Method for producing (alkylsulfonyl)pyridine derivatives

Abstract

The objective is to provide a shortened manufacturing method for (alkylsulfonyl)pyridine-N-substituted amidine derivatives or (alkylsulfonyl)pyridine-diazole heterocyclic derivatives that have pest control properties. [Solution] By reacting an (alkylsulfonyl)pyridine-amidine derivative with R6-O-NH2, the corresponding (alkylsulfonyl)pyridine-N-substituted amidine derivative can be directly produced. Furthermore, this manufacturing process provides a shortened manufacturing method for (alkylsulfonyl)pyridine-diazole heterocyclic derivatives.

Description

[Technical Field]

[0001] This invention relates to a method for producing (alkylsulfonyl)pyridine derivatives. [Background technology]

[0002] Heterocyclic compounds having sulfur-containing substituents that function as control agents for harmful arthropods are known. For example, Patent Document 1 describes an N-substituted amidine derivative having a sulfur-containing substituent. Also, Patent Document 2 discloses a diazole heterocyclic compound having a sulfur-containing substituent.

[0003] In obtaining diazole heterocyclic compounds containing sulfur substituents, the production of amide oxime compounds containing (alkylsulfonyl)pyridine is crucial. Patent Document 1 describes a method for producing amide oxime heterocyclic compounds, in which an amide compound containing (alkylsulfonyl)pyridine is chlorinated using carbon tetrachloride and triphenylphosphine, and then reacted with an aqueous solution of hydroxylamine. However, this method requires a lengthy process involving hydrolysis, oxidation, amide condensation, chlorination, and oximation from a pyridine carbonitride derivative to synthesize the amide oxime heterocyclic compound, making it not an industrially satisfactory method. Furthermore, Patent Document 2 describes a method for synthesizing a diazole heterocyclic compound having an alkylsulfonyl group by cyclizing an amidooxime heterocyclic compound with a carbonylating agent.

[0004] As a production method for synthesizing an amidoxime heterocyclic compound from an amine derivative and an amidine derivative, for example, Patent Document 3 describes a production method in which a salt of an amine derivative and an amidine derivative are reacted in hydrous methanol. Further, Non-Patent Document 1 describes a production method in which a salt of an amine derivative and an amidine derivative are reacted in water. Furthermore, Non-Patent Document 2 describes a production method in which a salt of an amine derivative and an amidine derivative are reacted in acetonitrile in the presence of triethylamine. However, in these methods, the yield of the target product is between 24% and 69%, leaving room for improvement, and a high-yield production method is required.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Patent Document 3

Non-Patent Documents

[0006]

Non-Patent Document 1

Non-Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0007] The present invention provides a production method for an amidoxime derivative having a (alkylsulfonyl)pyridine group by a shortening process.

Means for Solving the Problems

[0008] As a result of diligent research to achieve the above objectives, we have discovered a method for producing amidooxime derivatives that is advantageous for high yield and industrial-scale production by reacting amidine derivatives with amine derivatives. This invention is based on these findings.

[0009] The present invention relates to, but is not limited to, the following [1] to [3]. [1] A method for producing an amidooxime derivative represented by formula (1), [ka] [In formula (1), R2, R3, R4 and R5 are each independently a hydrogen atom, a halogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C2-C6) alkenyl group, an optionally substituted (C2-C6) alkynyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C2-C6) alkenyloxy group, an optionally substituted (C2-C6) alkynyloxy group, an optionally substituted (C3-C6) cycloalkoxy group, an optionally substituted (C1-C6) alkylcarbonyl group, an optionally substituted (C3-C6) cycloalkylcarbonyl group, an optionally substituted (C1-C6) alkoxycarbonyl group, an optionally substituted (C2-C6) alkenyloxycarbonyl group, or an optionally substituted (C2-C6) alkynyloxy group This represents a group selected from the group consisting of a carbonyl group, an optionally substituted (C1-C6) alkylcarbonyloxy group, an optionally substituted (C2-C6) alkenylcarbonyloxy group, an optionally substituted (C2-C6) alkynylcarbonyloxy group, an optionally substituted (C1-C6) alkylthio group, an optionally substituted (C1-C6) alkylsulfinyl group, an optionally substituted (C1-C6) alkylsulfonyl group, an optionally substituted (C1-C6) alkylsulfonyloxy group, an optionally substituted phenyl group, an optionally substituted heterocyclic group, an optionally substituted phenoxy group, an optionally substituted pyridyloxy group, a NY1Y2 group, a C(O)NY1Y2 group, a C(=NY2)Y3 group, a cyano group, a nitro group, a hydroxyl group, a mercapto group, an amino group, a formyl group, a carboxyl group, a trimethylsilyl group, a C(O)NH2 group, and an SF5 group. If multiple Y1 groups exist, each independently represents a group selected from the group consisting of a hydrogen atom and an alkyl group that may have substituents (C1-C6). If multiple Y2 groups exist, each Y2 group independently represents a group selected from the group consisting of a hydrogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C2-C6) alkenyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C1-C6) alkylcarbonyl group, an optionally substituted (C1-C6) alkoxycarbonyl group, an optionally substituted phenyl group, an optionally substituted heterocyclic group, a cyano group, and a hydroxyl group. If multiple Y3 groups exist, each independently represents a group selected from the group consisting of a hydrogen atom, a halogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C1-C6) alkylthio group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted phenyl group, and an NY1Y2 group (Y1 and Y2 are as defined above). R6 represents a group selected from the group consisting of a hydrogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkylcarbonyl group, and an optionally substituted (C3-C6) cycloalkylcarbonyl group. R a This represents a group selected from the group consisting of optionally substituted (C1-C6) alkyl groups and optionally substituted (C3-C6) cycloalkyl groups. R b , R c , and R dEach of these independently comprises a hydrogen atom, a halogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C2-C6) alkenyl group, an optionally substituted (C2-C6) alkynyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C2-C6) alkenyloxy group, an optionally substituted (C2-C6) alkynyloxy group, an optionally substituted (C3-C6) cycloalkoxy group, an optionally substituted (C1-C6) alkylcarbonyl group, an optionally substituted (C3-C6) cycloalkylcarbonyl group, an optionally substituted (C1-C6) alkoxycarbonyl group, an optionally substituted (C2-C6) alkenyloxycarbonyl group, an optionally substituted (C2-C6) alkynyloxycarbonyl group, and an optionally substituted (C This represents a group selected from the group consisting of (1-C6) alkylcarbonyloxy group, optionally substituted (C2-C6) alkenylcarbonyloxy group, optionally substituted (C2-C6) alkynylcarbonyloxy group, optionally substituted (C1-C6) alkylthio group, optionally substituted (C1-C6) alkylsulfinyl group, optionally substituted (C1-C6) alkylsulfonyl group, optionally substituted (C1-C6) alkylsulfonyloxy group, optionally substituted phenyl group, optionally substituted heterocyclic group, optionally substituted phenoxy group, optionally substituted pyridyloxy group, NY1Y2 group, C(O)NY1Y2 group, C(=NY2)Y3 group, cyano group, nitro group, hydroxyl group, mercapto group, amino group, formyl group, carboxyl group, trimethylsilyl group, C(O)NH2 group, and SF5 group (Y1, Y2, and Y3 are as defined above). The following steps: [Process A] In the presence of a solvent, the amidine derivative represented by formula (2) and [ka] [In equation (2), R2, R3, R4 and R5, and R a , R b , R c and R d This is synonymous with the above. Amine compound represented by formula (3) [ka] Step A: Reacting [In formula (3), R6 is the same as above.] A manufacturing method that includes this.

