Diisopropylethylamine → 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

3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-ethenylbenzonitrile (0.109 g, 0.361 mmol), 4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid (0.100 g, 0.361 mmol) and DIPEA (0.126 mL, 0.723 mmol) were combined in THF (3 mL) and treated with HATU (0.151 g, 0.397 mmol) at 25° C. overnight with stirring. The reaction mixture was concentrated to dryness, dissolved in EtOAc, washed with water, dried over MgSO4, filtered and concentrated to dryness. The residue was purified on 40 g silica gel eluted with 20 to 60% EtOAc/hexanes 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 (0.16 g, 0.285 mmol, 79% yield) as a clear oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.79 (t, J=5.63 Hz, 1H), 8.00 (s, 1H), 7.80 (s, 1H), 7.37-7.54 (m, 3H), 7.25 (s, 1H), 6.75 (dd, J=17.67, 11.08 Hz, 1H), 6.05 (d, J=17.67 Hz, 1H), 5.51 (s, 2H), 5.44 (d, J=10.99 Hz, 1H), 4.50 (d, J=5.59 Hz, 2H), 3.40 (t, J=8.10 Hz, 2H), 0.76 (t, J=8.06 Hz, 2H), −0.07 (s, 9H). LC-MS (ES−) m/z 559.13, 561.19 [M−1]. LC-MS (ES+) m/z 561.14, 563.12 [M+H].

Provenance & Evidence