1365970-45-1Relevant articles and documents
Development of a Large-Scale Route to Glecaprevir: Synthesis of the Macrocycle via Intramolecular Etherification
Cink, Russell D.,Ding, Chen,Engstrom, Kenneth M.,Fickes, Michael G.,Henle, Jeremy,Kallemeyn, Jeffrey M.,Lukin, Kirill A.,Marren, James,Morrill, Westin H.,Nere, Nandkishor K.,Pelc, Matthew J.,Ravn, Matthew M.,Shekhar, Shashank,Towne, Timothy B.,Vinci, John C.,Wei, Haojuan,Welch, Dennie S.,Zhao, Gang
, p. 1373 - 1392 (2020/10/12)
Glecaprevir was identified as a potent hepatitis C virus (HCV) protease inhibitor, and a large-scale synthesis was required to support the late-stage clinical trials and subsequent commercial launch. The large-scale synthetic route to glecaprevir required the development of completely new synthetic approaches to the two key structural features: the 18-membered macrocycle 3 and the difluoromethyl-substituted cyclopropyl amino acid 4. In this first manuscript, we describe the route development for the macrocycle 3; the second manuscript will describe the development of a new synthetic route to the difluoromethyl-substituted cyclopropyl amino acid 4 and the final assembly of glecaprevir. The large-scale synthetic route to the macrocycle employed a unique intramolecular etherification reaction as the key step in the macrocycle synthesis, avoiding the scalability limitations of the ring-closing metathesis (RCM) reaction of the enabling route. The large-scale synthetic route to the macrocycle was successfully used to produce the amount of glecaprevir required to support the late-stage clinical development.
Macrocyclic proline derived HCV serine protease inhibitors
-
, (2016/01/20)
The present invention discloses compounds of Formula I or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the com
