Synthesis of 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-]quinazolinones through a cyclized dearomatization and trichloromethylation cascade strategy.

A variety of 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-]quinazolinones were prepared in moderate to good yields with high regioselectivity through intramolecular 6- cyclization and trichloromethylation of 3-alkynyl-2-pyridinyl-tethered quinazolinones in chloroform. Mechanistic studies revealed that chloroform might serve as a trichloromethyl anion precursor. Furthermore, the reaction could be easily performed on gram scales and an estrone-derived 4-(trichloromethyl)pyrido[2',1':3,4]pyrazino[2,1-]quinazolinone was prepared over five steps.