JP-7855013-B2 - Method for producing 2-heteroarylpyridine compounds

Inventors

• 小林 真一
• 松田 浩一

Assignees

• 日本曹達株式会社

Dates

Publication Date

20260507

Application Date

20221116

Priority Date

20211119

Claims (6)

1. A method for producing a compound represented by formula (3), comprising chemically reacting a compound represented by formula (1) with a compound represented by formula (2) in the presence of a metal alkoxide or a base. (In formula (1), Q represents a substituted or unsubstituted 5-6 membered or 9-10 membered heteroaryl group, and R1 represents a C1-6 alkyl group.) (In formula (2), R 2 represents a hydrogen atom, a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted 5-6 membered heteroaryl group.) (In equation (3), Q, R1 , and R2 are the same as those in equations (1) and (2).)
2. The manufacturing method according to claim 1, wherein Q in formulas (1) and (3) is a group represented by formula (5). (In formula (5), * indicates a bonding site, R3 indicates a C1-6 alkyl group, and R4 indicates a hydrogen atom, a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, or a 1,3-dioxolan-2-yl group.)
3. Chemically reacting a compound represented by formula (3) with hydroxylamine or a salt thereof, and dehydrating the product of the chemical reaction. A method for producing a compound represented by formula (4), including the following. (In formula (3), Q represents a substituted or unsubstituted 5-6 membered or 9-10 membered heteroaryl group, R1 represents a C1-6 alkyl group, and R2 represents a hydrogen atom, a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted 5-6 membered heteroaryl group.) (In equation (4), Q, R1 , and R2 are the same as those in equation (3).)
4. Chemically reacting a compound represented by formula (3) with ammonia or an ammonium salt in the presence of an alcohol, and oxidizing the product of the chemical reaction in the presence of an organic oxidizing agent. A method for producing a compound represented by formula (4), including the following. (In formula (3), Q represents a substituted or unsubstituted 5-6 membered or 9-10 membered heteroaryl group, R1 represents a C1-6 alkyl group, and R2 represents a hydrogen atom, a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted 5-6 membered heteroaryl group.) (In equation (4), Q, R1 , and R2 are the same as those in equation (3).)
5. The manufacturing method according to claim 3 or claim 4, wherein Q in formulas (3) and (4) is a group represented by formula (5). (In formula (5), * indicates a bonding site, R3 indicates a C1-6 alkyl group, and R4 indicates a hydrogen atom, a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, or a 1,3-dioxolan-2-yl group.)
6. The compound represented by formula (3a). (In formula (3a), R1 represents a C1-6 alkyl group, R2 represents a hydrogen atom, a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted 5-6 membered heteroaryl group, R3 represents a C1-6 alkyl group, and R4 represents a hydrogen atom, a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, or a 1,3-dioxolan-2-yl group.)

