Route Selection and Process Development of a Multikilogram Route to the Inhaled A2a Agonist UK-432,097

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• 作者：Christopher P. Ashcroft ; Yann Dessi ; David A. Entwistle ; Lynsey C. Hesmondhalgh ; Adrian Longstaff ; Julian D Smith
• 刊名：Organic Process Research & Development
• 出版年：2012
• 出版时间：March 16, 2012
• 年：2012
• 卷：16
• 期：3
• 页码：470-483
• 全文大小：456K
• 年卷期：v.16,no.3(March 16, 2012)
• ISSN：1520-586X

文摘

This article describes the selection, process development, and scale-up of a synthetic route to a complex nucleoside analogue, the A_2a agonist UK-432,097 (1), that culminated in the manufacture of over 25 kg of the API. The key steps in the process were (1) a stereoselective glycosidation reaction; (2) a scalable bleach鈥揟EMPO oxidation; and (3) an unusual elevated temperature crystallization process for the final API. The problems that were encountered with the scale-up of the route together with how they were overcome are also presented.