Development of a scalable synthesis of a GPR40 receptor agonist

…, E DiVirgilio, L Huang, P Liu, H Morrison…

Index: Walker, Shawn D.; Borths, Christopher J.; Divirgilio, Evan; Huang, Liang; Liu, Pingli; Morrison, Henry; Sugi, Kiyoshi; Tanaka, Masahide; Woo, Jacqueline C. S.; Faul, Margaret M. Organic Process Research and Development, 2011 , vol. 15, # 3 p. 570 - 580

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Citation Number: 17

Abstract

Early process development and salt selection for AMG 837, a novel GPR40 receptor agonist, is described. The synthetic route to AMG 837 involved the convergent synthesis and coupling of two key fragments,(S)-3-(4-hydroxyphenyl) hex-4-ynoic acid (1) and 3- (bromomethyl)-4′-(trifluoromethyl) biphenyl (2). The chiral β-alkynyl acid 1 was prepared in 35% overall yield via classical resolution of the corresponding racemic acid (±)-1. An ...