Successful development and scale-up of a palladium-catalysed amination process in the manufacture of ZM549865

…, JC McManus, A O'Kearney-McMullan…

Index: Robinson, Graham E.; Cunningham, Oliver R.; Dekhane, Mouloud; McManus, Julie C.; O'Kearney-McMullan, Anne; Mirajkar, Abdurrazzaque M.; Mishra, Vikas; Norton, Alison K.; Venugopalan; Williams, Emyr G. Organic Process Research and Development, 2004 , vol. 8, # 6 p. 925 - 930

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Citation Number: 13

Abstract

Key steps in the synthesis of ZM549865 (a 5-HT receptor antagonist) are the palladium- catalysed amination of ethyl 8-bromo-6-fluoro-4-oxo-4 H-2-chromenecarboxylate and subsequent hydrolysis of the ester group. The development of a simple, robust process capable of making multikilogram amounts of the required intermediate is described. Performing the amination step at 125° C instead of 80° C and optimising the hydrolysis ...