Patent GB-640365-A (GB)
Title: Improvements in or relating to the preparation of new quinoline derivatives
Filed: 1947-05-19
Abstract: Quinoline compounds of the formula Y=N-R-CH(Ar)-CH2-NH-Q, and salts thereof, where Y=N- is a (lower alkyl)2 N-, piperidino- or morpholino-group, R is an aliphatic bridge having a chain of from 2 to 7 carbon atoms, Ar is a phenyl or substituted phenyl radical and Q is a 4-quinolyl radical, are obtained by condensing 4-halo-quinoline with a compound of the formula Y=N-R-CH(Ar)-CH2-NH2.  The condensation is effected by heating the reactants at 130 DEG  to 190 DEG  C. from 1 to 15 hours.  The group Y=N- may be dimethylamino, diethylamino, dipropylamino, methylbutylamino, N-piperidino or N-morpholino. Specified substituents on the phenyl radical Ar are alkyl, aralkyl, aryl, alkoxy, aryloxy or tertiary amino groups, or chlorine, bromine or iodine atoms.  Other substituents present must be protected during the preparation of the diamine, e.g. free hydroxyl groups may be etherified.  The quinolyl radical may carry the same substituents as those specified for the phenyl radical.  The starting materials are obtained by treating a substituted acetonitrile Ar.CH2.CN with an aminoalkyl halide Y=N-R-X (where X may be chlorine, bromine or iodine) in the presence of a strong metalating base such as an alkali metal amide or hydride to give an amino-nitrile Y=N-R-CH(Ar)CN.  This is then catalytically hydrogenated to the diamine Y=N-R-CH(Ar)-CH2-NH2.  The products of the invention may be converted into salts, e.g. with hydrohalic, sulphuric, phosphoric, acetic, tartaric, citric, gluconic, alkylsulphonic, 2 : 4-dihydroxy-benzoic, 2-hydroxy-3-naphthoic and methylene-bis-2-hydroxy-3-naphthoic acids.  Examples show the use of the following diamines: 4-diethylamino - 2 - phenyl - butylamino, 5 - diethylamino - 2 - phenyl - pentylamine, the 41 - chloro-, 31 : 41-dichloro- and 41-methoxy-phenyl compounds and also 2-(2-N-morpholinoethyl)-2-(41-chlorophenyl)-ethylamine, and the following haloquinolines: 4 : 7-dichloro-, 4 : 7-dichloro-3-methyl-, 4 : 6 : 8-trichloro-, 4-chloro-6-methoxy-and 4-bromo-2-methyl.  Where the phenyl group carries a 4-methoxy-substituent, this may be converted into the corresponding hydroxy group by treating the final product with hydrobromic acid.  4 : 6 : 8-Trichlorquinoline is obtained by condensing 2 : 4-dichloraniline with ethyl oxalacetate, cyclizing the product to 2-carbethoxy-6 : 8-dichlor-4-hydroxy-quinoline, hydrolysing to the free acid, decarboxylating and replacing the hydroxy group by chlorine.  In the Specification as open to inspection under Sect. 91, the aliphatic bridge R is not limited as to the number of carbon atoms, and may be interrupted with -O-, -S-, -SO-, -SO2- or -N(alkyl)-groups.  The radical Ar may be any carbocyclic or heterocyclic aromatic radical such as naphthyl, thienyl, pyridyl or quinolyl, which may bear substituents as specified for the phenyl radical above. 2-(3-N-Piperidylpropyl)-2-(2-naphthyl) ethylamine, 2 - (2 - (3 - dimethylaminopropylthio) ethyl) - 2 - (3 - pyridyl) ethylamine and 2 - (2 - (2-diethylaminoethoxy) ethyl)-2-(3-thienyl)-ethylamine are also specified as suitable for condensing with 4-halo-quinolines. This subject-matter does not appear in the Specification as accepted.