Facile Synthesis of Dabigatran Etexilate Mesylate, an Anticoagulant Drug, Using a Novel Synthon, -Hexyl-4-nitrophenyl Carbonate.

Facile synthesis for Dabigatran etexilate mesylate (), an anticoagulant drug, is reported using a novel synthon, -hexyl-4-nitrophenyl carbonate (), which substantially eliminates the formation of potential impurities -, which were generated due to the use of -hexyl chloroformate in previously reported methods. Pinner reaction to prepare a key and critical intermediate, amidine , was optimized using design of experiment software to establish critical process parameters to achieve in 97% yield. Nucleophilic substitution of with novel synthon -hexyl-4-nitrophenyl carbonate () furnished the dabigatran base , which was then converted to its mesylate salt using methane sulfonic acid to provide with an overall yield of 66% over three steps.