Route Development and Multikilogram GMP Delivery of a Somatostatin Receptor Antagonist

Route development and demonstration on multikilogram scale for the first GMP delivery of MK-4256 are described. Key aspects of the convergent route include a regioselective green iodination, one-pot oxadiazole synthesis, and an efficient ketone Pictet–Spengler reaction with diastereomeric upgrade vi...

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Bibliographic Details
Published in:Organic process research & development 2012-08, Vol.16 (8), p.1329-1337
Main Authors: Ruck, Rebecca T, Huffman, Mark A, Stewart, Gavin W, Cleator, Ed, Kandur, Wynne V, Kim, Mary M, Zhao, Dalian
Format: Article
Language:English
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Summary:Route development and demonstration on multikilogram scale for the first GMP delivery of MK-4256 are described. Key aspects of the convergent route include a regioselective green iodination, one-pot oxadiazole synthesis, and an efficient ketone Pictet–Spengler reaction with diastereomeric upgrade via crystallization to afford 6 kg of API. A recycle procedure augmented the yield of desired diastereomer in the Pictet–Spengler reaction from a mixture of diastereomers heavily enriched in the undesired diastereomer.
ISSN:1083-6160
1520-586X
DOI:10.1021/op300128c