NEW CRYSTAL FORM OF VASCULAR PERMEABILITY BLOCKER COMPOUND Russian patent published in 2023 - IPC C07J67/00 C07J9/00 C07J17/00 C07J7/00 A61K31/56 A61P35/00 A61P29/00 A61P3/10 

FIELD: pharmaceuticals.

SUBSTANCE: invention relates to a method of obtaining the crystalline form of (E)-methyl-6-((3S,8S,9S,10R,13S,14S,17R)-3-(((2S,5S,6R)-5-acetoxy-6-(acetoxymethyl)-5,6-dihydro-2H-pyran-2-yl)oxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-yl)hept-5-enoate, characterized by a powder X-ray pattern containing peaks at the following diffraction angles of 2Ɵ: 16.0° ±0.2°, 19.5° ±0.2°, 18.3° ±0.2°, 15.1° ±0.2°, 21.9° ±0.2°. The production method involves preparing a compound represented by formula 1 by reacting a compound of formula 2-1 in the presence of a catalyst containing lithium nonafluoro-1-butylsulfonate (Li-NFBS) and (s)-camphorsulfonic acid according to the reaction formula below (1 ). Then (E)-methyl-6-((3S,8S,9S,10R,13S,14S,17R)-3-(((2S,5S,6R)-5-acetoxy-6-(acetoxymethyl)-5),6-dihydro-2H-pyran-2-yl)oxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-yl)hept-5-enoate which is the α-isomer of the compound represented by Formula 1 in solid form is obtained. The resulting (E)-methyl-6-((3S,8S,9S,10R,13S,14S,17R)-3-(((2S,5S,6R)-5-acetoxy-6-(acetoxymethyl)-5,6-dihydro-2H-pyran-2-yl)oxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-yl)hept-5-enoate is dispersed in a solvent of relatively low solubility selected from water, methanol or ethanol; the resulting dispersion is mixed; the resulting wet solid is separated; and the resulting solid is dried. The invention also relates to a method of producing (E)-methyl-6-((3S,8S,9S,10R,13S,14S,17R)-3-(((2S,5S,6R)-5-acetoxy-6-( acetoxymethyl)-5,6-dihydro-2H-pyran-2-yl)oxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-yl)hept-5-enoate, according to the reaction formula (1) below.

EFFECT: production of (E)-methyl-6-((3S,8S,9S,10R,13S,14S,17R)-3-(((2S,5S,6R)-5-acetoxy-6-(acetoxymethyl)-5,6-dihydro-2H-pyran-2-yl)oxy)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-yl)hept-5-enoate in crystalline form with high purity and stability.

16 cl, 14 dwg, 15 tbl, 13 ex