Sodium hydride → HCID 10287372, compound

HRID 1386338

Reaction equation

HRID 1386338 reaction equation
[H-].[Na+].[C:3]([C:5]1[CH:13]=[C:12]2[C:8]([CH2:9][C:10](=[O:14])[NH:11]2)=[CH:7][CH:6]=1)#[N:4].Cl[C:16]1[C:25]2[C:20](=[CH:21][C:22]([O:28][CH2:29][CH2:30][O:31][CH3:32])=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]=[CH:18][N:17]=1>>[C:3]([C:5]1[CH:13]=[C:12]2[C:8]([CH:9]([C:16]3[C:25]4[C:20](=[CH:21][C:22]([O:28][CH2:29][CH2:30][O:31][CH3:32])=[C:23]([O:26][CH3:27])[CH:24]=4)[N:19]=[CH:18][N:17]=3)[C:10](=[O:14])[NH:11]2)=[CH:7][CH:6]=1)#[N:4]

Participants

4

Reactant 3

HCID 24758Sodium hydrideHCID 27733482-Oxindole-6-carbonitrileHCID 107306534-Chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline

Product 1

HCID 10287372HCID 10287372, compoundYield 29.1%

Procedure

Sodium hydride (100 mg, 2.6 mmol) was added to a solution of 6-cyanooxindole (350 mg, 2.2 mmol) in dry degassed DMF (10 ml) under argon and the suspension stirred for 30 minutes at ambient temperature. A solution of 4-chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline (200 mg, 0.74mmol), (prepared as described for the starting material in Example 2), in dry degassed DMF (2 ml) was added dropwise and the reaction mixture was heated at 60° C. for 2 hours. The mixture was allowed to cool and the DMF was removed by evaporation and the residue was partitioned between ethyl acetate (50 ml) and water (50 ml). The organic phase was separated and the aqueous phase was extracted with ethyl acetate (50 ml×3). The organic extracts were combined, dried (MgSO4) and the solvent removed by evaporation. The solid residue was purified by flash column chromatography eluting with methylene chloride/methanol/ammonia (99/1/1 and then 95/5/1). The purified solid was triturated in hot ether and collected by filtration and then triturated in hot methylene chloride/methanol (1/1), collected by filtration and dried to give 4-(6-cyanooxindol-3-yl)-6-methoxy-7-(2-methoxyethoxy)quinazoline (84 mg, 29%).

Workup

  1. customin dry
  2. customdegassed DMF (10 ml) under argon
  3. customin dry
  4. customdegassed DMF (2 ml)
  5. additionwas added dropwise
  6. temperaturethe reaction mixture was heated at 60° C. for 2 hours
  7. temperatureto cool
  8. customthe DMF was removed by evaporation
  9. customthe residue was partitioned between ethyl acetate (50 ml) and water (50 ml)
  10. customThe organic phase was separated
  11. extractionthe aqueous phase was extracted with ethyl acetate (50 ml×3)
  12. dry with materialdried (MgSO4)
  13. customthe solvent removed by evaporation
  14. customThe solid residue was purified by flash column chromatography
  15. washeluting with methylene chloride/methanol/ammonia (99/1/1
  16. customThe purified solid was triturated in hot ether
  17. filtrationcollected by filtration
  18. customtriturated in hot methylene chloride/methanol (1/1)
  19. filtrationcollected by filtration
  20. customdried

Sources & evidence

ORD record
ord-6e9b94cd498a4c96b03c51afc792a961
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Linked notes

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