[0010] [2] A method for producing (alkylsulfonyl)pyridine derivatives represented by formula (4), [ka] [In formula (4), R2, R3, R4 and R5 are each independently a hydrogen atom, a halogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C2-C6) alkenyl group, an optionally substituted (C2-C6) alkynyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C2-C6) alkenyloxy group, an optionally substituted (C2-C6) alkynyloxy group, an optionally substituted (C3-C6) cycloalkoxy group, an optionally substituted (C1-C6) alkylcarbonyl group, an optionally substituted (C3-C6) cycloalkylcarbonyl group, an optionally substituted (C1-C6) alkoxycarbonyl group, an optionally substituted (C2-C6) alkenyloxycarbonyl group, or an optionally substituted (C2-C6) alkynyloxy group This represents a group selected from the group consisting of a carbonyl group, an optionally substituted (C1-C6) alkylcarbonyloxy group, an optionally substituted (C2-C6) alkenylcarbonyloxy group, an optionally substituted (C2-C6) alkynylcarbonyloxy group, an optionally substituted (C1-C6) alkylthio group, an optionally substituted (C1-C6) alkylsulfinyl group, an optionally substituted (C1-C6) alkylsulfonyl group, an optionally substituted (C1-C6) alkylsulfonyloxy group, an optionally substituted phenyl group, an optionally substituted heterocyclic group, an optionally substituted phenoxy group, an optionally substituted pyridyloxy group, a NY1Y2 group, a C(O)NY1Y2 group, a C(=NY2)Y3 group, a cyano group, a nitro group, a hydroxyl group, a mercapto group, an amino group, a formyl group, a carboxyl group, a trimethylsilyl group, a C(O)NH2 group, and an SF5 group. If multiple Y1 groups exist, each independently represents a group selected from the group consisting of a hydrogen atom and an alkyl group that may have substituents (C1-C6). When there are a plurality of Y2, each independently represents a group selected from the group consisting of a hydrogen atom, a (C1-C6) alkyl group which may have a substituent, a (C2-C6) alkenyl group which may have a substituent, a (C3-C6) cycloalkyl group which may have a substituent, a (C1-C6) alkoxy group which may have a substituent, a (C1-C6) alkylcarbonyl group which may have a substituent, a (C1-C6) alkoxycarbonyl group which may have a substituent, a phenyl group which may have a substituent, a heterocyclic group which may have a substituent, a cyano group, and a hydroxy group. When there are a plurality of Y3, each independently represents a group selected from the group consisting of a hydrogen atom, a halogen atom, a (C1-C6) alkyl group which may have a substituent, a (C1-C6) alkoxy group which may have a substituent, a (C1-C6) alkylthio group which may have a substituent, a (C3-C6) cycloalkyl group which may have a substituent, a phenyl group which may have a substituent, and a NY1Y2 group (where Y1 and Y2 have the same meanings as described above). R a represents a group selected from the group consisting of a (C1-C6) alkyl group which may have a substituent and a (C3-C6) cycloalkyl group which may have a substituent. R b R c and R dEach of these independently comprises a hydrogen atom, a halogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C2-C6) alkenyl group, an optionally substituted (C2-C6) alkynyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C2-C6) alkenyloxy group, an optionally substituted (C2-C6) alkynyloxy group, an optionally substituted (C3-C6) cycloalkoxy group, an optionally substituted (C1-C6) alkylcarbonyl group, an optionally substituted (C3-C6) cycloalkylcarbonyl group, an optionally substituted (C1-C6) alkoxycarbonyl group, an optionally substituted (C2-C6) alkenyloxycarbonyl group, an optionally substituted (C2-C6) alkynyloxycarbonyl group, and an optionally substituted group. A group selected from the group consisting of (C1-C6) alkylcarbonyloxy group, optionally substituted (C2-C6) alkenylcarbonyloxy group, optionally substituted (C2-C6) alkynylcarbonyloxy group, optionally substituted (C1-C6) alkylthio group, optionally substituted (C1-C6) alkylsulfinyl group, optionally substituted (C1-C6) alkylsulfonyl group, optionally substituted (C1-C6) alkylsulfonyloxy group, optionally substituted phenyl group, optionally substituted heterocyclic group, optionally substituted phenoxy group, optionally substituted pyridyloxy group, NY1Y2 group, C(O)NY1Y2 group, C(=NY2)Y3 group, cyano group, nitro group, hydroxyl group, mercapto group, amino group, formyl group, carboxyl group, trimethylsilyl group, C(O)NH2 group, and SF5 group (Y1, Y2, and Y3 are as defined above). [This indicates...] The following steps: [Process A] In the presence of a solvent, the amidine derivative represented by formula (2) and [ka] [In equation (2), R2, R3, R4 and R5, and R a , R b , R c and R d This is synonymous with the above. Amine compound represented by formula (3) [ka] [In formula (3), R6 represents a group selected from the group consisting of a hydrogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkylcarbonyl group, and an optionally substituted (C3-C6) cycloalkylcarbonyl group. Reacting with ] Amidooxime derivative represented by formula (1) [ka] [In equation (1), R2, R3, R4, R5 and R6, and R a , R b , R c and R d This is synonymous with the above. ] includes step A, and [Process B] By reacting the amidooxime derivative represented by formula (1) with a carbonylating agent, the (alkylsulfonyl)pyridine derivative represented by formula (4) is obtained. [ka] [In equation (4), R2, R3, R4 and R5, and R a , R b , R c and R d This is synonymous with the above. Step B to obtain; A manufacturing method that includes this.

[0011] [3] The manufacturing method according to claim 1 or 2, wherein the solvent in [Step A] is a solvent comprising one or more selected from the group consisting of methanol, ethanol, 1-propanol, isopropanol, 1-butanol, 2-butanol, isobutanol, t-butanol, 1-pentanol, 2-pentanol, isopentanol, 1-hexanol, and 2-hexanol. [Effects of the Invention]

[0012] According to the manufacturing method of the present invention, an amidooxime derivative represented by formula (1) can be directly produced from the corresponding amidine derivative, and the compound having pest control activity and the oxadiazole heterocyclic compound produced therefrom can be produced in a short number of steps. [Modes for carrying out the invention]

[0013] The present invention includes a method for producing a (alkylsulfonyl)pyridine-amidooxime derivative represented by formula (1) (hereinafter also referred to as compound (1)).

[0014] [ka]

[0015] Another embodiment is a method for producing a (alkylsulfonyl)pyridine-oxadiazole derivative represented by formula (4) (hereinafter also referred to as compound (4)).

