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

…, DF Roberts, DA Entwistle, PA Glossop…

Index: Dillon, Barry R.; Roberts, Dannielle F.; Entwistle, David A.; Glossop, Paul A.; Knight, Craig J.; Laity, Daniel A.; James, Kim; Praquin, Celine F.; Strang, Ross S.; Watson, Christine A. L. Organic Process Research and Development, 2012 , vol. 16, # 2 p. 195 - 203

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Citation Number: 11

Abstract

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–H 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 ...