethylamine, N, N-dicyclo And organic bases such as cyclohexyl methyl amine.
  • Preferred bases are, for example, sodium carbonate, sodium hydrogen carbonate, potassium carbonate, sodium acetate, potassium acetate.
  • the amount of the base used may be appropriately selected usually in the range of 1 mol to 10 mol with respect to 1 mol of the compound represented by the general formula (4).
  • any solvent which does not significantly inhibit this reaction may be used.
  • linear or cyclic ethers such as diethyl ether, tetrahydrofuran (THF), dioxane, etc., benzene, toluene, xylene, etc.
  • Aromatic hydrocarbons such as chlorobenzene and dichlorobenzene, nitriles such as acetonitrile, esters such as ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, dimethyl sulfoxide, Polar solvents such as 1,3-dimethyl-2-imidazolidinone, alcohols such as methanol, ethanol and isopropanol, water and the like can be mentioned, with preference given to toluene, N, N-dimethylformamide, N, N- It is dimethylacetamide.
  • These inert solvents may be used alone or in combination of two or more. The amount thereof to be used may be appropriately selected usually in the range of 0.1 to 100 L with respect to 1 mole of the compound represented by the general formula (4).
  • reaction temperature is usually in the range of about 0 ° C. to 200 ° C.
  • reaction time varies depending on the reaction scale, reaction temperature and the like, and is not constant, but may be appropriately selected in the range of several minutes to 48 hours.
  • the desired product may be isolated from the reaction system containing the desired product by a conventional method, and the desired product can be produced by purification by recrystallization, column chromatography, etc., as necessary. It can also be used for the next reaction without isolation.
  • the compound represented by the general formula (1-1) is represented by the compound represented by the general formula (2) in the presence of a base and an inert solvent and represented by the formula (1-2) Can be produced by reacting ethanethiol or a salt thereof.
  • hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide
  • lithium carbonate lithium hydrogen carbonate, sodium hydrogen carbonate, sodium hydrogen carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, potassium hydrogen carbonate
  • Carbonates such as cesium, acetates such as lithium acetate, sodium acetate and potassium acetate, phosphates such as trisodium phosphate and tripotassium phosphate, sodium methoxide, sodium ethoxide, lithium tertiary butoxide, sodium tartha Metal oxides such as leavetoxide and potassium tert-butoxide, metal hydrides such as sodium hydride and potassium hydride, pyridine, picoline, lutidine, triethylamine, tributylamine, diisopropylethylamine, N, N-dicyclo And organic bases such as cyclohexyl methyl amine.
  • One or more species may be used. Preferred are lithium hydroxide, sodium hydroxide and potassium hydroxide.
  • the amount of the base used may be appropriately selected usually in the range of 1-fold mol to 10-fold mol with respect to 1 mol of the compound represented by the general formula (2).
  • tetra-n-butyl ammonium chloride tetra-n-butyl ammonium bromide, tetra-n-butyl ammonium iodide, tetra-n-octyl ammonium chloride, tetra-n-octyl ammonium bromide, Tetra-n-octyl ammonium iodide and the like
  • the amount thereof to be used may be appropriately selected usually from the range of 0.01 mol to 1 mol with respect to 1 mol of the compound represented by the general formula (2).
  • any solvent which does not significantly inhibit this reaction may be used.
  • linear or cyclic ethers such as diethyl ether, tetrahydrofuran (THF), dioxane, etc., benzene, toluene, xylene, etc.
  • Aromatic hydrocarbons such as chlorobenzene and dichlorobenzene, nitriles such as acetonitrile, esters such as ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, dimethyl sulfoxide, Polar solvents such as 1,3-dimethyl-2-imidazolidinone, alcohols such as methanol, ethanol and isopropanol, water, etc. may be mentioned, and these inert solvents may be used alone or in combination of two or more. You can also The amount thereof to be used may be appropriately selected usually in the range of 0.1 to 100 L per 1 mol of the compound represented by the general formula (2).
  • reaction temperature is usually in the range of about 0 ° C. to 200 ° C.
  • reaction time varies depending on the reaction scale, reaction temperature and the like, and is not constant, but may be appropriately selected in the range of several minutes to 48 hours.
  • the desired product may be isolated from the reaction system containing the desired product by a conventional method, and the desired product can be produced by purification by recrystallization, column chromatography, etc., as necessary. It can also be used for the next reaction without isolation.
  • the compound represented by the general formula (1) can be produced by reacting the compound represented by the general formula (1-1) with an oxidizing agent in an inert solvent .
  • peroxides such as a hydrogen-peroxide solution, a perbenzoic acid, m-chloro perbenzoic acid, etc. are mentioned, for example.
  • oxidizing agents can be appropriately selected usually in the range of 1-fold mol to 5-fold mol with respect to the compound represented by General Formula (1-1).
  • any solvent which does not significantly inhibit this reaction may be used.
  • linear or cyclic ethers such as diethyl ether, tetrahydrofuran and dioxane, aromatic carbonization such as benzene, toluene and xylene Hydrogens, halogenated hydrocarbons such as methylene chloride, chloroform and carbon tetrachloride, halogenated aromatic hydrocarbons such as chlorobenzene and dichlorobenzene, nitriles such as acetonitrile, esters such as ethyl acetate, formic acid, acetic acid and the like
  • polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, 1,3-dimethyl-2-imidazolidinone and water, and these inert solvents may be used alone or in combination. Two or more types can be mixed and used. The amount thereof to be used may be appropriately selected
  • the reaction temperature in this reaction may be appropriately selected usually in the range of ⁇ 10 ° C. to the reflux temperature of the inert solvent used.
  • the reaction time varies depending on the reaction scale, reaction temperature and the like, and although not constant, it may be appropriately selected usually in the range of several minutes to 48 hours.
  • the target product may be isolated from the reaction system containing the target product by a conventional method, and the target product can be produced by purification by recrystallization, column chromatography, etc., as necessary.
  • compound (1), compound (1-1), compound (2), compound (3) and compound (4) involved in the present invention include the case where a salt is formed.
  • salts include salts with inorganic acids such as hydrochloric acid, sulfuric acid and phosphoric acid, for example, salts with organic acids such as oxalic acid, acetic acid and succinic acid, salts with inorganic bases such as sodium and calcium, For example, salts with organic bases such as trimethylamine and triethylamine can be exemplified.
  • inorganic acids such as hydrochloric acid, sulfuric acid and phosphoric acid
  • organic acids such as oxalic acid, acetic acid and succinic acid
  • salts with inorganic bases such as sodium and calcium
  • salts with organic bases such as trimethylamine and triethylamine
  • the method for producing a fused heterocyclic compound according to the present invention can provide a fused heterocyclic compound in a short step and in a high yield, so the production method is industrially useful.

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Abstract

The compound represented by general formula (1) (wherein R1 and R2 represent a halo (C1-C6) alkyl group or a halo (C1-C6) alkylthio group) is useful as an agricultural pesticide, and there is a strong demand for the development of an industrially advantageous method of synthesizing the same in a short process. Provided is a method for producing the compound represented by general formula (1), the method including a step for producing a compound represented by general formula (2) through a coupling reaction of a compound represented by general formula (4) (wherein R1 is as defined previously) and a compound represented by general formula (3) (wherein R2 is as defined previously, X represents a halogen atom, and Y represents a halogen atom or a halo (C1-C6) alkylthio group).

Description

縮合複素環化合物の製造方法Method for producing fused heterocyclic compound
　本発明は、殺虫剤として有用な縮合複素環化合物の製造方法に関する。 The present invention relates to a process for producing fused heterocyclic compounds useful as insecticides.
　本発明の縮合複素環化合物は、殺虫剤、特に農園芸用殺虫剤及び動物用外部寄生虫防除薬として有用である。その製造方法として、特許文献１において開示されている、一旦アミド結合を形成してからの環化反応を行う方法等が報告されている。
　しかし、いずれの方法にも本発明のような置換ベンゾオキサゾールと、２位ハロゲン置換ピリジン誘導体とのＣ‐Ｈ結合活性化遷移金属触媒クロスカップリング反応を経由するような方法に関しては、具体的な開示も示唆もされていない。 The fused heterocyclic compound of the present invention is useful as an insecticide, particularly as an agricultural and horticultural insecticide and an animal ectoparasite control agent. As a production method thereof, a method of performing a cyclization reaction after forming an amide bond, which is disclosed in Patent Document 1, etc., is reported.
However, in any of the methods, as to the method via the CH bond activated transition metal catalyzed cross coupling reaction of a substituted benzoxazole according to the present invention with a 2-position halogen substituted pyridine derivative, There is no disclosure or suggestion.
国際公開２０１６／１２１９９７号パンフレットInternational Publication 2016/121997 brochure
　本発明の課題は、殺虫剤として有用な縮合複素環化合物の新規で工業的に有利な製造方法を提供することである。 The object of the present invention is to provide a novel and industrially advantageous process for producing fused heterocyclic compounds useful as insecticides.
　本発明者は前記課題を解決すべく鋭意研究を重ねた結果、置換ベンゾオキサゾールと、２位ハロゲン置換ピリジン誘導体とのＣ‐Ｈ結合活性化遷移金属触媒存在下におけるクロスカップリング反応と、それに続く反応により、殺虫剤として有用な縮合複素環化合物の、短工程かつ高収率な製造方法を見出し、本発明を完成させた。複雑な工程管理を必要とせず、産業上有利である。 As a result of intensive studies to solve the above problems, the present inventors have found that cross coupling reactions of substituted benzoxazoles and 2-position halogen substituted pyridine derivatives in the presence of a CH bond activated transition metal catalyst and subsequent reactions The present inventors have completed the present invention by finding a short-step and high-yield production method of a fused heterocyclic compound useful as an insecticide by the reaction. It is industrially advantageous without requiring complicated process control.
