GB886684A - Improvements in or relating to heterocyclic compounds and the manufacture thereof - Google Patents

Abstract

The invention comprises aminoethyl indoles of the formula <FORM:0886684/IV (b)/1> and acid addition salts thereof, wherein R1 is a C1-4 alkyl radical, R2 and R3 are hydrogen atoms or C1-4 alkyl radicals and R5 is hydroxy, a benzyloxy or benzhydryloxy radical bearing alkyl, alkoxy or halogen substituents and containing up to 15 carbon atoms or a C1-8 alkoxy radical, with the proviso that R2 and R3 cannot both be hydrogen; and comprises also processes for the preparation of compounds of the above type wherein R5 is hydroxyl, benzyloxy or benzyhydryloxy, with or without alkyl, alkoxy or halogen substituents, or an alkoxy group and without the proviso regarding R2 and R3, whereby the corresponding 3-nitro-ethyl indole is reduced and, if a 5-hydroxy-product is desired, a benzyloxy or benzhydryloxy group in the 5-position is removed by hydrogenolysis or a 5-alkoxy group is dealkylated with aluminium chloride. Hydrogenolysis or reduction by catalytic hydrogenation are effected in the presence of palladium platinum oxide or Raney nickel catalysts. Reduction of the nitro group may also be effected by reaction with lithium aluminium hydride. The products are suitably isolated as salts such as the sulphate, acetate and creatinine sulphate. Examples describe the preparation of 5-hydroxy-, methoxy-, benzyloxy-, p-methylbenzyloxy-, ethoxy-, p-chlorobenzyloxy-, n-butyloxy- and isopropoxy-, 3-aminoethyl indoles in which R2 and R3 may be hydrogen, methyl ethyl, propyl, propyl or butyl and R1 is methyl, ethyl, propyl or butyl. Intermediates. The 3-nitro­ethyl-indoles from which the aminoethyl-indoles of the invention are obtained by reduction are prepared by nitroalkylating a 3-dialkylaminomethyl-indole with an alkyl a -nitro-a -alkyl-acetate to produce an alkyl ester of a -alkyl-a -nitro-b -indolyl-(3)-propionic acid (optionally bearing a substituent R3 and in the 1-position and bearing an alkoxy or benzyloxy group in the 5-position), hydrolysing and decarboxylating with an alkali such as sodium hydroxide to give an alkali-metal salt of a 5-substituted-3-b -acinitroethyl-indole and acidifying to give the nitroethyl-indole. Alternatively, the 5-substituted-3-dialkylaminomethyl indole may be reacted with a nitro-alkane to give the 3-nitroethyl indoles. The 3-dialkylaminomethyl indoles substituted in the 1- and 5-positions are made by reacting the corresponding indoles with formaldehyde and a dialkylamine, e.g. dimethyl amine. 1-alkyl-5-substituted indoles are made by reacting the 5-substituted indole, e.g. a 5-benzyloxy-indole with an alkyl halide. The 5-alkoxy and 5-benzyloxy indoles are prepared by methods described in the literature. Reference has been directed by the Comptroller to Specifications 807,876 and 807,877.