Sodium hydride → 4-(5-Fluoro-1-diethoxymethyloxindol-3-yl)-6-methoxy-7-(2-methoxyethoxy)quinazoline

HRID 1386264Notes

Reaction equation

HRID 1386264 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH:13]([O:17][CH2:18][CH3:19])[O:14][CH2:15][CH3:16])[C:8](=[O:20])[CH2:7]2.Cl[C:22]1[C:31]2[C:26](=[CH:27][C:28]([O:34][CH2:35][CH2:36][O:37][CH3:38])=[C:29]([O:32][CH3:33])[CH:30]=2)[N:25]=[CH:24][N:23]=1>C1COCC1>[F:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH:13]([O:14][CH2:15][CH3:16])[O:17][CH2:18][CH3:19])[C:8](=[O:20])[CH:7]2[C:22]1[C:31]2[C:26](=[CH:27][C:28]([O:34][CH2:35][CH2:36][O:37][CH3:38])=[C:29]([O:32][CH3:33])[CH:30]=2)[N:25]=[CH:24][N:23]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 107306534-Chloro-6-methoxy-7-(2-methoxyethoxy)quinazolineHCID 21717300HCID 21717300, compound

Product 1

HCID 217172154-(5-Fluoro-1-diethoxymethyloxindol-3-yl)-6-methoxy-7-(2-methoxyethoxy)quinazolineYield 75.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (95 mg of a 60% suspension in paraffin oil, 2.4 mmol) was added to a solution of 5-fluoro-1-diethoxymethyloxindole (520 mg, 2.05 mmol) and 4-chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline (220 mg, 0.82 mmol), (prepared as described for the starting material in Example 2), in THF (20 ml). After stirring for 2 hours at ambient temperature, the volatiles were removed by evaporation. The residue was partitioned beween methylene chloride and water, the organic layer was washed with water and then brine, dried (MgSO4) and the solvent evaporated. The residue was purified by flash chromatography using an increasingly polar mixture of methylene chloride/ethyl acetate (100/0 to 0/100) as eluent to give 4-(5-fluoro-1-diethoxymethyloxindol-3-yl)-6-methoxy-7-(2-methoxyethoxy)quinazoline (300 mg, 68%) as a yellow solid.

Workup

  1. custom(prepared
  2. customthe volatiles were removed by evaporation
  3. customThe residue was partitioned beween methylene chloride and water
  4. washthe organic layer was washed with water
  5. dry with materialbrine, dried (MgSO4)
  6. customthe solvent evaporated
  7. customThe residue was purified by flash chromatography
  8. additionan increasingly polar mixture of methylene chloride/ethyl acetate (100/0 to 0/100) as eluent

Sources & evidence

ORD record
ord-2746c5b8d7374e8ab8371342bbdf784c
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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