Neue Cyclobutenderivate

摘要

The invention comprises compounds of formula wherein Ph is an o-phenylene group optionally substituted by one or more halogen atoms or alkyl, alkoxy, methylenedioxy or trifluoromethyl groups, Y is a substituted or unsubstituted amino group, R1 is a hydrogen atom or an alkyl or hydroxyalkyl group, and R11 is a hydrogen atom or an alkyl, aryl or aralkyl group, acid addition salts thereof, and their preparation by (a) reduction of a compound of formula with in one exemplified case simultaneous reduction of a carboxylic ester group in R1 to form a -CH2OH group, (b) reduction of a compound of formula (c) reaction of a compound of formula wherein X1 is a reactive esterified hydroxyl group, with ammonia or an amine YH, (d) reacting a compound of formula with ammonia, hydroxylamine, or an amine YH, with simultaneous or subsequent reduction of the Schiff's base formed, and (e) alkylation of a product by reaction with a reactive ester of an alkanol, or with formaldehyde and formic acid, or by acylation to the corresponding amide followed by reduction. 1-N-Furfurylcarbonyl-benzocyclobutene is prepared by reaction of the corresponding carboxylic acid with thionyl chloride, and reaction of the acid chloride thus formed with furfurylamine. 1-Acetal-benzocyclobutene is prepared by treatment of 1-cyano-benzocyclobutene with methyl magnesium iodide, followed by hydrolysis. 1 - Cyano - 1 - (b - carbethoxyethyl) - benzocyclobutene is prepared by reaction of 1-cyanobenzocyclobutene with ethyl acrylate in the presence of trimethylbenzyl ammonium chloride. 1-Cyano-5-methoxy-benzocyclobutene and 1-cyano-4,5-methylenedioxy-benzocyclobutene are prepared by reaction of 3-bromo-4-methoxybenzaldehyde or 6-bromo-piperonal with malonic acid to give the corresponding o-bromocinnamic acid derivative; hydrogenating this to give the corresponding o-bromo-hydrocinnamic acid derivative, converting this to the corresponding o-bromo-acid chloride by reaction with thionyl chloride, reacting this with ammonia to give the corresponding b -o-bromo-phenyl-propionamide, reacting this with p-toluene-sulphonyl chloride to give the corresponding b -o-bromophenyl-propionitrile and cyclizing this in the presence of potassium amide. The compounds of the invention have analgesic activity and may be used in pharmaceutical or veterinary compositions in combination with a carrier, for example in forms suitable for oral or parenteral administration such as tablets, capsules, dragees, solutions, suspensions or emulsions. They may also be used in animal foodstuffs. Reference has been directed by the Comptroller to Specification 1,001,070.