Pyridine-2-ylpyridinium compounds having sulfur-containing substituents and methods for using the same

Abstract

To provide a method for producing cyanopyridine derivatives having sulfur substituents, which are useful synthetic intermediates in the production of pyridine derivatives having sulfur substituents. [Solution] A method for producing a cyanopyridine derivative represented by formula (2), comprising reacting a compound represented by formula (1) with a cyanating agent. TIFF2026123795000065.tif55170 From the cyanopyridine derivative represented by formula (2), a pyridine derivative having a sulfur-containing substituent with pest control activity can be produced by known methods.

Description

[Technical Field]

[0001] The present invention relates to a sulfur-containing pyridine-2-ylpyridinium compound that is useful as a manufacturing intermediate for amidine compounds and amide compounds having insecticidal activity, and to a method of using the same. [Background technology]

[0002] Heterocyclic compounds having sulfur-containing substituents that function as pest control agents are known. For example, Patent Documents 1 to 4 disclose amidine compounds containing a heterocyclic group having a sulfur-containing substituent. Patent Document 5 discloses amide compounds containing a heterocyclic group having a sulfur-containing substituent. Furthermore, Patent Document 6 discloses oxadiazole-5(4H)-one derivatives containing a heterocyclic group having a sulfur-containing substituent. The production of these amidine and amide compounds involves the use of cyano derivatives of heterocyclic compounds having sulfur-containing substituents, and there is a need to establish efficient production methods. Patent document 7 describes a synthesis method for 2-cyano-3-ethylsulfonylpyridines, and patent document 8 describes pyridine-2-ylpyridinium compounds and their uses. However, the method described in patent document 7 requires the use of more than an equivalent amount of highly toxic copper cyanide, the post-treatment process is complicated, and the production cost is high. In addition, high temperatures are required for the reaction, which leads to a decrease in yield due to the formation of by-products. [Prior art documents] [Patent Documents]

[0003] [Patent Document 1] International Publication No. 2020 / 054712 [Patent Document 2] International Publication No. 2021 / 177410 [Patent Document 3] International Publication No. 2022 / 259985 [Patent Document 4] Japanese Patent Publication No. 2023-031268 [Patent Document 5] International Publication No. 2014 / 021468 [Patent Document 6] International Publication No. 2023 / 190286 [Patent Document 7] Japanese Patent Publication No. 2015-196668 [Patent Document 8] International Publication No. 2017 / 018409 [Overview of the Initiative] [Problems that the invention aims to solve]

[0004] The object of the present invention is to provide a method for producing a cyanopyridine derivative having a sulfur-containing substituent, which is a useful synthetic intermediate in the production of pyridine derivatives having a sulfur-containing substituent that has pest control activity. Furthermore, the object of the present invention is to provide a method for producing a pyridine derivative having a sulfur-containing substituent that has pest control activity, including this method for producing the cyanopyridine derivative. [Means for solving the problem]

[0005] As a result of diligent research to solve the above problems, the present inventors were able to produce a cyanopyridine derivative having a sulfur-containing substituent by reacting a pyridine-2-ylpyridinium compound having a sulfur-containing substituent with a cyanating agent. From this cyanopyridine derivative, a pyridine derivative having a sulfur-containing substituent known to have pest control activity can be produced. The present invention relates to the following [1] to

[11] .

[0006] [1] A compound represented by formula (1). [ka] [In formula (1), A ― This represents an ionic species selected from the group consisting of halogen ions, unsubstituted or substituted benzenesulfonate ions, and unsubstituted or substituted (C1-C8) alkylsulfonate ions. If there are multiple X's, each independently represents a group selected from the group consisting of a halogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, and an NY1Y2 group. Y1 and Y2 may each independently represent a hydrogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, or an unsubstituted or substituted (C1-C6) alkoxy group, or Y1 and Y2 may form an unsubstituted or substituted 3-8 member saturated heterocycle together with a nitrogen atom to which they are bonded. m is an integer between 0 and 5. If m is 2 or greater, X can be the same or different. n is an integer between 0 and 2. R a This represents a group selected from the group consisting of unsubstituted or substituted (C1-C6) alkyl groups, unsubstituted or substituted (C3-C6) cycloalkyl groups, and NY3Y4 groups. Y3 and Y4 each independently represent a group selected from the group consisting of a hydrogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, and an unsubstituted or substituted (C1-C6) alkoxy group, or Y3 and Y4 together may be alkylene groups that form a 3-8 membered ring cyclic amino group with the nitrogen atom to which they are bonded. R b , R c and R dEach of these independently comprises a hydrogen atom, a halogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C2-C6) alkenyl group, an unsubstituted or substituted (C2-C6) alkynyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, an unsubstituted or substituted (C2-C6) alkenyloxy group, or an unsubstituted or substituted (C2-C6) alkynyloxy group, unsubstituted or substituted (C3-C6) cycloalkoxy group, unsubstituted or substituted (C1-C6) alkylcarbonyl group, unsubstituted or substituted (C3-C6) cycloalkylcarbonyl group, unsubstituted or substituted (C1-C6) alkoxycarbonyl group, unsubstituted or substituted (C2-C6) alkenyloxycarbonyl group, unsubstituted or substituted (C2-C6) alkynyl Oxycarbonyl group, unsubstituted or substituted (C1-C6) alkylcarbonyloxy group, unsubstituted or substituted (C2-C6) alkenylcarbonyloxy group, unsubstituted or substituted (C2-C6) alkynylcarbonyloxy group, unsubstituted or substituted (C1-C6) alkylthio group, unsubstituted or substituted (C1-C6) alkylsulfinyl group, unsubstituted or substituted (C1-C6) alkylsulfonyl group This represents a group selected from the group consisting of unsubstituted or substituted (C1-C6) alkylsulfonyloxy groups, unsubstituted or substituted phenyl groups, unsubstituted or substituted heterocyclic groups, unsubstituted or substituted phenoxy groups, unsubstituted or substituted pyridyloxy groups, NY5Y6 groups, C(O)NY5Y6 groups, cyano groups, nitro groups, hydroxyl groups, mercapto groups, amino groups, formyl groups, carboxyl groups, trimethylsilyl groups, and SF5 groups. If multiple Y5 and Y6 exist, each independently represents a group selected from the group consisting of a hydrogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C2-C6) alkenyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, an unsubstituted or substituted (C1-C6) alkylcarbonyl group, an unsubstituted or substituted (C1-C6) alkoxycarbonyl group, an unsubstituted or substituted phenyl group, an unsubstituted or substituted heterocyclic group, a cyano group, and a hydroxyl group.

[0007] [2] In equation (1), m is 1 to 5, If there are multiple X groups, each X is independently selected from the group consisting of unsubstituted or substituted (C1-C6) alkoxy groups and NY1Y2 groups. The compound described in [1].

[0008] [3] In equation (1), R b , R c and R d Which one is A group selected from the group consisting of an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C2-C6) alkenyl group, an unsubstituted or substituted (C2-C6) alkynyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, an unsubstituted or substituted (C2-C6) alkenyloxy group, an unsubstituted or substituted (C2-C6) alkynyloxy group, an unsubstituted or substituted (C3-C6) cycloalkoxy group, an unsubstituted or substituted (C2-C6) alkenylcarbonyloxy group, an unsubstituted or substituted (C2-C6) alkynylcarbonyloxy group, an unsubstituted or substituted (C1-C6) alkylthio group, an unsubstituted or substituted (C1-C6) alkylsulfinyl group, an unsubstituted or substituted (C1-C6) alkylsulfonyl group, an unsubstituted or substituted (C1-C6) alkylsulfonyloxy group, an unsubstituted or substituted phenyl group, an unsubstituted or substituted heterocyclic group, an unsubstituted or substituted phenoxy group, and an unsubstituted or substituted pyridyloxy group, where the others are hydrogen atoms or halogen atoms, The compound according to [1] or [2].

[0009] [4] The compound represented by formula (1); [Chemical formula] [In formula (1), A - represents an ionic species selected from the group consisting of a halogen ion, an unsubstituted or substituted benzenesulfonic acid ion, and an unsubstituted or substituted (C1-C8) alkylsulfonic acid ion, X, when there are a plurality of them, each independently represents a group selected from the group consisting of a halogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, and a NY1Y2 group, Y1 and Y2 may each independently represent a hydrogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, or an unsubstituted or substituted (C1-C6) alkoxy group, or Y1 and Y2 may form an unsubstituted or substituted 3-8 member saturated heterocycle together with a nitrogen atom to which they are bonded. m is an integer between 0 and 5. If m is 2 or greater, X can be the same or different. n is an integer between 0 and 2. R a This represents a group selected from the group consisting of unsubstituted or substituted (C1-C6) alkyl groups, unsubstituted or substituted (C3-C6) cycloalkyl groups, and NY3Y4 groups. Y3 and Y4 each independently represent a group selected from the group consisting of a hydrogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, and an unsubstituted or substituted (C1-C6) alkoxy group, or Y3 and Y4 together may be alkylene groups that form a 3-8 membered ring cyclic amino group with the nitrogen atom to which they are bonded. R b , R c and R dEach of these independently comprises a hydrogen atom, a halogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C2-C6) alkenyl group, an unsubstituted or substituted (C2-C6) alkynyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, an unsubstituted or substituted (C2-C6) alkenyloxy group, or an unsubstituted or substituted (C2-C6) alkynyloxy group, unsubstituted or substituted (C3-C6) cycloalkoxy group, unsubstituted or substituted (C1-C6) alkylcarbonyl group, unsubstituted or substituted (C3-C6) cycloalkylcarbonyl group, unsubstituted or substituted (C1-C6) alkoxycarbonyl group, unsubstituted or substituted (C2-C6) alkenyloxycarbonyl group, unsubstituted or substituted (C2-C6) alkynyl Oxycarbonyl group, unsubstituted or substituted (C1-C6) alkylcarbonyloxy group, unsubstituted or substituted (C2-C6) alkenylcarbonyloxy group, unsubstituted or substituted (C2-C6) alkynylcarbonyloxy group, unsubstituted or substituted (C1-C6) alkylthio group, unsubstituted or substituted (C1-C6) alkylsulfinyl group, unsubstituted or substituted (C1-C6) alkylsulfonyl group This represents a group selected from the group consisting of unsubstituted or substituted (C1-C6) alkylsulfonyloxy groups, unsubstituted or substituted phenyl groups, unsubstituted or substituted heterocyclic groups, unsubstituted or substituted phenoxy groups, unsubstituted or substituted pyridyloxy groups, NY5Y6 groups, C(O)NY5Y6 groups, cyano groups, nitro groups, hydroxyl groups, mercapto groups, amino groups, formyl groups, carboxyl groups, trimethylsilyl groups, and SF5 groups. If multiple Y5 and Y6 exist, each independently represents a group selected from the group consisting of a hydrogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C2-C6) alkenyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, an unsubstituted or substituted (C1-C6) alkylcarbonyl group, an unsubstituted or substituted (C1-C6) alkoxycarbonyl group, an unsubstituted or substituted phenyl group, an unsubstituted or substituted heterocyclic group, a cyano group, and a hydroxyl group. Then, react with a cyanating agent, Cyanopyridine compounds represented by formula (2); [ka] [In formula (2), R a , R b , R c , R d , and n are the same as above. ], to manufacture, A method for producing cyanopyridine derivatives.

[0010] [5] The method for producing a product according to [4], wherein the cyanating agent is one or more compounds selected from the group consisting of HCN, LiCN, NaCN, KCN, BrCN, CuCN, Zn(CN)2, acetone cyanohydrin, and trimethylsilyl cyanide.

[0011] [6] m is 1 to 5, If there are multiple X groups, each X is independently selected from the group consisting of unsubstituted or substituted (C1-C6) alkoxy groups and NY1Y2 groups. The manufacturing method described in [4] or [5].

[0012] [7] [Step A]; Compound represented by formula (1); [ka] [In formula (1), A - This represents an ionic species selected from the group consisting of halogen ions, unsubstituted or substituted benzenesulfonate ions, and unsubstituted or substituted (C1-C8) alkylsulfonate ions. If there are multiple X's, each independently represents a group selected from the group consisting of a halogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, and an NY1Y2 group. Y1 and Y2 may each independently represent a hydrogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, or an unsubstituted or substituted (C1-C6) alkoxy group, or Y1 and Y2 may form an unsubstituted or substituted 3-8 member saturated heterocycle together with a nitrogen atom to which they are bonded. m is an integer between 0 and 5. If m is 2 or greater, X can be the same or different. n is an integer between 0 and 2. R a This represents a group selected from the group consisting of unsubstituted or substituted (C1-C6) alkyl groups, unsubstituted or substituted (C3-C6) cycloalkyl groups, and NY3Y4 groups. Y3 and Y4 each independently represent a group selected from the group consisting of a hydrogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, and an unsubstituted or substituted (C1-C6) alkoxy group, or Y3 and Y4 together may be alkylene groups that form a 3-8 membered ring cyclic amino group with the nitrogen atom to which they are bonded. R b , R c and R dEach of these independently comprises a hydrogen atom, a halogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C2-C6) alkenyl group, an unsubstituted or substituted (C2-C6) alkynyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, an unsubstituted or substituted (C2-C6) alkenyloxy group, or an unsubstituted or substituted (C2-C6) alkynyloxy group, unsubstituted or substituted (C3-C6) cycloalkoxy group, unsubstituted or substituted (C1-C6) alkylcarbonyl group, unsubstituted or substituted (C3-C6) cycloalkylcarbonyl group, unsubstituted or substituted (C1-C6) alkoxycarbonyl group, unsubstituted or substituted (C2-C6) alkenyloxycarbonyl group, unsubstituted or substituted (C2-C6) alkynyl Oxycarbonyl group, unsubstituted or substituted (C1-C6) alkylcarbonyloxy group, unsubstituted or substituted (C2-C6) alkenylcarbonyloxy group, unsubstituted or substituted (C2-C6) alkynylcarbonyloxy group, unsubstituted or substituted (C1-C6) alkylthio group, unsubstituted or substituted (C1-C6) alkylsulfinyl group, unsubstituted or substituted (C1-C6) alkylsulfonyl group This represents a group selected from the group consisting of unsubstituted or substituted (C1-C6) alkylsulfonyloxy groups, unsubstituted or substituted phenyl groups, unsubstituted or substituted heterocyclic groups, unsubstituted or substituted phenoxy groups, unsubstituted or substituted pyridyloxy groups, NY5Y6 groups, C(O)NY5Y6 groups, cyano groups, nitro groups, hydroxyl groups, mercapto groups, amino groups, formyl groups, carboxyl groups, trimethylsilyl groups, and SF5 groups. If multiple Y5 and Y6 exist, each independently represents a group selected from the group consisting of a hydrogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C2-C6) alkenyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, an unsubstituted or substituted (C1-C6) alkylcarbonyl group, an unsubstituted or substituted (C1-C6) alkoxycarbonyl group, an unsubstituted or substituted phenyl group, an unsubstituted or substituted heterocyclic group, a cyano group, and a hydroxyl group. Then, react with a cyanating agent, Cyanopyridine compounds represented by formula (2); [ka] [In formula (2), R a , R b , R c , R d , and n are the same as above. ] process for manufacturing [Step B]; the cyanopyridine compound of formula (2) Carboxy compounds represented by formula (3); [ka] [In equation (3), R a , R b , R c , R d The process of converting to ] [Step C]; A carboxyl compound represented by formula (3), Pyridylamine compounds of formula (4); [ka] [In equation (4), R2, R3, R4, and R5 are each independently a hydrogen atom, a halogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C2-C6) alkenyl group, an unsubstituted or substituted (C2-C6) alkynyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, an unsubstituted or substituted (C2-C6) alkenyloxy group, or an unsubstituted or ku is a substituted (C2-C6) alkynyloxy group, an unsubstituted or substituted (C3-C6) cycloalkoxy group, an unsubstituted or substituted (C1-C6) alkylcarbonyl group, an unsubstituted or substituted (C3-C6) cycloalkylcarbonyl group, an unsubstituted or substituted (C1-C6) alkoxycarbonyl group, an unsubstituted or substituted (C2-C6) alkenyloxycarbonyl group, an unsubstituted or substituted (C2-C6) ) Alkynyloxycarbonyl group, unsubstituted or substituted (C1-C6) alkylcarbonyloxy group, unsubstituted or substituted (C2-C6) alkenylcarbonyloxy group, unsubstituted or substituted (C2-C6) alkynylcarbonyloxy group, unsubstituted or substituted (C1-C6) alkylthio group, unsubstituted or substituted (C1-C6) alkylsulfinyl group, unsubstituted or substituted (C1-C6) alkylsulfonyl group This represents a group selected from the group consisting of a nyl group, an unsubstituted or substituted (C1-C6) alkylsulfonyloxy group, an unsubstituted or substituted phenyl group, an unsubstituted or substituted heterocyclic group, an unsubstituted or substituted phenoxy group, an unsubstituted or substituted pyridyloxy group, a NY5Y6 group, a C(O)NY5Y6 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, and an SF5 group. Y5 and Y6 are the same as above. ] react to Amide compounds represented by formula (5); [ka] [In equation (5), E is a group selected from the group consisting of a hydrogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, an unsubstituted or substituted (C1-C6) alkylcarbonyl group, or an unsubstituted or substituted (C3-C6) cycloalkylcarbonyl group. R a , R b , R c , R d n, R2, R3, R4, R5 are the same as above. The process includes manufacturing ] A method for producing pyridine derivatives having sulfur-containing substituents.

