A novel route for the synthesis of androgen receptor antagonist enzalutamide

A novel route of enzalutamide was developed in five steps. Starting from 4-amino-2-(trifluoromethyl)benzonitrile (7) and Boc-2-aminoisobutyric acid (16), condensation, deprotection, Ullmann coupling, cyclization and amination provided enzalutamide in 41.0% total yield. This route avoids the using of toxic chemical, unstable intermediate and high-risk reaction. It is a potential efficient and economical procedure for industrialization. (c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.