[0016] [ka]

[0017] The substituents in compound (1) and compound (4) will be described below. R2, R3, R4, and R5 can each be independently a hydrogen atom, a halogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C2-C6) alkenyl group, an optionally substituted (C2-C6) alkynyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C2-C6) alkenyloxy group, an optionally substituted (C2-C6) alkynyloxy group, an optionally substituted (C3-C6) cycloalkoxy group, an optionally substituted (C1-C6) alkylcarbonyl group, an optionally substituted (C3-C6) cycloalkylcarbonyl group, an optionally substituted (C1-C6) alkoxycarbonyl group, an optionally substituted (C2-C6) alkenyloxycarbonyl group, or an optionally substituted (C2-C6) alkynyloxycarbonyl group This represents a group selected from the group consisting of a nyl group, optionally substituted (C1-C6) alkylcarbonyloxy group, optionally substituted (C2-C6) alkenylcarbonyloxy group, optionally substituted (C2-C6) alkynylcarbonyloxy group, optionally substituted (C1-C6) alkylthio group, optionally substituted (C1-C6) alkylsulfinyl group, optionally substituted (C1-C6) alkylsulfonyl group, optionally substituted (C1-C6) alkylsulfonyloxy group, optionally substituted phenyl group, optionally substituted heterocyclic group, optionally substituted phenoxy group, optionally substituted pyridyloxy group, NY1Y2 group, C(O)NY1Y2 group, C(=NY2)Y3 group, cyano group, nitro group, hydroxyl group, mercapto group, amino group, formyl group, carboxyl group, trimethylsilyl group, C(O)NH2 group, and SF5 group. If multiple Y1 groups exist, each independently represents a group selected from the group consisting of a hydrogen atom and an alkyl group (C1-C6) which may have substituents. If there are multiple Y2 groups, each Y2 group independently represents a group selected from the group consisting of a hydrogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C2-C6) alkenyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C1-C6) alkylcarbonyl group, an optionally substituted (C1-C6) alkoxycarbonyl group, an optionally substituted phenyl group, an optionally substituted heterocyclic group, a cyano group, and a hydroxyl group. If multiple Y3 groups exist, each independently represents a group selected from the group consisting of a hydrogen atom, a halogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C1-C6) alkylthio group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted phenyl group, and an NY1Y2 group (Y1 and Y2 are as defined above). The substituents that may be present include halogen atoms, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, (C3-C6) cycloalkoxy groups, NY1Y2 groups, C(O)NY1Y2 groups, C(=NY2)Y3 groups, cyano groups, nitro groups, hydroxyl groups, mercapto groups, amino groups, formyl groups, carboxyl groups, trimethylsilyl groups, C(O)NH2 groups, and SF5 groups. When there are two or more substituents, each substituent may be the same or different from the others.

[0018] Preferably, R2, R3, R4, and R5 each independently represent a group selected from the group consisting of a hydrogen atom, a halogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C3-C6) cycloalkoxy group, an optionally substituted (C1-C6) alkylthio group, an optionally substituted (C1-C6) alkylsulfinyl group, and an optionally substituted (C1-C6) alkylsulfonyl group. In this case, the substituents that may be present are halogen atoms, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, cyano groups, nitro groups, hydroxyl groups, mercapto groups, amino groups, carboxyl groups, trimethylsilyl groups, C(O)NH2 groups, and SF5 groups. More preferably, R2 and R5 are hydrogen atoms, and R3 and R4 are each independently selected from the group consisting of hydrogen atoms, halogen atoms, and optionally substituted (C1-C6) alkyl groups. Particularly preferably, R2 and R5 are hydrogen atoms, and either R3 or R4 is optionally substituted (C1-C6) alkyl group, and the other is a hydrogen atom. In this case, the optionally substituted groups are halogen atoms, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, cyano groups, nitro groups, hydroxyl groups, mercapto groups, amino groups, carboxyl groups, trimethylsilyl groups, C(O)NH2 groups, and SF5 groups.

[0019] The aforementioned R a This group is selected from the group consisting of optionally substituted (C1-C6) alkyl groups and optionally substituted (C3-C6) cycloalkyl groups. The substituents that may be present include halogen atoms, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, (C3-C6) cycloalkoxy groups, NY1Y2 groups, C(O)NY1Y2 groups, C(=NY2)Y3 groups, cyano groups, nitro groups, hydroxyl groups, mercapto groups, amino groups, formyl groups, carboxyl groups, trimethylsilyl groups, C(O)NH2 groups, and SF5 groups. When there are two or more substituents, each substituent may be the same or different from the others. Preferably, R a is an alkyl group which may have substituents (C1-C6). More preferably, R a This is a halogen-substituted (C1-C3) alkyl group, and more preferably a methyl group or an ethyl group.

[0020] R b , R c and Rd Each of these independently comprises a hydrogen atom, a halogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C2-C6) alkenyl group, an optionally substituted (C2-C6) alkynyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C2-C6) alkenyloxy group, an optionally substituted (C2-C6) alkynyloxy group, an optionally substituted (C3-C6) cycloalkoxy group, an optionally substituted (C1-C6) alkylcarbonyl group, an optionally substituted (C3-C6) cycloalkylcarbonyl group, an optionally substituted (C1-C6) alkoxycarbonyl group, an optionally substituted (C2-C6) alkenyloxycarbonyl group, an optionally substituted (C2-C6) alkynyloxycarbonyl group, and an optionally substituted (C The group is selected from the group consisting of (1-C6) alkylcarbonyloxy group, optionally substituted (C2-C6) alkenylcarbonyloxy group, optionally substituted (C2-C6) alkynylcarbonyloxy group, optionally substituted (C1-C6) alkylthio group, optionally substituted (C1-C6) alkylsulfinyl group, optionally substituted (C1-C6) alkylsulfonyl group, optionally substituted (C1-C6) alkylsulfonyloxy group, optionally substituted phenyl group, optionally substituted heterocyclic group, optionally substituted phenoxy group, optionally substituted pyridyloxy group, NY1Y2 group, C(O)NY1Y2 group, C(=NY2)Y3 group, cyano group, nitro group, hydroxyl group, mercapto group, amino group, formyl group, carboxyl group, trimethylsilyl group, C(O)NH2 group, and SF5 group (Y1, Y2, and Y3 are as defined above). The substituents that may be present include halogen atoms, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, (C3-C6) cycloalkoxy groups, NY1Y2 groups, C(O)NY1Y2 groups, C(=NY2)Y3 groups, cyano groups, nitro groups, hydroxyl groups, mercapto groups, amino groups, formyl groups, carboxyl groups, trimethylsilyl groups, C(O)NH2 groups, and SF5 groups. When there are two or more substituents, each substituent may be the same or different from the others.