　即ち本発明は、　
［１］一般式（１）
Figure JPOXMLDOC01-appb-C000019
 ｛式中、Ｒ１は、
(a1) 水素原子；
(a2) ハロゲン原子；
(a3) （Ｃ１－Ｃ６）アルキル基；
(a4) ハロ（Ｃ１－Ｃ６）アルキル基；
(a5) （Ｃ１－Ｃ６）アルコキシ基;
(a6) ハロ（Ｃ１－Ｃ６）アルコキシ基;
(a7) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
(a8) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
(a9) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基を示す。
Ｒ２は、
(b1) 水素原子；
(b2) ハロゲン原子；
(b3) （Ｃ１－Ｃ６）アルキル基；
(b4) （Ｃ３－Ｃ６）シクロアルキル基；
(b5) （Ｃ１－Ｃ６）アルコキシ基；
(b6) ハロ（Ｃ１－Ｃ６）アルキル基；
(b7) ハロ（Ｃ３－Ｃ６）シクロアルキル基；
(b8) ハロ（Ｃ１－Ｃ６）アルコキシ基；
(b9) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
(b10) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
(b11) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基を示す。
ｎは、１又は２の整数を示す。}
で表される化合物を製造する方法であって、
一般式（４）
Figure JPOXMLDOC01-appb-C000020
 （式中、Ｒ１は、前記と同じ。）
で表される化合物と、一般式（３）
Figure JPOXMLDOC01-appb-C000021
 （式中、Ｒ２は、前記と同じくし、Ｘは、ハロゲン原子を示し、Ｙは、ハロゲン原子；又は（Ｃ１－Ｃ６）アルキルスルホニル基を示す。）
で表される化合物とを、反応させ、生成した一般式（２）
Figure JPOXMLDOC01-appb-C000022
 （式中、Ｒ１、Ｒ２及びＹは、前記に同じ。）
で表される化合物に対して、塩基存在下、エチルメルカプタンを反応させることにより生成した、一般式（１‐１）
Figure JPOXMLDOC01-appb-C000023
 （式中、Ｒ１及びＲ２は、前記に同じ。）
で表される化合物に対して、酸化反応を行うことを特徴とする、製造方法、
［２］一般式（１）
Figure JPOXMLDOC01-appb-C000024
 ｛式中、Ｒ１は、
(a1) 水素原子；
(a2) ハロゲン原子；
(a3) （Ｃ１－Ｃ６）アルキル基；
(a4) ハロ（Ｃ１－Ｃ６）アルキル基；
(a5) （Ｃ１－Ｃ６）アルコキシ基;
(a6) ハロ（Ｃ１－Ｃ６）アルコキシ基;
(a7) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
(a8) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
(a9) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基を示す。
Ｒ２は、
(b1) 水素原子；
(b2) ハロゲン原子；
(b3) （Ｃ１－Ｃ６）アルキル基；
(b4) （Ｃ３－Ｃ６）シクロアルキル基；
(b5) （Ｃ１－Ｃ６）アルコキシ基；
(b6) ハロ（Ｃ１－Ｃ６）アルキル基；
(b7) ハロ（Ｃ３－Ｃ６）シクロアルキル基；
(b8) ハロ（Ｃ１－Ｃ６）アルコキシ基；
(b9) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
(b10) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
(b11) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基を示す。
ｎは、１又は２の整数を示す。}
で表される化合物を製造する方法であって、
一般式（４）
Figure JPOXMLDOC01-appb-C000025
 （式中、Ｒ１は、前記に同じ。）
で表される化合物と、一般式（３）
Figure JPOXMLDOC01-appb-C000026
 （式中、Ｒ２は、前記に同じくし、Ｘは、ハロゲン原子を示し、Ｙは、ハロゲン原子；又は（Ｃ１－Ｃ６）アルキルスルホニル基を示す。）
で表される化合物とを、反応させることで、一般式（２）
Figure JPOXMLDOC01-appb-C000027
 （式中、Ｒ１、Ｒ２及びＹは、前記に同じ。）で表される化合物を製造する工程を含む、製造方法、
［３］一般式（１）
Figure JPOXMLDOC01-appb-C000028
 ｛式中、Ｒ１は、
(a1) 水素原子；
(a2) ハロゲン原子；
(a3) （Ｃ１－Ｃ６）アルキル基；
(a4) ハロ（Ｃ１－Ｃ６）アルキル基；
(a5) （Ｃ１－Ｃ６）アルコキシ基;
(a6) ハロ（Ｃ１－Ｃ６）アルコキシ基;
(a7) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
(a8) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
(a9) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基を示す。
Ｒ２は、
(b1) 水素原子；
(b2) ハロゲン原子；
(b3) （Ｃ１－Ｃ６）アルキル基；
(b4) （Ｃ３－Ｃ６）シクロアルキル基；
(b5) （Ｃ１－Ｃ６）アルコキシ基；
(b6) ハロ（Ｃ１－Ｃ６）アルキル基；
(b7) ハロ（Ｃ３－Ｃ６）シクロアルキル基；
(b8) ハロ（Ｃ１－Ｃ６）アルコキシ基；
(b9) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
(b10) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
(b11) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基を示す。
ｎは、１又は２の整数を示す。}
で表される化合物を製造する方法であって、
一般式（２）
Figure JPOXMLDOC01-appb-C000029
 （式中、Ｒ１及びＲ２は前記に同じくし、Ｙは、ハロゲン原子；又は（Ｃ１－Ｃ６）アルキルスルホニル基を示す。）
で表される化合物に対して、塩基存在下、エチルメルカプタンを反応させることにより、一般式（１‐１）
Figure JPOXMLDOC01-appb-C000030
 （式中、Ｒ１及びＲ２は、前記に同じ。）
で表される化合物を製造する工程を含む、製造方法、
［４］一般式（１）
Figure JPOXMLDOC01-appb-C000031
 ｛式中、Ｒ１は、
(a1) 水素原子；
(a2) ハロゲン原子；
(a3) （Ｃ１－Ｃ６）アルキル基；
(a4) ハロ（Ｃ１－Ｃ６）アルキル基；
(a5) （Ｃ１－Ｃ６）アルコキシ基;
(a6) ハロ（Ｃ１－Ｃ６）アルコキシ基;
(a7) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
(a8) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
(a9) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基を示す。
Ｒ２は、
(b1) 水素原子；
(b2) ハロゲン原子；
(b3) （Ｃ１－Ｃ６）アルキル基；
(b4) （Ｃ３－Ｃ６）シクロアルキル基；
(b5) （Ｃ１－Ｃ６）アルコキシ基；
(b6) ハロ（Ｃ１－Ｃ６）アルキル基；
(b7) ハロ（Ｃ３－Ｃ６）シクロアルキル基；
(b8) ハロ（Ｃ１－Ｃ６）アルコキシ基；
(b9) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
(b10) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
(b11) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基を示す。
ｎは、１又は２の整数を示す。}
で表される化合物を製造する方法であって、
一般式（１‐１）
Figure JPOXMLDOC01-appb-C000032
 （式中、Ｒ１及びＲ２は、前記に同じ。）
で表される化合物に対して、酸化反応を行う工程を含むことを特徴とする、製造方法、
［５］前記の、一般式（４）で表される化合物と、一般式(３)で表される化合物との反応において、遷移金属触媒存在下に反応を行うことを特徴とする、
前記［１］又は［２］に記載の製造方法、
［６］Ｒ１が、
(a2) ハロゲン原子；
(a4) ハロ（Ｃ１－Ｃ６）アルキル基；
(a6) ハロ（Ｃ１－Ｃ６）アルコキシ基;
(a7) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
(a8) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
(a9) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基である、
前記［１］乃至［５］のいずれかに記載の製造方法、
［７］Ｒ２が、
(b2) ハロゲン原子；
(b3) （Ｃ１－Ｃ６）アルキル基；
(b4) （Ｃ３－Ｃ６）シクロアルキル基；
(b6) ハロ（Ｃ１－Ｃ６）アルキル基；
(b8) ハロ（Ｃ１－Ｃ６）アルコキシ基；又は
(b9) ハロ（Ｃ１－Ｃ６）アルキルチオ基である、
前記［１］乃至［６］のいずれかに記載の製造方法、
［８］Ｒ１が、
(a2) ハロゲン原子；
(a4) ハロ（Ｃ１－Ｃ６）アルキル基；
(a7) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
(a8) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
(a9) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基であり、
Ｒ２が、
(b4) （Ｃ３－Ｃ６）シクロアルキル基である、
前記［１］乃至［５］のいずれかに記載の製造方法、
［９］
　一般式（４）
Figure JPOXMLDOC01-appb-C000033
 ｛式中、Ｒ１は、
(a1) 水素原子；
(a2) ハロゲン原子；
(a3) （Ｃ１－Ｃ６）アルキル基；
(a4) ハロ（Ｃ１－Ｃ６）アルキル基；
(a5) （Ｃ１－Ｃ６）アルコキシ基;
(a6) ハロ（Ｃ１－Ｃ６）アルコキシ基;
(a7) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
(a8) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
(a9) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基を示す。｝で表される化合物と、一般式（３）
Figure JPOXMLDOC01-appb-C000034
 （式中、
Ｒ２は、
(b1) 水素原子；
(b2) ハロゲン原子；
(b3) （Ｃ１－Ｃ６）アルキル基；
(b4) （Ｃ３－Ｃ６）シクロアルキル基；
(b5) （Ｃ１－Ｃ６）アルコキシ基；
(b6) ハロ（Ｃ１－Ｃ６）アルキル基；
(b7) ハロ（Ｃ３－Ｃ６）シクロアルキル基；
(b8) ハロ（Ｃ１－Ｃ６）アルコキシ基；
(b9) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
(b10) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
(b11) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基を示し、
Ｘは、ハロゲン原子を示し、
Ｙは、ハロゲン原子；又は（Ｃ１－Ｃ６）アルキルスルホニル基を示す。）
で表される化合物とを、反応させることで、一般式（２）
Figure JPOXMLDOC01-appb-C000035
 （式中、Ｒ１、Ｒ２及びＹは、前記に同じ。）で表される化合物を製造する工程の、
一般式（１）
Figure JPOXMLDOC01-appb-C000036
 ｛式中、Ｒ１及びＲ２は、前記に同じくし、ｎは、１又は２の整数を示す。}
で表される化合物製造のための使用、等に関する。 That is, the present invention
[1] General formula (1)
Figure JPOXMLDOC01-appb-C000019
 {In the formula, R 1 is
(a1) hydrogen atom;
(a2) halogen atom;
(a3) (C 1 -C 6 ) alkyl group;
(a4) halo (C 1 -C 6 ) alkyl group;
(a5) (C 1 -C 6 ) alkoxy group;
(a6) halo (C 1 -C 6 ) alkoxy;
(a7) halo (C 1 -C 6 ) alkylthio group;
(a8) halo (C 1 -C 6 ) alkylsulfinyl group; or
(a9) A halo (C 1 -C 6 ) alkylsulfonyl group is shown.
R 2 is
(b1) hydrogen atom;
(b2) halogen atom;
(b3) (C 1 -C 6 ) alkyl group;
(b4) (C 3 -C 6 ) cycloalkyl group;
(b5) (C 1 -C 6 ) alkoxy group;
(b6) halo (C 1 -C 6 ) alkyl groups;
(b7) halo (C 3 -C 6 ) cycloalkyl group;
(b8) halo (C 1 -C 6 ) alkoxy;
(b9) halo (C 1 -C 6 ) alkylthio group;
(b10) halo (C 1 -C 6 ) alkylsulfinyl group; or
(b11) a halo (C 1 -C 6 ) alkylsulfonyl group is shown.
n represents an integer of 1 or 2. }
A method of producing a compound represented by
General formula (4)
Figure JPOXMLDOC01-appb-C000020
 (Wherein, R 1 is the same as the above.)
And a compound represented by the general formula (3)
Figure JPOXMLDOC01-appb-C000021
 (Wherein, R 2 is as defined above, X is a halogen atom, and Y is a halogen atom; or (C 1 -C 6 ) alkylsulfonyl group).
Produced by reacting with a compound represented by the general formula (2)
Figure JPOXMLDOC01-appb-C000022
 (Wherein, R 1 , R 2 and Y are as defined above)
A compound represented by the general formula (1-1) was produced by reacting ethyl mercaptan in the presence of a base with respect to the compound represented by
Figure JPOXMLDOC01-appb-C000023
 (Wherein, R 1 and R 2 are as defined above)
A production method characterized in that an oxidation reaction is performed on the compound represented by
[2] General formula (1)
Figure JPOXMLDOC01-appb-C000024
 {In the formula, R 1 is
(a1) hydrogen atom;
(a2) halogen atom;
(a3) (C 1 -C 6 ) alkyl group;
(a4) halo (C 1 -C 6 ) alkyl group;
(a5) (C 1 -C 6 ) alkoxy group;
(a6) halo (C 1 -C 6 ) alkoxy;
(a7) halo (C 1 -C 6 ) alkylthio group;
(a8) halo (C 1 -C 6 ) alkylsulfinyl group; or
(a9) A halo (C 1 -C 6 ) alkylsulfonyl group is shown.
R 2 is
(b1) hydrogen atom;
(b2) halogen atom;
(b3) (C 1 -C 6 ) alkyl group;
(b4) (C 3 -C 6 ) cycloalkyl group;
(b5) (C 1 -C 6 ) alkoxy group;
(b6) halo (C 1 -C 6 ) alkyl groups;
(b7) halo (C 3 -C 6 ) cycloalkyl group;
(b8) halo (C 1 -C 6 ) alkoxy;
(b9) halo (C 1 -C 6 ) alkylthio group;
(b10) halo (C 1 -C 6 ) alkylsulfinyl group; or
(b11) a halo (C 1 -C 6 ) alkylsulfonyl group is shown.
n represents an integer of 1 or 2. }
A method of producing a compound represented by
General formula (4)
Figure JPOXMLDOC01-appb-C000025
 (Wherein, R 1 is the same as above)
And a compound represented by the general formula (3)
Figure JPOXMLDOC01-appb-C000026
 (Wherein, R 2 is the same as above, X is a halogen atom, and Y is a halogen atom; or (C 1 -C 6 ) alkylsulfonyl group).
By reacting with a compound represented by the general formula (2)
Figure JPOXMLDOC01-appb-C000027
 (Wherein, R 1 , R 2 and Y are as defined above), including the step of producing a compound represented by the formula:
[3] General formula (1)
Figure JPOXMLDOC01-appb-C000028
 {In the formula, R 1 is
(a1) hydrogen atom;
(a2) halogen atom;
(a3) (C 1 -C 6 ) alkyl group;
(a4) halo (C 1 -C 6 ) alkyl group;
(a5) (C 1 -C 6 ) alkoxy group;
(a6) halo (C 1 -C 6 ) alkoxy;
(a7) halo (C 1 -C 6 ) alkylthio group;
(a8) halo (C 1 -C 6 ) alkylsulfinyl group; or
(a9) A halo (C 1 -C 6 ) alkylsulfonyl group is shown.
R 2 is
(b1) hydrogen atom;
(b2) halogen atom;
(b3) (C 1 -C 6 ) alkyl group;
(b4) (C 3 -C 6 ) cycloalkyl group;
(b5) (C 1 -C 6 ) alkoxy group;
(b6) halo (C 1 -C 6 ) alkyl groups;
(b7) halo (C 3 -C 6 ) cycloalkyl group;
(b8) halo (C 1 -C 6 ) alkoxy;
(b9) halo (C 1 -C 6 ) alkylthio group;
(b10) halo (C 1 -C 6 ) alkylsulfinyl group; or
(b11) a halo (C 1 -C 6 ) alkylsulfonyl group is shown.
n represents an integer of 1 or 2. }
A method of producing a compound represented by
General formula (2)
Figure JPOXMLDOC01-appb-C000029
 (Wherein, R 1 and R 2 are as defined above, and Y is a halogen atom; or (C 1 -C 6 ) alkylsulfonyl group).
Is reacted with ethyl mercaptan in the presence of a base to the compound represented by the general formula (1-1)
Figure JPOXMLDOC01-appb-C000030
 (Wherein, R 1 and R 2 are as defined above)
A production method comprising the step of producing a compound represented by
[4] General formula (1)
Figure JPOXMLDOC01-appb-C000031
 {In the formula, R 1 is
(a1) hydrogen atom;
(a2) halogen atom;
(a3) (C 1 -C 6 ) alkyl group;
(a4) halo (C 1 -C 6 ) alkyl group;
(a5) (C 1 -C 6 ) alkoxy group;
(a6) halo (C 1 -C 6 ) alkoxy;
(a7) halo (C 1 -C 6 ) alkylthio group;
(a8) halo (C 1 -C 6 ) alkylsulfinyl group; or
(a9) A halo (C 1 -C 6 ) alkylsulfonyl group is shown.
