Process Development for ABT-472, a Benzimidazole PARP Inhibitor

A nine-step convergent process was developed for the synthesis
of ABT-472, a benzimidazole PARP inhibitor. The identity and
origin of several impurities were determined, and the process
was modified to reduce or eliminate these impurities. A number
of safety and control issues were investigated. The original
synthesis was shortened to 9 steps and streamlined while
maintaining a convergent strategy. A stable salt was selected,
and control of the API solid form was established. The process
was successfully scaled up to provide 8.5 kg of final product of
>99% purity in 33% yield over 9 steps.