[0021] Preferably, R b , R c and R d Each of these independently represents a group selected from the group consisting of a hydrogen atom, a halogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C3-C6) cycloalkoxy group, an optionally substituted (C1-C6) alkylthio group, an optionally substituted (C1-C6) alkylsulfinyl group, an optionally substituted (C1-C6) alkylsulfonyl group, an optionally substituted phenyl group, an optionally substituted heterocyclic group, an optionally substituted phenoxy group, and an optionally substituted pyridyloxy group. In this case, the substituents that may be present are halogen atoms, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, cyano groups, nitro groups, hydroxyl groups, mercapto groups, amino groups, carboxyl groups, trimethylsilyl groups, C(O)NH2 groups, and SF5 groups. Comfortable, R b and R d R is a hydrogen atom, c This group is selected from the group consisting of a hydrogen atom, a halogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkoxy group, an optionally substituted (C3-C6) cycloalkoxy group, an optionally substituted phenyl group, and an optionally substituted heterocyclic group. In this case, the substituents that may be present are halogen atoms, cyano groups, nitro groups, hydroxyl groups, mercapto groups, amino groups, carboxyl groups, trimethylsilyl groups, C(O)NH2 groups, and SF5 groups. More preferably, R b and R d R is a hydrogen atom, c This group is selected from the group consisting of a hydrogen atom, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted phenyl group, and an optionally substituted heterocyclic group. In this case, the optionally substituted groups are a halogen atom, an (C1-C6) alkoxy group, a halo(C1-C6) alkoxy group, a cyano group, a nitro group, a hydroxyl group, a mercapto group, an amino group, a carboxyl group, a trimethylsilyl group, a C(O)NH2 group, and an SF5 group.

[0022] R b , R c and R d Preferred forms of the phenyl group, which may have substituents, include 3-fluorophenyl group, 3-chlorophenyl group, 3-bromophenyl group, 3-iodophenyl group, 3-cyanophenyl group, 3-(trifluoromethyl)phenyl group, 3-(trifluoromethoxy)phenyl group, 4-fluorophenyl group, 4-chlorophenyl group, 4-bromophenyl group, 4-iodophenyl group, 4-cyanophenyl group, 4-(trifluoromethyl)phenyl group, 4-(trifluoromethoxy)phenyl group, 4-cyclopropylphenyl group, 4-(1-cyanocyclopropyl)phenyl group, 2,4-difluorophenyl group, 2,4,6-trifluorophenyl group, and 3,5-difluorophenyl group.

[0023] R2, R3, R4 and R5 in compound (1) and compound (4), and R b , R c and R dExamples of "heterocyclic groups" in this context include thiophen-2-yl, thiophen-3-yl, furan-2-yl, furan-3-yl, pyrrol-1-yl, pyrrol-2-yl, pyrrol-3-yl, oxazole-2-yl, oxazole-4-yl, oxazole-5-yl, isoxazole-3-yl, isoxazole-4-yl, isoxazole-5-yl, isoxazolin-3-yl, isoxazolin-4-yl, isoxazolin-5-yl, thiazole-2-yl, thiazole-4-yl, thiazole-5-yl, isothiazo Isothiazole-3-yl, isothiazole-4-yl, isothiazole-5-yl, pyrazole-1-yl, pyrazol-3-yl, pyrazole-4-yl, pyrazole-5-yl, imidazole-1-yl, imidazole-2-yl, imidazole-4-yl, 1,3,4-oxadiazole-2-yl, 1,2,4-oxadiazole-3-yl, 1,2,4-oxadiazole-5-yl, 1,3,4-thiadiazole-2-yl, 1,2,4-thiadiazole-3-yl, 1,2,4-thiadiazole-5-yl, 1,2,4-triazole-1-yl 1,2,4-triazole-3-yl, 1,2,4-triazole-5-yl, 1,2,3-thiadiazole-4-yl, 1,2,3-thiadiazole-5-yl, 1,2,3-triazole-1-yl, 1,2,3-triazole-2-yl, 1,2,3-triazole-4-yl, 1,2,3,4-tetrazol-1-yl, 1,2,3,4-tetrazol-2-yl, 1,2,3,4-tetrazol-5-yl, pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, pyrimidine-2-yl, pyrimidine-4-yl, pyrimidine-5 -yl, pyrazine-2-yl, pyridazine-3-yl, pyridazine-4-yl, 1,3,5-triazine-2-yl, 1,2,4-triazine-3-yl, 1,2,4-triazine-5-yl, 1,2,4-triazine-6-yl, benzothiophene-2-yl, benzothiophene-3-yl, benzothiophene-4-yl, benzothiophene-5-yl, benzothiophene-6-yl, benzothiophene-7-yl, benzofuran-2-yl, benzofuran-3-yl, benzofuran-4-yl, benzofuran-5-yl, benzofuran-6-yl,Benzofuran-7-yl, indole-1-yl, indole-2-yl, indole-3-yl, indole-4-yl, indole-5-yl, indole-6-yl, indole-7-yl, benzothiazole-2-yl, benzothiazole-4-yl, benzothiazole-5-yl, benzothiazole-6-yl, benzothiazole-7-yl, benzimidazole-1-yl, benzimidazole-2-yl, benzimidazole-4-yl, benzimidazole-5-yl, benzimidazole-6-yl, benzimidazole-7-yl, Benzoisoxazole-3-yl, benzoisoxazole-4-yl, benzoisoxazole-5-yl, benzoisoxazole-6-yl, benzoisoxazole-7-yl, benzoisothiazol-3-yl, benzoisothiazol-4-yl, benzoisothiazol-5-yl, benzoisothiazol-6-yl, benzoisothiazol-7-yl, indazole-1-yl, indazole-3-yl, indazole-4-yl, indazole-5-yl, indazole-6-yl, indazole-7-yl, benzoisoxazole-2-yl Benzoxazole-4-yl, Benzoxazole-5-yl, Benzoxazole-6-yl, Benzoxazole-7-yl, Quinoline-2-yl, Quinoline-3-yl, Quinoline-4-yl, Quinoline-5-yl, Quinoline-6-yl, Quinoline-7-yl, Quinoline-8-yl, Isoquinoline-1-yl, Isoquinoline-3-yl, Isoquinoline-4-yl, Isoquinoline-5-yl, Isoquinoline-6-yl, Isoquinoline-7-yl, Isoquinoline-8-yl, Quinoxaline-2-yl, Quinoxaline-3-yl, Quinoxaline-5-yl Examples include quinoxaline-6-yl, quinoxaline-7-yl, quinoxaline-8-yl, phthalazine-1-yl, phthalazine-4-yl, phthalazine-5-yl, phthalazine-6-yl, phthalazine-7-yl, phthalazine-8-yl, cinnoline-3-yl, cinnoline-4-yl, cinnoline-5-yl, cinnoline-6-yl, cinnoline-7-yl, cinnoline-8-yl, quinazolin-2-yl, quinazolin-4-yl, quinazolin-5-yl, quinazolin-6-yl, quinazolin-7-yl, or quinazolin-8-yl.

[0024] The R6 is a group selected from the group consisting of a hydrogen atom, an optionally substituted (C1-C6) alkyl group, an optionally substituted (C3-C6) cycloalkyl group, an optionally substituted (C1-C6) alkylcarbonyl group, and an optionally substituted (C3-C6) cycloalkylcarbonyl group. The substituents that may be present include halogen atoms, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, (C3-C6) cycloalkoxy groups, NY1Y2 groups, C(O)NY1Y2 groups, C(=NY2)Y3 groups, cyano groups, nitro groups, hydroxyl groups, mercapto groups, amino groups, formyl groups, carboxyl groups, trimethylsilyl groups, C(O)NH2 groups, and SF5 groups. When there are two or more substituents, each substituent may be the same or different from the others. Preferably, R6 is a group selected from a hydrogen atom, an optionally substituted (C1-C6) alkyl group, or an optionally substituted (C3-C6) cycloalkyl group. More preferably, R6 is a hydrogen atom.

