Hydride → HCID 21717236, compound

HRID 1386284Notes

Reaction equation

HRID 1386284 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[NH:8][C:7](=[O:14])[CH2:6]2.[H-].[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>C1COCC1.CN(C=O)C>[ClH:16].[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[NH:8][C:7](=[O:14])[CH:6]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

Participants

6

Reactant 3

HCID 166653HydrideHCID 2229935,6-Dimethoxyindolin-2-oneHCID 107306534-Chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline

Product 1

HCID 21717236HCID 21717236, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 5,6-dimethoxyoxindole (107 mg, 0.56 mmol), (Chem Pharm Bull. 1971, 19, 1325-1327), in a mixture of THF (1 ml) and DMF (1 ml) was added dropwise under nitrogen to a suspension of sodiumn hydride (22 mg, 0.55 mmol, prewashed with hexane) in THF (1 ml). The mixture was stirred for 20 minutes at ambient temperature and a solution of 4-chloro-6-methoxy-7-(2-methoxyethoxy)quinazoline (50 mg, 0.18 mmol), (prepared as described for the starting material in Example 2), in THF (1 ml) was added dropwise. The mixture was heated at 60° C. for 1.5 hours, allowed to cool and partitioned between ethyl acetate and water. The aqueous layer was adjusted to pH7 with 1M hydrochloric acid. The organic layer was washed with brine, dried (MgSO4), and volatiles removed by evaporation. The residue was purified by column flash chromatography eluting with methylene chloride/acetonitrile/methanol (60/38/2 followed by 60/35/5). The resulting solid was dissolved in methylene chloride/methanol and 3M ethereal hydrogen chloride was added. The mixture was concentrated by evaporation, the resulting precipitate was collected by filtration, washed with ether and dried under vacuum to give 4-(5,6-dimethoxyoxindol-3-yl)-6-methoxy-7-(2-methoxyethoxy)quinazoline hydrochloride (33 mg, 51%).

Workup

  1. additionwas added dropwise
  2. temperatureThe mixture was heated at 60° C. for 1.5 hours
  3. temperatureto cool
  4. custompartitioned between ethyl acetate and water
  5. washThe organic layer was washed with brine
  6. dry with materialdried (MgSO4), and volatiles
  7. customremoved by evaporation
  8. customThe residue was purified by column flash chromatography
  9. washeluting with methylene chloride/acetonitrile/methanol (60/38/2 followed by 60/35/5)
  10. dissolutionThe resulting solid was dissolved in methylene chloride/methanol
  11. addition3M ethereal hydrogen chloride was added
  12. concentrationThe mixture was concentrated by evaporation
  13. filtrationthe resulting precipitate was collected by filtration
  14. washwashed with ether
  15. customdried under vacuum

Sources & evidence

ORD record
ord-cad00292488043dbb1f8bb3bbfe89887
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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