Patent GB-804879-A (GB)
Title: Isocamphane compounds and processes for preparing them
Filed: 1956-05-29
Abstract: The invention comprises compounds having the formula: <FORM:0804879/IV (b)/1> wherein R is a C1-8 alkyl group and R1 is C1-8 alkyl group or a hydrogen atom, acid addition salts thereof, quaternary ammonium salts of 3-aminoisocamphane, and a process that comprises reducing a compound having the general formula: <FORM:0804879/IV (b)/2> wherein R1 is a hydrogen atom or a C1-8 alkyl radical and R0 is an acyl radical derived from a C1-8 aliphatic carboxylic acid.  The reduction may be effected by means of alkali metal hydride in an inert solvent, e.g. lithium aluminium hydride in ethyl ether, 2 mols. of hydride being employed per mol. of isocamphane starting material.  The product may be recovered as its hydrochloride salt. N-methyl-amino isocamphanes may be prepared by reacting 3-aminocamphane with formaldehyde and hydrogen in the presence of a hydrogenation catalyst of the platinum group, e.g. palladium on charcoal, and in the presence of water.  Instead of formaldehyde, C2-8 aliphatic aldehydes may be employed.  The products in which both R and R1 are C1-8 alkyl groups may be reacted with an alkyl halide to produce a quaternary ammonium salt of 3-aminoisocamphane.  A racemic mixture of the products may be separated by resolution with d-camphorsulphonic acid.  Examples describe the preparation of 3-(N-methylamino) isocamphane and the hydrochloride thereof, 3-(N,N-dimethyl-amino) isocamphane and the hydrochloride thereof, dl - 3 - (N - ethylamino) - isocamphane hydrochloride, 3 - (N,N - diethylamino) isocamphane, dl - 3 - (N - n - butylamino) - isocamphane hydrochloride, dl - 3 - (N - 3,3 - dimethylbutylamino) - isocamphane, the trimethylammonium iodide of 3-aminoisocamphane, and d- and l-3-(N-methylamino)isocamphane. Specification 804,880 is referred to.ALSO:The invention comprises a pharmaceutical composition containing as active ingredient a compound having the formula <FORM:0804879/VI/1> where R is a C1-8 alkyl group and R1 is a C1-8 alkyl group or a hydrogen atom, acid addition salts thereof, or a quaternary ammonium salt of-3-aminoisocamphane, together with a pharmaceutical carrier.  The products are valuable ganglionic blocking agents.  A composition for oral administration comprises 3-(N-methylamino) isocamphane hydrochloride, lactose, di-calcium phosphate, starch, acacia gum, talc and magnesium stearate. Solutions for parental injection comprise (1) 3-(N-methylamino) isocamphane hydrochloride, sodium chloride and pyrogen free water; (2) 3-(N-methylamino), isocamphane hydrochloride, sodium chloride, methylparaban, propylparaban and pyrogen free water. In these formulations the 3-(N-methylamino) isocamphane hydrochloride can be replaced by other acid salts of isocamphane, or other alkylated derivatives of 3-aminoisocamphane.  Alternatively, quaternary ammonium salts of the tertiary aminoisocamphane compounds, e.g. the methiodide of 3-(N,N-dimethylamino) isocamphane, the methochloride of 3-(N,N-diethylamino) isocamphane, and the methosulphate of 3-(N,N-diisopropylamino) isocamphane, can be used. Specification 804,880, [Group IV (b)], is referred to.