Sodium hydride → HCID 21717256, compound

HRID 1386359Notes

Reaction equation

HRID 1386359 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C:2]1=[O:10].[H-].[Na+].[Cl:13][C:14]1[C:23]2[C:18](=[CH:19][C:20]([O:26][CH2:27][CH2:28][O:29][CH2:30][CH2:31][O:32][CH3:33])=[C:21]([O:24][CH3:25])[CH:22]=2)[N:17]=[CH:16][N:15]=1>CN(C=O)C>[ClH:13].[CH3:25][O:24][C:21]1[CH:22]=[C:23]2[C:18](=[CH:19][C:20]=1[O:26][CH2:27][CH2:28][O:29][CH2:30][CH2:31][O:32][CH3:33])[N:17]=[CH:16][N:15]=[C:14]2[CH:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][C:2]1=[O:10]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 321710OxindoleHCID 22030960HCID 22030960, compound

Product 1

HCID 21717256HCID 21717256, compoundYield 73.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of oxindole (153 mg, 1.15 mmol) in DMF (3 ml) was added to a suspension of sodium hydride (46 mg, 1.15 mmol, prewashed with hexane) in DMF (1 ml) and the mixture was stirred for 30 minutes at ambient temperature. 4-Chloro-6-methoxy-7-(2-(2-methoxyethoxy)ethoxy)quinazoline (120 mg, 0.38 mmol) was added as a solid and the mixture was stirred for 10 minutes at ambient temperature and then for 45 minutes at 50° C. The mixture was allowed to cool and was partitioned between ether and water. The aqueous layer was separated and adjusted to pH7.5 with 1M hydrochloric acid. The resulting precipitate was collected by filtration washed with water followed by ether and dried over phosphorus pentoxide. The solid was dissolved in methylene chloride/methanol and 2.8M ethereal hydrogen chloride (1 ml) was added. The volatiles were removed by evaporation, the solid residue was triturated with ether, collected by filtration and dried under vacuum to give 6-methoxy-7-(2-(2-methoxyethoxy)ethoxy)-4-(oxindol-3-yl)quinazoline hydrochloride (124 mg, 73%).

Workup

  1. stirringthe mixture was stirred for 10 minutes at ambient temperature
  2. waitfor 45 minutes at 50° C
  3. temperatureto cool
  4. customwas partitioned between ether and water
  5. customThe aqueous layer was separated
  6. filtrationThe resulting precipitate was collected by filtration
  7. washwashed with water
  8. dry with materialdried over phosphorus pentoxide
  9. dissolutionThe solid was dissolved in methylene chloride/methanol
  10. addition2.8M ethereal hydrogen chloride (1 ml) was added
  11. customThe volatiles were removed by evaporation
  12. customthe solid residue was triturated with ether
  13. filtrationcollected by filtration
  14. customdried under vacuum

Sources & evidence

ORD record
ord-74267d6790df4648a579189134585a1a
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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