Trimethylsilylacetylene → 4-chloro-N-{[4-chloro-3-({3-chloro-5-[(trimethylsilyl)ethynyl]phenyl}oxy)-2-fluorophenyl]methyl}-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide

HRID 1875159Notes

Reaction equation

HRID 1875159 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:9][C:10]2[C:11]([F:35])=[C:12]([CH2:17][NH:18][C:19]([C:21]3[N:25]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[CH:24]=[N:23][C:22]=3[Cl:34])=[O:20])[CH:13]=[CH:14][C:15]=2[Cl:16])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[CH3:36][Si:37]([C:40]#[CH:41])([CH3:39])[CH3:38]>C1COCC1.[Cu](I)I>[Cl:34][C:22]1[N:23]=[CH:24][N:25]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:31])([CH3:33])[CH3:32])[C:21]=1[C:19]([NH:18][CH2:17][C:12]1[CH:13]=[CH:14][C:15]([Cl:16])=[C:10]([O:9][C:4]2[CH:3]=[C:2]([C:41]#[C:40][Si:37]([CH3:39])([CH3:38])[CH3:36])[CH:7]=[C:6]([Cl:8])[CH:5]=2)[C:11]=1[F:35])=[O:20]

Participants

5

Reactant 2

HCID 66111TrimethylsilylacetyleneHCID 68487164N-({3-[(3-bromo-5-chlorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)-4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide

Product 1

HCID 684866134-chloro-N-{[4-chloro-3-({3-chloro-5-[(trimethylsilyl)ethynyl]phenyl}oxy)-2-fluorophenyl]methyl}-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamideYield 81.5%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of N-({3-[(3-bromo-5-chlorophenyl)oxy]-4-chloro-2-fluorophenyl}methyl)-4-chloro-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide (145 mg, 0.232 mmol), copper iodide (2.213 mg, 0.012 mmol) and TEA (162 μL, 1.162 mmol) in THF (8 ml) was added trimethylsilylacetylene (43 μL, 0.302 mmol) and the reaction mixture was degassed for 5 minutes with nitrogen. The resulting mixture was heated with stirring at 60° C. for 4 hours under nitrogen. The solvent was removed and the crude material was purified via silica gel chromatography to give 4-chloro-N-{[4-chloro-3-({3-chloro-5-[(trimethylsilyl)ethynyl]phenyl}oxy)-2-fluorophenyl]methyl}-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide (121 mg, 0.189 mmol, 81% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.74 (t, 1H), 7.95 (s, 1H), 7.41-7.48 (m, 1H), 7.36 (t, 1H), 7.25 (s, 1H), 7.09 (t, 1H), 6.79 (s, 1H), 5.46 (s, 2H), 4.46 (d, 2H), 3.35 (t, 2H), 0.72 (t, 2H), 0.08-0.31 (m, 9H), −0.12 (s, 9H).

Workup

  1. customthe reaction mixture was degassed for 5 minutes with nitrogen
  2. temperatureThe resulting mixture was heated
  3. customThe solvent was removed
  4. customthe crude material was purified via silica gel chromatography

Sources & evidence

ORD record
ord-a43d383935574f4b9705b964777a1342
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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