ABSTRACT
A novel multicomponent reaction between IL-anchored 2-aminobenzoimidazoles, aldehydes, and electron-deficient dienophiles has been explored. The strategy was utilized to develop a rapid parallel synthesis for novel bis-heterocyclic skeleton of benzimidazole-linked dihydropyrimidine on an ionic liquid support. This multicomponent reaction is compatible with a wide range of substrates and furnishes the new chimeric scaffolds with high purity and excellent yields. Use of the ionic liquid as a soluble support facilitates purification by simple precipitation along with advantages like high loading capacity, homogeneous reaction conditions, and monitoring of the reaction progress by conventional NMR spectroscopy.
Subject(s)
Heterocyclic Compounds/chemistry , Ionic Liquids/chemistry , Benzimidazoles/chemistry , Catalysis , Lewis Bases/chemistry , Pyrimidines/chemistryABSTRACT
A novel base-catalyzed Povarov reaction of arylamines, aldehydes, and electron-deficient dienophiles has been developed. An unprecedented in situ [1,3] sigmatropic rearrangement leading to 4,10-dihydropyrimido[1,2-a]benzimidazoles has also been discovered. An insight of the plausible mechanism is discussed and supported by X-ray crystal study. This cascade reaction is achieved in a one-pot multicomponent fashion on soluble support under microwave conditions.
Subject(s)
Benzimidazoles/chemistry , Hydrogen/chemistry , Pyridines/chemistry , Catalysis , Crystallography, X-Ray , Models, Molecular , Molecular StructureABSTRACT
The synthesis of indoline substituted nitrobenzene on a PEG support and its further elaboration to structurally diverse benzene-fused pyrazino/diazepino indoles is disclosed. A reagent based diversification approach coupled with Pictet-Spengler type condensation reactions furnished these fused polycyclic scaffolds. Microwave irradiation was used as a means of rate acceleration for soluble polymer-supported reactions. The efficiency of these fused heterocyclic molecules to inhibit the vascular endothelial growth factor receptor 3 (VEGFR-3) was examined in vitro using kinase receptor activation enzyme-linked immunosorbant assay (KIRA-ELISA). Based on the preliminary results obtained, a small set of potential drug candidates were identified as novel leads in this therapeutic area to be further explored as anti-metastatic agents.
