Patent GB-970577-A (GB)
Title: New quaternary ammonium compounds and methods for the preparation thereof
Inventor: TEMPLE RICHARD WILLIAM
Filed: 1959-11-20
Abstract: The invention comprises: (1) compounds of general formula <FORM:0970577/C1/1> wherein: (a) R, R1 and R2 are each a saturated or unsaturated lower alkyl group, or (b) R is a saturated or unsaturated lower alkyl group, and R1 and R2 are joined together to form with the nitrogen atom a saturated hererocyclic ring optionally containing a further hetero atom; X is a nontoxic anion; R is an alkylene chain having 2 or 3 chain carbon atoms, the values of R, R1, R2 and A being chosen so that when A is an ethylene chain at least one of R, R1 and R2 is an unsaturated lower alkyl group (the term "lower alkyl group" means an alkyl group containing one to three carbon atoms, and the term "saturated lower alkyl group" embraces such groups when substituted by a further group which will not significantly alter the electron density around the 1-amino nitrogen atom (e.g. a hydroxy substituent) ); and their preparation by reacting in an appropriate solvent a compound of general formula <FORM:0970577/C1/2> with a compound of formula RX: (2) those compounds of general formula II wherein A is an alkylene chain having 2 or 3 chain carbon atoms, and wherein, when A is an alkylene chain containing 2 chain carbon atoms, R1 is an unsaturated lower alkyl group and R2 is a saturated or unsaturated lower alkyl group, and when A is an alkylene chain containing 3 chain carbon atoms, R1 and R2 are each a saturated or unsaturated lower alkyl group, or are joined together to form with the nitrogen atom a saturated heterocyclic ring optionally containing a further hetero atom; and their preparation substantially as described in examples wherein compounds of formula <FORM:0970577/C1/3> are reacted with amines R2NH2 and the intermediate 1-(R1-amino)-compounds are then N-methylated. Also mentioned are separation of optical isomers of quaternary compounds I, the preparation of certain quaternary compounds I by reacting compounds III and compounds NR.R1R2, and the preparation of tertiary amines II by reacting compounds III with compounds HNR1R2. Pharmaceutical compositions comprise quaternary and tertiary compounds of the invention with pharmaceutical carriers.  The compounds are adrenergic blocking agents useful in treating hypertension.  The Provisional Specification relates to compounds of formula I wherein R, R1 and R2 are (a) saturated or unsaturated lower alkyl groups optionally substituted, or (b) R is such a group and R1 and R2 form with the nitrogen a saturated or unsaturated heterocyclic ring optionally containing a further heteroatom, and A is an alkylene chain containing up to 3 carbon atoms which may be substituted on either of the two carbon atoms nearest to the aromatic ring and which may contain a further heteroatom; except that when R, R1 and R2 are methyl and A is unsubstituted ethylene, X is not iodine.  The quaternary compounds are prepared from tertiary amines by reaction with compounds RX, R1X and R2X.  Di-(lower alkyl)-tertiary amines (except dimethyl or diethyl) are said to be novel. In examples (1) the ethyl iodide, ethyl bromide and ethyl p-toluenesulphonate of 1-dimethylamino-indane are prepared, (2) N (1-indanyl) pyrrolidine is prepard from 1-chloroindane and pyrrolidine and yields an ethiodide. Specification 969,195 is referred to.