Journal
CHEMICAL PAPERS
Volume 73, Issue 5, Pages 1043-1051Publisher
SPRINGER INTERNATIONAL PUBLISHING AG
DOI: 10.1007/s11696-018-0654-9
Keywords
Favipiravir; 2-Aminopyrazine; Fluorination; Sandmeyer reaction
Categories
Funding
- National Science Foundation for Young Scientists of China [21502209]
Ask authors/readers for more resources
Favipiravir was first synthesized from an inexpensive and commercially available starting material, 2-aminopyrazine. The preferred route embedded within Scheme4 consisted of seven steps, and was highlighted by the novel and efficient synthesis of 3,6-dichloropyrazine-2-carbonitrile 8. This intermediate 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 8, 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 8. However, the key step of monofluorination at the pyrazine C6 position of intermediate 19 or 22 was not achieved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available