1,2-Dichloroethane → HCID 178436593、化合物

反応式

[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]

参加物

反応物 4

HCID 111,2-Dichloroethane

HCID 81531Diisopropylethylamine

HCID 68485225HCID 68485225、化合物

HCID 1784324485-bromo-2-methyl-1H-imidazole-4-carboxylic acid

生成物 1

HCID 178436593HCID 178436593、化合物収率 63.2%

実験手順

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].