Synthesis and Reactions of Pyrido[2,1-a]isoquinolin-4-yl Formimidate Derivatives and Antimicrobial Activities of Isolated Products

Treatment of arylidene malononitriles 2A-C with 1-cyanomethylisoquinoline 1 afforded 4-amino-2-arylpyrido[2,1-a]isoquinoline-1,3-dicarbonitrile derivatives 5A-C, which converted to formimidates 6A-Cvia reaction with triethylorthoformate. Treatment of the latter compounds with hydrazine hydrate gave the corresponding amino-imino compounds 7A-C, which underwent Dimroth rearrangement to afford 13-aryl-1-hydrazinylpyrimido[5,4:5,6]pyrido[2,1-a]isoquinoline-12-carbonitrile 8A-C. The latter reacted with aldehyde to give 9a-i. Oxidative cyclization of the latter compounds 9a-i gave [1,2,4]triazolo[4,3:1,6]-pyrimido[5,4:5,6]pyrido[2,1-a]isoquinolines 10a,d,g. Such compounds isomerized to the thermodynamically more stable isomers [1,2,4]triazolo[1,5:1,6]pyrimido[5,4:5,6]-pyrido[2,1-a]isoquinolines 11a,d,g. Antimicrobial activities for some compounds were studied.