A Novel and Practical
Synthesis of 5‑Fluoro-1-(2-fluorobenzyl)‑1H‑pyrazolo[3,4‑b]pyridine-3-carbonitrile,
a Key Intermediate of Vericiguat
Posted on 2023-03-30 - 20:14
5-Fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile (9) was a key intermediate
for the preparation of vericiguat (1). A new approach
for the synthesis of 9 was developed from 2-chloro-5-fluoronicotinic
acid (22), a commercially available material, in an overall
yield of 48.3%. The hydrazinolysis and intramolecular substitution
were completed in one step to obtain 5-fluoro-1H-pyrazolo[3,4-b]pyridin-3-ol (26). N-1 benzylation of 26 afforded 5-fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridin-3-ol (27),
whose structure was confirmed by 1H and 13C
NMR spectroscopy, mass spectrometry, and single-crystal X-ray crystallography.
Pd-catalyzed cyanation of 5-fluoro-1-(2-fluorobenzyl)-3-bromo-1H-pyrazolo[3,4-b]pyridine (28) was applied to prepare key intermediate 9. In the
route, compounds 26, 27, and 28 have not been reported in the previous literature.
CITE THIS COLLECTION
DataCiteDataCite
3 Biotech3 Biotech
3D Printing in Medicine3D Printing in Medicine
3D Research3D Research
3D-Printed Materials and Systems3D-Printed Materials and Systems
4OR4OR
AAPG BulletinAAPG Bulletin
AAPS OpenAAPS Open
AAPS PharmSciTechAAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität HamburgAbhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)ABI Technik (German)
Academic MedicineAcademic Medicine
Academic PediatricsAcademic Pediatrics
Academic PsychiatryAcademic Psychiatry
Academic QuestionsAcademic Questions
Academy of Management DiscoveriesAcademy of Management Discoveries
Academy of Management JournalAcademy of Management Journal
Academy of Management Learning and EducationAcademy of Management Learning and Education
Academy of Management PerspectivesAcademy of Management Perspectives
Academy of Management ProceedingsAcademy of Management Proceedings
Academy of Management ReviewAcademy of Management Review
Bi, Siju; Diao, Wenshuang; Tian, Ting; Zhou, Ting; Lin, Kuaile; Zhou, Weicheng (2023). A Novel and Practical
Synthesis of 5‑Fluoro-1-(2-fluorobenzyl)‑1H‑pyrazolo[3,4‑b]pyridine-3-carbonitrile,
a Key Intermediate of Vericiguat. ACS Publications. Collection. https://doi.org/10.1021/acs.oprd.3c00011