1,2-Dichloroethane → 4-chloro-N-({4-chloro-3-[(3-cyano-5-ethenylphenyl)oxy]-2-fluorophenyl}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide

Participants

Reaction Steps

To a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-ethenylbenzonitrile (630 mg, 2.081 mmol), 4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid (576 mg, 2.081 mmol) and HOBT (414 mg, 2.71 mmol) in DMF (10.0 ml) was added EDC (479 mg, 2.497 mmol) and the reaction mixture was stirred at rt for 30 minutes. The reaction mixture was diluted with EtOAc and washed with water. The solvent was removed and the crude material was purified via silica gel chromatography to give 4-chloro-N-({4-chloro-3-[(3-cyano-5-ethenylphenyl)oxy]-2-fluorophenyl}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide (1125 mg, 2.004 mmol, 96% yield), 1H NMR (400 MHz, DMSO-d6) δ ppm 8.76 (t, 1H), 7.92 (s, 1H), 7.77 (s, 1H), 7.43-7.49 (m, 1H), 7.32-7.42 (m, 2H), 7.22 (s, 1H), 6.72 (dd, 1H), 6.02 (d, 1H), 5.48 (s, 2H), 5.41 (d, 1H), 4.47 (d, 2H), 3.37 (t, 2H), 0.74 (t, 2H), −0.10 (s, 9H)

Provenance & Evidence