反应详情

温度

60 °C

To a solution of N-({3-[(3-bromo-5-chlorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)-4-chloro-1H-imidazole-5-carboxamide (125 mg, 0.253 mmol), tetrakistriphenylphosphine palladium(0) (35.6 mg, 0.051 mmol), copper(I) iodide (4.82 mg, 0.025 mmol) and TEA (0.177 ml, 1.266 mmol) in THF (5 ml) was added cyclopropylacetylene (0.043 ml, 0.507 mmol) and the reaction mixture was stirred for 5 hours at 60° C. The reaction mixture was adsorbed onto silica gel and the crude material was purified via silica gel chromatography to give 4-chloro-N-[(4-chloro-3-{[3-chloro-5-(cyclopropylethynyl)phenyl]oxy}-2-fluorophenyl)methyl]-1H-imidazole-5-carboxamide (95 mg, 0.198 mmol, 78% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.70 (s, 1H), 7.21-7.39 (m, 2H), 7.02 (s, 1H), 6.81 (s, 1H), 6.64 (s, 1H), 4.62 (br. s., 2H), 1.35-1.50 (m, 1H), 0.78-0.90 (m, 2H), 0.57-0.77 (m, 2H). LC-MS (ES+) m/z 477.87, [M+H].

1. customthe crude material was purified via silica gel chromatography