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

Abstract

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