4-Cyanobenzoic acid → 4-{5-[2-(2,6-Dichloro-phenyl)-3H-benzoimidazol-5-yl]-[1,3,4]oxadiazol-2-yl}-benzonitrile

Participants

Reaction Steps

Combine 4-cyano-benzoic acid (120 mg, 0.817 mmol), 2-(2,6-dichloro-phenyl)-3H-benzoimidazole-5-carboxylic acid hydrazide (250 mg, 0.778 mmol), HATU (445 mg, 1.17 mmol), EDIPA (204 uL, 1.17 mmol), and DMF (5 mL) and stir for 25 hr. Dilute the reaction with EtOAc (75 mL) and extract with water (15 mL). Dry the organic phase over Na2SO4 and concentrate under reduced pressure. Take the concentrate up in DMF (3 mL) and add Burgess reagent (555 mg, 2.33 mmol). Heat the reaction to 150° C. for 20 min by microwave irradiation. Dilute the reaction with EtOAc (75 mL) and extract with water (20 mL). Dry the organic phase over Na2SO4 and concentrate under reduced pressure. Purify the concentrate by silica gel chromatography (10-40% ACN/DCM) to afford a white solid. Suspend the solid in water and stir for 6 hr. Collect the solid by filtration and wash with Et2O. Dry the solid under vacuum at 40° C. for 2 days to afford the title compound (138 mg) as a white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 7.63-7.68 (m, 1H) 7.70-7.74 (m, 2H) 7.79-7.85 (tautomer, m, 1H) 7.96 (tautomer, d, J=8.59 Hz, 1H) 8.06-8.15 (m, 3H) 8.35-8.40 (m+tautomer, 2H) 8.52-8.60 (m, 1H) 13.39 (d, J=12.76 Hz, 1H); LCMS tR=1.35 min, MS (m/z) 432.0.

Provenance & Evidence