Department of Small Molecule Process Chemistry , Genentech, Inc. , 1 DNA Way , South San Francisco , California 94080 , United States.
J Org Chem. 2019 Apr 19;84(8):4796-4802. doi: 10.1021/acs.joc.8b02751. Epub 2018 Dec 27.
A practical convergent synthesis of PI3K inhibitor GDC-0908 (1) is described. The process features a dihydrobenzothienooxepine formation via palladium-catalyzed intramolecular direct C-H arylation and a Negishi coupling to construct the key C-C bonds. We further developed a general synthesis of dihydrobenzothienooxepines in good to excellent yields via palladium-catalyzed intramolecular direct C-H arylation, which tolerates both electronically and sterically diverse substituents on the phenyl ring.
本文描述了一种 PI3K 抑制剂 GDC-0908（1）的实用的汇聚式合成方法。该过程通过钯催化的分子内直接 C-H 芳基化反应形成二氢苯并噻吩并[3,2-e]氧杂环戊烯，并通过 Negishi 偶联构建关键的 C-C 键。我们进一步通过钯催化的分子内直接 C-H 芳基化反应，开发了一种通用的二氢苯并噻吩并[3,2-e]氧杂环戊烯的合成方法，该方法对芳环上电子和空间位阻不同的取代基均具有良好的耐受性。
