Development of an efficient synthesis of two CRF antagonists for the treatment of neurological disorders

…, MA Fitzgerald, C Lai, FG Buono, A Braem…

Index: Leahy, David K.; Li, Jun; Sausker, Justin B.; Zhu, Jason; Fitzgerald, Monica A.; Lai, Chiajen; Buono, Frederic G.; Braem, Alan; De Mas, Nuria; Manaloto, Zerene; Lo, Ehrlic; Merkl, William; Su, Bao-Ning; Gao, Qi; Ng, Alicia T.; Hartz, Richard A. Organic Process Research and Development, 2010 , vol. 14, # 5 p. 1221 - 1228

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Citation Number: 12

Abstract

BMS-764459 (1) and BMS-763534 (2) are CRF1 antagonists for the treatment of neurological disorders such as depression and anxiety. An efficient synthesis of 1 and 2 is described, which features an efficient palladium-catalyzed cyanation of a 5- chloropyrazinone where zinc acetate suppresses dehalogenation. This synthesis was applied to the preparation of> 5 kg of 1 and 2 for clinical studies.