Sodium hydride → 199328-11-5

HRID 1386328Notes

Reaction equation

HRID 1386328 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[CH2:8]2)=[O:4].[H-].[Na+].[Cl:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1>CN(C=O)C>[ClH:17].[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[CH:8]2[C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:34]3[CH2:35][CH2:36][O:37][CH2:38][CH2:39]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1)=[O:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2773516Methyl 2,3-dihydro-2-oxo-1H-indole-5-carboxylateHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline

Product 1

HCID 21717178199328-11-5Yield 34.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 5-methoxycarbonyloxindole (169 mg, 0.88 mmol), (Eur. J. Med. Chem. 1983, 18, 107-111), in DMF (2 ml) was added dropwise under nitrogen to sodium hydride (35 mg, 0.88 mmol, prewashed with hexane) in DMF (1.5 ml). The mixture was stirred for 20 minutes at ambient temperature and 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (100 mg, 0.3 mmol), (prepared as described for the starting material in Example 5), was added as a solid. The mixture was heated at 60° C. for 45 minutes, allowed to cool and partitioned between ethyl acetate and water. The aqueous layer was adjusted to pH8. The organic layer was separated, washed with brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (92/8). The solid was dissolved in methylene chloride/methanol and 3M ethereal hydrogen chloride (1 ml) was added. The volatiles were removed by evaporation, the solid residue suspended in ether, collected by filtration, washed with ether and dried under vacuum to give 4-(5-methoxycarbonyloxindol-3-yl)-6-methoxy-7-(3-morpholinopropoxy)quinazoline hydrochloride (55 mg. 32%).

Workup

  1. additionwas added as a solid
  2. temperatureThe mixture was heated at 60° C. for 45 minutes
  3. temperatureto cool
  4. custompartitioned between ethyl acetate and water
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. customthe solvent removed by evaporation
  9. customThe residue was purified by column chromatography
  10. washeluting with methylene chloride/methanol (92/8)
  11. dissolutionThe solid was dissolved in methylene chloride/methanol
  12. addition3M ethereal hydrogen chloride (1 ml) was added
  13. customThe volatiles were removed by evaporation
  14. filtrationcollected by filtration
  15. washwashed with ether
  16. customdried under vacuum

Sources & evidence

ORD record
ord-82152a105f924e0b8cc0a4e0458626d2
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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