Patent GB-968254-A (GB)
Title: New dihalogeno-amine-benzylamines
IPC: C07D295/135
Filed: 1962-11-09
Abstract: The invention comprises compounds of the formula: <FORM:0968254/C1/1> in which R1 represents a lower acyclic aliphatic hydrocarbon group containing from 1 to 5 carbon atoms, or a cycloalkyl, aralkyl or aryl group; and R represents hydrogen or any of the groups which may be represented by R1; or R and R1, together with the adjacent nitrogen atom, represent a pyrrolidinyl, piperidino or camphidinyl group either unsubstituted or substituted by a C1-5 alkyl group; and Hal represents chlorine or bromine; and non-toxic acid-addition salts thereof. The compounds may be prepared by reacting an amino-benzylamine of the formula: <FORM:0968254/C1/2> in which the amino group is in the 2- or 4-position, with at least a molar excess of a chlorinating or brominating agent in an inert organic solvent, or by reacting a dihalogeno-diacylamino-benzyl halide of the formula: <FORM:0968254/C1/3> in which X represents chlorine or bromine and Ac represents an acyl group, with an amine of the formula: <FORM:0968254/C1/4> in the presence of a hydrogen halide-binding agent and deacylating the compound so formed, or by reducing a dihalogeno-nitro-benzylamine of the formula:  <FORM:0968254/C1/5> Amino-benzylamines of formula II may be prepared by reacting the known nitro-benzyl halides with the corresponding secondary amine and subsequently reducing the nitro group.  Dihalogeno-diacylamino-benzyl bromides of formula III may be prepared by reacting the known 2- or 4-diacylamino-3, 5-dihalogeno-toluenes with N-bromo-succinimide. Dihalogeno-nitro-benzylamines of formula V may be prepared by brominating the known 2-or 4-nitro-3, 5-dihalogeno-toluenes with N-bromo-succinimide and reacting the resulting compound with the appropriate secondary amine.  N-[2-amino-benzyl]-isobutylamine is prepared by reacting 2-nitro-benzaldehyde with isobutylamine to form N-[2-nitro-benzylidene]-isobutylamine which is then catalytically hydrogenated with Pt/H2.  N-[4-amino-benzyl]-cyclohexylamine is prepared by catalytically hydrogenating N-[4-nitro-benzylidene]-cyclohexylamine with Pt/H2.ALSO:Pharmaceutical compositions comprise a compound of the formula <FORM:0968254/A5-A6/1> in which R1 represents a lower acyclic aliphatic hydrocarbon group containing from 1 to 5 carbon atoms, or a cycloalkyl, aralkyl or aryl group; and R represents hydrogen or any of the groups which may be represented by R1; or R and R1, together with the adjacent nitrogen atom, represent a pyrrolidinyl piperidino or camphidinyl group either unsubstituted or substituted by a C1-5 alkyl group; and Hal represents chlorine or bromine; or a non-toxic acid-addition salt thereof, in association with a pharmaceutical carrier or excipient.  The compositions which may be formulated as capsules, granules, coated tablets, emulsions, syrups, suspensions or ampoules for oral, rectal or parenteral administration, have, in general, secretolytic, cough-relieving, monoamine oxidase inhibiting and anti-pyretic activity.  Examples relate to compositions in tablet and syrup form comprising N-[2-amino 3,5 dibromobenzyl] - N - methyl - cyclohexylamine hydrochloride, 1 - (p - chlorophenyl) - 2,3 - dimethyl-4 - dimethylamino - butanol - (2) hydrochloride and 1 - (3,5 - dihydroxyphenyl) - 2 - isopropylamino-ethanol sulphate, together with, in the case of the syrup, sodium benzoate, ammonium chloride and menthol; and to a syrup comprising N - [2 - amino - 3,5 - dibromo - benzyl]-N - methyl - cyclohexylamine hydrochloride, sodium benzoate, ammonium chloride and menthol.