Synthesis of 1,3-Dimethyl-5-(9-nitro-7-phenyl-2,3,4,5-tetrahydro-1H-pyrrolo[1,2-a][1,3]diazepin-8-yl) pyrimidine-2,4,6-trione via a One-Pot, Three-Component Reaction

Pyrrolodiazepines have CNS depressant, anti-inflammatory, anti-convulsant and antihistamine activity.They are inhibitors of enzyme promoted prostaglandin synthesis, and protectors against the convulsive shock induced by metrazol in mice[1].Compounds based on barbituric acid show a high hypnotic and sedative activity[2].Heterocyclic ketene aminals are powerful and versatile intermediates in heterocyclic synthesis. Reactions of cyclic methylidene-aminals with a number of electrophilic reagents have been successfully used to synthesize five- and six-membered and fused heterocycles in recent years. These fused heterocyclic structures are frequently found in pharmacophores and play important roles in drug discovery. They are also used as pesticides, herbicides, antianxiety agents, and antibacterial drugs[3]. We have developed synthesis of new heterocyclic compoundsusing nitroketeneaminals multi-component reactions(Figure 1). The reaction of 1,3-dimethylbarbituric acid 1,arylglyoxals (2) and nitroketenaminal derivatives (3)in EtOH at reflux conditions produced pyrrolodiazepin derivatives (4) in excellent yields (85-90%). The 1H and 13C NMR spectra of the crude products clearly indicated the formation of title compounds. The work-up procedure is simple and easy. The structures of compounds 4 were confirmed by IR, MS, 1H- and 13CNMR analyses.