Patent GB-782820-A (GB)
Title: Novel therapeutically active amines and salts thereof and a process for the manufacture of same
Filed: 1955-09-06
Abstract: The invention comprises amines of the general formula <FORM:0782820/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:0782820/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-trimethyl-cyclohexen - (11) - yl] - butylamine with a compound of the general formula R1-X, wherein X represents an aldehyde group when R1 represents the substituted phenyl part of the above substituted benzyl radical, or X represents an 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 is the aldehyde group or a halogen atom respectively) and, if desired, converting the resulting amine into a normal or quaternary salt. Suitable basic agents are alkali-metal carbonates. The alkyl and alkylene radicals are preferably those containing 1 to 4 carbon atoms such as the methyl, ethyl, propyl, dimethylene and trimethylene radicals.  The alkylene radicals may be straight or branchedchain radicals.  The secondary amino radical R2 may be a dialkylamino radical such as a dimethylamino radical and saturated monocyclic 5- and 6-membered heterocyclic radicals-particularly the pyrrolidino, piperidino and morpholino radicals.  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 acid, or from quaternizing agents such as alkyl and aralkyl halides and dialkyl sulphates-particularly methyl bromide, ethyl iodide, butyl chloride, dimethyl sulphate and benzyl bromide.  In the examples the following compounds are prepared:-1-methyl-3-[21,61,61-trimethyl - cyclohexen - (11) - yl] - propyl 4 - (21-diethylamino-ethoxy)-benzyl amine and the corresponding 4-(21-dimethylamino-ethoxy)-, 3-(21 - diethylamino - ethoxy) -, 2 - (21 - diethyl-amino - ethoxy)-, 4 - (21 - dimethylamino - isopropoxy)-, 4 - (31 - diethylamino - propoxy)-, 4 - (31 - piperidino - propoxy) -, 4 - (31 - morpholino - (propoxy)-, 4 - (31 - dimethylaminopropoxy)-, 2 - (31 - piperidino - propoxy) - and 3 - (31 - piperidino - propoxy) - benzyl amines, 2 - methyl - 4 - [21,61,61 - trimethylcyclohexen -(11) - yl] - butyl 4 - (21 - diethylaminoethoxy) -benzyl amine and the corresponding 4-(21-dimethylamino - isopropoxy) -, 4 - (31 - dimethylamino-propoxy)-, 4 - (31 - diethylamino - propoxy)-, 4 - (31 - piperidino - propoxy)-, and 4 - (21 - piperidino - ethoxy) - benzyl amines, 1 - methyl - 3 - [21,61,61 - trimethyl - cyclohexe - (11)-yl] - propyl 3 - pyrrolidino - propyl amine and the corresponding 2-piperidino-ethyl and 3 - piperidino - propyl amines, 2 - methyl - 4 - [21,61,61 - trimethyl - cyclohexen - (11 - yl] - butyl 3 - pyrrolidinopropyl amine and the corresponding 2-piperidino-ethyl, 2-dimethylaminoisopropyl and 3-piperidino-propyl amines, N1-[2 - methyl - 4 - [21,61,61 - trimethyl - cyclohexen - (11) - yl] - butyl] - N2,N2 - dimethyl - ethylenediamine, N1 - [2 - methyl - 4 - [21,61,61-trimethyl - cyclohexen - (11) - yl] - butyl] - N2,N2 - dipropyl 1,3 - diamino - propane, N1-[2 - methyl - 4 - [21,61,61 - trimethyl - cyclohexene - (11) - yl] - butyl] - N2,N2 - diethyl 1,3-diamino - 2,2 - dimethyl - propane, and N1 -[1 - methyl - 3 - [21,61,61 - trimethyl - cyclo hexen - (11) - yl] - propyl] - N2,N2 - dipropyl 1,3-diamino-propane.  Salts prepared in the examples are derived from oxalic, hydrochloric and hydrobromic acids.  Starting compounds.  2 - Methyl - 4 [21,61,61-trimethyl - cyclohexen - (11) - yl] - butyl amine is prepared by the reductive amination of 2-methyl - 4 - [21,61,61 - trimethyl - cyclohexen - (11) - yl] - buten - (2) - ol - (1) using an alcoholic solution of ammonia in the presence of Raney nickel.  Aldehydes of the general formula R1-X, wherein X represents the aldehyde group and R1 the substituted phenyl part of the substituted benzyl radical referred to above, are prepared by reacting the sodium derivative of the required hydroxy-benzaldehyde with the required dialkylaminoalkyl halide, pyrrolidinoalkyl halide, piperidino-alkyl halide or morpholino alkyl halide in chlorobenzene solution.  In the examples the following compounds are prepared:-4 - (21 - dimethylamino - ethoxy) -, 3 - (21 - diethylamino - ethoxy) -, 2 - (21 - diethylamino - ethoxy) -, 4 - (21 - dimethylamino - isopropoxy) -, 4 - (31 - piperidino - propoxy) -, isopropoxy) -, 4 - (31 - piperidino - propoxy) -, 4 - (31 - morpholino - propoxy) -, 4 - (31 - dimethylamino - propoxy) -, 2 - (31 - piperidino - propoxy) -, 3 - (31 - piperidino - propoxy) -, and 4 - (21 - piperidino - ethoxy) - benzaldehyde.