Synthesis and properties of bioactive 2- and 3-amino-8-methyl-8H-quino[4,3,2-kl]acridine and 8,13-dimethyl-8H-quino[4,3,2-kl]acridinium salts

Abstract

Cyclisation of 9-(benzotriazol-1-yl)acridine 1 to the pentacycle 8H-quino[4,3,2-kl]acridine 5 in a range of low-boiling solvents is mechanistically distinct from previously published photochemical (carbene) and thermolytic (radical) cyclisations. Fragmentation of the triazole ring of 1 to a diazonium intermediate 7, and its subsequent heterolysis (–N₂) and cyclisation is facilitated by solvation of intermediate zwitterionic species. Derivatives of 2- and 3-aminoquinoacridines methylated in the 8-position can be converted to 8,13-dimethylquino[4,3,2-kl]acridinium iodide salts with methyl iodide and were required for biological examination as potential telomerase inhibitors. The chloro group in 3-chloro-8-methyl-8H-quino[4,3,2-kl]acridine can be replaced efficiently by benzylamino, 4-morpholinyl and cyano substituents in palladium(0) mediated reactions.