A Novel and Practical Synthesis of 5-Fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile, a Key Intermediate of Vericiguat,Organic Process Research & Development

当前位置： X-MOL 学术 › Org. Process Res. Dev. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

A Novel and Practical Synthesis of 5-Fluoro-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine-3-carbonitrile, a Key Intermediate of Vericiguat
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2023-03-30 , DOI: 10.1021/acs.oprd.3c00011
Siju Bi ₁ , Wenshuang Diao ₁ , Ting Tian ₁ , Ting Zhou ₁ , Kuaile Lin ₁ , Weicheng Zhou ₁

Affiliation

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.

更新日期：2023-03-30

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南