Patent GB-739741-A (GB)
Title: Improvements in or relating to substituted benzamidopropylamines and process of preparing the same
Filed: 1953-09-29
Abstract: The invention comprises compounds of formula <FORM:0739741/IV (b)/1> and acid addition salts thereof, wherein R is hydrogen or an alkoxy radical containing 1 or 2 carbon atoms or a cycloalkoxy, amino or dialkylamino radical, R1 and R2 each represent hydrogen or an alkyl radical containing 1 or 2 carbon atoms and R2 is a dialkylamino, piperidino, pipecolino or a pyrrolidino radical.  The compounds are prepared by reacting a propiophenone of formula <FORM:0739741/IV (b)/2> with hydroxylamine, hydrogenating the resulting oxime to form a propanediamine of formula <FORM:0739741/IV (b)/3> and acylating the latter compound with benzoyl or para - nitrobenzoyl chloride or a para - dialkylamino -, para - cycloalkoxy - or paraalkoxybenzoyl chloride (the alkoxy group containing 1 or 2 carbon atoms), the nitro group in the para - nitrobenzoylated product being subsequently reduced to an amino group.  Starting materials are preferably b  - pyrrolidinobutyrophenone, b  - piperidino -, a  - methyl - b  - piperidino -, b  - dimethylamino -, b  - (21 - methylpiperidino) -, or b  - dibutylaminopropiophenone, preferably in the form of their hydrochlorides.  4 - Cyclohexyloxy -, para - methoxy -, and para - dimethylamino - benzoyl chloride are also preferred as specific acylating agents.  The examples describe the preparation of 1-benzamido - 1 - phenyl - 3 - pyrrolidinobutane; 1 - benzamido - 1 - phenyl -, 1 - benzamido - 1-phenyl - 2 - methyl -, 1 - (4 - aminobenzamido)-1 - phenyl -, and 1 - (41 - cyclohexyloxybenzamido) - 1 - phenyl - 3 - piperidinopropane; 1-benzamido - 1 - phenyl -, 1 - (41 - dimethylaminobenzamido) - 1 - phenyl -, and 1 - (41-methoxybenzamido) - 1 - phenyl - 3 - dimethylaminopropane; 1 - benzamido - 1 - phenyl - 3-(21 - methylpiperidino) -, and 1 - benzamido - 1-phenyl - 3 - di - n - butylaminopropane; and salts thereof with hydrochloric, hydrobromic, nitric, sulphuric, phosphoric, acetic, propionic, butyric, lauric, maleic, citric, benzoic and salicylic acid.  The following intermediates are described: oximes of b  - pyrrolidinobutyrophenone, 3-piperidino -, a - methyl - b  - piperidino -, b  - (21-methylpiperidino) -, and -b  - di - n - butylaminopropiophenone (and hydrochlorides thereof); 1-(41 - nitrobenzamido) - 1 - phenyl - 3 - piperidinopropane; 1 - phenyl - 3 - pyrrolidinobutylamine, 1 - phenyl - 3 - piperidino -, 1 - phenyl - 2-methyl - 3 - piperidino -, 1 - phenyl - 3 - (21 - methylpiperidino) -, 1 - phenyl - 3 - dimethylamino-, and 1 - phenyl - 3 - di - n - butylaminopropylamine.  b  - (21 - methylpiperidino) - propiophenone is prepared by refluxing a mixture of acetophenone, 2 - pipercoline hydrochloride, paraformaldehyde, ethanol and concentrated hydrochloric acid.  b  - pyrrolidinobutyrophenone (hydrochloride described) is prepared by the dropwise addition of propenylphenylketone to a solution of pyrrolidine in toluene.ALSO:A composition for use as a local an sthetic comprises a benzamidopropylamine derivative of formula <FORM:0739741/VI/1> or acid addition salts thereof, wherein R is hydrogen or an alkoxy radical containing 1 or 2 carbon atoms or an amino, dialkylamino or cycloalkoxy radical, R1 and R2 each represent hydrogen or an alkyl radical containing 1 or 2 carbon atoms and R3 is a dialkylamino, piperidino, pipecolino or a pyrrolidino radical, and a pharmaceutical extending media such as ointments, jellies, oils and lotions; or a solution of the above acid addition salts in water.  Acid addition salts are preferably those of hydrochloric, hydrobromic, nitric, sulphuric, phosphoric, benzoic, acetic, salicylic, propionic, maleic, citric, lauric and butyric acid.