Patent GB-843264-A (GB)
Title: Improvements in or relating to amines and to processes for their preparation
Inventor: NICOLSON JULIUS
Filed: 1956-01-18
Abstract: The invention comprises compounds of the formula: <FORM:0843264/IV(b)/1> and acid addition salts thereof, where R1 and R2 are the same or different and are each hydrogen or a lower alkyl, hydroxyalkyl, polyhdroxyalkyl, or alkoxyalkyl group, A is a saturated hydrocarbon chain of 3-9 carbon atoms which may carry lower alkyl substituents, R is an alkyl, hydroxyalkyl, aralkyl or phenyl group or a phenyl group substituted, preferably in the para position, by an alkoxy, acyl, hydroxy, nitro, acylamido or sulphonamido group, and R11 is an alkoxy group of 1-4 carbon atoms; and sodium formaldehyde-bisulphite derivatives of the primary amines of the above formula.  The compounds are prepared by reacting a compound of the formula:  <FORM:0843264/IV(b)/2> with a compound of the formula Z2, wherein Y is a tertiary amino group or a group or atom capable of being replaced by or converted into a primary, secondary or tertiary amino group, Z1 and Z2 are respectively a group and a compound capable of reacting together to form the group -OA1-O-R1 (A1 being the group A or a corresponding less saturated hydrocarbon group and R1 being the group R or an atom or group replaceable by or convertible to R), and R111 is either the group R11 or a hydroxyl group; followed if necessary by conversion of the groups Y, R1, A1 and R111 respectively into the groups NR1R2, R, A and R11.  Suitably Y may be one of the following groups: (a) as a group convertible primary amino; acylamido, nitro, nitroso, carbonamido, anil, alkoxycarbonylamino and arylazo; (b) as a group convertible to secondary amino; acylalkylamido (by hydrolysis) and anil, alkoxycarbonylamino or acylamido (by reduction) and (c) as a group convertible to tertiary amino; quaternary ammonium (by pyrolysis) and acylalkylamino (by reduction).  The compounds are used pharmaceutically in the treatment of bilharziasis.  In Examples (1) potassium 2-methoxy-4-nitrophenoxide is treated with 5-phenoxypentyl bromide and the resulting 1-(2-methoxy-4-nitrophenoxy)-5-phenoxypentane is reduced to 1-(2-methoxy-4-aminophenoxy)-5-phenoxypentane; similarly prepared are the 1-[2-methoxy-4-(nitro-and amino)-phenoxy]-5-benzyloxy-pentanes; (2) p-acetamidophenol is treated with 1 : 5-dibromopentane and the resulting 5-p-acetamidophenoxypentyl bromide is treated with potassium 2-methoxy-4-nitrophenoxide to give 1-(2-methoxy-4-nitrophenoxy)-5-p-acetamidophenoxy pentane which is reduced to 1-(2-methoxy-4 aminophenoxy)-5-p-acetamidophenoxy pentane; (3) 1-(4-amino-2-methoxyphenoxy)-4-phenoxybutane is quaternated with methyl iodide and the resulting 1-(4-dimethylamino-2-methoxyphenoxy-4-phenoxybutane methiodide is pyrolysed to give 1-(4-dimethylamino-2-methoxyphenoxy)-4-phenoxy-butane and (4) 1-(4-amino-2-methoxyphenoxy)-4-phenoxybutane is treated with 2-chloroethyl chloroformate and the resulting 1-[4-(2-chloroethoxy) carbonylamino-2-methoxyphenoxy]-4-phenoxybutane is treated with sodium hydroxide in aqueous alcohol and 2-ethoxyethanol to give 1-[4-(2-hydroxyethyl)-amino-2-methoxyphenoxy]-4-phenoxybutane.ALSO:The rapeutic compositions for the treatment of bilharziasis comprise compounds of the formula <FORM:0843264/VI/1> and acid addition salts thereof, (see Group IVb), wherein R1 and R2 are each hydrogen or a lower alkyl, hydroxyalkyl, polyhydroxy-alkyl or alkoxyalkyl group, A is a saturated hydrocarbon chain of 3-9 carbon atoms, which may carry lower alkyl substituents, R is an alkyl, hydroxyalkyl or aralkyl group or a phenyl group optionally substituted in the para position by an alkoxy, acyl, hydroxy, nitro, acylamide or sulphonamido group and R11 is an alkoxy group of 1-4 carbon atoms, or sodium formaldehyde bisulphite derivatives of those of the above compounds which are primary amines, in association with a solid or liquid pharmaceutical carrier.  The compositions may be in the form of elixirs, tablets, powders or capsules for oral administration, suitable solid diluents being starch, lactose, talc, stearic acid, magnesium stearate and gums, or in the liquid form for parenteral injection, for example as a solution in a sterile liquid such as water.