[0025] In the compounds represented by formula (2) and formula (3) described later, R2, R3, R4 and R5, and R b , R c and R d , and R6 are synonymous with the above.

[0026] The present invention relates to a method for directly producing an (alkylsulfonyl)pyridine-amide oxime derivative (compound (1)) represented by formula (1), using an amidine derivative having a (alkylsulfonyl)pyridine group represented by formula (2) as a starting material. The present invention also relates to a method for producing an (alkylsulfonyl)pyridine-oxadiazole derivative (compound (4)) represented by formula (4) using the above production method. The details are described below.

[0027] [Process A] Compound (1) can be produced directly from compound (2) by reacting an amidine derivative having (alkylsulfonyl)pyridine represented by formula (2) (hereinafter referred to as compound (2)) with an amine compound represented by formula (3) (hereinafter referred to as compound (3)).

[0028] [ka]

[0029] The solvent used in [Step A] and the manufacturing method will be described below. The reaction between compound (2) and compound (3) may be carried out in the presence of a solvent. Examples of solvents include, but are not limited to, water; aromatic hydrocarbon solvents such as benzene, chlorobenzene, and toluene; halogenated aliphatic hydrocarbon solvents such as chloroform, dichloromethane, and 1,2-dichloroethane; alcohol solvents such as methanol, ethanol, and 1-butanol; nitrile solvents such as acetonitrile and propionitrile; aromatic heterocyclic solvents such as pyridine; sulfoxide solvents such as dimethyl sulfoxide and sulfolane; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; ether solvents such as tetrahydrofuran, diethyl ether, and 1,4-dioxane; or mixtures thereof. Preferably, an alcohol solvent is used, and it is preferable to use a solvent containing one or more alcohols selected from the group consisting of methanol, ethanol, 1-propanol, isopropanol, 1-butanol, 2-butanol, isobutanol, t-butanol, 1-pentanol, 2-pentanol, isopentanol, 1-hexanol, and 2-hexanol. More preferably, the solvent contains one or more alcohols selected from methanol, ethanol, isopropanol, and 1-butanol. The amount of solvent used is usually 1 to 100 parts by mass, preferably 1 to 20 parts by mass, relative to compound (2). A more preferable amount of solvent is 2 to 10 parts by mass. This is usually carried out by mixing compound (2) and compound (3). When using an alcohol solvent, it may also be used as a mixed solvent with another solvent that is miscible with the alcohol. In that case, the mixing ratio (volume) of the alcohol solvent to the other solvent is preferably 1:9 to 9:1, and more preferably 1:5 to 5:1.

[0030] The reaction temperature for the reaction between compound (2) and compound (3) is usually 10 to 200°C, preferably 20 to 150°C. The reaction is preferably carried out under a nitrogen atmosphere. The reaction time is typically 0.1 to 100 hours, preferably 0.1 to 24 hours.

[0031] The reaction between compound (2) and compound (3) may be carried out in the presence of a base. Examples of bases include, but are not limited to, pyridine compounds such as pyridine and 4-dimethylaminopyridine; tertiary amine compounds such as triethylamine and ethyldiisopropylamine; and carbonates such as sodium bicarbonate, sodium carbonate, and potassium carbonate. The amount of base used is usually 1 to 20 moles, preferably 1 to 10 moles, per mole of compound (2).

[0032] One method for extracting compound (1) from the reaction mixture is to concentrate the mixture after the reaction is complete, for example, to extract compound (1) from the resulting reaction mixture. The extracted reaction mixture may be used directly in step B, or it may be purified by liquid-liquid separation, filtration, etc. Alternatively, compound (4) may be isolated from the reaction mixture by conventional purification methods such as washing, filtration, column chromatography, and recrystallization.

[0033] [Process B] A (alkylsulfonyl)pyridine derivative represented by compound (4) can be produced from compound (1). [ka]

[0034] The carbonylating agent used in step B of the present invention, as well as the method for producing it, will be described below. Step B allows for the production of compound (4) by reacting an N-hydroxyamidine derivative (compound (1a)) in which R6 is a hydrogen atom with a carbonylating agent. Therefore, when applying the present invention to the production of compound (4), it is preferable to use a hydroxylamine in which R6 is a hydrogen atom as compound (3) represented by formula (3), to produce an N-hydroxyamidine derivative (compound 1a), which is then applied to [Step B]. When using compound (1) in which R6 is an alkyl group or an acyl group, it is necessary to convert it to an N-hydroxyamidine derivative (compound 1a) by an appropriate method.

[0035] Examples of carbonylating agents include, but are not limited to, 1,1-carbonyldiimidazole and halogenated carbamate compounds such as methyl chloroformate, ethyl chloroformate, phenyl chloroformate, and 4-nitrophenyl chloroformate. The amount of carbonylating agent used is usually 1 to 20 moles, preferably 1 to 5 moles, per mole of compound (1a).

[0036] The reaction between compound (1a) and the carbonylating agent may be carried out in the presence of a solvent. Examples of solvents include, but are not limited to, water; aromatic hydrocarbon solvents such as benzene, chlorobenzene, and toluene; halogenated aliphatic hydrocarbon solvents such as chloroform, dichloromethane, and 1,2-dichloroethane; alcohol solvents such as methanol, ethanol, and 1-butanol; nitrile solvents such as acetonitrile and propionitrile; aromatic heterocyclic solvents such as pyridine; sulfoxide solvents such as dimethyl sulfoxide and sulfolane; amide solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone; ether solvents such as tetrahydrofuran, diethyl ether, and 1,4-dioxane; or mixtures thereof. The amount of solvent used is usually 1 to 100 parts by mass, preferably 1 to 20 parts by mass, relative to compound (1a). A more preferable amount of solvent is 2 to 10 parts by mass. This is usually carried out by mixing compound (4) with the reactant.

[0037] The reaction temperature for the reaction between compound (1a) and the carbonylating agent is typically -20 to 100°C, preferably -10 to 50°C. The reaction is preferably carried out under a nitrogen atmosphere. The reaction time is typically 0.1 to 100 hours, preferably 0.1 to 24 hours.

[0038] The reaction between compound (1a) and the carbonylating agent may be carried out in the presence of a base. Examples of bases include, but are not limited to, pyridine compounds such as pyridine and 4-dimethylaminopyridine; tertiary amine compounds such as triethylamine and ethyldiisopropylamine; carbonates such as sodium bicarbonate, sodium carbonate, and potassium carbonate; and hydroxide salts such as lithium hydroxide and sodium hydroxide. The amount of base used is usually 1 to 20 moles, preferably 1 to 10 moles, per mole of compound (1a).

[0039] Compound (4) can be isolated from the reaction mixture by, for example, concentration after the reaction is complete. Alternatively, compound (4) may be isolated from the reaction mixture by conventional purification methods such as washing, filtration, column chromatography, and recrystallization. [Examples]

[0040] Example 1: Method for producing 3-(ethylsulfonyl)-N'-hydroxy-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide [ka] 3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide (500 mg, 0.96 mmol) was dissolved in methanol (10 mL). Hydroxylamine hydrochloride (335 mg, 4.82 mmol) was added, and the mixture was stirred under reflux conditions for 4 hours. The compounds in the reaction system 4 hours after the reaction were analyzed by high-performance liquid chromatography, and the results are summarized in Table 1.

