FIELD: chemistry.
SUBSTANCE: invention relates to a method for producing a crystalline polymorph of the form A of 3-[5-amino-4-(3-cyanobenzoyl)pyrazole-1-yl]-N-cyclopropyl-4-methylbenzamide, wherein said form A has a powder X-ray diffractogram measured using Cu Kα emission, with peaks at 2θ = approximately 9.3, 9.7, 10.2, 10.5, 11.7, 13.0, 14.5, 15.0, 15.5, 16.0, 16.4, 16.9, 17.8, 18.0, 20.0, 20.5, 20.9, 22.0, 22.3, 23.4, 24.2, and 24.5°, including (a) dissolving 3-[5-amino-4-(3-cyanobenzoyl)pyrazole-1-yl]-N-cyclopropyl-4-methylbenzamide at a temperature of at least 40°C in an anhydrous solvent or a mixture of anhydrous solvents, resulting in a solution wherein the solvent or solvents comprise less than approximately 5 wt.% water relative to the initial substance, 3-[5-amino-4-(3-cyanobenzoyl)pyrazole-1-yl]-N-cyclopropyl-4-methylbenzamide, and wherein the anhydrous solvent or mixture of anhydrous solvents is selected from the group consisting of C1-6 alcohols or mixtures thereof; (a') optionally introducing seeding into the solution of crystals of form A of 3-[5-amino-4-(3-cyanobenzoyl)pyrazole-1-yl]-N-cyclopropyl-4-methylbenzamide; (b) cooling the solution, thereby producing crystals of the polymorph of form A of 3-[5-amino-4-(3-cyanobenzoyl)pyrazole-1-yl]-N-cyclopropyl-4-methylbenzamide; (c) isolating crystals; wherein the stage of cooling (b) is executed at a speed of approximately 1 to 0.01°C /min, wherein the temperature applied during crystallisation does not exceed 80°C, wherein the solution of 3-[5-amino-4-(3-cyanobenzoyl)pyrazole-1-yl]-N-cyclopropyl-4-methylbenzamide is not exposed to temperatures over 70°C for longer than 24 hours.
EFFECT: selective production of a non-hygroscopic crystalline form A of 3-[5-amino-4-(3-cyanobenzoyl)pyrazole-1-yl]-N-cyclopropyl-4-methylbenzamide.
20 cl, 6 dwg, 4 tbl, 1 ex
