Sodium hydride → HCID 21717224, compound

HRID 1386285Notes

Reaction equation

HRID 1386285 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6]2)#[N:2].[H-].[Na+].[Cl:15][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>C1COCC1.CN(C=O)C>[ClH:15].[C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH:6]2[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)#[N:2]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 27733462-Oxo-2,3-dihydro-1H-indole-5-carbonitrileHCID 107306534-Chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline

Product 1

HCID 21717224HCID 21717224, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 5-cyanooxindole (285 mg, 1.8 mmol), (Tet. Lett., 1987, 28, 4027), in THF (12 ml) was added dropwise under nitrogen, to a suspension of sodium hydride (96 mg, 2.4 mmol, prewashed with hexane) in THF (5 ml). The mixture was stirred for 20 minutes at ambient temperature, and a solution of 4-chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline (162 mg, 0.6 mmol), (prepared as described for the starting material in Example 2), in DMF (0.5 ml) in THF (3 ml) was added dropwise. The mixture was stirred for 20 minutes at ambient temperature and then 1 hour at 65° C. The solvent was removed by evaporation and the residue was purified by column flash chromatography eluting with methylene chloride/methanol (97/3 followed by 96/4 and 90/10). The solid was collected by filtration, resuspended in methylene chloride and 2M ethereal hydrogen chloride was added. The solid was collected by filtration, washed with ether and dried under vacuum at 60° C. to give 4-(5-cyanooxindol-3-yl)-6-methoxy-7-(2-methoxyethoxy)quinazoline hydrochloride (92 mg, 40%).

Workup

  1. additionwas added dropwise
  2. stirringThe mixture was stirred for 20 minutes at ambient temperature
  3. custom1 hour
  4. customat 65° C
  5. customThe solvent was removed by evaporation
  6. customthe residue was purified by column flash chromatography
  7. washeluting with methylene chloride/methanol (97/3 followed by 96/4 and 90/10)
  8. filtrationThe solid was collected by filtration
  9. addition2M ethereal hydrogen chloride was added
  10. filtrationThe solid was collected by filtration
  11. washwashed with ether
  12. customdried under vacuum at 60° C.

Sources & evidence

ORD record
ord-0e16876c5cc24b67bf7f42fbd6eefb17
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

Loading…