立体控制α-氨基酸n -芳基化合成PI3K抑制剂GDC-0077

IF 2.1 3区化学 Q2 CHEMISTRY, ORGANIC

Tetrahedron Pub Date : 2019-08-09 DOI:10.1016/j.tet.2019.04.057

Chong Han, Sean M. Kelly, Theresa Cravillion, Scott J. Savage, Tina Nguyen, Francis Gosselin

引用次数: 14

摘要

报道了一种高效合成PI3K抑制剂GDC-0077的方法，该方法具有两个连续的cu催化CN偶联反应。所描述的合成路线包括手性二氟甲基取代的恶唑烷酮的化学选择性ullmann型偶联，具有高立体化学完整性的cu催化的l-丙氨酸n-芳基化，以及高收率的最终酰胺键形成步骤，以生产纯度为99.5%的GDC-0077。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Synthesis of PI3K inhibitor GDC-0077 via a stereocontrolled N-arylation of α-amino acids

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Synthesis of PI3K inhibitor GDC-0077 via a stereocontrolled N-arylation of α-amino acids

An efficient synthesis of PI3K inhibitor GDC-0077, featuring two consecutive Cu-catalyzed CN coupling reactions, is reported. The described synthetic route involves a chemoselective Ullmann-type coupling of a chiral difluoromethyl-substituted oxazolidinone, a Cu-catalyzed N-arylation of l-alanine with high stereochemical integrity, and a high-yielding final amide bond formation step to produce GDC-0077 in >99.5 area % HPLC purity.

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来源期刊

Tetrahedron 化学-有机化学

CiteScore

3.90

自引率

4.80%

发文量

439

审稿时长

34 days

期刊介绍： Tetrahedron publishes full accounts of research having outstanding significance in the broad field of organic chemistry and its related disciplines, such as organic materials and bio-organic chemistry. Regular papers in Tetrahedron are expected to represent detailed accounts of an original study having substantially greater scope and details than that found in a communication, as published in Tetrahedron Letters. Tetrahedron also publishes thematic collections of papers as special issues and ''Reports'', commissioned in-depth reviews providing a comprehensive overview of a research area.