Method for producing sulfonyl chloride compound

Patent metadata

Field	Value
Publication number	US-2016009646-A1
Application number	US-201414770914-A
Country	US
Kind code	A1
Filing date	Feb 27, 2014
Priority date	Feb 28, 2013
Publication date	Jan 14, 2016
Grant date	—

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

1 . A production method of a pyridine-3-sulfonyl chloride compound, comprising reacting a pyridine-3-sulfonic acid compound with phosphorus pentachloride in a solvent of chlorobenzene or trifluoromethylbenzene to give the pyridine-3-sulfonyl chloride compound.

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

wherein R 1 is an optionally substituted pyridin-3-yl group, R 2 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, and R 3 and R 4 are each independently a hydrogen atom, an optionally substituted alkyl group, an acyl group, an optionally substituted hydroxy group, an optionally substituted amino group or a halogen 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 the production method according to claim 1 , with a compound represented by the formula (III):

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

3 . A production method of a compound represented by the formula (VI):

wherein R 1 is an optionally substituted pyridin-3-yl group, R 2 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group, R 3 and R 4 are each independently a hydrogen atom, an optionally substituted alkyl group, an acyl group, an optionally substituted hydroxy group, an optionally substituted amino group or a halogen atom, and R 5 is an alkyl group 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 the production method according to claim 1 , with a compound represented by the formula (III):

wherein each symbol is as defined above, or a salt thereof to produce a compound represented by the formula (IV):

wherein each symbol is as defined above, or a salt thereof, and reacting the compound with a compound represented by the formula (V):
R 5 —NH 2   (V)

wherein R 5 is as defined above, or a salt thereof in the presence of a reducing agent.

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

5 . The production method according to claim 2 , wherein R 2 is an optionally substituted phenyl group.

6 . The production method according to claim 2 , 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.

7 . The production method according to claim 3 , wherein R 1 is an unsubstituted pyridin-3-yl group,
R 2 is a 2-fluorophenyl group, R 3 and R 4 are each a hydrogen atom, and R 5 is a methyl group.

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

9 . The production method according to claim 3 , wherein R 2 is an optionally substituted phenyl group.

Assignees

• Takeda Pharmaceutical

Inventors

• Majima Keisuke

Classifications

• C07D401/12 Primary

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

• C07D213/71 Primary

  to which a second hetero atom is attached · CPC title

• A61K9/2018

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

• A61K9/2866

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