Synthesis, In Silico and In Vivo Toxicity Assessment of Functionalized Pyridophenanthridinones via Sequential MW-Assisted Intramolecular Friedel-Crafts Alkylation and Direct C-H Arylation.

A rapid, efficient, and original synthesis of novel pyrido[3,2,1-]phenanthridin-6-ones is reported. First, the key cinnamamide intermediates - were easily prepared from commercial substituted anilines, cinnamic acid, and 2-bromobenzylbromide in a tandem amidation and -alkylation protocol. Then, these -aryl--(2-bromobenzyl) cinnamamides - were subjected to a TFA-mediated intramolecular Friedel-Crafts alkylation followed by a Pd-catalyzed direct C-H arylation to obtain a series of potentially bioactive 4-phenyl-4,5-dihydro-6,8-pyrido[3,2,1-]phenanthridin-6-one derivatives - in good yields.