Patent GB-782821-A (GB)
Title: Novel therapeutically active amines and salts thereof
Filed: 1955-09-06
Abstract: The invention comprises amines of the general formula <FORM:0782821/IV (a)/1> wherein n1 is 0 or 1, and R1 represents a tertiary amino substituted alkyl radical of the formula -alkylene-R2 or a substituted benzyl radical of the formula <FORM:0782821/IV (a)/2> wherein R2 represents a tertiary-amino group and n2 is 0 or 1, and salts thereof, and the preparation thereof by reacting 1-methyl-3-[21,61,61- - trimethyl - cyclohexen - (11) - yl] - propylamine or 2-methyl-4-[21,61,61-trimethylcyclohexen - (11) - yl] - butylamine with a compound of the formula R1-X, wherein X represents the aldehyde group when R1 represents the substituted phenyl part of the above substituted benzyl radical, or X represents the aldehyde group or a halogen atom when R1 represents the above tertiary-amino substituted alkyl radical, in the presence of catalytically active hydrogen or of a basic agent (according to whether X represents the aldehyde group or a halogen respectively), and alkylating the resulting amine and, if desired, converting the product into a normal or quaternary salt. The alkyl and alkylene radicals preferably contain from 1 to 4 carbon atoms, e.g. the methyl, ethyl, propyl, dimethylene and trimethylene radicals.  The alkylene radicals may be straight or branched-chain radicals.  The tertiary-amino group R2 may be a dialkylamino group such as a dimethylamino radical or a saturated monocyclic 5-membered or 6-membered heterocyclic radical-particularly the pyrrolidino, piperidino or morpholino radical.  The salts may be formed from inorganic acids such as hydrochloric, hydrobromic, hydriodic, sulphuric and phosphoric acids, or from organic acids such as oxalic, citric, acetic, lactic, tartaric and benzenesulphonic acids, or from quaternizing agents such as alkyl halides, dialkyl sulphates and aralkyl halides-particularly methyl bromide, ethyl iodide, butyl chloride, dimethyl sulphate and benzyl bromide.  Suitable basic agents for use in the above process are alkali-metal carbonates. The alkylation step may be carried out by acylation using an organic acid anhydride or halide followed by reduction of the N-acyl compound thus formed with lithium aluminium hydride, or methylation may be carried out using a mixture of formaldehyde and formic acid.  The reaction of the substituted propylamine or butylamine with the compound of the general formula R1-X, and the products so obtained are detailed in Specification 782,820.  In the examples: (1) ethyl 1-methyl-3-[21,61,61-trimethyl - cyclohexen - (11) -yl] - propyl 4 - (21-diethylaminoethoxy)-benzyl amine is prepared by treating 1 - methyl - 3 - [21,61,61 - trimethylcyclohexen - (11) - yl] - propyl 4 - (21 - diethylaminoethoxy)-benzyl amine with acetyl chloride to form the hydrochloride of acetyl 1-methyl3 - [21,61,61 - trimethyl - cyclohexen - (11) - yl] - propyl 4 - (21 - diethylaminoethoxy) - benzyl amine, and liberating the free base which is then reduced with lithium aluminium hydride; the dioxalate salt of the desired product is also prepared; (2) methyl 1-methyl-3-[21,61,61-trimethyl - cyclohexen - (11) - yl] - propyl 4 - (21 - dimethylaminoethoxy-benzyl amine is prepared by treating 1-methyl-3-[21,61,61-trimethyl cyclohexen - (11) - yl] - propyl 4 - (21 - dimethylaminoethoxy) - benzyl amine with formic acid and formaldehyde, and is converted into the dioxalate salt thereof; (3) methyl 1-methyl-3-[21,61,61-trimethyl-cyclohexen - (11) - yl - propyl 3 - (21 - diethylaminoethoxy) - benzyl amine and the dioxalate thereof are prepared as in (2); (4) methyl 1-methyl-3-[21,61,61-trimethyl-cyclohexen - (11) - yl] - propyl 2 - (21 - diethylaminoethoxy)-benzylamine and the dioxalate thereof are prepared as in (2); (5) methyl 1-methyl-3-[21,61,61 - trimethyl - cyclohexen - (11) - yl] - propyl 4 - (21 - dimethylamino - isopropoxy)-benzyl amine and the dioxalate thereof are prepared as in (2); (6) methyl 1-methyl-3-[21,61,61 trimethyl - cyclohexen - (11) - yl] - propyl 4 -(31 - diethylaminopropoxy) - benzyl amine and the dioxalate thereof are prepared as in (2); (7) methyl 1 - methyl - 3 - [21,61,61 - trimethylcyclohexen - (11) - yl] - propyl 4 - (31 - piperidinopropoxy)-benzyl amine and the dioxalate thereof are prepared as in (2); (8) methyl 2-methyl-4-[21,61,61 - trimethyl - cyclohexen - (11 - yl] - butyl 4 - (21 - diethylamino - ethoxy) - benzyl amine and the dioxalate thereof are prepared as in (2); (9) methyl 2-methyl-4-[21,61,61-trimethylcyclohexen - (11) - yl] - butyl 4 - (31 - diethylaminopropoxy)-benzyl amine and the dioxalate thereof are prepared as in (2); (10) methyl 2-methyl - 4 - [21,61,61 - trimethyl - cyclohexen - (11) - yl] - butyl 4 - (31 - piperidinopropoxy) - benzyl amine and the dioxalate thereof are prepared as in (2); (11) methyl 1-methyl-3-[21,61,61-trimethyl - cyclohexen - (11) - yl] - propyl 3-piperidinopropyl amine and the dioxalate thereof are prepared as in (2), the bis-methyl bromide thereof is also prepared; and (12) methyl 2 - methyl - 4 - [21,61,61 - trimethyl - cyclohexen - (11) - yl] - butyl 3 - piperidinopropyl amine and the dioxalate thereof are prepared as in (2).