58457-64-0Relevant articles and documents
REACTION OF METHYL ESTERS OF FLUORINE-CONTAINING α-KETO ACIDS WITH AMINES
Saloutin, V. I.,Piterskikh, I. A.,Pashkevich, K. I.,Kodess, M. I.
, p. 2312 - 2316 (1983)
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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.
Direct C?H Trifluoromethylation of Quinoxalin-2(1H)-ones under Transition-Metal-Free Conditions
Wang, Liping,Zhang, Yuecheng,Li, Fanfan,Hao, Xinyu,Zhang, Hong-Yu,Zhao, Jiquan
, p. 3969 - 3977 (2018/09/14)
Disclosed herein is a direct C?H trifluoromethylation of quinoxalin-2(1H)-ones with sodium trifluoromethanesulfinate. This protocol affords a series of 3-trifluoromethylquinoxalin-2(1H)-one derivatives in moderate to excellent yields under transition-metal-free conditions. The present methodology features utilization of the inexpensive trifluoromethyl source without transition-metal-catalysts, mild reaction conditions and high functional group tolerance, which promises a convenient and efficient access to pharmaceutically interesting quinoxalinones. (Figure presented.).
