Development of an asymmetric Michael addition in a practical synthesis of ABT-546.
ABT-546 is a selective antagonist of the endothelin A receptor. This review will present the development of a scalable synthesis of ABT-546 from early discovery to the route that was employed to prepare sufficient material for toxicology and phase I clinical trials. During the course of this project, an asymmetric conjugate addition of beta-ketoesters to nitrostyrenes was discovered that installed the absolute chirality of the molecule, thus forming the critical bond connection in 88% ee.
Barnes
D M
DM
Abbott Laboratories, PPD Process Research, Dept 45N, North Chicago, IL 60064, USA. david.barnes@abbott.com