Microwave‐assisted synthesis and heterocyclic functionalization of chromenopyridines on calixarene scaffold

Abstract

A three‐component one‐pot condensation reaction of chroman‐4‐one with ethyl 2‐cyanoacetate and various aldehydes in the presence of ammonium acetate afforded a series of 2‐oxo‐4‐phenyl‐1,5‐dihydro‐2H‐chromeno[4,3‐b]pyridine‐3‐carbonitrile. These heterocycles have been converted to chloropyridine derivatives and appended to macrocyclic calix[4]arene scaffold through aromatic nucleophilic substitution under microwave irradiation. In this study, the microwave‐assisted functionalization of the lower rim of calix[4]arene has been considered the only appropriate tool because the conventional heating did not lead to any new product after 72 hours of heating under thermal condition.

The Chromenopyridine Scaffold: A Privileged Platform in Drug Design

“…The use of chromanones as starting material for the preparation of chromenopyridines was also reported in the literature, and they present a similar chemical reactivity to that observed for chromones and substituted chromones. For example, to prepare new chromenopyridine derivatives 76, a four-component reaction was developed [75]. Chroman-4-one 72 reacted with aromatic aldehydes 73, ethyl cyanoacetate 74 and ammonium acetate under reflux in ethanol, affording compounds 75 in 65-82% isolated yield (Scheme 11A).…”