Synthesis of a Pinacol Boronate Precursor for [¹⁸F]Rucaparib Radiosynthesis

A novel synthetic approach toward pinacol boronate used as a precursor in the recent radiosynthesis of [¹⁸F]rucaparib is described in this study. The Heck reaction of an ortho-iodoaniline derivative bearing a chloride group at the meta-position with acrylonitrile produced the desired (E)-2-aminocinnamonitrile derivative. The subsequent cyanide-catalyzed imino-Stetter reaction of aldimine derived from the obtained 2-aminocinnamonitrile and aldehyde afforded the required trisubstituted indole-3-acetonitrile. The reduction of the nitrile group with cobalt boride followed by the construction of an azepinone scaffold generated indoloazepinone bearing a chloride substituent at the C6-position of the indole scaffold. The Suzuki–Miyaura borylation of the chloride substituent produced pinacol boronate previously used in the synthesis of [¹⁸F]rucaparib. Detailed outcomes of different approaches using different 2-aminocinnamonitriles were discussed as well.