A new cascade reaction: concurrent construction of six and five membered rings leading to novel fused quinazolinones

Abstract

A one-pot cascade reaction has been developed leading to the concurrent construction of six and five membered fused N-heterocyclic rings of indazolo[3,2-b]quinazolinones. The methodology involved the reaction of isatoic anhydride, a hydrazine and o-iodo benzaldehyde in the presence of Pd(PPh₃)₄ and BINAP in MeCN. The mechanism of this cascade reaction is discussed. A variety of indazolo[3,2-b]quinazolinone derivatives were prepared by using this methodology in good yields, some of which were tested for their PDE4 inhibitory properties in vitro. The dose response and docking study performed using a representative compound is presented.