An efficient and safe process for the preparation of ticagrelor a platelet aggregation inhibitor via resin-NO2 catalyzed formation of triazole ring

摘要

An efficient, safe and improved process for the preparation of ticagrelor >1, a platelet aggregation inhibitor is described. Synthesis comprises the condensation of pyrimidine amine derivative >14 with cyclopentyl derivative >13 in ethylene glycol followed by construction of triazole compound >16 by diazotization of the obtained intermediate >15 with a green and safer reagent “Resin-NO2” in water and acetonitrile mixture. Condensation of >16 with cyclopropylamine derivative >10 followed by deprotection of compound >12 with hydrochloric acid in dichloromethane (DCM) furnished ticagrelor >1 with an overall yield of 65 % and purity of 99.78 % by HPLC. Each reaction stage was optimized independently to establish the scalable and plant friendly process. An efficient and a safe process for key intermediate >14 which involve nitration reaction has also been developed. Safety parameters were established by understanding the thermal events of the reaction by DSC analysis.>Graphical abstractSynthesis of ticagrelor via resin-NO2 catalysed formation of triazole ring