Crystal of pyrrole derivative and method for producing the same

Patent metadata

Field	Value
Publication number	US-9499483-B2
Application number	US-201514879814-A
Country	US
Kind code	B2
Filing date	Oct 9, 2015
Priority date	Apr 10, 2013
Publication date	Nov 22, 2016
Grant date	Nov 22, 2016

Abstract

The present invention provides a production intermediate of an atropisomer of a pyrrole derivative having excellent mineralocorticoid receptor antagonistic activity, a method for producing the same, and a crystal thereof. A method for producing an atropisomer of a pyrrole derivative including a step of resolving a compound represented by the following general formula (I) [wherein R 1 represents a methyl group or a trifluoromethyl group, R 2 represents a hydrogen atom or a C1-C3 alkoxy group, and n represents an integer selected from 1 to 3] into its atropisomers, characterized by using an optically active amine having a cinchonine skeletal formula, and a crystal of (S)-1-(2-hydroxyethyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide.

First claim

The invention claimed is:

1. A method for resolving a compound represented by the following general formula (I):

[wherein R 1 represents a methyl group or a trifluoromethyl group, R 2 represents a hydrogen atom or a C1-C3 alkoxy group, and n represents an integer selected from 1 to 3] into its atropisomers, comprising stirring the compound with an optically active amine having a cinchonine skeletal formula.

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

3. The method according to claim 1 , wherein the optically active amine is quinine represented by the following formula:

4. The method according to claim 1 , wherein the method is performed in an organic solvent or a mixed solvent of an organic solvent and water.

5. The method according to claim 1 , wherein the compound represented by the general formula (I) is the following compound (Ia):

Assignees

• Daiichi Sankyo Co Ltd

Inventors

• Watanabe Masashi
• Okachi Takahiro
• Kawahara Michiaki
• Nagasawa Hiroshi
• Sato Noritada
• Takita Takashi
• Hasegawa Gen

Classifications

• A61P9/12

  Antihypertensives · CPC title

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title