Method for producing sulfonyl chloride compound

Patent metadata

Field	Value
Publication number	US-9932322-B2
Application number	US-201615266307-A
Country	US
Kind code	B2
Filing date	Sep 15, 2016
Priority date	Feb 28, 2013
Publication date	Apr 3, 2018
Grant date	Apr 3, 2018

Abstract

An object of the present invention is to provide a production method of an intermediate used in the production method of a sulfonylpyrrole compound useful as a pharmaceutical product. The present invention relates to a method of producing sulfonylpyrrole compound (VI) by reacting a pyridine-3-sulfonic acid compound with phosphorus pentachloride in a solvent of chlorobenzene or trifluoromethylbenzene to give a pyridine-3-sulfonyl chloride compound, reacting the compound without isolation with compound (III) to give compound (IV), and subjecting the compound (IV) to a reductive amination reaction.

wherein R 2 is a hydrocarbon group etc. and R 3 and R 4 are each a hydrogen atom etc.,

wherein R 1 is an optionally substituted pyridin-3-yl group, and the other symbols are as defined above,

wherein R 5 is an alkyl group and the other symbols are as defined above.

First claim

The invention claimed is:

1. A production method of a compound represented by the formula (IV):

wherein R 1 is a pyridin-3-yl group optionally substituted by 1 to 3 substituents selected from (i) halogen, (ii) cyano, (iii) C 1-6 alkyl optionally substituted by 1-5 halogens, (iv) C 1-6 alkoxy optionally substituted by 1-5 halogens, (v) an amino group optionally substituted by C 1-6 alkyl and (vi) alkoxy-carbonyl, R 2 is [1] a C 6-14 aryl group optionally substituted by 1-5 substituents selected from (i) a halogen atom, (ii) cyano, (iii) C 1-6 alkyl optionally substituted by 1-5 halogens, (iv) C 1-6 alkoxy optionally substituted by 1-5 halogens, (v) acetyl, (vi) C 3-7 cycloalkyl, (vii) C 1-6 alkylsulfonyl, (viii) C 1-6 alkylthio optionally substituted by 1-5 halogens and (ix) C 1-6 alkylsulfinyl, [2] a thienyl group optionally substituted by 1 to 3 substituents selected from (i) a halogen atom, (ii) cyano, (iii) C 1-6 alkyl optionally substituted by 1-5 halogens, (iv) C 1-6 alkoxy optionally substituted by 1-5 halogens and (v) acetyl, or [3] a pyridyl group optionally substituted by 1 to 4 substituents selected from (i) a halogen atom, (ii) cyano, (iii) C 1-6 alkyl optionally substituted by 1-5 halogens, (iv) C 1-6 alkoxy optionally substituted by 1-5 halogens, (v) acetyl and (vi) nitro, and R 3 and R 4 are each independently a hydrogen atom, a C 1-6 alkyl group, a C 1-6 alkyl-carbonyl group, a fluorine atom or a chlorine atom,
or a salt thereof, comprising reacting, without isolation, the pyridine-3-sulfonyl chloride compound represented by the following formula (II):
R 1 —SO 2 Cl  (II)

wherein R 1 is as defined above, which is obtained by reacting a pyridine-3-sulfonic acid compound with phosphors pentachloride in a solvent of chlorobenzene or trifluoromethylbenzene,
with a compound represented by the formula (III):

wherein each symbol is as defined above, or a salt thereof.

2. The production method according to claim 1 , wherein R 1 is an unsubstituted pyridin-3-yl group.

3. The production method according to claim 1 , wherein R 2 is a phenyl group optionally substituted by 1-5 substituents selected from (i) a halogen atom, (ii) cyano, (iii) C 1-6 alkyl optionally substituted by 1-5 halogens, (iv) C 1-6 alkoxy optionally substituted by 1-5 halogens, (v) acetyl, (vi) C 3-7 cycloalkyl, (vii) C 1-6 alkylsulfonyl, (viii) C 1-6 alkylthio optionally substituted by 1-5 halogens and (ix) C 1-6 alkylsulfinyl.

4. The production method according to claim 1 , wherein R 1 is an unsubstituted pyridin-3-yl group,
R 2 is a 2-fluorophenyl group, and
R 3 and R 4 are each a hydrogen atom.

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Majima Keisuke

Classifications

• C07D213/71

  to which a second hetero atom is attached · CPC title

• C07D401/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• A61K9/2866

  Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose · CPC title

• A61K9/2018

  Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates · CPC title