As part of our program chemistry effort for poly(ADP-ribose) polymerase (PARP) inhibitor MK–4827 (Niraparib), our group desired a method to selectively construct N-2 arylated indazoles in a manner that avoids handling bioactive intermediates. This poster will outline the optimization and scope of a novel arylation coupling that employs a protecting group strategy to enable exclusive formation of the desired N-2 aryl indazole regioisomer for a wide range of aryl halides. More importantly, the protected intermediates, which were shown to be inactive against PARP, could be easily converted to the desired primary amide via a mild and high yielding deprotection. Application of this strategy towards an efficient new route to MK–4827 will also be presented.

Development of a highly regioselective N-2 arylation of indazole carboxamides: Application toward the synthesis of MK-4827 (Niraparib)

249th National Meeting (2015)

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