Patent GB-761799-A (GB)
Title: Benzilamide derivatives
IPC: C07D295/13
Filed: 1954-03-30
Abstract: The invention comprises compounds having the general formula <FORM:0761799/IV(b)/1> wherein Y is lower alkylene of at least 2 carbon atoms, R and R1 are each lower alkyl or, together with N, form a heterocyclic ring, R11 is hydrogen, lower alkyl or aralkyl, and X is an anion.  (The terms "lower alkyl" and "lower alkylene" are meant to denote branched as well as straight chain groups having two to six carbon atoms.)  Such compounds, when they are hydrohalides, may be obtained by heating a diamine of the formula <FORM:0761799/IV(b)/2> with an a -halodiphenyl acetyl halide and then heating in the presence of dilute mineral acid or alkali.  The free base can then be liberated and reacted with other acids to form salts (e.g. hydrochloride, hydrobromide, hydroiodide, sulphate, citrate or tartrate) or with, for example, methyl chloride or bromide, ethyl bromide, dimethyl sulphate, ethyl nitrate or benzyl chloride to form quaternary compounds.  Alternatively the a -halodiphenyl acetyl halide is reacted with a methylaminoalkyl halide and the product is reacted with a secondary amine to give the aminoalkyl benzilamide or hydrohalide thereof.  In examples: (1) N,N-diethylN1 - methylethylene diamine is reacted with a -chlorodiphenylacetyl chloride and the mixture refluxed, cooled and treated with water.  Extraction with hydrochloric acid and heating the extract gives N-(2-diethylaminoethyl)-N-methyl benzilamide hydrochloride which on treatment with methyl chloride gives 2-(N-methylbenzilamido) ethyl diethyl methylammonium bromide; (2) and (3) the chloride and methosulphate are prepared similarly.  In further examples there are prepared by generally similar methods: (4) 2-(N-methylbenzilamido) ethyl triethyl ammonium bromide; (5) N-2-(di-isopropylaminoethyl)-N-methylbenzilamide hydrochloride and the corresponding methobromide; (6) 2-(N-methylbenzilamido) ethyl trimethyl ammonium bromide; (7) 2-(N-methylbenzilamido) ethyl dimethyl ethylammonium bromide; (8) 3-(N-methylbenzilamido) propyl trimethylammonium bromide; (9) the corresponding ethyl dimethylammonium compounds; (15) N-(morpholinoethyl) - N - methyl benzilamide, its hydrochloride and methobromide; (16) 2-(N-methylbenzilamido) ethyl diethyl benzylammonium chloride. In Examples (11) to (14), hydrochlorides corresponding to the free bases subjected to quaternation in Examples (1), (6), (8) and (10) respectively are isolated.  (10) 3-(N-methylbenzilamido) propyl methyl diethyl ammonium bromide.  Starting materials.  N,N - di - isopropyl - N1-methylethylenediamine is prepared by reacting 2-di-isopropylaminoethyl chloride hydrochloride with methylamine. N,N,N1-trimethyl ethylene diamine is prepared similarly. N,N,N1 - trimethyl - 1,3 - propanediamine is obtained by the reduction with lithium aluminium hydride of N,N-dimethyl-N1 - formyl - 1,3 - propanediamine, itself obtained by refluxing formic acid with dimethylaminopropylamine. Specification 438,659, [Group IV], is referred to.ALSO:A therapeutic composition comprises an antisecretory or antispasmodic compound of the general formula <FORM:0761799/VI/1> wherein Y is lower alkylene of at least 2 carbon atoms (preferably ethylene), R and R1 are each a lower alkyl radical (preferably of 1 to 3 carbon atoms) or, together with N, form a heterocyclic ring, R11 is hydrogen or (preferably) a lower alkyl or an aralkyl radical, and X is an anion (preferably chlorine, bromine, iodine or methosulphate), the terms "lower alkyl" and "lower alkylene" denoting branched as well as straight chain groups having two to six carbon atoms, together with a carrier, preferably solid but which may also be a liquid such as a syrup or aqueous-alcoholic medium.  Tablets, powder packets, capsules or other dosage forms may be prepared and other active ingredients such as neutralizers and/or antacids may be incorporated.  Lactose talc, stearic acid, magnesium stearate, carbomethoxycellulose and hydrated alumina are suitable excipients and starch is a suitable filler and disintegrator. One-piece gelatine capsules may contain the compounds mixed with corn oil.  Typical formul  for tablets contain 2-(N-methyl-benzilamido)-ethyl diethyl methyl ammonium bromide with (A) hydrated alumina, aqueous starch, stearic acid, magnesium stearate and cornstarch and (B) sodium carboxymethyl-cellulose, aqueous starch, magnesium stearate, isopropanol and cornstarch. Specification 438,659 [Group IV] is referred to.