Method for producing pyrrole derivative, and intermediate thereof

Patent metadata

Field	Value
Publication number	US-9765025-B2
Application number	US-201615043260-A
Country	US
Kind code	B2
Filing date	Feb 12, 2016
Priority date	Aug 27, 2013
Publication date	Sep 19, 2017
Grant date	Sep 19, 2017

Abstract

The present invention provides a method for producing an atropisomer of a pyrrole derivative having excellent mineralocorticoid receptor antagonistic activity, and an intermediate thereof. A method for producing an atropisomer of a pyrrole derivative using a compound represented by (B) [wherein R 1 represents a C1-C4 alkyl group, and R 2 represents a 2-hydroxyethyl group or a carboxymethyl group] as a production intermediate.

First claim

The invention claimed is:

1. A method for resolving an atropisomer of the following formula (C):

wherein R 1 represents a C1-C4 alkyl group, comprising:
(a) treating a compound of formula (C) with an optically active amine to provide an optically active amine salt comprised of an atropisomer of the compound and the optically active amine; and
(b) removing the optically active amine from the optically active amine salt obtained in step (a) under acidic condition to provide an atropisomer of the compound of formula (C).

2. The method according to claim 1 , wherein the optically active amine is one compound selected from the group of the following compounds:

3. The method according to claim 1 , wherein the optically active amine is (R)-(+)-1-(1-naphthyl)ethylamine.

4. A method for resolving an atropisomer of the following formula (II) comprising:

(a) treating a compound of formula (II) with an optically active amine to provide an optically active amine salt comprised of an atropisomer of the compound and the optically active amine; and
(b) removing the optically active amine from the optically active amine salt obtained in step (a) under acidic condition to provide an atropisomer of the compound of formula (II), the atropisomer of the compound of formula (II) having formula (IIa)

5. The method according to claim 1 , wherein the atropisomer of the compound of formula (C) is (S)-2-[4-ethoxycarbonyl-3-methyl-2-[2(trifluoromethyl)phenyl]-1H-pyrrol-1-yl]acetic acid.

6. A method for obtaining an optically active amine salt of an atropisomer of formula (C):

wherein R 1 represents a C1-C4 alkyl group, comprising treating a compound of formula (C) with an optically active amine to provide an optically active amine salt comprised of an atropisomer of the compound and the optically active amine.

7. The method according to claim 6 , wherein the optically active amine is one compound selected from the group of the following compounds:

8. The method according to claim 6 , wherein the optically active amine is (R)-(+)-1-(1-naphthyl)ethylamine.

Assignees

• Daiichi Sankyo Co Ltd

Inventors

• Watanabe Masashi
• Nagasawa Hiroshi
• Sato Noritada

Classifications

• C12P41/005

  by esterification of carboxylic acid groups in the enantiomers or the inverse reaction · CPC title

• C12P17/10

  Nitrogen as only ring hetero atom · CPC title

• C07B57/00

  Separation of optically-active compounds · CPC title

• C07D207/34 Primary

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms · CPC title

• C07D207/456 Primary

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms · CPC title