Sodium hydride → HCID 21717191, compound

HRID 1386310Notes

Reaction equation

HRID 1386310 reaction equation
[C:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][C:5]1=[O:13])(=[O:3])[CH3:2].[H-].[Na+].Cl[C:17]1[C:26]2[C:21](=[CH:22][C:23]([O:29][CH2:30][CH2:31][O:32][CH3:33])=[C:24]([O:27][CH3:28])[CH:25]=2)[N:20]=[CH:19][N:18]=1>CN(C=O)C>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]([C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:29][CH2:30][CH2:31][O:32][CH3:33])=[C:24]([O:27][CH3:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)[C:5]1=[O:13])(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 3237191-Acetylindolin-2-oneHCID 107306534-Chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline

Product 1

HCID 21717191HCID 21717191, compoundYield 47.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A solution of 1-acetyloxindole (251 mg, 1.6 mmol), ( J. Med. Chem. 1986, 1838), in DMF (3 ml) was added to a suspension of sodium hydride (50 mg, 2.4 mmol) in DMF (10 ml) and the mixture stirred for 10 minutes at ambient temperature. 4-Chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline (108 mg, 0.4 mmol), (prepared as described for the starting material in Example 2), in DMF (3 ml) was added and the mixture stirred for 1.5 hours at ambient temperature. The solvent was removed by evaporation and the residue was partitioned between methylene chloride and water. The organic layer was separated, washed with water, brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/ethyl acetate (70/30). The purified product was recrystallised from methylene chloride/ether, collected by filtration, washed with ether and dried under vacuum to give 4-(1-acetyloxindol-3-yl)-6-methoxy-7-(2-methoxyethoxy)quinazoline (77 mg, 47%).

Workup

  1. additionwas added
  2. stirringthe mixture stirred for 1.5 hours at ambient temperature
  3. customThe solvent was removed by evaporation
  4. customthe residue was partitioned between methylene chloride and water
  5. customThe organic layer was separated
  6. washwashed with water, 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/ethyl acetate (70/30)
  11. customThe purified product was recrystallised from methylene chloride/ether
  12. filtrationcollected by filtration
  13. washwashed with ether
  14. customdried under vacuum

Sources & evidence

ORD record
ord-11febdde603c46618c40a1ee0bb7f4b0
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

Loading…