Development of a Multi-Kilogram-Scale Synthesis of AZD1283: A Selective and Reversible Antagonist of the P2Y12 Receptor

…, M Bollmark, R Ehrl, P Schuisky, A Witt

Index: Andersen, Soren M.; Aurell, Carl-Johan; Zetterberg, Fredrik; Bollmark, Martin; Ehrl, Robert; Schuisky, Peter; Witt, Anette Organic Process Research and Development, 2013 , vol. 17, # 12 p. 1543 - 1551

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Citation Number: 4

Abstract

Ethyl 6-chloro-5-cyano-2-methylnicotinate (4) was coupled with 4-piperidinecarboxylic acid (isonipecotic acid) in 81% yield to pyridine acid 10. An amide coupling between 10 and benzylsulfonamide (6) afforded AZD1283 (1) in 79% yield using CDI as coupling reagent. The synthesis has been developed and scaled up to 20 kg batches of 1, supporting preclinical and clinical studies. Development work towards 2-chloropyridine 4 and ...