[0041] Example 2: Method for producing 3-(ethylsulfonyl)-N'-hydroxy-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide 3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide (500 mg, 0.96 mmol) was dissolved in ethanol (10 mL). Hydroxylamine hydrochloride (335 mg, 4.82 mmol) was added, and the mixture was stirred under reflux conditions for 4 hours. The compounds in the reaction system 4 hours after the reaction were analyzed by high-performance liquid chromatography, and the results are summarized in Table 1.

[0042] Example 3: Method for producing 3-(ethylsulfonyl)-N'-hydroxy-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide 3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide (500 mg, 0.96 mmol) was dissolved in 1-propanol (10 mL). Hydroxylamine hydrochloride (335 mg, 4.82 mmol) was added, and the mixture was stirred under reflux conditions for 4 hours. The compounds in the reaction system 4 hours after the reaction were analyzed by high-performance liquid chromatography, and the results are summarized in Table 1.

[0043] Example 4: Method for producing 3-(ethylsulfonyl)-N'-hydroxy-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide 3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide (500 mg, 0.96 mmol) was dissolved in isopropanol (10 mL). Hydroxylamine hydrochloride (335 mg, 4.82 mmol) was added, and the mixture was stirred under reflux conditions for 4 hours. The compounds in the reaction system 4 hours after the reaction were analyzed by high-performance liquid chromatography, and the results are summarized in Table 1.

[0044] Example 5: Method for producing 3-(ethylsulfonyl)-N'-hydroxy-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide 3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide (500 mg, 0.96 mmol) was dissolved in 1-butanol (10 mL). Hydroxylamine hydrochloride (335 mg, 4.82 mmol) was added, and the mixture was stirred under reflux conditions for 4 hours. The compounds in the reaction system 4 hours after the reaction were analyzed by high-performance liquid chromatography, and the results are summarized in Table 1.

[0045] Example 6: Method for producing 3-(ethylsulfonyl)-N'-hydroxy-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide 3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide (500 mg, 0.96 mmol) was dissolved in acetonitrile (10 mL). Hydroxylamine hydrochloride (335 mg, 4.82 mmol) was added, and the mixture was stirred under reflux conditions for 4 hours. The compounds in the reaction system 4 hours after the reaction were analyzed by high-performance liquid chromatography, and the results are summarized in Table 1.

[0046] Example 7: Method for producing 3-(ethylsulfonyl)-N'-hydroxy-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide 3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide (500 mg, 0.96 mmol) was dissolved in toluene (10 mL). Hydroxylamine hydrochloride (335 mg, 4.82 mmol) was added, and the mixture was stirred under reflux conditions for 4 hours. The compounds in the reaction system 4 hours after the reaction were analyzed by high-performance liquid chromatography, and the results are summarized in Table 1.

[0047] Example 8: Method for producing 3-(ethylsulfonyl)-N'-hydroxy-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide 3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide (500 mg, 0.96 mmol) was dissolved in N,N-dimethylacetamide (10 mL). Hydroxylamine hydrochloride (335 mg, 4.82 mmol) was added, and the mixture was stirred at 120°C for 4 hours. The compounds in the reaction system 4 hours after the reaction were analyzed by high-performance liquid chromatography, and the results are summarized in Table 1.

[0048] [Table 1] TIFF2026110532000014.tif63170

[0049] The high-performance liquid chromatography analysis conditions for Examples 1-8 are shown in Table 2. [Table 2] TIFF2026110532000015.tif42170

[0050] Example 9: Method for producing 3-(ethylsulfonyl)-N'-hydroxy-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide 3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide (23.05 g, 44.47 mmol) was dissolved in a mixed solvent of toluene (89 mL) and methanol (45 mL). Hydroxylamine hydrochloride (4.63 g, 66.71 mmol) was added to the mixture, and the mixture was stirred at 70°C for 5 hours. Analysis of the compounds in the reaction system 5 hours after the reaction was performed by high-performance liquid chromatography under the conditions shown in Table 2. The area percentage of the starting material was 0.49%, and the area percentage of the target product was 98.63%.

[0051] Example 10: Method for producing 3-(ethylsulfonyl)-N'-hydroxy-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide 3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide (10.61 g, 20.45 mmol) was dissolved in a mixed solvent of toluene (40 mL) and isopropanol (20 mL). Hydroxylamine hydrochloride (2.13 g, 30.68 mmol) was added to the mixture, and the mixture was stirred at 85°C for 7 hours. Analysis of the compounds in the reaction system after 7 hours of reaction by high-performance liquid chromatography under the conditions shown in Table 2 revealed that the area% of the starting materials was 0.10% and the area% of the target product was 99.59%.

[0052] Example 11: Method for producing 3-(ethylsulfonyl)-N'-hydroxy-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide 3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide (10.0 g, 19.3 mmol) was dissolved in 1-butanol (58 mL). Hydroxylamine hydrochloride (2.01 g, 29.0 mmol) was added, and the mixture was stirred at 85°C for 8 hours. Subsequently, the temperature was lowered to 60°C, water (19 mL) was added, and after standing, the solution was separated. Again, water (19 mL) was added at 60°C, and the pH of the aqueous layer was adjusted to 7 with a 12% NaOH aqueous solution, and the solution was separated. N,N-dimethylacetamide (12 mL) was added to the obtained organic layer, and after concentration under reduced pressure, crystallization was performed to obtain 10.10 g of the target product (purity: 94.4%, yield: 92.4%). 1 H NMR(CDCl3) δ8.96(1H, d, J=2.1Hz), 8.56(1H, d, J=2.1Hz), 8.17(1H, br), 7.99(1H, d, J=5.1Hz), 7.71(2H, d, J=8.4Hz), 7.40(2H, d, J=8.4Hz), 7.35(1H, br), 6.93(1H, d, J=4.8Hz), 6.75(1H, s), 3.58(2H, q, J=7.5Hz), 1.35(3H, t, J=7.5Hz)

[0053] Example 12: Method for producing 3-(3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)pyridine-2-yl)-4-(4-(trifluoromethyl)pyridine-2-yl)-1,2,4-oxadiazole-5(4H)-one [ka] 3-(ethylsulfonyl)-N'-hydroxy-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide (39.6 g, 74.1 mmol) was dissolved in tetrahydrofuran (300 mL) and cooled to 0°C. 1,1'-carbonyldiimidazole (18.0 g, 111 mmol) was added, and the mixture was then heated to room temperature and stirred overnight. After concentration under reduced pressure, the reaction mixture was diluted with water and dichloromethane and separated. The resulting organic layer was washed with saturated ammonium chloride aqueous solution and saturated brine, and dried over anhydrous magnesium sulfate. After filtration, it was concentrated under reduced pressure using a rotary evaporator. The resulting residue was purified by silica gel chromatography to obtain 35.15 g of the target product. 1 H NMR(CDCl3) δ9.02(1H, d, J=2.1Hz), 8.58(1H, d, J=2.1Hz), 8.34(1H, s), 8.15(1H, d, J=5.1Hz), 7.75-7.71(2H, m), 7.43(2H, d, J=8.1Hz), 7.38(1H, d, J=5.1Hz), 3.52(2H, q, J=7.5Hz), 1.39(3H, t, J=7.5Hz)