[0013] [8] [Step D]; The amide compound represented by formula (5) obtained in Step C, Amine compounds represented by formula (6); [ka] [In equation (6), 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 ] N-substituted amidine compounds represented by formula (7); [ka] [(In equation (7), R a , R b , R c , R d R2, R3, R4, R5, R6, E and n are the same as above. The process includes manufacturing ] A method for producing a sulfur-containing pyridine derivative as described in [7].

[0014] [9] [Step A]; Compound represented by formula (1); [ka] [In formula (1), A - This represents an ionic species selected from the group consisting of halogen ions, unsubstituted or substituted benzenesulfonate ions, and unsubstituted or substituted (C1-C8) alkylsulfonate ions. If there are multiple X's, each independently represents a group selected from the group consisting of a halogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, and an NY1Y2 group. Y1 and Y2 may each independently represent a hydrogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, or an unsubstituted or substituted (C1-C6) alkoxy group, or Y1 and Y2 may form an unsubstituted or substituted 3-8 member saturated heterocycle together with a nitrogen atom to which they are bonded. m is an integer between 0 and 5. If m is 2 or greater, X can be the same or different. n is an integer between 0 and 2. R a This represents a group selected from the group consisting of unsubstituted or substituted (C1-C6) alkyl groups, unsubstituted or substituted (C3-C6) cycloalkyl groups, and NY3Y4 groups. Y3 and Y4 each independently represent a group selected from the group consisting of a hydrogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, and an unsubstituted or substituted (C1-C6) alkoxy group, or Y3 and Y4 together may be alkylene groups that form a 3-8 membered ring cyclic amino group with the nitrogen atom to which they are bonded. R b , R c and Rd Each of these independently comprises a hydrogen atom, a halogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C2-C6) alkenyl group, an unsubstituted or substituted (C2-C6) alkynyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, an unsubstituted or substituted (C2-C6) alkenyloxy group, or an unsubstituted or substituted (C2-C6) alkynyloxy group, unsubstituted or substituted (C3-C6) cycloalkoxy group, unsubstituted or substituted (C1-C6) alkylcarbonyl group, unsubstituted or substituted (C3-C6) cycloalkylcarbonyl group, unsubstituted or substituted (C1-C6) alkoxycarbonyl group, unsubstituted or substituted (C2-C6) alkenyloxycarbonyl group, unsubstituted or substituted (C2-C6) alkynyl Oxycarbonyl group, unsubstituted or substituted (C1-C6) alkylcarbonyloxy group, unsubstituted or substituted (C2-C6) alkenylcarbonyloxy group, unsubstituted or substituted (C2-C6) alkynylcarbonyloxy group, unsubstituted or substituted (C1-C6) alkylthio group, unsubstituted or substituted (C1-C6) alkylsulfinyl group, unsubstituted or substituted (C1-C6) alkylsulfonyl group This represents a group selected from the group consisting of unsubstituted or substituted (C1-C6) alkylsulfonyloxy groups, unsubstituted or substituted phenyl groups, unsubstituted or substituted heterocyclic groups, unsubstituted or substituted phenoxy groups, unsubstituted or substituted pyridyloxy groups, NY5Y6 groups, C(O)NY5Y6 groups, cyano groups, nitro groups, hydroxyl groups, mercapto groups, amino groups, formyl groups, carboxyl groups, trimethylsilyl groups, and SF5 groups. If multiple Y5 and Y6 exist, each independently represents a group selected from the group consisting of a hydrogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C2-C6) alkenyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, an unsubstituted or substituted (C1-C6) alkylcarbonyl group, an unsubstituted or substituted (C1-C6) alkoxycarbonyl group, an unsubstituted or substituted phenyl group, an unsubstituted or substituted heterocyclic group, a cyano group, and a hydroxyl group. Then, react with a cyanating agent, Cyanopyridine compounds represented by formula (2); [ka] [In formula (2), R a , R b , R c , R d , and n are the same as above. ] process for manufacturing [Step E]; A cyanopyridine compound represented by formula (2), Pyridylamine compounds of formula (4); [ka] [In equation (4), R2, R3, R4, and R5 are each independently a hydrogen atom, a halogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C2-C6) alkenyl group, an unsubstituted or substituted (C2-C6) alkynyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, an unsubstituted or substituted (C2-C6) alkenyloxy group, or an unsubstituted or ku is a substituted (C2-C6) alkynyloxy group, an unsubstituted or substituted (C3-C6) cycloalkoxy group, an unsubstituted or substituted (C1-C6) alkylcarbonyl group, an unsubstituted or substituted (C3-C6) cycloalkylcarbonyl group, an unsubstituted or substituted (C1-C6) alkoxycarbonyl group, an unsubstituted or substituted (C2-C6) alkenyloxycarbonyl group, an unsubstituted or substituted (C2-C6) ) Alkynyloxycarbonyl group, unsubstituted or substituted (C1-C6) alkylcarbonyloxy group, unsubstituted or substituted (C2-C6) alkenylcarbonyloxy group, unsubstituted or substituted (C2-C6) alkynylcarbonyloxy group, unsubstituted or substituted (C1-C6) alkylthio group, unsubstituted or substituted (C1-C6) alkylsulfinyl group, unsubstituted or substituted (C1-C6) alkylsulfonyl group This represents a group selected from the group consisting of a nyl group, an unsubstituted or substituted (C1-C6) alkylsulfonyloxy group, an unsubstituted or substituted phenyl group, an unsubstituted or substituted heterocyclic group, an unsubstituted or substituted phenoxy group, an unsubstituted or substituted pyridyloxy group, a NY5Y6 group, a C(O)NY5Y6 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, and an SF5 group. Y5 and Y6 are the same as above. ] react to Amidine compounds represented by formula (8); [ka] [(In equation (8), E is a group selected from the group consisting of a hydrogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, an unsubstituted or substituted (C1-C6) alkylcarbonyl group, or an unsubstituted or substituted (C3-C6) cycloalkylcarbonyl group. R a , R b , R c , R d R2, R3, R4, R5 and n are the same as above. The process includes manufacturing ] A method for producing pyridine derivatives having sulfur-containing substituents.

[0015]

[10] [Step F]; The amidine compound represented by formula (8) obtained in Step E, Amine compounds represented by formula (6); [ka] [In equation (6), 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 ] N-substituted amidine compounds represented by formula (7); [ka] [(In equation (7), R a , R b , R c , R d R2, R3, R4, R5, R6, E and n are the same as above. The process includes manufacturing ] A method for producing a sulfur-containing pyridine derivative as described in [9].

[0016]

[11] [Step G]; The N-substituted amidine compound represented by formula (7) obtained in Step D or Step F, React with a carbonylating agent, Oxadiazolon compounds represented by formula (9); [ka] [In equation (9), R a , R b , R c , R d R2, R3, R4, R5 and n are the same as above. The process includes manufacturing ] A method for producing a pyridine derivative having a sulfur-containing substituent as described in [8] or

[10] . [Effects of the Invention]

[0017] Pyridine-2-ylpyridinium compounds having sulfur-containing substituents represented by formula (1) are useful as intermediates in the production of cyanopyridine derivatives represented by formula (2). A cyanopyridine derivative represented by formula (2) can be produced by reacting a pyridine-2-ylpyridinium compound having a sulfur-containing substituent represented by formula (1) with a cyanating agent. Furthermore, the cyanopyridine derivative represented by formula (2) is useful as a production intermediate for pyridine derivatives having sulfur-containing substituents that have pest control activity, and can provide a method for producing amide compounds represented by formula (5), N-substituted amidine compounds represented by formula (7), amidine compounds represented by formula (8), and oxadiazolon compounds represented by formula (9). [Modes for carrying out the invention]

[0018] The present invention relates to a pyridine-2-ylpyridinium compound having a sulfur substituent represented by formula (1) (hereinafter also referred to as compound (1)). Compound (1) is useful as a production intermediate for pyridine derivatives having sulfur substituents that have pest control activity.

[0019] [ka]

[0020] The substituents in compound (1) described above will be explained. R a This represents a group selected from the group consisting of unsubstituted or substituted (C1-C6) alkyl groups, unsubstituted or substituted (C3-C6) cycloalkyl groups, and NY3Y4 groups. Each of Y3 and Y4 independently represents a group selected from the group consisting of a hydrogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, and an unsubstituted or substituted (C1-C6) alkoxy group, or Y3 and Y4 together represent an alkylene group that forms a 3-8 membered cyclic amino group with a nitrogen atom to which they are bonded. The substituents that each group may have are halogen atoms, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, (C3-C6) cycloalkoxy groups, and NY a Y b Base, C(O)NY a Y b Examples include the group, cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxy group, trimethylsilyl group, C(O)NH2 group, and SF5 group. Here, Y a and Y b Each of these is independently a hydrogen atom, a (C1-C6) alkyl group, a halo(C1-C6) alkyl group, a (C3-C6) cycloalkyl group, a halo(C3-C6) cycloalkyl group, or Y a and Y b This is an alkylene group (C2-C7) that forms a 3-8 membered cyclic amino group with a nitrogen atom that is bonded together. When there are two or more substituents, each substituent may be the same or different from the others. Preferably, R a R is an unsubstituted or substituted (C1-C6) alkyl group. More preferably, aThis is an alkyl group (C1-C3) which may be substituted with a halogen atom, and more preferably a methyl group or an ethyl group.

[0021] n is an integer between 0 and 2. It is preferable that n is 2. That is, S(O) n R a Preferred forms of the group include a methylsulfonyl group, an ethylsulfonyl group, and a trifluoromethylsulfonyl group, and more preferably, S(O) n R a The group is an ethyl sulfonyl group.

[0022] R b , R c and R dEach of these independently comprises a hydrogen atom, a halogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C2-C6) alkenyl group, an unsubstituted or substituted (C2-C6) alkynyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, an unsubstituted or substituted (C2-C6) alkenyloxy group, or an unsubstituted or substituted (C2-C6) alkynyloxy group, unsubstituted or substituted (C3-C6) cycloalkoxy group, unsubstituted or substituted (C1-C6) alkylcarbonyl group, unsubstituted or substituted (C3-C6) cycloalkylcarbonyl group, unsubstituted or substituted (C1-C6) alkoxycarbonyl group, unsubstituted or substituted (C2-C6) alkenyloxycarbonyl group, unsubstituted or substituted (C2-C6) alkynyl This represents a group selected from the group consisting of an oxycarbonyl group, an unsubstituted or substituted (C1-C6) alkylcarbonyloxy group, an unsubstituted or substituted (C2-C6) alkenylcarbonyloxy group, an unsubstituted or substituted (C2-C6) alkynylcarbonyloxy group, an unsubstituted or substituted (C1-C6) alkylthio group, an unsubstituted or substituted (C1-C6) alkylsulfinyl group, an unsubstituted or substituted (C1-C6) alkylsulfonyl group, an unsubstituted or substituted (C1-C6) alkylsulfonyloxy group, an unsubstituted or substituted phenyl group, an unsubstituted or substituted heterocyclic group, an unsubstituted or substituted phenoxy group, an unsubstituted or substituted pyridyloxy group, a NY5Y6 group, a C(O)NY5Y6 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, and an SF5 group. If multiple Y5 and Y6 exist, each independently represents a group selected from the group consisting of a hydrogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C2-C6) alkenyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, an unsubstituted or substituted (C1-C6) alkylcarbonyl group, an unsubstituted or substituted (C1-C6) alkoxycarbonyl group, an unsubstituted or substituted phenyl group, an unsubstituted or substituted heterocyclic group, a cyano group, and a hydroxyl group. The substituents that each group may have are halogen atoms, (C1-C6) alkyl groups, halo(C1-C6) alkyl groups, (C3-C6) cycloalkyl groups, halo(C3-C6) cycloalkyl groups, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, halo(C3-C6) cycloalkoxy groups, (C1-C6) alkylthio groups, halo(C1-C6) alkylthio groups, (C1-C6) alkylsulfinyl groups, halo(C1-C6) alkylsulfinyl groups, (C1-C6) alkylsulfonyl groups, halo(C1-C6) alkylsulfonyl groups, NY a Y b Base, C(O)NY a Y b Examples include the group, cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxy group, C(O)NH2 group, trimethylsilyl group, and SF5 group. Here, Y a and Y b Each of these is independently a hydrogen atom, a (C1-C6) alkyl group, a halo(C1-C6) alkyl group, a (C3-C6) cycloalkyl group, a halo(C3-C6) cycloalkyl group, or Y a and Y b This is an alkylene group (C2-C7) that forms a 3-8 membered cyclic amino group with a nitrogen atom that is bonded together. When there are two or more substituents, each substituent may be the same or different from the others.

[0023] R b , R c , and RdExamples 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] Preferably, R b , R c and R d is any one of an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C2-C6) alkenyl group, an unsubstituted or substituted (C2-C6) alkynyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, an unsubstituted or substituted (C2-C6) alkenyloxy group, an unsubstituted or substituted (C2-C6) alkynyloxy group, an unsubstituted or substituted (C3-C6) cycloalkoxy group, an unsubstituted or substituted (C2-C6) alkenylcarbonyloxy group, an unsubstituted or substituted (C2-C6) alkynylcarbonyloxy group, an unsubstituted or substituted (C1-C6) alkylthio group, an unsubstituted or substituted (C1-C6) alkylsulfinyl group, an unsubstituted or substituted (C1-C6) alkylsulfonyl group, an unsubstituted or substituted (C1-C6) alkylsulfonyloxy group, an unsubstituted or substituted phenyl group, an unsubstituted or substituted heterocyclic group, an unsubstituted or substituted phenoxy group, an unsubstituted or substituted pyridyloxy group, and the other is a hydrogen atom or a halogen atom. More preferably, R b , R c and R dOne of them represents a group selected from the group consisting of an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, an unsubstituted or substituted (C3-C6) cycloalkoxy group, an unsubstituted or substituted (C1-C6) alkylthio group, an unsubstituted or substituted (C1-C6) alkylsulfinyl group, an unsubstituted or substituted (C1-C6) alkylsulfonyl group, an unsubstituted or substituted phenyl group, an unsubstituted or substituted heterocyclic group, an unsubstituted or substituted phenoxy group, and an unsubstituted or substituted pyridyloxy group, and the other is a hydrogen atom or a halogen atom. In this case, the substituents that may be present are a halogen atom, a (C1-C6) alkyl group, a halo(C1-C6) alkyl group, a (C3-C6) cycloalkyl group, a halo(C3-C6) cycloalkyl group, a (C1-C6) alkoxy group, a halo(C1-C6) alkoxy group, a halo(C3-C6) cycloalkoxy group, a (C1-C6) alkylthio group, a halo(C1-C6) alkylthio group, a (C1-C6) alkylsulfinyl group, a halo(C1-C6) alkylsulfinyl group, a (C1-C6) alkylsulfonyl group, a halo(C1-C6) alkylsulfonyl group, NY a Y b group, C(O)NY a Y b group, a cyano group, a nitro group, a hydroxy group, a mercapto group, an amino group, a formyl group, a carboxy group, a C(O)NH2 group, a trimethylsilyl group, and a SF5 group.

