“One-Pot” Synthesis of Molnupiravir from Cytidine

• DOI: 10.1021/acs.oprd.1c00419
• Publication Date: 2022-02-09T21:44:02Z
• Authors: Tianwen Hu; Yuanchao Xie; Fuqiang Zhu; Xudong Gong; Yin Liu; Haitao Xue; Haji A. Aisa; Jingshan Shen
• Keywords: Cytidine; Dimethyl formamide

A one-pot process for preparing molnupiravir from cytidine was developed. The advantages of this synthesis were as follows: (1) presence N,N-dimethylformamide dimethyl acetal (DMF-DMA) facilitated the selective protection 2′,3′-dihydroxyls and amino cytidine, which eliminated negative impact these groups on following isobutyrylation at 5′-hydroxyl. (2) Degradations product in deprotection stage avoided since a mild condition used. (3) achievement hydroxyamination one single step improved synthetic efficiency. (4) Molnupiravir with high purity (purity up to 99.7% analyzed by high-performance liquid chromatography (HPLC)) obtained yield 63% through crystallization.