GB859223A - Tryptamine compounds - Google Patents

Abstract

The invention comprise indole derivatives of the formula: <FORM:0859223/IV(b)/1> and acid addition salts thereof, wherein R1 is a divalent aliphatic hydrocarbon radical of 1-3 carbon atoms, R2 is hydrogen, C1-5 alkyl (e.g methyl) or an aryl substituted C1-5 alkyl group, R3 is hydrogen, C1-5 alkyl (e.g. methyl), aryl substituted C1-5 alkyl (e.g. benzyl), C1-6 alkanoyl, benzoyl or an aryl substituted C1-5 alkanoyl radical, R4 is hydrogen or methyl, each of R5 and R6 is a hydrogen atom or a C1-8 hydrocarbon radical or together with the nitrogen form a heterocyclic (e.g. pyrrolidyl) ring and n is one or two. The compounds are prepared by reacting a phenyl hydrazine of the formula: <FORM:0859223/IV(b)/2> with an aralkyl halide of the formula: <FORM:0859223/IV(b)/3> to produce a N:N-disubstituted hydrazine of the formula: <FORM:0859223/IV(b)/4> condensing this in an acidic medium at an elevated temperature with a halogenated ketone of the general formula: CH3,CO,CH2,CH2,CHX,R4, wherein X is a halogen atom to give the 3-b -haloethyl or b - halopropyl indole corresponding to the final products which is then treated with ammonia or an amine HNR5R6. Products in which -NR5R6 is an -NH2 group may also be prepared by reacting the phenyl hydrazine starting material R3O,C6H4.NHNH2 with 5-phthalimido-pentanone-(2) or 5-phthalimido-hexanone-(2) in an acidic medium at an elevated temperature to produce a phthalimidoalkyl indole which is reacted with the aralkyl halide II to give the phthalimido derivative of the desired 3-aminoalkyl-indole from which the phthalimido group is removed by treatment with hydrazine. Compounds wherein R3 is a hydrogen atom may be prepared by hydrogenolysis of corresponding benzyl ethers and compounds wherein R3 is an acyl group are prepared by acylating the hydroxy compounds. 1-p-Hydroxybenzyl-2-methyl-3-b -aminoethyl-5-hydroxyindole is prepared by heating the corresponding 1-p-methoxybenzyl compound in pyridine. Specified products include 1-p-methoxybenzyl-, 1-p-benzyloxybenzyl-, 1-p-hydroxybenzyl- and 1-p-methoxycinnamyl-2-methyl- 3-b -aminoethyl-5-methoxyindole; 1-p-methoxybenzyl-2-methyl-3-b -ethylamino and diethylamino-ethyl-5-methoxyindole; 1-p-methoxybenzyl-2-methyl-3-b -amino-ethyl-5-benzyloxy-and 5- hydroxy-indole 1-p-, methoxybenzyl-2-methyl-3-b -dimethylaminoethyl -5-hydroxy-, 5-acetoxy- and 5- isobutyroxy-, indole; 1-p-hydroxybenzyl-2-methyl-3-b -aminoethyl - 5 - hydroxyindole and 1- p - methoxy-benzyl-2-methyl-3-b -aminoethyl - 5 - acetoxy-indole. 5-Phthalimidopentanone-(2) and 5-phthalimido hexanone-(2) used as starting materials are made by the action of phthalimide in dimethyl formamide on 5-chloropentanone-(2) or 5-chlorohexanone-(2) in the presence of potassium carbonate.