Sodium hydride → HCID 21717222, compound

HRID 1386344Notes

Reaction equation

HRID 1386344 reaction equation
[NH2:1][S:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[CH2:8]2)(=[O:4])=[O:3].[H-].[Na+].[Cl:17][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>CN(C=O)C>[ClH:17].[NH2:1][S:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[CH:8]2[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)(=[O:4])=[O:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 101982322-Oxoindoline-5-sulfonamideHCID 107306534-Chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline

Product 1

HCID 21717222HCID 21717222, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A solution of 5-aminosulphonyloxindole (355 mg, 1.67 mmol) in DMF (3.5 ml) was added dropwise to sodium hydride (67 mg, 1.67 mmol, prewashed with THF) in DMF (5 ml). The mixture was stirred for 30 minutes at ambient temperature and a solution of 4-chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline (150 mg, 0.56 mmol), (prepared as described for the starting material in Example 2), in DMF (3 ml) was added. The mixture was heated at 65° C. for 2.5 hours and then stirred overnight at ambient temperature. The mixture was partitioned between ethyl acetate and water, the aqueous layer was adjusted to pH7 with 1M hydrochloric acid and left standing for 2 hours. The resulting precipitate was collected by filtration, washed with water and ether, and dried under vacuum. The solid was dissolved in methylene chloride/methanol and 2.2M ethereal hydrogen chloride (1ml) was added. The volatiles were removed by evaporation, the solid residue was triturated with ether, collected by filtration and dried under vacuum to give 4-(5-aminosulphonyloxindol-3-yl)-6-methoxy-7-(2-methoxyethoxy)quinazoline hydrochloride (144 mg, 60%).

Workup

  1. additionwas added
  2. temperatureThe mixture was heated at 65° C. for 2.5 hours
  3. stirringstirred overnight at ambient temperature
  4. customThe mixture was partitioned between ethyl acetate and water
  5. waitleft
  6. waitstanding for 2 hours
  7. filtrationThe resulting precipitate was collected by filtration
  8. washwashed with water and ether
  9. customdried under vacuum
  10. dissolutionThe solid was dissolved in methylene chloride/methanol
  11. addition2.2M ethereal hydrogen chloride (1ml) was added
  12. customThe volatiles were removed by evaporation
  13. customthe solid residue was triturated with ether
  14. filtrationcollected by filtration
  15. customdried under vacuum

Sources & evidence

ORD record
ord-a7b942aedf8747ef998fb0b7ddb69438
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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