Sodium hydride → HCID 21717217, compound

HRID 1386263Notes

Reaction equation

HRID 1386263 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]([O:15][CH2:16][CH3:17])[O:12][CH2:13][CH3:14])[C:6](=[O:18])[CH2:5]2.[H-].[Na+].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>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]([O:12][CH2:13][CH3:14])[O:15][CH2:16][CH3:17])[C:6](=[O:18])[CH:5]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 21717201HCID 21717201, compound

Product 1

HCID 21717217HCID 21717217, compoundYield 73.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

5-Bromo-1-diethoxymethyloxindole (942 mg, 3 mmol) and sodium hydride (138 mg, 5.8 mmol, pre-washed with petroleum ether) were added successively to a solution of 4-chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline (269 mg, 1 mmol), (prepared as described for the starting material in Example 2), in THF (25 ml) at ambient temperature. After stirning for 2 hours at ambient temperature, the volatiles were removed by evaporation and the residue dissolved in methylene chloride. The solution was washed with an aqueous saturated sodium chloride solution, dried (MgSO4) and the solvent evaporated. The residue was purified by column flash chromatography using an increasingly polar mixture of methylene chloride and ethyl acetate followed by a 7/3 mixture of methylene chloride/acetonitrile as eluent. The purified product was triturated with ether, collected by filtration, washed with a 1/1 mixture of ether/petroleum ether and dried under vacuum to give 4-(5-bromo-1-diethoxymethyloxindol-3-yl)-6-methoxy-7-(2-methoxyethoxy)quinazoline (400 mg, 73%) as a yellow-orange solid.

Workup

  1. custom(prepared
  2. customat ambient temperature
  3. customthe volatiles were removed by evaporation
  4. dissolutionthe residue dissolved in methylene chloride
  5. washThe solution was washed with an aqueous saturated sodium chloride solution
  6. dry with materialdried (MgSO4)
  7. customthe solvent evaporated
  8. customThe residue was purified by column flash chromatography
  9. additionan increasingly polar mixture of methylene chloride and ethyl acetate
  10. additionfollowed by a 7/3 mixture of methylene chloride/acetonitrile as eluent
  11. customThe purified product was triturated with ether
  12. filtrationcollected by filtration
  13. washwashed with a 1/1 mixture of ether/petroleum ether
  14. customdried under vacuum

Sources & evidence

ORD record
ord-5e9903341caa46e69792673376839be5
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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