1,2-Dichloroethane → 4-chloro-N-({4-chloro-3-[(3-cyano-5-ethenylphenyl)oxy]-2-fluorophenyl}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide

HRID 1875184Notes

Reaction equation

HRID 1875184 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]([CH:19]=[CH2:20])[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1.[Cl:22][C:23]1[N:24]=[CH:25][N:26]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:27]=1[C:28](O)=[O:29].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>CN(C=O)C.CCOC(C)=O>[Cl:22][C:23]1[N:24]=[CH:25][N:26]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[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]([CH:19]=[CH2:20])[CH:16]=[C:13]([C:14]#[N:15])[CH:12]=2)[C:4]=1[F:21])=[O:29]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 684855334-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acidHCID 684888433-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-ethenylbenzonitrile

Product 1

HCID 684870564-chloro-N-({4-chloro-3-[(3-cyano-5-ethenylphenyl)oxy]-2-fluorophenyl}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamideYield 96.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-ethenylbenzonitrile (630 mg, 2.081 mmol), 4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxylic acid (576 mg, 2.081 mmol) and HOBT (414 mg, 2.71 mmol) in DMF (10.0 ml) was added EDC (479 mg, 2.497 mmol) and the reaction mixture was stirred at rt for 30 minutes. The reaction mixture was diluted with EtOAc and washed with water. The solvent was removed and the crude material was purified via silica gel chromatography 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 (1125 mg, 2.004 mmol, 96% yield), 1H NMR (400 MHz, DMSO-d6) δ ppm 8.76 (t, 1H), 7.92 (s, 1H), 7.77 (s, 1H), 7.43-7.49 (m, 1H), 7.32-7.42 (m, 2H), 7.22 (s, 1H), 6.72 (dd, 1H), 6.02 (d, 1H), 5.48 (s, 2H), 5.41 (d, 1H), 4.47 (d, 2H), 3.37 (t, 2H), 0.74 (t, 2H), −0.10 (s, 9H)

Workup

  1. washwashed with water
  2. customThe solvent was removed
  3. customthe crude material was purified via silica gel chromatography

Sources & evidence

ORD record
ord-5f20cc29cad249c5aa86f5b10f915b8e
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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