R 2 is
(b1) hydrogen atom;
(b2) halogen atom;
(b3) (C 1 -C 6 ) alkyl group;
(b4) (C 3 -C 6 ) cycloalkyl group;
(b5) (C 1 -C 6 ) alkoxy group;
(b6) halo (C 1 -C 6 ) alkyl groups;
(b7) halo (C 3 -C 6 ) cycloalkyl group;
(b8) halo (C 1 -C 6 ) alkoxy;
(b9) halo (C 1 -C 6 ) alkylthio group;
(b10) halo (C 1 -C 6 ) alkylsulfinyl group; or
(b11) a halo (C 1 -C 6 ) alkylsulfonyl group is shown.
n represents an integer of 1 or 2. }
A method of producing a compound represented by
General formula (1-1)
Figure JPOXMLDOC01-appb-C000032
 (Wherein, R 1 and R 2 are as defined above)
A process of performing an oxidation reaction on the compound represented by
[5] A reaction between the compound represented by the general formula (4) and the compound represented by the general formula (3), characterized in that the reaction is performed in the presence of a transition metal catalyst,
The manufacturing method according to the above [1] or [2],
[6] R 1 is
(a2) halogen atom;
(a4) halo (C 1 -C 6 ) alkyl group;
(a6) halo (C 1 -C 6 ) alkoxy;
(a7) halo (C 1 -C 6 ) alkylthio group;
(a8) halo (C 1 -C 6 ) alkylsulfinyl group; or
(a9) halo (C 1 -C 6 ) alkylsulfonyl group,
The manufacturing method according to any one of the above [1] to [5],
[7] R 2 is
(b2) halogen atom;
(b3) (C 1 -C 6 ) alkyl group;
(b4) (C 3 -C 6 ) cycloalkyl group;
(b6) halo (C 1 -C 6 ) alkyl groups;
(b8) halo (C 1 -C 6 ) alkoxy group; or
(b9) halo (C 1 -C 6 ) alkylthio group,
The manufacturing method according to any one of the above [1] to [6],
[8] R 1 is
(a2) halogen atom;
(a4) halo (C 1 -C 6 ) alkyl group;
(a7) halo (C 1 -C 6 ) alkylthio group;
(a8) halo (C 1 -C 6 ) alkylsulfinyl group; or
(a9) halo (C 1 -C 6 ) alkylsulfonyl group,
R 2 is
(b 4) a (C 3 -C 6 ) cycloalkyl group,
The manufacturing method according to any one of the above [1] to [5],
[9]
General formula (4)
Figure JPOXMLDOC01-appb-C000033
 {In the formula, R 1 is
(a1) hydrogen atom;
(a2) halogen atom;
(a3) (C 1 -C 6 ) alkyl group;
(a4) halo (C 1 -C 6 ) alkyl group;
(a5) (C 1 -C 6 ) alkoxy group;
(a6) halo (C 1 -C 6 ) alkoxy;
(a7) halo (C 1 -C 6 ) alkylthio group;
(a8) halo (C 1 -C 6 ) alkylsulfinyl group; or
(a9) A halo (C 1 -C 6 ) alkylsulfonyl group is shown. And a compound represented by the general formula (3)
Figure JPOXMLDOC01-appb-C000034
 (In the formula,
R 2 is
(b1) hydrogen atom;
(b2) halogen atom;
(b3) (C 1 -C 6 ) alkyl group;
(b4) (C 3 -C 6 ) cycloalkyl group;
(b5) (C 1 -C 6 ) alkoxy group;
(b6) halo (C 1 -C 6 ) alkyl groups;
(b7) halo (C 3 -C 6 ) cycloalkyl group;
(b8) halo (C 1 -C 6 ) alkoxy;
(b9) halo (C 1 -C 6 ) alkylthio group;
(b10) halo (C 1 -C 6 ) alkylsulfinyl group; or
(b11) represents a halo (C 1 -C 6 ) alkylsulfonyl group;
X represents a halogen atom,
Y represents a halogen atom; or (C 1 -C 6 ) alkylsulfonyl group. )
By reacting with a compound represented by the general formula (2)
Figure JPOXMLDOC01-appb-C000035
 (Wherein, R 1 , R 2 and Y are the same as above) in the process of producing the compound
General formula (1)
Figure JPOXMLDOC01-appb-C000036
 {Wherein, R 1 and R 2 are as defined above, and n is an integer of 1 or 2. }
And the like, for use in producing the compound represented by
　本発明によれば、目的化合物を効率的且つ経済的有利に工業的規模で製造することができる。 According to the present invention, the target compound can be produced efficiently and economically advantageously on an industrial scale.
　本明細書中に記載する各置換基を説明する。「ハロ」とは「ハロゲン原子」を意味し、塩素原子、臭素原子、ヨウ素原子又はフッ素原子を示す。
「（Ｃ１－Ｃ６）アルキル基」とは、例えばメチル基、エチル基、ノルマルプロピル基、イソプロピル基、ノルマルブチル基、イソブチル基、セカンダリーブチル基、ターシャリーブチル基、ノルマルペンチル基、イソペンチル基、ターシャリーペンチル基、ネオペンチル基、２，３－ジメチルプロピル基、１－エチルプロピル基、１－メチルブチル基、２－メチルブチル基、ノルマルヘキシル基、イソヘキシル基、２－ヘキシル基、３－ヘキシル基、２－メチルペンチル基、３－メチルペンチル基、１，１，２－トリメチルプロピル基、３，３－ジメチルブチル基等の直鎖又は分岐鎖状の炭素原子数１～６個のアルキル基を示す。 Each substituent described in the present specification will be described. "Halo" means "halogen atom" and represents a chlorine atom, a bromine atom, an iodine atom or a fluorine atom.
The "(C 1 -C 6 ) alkyl group" is, for example, methyl group, ethyl group, normal propyl group, isopropyl group, normal butyl group, isobutyl group, secondary butyl group, tertiary butyl group, normal pentyl group, isopentyl group Tertiary pentyl group, neopentyl group, 2,3-dimethylpropyl group, 1-ethylpropyl group, 1-methylbutyl group, 2-methylbutyl group, normal hexyl group, isohexyl group, 2-hexyl group, 3-hexyl group, Indicates a linear or branched alkyl group having 1 to 6 carbon atoms, such as 2-methylpentyl group, 3-methylpentyl group, 1,1,2-trimethylpropyl group, 3,3-dimethylbutyl group, etc. .
　「（Ｃ３‐Ｃ６）シクロアルキル基」とは、例えばシクロプロピル基、シクロブチル基、シクロペンチル基、シクロヘキシル基等の炭素原子数３～６個の環状のアルキル基を示し、「（Ｃ１‐Ｃ６）アルコキシ基」としては、例えば、メトキシ基、エトキシ基、ノルマルプロポキシ基、イソプロポキシ基、ノルマルブトキシ基、セカンダリーブトキシ基、ターシャリーブトキシ基、ノルマルペンチルオキシ基、イソペンチルオキシ基、ターシャリーペンチルオキシ基、ネオペンチルオキシ基、２，３‐ジメチルプロピルオキシ基、１‐エチルプロピルオキシ基、１‐メチルブチルオキシ基、ノルマルヘキシルオキシ基、イソヘキシルオキシ基、１，１，２‐トリメチルプロピルオキシ基等の直鎖又は分岐鎖状の炭素原子数１～６個のアルコキシ基を示す。 The “(C 3 -C 6 ) cycloalkyl group” is a cyclic alkyl group having 3 to 6 carbon atoms, such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, etc., and “(C 1 − As C 6 ) alkoxy group ”, for example, methoxy group, ethoxy group, normal propoxy group, isopropoxy group, normal butoxy group, secondary butoxy group, tertiary butoxy group, normal pentyloxy group, isopentyloxy group, tertiary Pentyloxy group, neopentyloxy group, 2,3-dimethylpropyloxy group, 1-ethylpropyloxy group, 1-methylbutyloxy group, normal hexyloxy group, isohexyloxy group, 1,1,2-trimethylpropyl group A linear or branched chain having 1 to 6 carbon atoms, such as an oxy group It shows the Kokishi group.
「（Ｃ１‐Ｃ６）アルキルチオ基」としては、例えば、メチルチオ基、エチルチオ基、ノルマルプロピルチオ基、イソプロピルチオ基、ノルマルブチルチオ基、セカンダリーブチルチオ基、ターシャリーブチルチオ基、ノルマルペンチルチオ基、イソペンチルチオ基、ターシャリーペンチルチオ基、ネオペンチルチオ基、２，３‐ジメチルプロピルチオ基、１‐エチルプロピルチオ基、１‐メチルブチルチオ基、ノルマルヘキシルチオ基、イソヘキシルチオ基、１，１，２‐トリメチルプロピルチオ基等の直鎖又は分岐鎖状の炭素原子数１～６個のアルキルチオ基を示す。 Examples of “(C 1 -C 6 ) alkylthio group” include methylthio group, ethylthio group, normal propylthio group, isopropylthio group, normal butylthio group, secondary butylthio group, tertiary butylthio group, normal pentylthio group. Group, isopentylthio group, tertiary pentylthio group, neopentylthio group, 2,3-dimethylpropylthio group, 1-ethylpropylthio group, 1-methylbutylthio group, normal hexylthio group, isohexylthio group And a linear or branched alkylthio group having 1 to 6 carbon atoms, such as a 1,1,2-trimethylpropylthio group.
　「（Ｃ１‐Ｃ６）アルキルスルフィニル基」としては、例えば、メチルスルフィニル基、エチルスルフィニル基、ノルマルプロピルスルフィニル基、イソプロピルスルフィニル基、ノルマルブチルスルフィニル基、セカンダリーブチルスルフィニル基、ターシャリーブチルスルフィニル基、ノルマルペンチルスルフィニル基、イソペンチルスルフィニル基、ターシャリーペンチルスルフィニル基、ネオペンチルスルフィニル基、２，３‐ジメチルプロピルスルフィニル基、１‐エチルプロピルスルフィニル基、１‐メチルブチルスルフィニル基、ノルマルヘキシルスルフィニル基、イソヘキシルスルフィニル基、１，１，２‐トリメチルプロピルスルフィニル基等の直鎖又は分岐鎖状の炭素原子数１～６個のアルキルスルフィニル基を示す。 Examples of “(C 1 -C 6 ) alkylsulfinyl group” include methylsulfinyl group, ethylsulfinyl group, normal propylsulfinyl group, isopropylsulfinyl group, normal butylsulfinyl group, secondary butylsulfinyl group, tertiary butylsulfinyl group, Normal pentyl sulfinyl group, isopentyl sulfinyl group, tertiary pentyl sulfinyl group, neopentyl sulfinyl group, 2,3-dimethylpropyl sulfinyl group, 1-ethylpropylsulfinyl group, 1-methylbutylsulfinyl group, normal hexylsulfinyl group, iso Indicates a linear or branched C 1-6 alkylsulfinyl group such as hexylsulfinyl group or 1,1,2-trimethylpropylsulfinyl group .
「（Ｃ１‐Ｃ６）アルキルスルホニル基」としては、例えば、メチルスルホニル基、エチルスルホニル基、ノルマルプロピルスルホニル基、イソプロピルスルホニル基、ノルマルブチルスルホニル基、セカンダリーブチルスルホニル基、ターシャリーブチルスルホニル基、ノルマルペンチルスルホニル基、イソペンチルスルホニル基、ターシャリーペンチルスルホニル基、ネオペンチルスルホニル基、２，３‐ジメチルプロピルスルホニル基、１‐エチルプロピルスルホニル基、１‐メチルブチルスルホニル基、ノルマルヘキシルスルホニル基、イソヘキシルスルホニル基、１，１，２‐トリメチルプロピルスルホニル基等の直鎖又は分岐鎖状の炭素原子数１～６個のアルキルスルホニル基を示す。 Examples of the “(C 1 -C 6 ) alkylsulfonyl group” include a methylsulfonyl group, an ethylsulfonyl group, a normal propylsulfonyl group, an isopropylsulfonyl group, a normal butylsulfonyl group, a secondary butylsulfonyl group, and a tertiary butylsulfonyl group, Normal pentyl sulfonyl group, isopentyl sulfonyl group, tertiary pentyl sulfonyl group, neopentyl sulfonyl group, 2,3-dimethylpropyl sulfonyl group, 1-ethylpropyl sulfonyl group, 1-methyl butyl sulfonyl group, normal hexyl sulfonyl group, iso It represents a linear or branched alkylsulfonyl group having 1 to 6 carbon atoms, such as hexylsulfonyl group and 1,1,2-trimethylpropylsulfonyl group.
　上記「（Ｃ１‐Ｃ６）アルキル基」、「（Ｃ１‐Ｃ６）アルコキシ基」、「（Ｃ１‐Ｃ６）アルキルチオ基」、「（Ｃ１‐Ｃ６）アルキルスルフィニル基」、「（Ｃ１‐Ｃ６）アルキルスルホニル基」、「（Ｃ３‐Ｃ６）シクロアルキル基」の置換し得る位置に１又は２以上のハロゲン原子が置換されていても良く、置換されるハロゲン原子が２以上の場合は、ハロゲン原子は同一又は異なっていても良い。 The "(C 1 -C 6) alkyl group", "(C 1 -C 6) alkoxy group", "(C 1 -C 6) alkylthio group", "(C 1 -C 6) alkylsulfinyl group" One or more halogen atoms may be substituted at substitutable positions of “(C 1 -C 6 ) alkylsulfonyl group” and “(C 3 -C 6 ) cycloalkyl group”, and halogens are substituted When the number of atoms is 2 or more, the halogen atoms may be the same or different.
　それぞれ、「ハロ（Ｃ１‐Ｃ６）アルキル基」、「ハロ（Ｃ１‐Ｃ６）アルコキシ基」、「ハロ（Ｃ１‐Ｃ６）アルキルチオ基」、「ハロ（Ｃ１‐Ｃ６）アルキルスルフィニル基」、「ハロ（Ｃ１‐Ｃ６）アルキルスルホニル基」、「ハロ（Ｃ３‐Ｃ６）シクロアルキル基」と示す。 “Halo (C 1 -C 6 ) alkyl group”, “halo (C 1 -C 6 ) alkoxy group”, “halo (C 1 -C 6 ) alkylthio group”, “halo (C 1 -C 6 )” respectively It is referred to as "alkylsulfinyl group", "halo (C 1 -C 6 ) alkylsulfonyl group", and "halo (C 3 -C 6 ) cycloalkyl group".
　「（Ｃ１－Ｃ６）」、「（Ｃ１－Ｃ３）」等の表現は各種置換基の炭素原子数の範囲を示し、例えば、「（Ｃ１－Ｃ６）アルキル基」の場合は直鎖又は分岐鎖状の炭素数１～６個のアルキル基を示し、「（Ｃ１－Ｃ３）アルキル基」の場合は直鎖又は分岐鎖状の炭素数１～３個のアルキル基を示す。 The expressions “(C 1 -C 6 )”, “(C 1 -C 3 )” and the like indicate the range of carbon atoms in various substituents, and in the case of “(C 1 -C 6 ) alkyl group”, for example Represents a linear or branched alkyl group having 1 to 6 carbon atoms, and in the case of “(C 1 -C 3 ) alkyl group”, a linear or branched alkyl group having 1 to 3 carbon atoms Indicates
　本発明の製造方法に含まれる一般式（１）、（１－１）、（２）、（３）（４）で表される化合物は、その構造式中に１つ又は複数個の不斉中心を有する場合があり、２種以上の光学異性体及びジアステレオマーが存在する場合もあり、本発明の製造方法は各々の光学異性体及びそれらが任意の割合で含まれる混合物をも全て包含するものである。 The compounds represented by the general formulas (1), (1-1), (2) and (3) (4) included in the production method of the present invention have one or more asymmetric groups in their structural formulae. There may be a center, and there may be two or more optical isomers and diastereomers, and the production method of the present invention includes all of each optical isomer and a mixture containing them in any ratio. It is
　本発明の好ましい実施態様を示す。
Ｒ１として好ましくは、
(a2) ハロゲン原子；
(a4) ハロ（Ｃ１－Ｃ６）アルキル基；
(a6) ハロ（Ｃ１－Ｃ６）アルコキシ基; 
(a7) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
(a8) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
(a9) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基であり、
さらに好ましくは、
(a2) ハロゲン原子；
(a4) ハロ（Ｃ１－Ｃ６）アルキル基；
(a7) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
(a8) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
(a9) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基である。
Ｒ２として好ましくは、
(b2) ハロゲン原子；
(b3) （Ｃ１－Ｃ６）アルキル基；
(b4) （Ｃ３－Ｃ６）シクロアルキル基；
(b6) ハロ（Ｃ１－Ｃ６）アルキル基；
(b8) ハロ（Ｃ１－Ｃ６）アルコキシ基；又は
(b9) ハロ（Ｃ１－Ｃ６）アルキルチオ基であり、
さらに好ましくは、
(b4) （Ｃ３－Ｃ６）シクロアルキル基である。 1 shows a preferred embodiment of the present invention.
