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(PPh(3))(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.

Applications of Palladium-Catalyzed C–N Cross-Coupling Reactions

“…Alkylhydrazines were among the substrates utilized by Pal and co-workers in a multicomponent reaction (MCR) to access fused heterocycles 509 , as shown in Scheme 124 . 429 Through this novel transformation, a set of structurally diverse indazoloquinazolinones, potentially active against pulmonary diseases, was rapidly generated in a one-pot protocol. The multistep sequence began by reaction of the hydrazine with isatoic anhydride ( 506 ) to afford intermediate 507 after loss of CO 2 .…”

“…As an alternative, monosubstituted hydrazines are convenient coupling partners that typically react exclusively at the unsubstituted nitrogen center. Alkylhydrazines were among the substrates utilized by Pal and co-workers in a multicomponent reaction (MCR) to access fused heterocycles 509 , as shown in Scheme . Through this novel transformation, a set of structurally diverse indazoloquinazolinones, potentially active against pulmonary diseases, was rapidly generated in a one-pot protocol.…”

Survey of Recent Literature Related to the Biologically Active 4(3H)-Quinazolinones Containing Fused Heterocycles

“…A new cascade reaction was designed to prepare a series of indazolo[3,2-b]quinazolinones (65, Fig. 23) [87] similar to evodiamine. The molecules were evaluated as phosphodiesterase (PDE) inhibitors.…”