Synthesis of New trans-2-Benzyl-3-(furan-2-yl)-4-substituted-1234-tetrahydroisoquinolinones

摘要

The reaction of homophthalic anhydride and N-(furan-2-yl-methylidene)-benzylamine in different solvents and varying temperatures was studied in detail. Mixtures of the expected trans- and cis-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acids >trans->5 and >cis->5, alongwith by-products >6 and >7 were obtained in dichloroethane or benzene. In pyridine, used for the first time, the reaction became completely diastereoselective, giving only the trans isomer. The carboxylic acid group of >trans->5 was transformed in four steps into cyclic aminomethyl groups which yielded various new tetrahydroisoquinolinones >trans->11a->g, incorporating both a known fragment of pharmacological interest and various pharmacophoric substituents.