CRYSTALLINE FORMS OF LTA4H INHIBITOR Russian patent published in 2023 - IPC C07D401/12 A61K31/4439 A61P29/00 

FIELD: pharmaceuticals.

SUBSTANCE: invention relates to a method of obtaining crystalline form B of compound (S)-3-amino-4-(5-(4-((5-chloro-3-fluoropyridin-2-yl)oxy)phenyl)-2H-tetrazol-2-yl)butanoic acid in free form, which is characterized by a powder x-ray pattern including four or more values 2θ , selected from a group consisting of 11.3±0.2° 2θ, 12.8±0.2° 2θ, 15.2±0.2° 2θ, 19.7±0.2° 2θ, 20.0±0.2° 2θ, 20.3±0.2° 2θ, 21.0±0.2° 2θ, 22.6±0.2° 2θ, 24.1±0.2° 2θ, 24.4±0.2° 2θ, 25.1±0.2° 2θ, 26.3±0.2° 2θ, 28.5±0.2° 2θ and 30.0±0.2° 2θ, measured at a temperature of approximately 25°C, and at the x-ray wavelength,λ, which is 1.5418. The method is carried out by (a) suspension in methanol or suspension in a water/methanol mixture, wherein the said mixture has water activity less than or equal to 0.7, or suspension in a 1-propanol/water mixture at a ratio of 70/30% by weight of the hydrate crystalline form (S)-3-amino-4-(5-(4-((5-chloro-3-fluoropyridin-2-yl)oxy)phenyl)-2H-tetrazol-2-yl)butanoic acid (form H_B), which is characterized by a powder X-ray pattern including four or more values 2θ, selected from a group consisting of 13.4±0.2° 2θ, 20.8±0.2° 2θ, 22.1±0.2° 2θ, 23.5±0.2° 2θ, 23.5±0.2° 2θ, 23.8±0.2° 2θ, 24.7±0.2° 2θ, 26.1±0.2° 2θ, 26.9±0.2° 2θ, 28.7±0.2° 2θ, 30.4±0.2° 2θ, 31.2±0.2° 2θ, 33.8±0.2° 2θ and 38.7±0.2° 2θ, measured at a temperature of approximately 25°C, and at the x-ray wavelength,λ, which is 1.5418, with the formation of a mixture in the form of a suspension. Then (b) heat and stir the mixture as a suspension to a temperature of about 50°– 65°C when suspended in methanol, or to a temperature of approximately 50°– 68°C when suspended in a methanol/water mixture, or to a temperature of above 80°–90°C to achieve complete dissolution when suspended in a 1-propanol/water mixture. After (c) cool the solution to room temperature to form the mixture as a suspension; and (d) collect crystalline form B from the suspension, with the term “about” indicating deviation of ± 5%.

EFFECT: production of a highly crystalline and slightly hygroscopic crystalline form B of the compound (S)-3-amino-4-(5-(4-((5-chloro-3-fluoropyridin-2-yl)oxy)phenyl)-2H-tetrazole-2-yl)butanoic acid in free form.

19 cl, 6 dwg, 5 tbl, 2 ex