[0025] More preferably, R b and R d are hydrogen atoms, and R cThis group is selected from the group consisting of halogen atoms, unsubstituted or substituted (C1-C6) alkyl groups, unsubstituted or substituted (C3-C6) cycloalkyl groups, unsubstituted or substituted (C1-C6) alkoxy groups, unsubstituted or substituted (C3-C6) cycloalkoxy groups, unsubstituted or substituted phenyl groups, and unsubstituted or substituted heterocyclic groups. In this case, the substituents that may be present are halogen atoms, (C1-C6) alkyl groups, halo(C1-C6) alkyl groups, (C3-C6) cycloalkyl groups, halo(C3-C6) cycloalkyl groups, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, halo(C3-C6) cycloalkoxy groups, (C1-C6) alkylthio groups, halo(C1-C6) alkylthio groups, (C1-C6) alkylsulfinyl groups, halo(C1-C6) alkylsulfinyl groups, (C1-C6) alkylsulfonyl groups, halo(C1-C6) alkylsulfonyl groups, NY a Y b Base, C(O)NY a Y b These include the cyano group, nitro group, hydroxyl group, mercapto group, amino group, formyl group, carboxyl group, C(O)NH2 group, trimethylsilyl group, and SF5 group. More preferably, R b and R d R is a hydrogen atom, c This group is selected from the group consisting of unsubstituted or substituted (C3-C6) cycloalkyl groups, unsubstituted or substituted phenyl groups, and unsubstituted or substituted heterocyclic groups. In this case, the substituents that may be present are halogen atoms, (C1-C6) alkyl groups, halo(C1-C6) alkyl groups, (C3-C6) cycloalkyl groups, halo(C3-C6) cycloalkyl groups, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, halo(C3-C6) cycloalkoxy groups, (C1-C6) alkylthio groups, halo(C1-C6) alkylthio groups, (C1-C6) alkylsulfinyl groups, halo(C1-C6) alkylsulfonyl groups, halo(C1-C6) alkylsulfonyl groups, NY aY b Base, C(O)NY a Y b These include the cyano group, nitro group, hydroxyl group, mercapto group, amino group, formyl group, carboxyl group, C(O)NH2 group, trimethylsilyl group, and SF5 group.

[0026] In this invention, R b and R d R is a hydrogen atom, c It is particularly preferable that R is an unsubstituted or substituted phenyl group. In this case, R c Preferred substituents on the phenyl group include halogen atoms, (C1-C6) alkyl groups, halo(C1-C6) alkyl groups, (C3-C6) cycloalkyl groups, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, or cyano groups. Preferred embodiments include, for example, 4-fluorophenyl group, 4-chlorophenyl group, 4-bromophenyl group, 4-iodophenyl group, 4-cyanophenyl group, 4-(trifluoromethyl)phenyl group, 4-(trifluoromethoxy)phenyl group, 2,4-difluorophenyl group, 2,4,6-trifluorophenyl group, and 3,5-difluorophenyl group. More preferably, R c The substituent is preferably substituted at the 4-position of the phenyl group, and the substituent is preferably a halogen atom, a halo(C1-C6)alkyl group, a (C3-C6)cycloalkyl group, a halo(C1-C6)alkoxy group, or a cyano group. More preferably, it is a halogen atom, a halo(C1-C6)alkyl group, or a halo(C1-C6)alkoxy group substituted at the 4-position of the phenyl group. Examples of preferred embodiments include 4-fluorophenyl group, 4-chlorophenyl group, 4-bromophenyl group, 4-iodophenyl group, 4-cyanophenyl group, 4-(trifluoromethyl)phenyl group, and 4-(trifluoromethoxy)phenyl group.

[0027] If there are multiple X's, each independently represents a group selected from the group consisting of a halogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, and an NY1Y2 group. Y1 and Y2 may each independently represent a hydrogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, or an unsubstituted or substituted (C1-C6) alkoxy group, or Y1 and Y2 may together form an unsubstituted or substituted (C2-C7) alkylene group that forms a 3-8 membered cyclic amino group with a nitrogen atom. The substituents that may be present are halogen atoms, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, (C3-C6) cycloalkoxy groups, and NY a Y b Base, C(O)NY a Y b Examples include the group, cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxy group, trimethylsilyl group, C(O)NH2 group, and SF5 group. Here, Y a and Y b This is synonymous with the above. Preferably, if there are multiple X groups, each is independently selected from the group consisting of unsubstituted or substituted (C1-C6) alkyl groups or NY1Y2 groups, with NY1Y2 groups being more preferred. In this case, Y1 and Y2 are preferably independently unsubstituted or substituted (C1-C6) alkyl groups, or Y1 and Y2 are preferably unsubstituted or substituted (C2-C7) alkylene groups that form a 3-8 membered cyclic amino group with the nitrogen atom to which they are bonded together.

[0028] m is an integer between 0 and 5. If m is 2 or greater, X may be the same or different. m is preferably 1 or 2, and more preferably 1.

[0029] A -This represents an ionic species selected from the group consisting of halogen ions, unsubstituted or substituted benzenesulfonate ions, and unsubstituted or substituted (C1-C8) alkylsulfonate ions. The substituents that may be present are halogen atoms, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, (C3-C6) cycloalkoxy groups, and NY a Y b Base, C(O)NY a Y b Examples include the group, cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxy group, trimethylsilyl group, C(O)NH2 group, and SF5 group. Here, Y a and Y b This is synonymous with the above. Examples of halogen ions include fluoride ions, chloride ions, bromide ions, or iodide ions. Examples of unsubstituted or substituted benzenesulfonate ions include p-methylphenylsulfonate ions, p-trifluoromethylphenylsulfonate ions, and dodecylbenzenesulfonate ions. Examples of unsubstituted or substituted (C1-C8) alkylsulfonate ions include methanesulfonate ions and trifluoromethanesulfonate ions. Preferably, A - This is a halogen ion, more preferably a chloride ion, or a bromide ion.

[0030] Compound (1) most preferably has m = 1 and X = a group represented by NY1Y2. Y1 and Y2 may each independently represent an unsubstituted or substituted (C1-C6) alkyl group, in which case Y1 and Y2 are preferably a methyl group, an ethyl group, or an n-propyl group, more preferably a methyl group. Alternatively, Y1 and Y2 may together form a ring containing the nitrogen atom to which they are bonded as a constituent atom of the ring, in which case NY1Y2 is preferably a pyrrolidinyl group, a piperidinyl group, or a pyrrolinyl group, more preferably a pyrrolidinyl group. More preferably, when m = 1 and X is a group represented by NY1Y2 substituted at the 4-position, the compound is represented by formula (10).

[0031] [ka]

[0032] Preferred embodiments of the heterocyclic compound relating to formula (1) include the following compounds. 1-(3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride, 1-(3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide, 1-(3-(ethanesulfonyl)-5-fluoro-2-pyridyl)-4-(dimethylamino)pyridinium chloride, 1-(3-(ethanesulfonyl)-5-fluoro-2-pyridyl)-4-(dimethylamino)pyridinium bromide, 1-(5-chloro-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride, 1-(5-chloro-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide, 1-(5-bromo-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride, 1-(5-bromo-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide, 1-(3-(ethanesulfonyl)-5-(trifluoromethyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride, 1-(3-(ethanesulfonyl)-5-(trifluoromethyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide, 1-(3-(ethanesulfonyl)-5-(trifluoromethoxy)-2-pyridyl)-4-(dimethylamino)pyridinium chloride, 1-(3-(ethanesulfonyl)-5-(trifluoromethoxy)-2-pyridyl)-4-(dimethylamino)pyridinium bromide, 1-(5-cyclopropyl-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride, 1-(5-cyclopropyl-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide, 1-(5-(1-cyanocyclopropyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride, 1-(5-(1-cyanocyclopropyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide, 1-(3-(ethanesulfonyl)-5-(4-fluorophenyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride 1-(3-(ethanesulfonyl)-5-(4-fluorophenyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide 1-(5-(4-chlorophenyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride, 1-(5-(4-chlorophenyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide, 1-(5-(4-bromophenyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride, 1-(5-(4-bromophenyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide, 1-(3-(ethanesulfonyl)-5-(4-iodophenyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride 1-(3-(ethanesulfonyl)-5-(4-iodophenyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide 1-(3-(ethanesulfonyl)-5-(4-(trifluoromethyl)phenyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride 1-(3-(ethanesulfonyl)-5-(4-(trifluoromethyl))-2-pyridyl)-4-(dimethylamino)pyridinium bromide 1-(3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride 1-(3-(ethanesulfonyl)-5-(4-(trifluoromethoxy))-2-pyridyl)-4-(dimethylamino)pyridinium bromide 1-(5-(2,4-difluorophenyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride, 1-(5-(2,4-difluorophenyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide, 1-(5-(3,5-difluorophenyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride, 1-(5-(3,5-difluorophenyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide, 1-(5-(3,4-difluorophenyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride, 1-(5-(3,4-difluorophenyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide, 1-(5-(2,4-dichlorophenyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride, 1-(5-(2,4-dichlorophenyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide, 1-(5-(3,5-dichlorophenyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride, 1-(5-(3,5-dichlorophenyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide, 1-(5-(3,4-dichlorophenyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride, 1-(5-(3,4-dichlorophenyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide, 1-(5-(4-cyanophenyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride, 1-(5-(4-cyanophenyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide, 1-(3-(ethanesulfonyl)-5-(5-fluoropyridine-2-yl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride 1-(3-(ethanesulfonyl)-5-(5-fluoropyridine-2-yl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide 1-(5-(5-chloropyridine-2-yl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride, 1-(5-(5-chloropyridine-2-yl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide, 1-(3-(ethanesulfonyl)-5-(5-(trifluoromethyl)pyridin-2-yl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride 1-(3-(ethanesulfonyl)-5-(5-(trifluoromethyl)pyridin-2-yl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide 1-(3-(ethanesulfonyl)-5-(5-(trifluoromethoxy)pyridin-2-yl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride 1-(3-(ethanesulfonyl)-5-(5-(trifluoromethoxy)pyridin-2-yl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide 1-(5-(5-cyanopyridine-2-yl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride, 1-(5-(5-cyanopyridine-2-yl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide.

[0033] The present invention includes a method for producing a cyanopyridine derivative represented by formula (2) from compound (1) (hereinafter also referred to as compound (2)). R in compound (2) a , R b , R c , R d And n is synonymous with the corresponding compound (1).

[0034] Preferred embodiments of the cyanoheterocyclic compound (2) related to formula (2) include the following compounds. 3-(ethylsulfonyl)-5-fluoropiccolinonitrile, 5-chloro-3-(3-ethylsulfonyl)piccolinonitrile, 5-bromo-3-(ethylsulfonyl)piccolinonitrile, 3-(ethylsulfonyl)-5-iodopiccolinonitrile, 3-(ethylsulfonyl)-5-(trifluoromethyl)piccolinonitrile, 3-(ethylsulfonyl)-5-(trifluoromethoxy)piccolinonitrile, 3-(ethylsulfonyl)piccolinonitrile, 5-cyclopropyl-3-(ethylsulfonyl)piccolinonitrile, 5-(1-cyanocyclopropyl)-3-(ethylsulfonyl)piccolinonitrile, 3-(ethylsulfonyl)-5-(4-fluorophenyl)piccolinonitrile, 5-(4-chlorophenyl)-3-(ethylsulfonyl)piccolinonitrile, 5-( 4-bromophenyl)-3-(ethylsulfonyl)picolinonitrile, 3-(ethylsulfonyl)-5-(4-iodophenyl)picolinonitrile, 3-(ethylsulfonyl)-5-(4-(trifluoromethyl)phenyl)picolinonitrile, 3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)picolinonitrile, 5-(2,4-difluorophenyl)-3-(ethylsulfonyl)picolinonitrile, 3-(ethylsulfonyl)-5-(2,4,6-trifluorophenyl)picolinonitrile, 5-(3,5-difluorophenyl)-3-(ethylsulfonyl)picolinonitrile, 5-(4-cyanophenyl)-3-(ethylsulfonyl)picolinonitrile, 5'-(ethylsulfonyl)-[2,3'-bipyridine]-6'-carbonitrile.

[0035] The present invention includes a method for producing a pyridine derivative having a sulfur-containing substituent that exhibits pest control activity, which is an amide compound represented by formula (5) (hereinafter also referred to as compound (5)).

[0036] [ka]

[0037] Furthermore, the present invention includes a method for producing a pyridine derivative having a sulfur-containing substituent that exhibits pest control activity, which is an N-substituted amidine compound represented by formula (7) (hereinafter also referred to as compound (7)) or an amidine compound represented by formula (8) (hereinafter also referred to as compound (8)), including a route for producing compound (2) from compound (1).

[0038] [ka]

[0039] [ka]

[0040] Furthermore, the present invention includes a method for producing a pyridine derivative having a sulfur-containing substituent that exhibits pest control activity, which is an oxadiazolon compound represented by formula (9) (hereinafter also referred to as compound (9)).

[0041] [ka]

[0042] The substituents in compound (5), compound (7), compound (8), and compound (9) will be described below.

[0043] R a , R b , R c , R d And n is synonymous with the group in compound (1).

[0044] R2, R3, R4, and R5 are each independently a hydrogen atom, a halogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C2-C6) alkenyl group, an unsubstituted or substituted (C2-C6) alkynyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, an unsubstituted or substituted (C2-C6) alkenyloxy group, or an unsubstituted or ku is a substituted (C2-C6) alkynyloxy group, an unsubstituted or substituted (C3-C6) cycloalkoxy group, an unsubstituted or substituted (C1-C6) alkylcarbonyl group, an unsubstituted or substituted (C3-C6) cycloalkylcarbonyl group, an unsubstituted or substituted (C1-C6) alkoxycarbonyl group, an unsubstituted or substituted (C2-C6) alkenyloxycarbonyl group, an unsubstituted or substituted (C2-C6) ) Alkynyloxycarbonyl group, unsubstituted or substituted (C1-C6) alkylcarbonyloxy group, unsubstituted or substituted (C2-C6) alkenylcarbonyloxy group, unsubstituted or substituted (C2-C6) alkynylcarbonyloxy group, unsubstituted or substituted (C1-C6) alkylthio group, unsubstituted or substituted (C1-C6) alkylsulfinyl group, unsubstituted or substituted (C1-C6) alkylsulfonyl group This represents a group selected from the group consisting of a nyl group, an unsubstituted or substituted (C1-C6) alkylsulfonyloxy group, an unsubstituted or substituted phenyl group, an unsubstituted or substituted heterocyclic group, an unsubstituted or substituted phenoxy group, an unsubstituted or substituted pyridyloxy group, a NY5Y6 group, a C(O)NY5Y6 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, and an SF5 group. Note that Y5 and Y6 have the same meaning as above. The substituents that each group may have are halogen atoms, (C1-C6) alkyl groups, halo(C1-C6) alkyl groups, (C3-C6) cycloalkyl groups, halo(C3-C6) cycloalkyl groups, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, halo(C3-C6) cycloalkoxy groups, (C1-C6) alkylthio groups, halo(C1-C6) alkylthio groups, (C1-C6) alkylsulfinyl groups, halo(C1-C6) alkylsulfinyl groups, (C1-C6) alkylsulfonyl groups, halo(C1-C6) alkylsulfonyl groups, NY a Y b Base, C(O)NY a Y b Examples include the group, cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxy group, C(O)NH2 group, trimethylsilyl group, and SF5 group. a and Y b This is equivalent to the above. When there are two or more substituents, each substituent may be the same or different from the others.

