Patent GB-1000423-A (GB)
Title: Basic alkylated naphthalene-(1,4,5,8)-tetracarboxylic acid-diimides and di-(imido-amines)
IPC: C07D295/13
Filed: 1963-09-12
Abstract: The invention comprises compounds of the formula <FORM:1000423/C2/1> in which A is a direct linkage or a branched or unbranched alkylene chain containing up to 6 carbon atoms, R is a hydrogen atom or an alkyl group containing up to 8 carbon atoms, R1 is an alkyl radical containing up to 8 carbon atoms or R and R1 may be joined together, or one or both of R and R1 may be joined to A or to R6, optionally via a heteroatom, such as a nitrogen, sulphur or oxygen atom or via an aromatic or hydroaromatic ring or R and/or R1 may be substituted by an aromatic or hydroaromatic ring or by hydroxyl groups, R2, R3, R4 and R5 which may be the same or different, are hydrogen atoms or hydroxyl, amino or sulpho groups, R6 is a hydrogen atom or an alkyl group containing up to 4 carbon atoms and n is 1 or 2 when m is 1 or n is 1 when m is 0; their salts with non-toxic pharmaceutically-acceptable acids and the preparation thereof by reacting an anhydride of the formula <FORM:1000423/C2/2> or the corresponding tetracarboxylic acid with an amine of the general formula <FORM:1000423/C2/3> in a molten state or in the presence of a solvent or by reacting an imide of the general formula <FORM:1000423/C2/4> with a halide of the general formula <FORM:1000423/C2/5> or by reacting an amine R1-NH-R with a halide of the general formula <FORM:1000423/C2/6> or by reducing a nitrile of the formula <FORM:1000423/C2/7> wherein D is a direct linkage, in the presence of an aldehyde.  N - (2 - Aminoethyl) - 3 - azabicyclo - (3,2,2)-nonane is prepared by heating 3-azabicyclo-(3,2,2) - nonane (from 1,4 - bis - aminomethyl-cyclohexane and an aluminum hydroxide catalyst) with glycol nitrile to give N-cyanomethyl-3-azabicyclo-(3,2,2)-nonane and reducing this. Similarly is prepared N - cycloethyl-and N - (3 - aminopropyl) - 3 - azabicyclo-(3,2,2) - nonane.  N - (2 - Aminoethyl) - 3,3 - dimethyl-pyrroilidine is prepared by reducing a ,a  - dimethyl - succinimide to 3,3 - dimethyl-pyrroilidone, further reducing this to 3,3-dimethylpyrrolidine which with glycol nitrile gives N - (cyanomethyl) - 3,3 - dimethyl - pyrrolidine which is reduced. N,N1 - Tetramethyl-2-amino-propylene diamine is prepared by reacting dimethylamine, formaldehyde and nitromethane to give N, N1-tetra-methyl-2-nitropropylene diamine and reducing the nitro group.  1,3 - Bis - diethylaminopropyl - 2-amine together with some 2,3-bisdiethylaminopropyl-1-amine (formed by rearrangement) is prepared by reacting 1,3-dichloropropano-2-ol to give 1,3 - bis - diethylamino - propan - 2 - ol reacting this with thionyl chloride to give 1,3 - bis - diethylamino - 2 - chloropropane and treating this with ammonia.  g  - (4 - Methyl-piperidino)-propylamine is prepared by reacting 4 - methylpiperidine and acrylonitrile to give b  - 4 - methylpiperidino) - propionic acid nitrile and hydrogenating the cyano group. Similarly are prepared g -(2-methyl-piperidino)-, g  - (2 - ethyl - piperidino)-, g  - hexamethylene-imino, g  - (thiamorpholine - s - dioxide) and g  - [N - (b  - diethylaminoethyl) - piperazino)-propylamine and N-methyl-N-cyclohexyl-propylene - diamine.  b  - (N - Methyl - piperazino) ethylamine is prepared by reacting N-methyl-N1 - b  - hydroxyethylpiperazine with thionyl chloride to give N - methyl - N1 - b  - chloroethyl-piperazine and reacting this with ammonia. Similarly is prepared N-methyl-N-(b -phenylethyl)-, N - ethyl - N - (b  - phenylethyl) - and N,N - dibenzyl - ethylene diamine, b  - deca-hydroquinolino-, b  - decahydroisoquindino- and b  - isobutylamino - ethylamine.  g  - Piperidino-b  - dimethylpropylamine and g  - morpholino-b -dimethylpropylamine are prepared either by amination of the corresponding halo-derivative or by reductive amination of b -piperidino or BETA - morpholino - a  - dimethyl - propionaldehyde respectively.  Specification 883,337 is referred to.