FIELD: chemistry.
SUBSTANCE: process for the production of a 2-[4-(methylaminomethyl)phenyl]-5-fluoro-benzofuran-7-carboxamide hydrochloride polymorph as shown in Formula I, wherein the polymorph is a C crystalline form characterized by 2θ angle values selected from the group, consisting of 10.306; 12.666; 15.312; 17.436; 18.918; 20.748; 22.974; 24.553; 25.238; 26.241; 29.336; 32.739; 33.738; 34.118; 35.204. The method includes (a) dissolving crystalline form A of 2-[4-(methylaminomethyl)phenyl]-5-fluoro-benzofuran-7-carboxamide hydrochloride in alcohol or water-alcohol system at a temperature of 50 °C or 78 °C to form an alcoholic solution or an aqueous-alcoholic solution containing 2-[4-(methylaminomethyl)phenyl]-5-fluoro-benzofuran-7-carboxamide hydrochloride; (b) adjusting the pH of the alcoholic solution or water-alcohol solution obtained in step a) to maintain an acidic environment with hydrochloric acid, stirring at room temperature, settling and precipitating crystals; and (c) separating and drying the precipitated crystals to obtain crystalline form C of 2-[4-(methylaminomethyl)phenyl]-5-fluoro-benzofuran-7-carboxamide hydrochloride. Said water-alcohol system is selected from the group consisting of methanol-water, ethanol-water. In this case, the crystalline form A is obtained as follows: free mefurapine hydrochloride 59.6 g, 199.9 mmol, purity more than 97% was added to methanol/dichloromethane ν/ν = 1:1, 2000 ml and vigorously stirred; the solid phase dissolved completely, forming a suspension system, which was then cooled to 0 °C, after which a 8N solution of hydrochloric acid in ethyl acetate (250 ml) was slowly added dropwise, achieving complete dissolution of the system; after adding dropwise, the reaction system is continuously stirred at a temperature of from 0 ° C to 10 ° C for 12 hours, while a large amount of solid phase settles, which is filtered off to obtain a filter cake; filter cake dried under vacuum at a temperature of 50 to 55 °C to constant weight. Powder diffraction pattern of crystalline Form A is given in the claims.
EFFECT: obtaining polymorph of 2-[4-(methylaminomethyl)phenyl]-5-fluoro-benzofuran-7-carboxamide hydrochloride in a simple, effective and reproducible way.
1 cl, 15 dwg, 13 ex
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