Dimethyl Sulfoxide → 199328-79-5

HRID 1386363Notes

Reaction equation

HRID 1386363 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][CH2:34][CH2:35][O:36][CH3:37])=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.CS(C)=O>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][CH2:34][CH2:35][O:36][CH3:37])=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1)(=[O:4])=[O:3]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 24758Sodium hydrideHCID 101982322-Oxoindoline-5-sulfonamideHCID 22030960HCID 22030960, compound

Product 1

HCID 21717243199328-79-5Yield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A solution of 5-aminosulphonyloxindole (265 mg, 1.25 mmol), (prepared as described for the starting material in Example 60), in DMF (2.5 ml) was added to a suspension of sodium hydride (50 mg, 1.25 mmol, prewashed with pentane) in DMF (1.5 ml). The mixture was stirred for 30 minutes at ambient temperature and 4-chloro-6-methoxy-7-(2-(2-methoxyethoxy)ethoxy)quinazoline (265 mg, 1.25 mmol), (prepared as described for the starting material in Example 74), was added followed by DMF (2 ml) and DMSO (0.5 ml). The mixture was heated at 60° C. for 45 minutes, then allowed to cool and partitioned between ether and water. The aqueous layer was separated and adjusted to pH7 with 1M hydrochloric acid. 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 2.8M ethereal hydrogen chloride (1 ml) was added. The volatiles were removed by evaporation, the solid was triturated with ether, collected by filtration and dried under vacuum to give 4-(5-aminosulphonyloxindol-3-yl)-6-methoxy-7-(2-(2-methoxyethoxy)ethoxy)quinazoline hydrochloride (106 mg, 50%).

Workup

  1. additionwas added
  2. temperatureThe mixture was heated at 60° C. for 45 minutes
  3. temperatureto cool
  4. custompartitioned between ether and water
  5. customThe aqueous layer was separated
  6. filtrationThe resulting precipitate was collected by filtration
  7. washwashed with water and ether
  8. customdried under vacuum
  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 was triturated with ether
  13. filtrationcollected by filtration
  14. customdried under vacuum

Sources & evidence

ORD record
ord-6d4edb7d64234f72a4264a475e921a00
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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