Preferably R 1 is
(a2) halogen atom;
(a4) halo (C 1 -C 6 ) alkyl group;
(a6) halo (C 1 -C 6 ) alkoxy;
(a7) halo (C 1 -C 6 ) alkylthio group;
(a8) halo (C 1 -C 6 ) alkylsulfinyl group; or
(a9) halo (C 1 -C 6 ) alkylsulfonyl group,
More preferably,
(a2) halogen atom;
(a4) halo (C 1 -C 6 ) alkyl group;
(a7) halo (C 1 -C 6 ) alkylthio group;
(a8) halo (C 1 -C 6 ) alkylsulfinyl group; or
(a9) A halo (C 1 -C 6 ) alkylsulfonyl group.
Preferably R 2 is
(b2) halogen atom;
(b3) (C 1 -C 6 ) alkyl group;
(b4) (C 3 -C 6 ) cycloalkyl group;
(b6) halo (C 1 -C 6 ) alkyl groups;
(b8) halo (C 1 -C 6 ) alkoxy group; or
(b9) a halo (C 1 -C 6 ) alkylthio group,
More preferably,
(b4) (C 3 -C 6 ) cycloalkyl group.
　本発明に関与する反応は以下のように図示される。 The reactions involved in the present invention are illustrated as follows.
製造方法１
Figure JPOXMLDOC01-appb-C000037
 ｛式中、Ｒ１、Ｒ２、ｎ、Ｘ及びＹは前記に同じ。｝ Manufacturing method 1
Figure JPOXMLDOC01-appb-C000037
 In the formula, R 1 , R 2 , n, X and Y are as defined above. }
　即ち、下記工程［ａ］乃至［ｃ］の製造方法により、一般式（１）で表される化合物を製造することができる。
工程［ａ］　一般式（４）で表される化合物と、一般式（３）で表される化合物とを反応させることにより、一般式（２）で表される化合物を製造する工程。
工程［ｂ］　一般式（２）で表される化合物と、エタンチオール又はその塩等と反応させることにより、一般式（１－１）で表される化合物を製造する工程。
工程［ｃ］　一般式（１－１）で表される化合物を酸化することにより、一般式（１）で表される化合物を製造する工程。 That is, the compound represented by General formula (1) can be manufactured by the manufacturing method of following process [a] thru | or [c].
Process [a] The process of manufacturing the compound represented by General formula (2) by making the compound represented by General formula (4), and the compound represented by General formula (3) react.
Step [b] A step of producing a compound represented by the general formula (1-1) by reacting the compound represented by the general formula (2) with ethanethiol or a salt thereof and the like.
Step [c] A step of producing a compound represented by the general formula (1) by oxidizing the compound represented by the general formula (1-1).
工程［ａ］の製造方法
　一般式（２）で表される化合物は、一般式（４）で表される化合物と、一般式（３）で表される化合物とを、通常は遷移金属触媒及び塩基の存在下、不活性溶媒中反応させることにより製造することができる。この反応は公知の方法又は自体公知の方法に従って行われてよい。 Production Method of Step [a] The compound represented by the general formula (2) is generally a compound represented by the general formula (4) and a compound represented by the general formula (3), a transition metal catalyst and It can be produced by reacting in an inert solvent in the presence of a base. This reaction may be carried out according to known methods or methods known per se.
　本反応で使用することができる触媒としては入手可能な０価または２価のパラジウム金属やその塩（錯体を含む）などのパラジウム化合物を使用することができ、活性炭などに担持されていても良い。好ましくは、パラジウム（０）／炭素、酢酸パラジウム（ＩＩ）、トリフルオロ酢酸パラジウム（ＩＩ）、塩化パラジウム（ＩＩ）、ビス（トリフェニルホスフィン）パラジウム（ＩＩ）クロリド、テトラキス（トリフェニルホスフィン）パラジウム（０）、［１，１’‐ビス（ジフェニルホスフィノ）フェロセン］パラジウムジクロリド、［１，１’‐ビス（ジフェニルホスフィノ）プロパン］パラジウムジクロリド、［１，１’‐ビス（ジフェニルホスフィノ）ブタン］パラジウムジクロリド、ビス（ジベンジリデンアセトン）パラジウム、トリス（ジベンジリデンアセトン）ジパラジウム、ビス（アセトニトリル）パラジウム）ジクロリド、ビス（ベンゾニトリル）パラジウムジクロリド、ジクロロ(１，５‐シクロオクタジエン)パラジウム、アリルパラジウムクロリド２量体、シクロペンタジエニルアリルパラジウム、アリル［１，３‐ビス(メシチル)イミダゾール‐２‐イリデン］クロロパラジウム等公知のパラジウム触媒を挙げる事ができ、酢酸パラジウム（ＩＩ）、パラジウム（０）／炭素、アリル［１，３‐ビス(メシチル)イミダゾール‐２‐イリデン］クロロパラジウム等が好ましい。触媒としての使用量は、一般式（４）で表される化合物に対して通常０．００１モル％～１０モル％の範囲から適宜選択すればよい。 As a catalyst that can be used in this reaction, palladium compounds such as available zero-valent or divalent palladium metals and salts (including complexes) thereof can be used, and may be supported on activated carbon or the like . Preferably, palladium (0) / carbon, palladium (II) acetate, palladium (II) trifluoroacetate, palladium (II) chloride, bis (triphenyl phosphine) palladium (II) chloride, tetrakis (triphenyl phosphine) palladium ( 0), [1,1′-bis (diphenylphosphino) ferrocene] palladium dichloride, [1,1′-bis (diphenylphosphino) propane] palladium dichloride, [1,1′-bis (diphenylphosphino) butane] ] Palladiumdichloride, bis (dibenzylideneacetone) palladium, tris (dibenzylideneacetone) dipalladium, bis (acetonitrile) palladium) dichloride, bis (benzonitrile) palladium dichloride, dichloro (1,5-cyclooctadiene) para Known palladium catalysts such as lithium palladium, allylpalladium chloride dimer, cyclopentadienylallylpalladium, allyl [1,3-bis (mesityl) imidazole-2-ylidene] chloropalladium; palladium (II) acetate; Preferred are palladium (0) / carbon, allyl [1,3-bis (mesityl) imidazol-2-ylidene] chloropalladium and the like. The amount used as a catalyst may be appropriately selected usually from the range of 0.001 mol% to 10 mol% with respect to the compound represented by the general formula (4).
　本反応で使用することができるホスフィン系配位子としては、例えば、トリフェニルホスフィン（ＰＰｈ３）、メチルジフェニルホスフィン（Ｐｈ２ＰＣＨ３）、トリフリルホスフィン（Ｐ(２‐ｆｕｒｙｌ)３）、トリ（ｏ‐トリル）ホスフィン（Ｐ(o‐ｔｏｌ)３）、トリ（シクロヘキシル）ホスフィン（ＰＣｙ３）、ジシクロヘキシルフェニルホスフィン（ＰｈＰＣｙ２）、トリ（ｔ‐ブチル）ホスフィン（Ｐ(ｔ‐Ｂｕ)３）、トリ‐ｔｅｒｔ‐ブチルホスホニウムテトラフルオロボラート、トリ‐ｔｅｒｔ‐ブチルホスホニウムテトラフェニルボラート、トリ（ｔ‐ブチル）ホスフィン（Ｐ（ｔ‐Ｂｕ）３）・ＣＦ３ＳＯ３Ｈ、２‐（ジ‐ｔ‐ブチルホスフィノ）ビフェニル（ＪｏｈｎＰｈｏｓ）、２-ジシクロヘキシルホスフィノ‐２’，４’，６’‐トリイソプロピルビフェニル（Ｘｐｈｏｓ）、２，２’‐ビス（ジフェニルホスフィノ）‐１，１’‐ビナフチル（ＢＩＮＡＰ）、２，２’‐ビス（ジ‐ｐ‐トリルホスフィノ）-１,１'-ビナフチル（ＴｏｌＢＩＮＡＰ）、１，１’‐ビス（ジフェニルホスフィノ）フェロセン（ＤＰＰＦ）、１，１’‐ビス（ジ‐ｔ‐ブチルホスフィノ）フェロセン（ＤｔＢＰＦ）、Ｎ，Ｎ‐ジメチル‐１‐［２‐（ジフェニルホスフィノ）フェロセニル］エチルアミン、１‐［２‐（ジフェニルホスフィノ）フェロセニル］エチルメチルエーテル、４，５‐ビス(ジフェニルホスフィノ) ‐９，９ジメチルキサンテン（Ｘａｎｔｐｈｏｓ）、４，６‐ビス(ジフェニルホスフィノ)フェノキサジン（ＮＩＸａｎｔｐｈｏｓ）、ビス[２‐(ジフェニルホスフィノ)フェニル]エーテル（ＤＰＥｐｈｏｓ）、１，２‐ビス(ジフェニルホスフィノ)エタン、１，３‐ビス(ジフェニルホスフィノ)プロパン、１，４‐ビス(ジフェニルホスフィノ)ブタン、等のホスフィン系配位子や、イミダゾル‐２‐イリデンカルベン類等のホスフィンミミック系配位子（アンゲバンテ・ケミー・インターナショナル・エディション・イン・イングリッシュ（Ａｎｇｅｗａｎｄｔｅ Ｃｈｅｍｉｅ Ｉｎｔｅｒｎａｔｉｏｎａｌ Ｅｄｉｔｉｏｎ ｉｎ Ｅｎｇｌｉｓｈ) 第３６巻、第２１６３頁（１９９７年）参照）等が挙げられる。好ましくは、１，３‐ビス(ジフェニルホスフィノ)プロパン、２，２’‐ビス（ジフェニルホスフィノ）‐１，１’‐ビナフチル、４，５‐ビス(ジフェニルホスフィノ) ‐９，９ジメチルキサンテン、ビス[２‐(ジフェニルホスフィノ)フェニル]エーテル、２，２’‐ビス（ジ‐ｐ‐トリルホスフィノ）-１,１'-ビナフチル（ＴｏｌＢＩＮＡＰ）、が好ましい。配位子の使用量は、一般式（４）で表される化合物に対して通常０．００１モル％～２０モル％の範囲から適宜選択すればよい。 Examples of phosphine ligands that can be used in this reaction include triphenylphosphine (PPh 3 ), methyl diphenylphosphine (Ph 2 PCH 3 ), triflyl phosphine (P (2-furyl) 3 ), and triphenylphosphine (P (2-furyl) 3 ). (o-tolyl) phosphine (P (o-tol) 3 ), tri (cyclohexyl) phosphine (PCy 3), dicyclohexyl phenylphosphine (PhPCy 2), tri (t-butyl) phosphine (P (t-Bu) 3) Tri-tert-butylphosphonium tetrafluoroborate, tri-tert-butylphosphonium tetraphenylborate, tri (t-butyl) phosphine (P (t-Bu) 3 ) · CF 3 SO 3 H, 2- (di- -T-Butylphosphino) biphenyl (JohnPhos), 2-dicyclohexylphosphate Fino-2 ', 4', 6'-triisopropylbiphenyl (Xphos), 2,2'-bis (diphenylphosphino) -1,1'-binaphthyl (BINAP), 2,2'-bis (di-p) -Tolylphosphino) -1,1'-binaphthyl (TolBINAP), 1,1'-bis (diphenylphosphino) ferrocene (DPPF), 1,1'-bis (di-t-butylphosphino) ferrocene (DtBPF), N, N-Dimethyl-1- [2- (diphenylphosphino) ferrocenyl] ethylamine, 1- [2- (diphenylphosphino) ferrocenyl] ethyl methyl ether, 4,5-bis (diphenylphosphino) -9,9 Dimethyl xanthene (Xantphos), 4,6-bis (diphenylphosphino) phenoxazine (NIXantphos), bis [2- (diphene) Phosphine-based compounds such as (phosphino) phenyl] ether (DPEphos), 1,2-bis (diphenylphosphino) ethane, 1,3-bis (diphenylphosphino) propane and 1,4-bis (diphenylphosphino) butane Phosphine mimic ligands such as ligands and imidazol-2-ylidene carbenes (Angewandte Chemie International Edition in English) Vol. 36, p. 2163 (1997) ) And the like. Preferably, 1,3-bis (diphenylphosphino) propane, 2,2'-bis (diphenylphosphino) -1,1'-binaphthyl, 4,5-bis (diphenylphosphino) -9,9 dimethylxanthene And bis [2- (diphenylphosphino) phenyl] ether and 2,2'-bis (di-p-tolylphosphino) -1,1'-binaphthyl (TolBINAP) are preferred. The amount of the ligand used may be appropriately selected usually from the range of 0.001 mol% to 20 mol% with respect to the compound represented by the general formula (4).
