A Convenient and Cost Efficient Route Suitable for “One-Pot” Synthesis of Molnupiravir

Herein, we reported a convenient and cost efficient one-pot synthesis of molnupiravir from cytidine. This method utilized N,N-dimethylformamide dimethyl acetal (DMF-DMA) as an extraordinary protecting agent to achieve site specific esterification at 5’-hydroxyl group of the nucleoside easily, and afforded this promising drug candidate (purity up to 99%, HPLC a/a) in 70% overall yield without chromatography purification, which is superior to the existing methods in aspect of the yield, the cost and the operation, and shows great potential value for commercial production. Furthermore, this excellent protecting agent was also successfully used in the synthesis of remdesivr from its parent nucleoside with a high total yield (76%).