[0045] Examples of "heterocyclic groups" in R2, R3, R4, and R5 include thiophen-2-yl, thiophen-3-yl, fran-2-yl, fran-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 Lu-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-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-Thiadianazole-4-yl, 1,2,3-Thiadianazole-5-yl, 1,2,3-Triazole-1-yl, 1,2,3-Triazole-2-yl, 1,2,3-Triazole-4-yl, 1,2,3,4-Tetrazole-1-yl, 1,2,3,4-Tetrazole-2-yl, 1,2,3,4-Tetrazole-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- Il, Benzoimidazole-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, I Ndazole-7-yl, benzoxazole-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, quinoxa Phosphate-2-yl, quinoxaline-3-yl, quinoxaline-5-yl, 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, sinnoline-3-yl, sinnoline-4-yl, sinnoline-5-yl, sinnoline-6-yl, sinnoline-7-yl, sinnoline-8-yl, quinazolin-2-yl, quinazolin-4-yl, quinazolin-5-yl, quinazolin-6-yl,Quinazolin-7-yl or quinazolin-8-yl are specific examples.

[0046] Preferably, R2, R3, R4, and R5 each independently represent a group selected from the group consisting of a hydrogen atom, a halogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, an unsubstituted or substituted (C1-C6) alkoxy group, an unsubstituted or substituted (C3-C6) cycloalkoxy group, an unsubstituted or substituted (C1-C6) alkylthio group, an unsubstituted or substituted (C1-C6) alkylsulfinyl group, and an unsubstituted or substituted (C1-C6) alkylsulfonyl group. In this case, the substituents that may be present 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. More preferably, R2 and R5 are hydrogen atoms, and R3 and R4 are each independently a group selected from the group consisting of a hydrogen atom, a halogen atom, and an unsubstituted or substituted (C1-C6) alkyl group. Particularly preferably, R2 and R5 are hydrogen atoms, and either R3 or R4 is an unsubstituted or substituted (C1-C6) alkyl 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.

[0047] E is a group selected from the group consisting of a hydrogen atom, an unsubstituted or substituted (C1-C6) alkyl group, an unsubstituted or substituted (C3-C6) cycloalkyl group, an unsubstituted or substituted (C1-C6) alkylcarbonyl group, or an unsubstituted or substituted (C3-C6) cycloalkylcarbonyl group. The substituents that may be present are halogen atoms, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, (C3-C6) cycloalkoxy groups, and NY a Y b Base, C(O)NY a Y b Examples include the group, cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxy group, trimethylsilyl group, C(O)NH2 group, and SF5 group. a and Y b This is synonymous with the above. Preferably, E is a hydrogen atom or an unsubstituted or substituted (C1-C6) alkyl group, with a hydrogen atom being more preferred.

[0048] R6 represents a group selected from the group consisting of a hydrogen atom, optionally substituted (C1-C6) alkyl groups, optionally substituted (C3-C6) cycloalkyl groups, optionally substituted (C1-C6) alkylcarbonyl groups, and optionally substituted (C3-C6) cycloalkylcarbonyl groups. The substituents that may be present are halogen atoms, (C1-C6) alkoxy groups, halo(C1-C6) alkoxy groups, (C3-C6) cycloalkoxy groups, and NY a Y b Base, C(O)NY a Y b Examples include the group, cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxy group, trimethylsilyl group, C(O)NH2 group, and SF5 group. a and Y b This is synonymous with the above. Preferably, 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, or an optionally substituted (C1-C6) alkylcarbonyl group, with a hydrogen atom being more preferred.

[0049] <Compound (1); Method for producing pyridine-2-ylpyridinium compounds> A method for producing a pyridine-2-ylpyridinium compound (compound (1)) having a sulfur-containing substituent represented by formula (1), which is one embodiment of the present invention, will be described.

[0050] Compound (1) can be obtained, for example, by a method that involves reacting a compound represented by formula (11) with a compound represented by formula (12).

[0051] [ka] [where X, m, A, R a , R b , R c , R d And n is synonymous with the above.

[0052] This reaction may be carried out in the presence of a liquid solvent. Examples of solvents include aromatic hydrocarbon solvents such as benzene, chlorobenzene, and toluene; halogenated aliphatic hydrocarbon solvents such as chloroform and dichloromethane; alcohol solvents such as methanol, ethanol, and n-butanol; nitrile solvents such as acetonitrile and propylnitrile; 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, the solvent is an aromatic hydrocarbon solvent such as chlorobenzene or toluene, or a sulfoxide solvent or an amide solvent; more preferably, an aromatic hydrocarbon solvent or an amide solvent; and even more preferably, toluene and N,N-dimethylacetamide. The amount of solvent used is usually 0.5 to 100 parts by mass, preferably 0.5 to 20 parts by mass, relative to compound (12). A more preferable amount of solvent is 0.5 to 10 parts by mass.

[0053] The reaction temperature is typically 0 to 200°C, preferably 50 to 150°C, and more preferably 60 to 130°C. The reaction time varies depending on the size of the reaction apparatus, but is usually between 0.5 and 24 hours. The reaction is preferably carried out under a nitrogen atmosphere.

[0054] One method for separating compound (1) from the reaction mixture is to concentrate the mixture after the reaction is complete, for example, to separate compound (1) from the resulting reaction mixture. The separated reaction mixture may be used directly in [Step A], or it may be purified by liquid-liquid separation, filtration, etc. Alternatively, compound (1) may be isolated from the reaction mixture by conventional purification methods such as washing, filtration, column chromatography, and recrystallization.

[0055] <Method for producing cyanopyridine derivatives from compound (1) to compound (2)> The methods for producing compounds (5), (7), (8), and (9) using compound (1) all involve a method for producing compound (2) from compound (1). Therefore, the method for producing compound (2); a cyanopyridine derivative from compound (1); a pyridine-2-ylpyridinium compound will be described below.

[0056] [ka] [In the formula, R a , R b , R c , R d n, X, m, and A are the same as above.

[0057] The preparation of compound (2), a cyanopyridine derivative, from compound (1), a pyridine-2-ylpyridinium compound, is carried out using a cyanating agent. Examples of cyanating agents include cyanoalkali metal salts such as lithium cyanide, sodium cyanide, and potassium cyanide; cyanotransition metal salts such as copper cyanide (CuCN) and zinc cyanide (Zn(CN)2); organic cyanating agents such as trimethylsilyl cyanide and acetone cyanohydrin; cyanide bromide; and hydrogen cyanide. Preferably, a cyanoalkali metal salt selected from lithium cyanide, sodium cyanide, and potassium cyanide is used. More preferably, sodium cyanide or potassium cyanide is used. The amount of cyanating agent used is usually 1 to 10 moles, preferably 1 to 5 moles, and more preferably 1 to 2 moles, per mole of compound (1).

[0058] The above reaction may be carried out in the presence of a solvent. Examples of solvents include water; aromatic hydrocarbon solvents such as benzene, chlorobenzene, and toluene; halogenated aliphatic hydrocarbon solvents such as chloroform and dichloromethane; alcohol solvents such as methanol, ethanol, and n-butanol; nitrile solvents such as acetonitrile and propylnitrile; 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 reaction may also be carried out in a two-phase system of water and another solvent. The amount of solvent used is usually 1 to 100 parts by mass, preferably 1 to 20 parts by mass, per 1 part by mass of compound (1). This is usually done by mixing compound (1) with the cyanating agent.

[0059] The reaction temperature for the above reaction is typically 0 to 150°C, preferably 0 to 100°C, and more preferably 10 to 60°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.

[0060] The reaction between compound (1) and the cyanating agent may be carried out in the presence of a phase-transfer catalyst. Examples of phase-transfer catalysts include, but are not limited to, quaternary ammonium salts such as benzyltrimethylammonium chloride, tetrabutylammonium bromide, decyltrimethylammonium bromide, and cetyltrimethylammonium chloride; quaternary phosphonium salts such as tetrabutylphosphonium bromide, tetraphenylphosphonium chloride, and tetraethylphosphonium bromide; and crown ethers such as 15-crown-5-ether, 18-crown-6-ether, and dibenzo-18-crown-6-ether. The amount of phase transfer catalyst used is typically 0.005 to 1 mole per mole of compound (1), preferably 0.01 to 1 mole.

[0061] The reaction between compound (1) and the cyanating agent may be carried out in the presence of a transition metal catalyst. Examples of transition metal catalysts include palladium, rhodium, and nickel, with palladium being preferred. The amount of transition metal catalyst used is typically 0.01 to 10 mole percent, preferably 0.1 to 5 mole percent, per mole of compound (1).

[0062] The reaction between compound (1) and the cyanating agent may be carried out in the presence of a base. Examples of bases include, but are not limited to, alkali metal salts such as sodium carbonate, sodium bicarbonate, and potassium carbonate; tertiary amines such as triethylamine and N,N-diisopropylethylamine; and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine. The amount of base used should be appropriately selected within the range of approximately 1 to 5 times the molar equivalent of the compound represented by formula (1).

[0063] The reaction between compound (1) and the cyanating agent may be carried out in the presence of an inorganic salt. Examples of inorganic salts include, but are not limited to, phosphates such as tripotassium phosphate, trisodium phosphate, dipotassium hydrogen phosphate, disodium hydrogen phosphate, potassium dihydrogen phosphate, and sodium dihydrogen phosphate; acetates such as ammonium acetate, potassium acetate, and sodium acetate; sulfates such as sodium sulfate, potassium sulfate, and magnesium sulfate; and hydrochlorides such as sodium chloride, potassium chloride, and ammonium chloride. The amount of inorganic salt used should be appropriately selected within the range of approximately 0.1 to 5 times the molar amount of compound (1).

[0064] Compound (2); a cyanopyridine derivative obtained by the above reaction can be isolated by, for example, concentrating the reaction mixture. Alternatively, it may be isolated by extraction and washing from the resulting reaction mixture. The isolated compound (2) may be further purified by conventional purification methods such as washing, column chromatography, and recrystallization.

[0065] <Method for producing compound (5) an amide compound from compound (2); a cyanopyridine derivative> The present invention encompasses a method for producing compound (5) an amide compound, using compound (2) a cyanopyridine derivative obtained by the reaction of compound (1) a pyridine-2-ylpyridinium compound with a cyanating agent as a reaction substrate. The method for producing the amide compound can be carried out by the usual method for producing amide compounds from cyanopyridine compounds. For example, it can be produced in accordance with the method described in International Publication No. 2023 / 190286.

[0066] Compound (2); a cyanopyridine derivative can be used to produce compound (5); an amide compound, for example, by the method described in steps a-1 to a-2 or steps b and c below. Specifically, the process includes a step (a-1) of preparing a carboxypyridine compound according to formula (3) (also referred to as compound (3)) from compound (2); a cyanopyridine derivative, and then a step (a-2) of reacting compound (3); the carboxypyridine compound with a pyridylamine compound according to formula (4) (also referred to as compound (4)) to produce compound (5); an amide compound. Step a-2 may involve converting compound (3); a carboxyheterocyclic compound to the corresponding acid halide or active ester, and then reacting it with compound (4); a pyridylamine compound to produce compound (5); an amide compound. In this case, the corresponding acid halide or active ester may be isolated and subjected to the subsequent reaction with compound (4), or it may be carried out without isolation.

[0067] <Compound (5); Amide compound manufacturing process a-1 to a-2> [ka] [In the formula, R a , R b , R c , R d n, R2, R3, R4, and R5 are equivalent to those stated above.

[0068] <Process a-1> Compound (3); a carboxypyridine compound can be produced by reacting compound (2); a cyanopyridine derivative with a reagent. The reagents that can be used in step a-1 may be bases, for example, alkali metal salts such as lithium hydroxide, sodium hydroxide, potassium hydroxide, and sodium carbonate. The amount of base used should be appropriately selected in the range of approximately 0.5 to 10 times the molar amount of compound (2).

[0069] The reagents that can be used in step a-1 may be acids, including inorganic acids such as sulfuric acid, hydrochloric acid, and nitric acid; organic acids such as acetic acid and p-tosylic acid; and Lewis acids such as trimethylaluminum, aluminum chloride, and titanium tetrachloride. The amount of acid that can be used in this reaction should be appropriately selected in the range of approximately 1 to 10 times the molar amount of compound (2).

[0070] The solvents that can be used in step a-1 are those that do not significantly inhibit the reaction, and examples include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as dichloromethane and 1,2-dichloroethane; ethers such as tetrahydrofuran and 1,4-dioxane; polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and 1,3-dimethyl-2-imidazolinone; and water. These inert solvents can be used individually or in combination of two or more.

[0071] The reaction temperature in step a-1 can typically be anywhere from approximately -78°C to the boiling point of the solvent used, and the reaction time can be appropriately selected depending on the scale of the reaction, the reaction temperature, etc. For example, it can be appropriately selected within the range of a few minutes to 48 hours. Furthermore, this reaction can also be carried out under an atmosphere of an inert gas such as nitrogen or argon.

[0072] After the reaction is complete, the target product can be isolated from the reaction system by conventional methods, and if necessary, purified by recrystallization, column chromatography, etc. to produce the target product. The composition containing the target product may also be used in the next step without isolation.

[0073] <Process a-2> Compound (5) an amide compound can be produced by reacting compound (3); a carboxypyridine compound, compound (4); a pyridylamine compound, and a reactant in an inert solvent.

[0074] Examples of reagents that can be used in step a-2 include dicyclohexylcarbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride, HATU, PyBOP, and Mukaiyama reagents as condensing agents. Alternatively, examples include thionyl chloride, sulfuryl chloride, oxalyl chloride, phosphorus oxychloride, phosphorus pentachloride, phosgene, triphosgene, etc. The amount of reagent used should be appropriately selected within the range of approximately 1 to 3 times the molar amount of compound (3).

[0075] Examples of bases that can be used in step a-2 include alkali metal salts such as sodium hydride, sodium carbonate, and potassium carbonate; tertiary amines such as triethylamine and N,N-diisopropylethylamine; and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine. The amount of base used should be appropriately selected within the range of approximately 1 to 5 times the molar amount of compound (3).

[0076] The inert solvent that can be used in step a-2 is one that does not significantly inhibit the reaction, and examples include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as dichloromethane and 1,2-dichloroethane; and polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and 1,3-dimethyl-2-imidazolinone. These inert solvents can be used individually or in combination of two or more.

[0077] The reaction temperature in step a-2 should typically be within the range of approximately -78°C to the boiling point of the solvent used. The reaction time can be appropriately selected depending on the scale of the reaction, the reaction temperature, etc. For example, it can be selected within a range of a few minutes to 48 hours. Furthermore, this process may be carried out under the atmosphere of an inert gas, such as nitrogen gas or argon gas. Compound (3); the active ester intermediate or acid halide intermediate of the carboxypyridine compound and the reactant may be isolated and then used in the reaction with compound (4); the pyridylamine compound, or it may be used directly in the reaction with compound (4); the pyridylamine compound without isolation.

