A practical synthesis of renin inhibitor MK-1597 (ACT-178882) via catalytic enantioselective hydrogenation and epimerization of piperidine intermediate |
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Authors: | Molinaro Carmela Shultz Scott Roy Amélie Lau Stephen Trinh Thao Angelaud Rémy O'Shea Paul D Abele Stefan Cameron Mark Corley Ed Funel Jacques-Alexis Steinhuebel Dietrich Weisel Mark Krska Shane |
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Institution: | Department of Process Research, Merck, 16711 Autoroute Transcanadienne, Kirkland, Que?bec, Canada H9H 3L1. carmela_molinaro@merck.com |
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Abstract: | A practical enantioselective synthesis of renin inhibitor MK-1597 (ACT-178882), a potential new treatment for hypertension, is described. The synthetic route provided MK-1597 in nine steps and 29% overall yield from commercially available p-cresol (7). The key features of this sequence include a catalytic asymmetric hydrogenation of a tetrasubstituted ene-ester, a highly efficient epimerization/saponification sequence of 4 which sets both stereocenters of the molecule, and a short synthesis of amine fragment 2. |
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