CRYSTALLINE FORMS OF MAGL INHIBITOR Russian patent published in 2023 - IPC C07D403/10 

FIELD: organic chemistry.

SUBSTANCE: invention relates to a method of obtaining a crystalline form of monohydrochloride 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin-1- carboxylate, the process comprising the following steps: i) preparing a saturated solution of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl monohydrochloride )piperazine-1-carboxylate in a solvent selected from acetone, ethanol and tert-butyl methyl ether at a temperature of approximately 60°C; ii) adding a heptane antisolvent to the saturated solution at a temperature of approximately 60°C; iii) cooling to a temperature from about -5°C to about 15°C; iv) collecting the solid substance in the presence of a precipitate and evaporating the solvent to collect the solid substance in the absence of a precipitate; and v) optionally drying. The crystalline form of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate monohydrochloride obtained by this method is Form 2, characterized by X-ray powder diffractometry (XRPD) with characteristic peaks at 8.6° 2-theta, 14.3° 2-theta, 15.6° 2-theta, 19.0° 2-theta, 19.8° 2-theta and 20.7° 2-theta.

EFFECT: method of obtaining a crystalline form of 1,1,1,3,3,3-hexafluoropropan-2-yl-4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazin-1monohydrochloride-carboxylate with improved stability and solubility as a MAGL inhibitor.

2 cl, 57 dwg, 2 tbl, 19 ex