　本反応で使用できる塩基としては、例えば、水酸化リチウム、水酸化ナトリウム、水酸化カリウム等の水酸化物、炭酸リチウム、炭酸水素リチウム、炭酸ナトリウム、炭酸水素ナトリウム、炭酸カリウム、炭酸水素カリウム、炭酸セシウム等の炭酸塩、酢酸リチウム、酢酸ナトリウム、酢酸カリウム等の酢酸塩、りん酸三ナトリウム、りん酸三カリウム等のリン酸塩、ナトリウムメトキサイド、ナトリウムエトキサイド、リチウムターシャリーブトキサイド、ナトリウムターシャリーブトキサイド、カリウムターシャリーブトキサイド等のアルコキサイド等、水素化ナトリウム、水素化カリウム等の金属ヒドリド類、ピリジン、ピコリン、ルチジン、トリエチルアミン、トリブチルアミン、ジイソプロピルエチルアミン、Ｎ，Ｎ‐ジシクロヘキシルメチルアミン等の有機塩基等が挙げられる。１種又は２種以上を使用してもよい。好ましい塩基は、例えば炭酸ナトリウム、炭酸水素ナトリウム、炭酸カリウム、酢酸ナトリウム、酢酸カリウムである。塩基の使用量としては、一般式（４）で表される化合物１モルに対して通常１倍モル～１０倍モルの範囲から適宜選択すればよい。 As a base which can be used in this reaction, for example, hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide, lithium carbonate, lithium hydrogen carbonate, sodium hydrogen carbonate, sodium hydrogen carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, potassium hydrogen carbonate Carbonates such as cesium, acetates such as lithium acetate, sodium acetate and potassium acetate, phosphates such as trisodium phosphate and tripotassium phosphate, sodium methoxide, sodium ethoxide, lithium tertiary butoxide, sodium tartha Metal oxides such as leavetoxide and potassium tert-butoxide, metal hydrides such as sodium hydride and potassium hydride, pyridine, picoline, lutidine, triethylamine, tributylamine, diisopropylethylamine, N, N-dicyclo And organic bases such as cyclohexyl methyl amine. One or more species may be used. Preferred bases are, for example, sodium carbonate, sodium hydrogen carbonate, potassium carbonate, sodium acetate, potassium acetate. The amount of the base used may be appropriately selected usually in the range of 1 mol to 10 mol with respect to 1 mol of the compound represented by the general formula (4).
　本反応で使用できる不活性溶媒としては、本反応を著しく阻害しないものであれば良く、例えば、ジエチルエーテル、テトラヒドロフラン（ＴＨＦ）、ジオキサン等の鎖状又は環状エーテル類、ベンゼン、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン、ジクロロベンゼン等のハロゲン化芳香族炭化水素類、アセトニトリル等のニトリル類、酢酸エチル等のエステル類、Ｎ，Ｎ－ジメチルホルムアミド、Ｎ，Ｎ－ジメチルアセトアミド、ジメチルスルホキシド、１，３－ジメチル－２－イミダゾリジノン等の極性溶媒、メタノール、エタノール、イソプロパノール等のアルコール類、水等を挙げることができ、好ましくは、トルエン、Ｎ，Ｎ‐ジメチルホルムアミド、Ｎ,Ｎ‐ジメチルアセトアミドである。これらの不活性溶媒は単独で又は２種以上混合して使用することもできる。その使用量としては、一般式（４）で表される化合物１モルに対して通常０．１～１００Ｌの範囲から適宜選択すればよい。 As an inert solvent which can be used in this reaction, any solvent which does not significantly inhibit this reaction may be used. For example, linear or cyclic ethers such as diethyl ether, tetrahydrofuran (THF), dioxane, etc., benzene, toluene, xylene, etc. Aromatic hydrocarbons, halogenated aromatic hydrocarbons such as chlorobenzene and dichlorobenzene, nitriles such as acetonitrile, esters such as ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, dimethyl sulfoxide, Polar solvents such as 1,3-dimethyl-2-imidazolidinone, alcohols such as methanol, ethanol and isopropanol, water and the like can be mentioned, with preference given to toluene, N, N-dimethylformamide, N, N- It is dimethylacetamide. These inert solvents may be used alone or in combination of two or more. The amount thereof to be used may be appropriately selected usually in the range of 0.1 to 100 L with respect to 1 mole of the compound represented by the general formula (4).
　本反応は等モル反応であるので、各化合物を等モル使用すればよいが、いずれかの化合物を過剰に用いることもできる。反応温度は通常約０℃から２００℃の範囲で行えば良く、反応時間は反応規模、反応温度等により変化し、一定ではないが、数分～４８時間の範囲で適宜選択すれば良い。反応終了後、目的物を含む反応系から目的物を常法により単離すれば良く、必要に応じて再結晶、カラムクロマトグラフィー等で精製することにより目的物を製造することができる。また単離せずに次の反応に用いることもできる。 Since this reaction is an equimolar reaction, equimolar amounts of each compound may be used, but any compound may be used in excess. The reaction temperature is usually in the range of about 0 ° C. to 200 ° C. The reaction time varies depending on the reaction scale, reaction temperature and the like, and is not constant, but may be appropriately selected in the range of several minutes to 48 hours. After completion of the reaction, the desired product may be isolated from the reaction system containing the desired product by a conventional method, and the desired product can be produced by purification by recrystallization, column chromatography, etc., as necessary. It can also be used for the next reaction without isolation.
工程［ｂ］の製造方法
　一般式（１－１）で表される化合物は、一般式（２）で表される化合物に、塩基及び不活性溶媒存在下で式（１‐２）で表されるエタンチオール又はその塩を反応させることにより製造することができる。 Process for Producing Step [b] The compound represented by the general formula (1-1) is represented by the compound represented by the general formula (2) in the presence of a base and an inert solvent and represented by the formula (1-2) Can be produced by reacting ethanethiol or a salt thereof.
　本反応で使用できる塩基としては、例えば、水酸化リチウム、水酸化ナトリウム、水酸化カリウム等の水酸化物、炭酸リチウム、炭酸水素リチウム、炭酸ナトリウム、炭酸水素ナトリウム、炭酸カリウム、炭酸水素カリウム、炭酸セシウム等の炭酸塩、酢酸リチウム、酢酸ナトリウム、酢酸カリウム等の酢酸塩、りん酸三ナトリウム、りん酸三カリウム等のリン酸塩、ナトリウムメトキサイド、ナトリウムエトキサイド、リチウムターシャリーブトキサイド、ナトリウムターシャリーブトキサイド、カリウムターシャリーブトキサイド等のアルコキサイド等、水素化ナトリウム、水素化カリウム等の金属ヒドリド類、ピリジン、ピコリン、ルチジン、トリエチルアミン、トリブチルアミン、ジイソプロピルエチルアミン、Ｎ，Ｎ‐ジシクロヘキシルメチルアミン等の有機塩基等が挙げられる。１種又は２種以上を使用してもよい。好ましくは、水酸化リチウム、水酸化ナトリウム、水酸化カリウムである。塩基の使用量は、一般式（２）で表される化合物１モルに対して通常１倍モル～１０倍モルの範囲から適宜選択すればよい。 As a base which can be used in this reaction, for example, hydroxides such as lithium hydroxide, sodium hydroxide and potassium hydroxide, lithium carbonate, lithium hydrogen carbonate, sodium hydrogen carbonate, sodium hydrogen carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, potassium hydrogen carbonate Carbonates such as cesium, acetates such as lithium acetate, sodium acetate and potassium acetate, phosphates such as trisodium phosphate and tripotassium phosphate, sodium methoxide, sodium ethoxide, lithium tertiary butoxide, sodium tartha Metal oxides such as leavetoxide and potassium tert-butoxide, metal hydrides such as sodium hydride and potassium hydride, pyridine, picoline, lutidine, triethylamine, tributylamine, diisopropylethylamine, N, N-dicyclo And organic bases such as cyclohexyl methyl amine. One or more species may be used. Preferred are lithium hydroxide, sodium hydroxide and potassium hydroxide. The amount of the base used may be appropriately selected usually in the range of 1-fold mol to 10-fold mol with respect to 1 mol of the compound represented by the general formula (2).
　本反応で使用できる触媒としては、テトラ‐ｎ‐ブチルアンモニウムクロリド、テトラ‐ｎ‐ブチルアンモニウムブロミド、テトラ‐ｎ‐ブチルアンモニウムヨージド、テトラ‐ｎ‐オクチルアンモニウムクロリド、テトラ‐ｎ‐オクチルアンモニウムブロミド、テトラ‐ｎ‐オクチルアンモニウムヨージド等が挙げられ、その使用量は、一般式（２）で表される化合物１モルに対して通常０．０１モル～１モルの範囲から適宜選択すれば良い。 As a catalyst which can be used in this reaction, tetra-n-butyl ammonium chloride, tetra-n-butyl ammonium bromide, tetra-n-butyl ammonium iodide, tetra-n-octyl ammonium chloride, tetra-n-octyl ammonium bromide, Tetra-n-octyl ammonium iodide and the like can be mentioned, and the amount thereof to be used may be appropriately selected usually from the range of 0.01 mol to 1 mol with respect to 1 mol of the compound represented by the general formula (2).
　本反応で使用できる不活性溶媒としては、本反応を著しく阻害しないものであれば良く、例えば、ジエチルエーテル、テトラヒドロフラン（ＴＨＦ）、ジオキサン等の鎖状又は環状エーテル類、ベンゼン、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン、ジクロロベンゼン等のハロゲン化芳香族炭化水素類、アセトニトリル等のニトリル類、酢酸エチル等のエステル類、Ｎ，Ｎ－ジメチルホルムアミド、Ｎ，Ｎ－ジメチルアセトアミド、ジメチルスルホキシド、１，３－ジメチル－２－イミダゾリジノン等の極性溶媒、メタノール、エタノール、イソプロパノール等のアルコール類、水等を挙げることができ、これらの不活性溶媒は単独で又は２種以上混合して使用することもできる。その使用量は、一般式（２）で表される化合物１モルに対して通常０．１～１００Ｌの範囲から適宜選択すればよい。 As an inert solvent which can be used in this reaction, any solvent which does not significantly inhibit this reaction may be used. For example, linear or cyclic ethers such as diethyl ether, tetrahydrofuran (THF), dioxane, etc., benzene, toluene, xylene, etc. Aromatic hydrocarbons, halogenated aromatic hydrocarbons such as chlorobenzene and dichlorobenzene, nitriles such as acetonitrile, esters such as ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, dimethyl sulfoxide, Polar solvents such as 1,3-dimethyl-2-imidazolidinone, alcohols such as methanol, ethanol and isopropanol, water, etc. may be mentioned, and these inert solvents may be used alone or in combination of two or more. You can also The amount thereof to be used may be appropriately selected usually in the range of 0.1 to 100 L per 1 mol of the compound represented by the general formula (2).
　本反応は等モル反応であるので、各化合物を等モル使用すればよいが、いずれかの化合物を過剰に用いることもできる。反応温度は通常約０℃から２００℃の範囲で行えば良く、反応時間は反応規模、反応温度等により変化し、一定ではないが、数分～４８時間の範囲で適宜選択すれば良い。反応終了後、目的物を含む反応系から目的物を常法により単離すれば良く、必要に応じて再結晶、カラムクロマトグラフィー等で精製することにより目的物を製造することができる。また単離せずに次の反応に用いることもできる。 Since this reaction is an equimolar reaction, equimolar amounts of each compound may be used, but any compound may be used in excess. The reaction temperature is usually in the range of about 0 ° C. to 200 ° C. The reaction time varies depending on the reaction scale, reaction temperature and the like, and is not constant, but may be appropriately selected in the range of several minutes to 48 hours. After completion of the reaction, the desired product may be isolated from the reaction system containing the desired product by a conventional method, and the desired product can be produced by purification by recrystallization, column chromatography, etc., as necessary. It can also be used for the next reaction without isolation.
工程［ｃ］の製造方法
　一般式（１）で表される化合物は、一般式（１‐１）で表される化合物を、不活性溶媒中、酸化剤と反応させることにより製造することができる。 Process for Producing Step [c] The compound represented by the general formula (1) can be produced by reacting the compound represented by the general formula (1-1) with an oxidizing agent in an inert solvent .
　本反応で使用する酸化剤としては、例えば、過酸化水素水、過安息香酸、ｍ‐クロル過安息香酸などの過酸化物などが挙げられる。これら酸化剤は、一般式（１‐１）で表される化合物に対して通常１倍モル～５倍モルの範囲で適宜選択することができる。 As an oxidizing agent used by this reaction, peroxides, such as a hydrogen-peroxide solution, a perbenzoic acid, m-chloro perbenzoic acid, etc. are mentioned, for example. These oxidizing agents can be appropriately selected usually in the range of 1-fold mol to 5-fold mol with respect to the compound represented by General Formula (1-1).
　本反応で使用できる不活性溶媒としては、本反応を著しく阻害しないものであれば良く、例えば、ジエチルエーテル、テトラヒドロフラン、ジオキサン等の鎖状又は環状エーテル類、ベンゼン、トルエン、キシレン等の芳香族炭化水素類、塩化メチレン、クロロホルム、四塩化炭素等のハロゲン化炭化水素類、クロロベンゼン、ジクロロベンゼン等のハロゲン化芳香族炭化水素類、アセトニトリル等のニトリル類、酢酸エチル等のエステル類、蟻酸、酢酸等の有機酸類、Ｎ，Ｎ‐ジメチルホルムアミド、Ｎ，Ｎ‐ジメチルアセトアミド、１，３‐ジメチル‐２‐イミダゾリジノン、水等の極性溶媒を挙げることができ、これらの不活性溶媒は単独で又は２種以上混合して使用することができる。その使用量は、一般式（１－１）で表される化合物１モルに対して通常０．１～１００Ｌの範囲から適宜選択すればよい。 As the inert solvent which can be used in this reaction, any solvent which does not significantly inhibit this reaction may be used. For example, linear or cyclic ethers such as diethyl ether, tetrahydrofuran and dioxane, aromatic carbonization such as benzene, toluene and xylene Hydrogens, halogenated hydrocarbons such as methylene chloride, chloroform and carbon tetrachloride, halogenated aromatic hydrocarbons such as chlorobenzene and dichlorobenzene, nitriles such as acetonitrile, esters such as ethyl acetate, formic acid, acetic acid and the like And polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, 1,3-dimethyl-2-imidazolidinone and water, and these inert solvents may be used alone or in combination. Two or more types can be mixed and used. The amount thereof to be used may be appropriately selected usually in the range of 0.1 to 100 L with respect to 1 mol of the compound represented by the general formula (1-1).
