Early Kilogram Scale Delivery of MK-7845 as a Potential COVID-19 Therapy: Rapid Process Development of Key Intermediates

Abstract

MK-7845 was designed as a 3C-like protease inhibitor for the treatment of COVID-19. To enable a rapid kilo-scale delivery of MK-7845 to accelerate its First-in-Human studies, we developed a fit-for-purpose process to produce two key building blocks in less than two months. The key discoveries were a highly diastereoselective Ellman addition route for β-aminoamide 6 and crystallization isolation methods to produce 6 and acid 9 with good quality control.

Rapid End-Game Process Development and First GMP Production of MK-7845: An Experimental Antiviral Treatment for COVID-19

“…We began our end-game optimization by focusing on the coupling of acid 2 with amine 3 to access the penultimate intermediate 4 . To progress MK-7845 ( 1 ) through critical safety studies and enable clinical studies to begin as rapidly as possible, the chemistry development and large-scale deliveries of building blocks 2 and 3 occurred while we conducted the end-game process development.…”