Periodical
Asymmetric Synthesis of Akt Kinase Inhibitor Ipatasertib
| العنوان: | Asymmetric Synthesis of Akt Kinase Inhibitor Ipatasertib |
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| المؤلفون: | Han, Chong, Savage, Scott, Al-Sayah, Mohammad, Yajima, Herbert, Remarchuk, Travis, Reents, Reinhard, Wirz, Beat, Iding, Hans, Bachmann, Stephan, Fantasia, Serena M., Scalone, Michelangelo, Hell, André, Hidber, Pirmin, Gosselin, Francis |
| المصدر: | Organic Letters; 20240101, Issue: Preprints |
| مستخلص: | A highly efficient asymmetric synthesis of the Akt kinase inhibitor ipatasertib (1) is reported. The bicyclic pyrimidine 2starting 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 3in high yield and enantioselectivity. The API was assembled in a convergent manner through a late-stage amidation/deprotection/monohydrochloride salt formation sequence. |
| قاعدة البيانات: | Supplemental Index |
| تدمد: | 15237060 15237052 |
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| DOI: | 10.1021/acs.orglett.7b02228 |