Ammonia → Dabigatran ethyl ester mesylate

Participants

Reaction Conditions

Reaction Steps

Hydrogen chloride gas was passed into a mixture of calcium chloride (125 g) and ethanol (1500 ml) at a temperature below 20° C. for a period of 30 minutes. The reaction mixture was cooled to −15 to −5° C. and stirred for 15 minutes. Ethyl 3-(2-((4-cyanophenylamino)methyl)-1-methyl-N-(pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxamido)propanoate mesylate compound of formula-10 (500 g) was added to the reaction mixture. Hydrogen chloride gas was slowly purged into the reaction mixture for a period of 3 hours. The temperature of the reaction mixture was raised to 25-35° C. and stirred for 10 hours. After completion of the reaction, expell the hydrogen chloride gas present in the reaction mixture under nitrogen atmosphere. Ethanol (2500 ml), followed by ammonium carbonate (2000 g) were added to the reaction mixture and stirred for 40 minutes at −30±5° C. The reaction mixture was cooled to 0-5° C. and ammonia gas was passed into the reaction mixture for 3 hours. The temperature of the reaction mixture was raised to 20-30° C. and stirred for 20 hours. After completion of the reaction, filtered the reaction mixture and the filtrate was concentrated to get title compound. Purity by HPLC: 80.61%;

Provenance & Evidence