P. Solanki, Sekhar Babu Uppelli, R. B. Patil
May 29, 2018
Citations
0
Influential Citations
2
Citations
Journal
ACS Omega
Abstract
Facile synthesis for Dabigatran etexilate mesylate (1), an anticoagulant drug, is reported using a novel synthon, n-hexyl-4-nitrophenyl carbonate (32), which substantially eliminates the formation of potential impurities 20–27, which were generated due to the use of n-hexyl chloroformate in previously reported methods. Pinner reaction to prepare a key and critical intermediate, amidine 8, was optimized using design of experiment software to establish critical process parameters to achieve 8 in 97% yield. Nucleophilic substitution of 8 with novel synthon n-hexyl-4-nitrophenyl carbonate (32) furnished the dabigatran base 9, which was then converted to its mesylate salt using methane sulfonic acid to provide 1 with an overall yield of 66% over three steps.