Development of a Scaleable Synthesis of a Geminal Dimethyl Tertiary Amine as an Inhaled Muscarinic Antagonist for the Treatment of COPD

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• 作者：Barry R. Dillon ; Dannielle F. Roberts ; David A. Entwistle ; Paul A. Glossop ; Craig J. Knight ; Daniel A. Laity ; Kim James ; Celine F. Praquin ; Ross S. Strang ; Christine A. L. Watson
• 刊名：Organic Process Research & Development
• 出版年：2012
• 出版时间：February 17, 2012
• 年：2012
• 卷：16
• 期：2
• 页码：195-203
• 全文大小：467K
• 年卷期：v.16,no.2(February 17, 2012)
• ISSN：1520-586X

文摘

An efficient and scalable process for the synthesis of muscarinic antagonist, PF-3635659 1, is described, illustrating redesign of an analogue-targeted synthesis which contained a scale-limiting rhodium-activated C鈥揌 amination step. The final route includes a reproducible modified Bouveault reaction which has not previously been reported on a substrate of this complexity, or on such a scale with over 5 kg of the requisite gem-dimethylamine prepared via this methodology.