960化工网
Continuous flow synthesis of the URAT1 inhibitor lesinurad†
Mariana C. F. C. B. Damião,Henrique M. Marçon,Julio Cezar Pastre
Reaction Chemistry & Engineering Pub Date : 01/27/2020 00:00:00 , DOI:10.1039/C9RE00483A
Abstract

Herein, the urate anion exchange transporter 1 (URAT1) inhibitor lesinurad is synthesized from commercially available building blocks by a five-step linear continuous flow sequence. Our previously developed continuous flow platform was successfully applied to generate the 3-thio-1,2,4-triazole key intermediate 2 in 88% yield, after 55 minutes of residence time. Condensation, cyclization and S-alkylation were telescoped in a single operation without conducting solvent exchanges and intermediate purifications. Next, 1,2,4-triazole bromination and ester hydrolysis were also performed in continuous flow regime to deliver lesinurad in 68% overall yield in a total residence time of 2 hours. Our approach enables the fast generation of lesinurad and can be directly applied to produce major quantities of this important API.

Graphical abstract: Continuous flow synthesis of the URAT1 inhibitor lesinurad
平台客服
平台客服
平台在线客服