FIELD: chemistry.
SUBSTANCE: present invention relates to a method for producing crystalline fumarate salt of (S)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl][3-hydroxy-3-(piperidine-2-yl)azetidine-1-yl]methanone of the compound I, designated as the Form A, characterized in at least one of the following (iii) a solid phase 13C NMR spectrum with three or more peaks selected from 175.3, 173.6, 117.5, 155.5 and 153.5 ± 0.2 ppm; (v) a diagram of powder X-ray diffraction (CuKα λ=1,5418Å) containing three or more 2θ values selected from 4.6, 12.1, 13.2, 13.6 and 14.5 ± 0.2°2θ, when measuring a crystalline form at a room temperature; or a diagram of powder X-ray diffraction (CuKα λ=1,5418Å), when measuring a crystalline form at a room temperature, containing 2θ ± 0.2°2θ values equal to 4.6, 12.1, 13.2, 13.8, 14.5, 16.3, 16.6, 17.8, 18.5, 19.7, 21.1, 22.6, 23.0, 23.3, 24.5; where the method includes the addition of fumaric acid dissolved in a solvent to a mixture of the compound I dissolved in a solvent to obtain crystalline fumarate salt of the compound I, designated as the Forma A; and the collection of obtained crystals of crystalline fumarate salt of the compound I, designated as the Forma A, and where the solvent includes a polar proton solvent, an aproton solvent or a mixture thereof. The polar proton solvent is selected from a group consisting of methanol, ethanol, n-propanol, isopropanol, water and mixtures thereof, and the aproton solvent is selected from a group consisting of tetrahydrofuran, acetonitrile dichloromethane and mixtures thereof.
EFFECT: producing thermodynamically stable, non-hygroscopic crystalline fumarate salt of (S)-[3,4-difluoro-2-(2-fluoro-4-iodophenylamino)phenyl][3-hydroxy-3-(piperidine-2-yl)azetidine-1-yl]methanone.
3 cl, 13 dwg, 13 tbl
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