Claims

1. A method for producing an amidooxime derivative represented by formula (1), 【Chemistry 1】 [In formula (1), R ２ , R ３ , R ４ and R ５ Each of them operates independently. hydrogen atom, halogen atom, It may have substituents (C １ ~C ６ ) alkyl group, It may have substituents (C ２ ~C ６ ) Alkenyl group, which may have a substituent, (C ２ ~C ６ ) alkynyl group, It may have substituents (C ３ ~C ６ ) Cycloalkyl groups, It may have substituents (C １ ~C ６ ) Alkoxy group, It may have substituents (C ２ ~C ６ ) Alkenyloxy group, It may have substituents (C ２ ~C ６ ) Alkynyloxy group, It may have substituents (C ３ ~C ６ ) Cycloalkoxy group, It may have substituents (C １ ~C ６ ) Alkyl carbonyl group, It may have substituents (C ３ ~C ６ ) Cycloalkylcarbonyl group, It may have substituents (C １ ~C ６ ) Alkoxycarbonyl group, It may have substituents (C ２ ~C ６ ) Alkenyloxycarbonyl group, It may have substituents (C ２ ~C ６ ) Alkynyloxycarbonyl group, It may have substituents (C １ ~C ６ ) Alkylcarbonyloxy group, It may have substituents (C ２ ~C ６ ) Alkenylcarbonyloxy group, It may have substituents (C ２ ~C ６ ) Alkynylcarbonyloxy group, It may have substituents (C １ ~C ６ ) alkylthio group, It may have substituents (C １ ~C ６ ) alkylsulfinyl group, It may have substituents (C １ ~C ６ ) alkylsulfonyl group, It may have substituents (C １ ~C ６ ) Alkyl sulfonyl oxy group, A phenyl group which may have substituents, A heterocyclic group which may have substituents, A phenoxy group which may have a substituent, A pyridyloxy group which may have substituents, NY １ Y ２ Base, C(O)NY １ Y ２ Base, C (=NY ２ ) Y ３ Group, cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxyl group, trimethylsilyl group, C(O)NH ２ Base, and SF ５ This represents a group selected from a group consisting of the groups, The aforementioned Y １ If there are multiple such atoms, each may independently have a hydrogen atom and a substituent (C １ ~C ６ ) Represents a group selected from the group consisting of alkyl groups, The aforementioned Y ２ If there are multiple such atoms, each may independently have a hydrogen atom or a substituent (C １ ~C ６ ) alkyl groups may have substituents (C ２ ~C ６ ) may have an alkenyl group, or a substituent (C ３ ~C ６ ) Cycloalkyl groups may have substituents (C １ ~C ６ ) It may have an alkoxy group or substituent (C １ ~C ６ ) an alkylcarbonyl group, which may have substituents (C １ ~C ６ ) Represents a group selected from the group consisting of an alkoxycarbonyl group, a optionally substituted phenyl group, an optionally substituted heterocyclic group, a cyano group, and a hydroxyl group. The aforementioned Y ３ If there are multiple such atoms, each may independently have a hydrogen atom, a halogen atom, or a substituent (C １ ~C ６ ) alkyl groups may have substituents (C １ ~C ６ ) It may have an alkoxy group or substituent (C １ ~C ６ ) The alkylthio group may have substituents (C ３ ~C ６ ) Cycloalkyl groups, optionally substituted phenyl groups, and NY １ Y ２ This represents a group selected from a group consisting of (Y １ and Y ２ (This is synonymous with the above.) R 6 teeth, hydrogen atom, It may have substituents (C １ ~C ６ ) alkyl group, It may have substituents (C 3 ~C ６ ) Cycloalkyl groups, It may have substituents (C １ ~C ６ ) alkylcarbonyl group, and which may have a substituent, a (C 3 ~C ６ ) cycloalkylcarbonyl group, This represents a group selected from the group consisting of, R ａ teeth, It may have substituents (C １ ~C ６ ) alkyl groups, and It may have substituents (C ３ ~C ６ ) Cycloalkyl groups This represents a group selected from the group consisting of, R ｂ , R ｃ , and R ｄ are each independently hydrogen atom, halogen atom, It may have substituents (C １ ~C ６ ) alkyl group, It may have substituents (C ２ ~C ６ ) Alkenyl group, It may have substituents (C ２ ~C ６ ) Alkynyl group, It may have substituents (C ３ ~C ６ ) Cycloalkyl groups, It may have substituents (C １ ~C ６ ) Alkoxy group, It may have substituents (C ２ ~C ６ ) Alkenyloxy group, It may have substituents (C ２ ~C ６ ) Alkynyloxy group, It may have substituents (C ３ ~C ６ ) Cycloalkoxy group, It may have substituents (C １ ~C ６ ) Alkyl carbonyl group, It may have substituents (C ３ ~C ６ ) Cycloalkylcarbonyl group, It may have substituents (C １ ~C ６ ) Alkoxycarbonyl group, It may have substituents (C ２ ~C ６ ) Alkenyloxycarbonyl group, It may have substituents (C ２ ~C ６ ) Alkynyloxycarbonyl group, It may have substituents (C １ ~C ６ ) Alkylcarbonyloxy group, It may have substituents (C ２ ~C ６ ) Alkenylcarbonyloxy group, It may have substituents (C ２ ~C ６ ) Alkynylcarbonyloxy group, It may have substituents (C １ ~C ６ ) alkylthio group, It may have substituents (C １ ~C ６ ) alkylsulfinyl group, It may have substituents (C １ ~C ６ ) alkylsulfonyl group, It may have substituents (C １ ~C ６ ) Alkyl sulfonyl oxy group, A phenyl group which may have substituents, A heterocyclic group which may have substituents, A phenoxy group which may have a substituent, A pyridyloxy group which may have substituents, NY １ Y ２ Base, C(O)NY １ Y ２ Base, C (=NY ２ ) Y ３ Group, cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxyl group, trimethylsilyl group, C(O)NH ２ Base, and SF ５ A group selected from the group consisting of (Y １ , Y ２ and Y ３ (This is synonymous with the above.) [This indicates...] The following steps: [Process A] In the presence of a solvent, the amidine derivative represented by formula (2) and 【Chemistry 2】 [In formula (2), R ２ , R ３ , R ４ and R ５ , and R ａ , R ｂ , R ｃ and R ｄ This is synonymous with the above. Amine compound represented by formula (3) 【Transformation 3】 [In formula (3), R 6 This is synonymous with the above. Step A to cause a reaction; A manufacturing method that includes [details omitted].

