Synthesis of Eleven-Membered Cyclic Urea Fused Quinazolinones

Straightforward synthesis of quinazolinones having N-fused medium-sized ring urea was accomplished. Key intermediates were tert-butyl {2-[4 -oxo-2-(4-oxopentyl)quinazolin-3(4H)-yl]ethyl]carbamates derived from copper-catalyzed domino reaction of tert-butyl [2-(2 io-dobenzamido)ethyl]carbamates and cyclic enaminones. Steric hindrance of cyclic enaminones played an important role in the formation of quinazolinone ring. The eleven-membered ring urea moiety was readily achieved by direct cyclization using 1,1 '-carbonyldiimidazole (CDI) of diamino intermediate generated by readily reductive amination and deprotection of tert-butyl {2-[4-oxo-2-(4-oxopentyl)quinazolin-3(4H)-yl]ethyl}carbamates.