Synthesis of benzo[c][1,8]phenanthrolin-6-one through cyclization of N-(isoquinol-5-yl)-2-bromo-benzamide derivatives.

摘要

In the course of our search for compounds with potential antitumor properties we have undertaken the synthesis of benzo[c][1,8]phenanthroline derivatives. Our project required the preparation of 8,9-dimethoxy benzo[c][1,8]phenanthrolin-6-ones. This was first attempted by the lithiumdiisopropylamide cyclization of N-(isoquinol-5-yl)-2-bromo-4,5-dimethoxybenzamide. The reaction led to 40% of the unexpected internal Diels-Alder adduct 3,4-dimethoxy-6H-pyrido[2,3-i]6,8a-ethenoindolo[cd]isoquinoline-2(1H)-one, which arose from a benzyne intermediate. In a second and more successful approach, the internal biaryl palladium diacetate-assisted coupling reaction of properly N-protected N-(isoquinol-5-yl)-2-bromo-4,5-dimethoxybenzamide was studied. The optimisation of the protecting group necessary for this procedure led to a 64% yield of the target compound starting from N,N-(isoquinol-5-yl)-bis-(2-bromo-4,5dimethoxybenzamide).