[0078] After the reaction is complete, the target product can be isolated from the reaction system by conventional methods, and if necessary, purified by recrystallization, column chromatography, etc. to produce the target product. The composition containing the target product may also be used in the next step without isolation.

[0079] Furthermore, if compound (5) is an amide compound in which E is an alkyl group, cycloalkyl group, alkylcarbonyl group, or cycloalkylcarbonyl group other than hydrogen, the desired compound (5) can be produced by reacting it with a suitable alkylating agent or acyling agent after step a-2.

[0080] Furthermore, a method for producing compound (5); amide compound of the present invention also includes a method (step c) for producing compound (5); amide compound via compound (7); N-substituted amidine compound or compound (8); amidine compound (steps b-1 to b-2) from compound (2); cyanopyridine derivative, as described later. Specifically, the process includes: step b-1, reacting compound (2); a cyanopyridine derivative with compound (4); a pyridylamine compound to prepare compound (8); an amidine compound; step b-2, preparing formula (7); an N-substituted amidine compound from compound (8); and step c, producing compound (5); an amide compound from compound (8) or compound (7). Processes b-1 and b-2 will be described later; here, we will explain process c.

[0081] <Compound (5); amide compound manufacturing process b1-b2 and step c> [ka] [In the formula, R a , Rb , R c , R d R2, R3, R4, R5, R6, and n are equivalent to those stated above.

[0082] <Process c> Compound (8); an amidine compound or compound (7); an N-substituted amidine compound can be prepared from compound (2); a cyanopyridine derivative by steps b-1 to b-2, and compound (5); an amide compound can be produced by reacting this with a reactant in an inert solvent. Furthermore, the compound (8) or compound (7) produced by steps b-1 to b-2 may be carried out directly in the reaction system without isolation during step c.

[0083] The reagents that can be used in step c may be bases, and examples include alkali metal salts such as sodium hydride, sodium hydroxide, sodium carbonate, and potassium carbonate; tertiary amines such as triethylamine and N,N-diisopropylethylamine; and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine. The amount of base to be used should be appropriately selected within the range of approximately 1 to 5 molars relative to compound (8); N-substituted amidine compound or compound (7); amidine compound.

[0084] The reagents that can be used in step c may be acids, for example, inorganic acids such as sulfuric acid, hydrochloric acid, and nitric acid; organic acids such as acetic acid and p-tosylic acid; and Lewis acids such as trimethylaluminum, aluminum chloride, and titanium tetrachloride. The amount of reagent used in this reaction should be appropriately selected within the range of approximately 1 to 10 molars relative to compound (8); the N-substituted amidine compound or compound (7); the amidine compound.

[0085] Any inert solvent that does not significantly inhibit the reaction can be used in step c. Examples include ethers such as tetrahydrofuran, ethylene glycol dimethyl ether, and 1,4-dioxane; aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as dichloromethane and 1,2-dichloroethane; polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and 1,3-dimethyl-2-imidazolinone; and water. These inert solvents can be used individually or in combination of two or more.

[0086] The reaction temperature in step c should typically be within the range of approximately -78°C to the boiling point of the solvent used. The reaction time can be appropriately selected depending on the scale of the reaction, the reaction temperature, etc. For example, it can be selected within a range of a few minutes to 48 hours. Furthermore, this reaction can also be carried out under the atmosphere of an inert gas, such as nitrogen or argon.

[0087] After the reaction is complete, the target product can be isolated from the reaction system by conventional methods, and if necessary, purified by recrystallization, column chromatography, etc. to produce the target product. The composition containing the target product may also be used in the next step without isolation.

[0088] Furthermore, if compound (5) is an amide compound in which E is an alkyl group, cycloalkyl group, alkylcarbonyl group, or cycloalkylcarbonyl group other than hydrogen, the desired compound (5) can be produced by reacting it with a suitable alkylating agent or acyling agent after step a-2.

[0089] <Method for producing compound (8) an amidine compound and compound (7) an N-substituted amidine compound from compound (2) a cyanopyridine derivative> The present invention includes methods for producing compound (8) an amidine compound and compound (7) an N-substituted amidine compound, using compound (2) a cyanopyridine derivative obtained by the reaction of compound (1) a pyridine-2-ylpyridinium compound with a cyanating agent as a reaction substrate. The manufacturing method can be used to prepare the amidine compound from a cyanopyridine derivative using the standard manufacturing method. For example, compound (7); the N-substituted amidine compound can be manufactured from compound (2); the cyanopyridine derivative in accordance with the method described in International Publication No. 2020 / 054712, International Publication No. 2021 / 177410, or International Publication No. 2023 / 190286. Furthermore, compound (8); the amidine compound can be manufactured from compound (2); the cyanopyridine derivative in accordance with the method described in International Publication No. 2020 / 054712 or International Publication No. 2021 / 177410.

[0090] In the present invention, the method for producing compound (2) obtained by the reaction of compound (1) with a cyanating agent, amidine compound (8) using a cyanopyridine derivative as a reaction substrate, and N-substituted amidine compound (7) can be carried out by the method described in steps b-1 to b-2, but is not limited to this. In other words, this is a method for producing compound (8) an amidine compound and compound (7) an amidine compound by reacting compound (2) a cyanopyridine derivative with compound (4) a pyridylamine compound.

[0091] <Compound (8); Amidine compound and Compound (7); N-substituted amidine compound: Manufacturing process b-1 to b-2> [ka] [In the formula, R a , R b , R c , R d R2, R3, R4, R5, R6, and n are equivalent to those stated above.

[0092] <Process b-1> Examples of reagents that can be used in step b-1 include Lewis acids such as trimethylaluminum and aluminum chloride. The amount of reagent used is typically in the range of 1 mole to 10 moles relative to compound (2).

[0093] Examples of bases that can be used in step b-1 include alkali metal hydrides such as lithium hydride, sodium hydride, potassium hydride, and calcium hydride, and organometallic amides such as n-butyllithium, sodium bis(trimethylsilyl)amide, lithium bis(trimethylsilyl)amide, potassium bis(trimethylsilyl)amide, and lithium diisopropylamide. The amount of base used is typically in the range of approximately 1 mole to 10 moles relative to compound (2).

[0094] The inert solvent that can be used in step b-1 is one that does not significantly inhibit the reaction, and examples include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as dichloromethane and 1,2-dichloroethane; ethers such as tetrahydrofuran and 1,4-dioxane; and polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and 1,3-dimethyl-2-imidazolinone. These inert solvents can be used individually or in combination of two or more.

[0095] The reaction temperature in step b-1 should typically be within the range of approximately -78°C to the boiling point of the solvent used. The reaction time can be appropriately selected depending on the scale of the reaction, the reaction temperature, etc. For example, it can be selected within a range of a few minutes to 48 hours. Furthermore, this reaction can also be carried out under the atmosphere of an inert gas, such as nitrogen or argon.

[0096] After the reaction is complete, the target product can be isolated from the reaction system by conventional methods, and if necessary, purified by recrystallization, column chromatography, etc. to produce the target product. The composition containing the target product may also be used in the next step without isolation.

[0097] Furthermore, if compound (8) is an amidine compound in which E is an alkyl group, cycloalkyl group, alkylcarbonyl group, or cycloalkylcarbonyl group other than hydrogen, the desired compound (8) can be produced by reacting it with a suitable alkylating agent or acyling agent after step b-1.

[0098] <Process b-2> Compound (7); an N-substituted amidine compound can be produced by reacting compound (8); an amidine compound with an amino compound represented by formula (6) (hereinafter also referred to as compound (6)) in an inert solvent, and optionally in the presence of a base.

[0099] Examples of usable 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, relative to compound (8).

[0100] The inert solvents that can be used in step b-2 are those that do not significantly inhibit the reaction. Examples include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as dichloromethane and 1,2-dichloroethane; ethers such as tetrahydrofuran and 1,4-dioxane; polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and 1,3-dimethyl-2-imidazolinone; and alcoholic solvents such as methanol, ethanol, and 1-butanol. These inert solvents can be used individually or in combination of two or more.

[0101] In Engineering b-2, the reaction temperature may generally be within the range from about -78°C to the boiling point of the solvent used. The reaction time may be appropriately selected according to the reaction scale, reaction temperature, etc., and for example, it may be appropriately selected within the range of several minutes to 48 hours. This reaction can also be carried out, for example, under an atmosphere of an inert gas such as nitrogen gas or argon gas.

[0102] After the reaction is completed, the target product can be isolated from the reaction system containing the target product by a conventional method, and if necessary, the target product can be produced by purification with recrystallization, column chromatography, etc. The composition containing the target product may also be used in the next step without isolation.

[0103] In addition, when the compound (7) is an N-substituted amidine compound and E is other than hydrogen, an alkyl group, a cycloalkyl group, an alkylcarbonyl group, or a cycloalkylcarbonyl group, the desired compound (7) can be produced by reacting with an appropriate alkylating agent or acylating agent after <Step b-2>.

[0104] The compound (8), an amidine compound, and the compound (7), an N-substituted amidine compound, can also be produced via the compound (5), an amide compound. Here, the method for producing the compound (5), an amide compound, may include production according to the above Steps a-1 to a-2 or Step c. That is, a step of producing the compound (5), an amide compound, from the compound (2), a cyanopyridine derivative, then a step of producing the compound (8), an amidine compound, from the compound (5), an amide compound (Step d-1), and a step of reacting the amide compound related to the compound (5) with the compound (6), an amine compound, to produce the compound (7), an N-substituted amidine compound (Step d-2) can be mentioned.

[0105] 〈Production Steps d-1 to d-2 of the compound (8) and the compound (7), an amidine compound〉

Chemical formula

[0106] <Process d-1> Compound (2); a cyanopyridine derivative can be produced by the method described in steps a-1 to a-2 or step c. Compound (5); an amide compound can be produced by reacting ammonia or an ammonium compound with a reactant in an inert solvent, thereby producing compound (8); an amidine compound.

[0107] Examples of ammonium compounds that can be used in step d-1 include, but are not limited to, ammonium chloride, ammonium acetate, ammonium formate, ammonium hydroxide, and ammonium carbonate. The amount of ammonia or ammonium compound used should be appropriately selected within the range of approximately 1 to 10 times the molar amount relative to compound (5); amide compound.

[0108] Examples of reagents that can be used in step d-1 include Lewis acids such as trimethylaluminum and aluminum chloride, and chlorinating agents such as phosphorus oxychloride, phosphorus pentachloride, and carbon tetrachloride-triphenylphosphine. The amount of reagent used should be appropriately selected within the range of approximately 1 to 10 times the molar equivalent of compound (5); amide compound. Furthermore, by adding an excess of reagents such as phosphorus oxychloride, the reaction can be carried out without a solvent. A base may be applied in step d-1. Examples include alkali metal salts such as sodium hydride, sodium hydroxide, sodium carbonate, and potassium carbonate; tertiary amines such as triethylamine and N,N-diisopropylethylamine; and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine. The amount of base to be used should be appropriately selected within the range of approximately 1 to 5 molars relative to compound (5); amide compound.

[0109] Any inert solvent that does not significantly inhibit the reaction can be used in step d-1. Examples include ethers such as tetrahydrofuran, ethylene glycol dimethyl ether, and 1,4-dioxane; aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as dichloromethane and 1,2-dichloroethane; polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and 1,3-dimethyl-2-imidazolinone; and water. These inert solvents can be used individually or in combination of two or more.

[0110] The reaction temperature in step d-1 should typically be within the range of approximately -78°C to the boiling point of the solvent used. The reaction time can be appropriately selected depending on the scale of the reaction, the reaction temperature, etc. For example, it can be selected within a range of a few minutes to 48 hours. Furthermore, this reaction can also be carried out under the atmosphere of an inert gas, such as nitrogen or argon.

[0111] After the reaction is complete, the target product can be isolated from the reaction system by conventional methods, and if necessary, purified by recrystallization, column chromatography, etc. to produce the target product. The composition containing the target product may also be used in the next step without isolation.

[0112] Furthermore, if compound (8) is an amidine compound in which E is an alkyl group, cycloalkyl group, alkylcarbonyl group, or cycloalkylcarbonyl group other than hydrogen, the desired compound (8) can be produced by reacting it with a suitable alkylating agent or acyling agent after step d-1.

[0113] <Process d-2> Compound (7); an N-substituted amidine compound can be produced by reacting compound (5); an amide compound, which can be produced from compound (2); a cyanopyridine derivative by the method described in steps a-1 to a-2 or step c, with compound (6); an amine compound in an inert solvent with a reactant. Compound (6); an amine compound may be a salt formed with any acid.

[0114] Examples of reagents that can be used in step d-2 include Lewis acids such as trimethylaluminum and aluminum chloride, and chlorinating agents such as phosphorus oxychloride, phosphorus pentachloride, and carbon tetrachloride-triphenylphosphine. The amount of reagent used should be appropriately selected within the range of approximately 1 to 10 times the molar equivalent of compound (5); amide compound. Furthermore, by adding an excess of reagents such as phosphorus oxychloride, the reaction can be carried out without a solvent. A base may be applied in step d-2. Examples include alkali metal salts such as sodium hydride, sodium hydroxide, sodium carbonate, and potassium carbonate; tertiary amines such as triethylamine and N,N-diisopropylethylamine; and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine. The amount of base to be used should be appropriately selected within the range of approximately 1 to 5 molars relative to compound (5); amide compound.

[0115] The inert solvents that can be used in step d-2 are those that do not significantly inhibit the reaction, and examples include ethers such as tetrahydrofuran, ethylene glycol dimethyl ether, and 1,4-dioxane; aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as dichloromethane and 1,2-dichloroethane; polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and 1,3-dimethyl-2-imidazolinone; and water. These inert solvents can be used individually or in combination of two or more.

[0116] In Engineering d-2, the reaction temperature can generally be within the range from about -78°C to the boiling point of the solvent to be used. The reaction time can be appropriately selected according to the reaction scale, reaction temperature, etc., and for example, it can be appropriately selected within the range of several minutes to 48 hours. This reaction can also be carried out, for example, under an atmosphere of an inert gas such as nitrogen gas or argon gas.

[0117] After the reaction is completed, the target product can be isolated from the reaction system containing the target product by a conventional method, and if necessary, the target product can be produced by purification with recrystallization, column chromatography, etc. The composition containing the target product may also be used in the next step without isolation.

[0118] In addition, in the case of compound (7); an N-substituted amidine compound, when E is other than hydrogen and is an alkyl group, cycloalkyl group, alkylcarbonyl group, or cycloalkylcarbonyl group, the desired compound (7) can be produced by reacting with an appropriate alkylating agent or acylating agent after <Step d-2>.

[0119] <Method for producing compound (9); oxadiazolone compound from compound (2); cyanopyridine derivative> The present invention includes a method for producing compound (9); an oxadiazolone compound using compound (2); a cyanopyridine derivative obtained by the reaction of compound (1); a pyridin-2-ylpyridinium compound and a cyanating agent as a reaction substrate. The production method can be prepared by a commonly used production method for producing a cyclic compound via an amidine form from the cyanopyridine derivative.

[0120] In the method for producing compound (7); an N-substituted amidine compound using compound (2) obtained by the reaction of compound (1) and a cyanating agent as a reaction substrate, it can be produced by the method presented in Steps b-1 to b-2 or Step d-2, but it is not limited to this. Specifically, the process involves producing compound (7) an N-substituted amidine compound from compound (2) a cyanopyridine derivative (steps b-1 to b-2 or d-2), followed by producing compound (9) an oxadiazolon compound from compound (7) an N-substituted amidine compound (step e). A specific example of this is that the production method can be established in accordance with the method described in International Publication No. 2023 / 190286.

[0121] <Compound (9); Oxadiazolon compound manufacturing process e> [ka] [In the formula, R a , R b , R c , R d n, R2, R3, R4, R5, E, and R6 are equivalent to those stated above.