　本反応における反応温度は、通常－１０℃から使用する不活性溶媒の還流温度の範囲で適宜選択すればよい。反応時間は反応規模、反応温度などにより変化し、一定ではないが通常数分～４８時間の範囲で適宜選択すればよい。反応終了後、目的物を含む反応系から常法により目的物を単離すれば良く、必要に応じて再結晶、カラムクロマトグラフィー等で精製することにより目的物を製造することができる。本発明に関与する、例えば、化合物（１）、化合物（１－１）、化合物（２）、化合物（３）及び化合物（４）は、塩を形成している場合を含む。塩としては、例えば、塩酸、硫酸、リン酸などの無機酸との塩、例えば、シュウ酸、酢酸、コハク酸などの有機酸との塩、例えば、ナトリウム、カルシウム等の無機塩基との塩、例えば、トリメチルアミン、トリエチルアミン等の有機塩基との塩等が例示できる。本発明に関与する化合物が、塩であるときは、これを遊離化合物に、また遊離化合物であるときはこれを塩に、変換できる。これは周知技術であって従来よく確立されているから、本発明でもそれに従ってよい。 The reaction temperature in this reaction may be appropriately selected usually in the range of −10 ° C. to the reflux temperature of the inert solvent used. The reaction time varies depending on the reaction scale, reaction temperature and the like, and although not constant, it may be appropriately selected usually in the range of several minutes to 48 hours. After completion of the reaction, the target product may be isolated from the reaction system containing the target product by a conventional method, and the target product can be produced by purification by recrystallization, column chromatography, etc., as necessary. For example, compound (1), compound (1-1), compound (2), compound (3) and compound (4) involved in the present invention include the case where a salt is formed. Examples of salts include salts with inorganic acids such as hydrochloric acid, sulfuric acid and phosphoric acid, for example, salts with organic acids such as oxalic acid, acetic acid and succinic acid, salts with inorganic bases such as sodium and calcium, For example, salts with organic bases such as trimethylamine and triethylamine can be exemplified. When the compound involved in the present invention is a salt, it can be converted to the free compound, and when it is a free compound, it can be converted to a salt. This is a well-known technique and is well established in the art, so the invention may also be according to it.
　以下に本発明の代表的な実施例を例示するが、本発明はこれらに限定されるものではない。 Hereinafter, representative examples of the present invention will be illustrated, but the present invention is not limited thereto.
実施例１．
　２‐（３‐クロロ‐５‐シクロプロピルピリジン‐２‐イル）‐５‐トリフルオロメチルチオ‐ベンゾオキサゾールの製造
Figure JPOXMLDOC01-appb-C000038
 　５-トリフルオロメチルチオベンズオキサゾール（９０．８ｍｇ、０．４０ｍｍｏｌ)、　５‐シクロプロピル‐２,３‐ジクロロピリジン（７４．８ｍｇ、０．３２ｍｍｏｌ）、炭酸カリウム（１１０．９ｍｇ、０．８０ｍｍｏｌ）、酢酸パラジウム（４．７ｍｇ、０．０２ｍｍｏｌ）、１，３‐ビス(ジフェニルホスフィノ)プロパン（１７．７ｍｇ、０．０４ｍｍｏｌ）及び１．６ｍＬのＮ，Ｎ-ジメチルアセトアミドの混合物を１２０℃で５時間撹拌した。反応混合物を室温まで冷却、水を加えて酢酸エチルで抽出、抽出液を飽和食塩水で洗浄後、有機層を無水硫酸ナトリウムで乾燥した。乾燥後、減圧濃縮して得られた残渣をシリカゲルカラムクロマトグラフィーで精製することで、表題の化合物（９２．６ｍｇ）を得た。
収率：９５％
物性：１Ｈ　ＮＭＲ（ＣＤＣｌ３，ＴＭＳ )　δ（ｐｐｍ）　８．５３（１Ｈ，ｄ），８．２３（１Ｈ，ｓ），７．７２（２Ｈ，ｄ），７．５０（１Ｈ，ｄ），２．０５－１．９８（１Ｈ，ｍ），１．２４－１．１９（２Ｈ，ｍ），０．９１－０．８７（２Ｈ，ｍ） Example 1
Preparation of 2- (3-Chloro-5-cyclopropylpyridin-2-yl) -5-trifluoromethylthio-benzoxazole
Figure JPOXMLDOC01-appb-C000038
 5-trifluoromethylthiobenzoxazole (90.8 mg, 0.40 mmol), 5-cyclopropyl-2,3-dichloropyridine (74.8 mg, 0.32 mmol), potassium carbonate (110.9 mg, 0.80 mmol), A mixture of palladium acetate (4.7 mg, 0.02 mmol), 1,3-bis (diphenylphosphino) propane (17.7 mg, 0.04 mmol) and 1.6 mL of N, N-dimethylacetamide at 120 ° C. 5 Stir for hours. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and the organic layer was dried over anhydrous sodium sulfate. After drying, the residue obtained by concentration under reduced pressure was purified by silica gel column chromatography to obtain the title compound (92.6 mg).
Yield: 95%
Physical properties: 1 H NMR (CDCl 3 , TMS) δ (ppm) 8.53 (1 H, d), 8.23 (1 H, s), 7.72 (2 H, d), 7. 50 (1 H, d) , 2.05-1.98 (1H, m), 1.24-1.19 (2H, m), 0.91-0.87 (2H, m)
実施例２．
　２‐（３‐エチルチオ‐５‐シクロプロピルピリジン‐２‐イル）‐５‐トリフルオロメチルチオ‐ベンゾオキサゾールの製造
Figure JPOXMLDOC01-appb-C000039
 　２‐（３‐クロロ‐５‐シクロプロピルピリジン‐２‐イル）‐５‐トリフルオロメチルチオ‐ベンゾオキサゾール（０．３７ｇ、１ｍｍｏｌ）、４ｍLのトルエン及び４ｍLの４０％水酸化ナトリウム水溶液の混合物を５℃まで冷却した。ここにエチルメルカプタン（０．１２ｇ、１．９ｍｍｏｌ）及びテトラ-ｎ-オクチルアンモニウムブロミド（５５ｍｇ、０．１ｍｍｏｌ）を加えた後、４０℃で１時間攪拌した。反応混合物を室温まで冷却、水を加えてトルエンで抽出、有機層を無水硫酸ナトリウムで乾燥した。乾燥後、減圧濃縮して得られた残渣をシリカゲルカラムクロマトグラフィーで精製することで、表題の化合物（０．３９ｇ）を得た。
収率：９９％
物性：１Ｈ　ＮＭＲ（ＣＤＣｌ３，ＴＭＳ ）　δ（ｐｐｍ）　８．３２（１Ｈ，ｄ），８．２４（１Ｈ，ｓ），７．７２－７．６７（２Ｈ，ｍ），７．３５（１Ｈ，ｄ），３．０５（２Ｈ，ｑ），２．０４－１．９７（１Ｈ，ｍ），１．４７（３Ｈ，ｔ），１．２１－１．１６（２Ｈ，ｍ），０．９０－０．８６（２Ｈ，ｍ） Example 2
Preparation of 2- (3-ethylthio-5-cyclopropylpyridin-2-yl) -5-trifluoromethylthio-benzoxazole
Figure JPOXMLDOC01-appb-C000039
 2- (3-Chloro-5-cyclopropylpyridin-2-yl) -5-trifluoromethylthio-benzoxazole (0.37 g, 1 mmol), a mixture of 4 mL of toluene and 4 mL of 40% aqueous sodium hydroxide solution It cooled to ° C. After ethyl mercaptan (0.12 g, 1.9 mmol) and tetra-n-octyl ammonium bromide (55 mg, 0.1 mmol) were added thereto, the mixture was stirred at 40 ° C. for 1 hour. The reaction mixture was cooled to room temperature, water was added and extraction was performed with toluene, and the organic layer was dried over anhydrous sodium sulfate. After drying, the residue obtained by concentration under reduced pressure was purified by silica gel column chromatography to give the title compound (0.39 g).
Yield: 99%
Physical properties: 1 H NMR (CDCl 3 , TMS) δ (ppm) 8.32 (1 H, d), 8.24 (1 H, s), 7.72-7.67 (2 H, m), 7.35 ( 1H, d), 3.05 (2H, q), 2.04-1.97 (1H, m), 1.47 (3H, t), 1.21-1. 16 (2H, m), 0 .90-0.86 (2H, m)
実施例３．
　２‐（３‐エチルスルホニル‐５‐シクロプロピルピリジン‐２‐イル）‐５‐トリフルオロメチルチオ‐ベンゾオキサゾールの製造
Figure JPOXMLDOC01-appb-C000040
 　２‐（３‐エチルチオ‐５‐シクロプロピルピリジン‐２‐イル）‐５‐トリフルオロメチルチオ‐ベンゾオキサゾール（０．３９ｇ、０．９８ｍｍｏｌ）、メタンスルホン酸（９．６ｍｇ、０．１ｍｍｏｌ）、酢酸（０．１３ｇ、２ｍｍｏｌ）　及び４ｍLのトルエンの混合物を５０℃まで加温した。ここに３５％過酸化水素水（０．２９ｇ、３ｍｍｏｌ）を３時間かけて分割添加、更に同温度で２時間攪拌した。反応混合物を室温まで冷却、炭酸水素ナトリウム水溶液、チオ硫酸ナトリウム水溶液で洗浄、有機層を無水硫酸ナトリウムで乾燥した。乾燥後、減圧濃縮して得られた残渣をシリカゲルカラムクロマトグラフィーで精製することで、表題の化合物（０．３６ｇ）を得た。
収率：８５％
物性：１ＨＮＭＲ　(ＣＤＣｌ３,ＴＭＳ)　δ（ｐｐｍ）　８．７６（１Ｈ，ｄ），８．１６（１Ｈ，ｄ），８．１２（１Ｈ，ｄ），７．７５（１Ｈ，ｄｄ），７．７１（１Ｈ，ｄｄ），４．０３（２Ｈ，ｑ），２．１５－２．０９（１Ｈ，ｍ），１．４２（３Ｈ，ｔ），１．３１－１．２６（２Ｈ，ｍ），０．９９－０．９５（２Ｈ，ｍ） Example 3
Preparation of 2- (3-ethylsulfonyl-5-cyclopropylpyridin-2-yl) -5-trifluoromethylthio-benzoxazole
Figure JPOXMLDOC01-appb-C000040
 2- (3-Ethylthio-5-cyclopropylpyridin-2-yl) -5-trifluoromethylthio-benzoxazole (0.39 g, 0.98 mmol), methanesulfonic acid (9.6 mg, 0.1 mmol), acetic acid A mixture of (0.13 g, 2 mmol) and 4 mL of toluene was warmed to 50 ° C. 35% hydrogen peroxide solution (0.29 g, 3 mmol) was added thereto in three hours, and the mixture was further stirred at the same temperature for 2 hours. The reaction mixture was cooled to room temperature, washed with aqueous sodium hydrogen carbonate solution and aqueous sodium thiosulfate solution, and the organic layer was dried over anhydrous sodium sulfate. After drying, the residue obtained by concentration under reduced pressure was purified by silica gel column chromatography to obtain the title compound (0.36 g).
Yield: 85%
Physical properties: 1 H NMR (CDCl 3 , TMS) δ (ppm) 8.76 (1H, d), 8.16 (1 H, d), 8.12 (1 H, d), 7.75 (1 H, dd), 7.71 (1H, dd), 4.03 (2H, q), 2.15-2.09 (1H, m), 1.42 (3H, t), 1.31-1.26 (2H, 2H) m), 0.99-0.95 (2H, m)
実施例４
　２‐（３‐エチルスルホニル‐５‐シクロプロピルピリジン‐２‐イル）‐５‐トリフルオロメチルスルフィニル‐ベンゾオキサゾールの製造
Figure JPOXMLDOC01-appb-C000041
 　５‐トリフルオロメチルスルフィニルベンズオキサゾール（１０７．６ｍｇ、　０．４６ｍｍｏｌ)、　２‐クロロ‐５‐シクロプロピル‐３‐エチルスルホニルピリジン（７３．５ｍｇ、０．３０ｍｍｏｌ）、炭酸カリウム（１１０．９ｍｇ、０．６０ｍｍｏｌ）、酢酸パラジウム（３．９ｍｇ、０．０２ｍｍｏｌ）、２,２’-ビス(ジ-ｐ-トリルホスフィノ)-１,１'-ビナフチル（２２．１ｍｇ、０．０３ｍｍｏｌ）及びＮ，Ｎ-ジメチルアセトアミド（１．２ｍＬ）の混合物を１００℃で４時間撹拌した。反応混合物を室温まで冷却、水を加えて酢酸エチルで抽出、抽出液を飽和食塩水で洗浄後、有機層を無水硫酸ナトリウムで乾燥した。乾燥後、減圧濃縮して得られた残渣をシリカゲルカラムクロマトグラフィーで精製することで、表題の化合物（１２３．３ｍｇ）を得た。
収率：９３％
物性：１ＮＭＲ（ＣＤＣＬ３，ＴＭＳ） δ（ｐｐｍ）　８．７８（１Ｈ，ｄ），８．３３（１Ｈ，ｓ），８．１３（１Ｈ，ｄ），７．９２－７．８５（２Ｈ，ｍ），４．０２（２Ｈ，ｑ），２．１７－２．１０（１Ｈ，ｍ），１．４３（３Ｈ，ｔ），１．３３－１．２８（２Ｈ，ｍ），１．００－０．９６（２Ｈ，ｍ）

実施例５
　２‐（３‐エチルスルホニル‐５‐シクロプロピルピリジン‐２‐イル）‐５‐トリフルオロメチルスルホニル‐ベンゾオキサゾールの製造
Figure JPOXMLDOC01-appb-C000042
 　５‐トリフルオロメチルスルホニルベンズオキサゾール（１１４．４ ｍｇ、０．４６ｍｍｏｌ)、　２‐クロロ‐５‐シクロプロピル‐３‐エチルスルホニルピリジン（７３．６ｍｇ、０．３０ｍｍｏｌ）、炭酸カリウム（８２．９ｍｇ、０．６０ｍｍｏｌ）、酢酸パラジウム（３．８ｍｇ、０．０２ｍｍｏｌ）、２,２’-ビス(ジ-ｐ-トリルホスフィノ)-１,１'-ビナフチル（２０．６ｍｇ、０．０３ｍｍｏｌ）及びＮ，Ｎ‐ジメチルアセトアミド（１．２ｍＬ）の混合物を１００℃で４時間撹拌した。反応混合物を室温まで冷却、水を加えて酢酸エチルで抽出、抽出液を飽和食塩水で洗浄後、有機層を無水硫酸ナトリウムで乾燥した。乾燥後、減圧濃縮して得られた残渣をシリカゲルカラムクロマトグラフィーで精製することで、表題の化合物（６５．６ｍｇ）を得た。
収率：４８％
物性：１ＨＮＭＲ(ＣＤＣｌ３,ＴＭＳ) δ（ｐｐｍ)　８．７８（１Ｈ，ｄ），８．５６（１Ｈ，ｄ），８．１６－８．１３（２Ｈ，ｍ），７．９４（１Ｈ，ｄ），３．９９（２Ｈ，ｑ），２．１７－２．１１（１Ｈ，ｍ），１．４４（３Ｈ，ｔ），１．３4－１．２９（２Ｈ，ｍ），１．０１－０．９７（２Ｈ，ｍ） Example 4
Preparation of 2- (3-ethylsulfonyl-5-cyclopropylpyridin-2-yl) -5-trifluoromethylsulfinyl-benzoxazole
Figure JPOXMLDOC01-appb-C000041
 5-trifluoromethylsulfinylbenzoxazole (107.6 mg, 0.46 mmol), 2-chloro-5-cyclopropyl-3-ethylsulfonylpyridine (73.5 mg, 0.30 mmol), potassium carbonate (110.9 mg, 0 .60 mmol), palladium acetate (3.9 mg, 0.02 mmol), 2,2'-bis (di-p-tolylphosphino) -1,1'-binaphthyl (22.1 mg, 0.03 mmol) and N, N- The mixture of dimethylacetamide (1.2 mL) was stirred at 100 ° C. for 4 hours. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and the organic layer was dried over anhydrous sodium sulfate. After drying, the residue obtained by concentration under reduced pressure was purified by silica gel column chromatography to obtain the title compound (123.3 mg).
