1,2-Dichloroethane → HCID 178436593, compound
Reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([F:21])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17]([CH2:19][CH3:20])[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1.[Br:22][C:23]1[N:24]=[C:25]([CH3:31])[NH:26][C:27]=1[C:28](O)=[O:29].CCN(C(C)C)C(C)C.C(Cl)CCl>>[Br:22][C:23]1[N:24]=[C:25]([CH3:31])[NH:26][C:27]=1[C:28]([NH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([Cl:9])=[C:5]([O:10][C:11]2[CH:18]=[C:17]([CH2:19][CH3:20])[CH:16]=[C:13]([C:14]#[N:15])[CH:12]=2)[C:4]=1[F:21])=[O:29]Participants
5
Procedure
3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-ethylbenzonitrile (0.053 g, 0.174 mmol), 4-bromo-2-methyl-1H-imidazole-5-carboxylic acid (0.036 g, 0.174 mmol) and DIEA (0.061 mL, 0.348 mmol) were combined and treated with EDC (0.067 g, 0.348 mmol) at 25° C. overnight with stirring. The reaction mixture was concentrated to dryness and partitioned between EtOAc and water. The organic phase was isolated, dried over MgSO4, filtered and concentrated to dryness. The residue was purified on 40 g silica gel eluted with 0 to 10% CH3OH/DCM to give 4-bromo-N-({4-chloro-3-[(3-cyano-5-ethylphenyl)oxy]-2-fluorophenyl}methyl)-2-methyl-1H-imidazole-5-carboxamide (0.054 g, 0.110 mmol, 63.1%) as a white solid. 1H NMR (400 MHz, DMSO-d6+1 drop D2O) δ ppm 7.40-7.51 (m, 2H), 7.32 (t, J=7.83 Hz, 1H), 7.14 (d, J=6.73 Hz, 2H), 4.47 (s, 2H), 2.62 (q, J=7.51 Hz, 2H), 2.24 (s, 3H), 1.12 (t, J=7.49 Hz, 3H). LC-MS (ES−) m/z 488.97, 490.93, 492.87 [M−1]. LC-MS (ES+) m/z 491.10, 493.10, 495.07 [M+H].