PDF icon Download PDF
Synfacts 2013; 9(6): 0581
DOI: 10.1055/s-0033-1338723
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of BI 201302

Contributor(s):
Philip Kocienski
Wei X * et al. Boehringer-Ingelheim Pharmaceuticals, Ridgeway, USA
A Highly Convergent and Efficient Synthesis of a Macrocyclic Hepatitis C Virus Protease Inhibitor BI 201302.

Org. Lett. 2013;
15: 1016-1019
CrossrefPubMedSearch in Google Scholar
Further Information

Publication History

Publication Date:
16 May 2013 (online)

 
 PDF Download Permissions and Reprints

Key words

BI 201302 - HCV protease inhibitor - ring-closing metathesis - macrocyclization - Grela catalyst

Significance

The synthesis of the HCV protease inhibitor BI 201302 features an efficient ruthenium-catalyzed ring-closing metathesis reaction (0.1–0.2 M) requiring only 0.1 mol% of the Grela catalyst E to generate the 15-membered macrocycle F. This enhanced efficiency was achieved by installing a Boc substituent on the nitrogen of fragment D.


 

Comment

The SNAr reaction using a phenylsulfonyl leaving group in quinoline derivative H was more efficient than the reaction with the corresponding chloride (92% vs 40% yield). Potassium 3,7-dimethyl-3-octanoxide (KDMO) was used as a base instead of t-BuOK because transcarbamoylation byproducts (1–2%) were easily removed by crystallization.


 

 


  Permissions and Reprints