Description

This invention relates to a method for producing 2-heteroarylpyridine compounds. Nitrogen-containing heterocycles are major substructures (building blocks) that constitute compounds that serve as active ingredients for pharmaceuticals and agrochemicals. In recent years, there has been a surge in the development of pest control agents containing pyridine rings. For example, Patent Documents 1 to 5 describe pyridine compounds having a five-membered heteroaryl group and a sulfur-containing hydrocarbon group. Furthermore, Non-Patent Document 1 discloses the production of 3-phenyl-5-chloro-2-pyridone (4g) and 3-hydroxycarbonyl-5-chloro-2-pyridone (4h) by the reaction of 2-chloro-N,N-dimethylaminotrimethinium hexafluorophosphate with methylphenyl acetate and 3-methoxy-3-oxopropanoic acid. Patent document 6 discloses a method for constructing a pyridine ring according to the following scheme. In the above scheme, Q represents a pyridyl group, R1 represents a C1-C6 alkyl group which may have one or more halogen atoms, R2 represents a C1-C6 alkyl group which may have one or more halogen atoms, R3 , R4 , and R5 represent a hydrogen atom, and n represents 0. WO 2017/016910AWO 2017/050685AWO 2020/050212AWO 2020/071304AWO 2020/090585AWO 2018/194077A Jean-Francuois Marcoux et al. "A General Preparation of Pyridines and Pyridones via the Annulation of Ketones and Esters" J. Org. Chem., Vol. 66, No. 12, 2001, 4194-4199 In this invention, the term "unsubstituted" means that only the core group is present. When the term "substituted" is not used and only the name of the core group is given, it means "unsubstituted" unless otherwise specified. On the other hand, the term "substitution" means that one of the hydrogen atoms of the core group is substituted by a group (substituent) that has the same or different structure as the core group. Therefore, a "substituent" is another group bonded to the core group. There may be one substituent or two or more substituents. The two or more substituents may be the same or different. Terms such as "C1-C6" indicate that the parent group has 1 to 6 carbon atoms. This number of carbon atoms does not include the number of carbon atoms in substituents. For example, a butyl group with an ethoxy group as a substituent is classified as a C2 alkoxy C4 alkyl group. The "substituents" are chemically acceptable and not particularly limited insofar as they have the effects of the present invention. The following are examples of groups that can act as "substituents". C1-6 alkyl groups such as methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, s-butyl group, i-butyl group, t-butyl group, n-pentyl group, and n-hexyl group; C2-6 alkenyl groups such as vinyl group, 1-propenyl group, 2-propenyl group (allyl group), 1-butenyl group, 2-butenyl group, 3-butenyl group, 1-methyl-2-propenyl group, and 2-methyl-2-propenyl group; C2-6 alkynyl groups such as ethynyl group, 1-propynyl group, 2-propynyl group, 1-butynyl group, 2-butynyl group, 3-butynyl group, and 1-methyl-2-propynyl group; C3-6 cycloalkyl groups such as cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl groups; Phenyl group; 3- to 6-membered heterocyclyl groups; C1-6 alkoxy groups such as methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy, i-butoxy, and t-butoxy groups; C6-10 aryloxy groups such as phenoxy and naphthoxy groups; Five- to six-membered heteroaryloxy groups such as thiazolyloxy and pyridyloxy groups; C1-6 alkoxycarbonyl groups such as methoxycarbonyl group, ethoxycarbonyl group, n-propoxycarbonyl group, i-propoxycarbonyl group, n-butoxycarbonyl group, and t-butoxycarbonyl group; Halogeno groups such as fluoro groups, chloro groups, bromo groups, and iod groups; C1-6 haloalkyl groups such as chloromethyl group, chloroethyl group, trifluoromethyl group, 1,2-dichloro-n-propyl group, 1-fluoro-n-butyl group, and perfluoro-n-pentyl group; C1-6 haloalkoxy groups such as trifluoromethoxy, 2-chloro-n-propoxy, and 2,3-dichlorobutoxy; Formylamino group; C1-6 alkylcarbonylamino groups such as acetylamino groups, propanoylamino groups, butyrylamino groups, and i-propylcarbonylamino groups; C1-6 alkoxycarbonylamino groups such as methoxycarbonylamino groups, ethoxycarbonylamino groups, n-propoxycarbonylamino groups, and i-propoxycarbonylamino groups; Unsubstituted or substituted aminocarbonyl groups such as aminocarbonyl groups, dimethylaminocarbonyl groups, phenylaminocarbonyl groups, and N-phenyl-N-methylaminocarbonyl groups; C1-6 alkylthio groups such as methylthio group, ethylthio group, n-propylthio group, i-propylthio group, n-butylthio group, i-butylthio group, s-butylthio group, and t-butylthio group; C1-6 haloalkylthio groups such as trifluoromethylthio group and 2,2,2-trifluoroethylthio group; C1-6 alkylsulfonyl groups such as methylsulfonyl groups, ethylsulfonyl groups, and t-butylsulfonyl groups; C1-6 haloalkylsulfonyl groups such as trifluoromethylsulfonyl group and 2,2,2-trifluoroethylsulfonyl group; Cyano