ΜΕΘΟΔΟΣ ΠΑΡΑΓΩΓΗΣ ΕΝΟΣ ΠΑΡΑΓΩΓΟΥ ΒΕΝΖΙΜΙΔΑΖΟΛΙΟΥ

Η εφεύρεση σχετίζεται με μια μέθοδο παρασκευής της ένωσης του τύπου 1, ενός πολυτίμου ενδιάμεσου προϊόντος στη σύνθεση της φαρμακευτικής δραστικής ουσίας ετεξιλική δαβιγατράνη. Preparation of 3-({2-[(4-carbamimidoyl-phenylamino)-methyl]-1-methyl-1H-benzoimidazole-5-carbonyl}-pyridin-2-yl-amino)-propionic acid ethyl ester (I) involves reacting 3-[(3-amino-4-methylamino-benzoyl)-pyridin-2-yl-amino]-propionic acid ethyl ester (II) with (4-cyano-phenylamino)-acetic acid (III) in presence of coupling agent to form 3-({2-[(4-cyano-phenylamino)-methyl]-1-methyl-1H-benzoimidazole-5-carbonyl}-pyridin-2-yl-amino)-propionic acid ethyl ester (IV), which is converted without isolation into hydrobromide salt of (IV) (V), which is converted to (I). Preparation of 3-({2-[(4-carbamimidoyl-phenylamino)-methyl]-1-methyl-1H-benzoimidazole-5-carbonyl}-pyridin-2-yl-amino)-propionic acid ethyl ester of formula (I) optionally in the form of its acid addition salt involves reacting 3-[(3-amino-4-methylamino-benzoyl)-pyridin-2-yl-amino]-propionic acid ethyl ester (II) with (4-cyano-phenylamino)-acetic acid (III) in presence of coupling agent to form 3-({2-[(4-cyano-phenylamino)-methyl]-1-methyl-1H-benzoimidazole-5-carbonyl}-pyridin-2-yl-amino)-propionic acid ethyl ester (IV), which is converted without isolation into hydrobromide salt of 3-({2-[(4-cyano-phenylamino)-methyl]-1-methyl-1H-benzoimidazole-5-carbonyl}-pyridin-2-yl-amino)-propionic acid ethyl ester of formula (V), which is converted to (I). An independent claim is included for new intermediate hydrobromide salt of 3-({2-[(4-cyano-phenylamino)-methyl]-1-methyl-1H-benzoimidazole-5-carbonyl}-pyridin-2-yl-amino)-propionic acid ethyl ester (V). [Image].