New polymorphs of ethyl 3-[(2-{[4-(hexyloxycarbonylamino-imino- methyl)-phenylamino]-methyl-1-methyl-1h-benzimidazole-5-carbonyl) -pyridin-2-yl-amino]-propionate

Process for preparing the anhydrous form III of ethyl 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazole-5-carbonyl)-pyridin-2-yl-amino]-propionate, characterised in that

• a) ethyl 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazole-5-carbonyl)-pyridin-2-yl-amino]-propionate base is dissolved in a solvent mixture of diisopropylether/THF=60:40 at 60° C. with a concentration of approx. 120 mg/ml,
• b) the solution is cooled at a cooling rate of 1° C./h to a temperature of approx. 25° C. and left to stand for a further 72 h,
• c) the precipitated crystals are suction filtered, and
• d) the product thus obtained is dried at ambient temperature.

Process for preparing the anhydrous form IV of ethyl 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazole-5-carbonyl)-pyridin-2-yl-amino]-propionate, characterised in that

• ethyl 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazole-5-carbonyl)-pyridin-2-yl-amino]-propionate base is dissolved in 1,4-dioxane at ambient temperature with a concentration of approx. 120 mg/ml,
• b) the solution is left to equilibrate for 2 h with stirring at ambient temperature and then filtered off,
• c) hexane (as antisolvent) is added to the clear solution at ambient temperature in a molar ratio of 1:1 to 1,4-dioxane,
• d) the precipitated crystals are suction filtered and
• e) the product thus obtained is dried at ambient temperature.

Method of preparing the monohydrate I of ethyl 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazole-5-carbonyl)-pyridin-2-yl-amino]-propionate, characterised in that

• a) ethyl 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazole-5-carbonyl)-pyridin-2-yl-amino]-propionate base is dissolved in a solvent mixture of DMSO/cyclohexanone=80:20 at 60° C. with a concentration of approx. 120 mg/ml,
• b) the solution is cooled at a cooling rate of 1° C./h to a temperature of approx. 5° C. and left to stand for a further 24 h at this temperature,
• c) the precipitated crystals are suction filtered and
• d) the product thus obtained is dried at ambient temperature.

Method of preparing the monohydrate II of ethyl 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazole-5-carbonyl)-pyridin-2-yl-amino]-propionate, characterised in that

• a) ethyl 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazole-5-carbonyl)-pyridin-2-yl-amino]-propionate base is dissolved in a solvent mixture of acetonitrile/acetone=60:40 at 60° C. with a concentration of approx. 60 mg/ml,
• b) the solution is cooled at a cooling rate of 1° C./h to a temperature of approx. 5° C. and left to stand for a further 24 h at this temperature,
• c) the precipitated crystals are suction filtered and
• d) the product thus obtained is dried at ambient temperature.

Method of preparing the solvate I of ethyl 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazole-5-carbonyl)-pyridin-2-yl-amino]-propionate, characterised in that

• a) ethyl 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-phenylamino]-methyl}-1-methyl-1H-benzimidazole-5-carbonyl)-pyridin-2-yl-amino]-propionate base is suspended in nitrobenzene at 50° C. with a concentration of approx. 333 mg/ml,
• b) the suspension is filtered hot (50° C.) and the resulting saturated solution is cooled to a temperature of approx. 20° C. at a cooling rate of 30° C./h to and left to stand for a further 24 h,
• c) optionally, in the event that no crystals are formed within these 24 h, the solution is evaporated down until crystallisation sets in,
• d) the precipitated crystals are suction filtered and
• d) the product thus obtained is dried at ambient temperature.