[0122] <Process e> Compound (7); an N-substituted amidine compound, which can be produced from compound (2); a cyanopyridine derivative by the method described in steps b-1 to b-2 or step d-2, can be reacted with a reagent in an inert solvent to produce compound (9); an oxadiazolon compound. In compound (7), which is a precursor for producing compound (9), R6 is a hydrogen atom and E is a hydrogen atom. Therefore, if compound (7) has R6 and E other than hydrogen atoms, it is necessary to convert it to compound (7) in which R6 and E are hydrogen atoms by an appropriate method before applying it to step e.

[0123] The reagents that can be used in step e are carbonylating agents, and examples include 1,1-carbonyldiimidazole, 1,1-thiocarbonyldiimidazole, methyl chloroformate, ethyl chloroformate, phenyl chloroformate, 4-nitrophenyl chloroformate, dibromomethane, bromochloromethane, 1,2-dichloroethane, 1,2-dibromoethane, chloroacetyl chloride, bromoacetyl chloride, and the like. The amount of reagent used should be appropriately selected within the range of approximately 1 to 20 molar equivalents relative to compound (7); the N-substituted amidine compound. A base may be used in step e. Examples include alkali metal carbonates such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and sodium bicarbonate; tertiary amines such as triethylamine and N,N-diisopropylethylamine; and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine. The amount of base used should be appropriately selected within the range of approximately 1 to 20 molar equivalents relative to compound (7); the N-substituted amidine compound.

[0124] Any inert solvent that does not significantly inhibit the reaction can be used in step e. Examples include ethers such as diethyl ether, tetrahydrofuran, and dioxane; aromatic hydrocarbons such as benzene, toluene, and xylene; polar solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, and 1,3-dimethyl-2-imidazolinone; and halogenated hydrocarbons such as dichloromethane and 1,2-dichloroethane. These inert solvents can be used individually or in combination of two or more.

[0125] The reaction temperature in step e should typically be within the range of approximately -78°C to the boiling point of the solvent used. The reaction time varies depending on the scale of the reaction, the reaction temperature, etc., but it can be appropriately selected within the range of a few minutes to 48 hours. Furthermore, this reaction can also be carried out under the atmosphere of an inert gas, such as nitrogen or argon.

[0126] After the reaction is complete, the target product can be isolated from the reaction system by conventional methods, and if necessary, purified by recrystallization, column chromatography, etc. to produce the target product. The composition containing the target product may also be used in the next step without isolation. [Examples]

[0127] Example 1: Synthesis of 1-(5-(4-chlorophenyl)-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide [ka] 2-Bromo-5-(4-chlorophenyl)-3-(ethanesulfonyl)pyridine (505 mg, 1.40 mmol) and 4-dimethylaminopyridine (188 mg, 1.54 mmol) were dissolved in N,N-dimethylacetamide (1 mL) and stirred at 120°C for 5 hours to obtain a slurry. The mixture was cooled to 20°C, toluene (10 mL) was added and stirred, then filtered by suction to obtain a solid. The solid was washed with toluene (10 mL). The obtained solid was dried with hot air to obtain 641 mg of the compound as a white solid (crude yield 94.8%). 1 H NMR(CDCl3) δ8.97(1H, s), 8.91(2H, d, J=7.8Hz), 8.62(1H, s), 7.63(2H, d, J=8.4Hz), 7.55(2H, d, J=8.4Hz), 7.12(2H, d, J=7.5Hz), 3.66(2H, q, J=7.4Hz), 3.39(6H, s), 1.44(3H, t, J= 7.4Hz)

[0128] Example 2-1: Synthesis of 1-(3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide [ka] 2-Bromo-3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)pyridine (16.6 g, 40.0 mmol in purity) and 4-dimethylaminopyridine (5.38 g, 44.0 mmol) were dissolved in N,N-dimethylacetamide (20 mL) and stirred at 120°C for 5 hours to obtain a slurry. The mixture was cooled to 20°C, toluene (160 mL) was added and stirred, then filtered by suction to obtain a solid. The solid was washed with toluene (80 mL). The obtained solid was dried with hot air to obtain 20.54 g of the compound as a white solid. 1 H NMR(CDCl3) δ8.98(1H, d, J=2.1Hz), 8.90(2H, d, J=7.8Hz), 8.63(1H, d, J=2.1Hz), 7.73(2H, d, J=8.4Hz), 7.42(2H, d, J=8.1Hz), 7.13(2H, d, J=7.8Hz), 3.65(2H, q, J=7.3Hz), 3.40(6H, s), 1.43(3H, t, J= 7.4Hz)

[0129] Example 2-2: Synthesis of 3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)picolinonitrile using 1-(3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide [ka] To the 1-(3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide (10.26 g) obtained by the method of Example 2-1, toluene (40 mL), dimethyl sulfoxide (10 mL), sodium cyanide (1.47 g), and water (3.0 mL) were added and the mixture was stirred at 40°C. After 5 hours, water was added and the mixture was separated, and the organic layer was washed with 10% hydrochloric acid and water. N,N-dimethylacetamide was added to concentrate the toluene, and the concentrate was added to 50% methanol for crystallization to obtain a solid. The obtained solid was washed with 50% methanol and dried with hot air to obtain 6.21 g of crude crystals of 3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)picolinonitrile (2 steps; crude yield 87.1%). 1H NMR(CDCl3) δ9.13(1H, d, J=2.1Hz), 8.58(1H, d, J=2.1Hz), 7.77-7.70(2H, m), 7.43(2H, d, J=7.8Hz), 3.52(2H, q, J=7.5Hz), 1.41(3H, t, J= 7.5Hz)

[0130] Example 3-1: Synthesis of 1-(3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride [ka] 2-Chloro-3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)pyridine (8.77 g, 21.4 mmol in purity) and 4-dimethylaminopyridine (3.14 g, 25.7 mmol) were dissolved in N,N-dimethylacetamide (10 mL) and stirred at 120°C for 4 hours to obtain a slurry. The mixture was cooled to 20°C, toluene (66 mL) was added and stirred, then filtered by suction to obtain a solid. The solid was washed with toluene (33 mL). The solid was dried with warm air to obtain 11.8 g of the compound as a white solid. 1 H NMR(CDCl3) 8.98(2H, d, J=6.9Hz),δ8.97(1H, s), 8.63(1H, s), 7.73(2H, d, J=8.4Hz), 7.43(2H, d, J=8.4Hz), 7.13(2H, d, J=7.2Hz), 3.72(2H, q, J=7.1Hz), 3.39(6H, s), 1.45(3H, t, J= 7.2Hz)

[0131] Example 3-2: Synthesis of 3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)picolinonitrile using 1-(3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride [ka] 11.8 g of 1-(3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride obtained by the method of Example 3-1 was mixed with dichloromethane (40 mL) and heated to 40°C. Sodium cyanide (1.47 g) was dissolved in water (3.0 mL) and added to the reaction mixture, and the mixture was stirred at the same temperature. After 3 hours, water was added and the mixture was separated, and the organic layer was washed with 10% hydrochloric acid and water. N,N-dimethylacetamide was added to concentrate the dichloromethane, and the concentrate was added to 50% methanol for crystallization to obtain a solid. The obtained solid was washed with 50% methanol and dried with hot air to obtain 6.80 g of crude crystals of 3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)picolinonitrile (2 steps; crude yield 89.2%). 1 H NMR(CDCl3) δ9.13(1H, d, J=2.1Hz), 8.58(1H, d, J=2.1Hz), 7.77-7.70(2H, m), 7.43(2H, d, J=7.8Hz), 3.52(2H, q, J=7.5Hz), 1.41(3H, t, J= 7.5Hz)

[0132] Example 3-3: Synthesis of 1-(3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride [ka] 2-Chloro-3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)pyridine (6.62 g, 16.4 mmol in purity) and 4-dimethylaminopyridine (2.41 g, 19.7 mmol) were added to toluene (20 mL) and stirred at 120°C for 5 hours to obtain a slurry. The mixture was cooled to 20°C, toluene (20 mL) was added and stirred, then filtered by suction to obtain a solid. The solid was washed with toluene (30 mL). The solid was dried with warm air to obtain 8.57 g of the compound as a white solid. 1H NMR(CDCl3) 8.98(2H, d, J=6.9Hz),δ8.97(1H, s), 8.63(1H, s), 7.73(2H, d, J=8.4Hz), 7.43(2H, d, J=8.4Hz), 7.13(2H, d, J=7.2Hz), 3.72(2H, q, J=7.1Hz), 3.39(6H, s), 1.45(3H, t, J= 7.2Hz)

[0133] Examples 3-4: Synthesis of 3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)picolinonitrile using 1-(3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride 1-(3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)-2-pyridyl)-4-(dimethylamino)pyridinium chloride (19.4 g, purity equivalent to 37.0 mmol) synthesized by the same method as in Example 3-3 was mixed with N,N-dimethylacetamide (56 mL). In a separate container, sodium cyanide (2.36 g), water (7.4 mL), and acetic acid (0.15 mL) were added to prepare an aqueous solution, which was then added to the reaction mixture and stirred at 20-25°C. After 8 hours, dichloroethane, water, and an 8% sodium hypochlorite aqueous solution were added and stirred. Then, an aqueous sodium thiosulfate solution was added and liquid-liquid was separated, and the organic layer was washed with 10% hydrochloric acid and water. After concentrating the dichloroethane with N,N-dimethylacetamide, the concentrate was added to 50% methanol and crystallized to obtain a solid. The obtained solid was washed with 50% methanol and dried with hot air to obtain 12.0 g of crude crystals of 3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)picolinonitrile (crude yield 90.9%). 1 H NMR(CDCl3) δ9.13(1H, d, J=2.1Hz), 8.58(1H, d, J=2.1Hz), 7.77-7.70(2H, m), 7.43(2H, d, J=7.8Hz), 3.52(2H, q, J=7.5Hz), 1.41(3H, t, J= 7.5Hz)

[0134] Example 4-1: Synthesis of 1-(3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)-2-pyridyl)-4-(1-pyrrolidyl)pyridinium bromide [ka] 2-Bromo-3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)pyridine (802 mg, 2.00 mmol) and 4-pyrrolidinopyridine (326 mg, 2.20 mmol) were dissolved in N,N-dimethylformamide (1 mL) and stirred at 110°C for 5 hours. The mixture was cooled to 20°C, toluene (10 mL) was added and stirred, then filtered by suction to obtain a solid. The solid was washed with toluene (10 mL). The solid was dried with warm air to obtain 1.14 g of the compound as a white solid. 1 H NMR(CDCl3) δ8.98(1H, s), 8.87(2H, d, J=7.2Hz), 8.63(1H, s), 7.73(2H, d, J=8.4Hz), 7.43(2H, d, J=8.4Hz), 6.98(2H, d, J=7.2Hz), 3.69-3.62(6H, m), 2.22(4H, br), 1.44(3H, t, J= 7.2Hz)

[0135] Example 4-2: Synthesis of 3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)picolinonitrile using 1-(3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)-2-pyridyl)-4-(1-pyrrolidyl)pyridinium bromide [ka] 1.14 g of 1-(3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)-2-pyridyl)-4-(1-pyrrolidyl)pyridinium bromide obtained by the method of Example 4-1 was mixed with dichloromethane (5.0 mL) and stirred. Sodium cyanide (147 mg) was dissolved in water (0.50 mL) and added to the reaction mixture, and stirred at 40°C. After 4 hours, water was added and the mixture was separated, and the organic layer was washed with saturated ammonium chloride aqueous solution. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain 0.36 g of 3-(ethanesulfonyl)-5-(4-(trifluoromethoxy)phenyl)picolinonitrile. 1 H NMR(CDCl3) δ9.13(1H, d, J=2.1Hz), 8.58(1H, d, J=2.1Hz), 7.77-7.70(2H, m), 7.43(2H, d, J=7.8Hz), 3.52(2H, q, J=7.5Hz), 1.41(3H, t, J= 7.5Hz)

[0136] Example 5-1: Synthesis of 1-(5-cyclopropyl-3-(ethanesulfonyl)-2-pyridyl)-4-(dimethylamino)pyridinium bromide [ka] 2-Bromo-5-cyclopropyl-3-(ethanesulfonyl)pyridine (290 mg, 0.80 mmol) and 4-dimethylaminopyridine (58.8 mg, 1.20 mmol) were dissolved in N,N-dimethylformamide (0.5 mL) and stirred at 110°C for 5 hours. The mixture was cooled to 20°C, toluene (10 mL) was added and stirred, then filtered by suction to obtain a solid. The solid was washed with toluene (10 mL). The solid was dried with hot air to obtain 327 mg of the compound as a white solid. 1 H NMR(CDCl3) δ8.75(2H, d, J=4.8Hz), 8.56(1H, s), 8.05(1H, s), 7.13(2H, d, J=7.2Hz), 3.54(2H, q, J=7.2Hz), 3.38(6H, s), 2.14-2.09(1H, m), 1.39(3H, t, J= 7.4Hz), 1.32-1.28(2H, m), 0.98-0.95(2H, m)

[0137] From the 3-(ethanesulfonyl)picolinonitrile derivative corresponding to compound (2) in this application, the corresponding compound (5); amide compound can be produced in accordance with the method described in International Publication 2023 / 190286. From the 3-(ethanesulfonyl)picolinonitrile derivative corresponding to compound (2) in this application, the corresponding compound (7); N-substituted amidine compound can be produced in accordance with the methods described in International Publication 2020 / 054712, International Publication 2021 / 177410, or International Publication 2023 / 190286. From the 3-(ethanesulfonyl)picolinonitrile derivative corresponding to compound (2) in this application, the corresponding compound (8); amidine compound can be produced in accordance with the methods described in International Publication 2020 / 054712 and International Publication 2021 / 177410. From the 3-(ethanesulfonyl)picolinonitrile derivative corresponding to compound (2) in this application, the corresponding compound (9); oxadiazolon compound can be produced in accordance with the method described in International Publication 2023 / 190286.

[0138] The synthesis methods for compounds (5), (7), (8), and (9) corresponding to compound (2) are described below.

