Diversity-Oriented Synthesis of Angular Bis-benzimidazole Derivatives under Microwave Irradiation

Abstract

Pharmaceutically interesting, angular bis-benzimidazoles with three appendages have been synthesized successfully through a diversity-oriented approach with soluble support under microwave irradiation. Polymer immobilized o-phenylenediamine was selectively N-acylated with 2-chloro-3-nitrobenzoic acid in a primary aromatic amino moiety. The obtained amide was cyclized to benzimidazole in an acidic condition, and subsequently nucleophilic aromatic substitution with different amines was performed. Successive reduction, cyclization with various aldehydes and activated isothiocyanates yielded angular biheterocyclic benzimidazoles in good quantities. Reaction progress on polymer support was precisely monitored using the conventional proton NMR spectroscopy. Preliminary screening results showed some of these interesting compounds exhibited moderately to good inhibition against vascular endothelial growth factor receptor 3 (VEGFR-3), which is related to invasion and migration of cancer cells.

3D QSAR-based design and liquid phase combinatorial synthesis of 1,2-disubstituted benzimidazole-5-carboxylic acid and 3-substituted-5H-benzimidazo[1,2-d][1,4]benzodiazepin-6(7H)-one derivatives as anti-mycobacterial agents

“…The reaction mixture was further stirred at 80 °C. 23,[30][31][32] The progression of the reaction was examined by TLC (mobile phase used: 5% methanol in chloroform) and the desired product was formed after 7 h of stirring at 90 °C. The reaction mixture was added to cold diethyl ether.…”

“…at 5 °C. 23,[30][31][32] Further, stirring of the resulting solution was continued for 12 h at 25 °C. The progression of the reaction was examined by TLC (mobile phase used: 5% methanol in toluene) and the formation of the desired product was observed after 12 h of stirring at 25 °C.…”

Divergent Synthesis of Unsymmetrical Annulated Biheterocyclic Compound Libraries: Benzimidazole Linked Indolo-benzodiazepines/quinoxaline

“…IR spectra were recorded on an FT-IR spectrophotometer. 1 H and 13 C NMR spectra were recorded on a 300 and 75 MHz spectrometer, respectively. Chemical shifts are reported in parts per million (ppm) on the scale from an internal standard.…”

“…Synthesis of Key Intermediate (13). PEG 6000 (1.2 g, 0.2 mmol), FNBA 6 (0.222 g, 1.2 mmol), DCC (0.247 g, 1.2 mmol), and DMAP (0.015 g, 0.12 mmol) in dry CH 2 Cl 2 (15 mL) were stirred in a round-bottom flask at 25 °C for 24 h. Upon completion of the reaction, CH 2 Cl 2 (10 mL) was added, and the reaction mixture was cooled to 0 °C.…”

“…A new series of benzimidazolyl-thiadiazepines 3 was synthesized and evaluated as antibacterial agents . We earlier reported the synthesis of pharmaceutically interesting angular-bisbenzimidazoles 4 having potential vascular endothelial growth factor receptor 3 inhibition activity . To the best of our knowledge, no report on the synthesis of benzimidazole linked heterocycles with four annulated rings exists in the literature.…”