p-Toluenesulfonic acid monohydrate → Edoxaban tosylate monohydrate

Participants

Reaction Conditions

Reaction Steps

N-(5-Chloropyridin-2-yl)-N′-[(1S,2R,4S)-4-(dimethylcarbamoyl)-2-{[(5-methyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexyl]ethanediamide p-toluenesulfonic acid (86.8 g) was dissolved in 30% hydrous ethanol (418 mL) at 60° C., and a solution (167 mL) of p-toluenesulfonic acid monohydrate (29.0 g) in 30% hydrous ethanol was added to the solution. The mixture was stirred at 70° C. for 1 hour, and then gradually cooled. At room temperature, ethanol was added to the cooled mixture, followed by stirring for 16 hours. The reaction mixture was stirred under ice-cooling for 1 hour, and the formed crystals were recovered by filtration, to thereby yield 102.9 g of the title compound.

Provenance & Evidence