Sodium hydride → 4-(7-Azaoxindol-3-yl)-7-(2-(imidazol-1-yl)ethoxy)-6-methoxyquinazoline

HRID 1597223Notes

Reaction equation

HRID 1597223 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][N:8]=2)[CH2:3][C:2]1=[O:10].[H-].[Na+].Cl[C:14]1[C:23]2[C:18](=[CH:19][C:20]([O:26][CH2:27][CH2:28][N:29]3[CH:33]=[CH:32][N:31]=[CH:30]3)=[C:21]([O:24][CH3:25])[CH:22]=2)[N:17]=[CH:16][N:15]=1>CN(C=O)C>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][N:8]=2)[CH:3]([C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:26][CH2:27][CH2:28][N:29]4[CH:33]=[CH:32][N:31]=[CH:30]4)=[C:21]([O:24][CH3:25])[CH:22]=3)[N:17]=[CH:16][N:15]=2)[C:2]1=[O:10]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 111412614-Chloro-6-methoxy-7-(2-(imidazol-1-yl)ethoxy)quinazolineHCID 138640951,3-Dihydro-2H-pyrrolo(2,3-b)pyridin-2-one

Product 1

HCID 101508054-(7-Azaoxindol-3-yl)-7-(2-(imidazol-1-yl)ethoxy)-6-methoxyquinazolineYield 66.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A solution of 7-azaoxindole (165 mg, 1.23 mmol), (prepared as described for the starting material in Example 2), in DMF (3 ml) was added dropwise to a suspension of sodium hydride (50 mg, 1.23 mmol, prewashed with hexane) in DMF (3 ml). After stirring for 30 minutes at ambient temperature, 4-chloro-7-(2-(imidazol-1-yl)ethoxy)-6-methoxyquinazoline (125 mg, 0.41 mmol) in DMF (3 ml) was added. The mixture was heated at 65° C. for 30 minutes. After cooling the mixture was partitioned between saturated aqueous ammonium chloride and methylene chloride. The precipitate was collected by filtration, dried and purified by flash chromatography eluting with methylene chloride/methanol (8/2). After evaporation of the solvent, the solid was dissolved in methylene chloride/methanol and 2.2 M hydrogen chloride in ether was added. After stirring for 10 minutes at ambient temperature, the volatiles were removed by evaporation. The residue was triturated with ether, collected by filtration and dried under vacuum to give 4-(7-azaoxindol-3-yl)-7-(2-(imidazol-1-yl)ethoxy)-6-methoxyquinazoline (110 mg, 53%).

Workup

  1. temperatureThe mixture was heated at 65° C. for 30 minutes
  2. temperatureAfter cooling the mixture
  3. customwas partitioned between saturated aqueous ammonium chloride and methylene chloride
  4. filtrationThe precipitate was collected by filtration
  5. customdried
  6. custompurified by flash chromatography
  7. washeluting with methylene chloride/methanol (8/2)
  8. customAfter evaporation of the solvent
  9. dissolutionthe solid was dissolved in methylene chloride/methanol
  10. addition2.2 M hydrogen chloride in ether was added
  11. stirringAfter stirring for 10 minutes at ambient temperature
  12. customthe volatiles were removed by evaporation
  13. customThe residue was triturated with ether
  14. filtrationcollected by filtration
  15. customdried under vacuum

Sources & evidence

ORD record
ord-c4317db03a9b44b28738a85544a8dc2c
Source dataset
uspto-grants-2001_09
Patent number
US06294532B1

Reaction notes

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