Improvements in or relating to substituted 7-aminoalkylbicyclo[4.2.0]octa-1,3,5-trienes

摘要

The invention comprises compounds of the formula in which R is C1-3-alkyl, R1, R2 and Z are hydrogen or C1-3-alkyl, n is 0 or 1 and Y is hydrogen, chlorine, bromine, fluorine, C1- 3-alkyl, C1- 3-alkoxy or trifluoromethyl, and non-toxic pharmaceutically acceptable acid-addition salts thereof. The compounds where n is 0 and R1 and R2 are both hydrogen are prepared by the processes: Alternatively, the above bicyclo[4,2,0]octa-1,3,5-triene-7 -carbonyl derivative is catalytically reduced in the presence of an excess of ammonia or a C1-3-alkylamine and hydrogen with a platinum or nickel hydrogenation catalyst to give the corresponding 7-aminoalkyl or 7-mono-C1-3-alkyl-aminoalkyl products. The compounds where n is 1 and R1 and R2 are both hydrogen are prepared by the following processes:- When n is 1, the N-C1-3-alkyl compounds are prepared by refluxing the corresponding primary amine with ethyl formate for 12 to 24 hours, reacting the resulting N-formyl compound with sodium amide or a suspension of sodium hydroxide or hydride in mineral oil to give the sodio derivatives which is alkylated with a C1-3-alkyl iodide to give the N-formyl-N-C1-3-alkylamine and this is then hydrolysed in hydrochloric acid solution. When n is 0 or 1, the di-C1-3-alkyl-amino compounds are prepared by exhaustive alkylation of the primary amine. The acids used as starting materials in the first reaction scheme above, are prepared by the following processes: 2 - Trifluoromethyl - bicyclo[4,2,0] - octa-1,3,5 - triene - 7 - carboxylic acid is prepared by reacting acrylonitrile with 2 - chloro - 4 -trifluoromethylbenzene diazonium chloride (obtained by diazotization of 2-chloro-4-trifluoromethylaniline) to form a -chloro-b -(2-chloro-4-trifluoromethylphenyl) propionitrile, catalytically hydrogenating this to form b -(2-chloro-4-trifluoromethylphenyl) propionitrile, treating this with excess potassium amide to form 2-trifluoromethyl - bicyclo[4,2,0]octa - 1,3,5 - triene - 7-nitrile and hydrolysing this with hydrochlov acid. Bicyclo[4,2,0]octa - 1,3,5 - triene - 7 - aldehyde is prepared by reaction of bicyclo[4,2,0] octa-1,3,5-triene-7-carboxylic acid chloride with lithium tri-t-butoxyaluminohydride. Pharmaceutical compositions having anorectic and hypotensive activity comprise a compound of the invention with a pharmaceutical carrier or diluent, preferably in dosage unit form suitable for oral administration. Salts specified include those with ascorbic and theophyllineacetic acids and 8-halotheophyl-lines.