Multkilogram Scale-Up of a Reductive Alkylation Route to a Novel PARP Inhibitor

…, E Kougoulos, JS Mathew, L McMillan…

Index: Gillmore, Adam T.; Badland, Matthew; Crook, Clare L.; Castro, Nieves M.; Critcher, Douglas J.; Fussell, Steven J.; Jones, Katherine J.; Jones, Matthew C.; Kougoulos, Eleftherios; Mathew, Jinu S.; McMillan, Lynne; Pearce, John E.; Rawlinson, Fiona L.; Sherlock, Alexandra E.; Walton, Robert Organic Process Research and Development, 2012 , vol. 16, # 12 p. 1897 - 1904

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Citation Number: 8

Abstract

Novel PARP inhibitor 1 is a promising new candidate for treatment of breast and ovarian cancer. A modified synthetic route to 1 has been developed and demonstrated on 7 kg scale. In order to scale up the synthesis to multikilogram scale, several synthetic challenges needed to be overcome. The key issues included significant thermal hazards present in a Leimgruber–Batcho indole synthesis, a low-yielding side-chain installation, a nonrobust ...