Patent GB-965909-A (GB)
Filed: 1960-11-16
Abstract: The invention comprises compounds of the general formula: <FORM:0965909/C1/1> (wherein R1 represents a C1-6 alkyl radical, an aryl radical, or an aralkyl radical in which the alkyl portion contains 1 to 6 carbon atoms, R2 represents a hydrogen atom or a C1-6 alkyl radical, X1 and X2 represent hydrogen atoms or jointly an additional linkage, Y represents a hydrogen or halogen atom or a C1-6 alkyl radical, Z represents a straight- or branched-chain C2-6 alkylene radical, and Am represents a dialkylamino group having at most 6 carbon atoms in each alkyl residue, while one of the alkyl residues of Am may be directly linked to Z or both of them may be linked together directly or through an oxygen atom or an alkylimino or hydroxyalkylimino group) and their acid addition and quaternary ammonium salts, and the preparation thereof by (a) reacting the corresponding N-unsubstituted compounds (II) with reactive esters of aminoalcohols HO-Z-Am (III) in the presence of a basic condensing agent, and, if desired, converting the products into salts with an inorganic or organic acid, or into a quaternary ammonium salt by addition of a reactive ester of an aliphatic or araliphatic alcohol, or (b) heating a compound of the general formula: <FORM:0965909/C1/2> until one molecular proportion of carbon dioxide is split off, or (c) (except where an alkyl residue of Am is linked to Z) reacting a reactive ester of a compound of the general formula: <FORM:0965909/C1/3> with a secondary amine Am-H, or (d) (when Am represents a dialkylamino group) alkylating a corresponding primary amino or monoalkylamino compound (VII), or (e) reducing, by means of an alkali metal-earth metal hydride, a compound of the general formula: <FORM:0965909/C1/4> (wherein Z1 and Am2 represent residues corresponding to Z and Am except that in at least one of them there is at least one carbonyl group, instead of a methylene group, linked to a nitrogen atom.  The products have antiallergic, antiemetic, antispasmodic, sedative and narcoticpotentiating activity, whilst the quaternary ammonium salts also act as garglioplegics.  Starting materials:  Compounds (IV) are prepared by reacting the corresponding N-unsubstituted compounds (II) with phosgene and the resulting 5-chlorocarbonyl compounds with aminoalcohols (III). Reactive esters of compounds (V) are prepared by reacting alkali metal derivatives of compounds (II) with alkylene oxides and reacting the resulting compounds (V) with inorganic acid halides, methanesulphonic acid chloride or arylsulphonic acid chlorides, or directly by reacting alkali metal derivatives of compounds (II) with non-geminal dihaloalkanes or with arylsulphonic acid haloalkyl esters. Primary and secondary amines (VII) are obtained by using ammonia or a monoalkylamine in place of the secondary amine Am-H in process (c) above.  Compounds (VIII) are prepared by reacting alkali metal derivatives of compounds (II) with a -bromoalkenecarboxylic acid dialkylamides, pyrrolidides, piperidides, morpholides or 4-alkylpiperazides, or with haloalkanecarboxylic acid halides followed by reaction of the resulting 5-haloalkanoyl compounds with amines Am-H, or by reacting reactive esters of compounds (V) with alkali metal compounds of alkanecarboxylic acid N-alkylamides, dialkanecarboxylic acid imides, succinimide or glutarimide, or by arylation of compounds (VII).  Specifications 943,277 and 961,444 are referred to.