Substituted �-carboline derivatives, including MK-4256, have been shown to be selective antagonists of the somatostatin subtype receptor (SSTR3) and useful for treatment of Type 2 diabetes and its associated conditions. The medicinal chemistry synthesis of MK-4256 provided a convergent route to API. This talk will focus on the chemistry developed to allow processing on the necessary 3 kg scale for the first GMP delivery. Developments include: a green protocol for pyrazole iodination, a one-pot oxadiazole synthesis, and efficient ketone Pictet-Spengler reaction, and an epimerization procedure to recycle the undesired diastereomer formed in the Pictet-Spengler reaction.

Process chemistry for the first GMP delivery of SSTR3 antagonist MK-4256

243rd National Meeting (2012)

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