CRYSTALS OF ALKYNYL-CONTAINING COMPOUND, SALT AND SOLVATE THEREOF, METHOD OF PRODUCTION AND WAYS OF APPLICATION THEREOF Russian patent published in 2024 - IPC C07D471/04 A61K31/496 A61P35/00 A61P35/02 

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing crystalline form I 3-((1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide, characterized by characteristic peaks at the following positions on the XRPD diagram, expressed in values of angle 2θ: 9.498 ± 0.2°, 12.293 ± 0.2°, 13.045 ± 0.2°, 15.899 ± 0.2°, 16.199 ± 0.2°, 18.183 ± 0.2°, 18.327 ± 0.2°, 21.755 ± 0.2°, 22.362 ± 0.2°, 25.690 ± 0.2°, or characteristic peaks at 8.968± 0.2°, 9.498 ± 0.2°, 12.293 ± 0.2°, 13.045 ± 0.2°, 15.899 ± 0.2°, 16.199 ± 0.2°, 16.533 ± 0.2°, 16.908 ± 0.2°, 18.183 ± 0.2°, 18.327 ± 0.2°, 20.042 ± 0.2°, 20.271 ± 0.2°, 21.755 ± 0.2°, 22.362 ± 0.2°, 25.690 ± 0.2°. Method involves crystallisation 3-((1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide in an organic solvent, wherein the crystallisation method is stirring at room temperature or adding an anti-solvent; crystallization temperature is 20–50 °C. If crystallisation is carried out by means of a stirring method at room temperature, the organic solvent is heptane, methanol, ethanol, isopropanol, methyl-tert-butyl ether, acetonitrile, acetone, 2-butanone, ethyl acetate and isopropyl acetate; if an anti-solvent is used for crystallisation, the organic solvent is DMSO; anti-solvent is water, isopropanol and acetonitrile.

EFFECT: obtaining crystalline form I 3-((1H-pyrazolo[3,4-b]pyridin-5-yl)ethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide, having good stability, with high reproducibility.

5 cl, 59 dwg, 24 tbl, 30 ex