反应详情

A solution of 2-azido-4-chloro-1H-imidazole-5-carboxylic acid (0.26 g, 1.4 mmol), 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.44 g, 1.40 mmol), 1-Ethyl-3-(3-dimethyllaminopropyl)carbodiimide hydrochloride (0.32 g, 1.68 mmol) and N-hydroxybenzotriazole (0.28 g, 1.82 mmol) was stirred at RT overnight. NaHCO3 was added and the solution was extracted with 9:1 CH2Cl2:MeOH. The combined organic phase was dried (Na2SO4), filtered, and concentrated to give 2-azido-4-chloro-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-imidazole-5-carboxamide which was used without further purification after extraction. A solution of the above crude azide and catalytic Pd/CaCO3 (poisoned with lead) in EtOAc (20 mL) was then stirred under 50 psi hydrogen gas for 2 h. The solution was filtered through celite, evaporated and purified by silica gel chromatography (0-10% MeOH/CH2Cl2) to afford the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.95 (s, 1H), 7.82 (s, 1H), 7.77 (t, J=5.86 Hz, 1H), 7.48-7.54 (m, 2H), 7.46 (t, J=2.01 Hz, 1H), 7.34 (t, J=7.97 Hz, 1H), 5.82 (s, 2H), 4.49 (d, J=5.77 Hz, 2H). ES-LCMS: m/z 454.0, 456.0, 458.0 (M+1).

1. extractionthe solution was extracted with 9:1 CH2Cl2
2. dry with materialThe combined organic phase was dried (Na2SO4)
3. filtrationfiltered
4. concentrationconcentrated