[0139] Example 6-1: Synthesis of 3-(ethylthio)-5-(4-(trifluoromethoxy)phenyl)-picolinic acid [ka] 3-(ethylthio)-5-(4-(trifluoromethoxy)phenyl)picolinonitrile (2.00 g, 6.17 mmol) was dissolved in ethanol (60 mL) and dioxane (20 mL), and 25% sodium hydroxide aqueous solution (50.0 g, 308 mmol) was added, and the mixture was stirred under reflux for 5 hours. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The resulting residue was diluted with water and 1N hydrochloric acid, and then extracted three times with ethyl acetate. The resulting organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure, and the resulting composition was suspended in a mixture of ethyl acetate and hexane. The suspension was filtered to obtain the target product (2.18 g, quant.) as a filtrate. 1 H NMR(CDCl3) δ 10.90 (1H, br), 8.47 (1H, d, J = 1.8 Hz), 7.49 (1H, d, J = 1.5 Hz), 7.66-7.61 (2H, m), 7.39 (2H, d, J = 8.1 Hz), 3.04 (2H, q, J = 7.5 Hz), 1.48 (3H, t, J = 7.5 Hz)

[0140] Example 6-2-3: Synthesis of 3-(ethylthio)-5-(4-(trifluoromethoxy)phenyl)-N-(5-(trifluoromethyl)pyridine-2-yl)picolinamide [ka] The product from Example 6-1 (5.22 g, 15.2 mmol) was dissolved in dichloromethane (140 mL), and oxalyl chloride (2.61 mL, 30.4 mmol) and dimethylformamide (500 μL) were added, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was then concentrated under reduced pressure, and the resulting residue was dissolved in tetrahydrofuran (120 mL). 2-amino-5-trifluoromethylpyridine (3.20 g, 19.7 mmol) and triethylamine (11 mL, 78.9 mmol) were added, and the mixture was stirred at room temperature for 4.5 hours. Water and saturated saline solution were added to the reaction mixture, and the mixture was extracted three times with ethyl acetate. The resulting organic layer was dried over anhydrous magnesium sulfate and then filtered. The filtrate was then concentrated under reduced pressure, and the resulting crude product was purified by silica gel chromatography to obtain the target product (3.46 g, 46.7%). 1H NMR(CDCl3) δ 10.83 (1H, s), 8.63-8.60 (2H, m), 8.53 (1H, d, J = 1.8 Hz), 7.97 (1H, dd, J = 9.0, 1.8 Hz), 7.81 (1H, d, J = 1.5 Hz), 7.65 (2H, d, J = 8.7 Hz), 7.39 (2H, d, J = 8.4 Hz), 3.04 (2H, q, J = 7.5 Hz), 1.49 (3H, t, J = 7.2 Hz)

[0141] Example 6-3: Synthesis of 3-(ethylsulfonyl)-5-(4-(trifluoromethoxyphenyl)-N-(5-(trifluoromethyl)pyridine-2-yl)picolinamide [ka] The product from Example 6-2 (190 mg, 0.390 mmol) was dissolved in dichloromethane (7 mL), and 3-chloroperbenzoic acid (65%, 208 mg, 0.783 mmol) was added, and the mixture was stirred at room temperature for 7 hours. After adding an aqueous sodium bicarbonate solution to the reaction mixture, it was extracted with ethyl acetate. The resulting organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was then concentrated under reduced pressure, and the resulting crude product was purified by silica gel chromatography to obtain the target product (177 mg, 87.4%). 1 H NMR(CDCl3) δ 10.35 (1H, s), 9.04 (1H, d, J = 2.1 Hz), 8.82 (1H, d, J = 2.1 Hz), 8.65 (1H, br), 8.56 (1H, d, J = 8.7 Hz), 8.01 (1H, dd, J = 9.0, 2.4 Hz), 7.76-7.73 (2H, m), 7.43 (2H, d, J = 8.1 Hz), 4.00 (2H, q, J = 7.5 Hz), 1.41 (3H, t, J = 7.5 Hz)

[0142] Example 6-4: Synthesis of 3-(ethylsulfonyl)-N'-hydroxy-5-(4-(trifluoromethoxy)phenyl)-N-(5-(trifluoromethyl)pyridine-2-yl)picoline imidamide [ka] 3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)-N-(5-(trifluoromethyl)pyridine-2-yl)picolinamide (218 mg, 0.42 mmol) prepared in Example 6-3 was dissolved in acetonitrile (7 mL), carbon tetrachloride (122 μL, 1.25 mmol) and triphenylphosphine (0.66 g, 2.52 mmol) were added, and the mixture was stirred under reflux for 1 hour. After cooling to room temperature, 1 mL of a 50% hydroxylamine aqueous solution was added dropwise, and the mixture was stirred overnight at room temperature. Most of the acetonitrile in the reaction mixture was removed by distillation, and the mixture was purified by silica gel chromatography to obtain the target product (185 mg, 87.7%). 1 H NMR(CDCl3)δ8.97(1H, d, J=2.4Hz), 8.57(1H, d, J=2.1Hz), 8.14(1H, s), 7.76-7.6 9(2H, m), 7.65(1H, dd, J=8.7, 2.4Hz), 7.40(2H, d, J=8.1Hz), 6.63(1H, d, J=8.7Hz), 3.60(2H, q, J=7.5Hz), 1.36(3H, t, J=7.5Hz)

[0143] Example 6-5: Synthesis of 3-(3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)pyridine-2-yl)-4-(5-(trifluoromethyl)pyridine-2-yl)-1,2,4-oxadiazole-(4H)-one) [ka] 3-(ethylsulfonyl)-N'-hydroxy-5-(4-(trifluoromethoxy)phenyl)-N-(6-(trifluoromethyl)pyridine-3-yl)picoline imidamide (110 mg, 0.21 mmol) prepared in Example 6-4 was dissolved in tetrahydrofuran (13 mL), 1,1'-carbonylimidazole (52 mg, 0.31 mmol) was added, and the mixture was stirred at room temperature for 3 hours. Most of the tetrahydrofuran in the reaction mixture was removed by distillation, and the mixture was purified by silica gel chromatography to obtain the target product (85 mg, 73.4%). 1 H NMR(CDCl3)δ9.05(1H, d, J=2.1Hz), 8.58(1H, d, J=2.1Hz), 8.26(2H, d, J=9.3Hz), 8.08(1H, dd, J=2.4, 7.9Hz), 7.78-7.74(2H, m), 7.45(2H, d, J=7.8Hz), 3.51(2H, q, J=7.5Hz), 1.39(3H, t, J=7.5Hz)

[0144] Example 7-1: Synthesis of 3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)-N-(4-(trifluoromethyl)pyridine-2-yl)picoline imidamide [ka] 3-(ethylsulfonyl)-5-(4-(trifluoromethoxy)phenyl)picolinonitrile (122.0 g, 0.34 mol) and 4-(trifluoromethyl)pyridine-2-amine (58.0 g, 0.36 mol) were dissolved in toluene (760 mL) and the mixture was heated to 60°C. Titanium tetrachloride (49.0 mL, 0.45 mol) was added, and the mixture was stirred at 90°C for 4 hours. In a separate flask, an aqueous solution of sodium bicarbonate (water: 840 mL, sodium bicarbonate: 220 g) and isopropanol (200 mL) were added. After cooling to 0-10°C, the reaction was terminated by adding the reaction solution dropwise. The residue remaining in the reaction flask was dissolved in isopropanol (220 mL) and toluene (77 mL) and added dropwise in the same manner. The mixture was stirred at room temperature for 10 minutes, then heated to 70°C, and separated. The resulting organic layer was washed with water (680 mL), and N,N-dimethylacetamide (680 mL) was added and dissolved. Insoluble titanium residue was removed by Kiriyama filtration. Subsequently, solvent removal and crystallization were performed to obtain 155.76 g of the target product (purity: 98.3%, yield: 87.7%). 1 H NMR(CDCl3) δ9.01(1H, d, J=2.1Hz), 8.68(1H, d, J=2.1Hz), 8.57(1H, d, J=5.4Hz), 7.74-7.69(2H, m), 7.41(2H, d, J=8.1Hz), 7.30(1H, s), 7.21(1H, dd, J=1.2, 5.3Hz), 4.07(2H, q, J=7.5Hz), 1.43(3H, t, J=7.5Hz)

[0145] Example 7-2: Synthesis of 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 (38.34 g, 78.8 mmol) and hydroxyamine hydrochloride (21.90 g, 315 mmol) were dissolved in acetonitrile (500 mL). After stirring under reflux conditions for 4 hours, the mixture was filtered. Subsequently, 100 mL of the solvent was removed using a rotary evaporator, and 400 mL of water was added. The mixture was then filtered again, and the residue was washed three times with water (50 mL) to obtain 37.18 g of the target product. 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)

[0146] Example 7-3: Synthesis of 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 THF (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. 1H 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 compound represented by formula (1). 【Chemistry 1】 [In formula (1), A － This includes halogen ions, unsubstituted or substituted benzenesulfonate ions, and unsubstituted or substituted (C １ ~C ８ ) Represents an ionic species selected from the group consisting of alkyl sulfonate ions, X, when there are a plurality of them, each independently represents a halogen atom, an unsubstituted or substituted (C １ ~C ６ ) alkyl group, an unsubstituted or substituted (C １ ~C ６ ) alkoxy group, and a group selected from the group consisting of NY １ Y ２ groups, Y １ and Y ２ Each of these independently consists of a hydrogen atom, an unsubstituted or substituted (C １ ~C ６ ) alkyl groups, unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, or unsubstituted or substituted (C １ ~C ６ ) Represents an alkoxy group, or Y １ and Y ２ This may be an unsubstituted or substituted 3- to 8-membered saturated heterocycle formed together with the nitrogen atom to which it is bonded. m is an integer between 0 and 5. If m is 2 or greater, X can be the same or different. n is an integer between 0 and 2. R a (C) is either unsubstituted or substituted. １ ~C ６ ) alkyl groups, unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, and NY ３ Y ４ This represents a group selected from a group of groups, Y ３ and Y ４ Each of these independently consists of a hydrogen atom, an unsubstituted or substituted (C １ ~C ６ ) alkyl groups, unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, and unsubstituted or substituted (C １ ~C ６ ) Represents a group selected from the group consisting of alkoxy groups, or Y ３ and Y ４ This may be an alkylene group that forms a 3-8 membered ring cyclic amino group with a nitrogen atom that is bonded together. R ｂ , R ｃ and R ｄ Each of them operates independently. hydrogen atom, halogen atom, Unsubstituted or substituted (C １ ~C ６ ) alkyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynyl group, Unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, Unsubstituted or substituted (C １ ~C ６ ) Alkoxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenyloxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynyloxy group, Unsubstituted or substituted (C ３ ~C ６ ) Cycloalkoxy group, Unsubstituted or substituted (C １ ~C ６ ) Alkyl carbonyl group, Unsubstituted or substituted (C ３ ~C ６ ) Cycloalkylcarbonyl group, Unsubstituted or substituted (C １ ~C ６ ) Alkoxycarbonyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenyloxycarbonyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynyloxycarbonyl group, Unsubstituted or substituted (C １ ~C ６ ) Alkylcarbonyloxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenylcarbonyloxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynylcarbonyloxy group, Unsubstituted or substituted (C １ ~C ６ ) alkylthio group, Unsubstituted or substituted (C １ ~C ６ ) alkylsulfinyl group, Unsubstituted or substituted (C １ ~C ６ ) alkylsulfonyl group, Unsubstituted or substituted (C １ ~C ６ ) Alkyl sulfonyl oxy group, Unsubstituted or substituted phenyl groups, Unsubstituted or substituted heterocyclic groups, Unsubstituted or substituted phenoxy groups, Unsubstituted or substituted pyridyloxy groups, NY ５ Y ６ Base, C(O)NY ５ Y ６ Groups: cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxyl group, trimethylsilyl group, and SF ５ This represents a group selected from a group of groups, Y ５ and Y ６ When there are a plurality of them, each independently represents a hydrogen atom, an unsubstituted or substituted (C １ ~C ６ alkyl group, an unsubstituted or substituted (C ２ ~C ６ alkenyl group, an unsubstituted or substituted (C ３ ~C ６ cycloalkyl group, an unsubstituted or substituted (C １ ~C ６ alkoxy group, an unsubstituted or substituted (C １ ~C ６ alkylcarbonyl group, an unsubstituted or substituted (C １ ~C ６ alkoxycarbonyl group, an unsubstituted or substituted phenyl group, an unsubstituted or substituted heterocyclic group, a cyano group, or a hydroxy group, and represents a group selected from the group consisting of these.]]

2. m is between 1 and 5. If there are multiple X's, each can be independently either unsubstituted or substituted (C １ ~C ６ ) Alkoxy group, and NY １ Y ２ A group selected from the group consisting of, The compound according to claim 1.

3. R ｂ , R ｃ and R ｄ Which one is Unsubstituted or substituted (C １ ~C ６ ) alkyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynyl group, Unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, Unsubstituted or substituted (C １ ~C ６ ) Alkoxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenyloxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynyloxy group, Unsubstituted or substituted (C ３ ~C ６ ) Cycloalkoxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenylcarbonyloxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynylcarbonyloxy group, Unsubstituted or substituted (C １ ~C ６ ) alkylthio group, Unsubstituted or substituted (C １ ~C ６ ) alkylsulfinyl group, Unsubstituted or substituted (C １ ~C ６ ) alkylsulfonyl group, Unsubstituted or substituted (C １ ~C ６ ) Alkyl sulfonyl oxy group, Unsubstituted or substituted phenyl groups, Unsubstituted or substituted heterocyclic groups, Unsubstituted or substituted phenoxy groups, Unsubstituted or substituted pyridyloxy groups, This represents a group selected from the group consisting of, The others are hydrogen atoms or halogen atoms. The compound according to claim 1 or 2.

4. Compound represented by formula (1); 【Chemistry 2】 [In formula (1), A － This includes halogen ions, unsubstituted or substituted benzenesulfonate ions, and unsubstituted or substituted (C １ ~C ８ ) Represents an ionic species selected from the group consisting of alkyl sulfonate ions, If there are multiple X atoms, each can independently be a halogen atom, unsubstituted, or substituted (C １ ~C ６ ) alkyl groups, unsubstituted or substituted (C １ ~C ６ ) Alkoxy group, and NY １ Y ２ This represents a group selected from a group of groups, Y １ and Y ２ Each of these independently consists of a hydrogen atom, an unsubstituted or substituted (C １ ~C ６ ) alkyl groups, unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, or unsubstituted or substituted (C １ ~C ６ ) Represents an alkoxy group, or Y １ and Y ２ This may be an unsubstituted or substituted 3- to 8-membered saturated heterocycle formed together with the nitrogen atom to which it is bonded. m is an integer between 0 and 5. If m is 2 or greater, X can be the same or different. n is an integer between 0 and 2. R a (C) is either unsubstituted or substituted. １ ~C ６ ) alkyl groups, unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, and NY ３ Y ４ This represents a group selected from a group of groups, Y ３ and Y ４ Each of these independently consists of a hydrogen atom, an unsubstituted or substituted (C １ ~C ６ ) alkyl groups, unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, and unsubstituted or substituted (C １ ~C ６ ) Represents a group selected from the group consisting of alkoxy groups, or Y ３ and Y ４ This may be an alkylene group that forms a 3-8 membered ring cyclic amino group with a nitrogen atom that is bonded together. R ｂ , R ｃ and R ｄ Each of them operates independently. hydrogen atom, halogen atom, Unsubstituted or substituted (C １ ~C ６ ) alkyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynyl group, Unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, Unsubstituted or substituted (C １ ~C ６ ) Alkoxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenyloxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynyloxy group, Unsubstituted or substituted (C ３ ~C ６ ) Cycloalkoxy group, Unsubstituted or substituted (C １ ~C ６ ) Alkyl carbonyl group, Unsubstituted or substituted (C ３ ~C ６ ) Cycloalkylcarbonyl group, Unsubstituted or substituted (C １ ~C ６ ) Alkoxycarbonyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenyloxycarbonyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynyloxycarbonyl group, Unsubstituted or substituted (C １ ~C ６ ) Alkylcarbonyloxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenylcarbonyloxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynylcarbonyloxy group, Unsubstituted or substituted (C １ ~C ６ ) alkylthio group, Unsubstituted or substituted (C １ ~C ６ ) alkylsulfinyl group, Unsubstituted or substituted (C １ ~C ６ ) alkylsulfonyl group, Unsubstituted or substituted (C １ ~C ６ ) Alkyl sulfonyl oxy group, Unsubstituted or substituted phenyl groups, Unsubstituted or substituted heterocyclic groups, Unsubstituted or substituted phenoxy groups, Unsubstituted or substituted pyridyloxy groups, NY ５ Y ６ Base, C(O)NY ５ Y ６ Groups: cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxyl group, trimethylsilyl group, and SF ５ This represents a group selected from a group of groups, Y ５ and Y ６ If multiple atoms exist, each will independently be a hydrogen atom, unsubstituted, or substituted (C １ ~C ６ ) alkyl groups, unsubstituted or substituted (C ２ ~C ６ ) Alkenyl group, unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, unsubstituted or substituted (C １ ~C ６ ) an alkoxy group, unsubstituted or substituted (C １ ~C ６ ) Alkylcarbonyl group, unsubstituted or substituted (C １ ~C ６ ) This represents a group selected from the group consisting of an alkoxycarbonyl group, an unsubstituted or substituted phenyl group, an unsubstituted or substituted heterocyclic group, a cyano group, and a hydroxyl group. Then, react with a cyanating agent, A cyanopyridine compound represented by formula (2); 【Transformation 3】 [In formula (2), R a , R ｂ , R ｃ , R ｄ , and n are the same as above. ], to manufacture, A method for producing cyanopyridine derivatives.

