Patent GB-640196-A (GB)
Title: Improvements in or relating to the preparation of vasoconstrictive compounds
IPC: C07D285/135
Filed: 1947-12-27
Abstract: Vasoconstrictive derivatives are formed by reacting 2 - sulphanilamido - 5 - methyl - 1,3,4-thiodiazole with phenylalkylamines, phenylalkanolamines, 2-aralkylimidazolines, 2-aminoheptanes or salts thereof.  The reaction may be carried out in a solvent, e.g. a therapeutic liquid so that a solution of the compound is obtained directly for clinical use.  In examples: (1) N1-methyl-thiodiazolyl-N1-phenyl-isopropyl-methyl -ammonium-sulphanilamide is obtained from 2 - sulphanilamido - 5 - methyl - 1,3,4 - thiodiazole in ethanol and dl-phenyl-isopropyl-methylamine in benzene; (2) the same compound as in (1) is made from sodium-2-sulphanilamido - 5 - methyl - 1,3,4-thiodiazole and phenyl-isopropyl-methylamine hydrochloride in water; (3) and (4) N1-methyl-thiodiazolyl-N1-phenyl-isopropyl-ammonium -sulphanilamide is made from dl-phenyl-isopropylamine and 2-sulphanilamido-5-methyl-1,3,4-thiodiazole in water or alcohol; (5) N1-methyl-thiodiazolyl-N1-phenyl-isopropanol-methyl -ammonium-sulphanilamide is made from 2-sulphanilamido-5-methyl-1,3,4-thiodiazole and ephedrine base in water; (6) N1-methyl-thiodiazolyl-N1-d-phenyl-isopropyl-methyl -ammonium-sulphanilamide is obtained from 2 - sulphanilamido - 5 - methyl - 1,3,4 - thiodiazole and d-phenyl-isopropyl-methylamine in water; and (7) N1-methyl-thiodiazolyl-N1-(b -p-hydroxyphenyliso - propyl) - methyl-ammonium-sulphanilamide is made from sodium-2-sulphanilamido - 5 - methyl - 1,3,4 - thiodiazole and (b  - p-hydroxyphenyl) - isopropyl - methylamino - sulphate in water.  The preparation of the following also is referred to, N1-methyl-thiodiazolyl - N1 - 2 - (a  - naphthylmethyl) - imidazolinium-sulphanilamide; N1-methyl-thiodiazolyl-N1-2-n-heptyl-ammonium -sulphanilamide; and N1 - methyl - thiodiazolyl - N1 - b  - (3,4 - dihydroxy - phenyl1-ethanol-ammonium-sulphanilamide.ALSO:Vasoconstrictive derivatives are formed by reacting 2-sulphanilamido-5-methyl-1,-3,4-thiodiazole with phenylalkylamines, phenylalkanolamines, 2 - aralkylimidazo - lines 2-aminoheptanes or salts thereof.  The reaction may be carried out in a solvent, e.g., a therapeutic liquid, so that a solution of the compound is obtained directly for clinical use.  In examples, (1) N'-methyl-thiodiazolyl - N' - phenyl - isopropyl - methyl - ammonium - sulphanilamide is obtained from 2-sulphanilamido-5-methyl-1, 3, 4-thio-diazole in ethanol and dl-phenyl-isopropyl-methylamine in benzene, (2) the same compound as in (1) is made from sodium - 2 - sulphanilamido - 5 - methyl - 1, 3, 4-thiodiazole and phenyl-isopropyl-methylamine hydrochloride in water.  (3) and (4) N'-methyl-thiodiazolyl-N'-phenylisopropyl - ammonium - sulphanilamide is made from dl-phenyl-isopropylamine and 2-sulphanilamide-5-methyl-1, 3, 4-thiodiazole in water or alcohol, (5) N'-methylthiodiazolyl - N' - phenyl - isopropanol - methyl - ammonium - sulphanilamide is made from 2-sulphanilamido 5-methyl-1, 3, 4-thiodiazole and ephedrine base in water, (6) N'-methyl-thiodiazolyl-N'-d-phenyl - isopropyl - methyl - ammonium - sulphanilamide is obtained from 2-sulphanilamido-5-methyl-1, 3, 4-thiosiazole and d-phenyl-isopropyl-methylamine in water, and (7) N'-methyl-thiodiazolyl-N'-(b -p-hydroxyphenyliso - propyl) - methyl - ammonium-sulphanilamide is made from sodium - 2 - sulphanilamido - 5 - methyl - 1, 3, 4-thiodiazole and (b -p-hydroxyphenyl)-isopropyl-methylaminosulphate in water.  The preparation of the following also is referred to, N'-methyl-thiodiazolyl-N'-2-( -naphthylmethyl) - imidazolinium - sulphanilamide; N'-methyl-thiodiazolyl-N'-2-n - heptyl - ammonium - sulphanilamide; and N' - methyl - thiodiazolyl - N' - b  - (3, 4 - dihydroxy - phenyl) - ethanol - ammonium-sulphanilamide.