Practical and efficient synthesis of the (R)-atropisomer of a 4-phenyl 1,2,4-triazole derivative as a selective GlyT1 inhibitor

Abstract

Herein we describe a novel and efficient method for synthesizing the (R)-atropisomer of 3-[3-ethyl-5-(6-phenylpyridin-3-yl)-4H-1,2,4-triazol-4-yl]-2-methylbenzonitrile 1, a novel GlyT1 inhibitor. The diastereomeric salt formation of 3-[3-ethyl-5-(6-phenylpyridin-3-yl)-4H-1,2,4-triazol-4-yl]-2-methylbenzoic acid 7 with (1R,2S)-(−)-2-amino-1,2-diphenylethanol afforded the desired (R)-atropisomer. We also report the determination of the absolute configuration of (R)-7 by powder X-ray diffraction.