METHOD FOR PRODUCING POLYMORPH FORM OF 3-[5-AMINO-4-(3-CYANOBENZOYL)PYRAZOLE-1-YL]-N-CYCLOPROPYL-4-METHYLBENZAMIDE Russian patent published in 2022 - IPC C07D231/38 A61K31/415 

FIELD: organic chemistry.

SUBSTANCE: group of inventions relates to organic chemistry and represents methods for producing a form B of 3-[5-amino-4-(3-cyanobenzoyl)pyrazole-1-yl]-N-cyclopropyl-4-methylbenzamide having a powder X-ray diffraction pattern measured using Cu Kα radiation with peaks at 2θ approximately = 9.6, 10.1, 11.4, 13.1, 13.9, 14.8, 15.4, 15.8, 17.0, 17.4, 18.5, 18.8, 19.7, 19.9, 20.5, 21.0, 21.9, 22.9, 23.6, 24.6 and 25.7°. Methods are carried out by dissolving 3-[5-amino-4-(3-cyanobenzoyl)pyrazole-1-yl]-N-cyclopropyl-4-methylbenzamide at a temperature of at least 75°C in a solvent or a mixture of solvents selected from a group consisting of C_1-6 alcohols or mixtures thereof and containing less than approximately 5% by weight of water relatively to initial substance. The resulting solution is cooled at a temperature not exceeding 40°C. Then, isolated crystals are heated at a temperature from 75 to 210°C for more than 1 min, obtaining the form B of 3-[5-amino-4-(3-cyanobenzoyl)pyrazole-1-yl]-N-cyclopropyl-4-methylbenzamide. An alternative method for the production includes: dissolution of 3-[5-amino-4-(3-cyanobenzoyl)pyrazole-1-yl]-N-cyclopropyl-4-methylbenzamide at a temperature of 105°C in an anhydrous solvent or a mixture of anhydrous solvents selected from a group consisting of C_1-6 alcohols or mixtures thereof; optional filtration of the resulting solution to remove particles with a maximum diameter of more than 100 mcm; cooling of the solution to 85°C; introduction of a seed in a solution of crystals of the form B of 3-[5-amino-4-(3-cyanobenzoyl)pyrazole-1-yl]-N-cyclopropyl-4-methylbenzamide; optional additional cooling of the solution; optional addition of a seed to the solution of crystals of the form B of 3-[5-amino-4-(3-cyanobenzoyl)pyrazole-1-yl]-N-cyclopropyl-4-methylbenzamide; cooling of the solution to less than 70°C and isolation of crystals of the form B of 3-[5-amino-4-(3-cyanobenzoyl)pyrazole-1-yl]-N-cyclopropyl-4-methylbenzamide.

EFFECT: methods make it possible to obtain a crystalline modification of 3-[5-amino-4-(3-cyanobenzoyl)pyrazole-1-yl]-N-cyclopropyl-4-methylbenzamide, which has a combination of several properties, namely improved hygroscopicity, thermodynamic stability and solubility.

32 cl, 9 dwg, 3 tbl, 3 ex