CRYSTALLINE (2S,4R)-5-(5'-CHLOR-2'-FLUORO-[1,1'-BIPHENYL]-4-YL)-2-(ETHOXYMETHYL)-4-(3-HYDROXYISOXAZOL-5-CARBOXAMIDO)-2-METHYLPENTANIC ACID AND ITS APPLICATIONS Russian patent published in 2021 - IPC C07D261/18 A61K31/42 A61P9/00 

FIELD: chemistry.

SUBSTANCE: invention relates to a method for producing a crystalline form of (2S,4R)-5-(5'-chlor-2'-fluoro-[1,1'-biphenyl]-4-yl)-2-(ethoxymethyl)-4-(3-hydroxyisoxazol-5-carboxamido)-2-methylpentanic acid, including (a) forming a solution including (2S,4R)-5-(5'-chlor-2'-fluoro-[1,1'-biphenyl]-4-yl)-2-(ethoxymethyl)-4-(3-hydroxyisoxazol-5-carboxamido)-2-methylpentanic acid and a mixture of ethyl acetate and water, ethyl acetate or ethanol at an increased temperature; (b) cooling the solution to a temperature between about -20°C and 5°C; and (c) isolating obtained solids with obtaining a crystalline form. The solution from the stage (a) additionally contains a metal acceptor, such as SiliaMetS® Thiol. A temperature at the stage (a) is between about 60°C and 95°C. Isolating solids at the stage (c) includes filtering, washing with one or several solvents, drying in the air or in a vacuum or a combination of these stages. Drying in a vacuum is carried out at a temperature between 25°C and 70°C.

EFFECT: crystalline form of (2S,4R)-5-(5'-chlor-2'-fluoro-[1,1'-biphenyl]-4-yl)-2-(ethoxymethyl)-4-(3-hydroxyisoxazol-5-carboxamido)-2-methylpentanic acid having stability, high melting point and low hygroscopicity.

7 cl, 10 dwg, 9 tbl, 6 ex