Merck Sharp + Dohme Corp.

Paul Gerard Bulger

Guy R Humphrey

Mark E Scott

Kevin Michael Belyk

John Limanto

Cheol Keun Chung

Birgit Kosjek

Nelo R Rivera

A novel process is provided for the efficient preparation of an asymmetric compound of structural formula I: comprising a copper-catalyzed, carbon-nitrogen cross-coupling step. The process described as part of the present invention can be used to manufacture poly (ADP-ribose) polymerase (PARP) inhibitors, which may be useful for the treatment of cancer. In particular, the present invention describes a process for the manufacture of the PARP inhibitor, 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide.

Regioselective N-2 arylation of indazoles

A novel process is provided for the efficient preparation of an asymmetric compound of structural formula I: employing dynamic kinetic resolution (DKR). The DKR process involves an enzymatic enantioselective amination reaction catalyzed by transaminases. The process can be used to manufacture key intermediates in the preparation of poly (ADP-ribose) polymerase (PARP) inhibitors which may be useful for the treatment of cancer.

Biocatalytic transamination process

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Jersey City, NJ, United States of America

Paul Gerard Bulger