Route Development and Multikilogram GMP Delivery of a Somatostatin Receptor Antagonist

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• 作者：Rebecca T. Ruck ; Mark A. Huffman ; Gavin W. Stewart ; Ed Cleator ; Wynne V. Kandur ; Mary M. Kim ; Dalian Zhao
• 刊名：Organic Process Research & Development
• 出版年：2012
• 出版时间：August 17, 2012
• 年：2012
• 卷：16
• 期：8
• 页码：1329-1337
• 全文大小：416K
• 年卷期：v.16,no.8(August 17, 2012)
• ISSN：1520-586X

文摘

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鈥揝pengler reaction with diastereomeric upgrade via crystallization to afford 6 kg of API. A recycle procedure augmented the yield of desired diastereomer in the Pictet鈥揝pengler reaction from a mixture of diastereomers heavily enriched in the undesired diastereomer.