Guo, Qi published the artcileThe complete synthesis of favipiravir from 2-aminopyrazine, Related Products of pyrazines, the main research area is favipiravir preparation.
Favipiravir was synthesized from an inexpensive and com. available starting material, 2-aminopyrazine. The preferred route embedded within seven steps and was highlighted by the novel and efficient synthesis of 3,6-dichloropyrazine-2-carbonitrile. The intermediate 3,6-dichloropyrazine-2-carbonitrile was prepared in four successive steps which were regioselective chlorination of the pyrazine ring, bromination, Pd-catalyzed cyanation and Sandmeyer diazotization/chlorination. This protocol eliminated the hazardous POCl3 of previous synthetic methods and offered a better yield (48%) which was 1.3-fold higher than a recently published procedure. From intermediate 3,6-dichloropyrazine-2-carbonitrile, the subsequent nucleophilic fluorination, nitrile hydration and hydroxyl substitution efficiently afforded the target product. Another synthetic approach with the same starting material was also investigated to bypass the allergy-causing dichloro intermediate 3,6-dichloropyrazine-2-carbonitrile. The key step of monofluorination at the pyrazine C6 position of intermediate 6-chloro/bromo-3-aminopyrazine-2-carbonitriles and 6-chloro/bromo-3-hydroxylpyrazine-2-carbonitriles was not achieved.
Chemical Papers published new progress about. 356783-29-4 belongs to class pyrazines, name is 3,6-Difluoropyrazine-2-carboxamide, and the molecular formula is C5H3F2N3O, Related Products of pyrazines.