ABT-472

A nine-step convergent process was developed for the synthesis of a benzimidazole PARP inhibitor I (succinate salt) (ABT-472).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.