Organic Letters
Organic Letters
5 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

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.