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

Abstract

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 amidecoupling, 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.

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

“…With 6 and 9 in hand, we were able to successfully deliver 2 kg of high-quality API MK-7845 ( 1 ) in the end-game campaign through amide coupling and oxidation. Further details will be provided in the next report …”