An economical and practical procedure of favipiravir synthesis for the treatment of Covid-19

Abstract

Favipiravir is a wide-spectrum antiviral generic drug that has received large attention during the recent COVID-19 pandemic. While there are synthetic strategies for favipiravir synthesis, economical procedures could contribute to industrial scale synthesis and availability. Accordingly, our efforts focused on an economic and scalable procedure for favipiravir synthesis via the 3,6-dichloropyrazine-2-carbonitrile intermediate obtained from 3-aminopyrazine-2-carboxylic acid. The process afforded favipiravir with 43% yield (from 3,6-dichloropyrazine-2-carbonitrile, by fluorination, hydroxylation, and nitrile hydrolysis reactions) and greater than 99% purity without a chromatographic purification step. Graphical abstract: [Figure not available: see fulltext.]