4 years ago

Asymmetric Synthesis of Akt Kinase Inhibitor Ipatasertib

Asymmetric Synthesis of Akt Kinase Inhibitor Ipatasertib
Francis Gosselin, Mohammad Al-Sayah, Travis Remarchuk, Herbert Yajima, André Hell, Hans Iding, Michelangelo Scalone, Stephan Bachmann, Pirmin Hidber, Chong Han, Serena M. Fantasia, Beat Wirz, Reinhard Reents, Scott Savage
A highly efficient asymmetric synthesis of the Akt kinase inhibitor ipatasertib (1) is reported. The bicyclic pyrimidine 2 starting material was prepared via a nitrilase biocatalytic resolution, halogen–metal exchange/anionic cyclization, and a highly diastereoselective biocatalytic ketone reduction as key steps. The route also features a halide activated, Ru-catalyzed asymmetric hydrogenation of a vinylogous carbamic acid to produce α-aryl-β-amino acid 3 in high yield and enantioselectivity. The API was assembled in a convergent manner through a late-stage amidation/deprotection/monohydrochloride salt formation sequence.

Publisher URL: http://dx.doi.org/10.1021/acs.orglett.7b02228

DOI: 10.1021/acs.orglett.7b02228

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