Progress Toward a Large-Scale Synthesis of Molnupiravir (MK-4482, EIDD-2801) from Cytidine

• DOI: 10.1021/acsomega.1c00772
• Publication Date: 2021-04-15T00:15:57Z
• Authors: Grace P. Ahlqvist; Catherine P. McGe...; Chris Senanayake; Joseph D. Armstrong; Ajay Yadaw; Sarabindu Roy; Saeed Ahmad; David R. Snead; Timothy F. Jamison
• Keywords: Transamination; Cytidine

Molnupiravir (MK-4482, EIDD-2801) is a promising orally bioavailable drug candidate for the treatment of COVID-19. Herein, we describe supply-centered and chromatography-free synthesis molnupiravir from cytidine, consisting two steps: selective enzymatic acylation followed by transamination to yield final product. Both steps have been successfully performed on decagram scale: first step at 200 g second 80 g. Overall, has obtained in 41% overall isolated compared maximum 17% patented route. This route provides many advantages initial described patent literature would decrease cost this pharmaceutical should it prove safe efficacious ongoing clinical trials.