Improved Practical Synthesis of DY‐038, an Oral Available Antiplatelet Agent

Recently, we reported the promising activity of a series of novel bicyclic pyridine derivatives as antiplatelet agents. Herein, we describe a modified and improved chemical synthesis of the lead compound, 1-(3-cyano-5-oxo-5,7-dihydrofuro[3,4-b]pyridin-2-yl)-4-methyl-N-((4-methylbenzyl)sulfonyl)piperidine-4-carboxamide (1), with the aim to produce from milligrams to 10 g of the pure compound that is necessary for the preclinical studies. This novel process is one step shorter and starts from cheap materials, achieving a sevenfold of the total yield from 0.7 % to 5 %. Additionally, it also avoids the use of palladium on carbon as well as all of the steps involve simple purifications without chromatography.