POLYMORPHOUS FORM OF THE MONOPOSPHATE HYDRATE SALT OF THE KNOWN TETRAHYDROISOQUINOLINE DERIVATIVE Russian patent published in 2023 - IPC C07D487/04 A61K31/519 A61P35/00 

FIELD: chemical industry.

SUBSTANCE: invention relates to a method for obtaining crystalline (1S,2S,3S,5R)-3-((6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl)oxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentan-1,2-diol monophosphate hydrate, characterized by a diffraction pattern measured using Cu K-alpha radiation having the following list of PXRD peaks°2θ: 4.5, 5.8, 7.2, 8.9, 10.5, 10.7, 11.5, 12.2, 13.1, 14.7, 15.3, 16.6, 17.5, 18.0, 18.6, 19.3, 21.0, 21.6, 22.7, 23.1, 23.5, 24.8 The method according to the invention is carried out by obtaining a mixture of (1S,2S,3S,5R)-3-((6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl)oxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentan-1,2-diol, 2-propanol and water; subsequent addition of phosphoric acid and 2-propanol to form a solution; heating the solution to a crystallization temperature and adding more 2-propanol to the solution; and maintaining the solution at the crystallization temperature to form crystalline (1S,2S,3S,5R)-3-((6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl)oxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentan-1,2-diol monophosphate hydrate.

EFFECT: obtaining crystalline (1S,2S,3S,5R)-3-((6-(difluoromethyl)-5-fluoro-1,2,3,4-tetrahydroisoquinolin-8-yl)oxy)-5-(4-methyl-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentan-1,2-diol monophosphate hydrate having low hygroscopicity.

12 cl, 8 dwg, 7 tbl, 13 ex