Development of a Potential Manufacturing Route to PF-00610355: A Novel Inhaled 尾2-Adrenoreceptor Agonist

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• 作者：Pieter D. de Koning ; Nieves Castro ; Iain R. Gladwell ; Natalie A. Morrison ; Ian B. Moses ; Maninder S. Panesar ; Alan J. Pettman ; Nicholas M. Thomson
• 刊名：Organic Process Research & Development
• 出版年：2011
• 出版时间：November 18, 2011
• 年：2011
• 卷：15
• 期：6
• 页码：1256-1265
• 全文大小：935K
• 年卷期：v.15,no.6(November 18, 2011)
• ISSN：1520-586X

文摘

The development of a practical, scalable route to PF-00610355 (8) is described. In this convergent approach, amine 9 is coupled to protected bromohydrin 1 to give the doubly protected intermediate 26. TBS-Deprotection of 26 affords the benzyl protected penultimate intermediate 25 which is crystallized as the corresponding hemifumarate salt 25a. On the basis of solubility data, the final debenzylation was conducted in aqueous THF, and the API (8) is isolated from acetonitrile by an unusual distillative crystallization process. The development of an efficient process to prepare amine 9 is also described.