ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

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

Hacer Karatas, Essam Hamied Ahmed Hanashalshahaby, Unal Catal, Yasar Enes Butun, Elif Kurt, Sahin Gursel, Adil Kaya, and Mustafa Guzel

Department of Pharmaceutical Chemistry, School of Pharmacy, Istanbul Medipol University, Beykoz, Turkey

E-mail: hacer.karatas@medipol.edu.tr

Received: 6 May 2022  Accepted: 16 November 2022

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

Keywords: Favipiravir synthesis; 3,6-Dichloropyrazine-2-carbonitrile; Covid-19 treatment; Process development; Active Pharmaceutical Ingredient (API) synthesis

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-022-02595-1

Chemical Papers 77 (3) 1695–1702 (2023)