GB788936A - Basically substituted acid amides and process for their manufacture - Google Patents

Abstract

The invention comprises compounds of the general formula <FORM:0788936/IV (b)/1> in which R1 is an alkylene group of 1-4 carbon atoms, and R2 and R3 are each hydrogen atoms or alkyl radicals of 1-4 carbon atoms or together with the nitrogen atom form a saturated heterocyclic ring, and their acid addition salts. The compounds are made by acylating a 2-nitro-6-chloro-aniline with an amino-alkyl carboxylic acid and reducing the product, if necessary after alkylation at the amino group of the amino-acid residue. They are also prepared by acylating the 2-nitro-6-chloro-aniline with a halogeno-alkyl carboxylic acid, condensing the resulting halogeno-acylamide with ammonia or a primary or secondary amine and reducing the amino-acylamide obtained. The acylation reactions are suitably carried out using the acid chlorides of the amino- or halogeno-alkyl carboxylic acids, in the presence of a solvent and in the presence of an acid binding agent which may be sodium hydroxide or sodium acetate or may be an excess of the 2-nitro-6-chloroaniline itself. In the absence of an acid binding agent hydrogen halide liberated during the acylation is removed by heating. Specified amino-alkyl carboxylic acids include amino, monoalkylamino and dialkylamino acetic, propionic and butyric acids, a -piperidinoacetic acid, b -piperidinopropionic acid and a -pyrrolidinoacetic acid. The reduction of the nitro group to the amino group may be effected by means of tin and hydrochloric acid, sodium dithionite or by catalytic reduction using Raney nickel as a catalyst. Where it is necessary to alkylate a primary or secondary amine prior to reduction, this may be effected for example by means of alkyl halides. The free bases may be converted into their salts with hydrohalic, sulphuric, phosphoric, acetic, lactic, maleic, malic, amidosulphonic, phenol-sulphonic, oxalic, succinic, hydroxyethane sulphonic or aceturic acid. In examples: (1) 2-nitro-6-chloroaniline is acetylated with chloracetyl chloride, the resulting 1-(chloroacetylamino) - 2 - nitro - 6 - chloro - benzene is treated with diethylamine to give 1 - (diethylamino-acetylamino) - 2 - nitro - 6 - chloro - benzene as the hydrochloride, which is reduced by hydrogen and Raney nickel to give 1-(diethylamino-acetylamino) - 2 - amino - 6 - chlorobenzene; (2) 1 - (chloroacetylamino) - 2 - nitro - 6 - chlorobenzene is treated with butylamine and the resulting 1 - (butylamino - acetylamino) - 2 - nitro - 6 - chlorobenzene, which is isolated as the hydrochloride, is reduced to 1-(butylamino-acetylamino) - 2 - amino - 6 - chlorobenzene hydrochloride; and (3) 2-nitro-6-chloroaniline treated with b -piperidino-propionic acid chloride and the resulting 1-(b -piperidino-propionylamino) - 2 - nitro - 6 - chlorobenzene hydrochloride is reduced to 1-(b -piperidino-propionylamino)-2-amino-6-chlorobenzene hydrochloride.