Patent ID: 6506937
Filing Date: 2003-01-14
Classification: A61P,C07C,Y10S

Abstract:
A process for the preparation of a substituted benzenesulfonylurea or -thiourea of the formula I or of a physiologically acceptable salt thereof, wherein R(1) is hydrogen or methyl, R(2) is hydrogen, F, Cl, Br, I, (C1-C6)-alkyl or (C1-C6)-alkoxy, E is oxygen or sulfur, Y is a hydrocarbon chain of the formula â€”{CR(3)2}nâ€”where R(3)=H or (C1-C2)-alkyl and n=1,2,3 or 4,X is hydrogen, F, Cl, Br, I or (C1-C6)-alkyl, Z is F, Cl, Br, I, NO2, (C1-C4)-alkoxy or (C1-C4)-alkyl, comprising (a) preparing a substituted benzenesulfonylurea of the formula Ia by reacting an aromatic sulfonamide of the formula II or a salt thereof of the formula III, wherein the cation M in the salt of the formula III is an alkali metal or alkaline earth metal ion or a tetraalkylammonium ion,with an R(1)-substituted isocyanate of the formula IV R(1)-N&boxH;C&boxH;Oâ€ƒâ€ƒIV; or(b) preparing an unsubstituted benzenesulfonylurea of the formula Ia, wherein R(1) is hydrogen, by reacting an aromatic benzenesulfonamide of the formula II or its salt of the formula III with a trialkylsilyl isocyanate or silicon tetraisocyanate and hydrolysis of the primary silicon-substituted benzenesulfonylurea; or (c) preparing a benzenesulfonylurea of the formula Ia by reacting an aromatic benzenesulfonamide of the formula II or its salt of the formula III with an R(1)-substituted trichloroacetamide of the formula V in the absence of a base; or(d) preparing a benzenesulfonylthiourea of the formula Ib by reacting an aromatic sulfonamide of the formula II or its salt of the formula III with an R(1)-substituted isothiocyanate of the formula VIR(1)-N&boxH;C&boxH;Sâ€ƒâ€ƒVI; or(e) preparing an unsubstituted benzenesulfonylthiourea of the formula Ib, wherein R(1) is hydrogen, by reacting an aromatic benzenesulfonamide of the formula II or its salt of the formula III with trimethylsilyl isothiocyanate or silicon tetraisothiocyanate and hydrolysis of the silicon-substituted benzenesulfonylthiourea, or by reacting an aromatic benzenesulfonamide of the formula II or its salts of the formula III with benzoyl isothiocyanate and reacting the benzoyl-substituted benzenesulfonylthiourea intermediately formed with aqueous mineral acid; or(f) preparing a substituted benzenesulfonylurea of the formula Ia by a conversion reaction from the corresponding benzenesulfonylthiourea of the formula Ib; or(g) preparing a benzenesulfonylurea of the formula Ia by reacting a benzenesulfonyl halide of the formula VII with R(1)-substituted urea or an R(1)-substituted bis(trialkylsilyl)urea and removing the trialkylsilyl protective group;or(h) preparing a benzenesulfonylurea of the formula Ia by reacting an amine of the formula R(1)-NH2 with a benzenesulfonyl isocyanate of the formula VIII or(i) preparing a benzenesulfonylthiourea of the formula Ib by reacting an amine of the formula R(1)-NH2 with a benzenesulfonylisothiocyanate of the formula IX or(j) preparing a substituted benzenesulfonylurea of the formula Ia by oxidizing a correspondingly substituted benzenesulfenyl- or benzenesulfinylurea.