CRYSTAL OF PYRROLE DERIVATIVE AND METHOD FOR PRODUCING THE SAME

摘要

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 R1 represents a methyl group or a trifluoromethyl group, R2 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.;

主权项

1. A method for producing (S)-1-(2-hydroxyethyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide represented by the following formula (A):characterized by obtaining one atropisomer of (RS)-1-(2-hydroxyethyl)-4-methyl-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxylic acid represented by the following formula (Ia):by resolution using an optically active amine having a cinchonine skeletal formula, removing the optically active amine under acidic conditions, followed by reaction with oxalyl chloride, thereby forming the following intermediate compound (IIa):and then further reacting the intermediate compound (IIa) with 4-(methylsulfonyl)aniline, thereby forming the following intermediate compound (IIIa):followed by a base treatment.