Potassium Carbonate → 5-((5-(2-(3,4-Dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-2-fluorobenzonitrile

HRID 1627251Notes

Reaction equation

HRID 1627251 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]([C:12]2[N:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[C:15](=[S:24])[NH:14][CH:13]=2)([CH3:11])[CH3:10])[CH:5]=[CH:6][C:7]=1[Cl:8].C([O-])([O-])=O.[K+].[K+].Br[CH2:32][C:33]1[CH:34]=[CH:35][C:36]([F:41])=[C:37]([CH:40]=1)[C:38]#[N:39]>CC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]([C:12]2[N:16]([C:17]3[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=3)[C:15]([S:24][CH2:32][C:33]3[CH:34]=[CH:35][C:36]([F:41])=[C:37]([CH:40]=3)[C:38]#[N:39])=[N:14][CH:13]=2)([CH3:11])[CH3:10])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27739315-(Bromomethyl)-2-fluorobenzonitrileHCID 667403425-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole-2-thiol

Product 1

HCID 667401155-((5-(2-(3,4-Dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-2-fluorobenzonitrileYield 86%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a pre-stirred mixture of 5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole-2(3H)-thione (1.50 g, 3.93 mmol) and K2CO3 (0.82 g, 5.90 mmol) in acetone (60 mL) was added 5-(bromomethyl)-2-fluorobenzonitrile (1.09 g, 5.11 mmol), and the reaction mixture was heated at reflux 2 h. After cooling, the reaction mixture was filtered through Celite™ and concentrated. Purification by flash chromatography (Hex/EtOAc, 2:1) afforded the title product (1.74 g, 3.38 mmol, 86%) as a white solid. 1H NMR (CDCl3, 400 MHz): δ 1.53 (s, 6H) 4.21 (s, 2H), 6.36 (m, 2H), 6.84 (m, 3H), 6.96 (s, 1H), 7.11 (t, 1H), 7.18 (s, 1H), 7.26 (d, 1H), 7.52 (m, 2H); MS (EI) m/z 514 (MH+).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux 2 h
  3. temperatureAfter cooling
  4. filtrationthe reaction mixture was filtered through Celite™
  5. concentrationconcentrated
  6. customPurification by flash chromatography (Hex/EtOAc, 2:1)

Sources & evidence

ORD record
ord-850ff1275ece4308beb8f1e4f7d00375
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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