CRYSTALLINE SUBSTANCE Russian patent published in 2025 - IPC C07D241/20 A61K31/4965 A61P1/04 A61P11/00 A61P11/06 A61P11/14 A61P13/12 A61P17/02 A61P25/02 A61P25/00 A61P7/02 A61P9/08 A61P9/10 A61P9/12 

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing crystalline form-II 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}acetic acid (Compound B). Method of production includes steps of dissolving 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}acetic acid in a solution containing a mixture of isopropyl alcohol and aqueous sodium hydroxide solution to produce a mixed solution; bringing the pH of the obtained mixed solution to 5–6, cooling the obtained mixed solution to below 10 °C before formation of crystals of form-II 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}acetic acid; where crystalline form-II 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}acetic acid shows diffraction peaks at diffraction angles (2θ) 9.6°, 11.4°, 11.7°, 16.3°, 17.5°, 18.5°, 18.7°, 19.9°, 20.1°, 21.0° and 24.6° in powder X-ray diffraction spectrum obtained using Cu-Kα-radiation (λ=1.54 Å), shows absorption peaks at wave numbers 2867 cm^-1, 1749 cm^-1, 1568 cm^-1, 1382 cm^-1, 1131 cm^-1 and 701 cm^-1 in the infrared absorption spectrum, and has an endothermic peak at 147 °C in differential scanning calorimetry. Invention also relates to a method of producing crystalline form-II 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}acetic acid (Compound B), comprising a step of heating crystalline form-III 2-{4-[N-(5),6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}acetic acid for conversion of crystalline form-III into crystalline form-II of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}acetic acid at temperature of 90 °C; where crystalline form-III 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}acetic acid shows diffraction peaks at diffraction angles (2θ) 8.4°, 12.6°, 13.4°, 14.3°, 14.6°, 15.9°, 16.9°, 18.0°, 18.8°, and 19.4° in powder X-ray diffraction spectrum obtained using Cu-Kα-radiation (λ=1.54 Å).

EFFECT: obtaining a crystalline substance of compound B, having physical and chemical stability.

13 cl, 9 dwg, 2 tbl, 4 ex