Sodium hydride → HCID 21717200, compound

HRID 1386331Notes

Reaction equation

HRID 1386331 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]1[CH:11]=[C:10]2[C:6]([CH2:7][C:8](=[O:12])[NH:9]2)=[CH:5][CH:4]=1.[H-].[Na+].Cl[C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][O:33][CH3:34])=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1>>[CH3:29][O:28][C:25]1[CH:26]=[C:27]2[C:22](=[CH:23][C:24]=1[O:30][CH2:31][CH2:32][O:33][CH3:34])[N:21]=[CH:20][N:19]=[C:18]2[CH:7]1[C:6]2[C:10](=[CH:11][C:3]([C:2]([F:1])([F:13])[F:14])=[CH:4][CH:5]=2)[NH:9][C:8]1=[O:12]

Participants

4

Reactant 3

HCID 24758Sodium hydrideHCID 6084876-TrifluoromethyloxindoleHCID 107306534-Chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline

Product 1

HCID 21717200HCID 21717200, compoundYield 69.5%

Procedure

6-Trifluoromethyloxindole (270 mg, 1.3 mmol) was dissolved in dry, degassed DMF (5 ml) under argon. Sodium hydride (63 mg, 1.6 mmol) was added and the suspension stirred for 30 minutes at ambient temperature. A solution of 4-chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline (111 mg, 0.332 mmol), (prepared as described for the starting material in Example 2), in dry, degassed DMF (5 ml) was added dropwise and the mixture heated at 100° C. for 2 hours. The mixture was allowed to cool and the DMF was removed by evaporation. The residue was purified by flash column chromatography eluting with methylene chloride/methanol (100/0 and then 15/1). The purified orange solid was triturated with ether, collected by filtration and dried under vacuum at 40° C. to give 6-methoxy-7-(2-methoxyethoxy)-4-(6-trifluoromethyloxindol-3-yl)quinazoline (100 mg, 52%).

Workup

  1. customin dry
  2. customdegassed DMF (5 ml) under argon
  3. customin dry
  4. customdegassed DMF (5 ml)
  5. additionwas added dropwise
  6. temperaturethe mixture heated at 100° C. for 2 hours
  7. temperatureto cool
  8. customthe DMF was removed by evaporation
  9. customThe residue was purified by flash column chromatography
  10. washeluting with methylene chloride/methanol (100/0
  11. customThe purified orange solid was triturated with ether
  12. filtrationcollected by filtration
  13. customdried under vacuum at 40° C.

Sources & evidence

ORD record
ord-42a4d8f578594d819dd70f7506a13422
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

Loading…