Sodium hydride → HCID 21717302, compound

HRID 1386252Notes

Reaction equation

HRID 1386252 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[CH2:24]([O:26][CH:27]([O:38][CH2:39][CH3:40])[N:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH2:30][C:29]1=[O:37])[CH3:25].[H-].[Na+]>C1COCC1>[CH2:39]([O:38][CH:27]([O:26][CH2:24][CH3:25])[N:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[CH:30]([C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][N:3]=2)[C:29]1=[O:37])[CH3:40]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10879089HCID 10879089, compoundHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline

Product 1

HCID 21717302HCID 21717302, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-Chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (338 mg, 1 mmol) was dissolved in THF (20 ml) at 40° C., and 1-diethoxymethyloxindole (705 mg, 3 mmol), (prepared according to Synthesis 1975, 168), and sodium hydride (138 mg, 5.8 mmol, pre-washed with petroleum ether) were added successively to the solution at ambient temperature. After stirring for 45 minutes, 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 removed by evaporation. The residue was purified by column flash chromatography using methylene chloride/ethyl acetate (1/1) followed by an increasingly polar mixture of methylene chloride and methanol (2 to 4%) 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-(1-diethoxymethyloxindol-3-yl)-6-methoxy-7-(3-morpholinopropoxy)quinazoline (425 mg, 84%) as a yellow-orange solid.

Workup

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

Sources & evidence

ORD record
ord-2bf102ec08144019970342286deed8d8
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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