Development of a Green & Sustainable Manufacturing Process for MK-7264
Dr. Kallol Basu(Merck)

ABSTRACT:  MK-7264 (gefapixant) is a P2X3 antagonist currently in Phase III clinical trials for the treatment of chronic cough. The 1^st generation manufacturing route consists of 11 steps with a PMI (process mass intensity) of 366 and overall yield of 16%.  Therefore, Process Research & Development was tasked with the challenge of developing a robust and sustainable process with a low process mass intensity (PMI), short synthetic sequence, high overall yield, minimal environmental impact, and significantly reduced API costs. A 2^nd generation manufacturing route has been developed with a PMI of 76 (a 5-fold reduction compared to the 1^st generation route) and a significantly higher overall yield (16%→60% yield).  The key breakthrough in the 2^nd generation route was the development of a novel pyrimidine synthesis in flow to afford the core structure of MK-7264 in high yield.  This presentation will detail the innovations made in synthetic chemistry, flow chemistry, and process chemistry in route to a commercial manufacturing route for MK-7264.

BIO:  Dr. Basu completed his M.Sc. at the Indian Institute of Technology (Kanpur, India) before earning his Ph.D. in 2004 under the supervision of Prof. Leo A. Paquette at The Ohio State University. After completing a post-doctoral fellowship at the University of Pennsylvania with Prof. Amos B. Smith III, Dr. Basu began his career as a discovery chemist at Schering Plough/Merck before becoming a process chemist at Merck in 2015. He holds a number of patents related to drug discovery and continues to co-author publications on the optimization of stereoselective and scalable processes. 

Dr. Basu is the guest of Dr. Pat Forgione.