Sodium hydride → HCID 21717278, compound

HRID 1386325Notes

Reaction equation

HRID 1386325 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8](=[O:13])[CH2:7]2)(=[O:3])[CH3:2].[H-].[Na+].[Cl:16][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>[ClH:16].[C:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8](=[O:13])[CH:7]2[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)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 102196435-acetyl-2,3-dihydro-1H-indol-2-oneHCID 107306534-Chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline

Product 1

HCID 21717278HCID 21717278, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 5-acetyloxindole (352 mg, 2 mmol), (EP 0155828 A2), in DMF (5 ml) was added to a suspension of sodium hydride (80 mg, 2 mmol, prewashed with hexane) in DMF (1 ml) and the mixture stirred for 30 minutes at ambient temperature. 4-Chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline (180 mg, 0.67 mmol), (prepared as described for the starting material in Example 2), was added and the mixture was heated at 50° C. for 1.5 hours. The mixture was partitioned between water and ether and the aqueous layer was adjusted to pH7 with 2M hydrochloric acid. The precipitate was collected by filtration, washed with water and dried under vacuum. The solid was dissolved in methylene chloride/methanol (30 ml/30 ml) and 7M ethanolic hydrogen chloride (1 ml) was added. The mixture was left to stand for 15 minutes at ambient temperature, the resulting precipitate was collected by filtration, washed with ether and dried under vacuum to give 4-(5-acetyloxindol-3-yl)-6-methoxy-7-(2-methoxyethoxy)quinazoline hydrochloride (195 mg, 71%).

Workup

  1. additionwas added
  2. temperaturethe mixture was heated at 50° C. for 1.5 hours
  3. customThe mixture was partitioned between water and ether
  4. filtrationThe precipitate was collected by filtration
  5. washwashed with water
  6. customdried under vacuum
  7. dissolutionThe solid was dissolved in methylene chloride/methanol (30 ml/30 ml)
  8. addition7M ethanolic hydrogen chloride (1 ml) was added
  9. waitThe mixture was left
  10. waitto stand for 15 minutes at ambient temperature
  11. filtrationthe resulting precipitate was collected by filtration
  12. washwashed with ether
  13. customdried under vacuum

Sources & evidence

ORD record
ord-c3f1d9534d6343a09a721f4706c7f934
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

Loading…