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

We describe the rapid end-game process development for the first good manufacturing process (GMP) delivery of the 3C-like protease inhibitor MK-7845 ( 1 ), an experimental treatment for SARS-CoV-2. Three operations, including an amide-coupling, oxidation, and crystallization, were rapidly developed and implemented on a kilogram scale to enable critical safety studies and phase 1 clinical trials to move forward on a highly accelerated timeline. Key to the success of this undertaking was our focus on purging key impurities formed in the amide-coupling step, identifying a safe and scalable TEMPO/NaOCl oxidation to access 1, and developing an active pharmacutical ingredient (API) crystallization that addressed challenges associated with gumming, oiling, and agglomeration. Notably, this delivery was completed within an approximately six-week time frame, and challenges associated with this highly accelerated delivery are also discussed.