Yield: 93%
Physical properties: 1 NMR (CDCL3, TMS) δ (ppm) 8.78 (1 H, d), 8.33 (1 H, s), 8.13 (1 H, d), 7. 9-7. 85 (2 H, 2) m), 4.02 (2H, q), 2.17-2.10 (1H, m), 1.43 (3H, t), 1.33-1.28 (2H, m), 1.00 -0.96 (2H, m)

Example 5
Preparation of 2- (3-ethylsulfonyl-5-cyclopropylpyridin-2-yl) -5-trifluoromethylsulfonyl-benzoxazole
Figure JPOXMLDOC01-appb-C000042
 5-trifluoromethylsulfonylbenzoxazole (114.4 mg, 0.46 mmol), 2-chloro-5-cyclopropyl-3-ethylsulfonylpyridine (73.6 mg, 0.30 mmol), potassium carbonate (82.9 mg, 0.60 mmol), palladium acetate (3.8 mg, 0.02 mmol), 2,2'-bis (di-p-tolylphosphino) -1,1'-binaphthyl (20.6 mg, 0.03 mmol) and N, N -A mixture of dimethylacetamide (1.2 mL) was stirred at 100 ° C. for 4 hours. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and the organic layer was dried over anhydrous sodium sulfate. After drying, the residue obtained by concentration under reduced pressure was purified by silica gel column chromatography to obtain the title compound (65.6 mg).
Yield: 48%
Physical properties: 1 H NMR (CDCl 3 , TMS) δ (ppm) 8.78 (1 H, d), 8.56 (1 H, d), 8.16-8.13 (2 H, m), 7.94 (1 H) , D), 3.99 (2H, q), 2.17-2.11 (1H, m), 1.44 (3H, t), 1.34-1.29 (2H, m), 01-0.97 (2H, m)
参考例１
　５‐シクロプロピル‐２,３‐ジクロロピリジンの製造
Figure JPOXMLDOC01-appb-C000043
 　酢酸パラジウム（２８．４ｍｇ、０．１３ｍｍｏｌ）、 トリ(ｏ-トリル)ホスフィン（７７．９ｍｇ、０．２６　ｍｍｏｌ）、 炭酸カリウム（２．０７ｇ、１５ｍｍｏｌ）、 シクロプロピルボロン酸（０．５１ｇ、５．９ｍｍｏｌ）、　５-ブロモ-２,３-ジクロロピリジン（１．１４ｇ、５　ｍｍｏｌ）、１８ｍＬのトルエン及び１ｍＬの水の混合物を８０℃、４時間撹拌した。反応混合物を室温まで冷却、水を加えてトルエンで抽出、有機層を無水硫酸ナトリウムで乾燥した。減圧濃縮して得られた残渣をシリカゲルカラムクロマトグラフィーで精製することで、表題の化合物（０．８７ｇ）を得た。
収率：９２％
物性：１Ｈ　ＮＭＲ(ＣＤＣｌ３,ＴＭＳ)　δ（ｐｐｍ）　８．１０（１Ｈ，ｄ），７．３７（１Ｈ，ｄ），１．９２－１．８５（１Ｈ，ｍ），１．１１－１．０４（２Ｈ，ｍ），０．７５－０．７１（２Ｈ，ｍ） Reference Example 1
Preparation of 5-cyclopropyl-2,3-dichloropyridine
Figure JPOXMLDOC01-appb-C000043
 Palladium acetate (28.4 mg, 0.13 mmol), tri (o-tolyl) phosphine (77.9 mg, 0.26 mmol), potassium carbonate (2.07 g, 15 mmol), cyclopropylboronic acid (0.51 g, 5) .9 mmol), a mixture of 5-bromo-2,3-dichloropyridine (1.14 g, 5 mmol), 18 mL of toluene and 1 mL of water was stirred at 80 ° C. for 4 hours. The reaction mixture was cooled to room temperature, water was added and extraction was performed with toluene, and the organic layer was dried over anhydrous sodium sulfate. The residue obtained by concentration under reduced pressure was purified by silica gel column chromatography to obtain the title compound (0.87 g).
Yield: 92%
Physical properties: 1 H NMR (CDCl 3 , TMS) δ (ppm) 8.10 (1 H, d), 7.37 (1 H, d), 1.92-1. 85 (1 H, m), 1.11- 1.04 (2H, m), 0.75-0.71 (2H, m)
　次に、本発明の製造方法を用いて製造することができる化合物の具体例を表１に示すが、本発明はこれらに限定されるものではない。ＮＭＲデータは第２表に示す。 Next, although the specific example of a compound which can be manufactured using the manufacturing method of this invention is shown in Table 1, this invention is not limited to these. NMR data are shown in Table 2.
Figure JPOXMLDOC01-appb-C000044
Figure JPOXMLDOC01-appb-C000044
Figure JPOXMLDOC01-appb-T000045
Figure JPOXMLDOC01-appb-T000045
Figure JPOXMLDOC01-appb-T000046
Figure JPOXMLDOC01-appb-T000046
　本発明に係る縮合複素環化合物の製造方法により、短工程かつ高収率で縮合複素環化合物を提供できるため、当該製造方法は、産業上有用である。 The method for producing a fused heterocyclic compound according to the present invention can provide a fused heterocyclic compound in a short step and in a high yield, so the production method is industrially useful.

Claims (9)

  1. 　一般式（１）
    Figure JPOXMLDOC01-appb-C000001
     ｛式中、Ｒ１は、
    (a1) 水素原子；
    (a2) ハロゲン原子；
    (a3) （Ｃ１－Ｃ６）アルキル基；
    (a4) ハロ（Ｃ１－Ｃ６）アルキル基；
    (a5) （Ｃ１－Ｃ６）アルコキシ基;
    (a6) ハロ（Ｃ１－Ｃ６）アルコキシ基;
    (a7) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
    (a8) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
    (a9) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基を示す。
    Ｒ２は、
    (b1) 水素原子；
    (b2) ハロゲン原子；
    (b3) （Ｃ１－Ｃ６）アルキル基；
    (b4) （Ｃ３－Ｃ６）シクロアルキル基；
    (b5) （Ｃ１－Ｃ６）アルコキシ基；
    (b6) ハロ（Ｃ１－Ｃ６）アルキル基；
    (b7) ハロ（Ｃ３－Ｃ６）シクロアルキル基；
    (b8) ハロ（Ｃ１－Ｃ６）アルコキシ基；
    (b9) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
    (b10) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
    (b11) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基を示す。
    ｎは、１又は２の整数を示す。}
    で表される化合物を製造する方法であって、
    一般式（４）
    Figure JPOXMLDOC01-appb-C000002
     （式中、Ｒ１は、前記と同じ。）
    で表される化合物と、一般式（３）
    Figure JPOXMLDOC01-appb-C000003
     （式中、Ｒ２は、前記と同じくし、Ｘは、ハロゲン原子を示し、Ｙは、ハロゲン原子；又は（Ｃ１－Ｃ６）アルキルスルホニル基を示す。）
    で表される化合物とを、反応させ、生成した一般式（２）
    Figure JPOXMLDOC01-appb-C000004
     （式中、Ｒ１、Ｒ２及びＹは、前記に同じ。）
    で表される化合物に対して、塩基存在下、エチルメルカプタンを反応させることにより生成した、一般式（１‐１）
    Figure JPOXMLDOC01-appb-C000005
     （式中、Ｒ１及びＲ２は、前記に同じ。）
    で表される化合物に対して、酸化反応を行うことを特徴とする、製造方法。     General formula (1)
    Figure JPOXMLDOC01-appb-C000001
     {In the formula, R 1 is
    (a1) hydrogen atom;
    (a2) halogen atom;
    (a3) (C 1 -C 6 ) alkyl group;
    (a4) halo (C 1 -C 6 ) alkyl group;
    (a5) (C 1 -C 6 ) alkoxy group;
    (a6) halo (C 1 -C 6 ) alkoxy;
    (a7) halo (C 1 -C 6 ) alkylthio group;
    (a8) halo (C 1 -C 6 ) alkylsulfinyl group; or
    (a9) A halo (C 1 -C 6 ) alkylsulfonyl group is shown.
    R 2 is
    (b1) hydrogen atom;
    (b2) halogen atom;
    (b3) (C 1 -C 6 ) alkyl group;
    (b4) (C 3 -C 6 ) cycloalkyl group;
    (b5) (C 1 -C 6 ) alkoxy group;
    (b6) halo (C 1 -C 6 ) alkyl groups;
    (b7) halo (C 3 -C 6 ) cycloalkyl group;
    (b8) halo (C 1 -C 6 ) alkoxy;
    (b9) halo (C 1 -C 6 ) alkylthio group;
    (b10) halo (C 1 -C 6 ) alkylsulfinyl group; or
    (b11) a halo (C 1 -C 6 ) alkylsulfonyl group is shown.
    n represents an integer of 1 or 2. }
    A method of producing a compound represented by
    General formula (4)
    Figure JPOXMLDOC01-appb-C000002
     (Wherein, R 1 is the same as the above.)
    And a compound represented by the general formula (3)
    Figure JPOXMLDOC01-appb-C000003
     (Wherein, R 2 is as defined above, X is a halogen atom, and Y is a halogen atom; or (C 1 -C 6 ) alkylsulfonyl group).
    Produced by reacting with a compound represented by the general formula (2)
    Figure JPOXMLDOC01-appb-C000004
     (Wherein, R 1 , R 2 and Y are as defined above)
    A compound represented by the general formula (1-1) was produced by reacting ethyl mercaptan in the presence of a base with respect to the compound represented by
    Figure JPOXMLDOC01-appb-C000005
     (Wherein, R 1 and R 2 are as defined above)
    An oxidation reaction is performed on the compound represented by
  2. 　一般式（１）
    Figure JPOXMLDOC01-appb-C000006
     ｛式中、Ｒ１は、
    (a1) 水素原子；
    (a2) ハロゲン原子；
    (a3) （Ｃ１－Ｃ６）アルキル基；
    (a4) ハロ（Ｃ１－Ｃ６）アルキル基；
    (a5) （Ｃ１－Ｃ６）アルコキシ基;
    (a6) ハロ（Ｃ１－Ｃ６）アルコキシ基;
    (a7) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
    (a8) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
    (a9) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基を示す。
    Ｒ２は、
    (b1) 水素原子；
    (b2) ハロゲン原子；
    (b3) （Ｃ１－Ｃ６）アルキル基；
    (b4) （Ｃ３－Ｃ６）シクロアルキル基；
    (b5) （Ｃ１－Ｃ６）アルコキシ基；
    (b6) ハロ（Ｃ１－Ｃ６）アルキル基；
    (b7) ハロ（Ｃ３－Ｃ６）シクロアルキル基；
    (b8) ハロ（Ｃ１－Ｃ６）アルコキシ基；
    (b9) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
    (b10) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
    (b11) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基を示す。
    ｎは、１又は２の整数を示す。}
    で表される化合物を製造する方法であって、
    一般式（４）
    Figure JPOXMLDOC01-appb-C000007
     （式中、Ｒ１は、前記に同じ。）
    で表される化合物と、一般式（３）
    Figure JPOXMLDOC01-appb-C000008
     （式中、Ｒ２は、前記に同じくし、Ｘは、ハロゲン原子を示し、Ｙは、ハロゲン原子；又は（Ｃ１－Ｃ６）アルキルスルホニル基を示す。）
    で表される化合物とを、反応させることで、一般式（２）
    Figure JPOXMLDOC01-appb-C000009
     （式中、Ｒ１、Ｒ２及びＹは、前記に同じ。）で表される化合物を製造する工程を含む、製造方法。     General formula (1)
    Figure JPOXMLDOC01-appb-C000006
     {In the formula, R 1 is
    (a1) hydrogen atom;
    (a2) halogen atom;
    (a3) (C 1 -C 6 ) alkyl group;
    (a4) halo (C 1 -C 6 ) alkyl group;
    (a5) (C 1 -C 6 ) alkoxy group;
    (a6) halo (C 1 -C 6 ) alkoxy;
    (a7) halo (C 1 -C 6 ) alkylthio group;
    (a8) halo (C 1 -C 6 ) alkylsulfinyl group; or
    (a9) A halo (C 1 -C 6 ) alkylsulfonyl group is shown.
    R 2 is
    (b1) hydrogen atom;
    (b2) halogen atom;
    (b3) (C 1 -C 6 ) alkyl group;
    (b4) (C 3 -C 6 ) cycloalkyl group;
    (b5) (C 1 -C 6 ) alkoxy group;
    (b6) halo (C 1 -C 6 ) alkyl groups;
    (b7) halo (C 3 -C 6 ) cycloalkyl group;
    (b8) halo (C 1 -C 6 ) alkoxy;
    (b9) halo (C 1 -C 6 ) alkylthio group;
    (b10) halo (C 1 -C 6 ) alkylsulfinyl group; or
    (b11) a halo (C 1 -C 6 ) alkylsulfonyl group is shown.
    n represents an integer of 1 or 2. }
    A method of producing a compound represented by
    General formula (4)
    Figure JPOXMLDOC01-appb-C000007
     (Wherein, R 1 is the same as above)
    And a compound represented by the general formula (3)
    Figure JPOXMLDOC01-appb-C000008
     (Wherein, R 2 is the same as above, X is a halogen atom, and Y is a halogen atom; or (C 1 -C 6 ) alkylsulfonyl group).