2. A method for producing an (alkylsulfonyl)pyridine derivative represented by formula (4), 【Chemistry 4】 [In formula (4), R ２ , R ３ , R ４ and R ５ Each of them operates independently. hydrogen atom, halogen atom, It may have substituents (C １ ~C ６ ) alkyl group, It may have substituents (C ２ ~C ６ ) Alkenyl group, It may have substituents (C ２ ~C ６ ) Alkynyl group, It may have substituents (C ３ ~C ６ ) Cycloalkyl groups, It may have substituents (C １ ~C ６ ) Alkoxy group, It may have substituents (C ２ ~C ６ ) Alkenyloxy group, It may have substituents (C ２ ~C ６ ) Alkynyloxy group, It may have substituents (C ３ ~C ６ ) Cycloalkoxy group, It may have substituents (C １ ~C ６ ) Alkyl carbonyl group, It may have substituents (C ３ ~C ６ ) Cycloalkylcarbonyl group, It may have substituents (C １ ~C ６ ) Alkoxycarbonyl group, It may have substituents (C ２ ~C ６ ) Alkenyloxycarbonyl group, It may have substituents (C ２ ~C ６ ) Alkynyloxycarbonyl group, It may have substituents (C １ ~C ６ ) Alkylcarbonyloxy group, It may have substituents (C ２ ~C ６ ) Alkenylcarbonyloxy group, It may have substituents (C ２ ~C ６ ) Alkynylcarbonyloxy group, It may have substituents (C １ ~C ６ ) alkylthio group, It may have substituents (C １ ~C ６ ) alkylsulfinyl group, It may have substituents (C １ ~C ６ ) alkylsulfonyl group, It may have substituents (C １ ~C ６ ) Alkyl sulfonyl oxy group, A phenyl group which may have substituents, A heterocyclic group which may have substituents, A phenoxy group which may have a substituent, A pyridyloxy group which may have substituents, NY １ Y ２ Base, C(O)NY １ Y ２ Base, C (=NY ２ ) Y ３ Group, cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxyl group, trimethylsilyl group, C(O)NH ２ Base, and SF ５ This represents a group selected from a group consisting of the groups, The aforementioned Y １ If there are multiple such atoms, each may independently have a hydrogen atom and a substituent (C １ ~C ６ ) Represents a group selected from the group consisting of alkyl groups, The aforementioned Y ２ If there are multiple such atoms, each may independently have a hydrogen atom or a substituent (C １ ~C ６ ) alkyl groups may have substituents (C ２ ~C ６ ) may have an alkenyl group, or a substituent (C ３ ~C ６ ) Cycloalkyl groups may have substituents (C １ ~C ６ ) It may have an alkoxy group or substituent (C １ ~C ６ ) an alkylcarbonyl group, which may have substituents (C １ ~C ６ ) Represents a group selected from the group consisting of an alkoxycarbonyl group, a optionally substituted phenyl group, an optionally substituted heterocyclic group, a cyano group, and a hydroxyl group. The aforementioned Y ３ If there are multiple such atoms, each may independently have a hydrogen atom, a halogen atom, or a substituent (C １ ~C ６ ) alkyl groups may have substituents (C １ ~C ６ ) It may have an alkoxy group or substituent (C １ ~C ６ ) The alkylthio group may have substituents (C ３ ~C ６ ) Cycloalkyl groups, optionally substituted phenyl groups, and NY １ Y ２ This represents a group selected from a group consisting of (Y １ and Y ２ (This is synonymous with the above.) R ａ teeth, It may have substituents (C １ ~C ６ ) alkyl groups, and It may have substituents (C ３ ~C ６ ) Cycloalkyl groups, This represents a group selected from the group consisting of, R ｂ , R ｃ and R ｄ Each of them operates independently. hydrogen atom, halogen atom, It may have substituents (C １ ~C ６ ) alkyl group, It may have substituents (C ２ ~C ６ ) Alkenyl group, It may have substituents (C ２ ~C ６ ) Alkynyl group, It may have substituents (C ３ ~C ６ ) Cycloalkyl groups, It may have substituents (C １ ~C ６ ) Alkoxy group, It may have substituents (C ２ ~C ６ ) Alkenyloxy group, It may have substituents (C ２ ~C ６ ) Alkynyloxy group, It may have substituents (C ３ ~C ６ ) Cycloalkoxy group, It may have substituents (C １ ~C ６ ) Alkyl carbonyl group, It may have substituents (C ３ ~C ６ ) Cycloalkylcarbonyl group, It may have substituents (C １ ~C ６ ) Alkoxycarbonyl group, It may have substituents (C ２ ~C ６ ) Alkenyloxycarbonyl group, It may have substituents (C ２ ~C ６ ) Alkynyloxycarbonyl group, It may have substituents (C １ ~C ６ ) Alkylcarbonyloxy group, It may have substituents (C ２ ~C ６ ) Alkenylcarbonyloxy group, It may have substituents (C ２ ~C ６ ) Alkynylcarbonyloxy group, It may have substituents (C １ ~C ６ ) alkylthio group, It may have substituents (C １ ~C ６ ) alkylsulfinyl group, It may have substituents (C １ ~C ６ ) alkylsulfonyl group, It may have substituents (C １ ~C ６ ) Alkyl sulfonyl oxy group, A phenyl group which may have substituents, A heterocyclic group which may have substituents, A phenoxy group which may have a substituent, A pyridyloxy group which may have substituents, NY １ Y ２ Base, C(O)NY １ Y ２ Base, C (=NY ２ ) Y ３ Group, cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxyl group, trimethylsilyl group, C(O)NH ２ Base, and SF ５ A group selected from the group consisting of (Y １ , Y ２ , and Y ３ (This is synonymous with the above.) [This indicates...] The following steps: [Process A] In the presence of a solvent, the amidine derivative represented by formula (2) and 【Transformation 5】 [In formula (2), R ２ , R ３ , R ４ and R ５ , and R ａ , R ｂ , R ｃ and R ｄ This is synonymous with the above. Amine compound represented by formula (3) 【Transformation 6】 [In formula (3), R ６ teeth, hydrogen atom, It may have substituents (C １ ~C ６ ) alkyl group, It may have substituents (C 3 ~C ６ ) Cycloalkyl groups, It may have substituents (C １ ~C ６ ) alkylcarbonyl group, and It may have substituents (C 3 ~C ６ ) Cycloalkylcarbonyl group, This represents a base selected from the group consisting of [the specified elements]. By reacting them, an amide oxime derivative represented by formula (1) is obtained. 【Transformation 7】 [In formula (1), R ２ , R ３ , R ４ , R ５ and R 6 , and R ａ , R ｂ , R ｃ and R ｄ This is synonymous with the above. Step A, which includes obtaining; and [Process B] By reacting the amide oxime derivative represented by formula (1) with a carbonylating agent, a (alkylsulfonyl)pyridine derivative represented by formula (4) is obtained. 【Transformation 8】 [In formula (4), R ２ , R ３ , R ４ and R ５ , and R ａ , R ｂ , R ｃ and R ｄ This is synonymous with the above. Step B to obtain; A manufacturing method that includes [details omitted].

3. The manufacturing method according to claim 1 or 2, wherein the solvent in [Step A] is a solvent comprising one or more selected from the group consisting of methanol, ethanol, 1-propanol, isopropanol, 1-butanol, 2-butanol, isobutanol, t-butanol, 1-pentanol, 2-pentanol, isopentanol, 1-hexanol, and 2-hexanol.

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