Imidazole → HCID 136171540, compound

HRID 1596252Notes

Reaction equation

HRID 1596252 reaction equation
N1C=CN=C1.C([O:13][C:14]1[CH:23]=[C:22]2[C:17]([C:18]([NH:24][C:25]3[CH:30]=[CH:29][C:28]([CH3:31])=[C:27]([OH:32])[CH:26]=3)=[N:19][CH:20]=[N:21]2)=[CH:16][C:15]=1[O:33][CH3:34])C1C=CC=CC=1.[Si:35](Cl)([C:48]([CH3:51])([CH3:50])[CH3:49])([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1.C(=O)([O-])O.[Na+]>CN(C=O)C.CO.C(OCC)(=O)C.[Pd]>[Si:35]([O:32][C:27]1[CH:26]=[C:25]([CH:30]=[CH:29][C:28]=1[CH3:31])[NH:24][C:18]1[C:17]2[C:22](=[CH:23][C:14]([OH:13])=[C:15]([O:33][CH3:34])[CH:16]=2)[N:21]=[CH:20][N:19]=1)([C:48]([CH3:51])([CH3:50])[CH3:49])([C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

9

Reactant 4

HCID 795ImidazoleHCID 94078tert-ButyldiphenylchlorosilaneHCID 516892Sodium BicarbonateHCID 21701585HCID 21701585, compound

Product 1

HCID 136171540HCID 136171540, compoundYield 42.8%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Imidazole (1.45 g, 21.6 mmol) was added to 7-benzyloxy-4-(3-hydroxy-4-methylanilino)-6-methoxyquinazoline (4.11 g, 9.69 mmol) in DMF (50 ml) and the mixture was stirred at ambient temperature until complete dissolution was achieved. t-Butyldiphenylsilyl chloride (2.5 ml, 9.6 mmol) was added dropwise and the reaction mixture stirred at ambient temperature for 72 hours. Saturated aqueous sodium hydrogen carbonate solution was added, and the product was extracted with methylene chloride. The solvent was removed by evaporation to give a damp solid which was dissolved in a mixture of DMF (40 ml), methanol (40 ml), and ethyl acetate (40 ml). 10% Palladium-on-charcoal catalyst (500 mg) was added and the mixture stirred under hydrogen at 1 atmosphere pressure for 36 hours. The catalyst was removed by filtration through diatomaceous earth, and the solvent removed from the filtrate by evaporation. The crude product was purified by flash chromatography eluting with methanol/methylene chloride (1/9) to give 4-(3-t-butyldiphenylsilyloxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline (2.2 g, 42% over two steps) as a yellow solid.

Workup

  1. stirringthe reaction mixture stirred at ambient temperature for 72 hours
  2. extractionthe product was extracted with methylene chloride
  3. customThe solvent was removed by evaporation
  4. customto give a damp solid which
  5. stirringthe mixture stirred under hydrogen at 1 atmosphere pressure for 36 hours
  6. customThe catalyst was removed by filtration through diatomaceous earth
  7. customthe solvent removed from the filtrate by evaporation
  8. customThe crude product was purified by flash chromatography
  9. washeluting with methanol/methylene chloride (1/9)

Sources & evidence

ORD record
ord-2281ea0e69d7472598e38caa86fdaa75
Source dataset
uspto-grants-2001_09
Patent number
US06291455B1

Reaction notes

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