    By reacting with a compound represented by the general formula (2)
    Figure JPOXMLDOC01-appb-C000009
     (Wherein R 1 , R 2 and Y are as defined above), which comprises the step of producing a compound represented by the formula:
  3. 　一般式（１）
    Figure JPOXMLDOC01-appb-C000010
     ｛式中、Ｒ１は、
    (a1) 水素原子；
    (a2) ハロゲン原子；
    (a3) （Ｃ１－Ｃ６）アルキル基；
    (a4) ハロ（Ｃ１－Ｃ６）アルキル基；
    (a5) （Ｃ１－Ｃ６）アルコキシ基;
    (a6) ハロ（Ｃ１－Ｃ６）アルコキシ基;
    (a7) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
    (a8) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
    (a9) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基を示す。
    Ｒ２は、
    (b1) 水素原子；
    (b2) ハロゲン原子；
    (b3) （Ｃ１－Ｃ６）アルキル基；
    (b4) （Ｃ３－Ｃ６）シクロアルキル基；
    (b5) （Ｃ１－Ｃ６）アルコキシ基；
    (b6) ハロ（Ｃ１－Ｃ６）アルキル基；
    (b7) ハロ（Ｃ３－Ｃ６）シクロアルキル基；
    (b8) ハロ（Ｃ１－Ｃ６）アルコキシ基；
    (b9) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
    (b10) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
    (b11) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基を示す。
    ｎは、１又は２の整数を示す。}
    で表される化合物を製造する方法であって、
    一般式（２）
    Figure JPOXMLDOC01-appb-C000011
     （式中、Ｒ１及びＲ２は前記に同じくし、Ｙは、ハロゲン原子；又は（Ｃ１－Ｃ６）アルキルスルホニル基を示す。）
    で表される化合物に対して、塩基存在下、エチルメルカプタンを反応させることにより、一般式（１‐１）
    Figure JPOXMLDOC01-appb-C000012
     （式中、Ｒ１及びＲ２は、前記に同じ。）
    で表される化合物を製造する工程を含む、製造方法。     General formula (1)
    Figure JPOXMLDOC01-appb-C000010
     {In the formula, R 1 is
    (a1) hydrogen atom;
    (a2) halogen atom;
    (a3) (C 1 -C 6 ) alkyl group;
    (a4) halo (C 1 -C 6 ) alkyl group;
    (a5) (C 1 -C 6 ) alkoxy group;
    (a6) halo (C 1 -C 6 ) alkoxy;
    (a7) halo (C 1 -C 6 ) alkylthio group;
    (a8) halo (C 1 -C 6 ) alkylsulfinyl group; or
    (a9) A halo (C 1 -C 6 ) alkylsulfonyl group is shown.
    R 2 is
    (b1) hydrogen atom;
    (b2) halogen atom;
    (b3) (C 1 -C 6 ) alkyl group;
    (b4) (C 3 -C 6 ) cycloalkyl group;
    (b5) (C 1 -C 6 ) alkoxy group;
    (b6) halo (C 1 -C 6 ) alkyl groups;
    (b7) halo (C 3 -C 6 ) cycloalkyl group;
    (b8) halo (C 1 -C 6 ) alkoxy;
    (b9) halo (C 1 -C 6 ) alkylthio group;
    (b10) halo (C 1 -C 6 ) alkylsulfinyl group; or
    (b11) a halo (C 1 -C 6 ) alkylsulfonyl group is shown.
    n represents an integer of 1 or 2. }
    A method of producing a compound represented by
    General formula (2)
    Figure JPOXMLDOC01-appb-C000011
     (Wherein, R 1 and R 2 are as defined above, and Y is a halogen atom; or (C 1 -C 6 ) alkylsulfonyl group).
    Is reacted with ethyl mercaptan in the presence of a base to the compound represented by the general formula (1-1)
    Figure JPOXMLDOC01-appb-C000012
     (Wherein, R 1 and R 2 are as defined above)
    The manufacturing method including the process of manufacturing the compound represented by these.
  4. 　一般式（１）
    Figure JPOXMLDOC01-appb-C000013
     ｛式中、Ｒ１は、
    (a1) 水素原子；
    (a2) ハロゲン原子；
    (a3) （Ｃ１－Ｃ６）アルキル基；
    (a4) ハロ（Ｃ１－Ｃ６）アルキル基；
    (a5) （Ｃ１－Ｃ６）アルコキシ基;
    (a6) ハロ（Ｃ１－Ｃ６）アルコキシ基;
    (a7) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
    (a8) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
    (a9) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基を示す。
    Ｒ２は、
    (b1) 水素原子；
    (b2) ハロゲン原子；
    (b3) （Ｃ１－Ｃ６）アルキル基；
    (b4) （Ｃ３－Ｃ６）シクロアルキル基；
    (b5) （Ｃ１－Ｃ６）アルコキシ基；
    (b6) ハロ（Ｃ１－Ｃ６）アルキル基；
    (b7) ハロ（Ｃ３－Ｃ６）シクロアルキル基；
    (b8) ハロ（Ｃ１－Ｃ６）アルコキシ基；
    (b9) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
    (b10) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
    (b11) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基を示す。
    ｎは、１又は２の整数を示す。}
    で表される化合物を製造する方法であって、
    一般式（１‐１）
    Figure JPOXMLDOC01-appb-C000014
     （式中、Ｒ１及びＲ２は、前記に同じ。）
    で表される化合物に対して、酸化反応を行う工程を含むことを特徴とする、製造方法。     General formula (1)
    Figure JPOXMLDOC01-appb-C000013
     {In the formula, R 1 is
    (a1) hydrogen atom;
    (a2) halogen atom;
    (a3) (C 1 -C 6 ) alkyl group;
    (a4) halo (C 1 -C 6 ) alkyl group;
    (a5) (C 1 -C 6 ) alkoxy group;
    (a6) halo (C 1 -C 6 ) alkoxy;
    (a7) halo (C 1 -C 6 ) alkylthio group;
    (a8) halo (C 1 -C 6 ) alkylsulfinyl group; or
    (a9) A halo (C 1 -C 6 ) alkylsulfonyl group is shown.
    R 2 is
    (b1) hydrogen atom;
    (b2) halogen atom;
    (b3) (C 1 -C 6 ) alkyl group;
    (b4) (C 3 -C 6 ) cycloalkyl group;
    (b5) (C 1 -C 6 ) alkoxy group;
    (b6) halo (C 1 -C 6 ) alkyl groups;
    (b7) halo (C 3 -C 6 ) cycloalkyl group;
    (b8) halo (C 1 -C 6 ) alkoxy;
    (b9) halo (C 1 -C 6 ) alkylthio group;
    (b10) halo (C 1 -C 6 ) alkylsulfinyl group; or
    (b11) a halo (C 1 -C 6 ) alkylsulfonyl group is shown.
    n represents an integer of 1 or 2. }
    A method of producing a compound represented by
    General formula (1-1)
    Figure JPOXMLDOC01-appb-C000014
     (Wherein, R 1 and R 2 are as defined above)
    A method of production, comprising the step of performing an oxidation reaction on the compound represented by
  5. 　前記の、一般式（４）で表される化合物と、一般式(３)で表される化合物との反応において、遷移金属触媒存在下に反応を行うことを特徴とする、請求項１又は２に記載の製造方法。 The reaction between the compound represented by the general formula (4) and the compound represented by the general formula (3), characterized in that the reaction is carried out in the presence of a transition metal catalyst. The manufacturing method described in.
  6. 　Ｒ１が、
    (a2) ハロゲン原子；
    (a4) ハロ（Ｃ１－Ｃ６）アルキル基；
    (a6) ハロ（Ｃ１－Ｃ６）アルコキシ基;
    (a7) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
    (a8) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
    (a9) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基である、
    請求項1乃至５のいずれか一項に記載の製造方法。     R 1 is
    (a2) halogen atom;
    (a4) halo (C 1 -C 6 ) alkyl group;
    (a6) halo (C 1 -C 6 ) alkoxy;
    (a7) halo (C 1 -C 6 ) alkylthio group;
    (a8) halo (C 1 -C 6 ) alkylsulfinyl group; or
    (a9) halo (C 1 -C 6 ) alkylsulfonyl group,
    The manufacturing method according to any one of claims 1 to 5.
  7. 　Ｒ２が、
    (b2) ハロゲン原子；
    (b3) （Ｃ１－Ｃ６）アルキル基；
    (b4) （Ｃ３－Ｃ６）シクロアルキル基；
    (b6) ハロ（Ｃ１－Ｃ６）アルキル基；
    (b8) ハロ（Ｃ１－Ｃ６）アルコキシ基；又は
    (b9) ハロ（Ｃ１－Ｃ６）アルキルチオ基である、
    請求項１乃至６のいずれか一項に記載の製造方法。     R 2 is
    (b2) halogen atom;
    (b3) (C 1 -C 6 ) alkyl group;
    (b4) (C 3 -C 6 ) cycloalkyl group;
    (b6) halo (C 1 -C 6 ) alkyl groups;
    (b8) halo (C 1 -C 6 ) alkoxy group; or
    (b9) halo (C 1 -C 6 ) alkylthio group,
    The manufacturing method according to any one of claims 1 to 6.
  8. 　Ｒ１が、
    (a2) ハロゲン原子；
    (a4) ハロ（Ｃ１－Ｃ６）アルキル基；
    (a7) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
    (a8) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
    (a9) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基であり、
    Ｒ２が、
    (b4) （Ｃ３－Ｃ６）シクロアルキル基である、
    請求項１乃至５のいずれか一項に記載の製造方法。     R 1 is
    (a2) halogen atom;
    (a4) halo (C 1 -C 6 ) alkyl group;
    (a7) halo (C 1 -C 6 ) alkylthio group;
    (a8) halo (C 1 -C 6 ) alkylsulfinyl group; or
    (a9) halo (C 1 -C 6 ) alkylsulfonyl group,
    R 2 is
    (b 4) a (C 3 -C 6 ) cycloalkyl group,
    The manufacturing method according to any one of claims 1 to 5.
  9. 　一般式（４）
    Figure JPOXMLDOC01-appb-C000015
     ｛式中、Ｒ１は、
    (a1) 水素原子；
    (a2) ハロゲン原子；
    (a3) （Ｃ１－Ｃ６）アルキル基；
    (a4) ハロ（Ｃ１－Ｃ６）アルキル基；
    (a5) （Ｃ１－Ｃ６）アルコキシ基;
    (a6) ハロ（Ｃ１－Ｃ６）アルコキシ基;
    (a7) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
    (a8) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
    (a9) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基を示す。｝で表される化合物と、一般式（３）
    Figure JPOXMLDOC01-appb-C000016
     （式中、
    Ｒ２は、
    (b1) 水素原子；
    (b2) ハロゲン原子；
    (b3) （Ｃ１－Ｃ６）アルキル基；
    (b4) （Ｃ３－Ｃ６）シクロアルキル基；
    (b5) （Ｃ１－Ｃ６）アルコキシ基；
    (b6) ハロ（Ｃ１－Ｃ６）アルキル基；
    (b7) ハロ（Ｃ３－Ｃ６）シクロアルキル基；
    (b8) ハロ（Ｃ１－Ｃ６）アルコキシ基；
    (b9) ハロ（Ｃ１－Ｃ６）アルキルチオ基；
    (b10) ハロ（Ｃ１－Ｃ６）アルキルスルフィニル基；又は
    (b11) ハロ（Ｃ１－Ｃ６）アルキルスルホニル基を示し、
    Ｘは、ハロゲン原子を示し、
    Ｙは、ハロゲン原子；又は（Ｃ１－Ｃ６）アルキルスルホニル基を示す。）
    で表される化合物とを、反応させることで、一般式（２）
    Figure JPOXMLDOC01-appb-C000017
     （式中、Ｒ１、Ｒ２及びＹは、前記に同じ。）で表される化合物を製造する工程の、
    一般式（１）
    Figure JPOXMLDOC01-appb-C000018
     ｛式中、Ｒ１及びＲ２は、前記に同じくし、ｎは、１又は２の整数を示す。}
    で表される化合物製造のための使用。     General formula (4)
    Figure JPOXMLDOC01-appb-C000015
     {In the formula, R 1 is
    (a1) hydrogen atom;
    (a2) halogen atom;
    (a3) (C 1 -C 6 ) alkyl group;
    (a4) halo (C 1 -C 6 ) alkyl group;
    (a5) (C 1 -C 6 ) alkoxy group;
    (a6) halo (C 1 -C 6 ) alkoxy;
    (a7) halo (C 1 -C 6 ) alkylthio group;
    (a8) halo (C 1 -C 6 ) alkylsulfinyl group; or
    (a9) A halo (C 1 -C 6 ) alkylsulfonyl group is shown. And a compound represented by the general formula (3)
    Figure JPOXMLDOC01-appb-C000016
     (In the formula,
    R 2 is
    (b1) hydrogen atom;
    (b2) halogen atom;
    (b3) (C 1 -C 6 ) alkyl group;
    (b4) (C 3 -C 6 ) cycloalkyl group;
    (b5) (C 1 -C 6 ) alkoxy group;
    (b6) halo (C 1 -C 6 ) alkyl groups;
    (b7) halo (C 3 -C 6 ) cycloalkyl group;
    (b8) halo (C 1 -C 6 ) alkoxy;
    (b9) halo (C 1 -C 6 ) alkylthio group;
    (b10) halo (C 1 -C 6 ) alkylsulfinyl group; or
    (b11) represents a halo (C 1 -C 6 ) alkylsulfonyl group;
    X represents a halogen atom,
    Y represents a halogen atom; or (C 1 -C 6 ) alkylsulfonyl group. )
    By reacting with a compound represented by the general formula (2)
    Figure JPOXMLDOC01-appb-C000017
     (Wherein, R 1 , R 2 and Y are the same as above) in the process of producing the compound
    General formula (1)
    Figure JPOXMLDOC01-appb-C000018
     {Wherein, R 1 and R 2 are as defined above, and n is an integer of 1 or 2. }
    Use for the production of a compound represented by
PCT/JP2018/025615 2017-07-07 2018-07-06 Method for producing condensed heterocyclic compound WO2019009387A1 (en)

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