POLYMORPHIC FORM OF [5-FLUORINE-3-({ 2-[(4-FLUOROBENZENE) SULFONYL]PYRIDINE-3-YL} METHYL)-2-METHYLINDOLE-1-YL]-ACETIC ACID Russian patent published in 2021 - IPC C07D401/06 A61K31/4439 A61P31/00 

FIELD: chemistry.

SUBSTANCE: present invention relates to a method for producing a polymorphic form of [5-fluorine-3-({2-[(4-fluorobenzene)sulfonyl]pyridine-3-yl}methyl)-2-methylindole-1-yl]-acetic acids. Method for producing the polymorphic form 2 of [5-fluorine-3-({2-[(4-fluorobenzene)sulfonyl]pyridine-3-yl}methyl)-2-methylindole-1-yl]acetic acid (compound 1) is characterized by Raman spectrum with Fourier transformation with characteristic peaks at 3063 ± 2 cm^-1, 1578 ± 2 cm^-1, 1423 ± 2 cm^-1, 1209 ± 2 cm^-1, 1187 ± 2 cm^-1, 1166 ± 2 cm^-1, 1150 ± 2 cm^-1, 930 ± 2 cm^-1, 883 ± 2 cm^-1, 770 ± 2 cm^-1, 356 ± 2 cm^-1, 304 ± 2 cm^-1, 167 ± 2 cm^-1, 119 ± 2 cm^-1 or the following crystal lattice parameters:

a 10.8 ± 0.1 Å b 13.9 ± 0.1 Å c 7.8 ± 0.1 Å α 101 ± 1° β 110 ± 1° γ 79 ± 1° cell volume 1.068 ų RP 4.9% weighted RP 7.1%

The method is carried out by (a) suspending compound 1 in a solvent containing acetonitrile, a mixture of acetonitrile and water or a ketone solvent selected from methyl isobutyl ketone, methyl ethyl ketone and mixtures thereof, wherein compound 1 is in an amorphous form, in a crystalline form other than polymorphic form 2, or in the form of a mixture of polymorphic form 2 with one or more other polymorphic forms; (b) mixing the suspension at a temperature of about 15 to 25 °C for 15 to 30 days; and (c) separating and drying the solid [5-fluorine-3-({2-[(4-fluorobenzene)sulfonyl]pyridine-3-yl}methyl)-2-methylindole-1-yl]acetic acid. The invention also relates to a method for producing a polymorphic form of 2 [5-fluorine-3-({2-[(4-fluorobenzene)sulfonyl]pyridine-3-yl}methyl)-2-methylindole-1-yl]acetic acid (compound 1) by obtaining a saturated solution of compound 1 in a solvent selected from acetonitrile, acetonitrile and water or a ketone solvent selected from methyl isobutyl ketone, methyl ethyl ketone or a mixture thereof; seeding the specified saturated solution with crystals of the polymorphic form 2 of compound 1; holding with crystallization; and separating crystals of polymorphic form 2 of compound 1.

EFFECT: production of a thermodynamically stable polymorphic form of 2 [5-fluorine-3-({2-[(4-fluorobenzene)sulfonyl]pyridine-3-yl}methyl)-2-methylindole-1-yl]acetic acid.

6 cl, 18 dwg, 3 tbl, 9 ex