Water → ethyl 3-(2-((4-(N-(hexyloxycarbonyl)carbamimidoyl)phenylamino)methyl)-1-methyl-N-(pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxamido)propanoate

Participants

Reaction Steps

73 gm ethyl 3-(2-((4-carbamimidoylphenylamino)methyl)-1-methyl-N-(pyridin-2-yl)-1H-benzo[d]imidazole-5-carboxamido)propanoate hydrochloride of Formula (E) in 1460 mL methylene dichloride were stirred 25° C. to 35° C. and cooled to 0° C. to 5° C. To the reaction mixture was treated with 61.1 mL triethylamine at 0° C. to 5° C. and stirred for 30 minutes followed by addition of n-hexyl chloroformate solution (31.35 mL in 365 mL methylene dichloride for 2 hrs. The residue was treated with 730 mL water and extracted with 370 mL methylene dichloride. The methylene dichloride was distilled and the residue was purified using mixture of methylene dichloride and ethanol to afforded amorphous form of dabigatran Etexilate of Formula (F). The amorphous form of dabigatran etexilate of Formula (F) is characterized by x-ray powder diffraction pattern as depicted in FIG. 4.

Provenance & Evidence