5. The cyanating agents are HCN, LiCN, NaCN, KCN, BrCN, CuCN, and Zn(CN). ２ The manufacturing method according to claim 4, wherein the compound is one or more compounds selected from the group consisting of acetone cyanohydrin and trimethylsilyl cyanide.

6. m is between 1 and 5. If there are multiple X's, each can be independently either unsubstituted or substituted (C １ ~C ６ ) Alkoxy group, and NY １ Y ２ A group selected from the group consisting of, The manufacturing method according to claim 4 or 5.

7. [Step A]; Compound represented by formula (1); 【Chemistry 4】 [In formula (1), A － This includes halogen ions, unsubstituted or substituted benzenesulfonate ions, and unsubstituted or substituted (C １ ~C ８ ) Represents an ionic species selected from the group consisting of alkyl sulfonate ions, If there are multiple X atoms, each can independently be a halogen atom, unsubstituted, or substituted (C １ ~C ６ ) alkyl groups, unsubstituted or substituted (C １ ~C ６ ) Alkoxy group, and NY １ Y ２ This represents a group selected from a group of groups, Y １ and Y ２ Each of these independently consists of a hydrogen atom, an unsubstituted or substituted (C １ ~C ６ ) alkyl groups, unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, or unsubstituted or substituted (C １ ~C ６ ) Represents an alkoxy group, or Y １ and Y ２ This may be an unsubstituted or substituted 3- to 8-membered saturated heterocycle formed together with the nitrogen atom to which it is bonded. m is an integer between 0 and 5. If m is 2 or greater, X can be the same or different. n is an integer between 0 and 2. R a (C) is either unsubstituted or substituted. １ ~C ６ ) alkyl groups, unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, and NY ３ Y ４ This represents a group selected from a group of groups, Y ３ and Y ４ Each of these independently consists of a hydrogen atom, an unsubstituted or substituted (C １ ~C ６ ) alkyl groups, unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, and unsubstituted or substituted (C １ ~C ６ ) Represents a group selected from the group consisting of alkoxy groups, or Y ３ and Y ４ This may be an alkylene group that forms a 3-8 membered ring cyclic amino group with a nitrogen atom that is bonded together. R ｂ , R ｃ and R ｄ Each of them operates independently. hydrogen atom, halogen atom, Unsubstituted or substituted (C １ ~C ６ ) alkyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynyl group, Unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, Unsubstituted or substituted (C １ ~C ６ ) Alkoxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenyloxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynyloxy group, Unsubstituted or substituted (C ３ ~C ６ ) Cycloalkoxy group, Unsubstituted or substituted (C １ ~C ６ ) Alkyl carbonyl group, Unsubstituted or substituted (C ３ ~C ６ ) Cycloalkylcarbonyl group, Unsubstituted or substituted (C １ ~C ６ ) Alkoxycarbonyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenyloxycarbonyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynyloxycarbonyl group, Unsubstituted or substituted (C １ ~C ６ ) Alkylcarbonyloxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenylcarbonyloxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynylcarbonyloxy group, Unsubstituted or substituted (C １ ~C ６ ) alkylthio group, Unsubstituted or substituted (C １ ~C ６ ) alkylsulfinyl group, Unsubstituted or substituted (C １ ~C ６ ) alkylsulfonyl group, Unsubstituted or substituted (C １ ~C ６ ) Alkyl sulfonyl oxy group, Unsubstituted or substituted phenyl groups, Unsubstituted or substituted heterocyclic groups, Unsubstituted or substituted phenoxy groups, Unsubstituted or substituted pyridyloxy groups, NY ５ Y ６ Base, C(O)NY ５ Y ６ Groups: cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxyl group, trimethylsilyl group, and SF ５ This represents a group selected from a group of groups, Y ５ and Y ６ If multiple atoms exist, each will independently be a hydrogen atom, unsubstituted, or substituted (C １ ~C ６ ) alkyl groups, unsubstituted or substituted (C ２ ~C ６ ) Alkenyl group, unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, unsubstituted or substituted (C １ ~C ６ ) an alkoxy group, unsubstituted or substituted (C １ ~C ６ ) Alkylcarbonyl group, unsubstituted or substituted (C １ ~C ６ ) This represents a group selected from the group consisting of an alkoxycarbonyl group, an unsubstituted or substituted phenyl group, an unsubstituted or substituted heterocyclic group, a cyano group, and a hydroxyl group. Then, react with a cyanating agent, Cyanopyridine compounds represented by formula (2); 【Transformation 5】 [In formula (2), R a , R ｂ , R ｃ , R ｄ , and n are the same as above. The process of manufacturing ] [Step B]; the cyanopyridine compound of formula (2) Carboxy compounds represented by formula (3); 【Transformation 6】 [In equation (3), R ａ , R ｂ , R ｃ , R ｄ And n is the same as above. ], the process of converting, [Step C]; A carboxyl compound represented by formula (3), Pyridylamine compound of formula (4); 【Transformation 7】 [In equation (4), R ２ , R ３ , R ４ and R ５ Each of them operates independently. hydrogen atom, halogen atom, Unsubstituted or substituted (C １ ~C ６ ) alkyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynyl group, Unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, Unsubstituted or substituted (C １ ~C ６ ) Alkoxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenyloxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynyloxy group, Unsubstituted or substituted (C ３ ~C ６ ) Cycloalkoxy group, Unsubstituted or substituted (C １ ~C ６ ) Alkyl carbonyl group, Unsubstituted or substituted (C ３ ~C ６ ) Cycloalkylcarbonyl group, Unsubstituted or substituted (C １ ~C ６ ) Alkoxycarbonyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenyloxycarbonyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynyloxycarbonyl group, Unsubstituted or substituted (C １ ~C ６ ) Alkylcarbonyloxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenylcarbonyloxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynylcarbonyloxy group, Unsubstituted or substituted (C １ ~C ６ ) alkylthio group, Unsubstituted or substituted (C １ ~C ６ ) alkylsulfinyl group, Unsubstituted or substituted (C １ ~C ６ ) alkylsulfonyl group, Unsubstituted or substituted (C １ ~C ６ ) Alkyl sulfonyl oxy group, Unsubstituted or substituted phenyl groups, Unsubstituted or substituted heterocyclic groups, Unsubstituted or substituted phenoxy groups, Unsubstituted or substituted pyridyloxy groups, NY ５ Y ６ Base, C(O)NY ５ Y ６ Groups: cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxyl group, trimethylsilyl group, and SF ５ This represents a group selected from a group of groups, Y ５ and Y ６ This is synonymous with the above. ] reacts with, Amide compounds represented by formula (5); 【Transformation 8】 [In equation (5), E is a hydrogen atom, unsubstituted or substituted (C １ ~C ６ ) alkyl groups, unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, unsubstituted or substituted (C １ ~C ６ ) Alkylcarbonyl group, unsubstituted or substituted (C ３ ~C ６ ) A group selected from the group consisting of cycloalkylcarbonyl groups, R a , R ｂ , R ｃ , R ｄ ,n,R ２ , R ３ , R ４ , R ５ This is synonymous with the above. The process includes manufacturing ] A method for producing pyridine derivatives having sulfur-containing substituents.

8. [Step D]; The amide compound represented by formula (5) obtained in Step C, Amine compounds represented by formula (6); 【Chemistry 9】 [In equation (6), 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 ) Alkyl carbonyl group, It may have substituents (C 3 ~C ６ ) Cycloalkylcarbonyl group It represents a group selected from the group consisting of . ] reacts with , N-substituted amidine compounds represented by formula (7); 【Chemistry 10】 [(In equation (7), R ａ , R ｂ , R ｃ , R ｄ , R ２ , R ３ , R ４ , R ５ , R ６ , E and n are as defined above. The process includes manufacturing ] A method for producing a pyridine derivative having a sulfur-containing substituent as described in claim 7.

9. [Step A]; Compound represented by formula (1); 【Chemistry 11】 [In formula (1), A － This includes halogen ions, unsubstituted or substituted benzenesulfonate ions, and unsubstituted or substituted (C １ ~C ８ ) Represents an ionic species selected from the group consisting of alkyl sulfonate ions, If there are multiple X atoms, each can independently be a halogen atom, unsubstituted, or substituted (C １ ~C ６ ) alkyl groups, unsubstituted or substituted (C １ ~C ６ ) Alkoxy group, and NY １ Y ２ This represents a group selected from a group of groups, Y １ and Y ２ Each of these independently consists of a hydrogen atom, an unsubstituted or substituted (C １ ~C ６ ) alkyl groups, unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, or unsubstituted or substituted (C １ ~C ６ ) Represents an alkoxy group, or Y １ and Y ２ This may be an unsubstituted or substituted 3- to 8-membered saturated heterocycle formed together with the nitrogen atom to which it is bonded. m is an integer between 0 and 5. If m is 2 or greater, X can be the same or different. n is an integer between 0 and 2. R a (C) is either unsubstituted or substituted. １ ~C ６ ) alkyl groups, unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, and NY ３ Y ４ This represents a group selected from a group of groups, Y ３ and Y ４ Each of these independently consists of a hydrogen atom, an unsubstituted or substituted (C １ ~C ６ ) alkyl groups, unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, and unsubstituted or substituted (C １ ~C ６ ) Represents a group selected from the group consisting of alkoxy groups, or Y ３ and Y ４ This may be an alkylene group that forms a 3-8 membered ring cyclic amino group with a nitrogen atom that is bonded together. R ｂ , R ｃ and R ｄ Each of them operates independently. hydrogen atom, halogen atom, Unsubstituted or substituted (C １ ~C ６ ) alkyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynyl group, Unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, Unsubstituted or substituted (C １ ~C ６ ) Alkoxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenyloxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynyloxy group, Unsubstituted or substituted (C ３ ~C ６ ) Cycloalkoxy group, Unsubstituted or substituted (C １ ~C ６ ) Alkyl carbonyl group, Unsubstituted or substituted (C ３ ~C ６ ) Cycloalkylcarbonyl group, Unsubstituted or substituted (C １ ~C ６ ) Alkoxycarbonyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenyloxycarbonyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynyloxycarbonyl group, Unsubstituted or substituted (C １ ~C ６ ) Alkylcarbonyloxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenylcarbonyloxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynylcarbonyloxy group, Unsubstituted or substituted (C １ ~C ６ ) alkylthio group, Unsubstituted or substituted (C １ ~C ６ ) alkylsulfinyl group, Unsubstituted or substituted (C １ ~C ６ ) alkylsulfonyl group, Unsubstituted or substituted (C １ ~C ６ ) Alkyl sulfonyl oxy group, Unsubstituted or substituted phenyl groups, Unsubstituted or substituted heterocyclic groups, Unsubstituted or substituted phenoxy groups, Unsubstituted or substituted pyridyloxy groups, NY ５ Y ６ Base, C(O)NY ５ Y ６ Groups: cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxyl group, trimethylsilyl group, and SF ５ This represents a group selected from a group of groups, Y ５ and Y ６ If multiple atoms exist, each will independently be a hydrogen atom, unsubstituted, or substituted (C １ ~C ６ ) alkyl groups, unsubstituted or substituted (C ２ ~C ６ ) Alkenyl group, unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, unsubstituted or substituted (C １ ~C ６ ) an alkoxy group, unsubstituted or substituted (C １ ~C ６ ) Alkylcarbonyl group, unsubstituted or substituted (C １ ~C ６ ) This represents a group selected from the group consisting of an alkoxycarbonyl group, an unsubstituted or substituted phenyl group, an unsubstituted or substituted heterocyclic group, a cyano group, and a hydroxyl group. Then, react with a cyanating agent, Cyanopyridine compounds represented by formula (2); 【Chemistry 12】 [In formula (2), R a , R ｂ , R ｃ , R ｄ , and n are the same as above. The process of manufacturing ] [Step E]; A cyanopyridine compound represented by formula (2), Pyridylamine compound of formula (4); 【Chemistry 13】 [In equation (4), R ２ , R ３ , R ４ and R ５ Each of them operates independently. hydrogen atom, halogen atom, Unsubstituted or substituted (C １ ~C ６ ) alkyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynyl group, Unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, Unsubstituted or substituted (C １ ~C ６ ) Alkoxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenyloxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynyloxy group, Unsubstituted or substituted (C ３ ~C ６ ) Cycloalkoxy group, Unsubstituted or substituted (C １ ~C ６ ) Alkyl carbonyl group, Unsubstituted or substituted (C ３ ~C ６ ) Cycloalkylcarbonyl group, Unsubstituted or substituted (C １ ~C ６ ) Alkoxycarbonyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenyloxycarbonyl group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynyloxycarbonyl group, Unsubstituted or substituted (C １ ~C ６ ) Alkylcarbonyloxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkenylcarbonyloxy group, Unsubstituted or substituted (C ２ ~C ６ ) Alkynylcarbonyloxy group, Unsubstituted or substituted (C １ ~C ６ ) alkylthio group, Unsubstituted or substituted (C １ ~C ６ ) alkylsulfinyl group, Unsubstituted or substituted (C １ ~C ６ ) alkylsulfonyl group, Unsubstituted or substituted (C １ ~C ６ ) Alkyl sulfonyl oxy group, Unsubstituted or substituted phenyl groups, Unsubstituted or substituted heterocyclic groups, Unsubstituted or substituted phenoxy groups, Unsubstituted or substituted pyridyloxy groups, NY ５ Y ６ Base, C(O)NY ５ Y ６ Groups: cyano group, nitro group, hydroxy group, mercapto group, amino group, formyl group, carboxyl group, trimethylsilyl group, and SF ５ This represents a group selected from a group of groups, Y ５ and Y ６ This is synonymous with the above. ] reacts with, Amidine compounds represented by formula (8); 【Chemistry 14】 [(In equation (8), E is a hydrogen atom, unsubstituted or substituted (C １ ~C ６ ) alkyl groups, unsubstituted or substituted (C ３ ~C ６ ) Cycloalkyl groups, unsubstituted or substituted (C １ ~C ６ ) Alkylcarbonyl group, unsubstituted or substituted (C ３ ~C ６ ) A group selected from the group consisting of cycloalkylcarbonyl groups, R ａ , R ｂ , R ｃ , R ｄ , R ２ , R ３ , R ４ , R ５ And n is the same as above. The process includes manufacturing ] A method for producing pyridine derivatives having sulfur-containing substituents.

10. [Step F]; The amidine compound represented by formula (8) obtained in Step E, Amine compounds represented by formula (6); 【Chemistry 15】 [In equation (6), 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 ) Alkyl carbonyl group, It may have substituents (C 3 ~C ６ ) Cycloalkylcarbonyl group It represents a group selected from the group consisting of . ] reacts with , N-substituted amidine compounds represented by formula (7); 【Chemistry 16】 [(In equation (7), R ａ , R ｂ , R ｃ , R ｄ , R ２ , R ３ , R ４ , R ５ , R ６ , E and n are as defined above. The process includes manufacturing ] A method for producing a pyridine derivative having a sulfur-containing substituent as described in claim 9.

11. [Step G]; an N-substituted amidine compound represented by formula (7) obtained in step D or step F, React with a carbonylating agent, Oxadiazolon compounds represented by formula (9); 【Chemistry 17】 [In equation (9), R ａ , R ｂ , R ｃ , R ｄ , R ２ , R ３ , R ４ , R ５ And n is the same as above. The process includes manufacturing ] A method for producing a pyridine derivative having a sulfur-containing substituent according to claim 8 or 10.

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