4-METHYL-3-(4-METHYLIMIDAZOL-1-YL)-5-TRIFLUOROMETHYLPHENYL-3-(4-PYRIDIN-3-YLPYRIMIDIN-2-YLAMINO)BENZAMIDE SALTS

摘要

FIELD: chemistry.;SUBSTANCE: invention relates to a novel salt - monohydrate of monohydrochloride of 4-methyl-N-[3-(4-methylimidazol-1-yl)-5-trifluoromethylphenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)benzamide, having protein kinase inhibiting properties. The invention also relates to a method of obtaining said compound. The method involves the following steps: (a) merging 4-methyl-N-[3-(4-methylimidazol-1-yl)-5-trifluoromethylphenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)benzamide in form of a free base and hydrochloric acid in methanol in a nitrogen atmosphere; (b) heating the reaction mixture to temperature in the range of approximately 42-50°C; (c) stirring the reaction mixture; (d) filtering the reaction mixture while maintaining temperature higher than 40°C to obtain a transparent solution; (e) cooling the transparent solution to approximately 30°C while stirring in a nitrogen atmosphere; (f) adding an inoculant to the solution; (g) cooling the solution containing the inoculant to approximately 23°C; (h) stirring the solution to obtain a suspension; (i) cooling the obtained suspension to approximately -10°C; (j) stirring the obtained suspension; (k) filtering solid substances, washing the solid substance with cold methanol; and (l) drying the solid substance at approximately 50-55°C and 10-20 torr to obtain the end product.;EFFECT: monohydrate of monohydrochloride of said compound has high solubility compared to a base and hydrochloride salt and has high bioavailability in vivo compared to said compounds.;4 cl, 17 tbl, 11 ex