Sodium hydride → HCID 9910842, compound

HRID 1597208Notes

Reaction equation

HRID 1597208 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][N:8]=2)[CH2:3][C:2]1=[O:10].[H-].[Na+].Cl[C:14]1[C:23]2[C:18](=[CH:19][C:20]([O:26][CH2:27][CH2:28][CH2:29][N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)=[C:21]([O:24][CH3:25])[CH:22]=2)[N:17]=[CH:16][N:15]=1>C1COCC1.CN(C=O)C>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][N:8]=2)[CH:3]([C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:26][CH2:27][CH2:28][CH2:29][N:30]4[CH2:31][CH2:32][O:33][CH2:34][CH2:35]4)=[C:21]([O:24][CH3:25])[CH:22]=3)[N:17]=[CH:16][N:15]=2)[C:2]1=[O:10]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazolineHCID 138640951,3-Dihydro-2H-pyrrolo(2,3-b)pyridin-2-one

Product 1

HCID 9910842HCID 9910842, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 7-azaoxindole (284 mg, 2.1 mmol), (prepared as described for the starting material in Example 2), in THF (10 mn) was added to a suspension of sodium hydride (112 mg, 2.8 mmol, prewashed with petroleum ether) in THF (6 ml). After stirring for 20 minutes at ambient temperature, a solution of 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (238 mg, 0.7 mmol) in a mixture of THF (3 ml) and DMF (1 ml) was added. After stirring for 1 hour at 65° C., the volatiles were removed by evaporation. The residue was partitioned between water and ether. The aqueous layer was separated and adjusted to pH7 with 2M hydrochloric acid. After evaporation of water, the precipitate was triturated with ether, collected by filtration, washed with ether, and dried under vacuum. The residue was purified by column chromatography eluting with methylene chloride/methanol (9515 followed by 90110). After evaporation of the solvent, the residue was suspended in methylene chloride/methanol (1/1) and 3M hydrogen chloride in ether was added. After removal of the solvent by evaporation, the solid was collected by filtration, washed with ether and dried under vacuum to give 4-(7-azaoxindol-3-yl)-6-methoxy-7-(3-morpholinopropoxy)quinazoline (150 mg, 51%).

Workup

  1. additionwas added
  2. stirringAfter stirring for 1 hour at 65° C.
  3. customthe volatiles were removed by evaporation
  4. customThe residue was partitioned between water and ether
  5. customThe aqueous layer was separated
  6. customAfter evaporation of water
  7. customthe precipitate was triturated with ether
  8. filtrationcollected by filtration
  9. washwashed with ether
  10. customdried under vacuum
  11. customThe residue was purified by column chromatography
  12. washeluting with methylene chloride/methanol (9515 followed by 90110)
  13. customAfter evaporation of the solvent
  14. addition3M hydrogen chloride in ether was added
  15. customAfter removal of the solvent
  16. customby evaporation
  17. filtrationthe solid was collected by filtration
  18. washwashed with ether
  19. customdried under vacuum

Sources & evidence

ORD record
ord-8bd51208fe674f3885da58a8fb9b7521
Source dataset
uspto-grants-2001_09
Patent number
US06294532B1

Reaction notes

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