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

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Karatas H., Hanashalshahaby E. H. A., Catal U., Butun Y. E., Kurt E., Gursel S., ...More

Chemical Papers, vol.77, no.3, pp.1695-1702, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 77 Issue: 3
  • Publication Date: 2023
  • Doi Number: 10.1007/s11696-022-02595-1
  • Journal Name: Chemical Papers
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core
  • Page Numbers: pp.1695-1702
  • Keywords: Favipiravir synthesis, 3,6-Dichloropyrazine-2-carbonitrile, Covid-19 treatment, Process development, Active Pharmaceutical Ingredient (API) synthesis
  • Istanbul Medipol University Affiliated: Yes


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.]