AI Article Synopsis
- Two new methods have been created to synthesize a specific CGRP receptor antagonist, telcagepant (MK-0974).
- The first method uses a ring-closing metathesis process with styrene as a crucial step, while the second method involves a selective Rh-catalyzed reaction to add arylboronic acid to a nitroalkene.
- The second route has been successfully used to produce large amounts of telcagepant for thorough preclinical testing.
Article Abstract
Two novel routes have been developed to the (3 R,6 S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-one 2 of the CGRP receptor antagonist clinical candidate telcagepant (MK-0974, 1). The first employs a ring-closing metathesis of the styrene 7 as the key reaction, while the second makes use of a highly diastereoselective Hayashi-Miyaura Rh-catalyzed arylboronic acid addition to nitroalkene 16. The latter route has been implemented to produce multigram quantities of telcagepant for extensive preclinical evaluation.
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| http://dx.doi.org/10.1021/ol8011524 | DOI Listing |
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