CRYSTALLINE FORM LNP023 Russian patent published in 2024 - IPC C07D401/06 A61K31/454 A61P27/00 

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing a crystalline hydrated form of hydrochloride LNP023 (form HB), having formula (A), characterized by a powder X-ray diffraction pattern containing at least five peaks at 2-theta angles selected from (4.6±0.2)°, (6.8±0.2)°, (9.2±0.2)°, (10.0±0.2)°, (12.2±0.2)°, (12.6±0.2)°, (15.3±0.2)°, (16.6±0.2)°, (17.2±0.2)°, (19.1±0.2)°, (20.7±0.2)°, (21.3±0.2)°, (22.2±0.2)°, (24.0±0.2)°, (24.6±0.2)° and (28.0±0.2) when measured at a temperature in range from 20 to 30 °C using Cu-Calfa_1.2 radiation with wavelength of 0.15419 nm. Method comprises steps of (i) providing LNP023 hydrochloride in solid form; (ii) suspending LNP023 hydrochloride provided in step (i), in a first solvent containing acetone and water, in a weight ratio of acetone to water from 60:40 to 90:10, and heating to a temperature in range of 30 to 56 °C to dissolve a solid to obtain a solution; (iii) cooling the solution obtained in step (ii) and adding a second solvent containing acetone and ethyl acetate in a weight ratio of acetone to ethyl acetate from 0.5:3 to 1:1, with further cooling to a temperature in the range of about 0 to 25 °C to isolate crystals in the mother solution; (iv) separating at least a portion of the crystals obtained in step (iii) from the mother solution; (v) optionally washing the separated crystals obtained in step (iv) with a suitable solvent; and (vi) drying crystals obtained in step (iv) or (v). At step (v), a suitable organic solvent is selected from acetone and ethyl acetate.

EFFECT: obtaining crystalline hydrated form of hydrochloride LNP023 (form HB), having favorable physical and chemical properties.

7 cl, 8 dwg, 2 tbl, 5 ex