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Practical Large‐Scale Synthesis of the Hepatitis C Virus Protease Inhibitor BI 201335

Practical Large‐Scale Synthesis of the Hepatitis C Virus Protease Inhibitor BI 201335 A concise synthetic route for large‐scale manufacture of the hepatitis C virus (HCV) protease inhibitor BI 201335 has been developed. A convergent synthetic design was achieved by using three advanced intermediates: a densely functionalized thiazole‐quinoline, a hydroxyproline‐containing dipeptide acid, and an optically pure vinylcyclopropane. Only three subsequent synthetic steps were then required for the final assembly of this complex target. The first step is a critical CO bond formation to join the heterocycle and the peptidic portion of the molecule, which was done by using a newly‐designed heterocyclic sulfone. The second step uses an inexpensive peptide coupling of the aminocyclopropane and ester saponification, then recrystallization completes the route. This economical and practical process is suitable for large scale production of BI 201335, requires no protecting groups or chromatography, and every isolated intermediate is a crystalline solid. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Asian Journal of Organic Chemistry Wiley

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References (28)

Publisher
Wiley
Copyright
Copyright © 2012 Wiley Subscription Services, Inc., A Wiley Company
ISSN
2193-5807
eISSN
2193-5815
DOI
10.1002/ajoc.201200014
Publisher site
See Article on Publisher Site

Abstract

A concise synthetic route for large‐scale manufacture of the hepatitis C virus (HCV) protease inhibitor BI 201335 has been developed. A convergent synthetic design was achieved by using three advanced intermediates: a densely functionalized thiazole‐quinoline, a hydroxyproline‐containing dipeptide acid, and an optically pure vinylcyclopropane. Only three subsequent synthetic steps were then required for the final assembly of this complex target. The first step is a critical CO bond formation to join the heterocycle and the peptidic portion of the molecule, which was done by using a newly‐designed heterocyclic sulfone. The second step uses an inexpensive peptide coupling of the aminocyclopropane and ester saponification, then recrystallization completes the route. This economical and practical process is suitable for large scale production of BI 201335, requires no protecting groups or chromatography, and every isolated intermediate is a crystalline solid.

Journal

Asian Journal of Organic ChemistryWiley

Published: Sep 1, 2012

Keywords: ; ; ;

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