Total Synthesis of Rucaparib br

Abstract

A concise total synthesis of rucaparib, an FDA-approved drug for ovarian and prostate cancers, is reported. TheHeck reaction of the commercially available aryl iodide withacrylonitrile provided the desired (E)-2-aminocinnamonitrile deriva-tive. A subsequent imino-Stetter reaction of the aldimine derived from2-aminocinnamonitrile and aldehyde furnished indole-3-acetonitrilebearing the desired substituents at appropriate positions. Theconstruction of thefinal azepinone scaffold via reduction of thenitrile group followed by seven-membered lactamization affordedrucaparib. Notably, the synthesis of rucaparib is achieved usingcommercially available starting materials in only three separationoperations with 54% overall yield.