Sodium hydride → HCID 21717186, compound

HRID 1386282Notes

Reaction equation

HRID 1386282 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:34][CH3:35])=[C:21]([O:24][CH2:25][CH2:26][CH2:27][N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[CH:22]=2)[N:17]=[CH:16][N:15]=1>C1COCC1.CN(C=O)C>[ClH:13].[CH3:35][O:34][C:20]1[CH:19]=[C:18]2[C:23]([C:14]([CH:3]3[C:4]4[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=4)[NH:1][C:2]3=[O:10])=[N:15][CH:16]=[N:17]2)=[CH:22][C:21]=1[O:24][CH2:25][CH2:26][CH2:27][N:28]1[CH2:29][CH2:30][O:31][CH2:32][CH2:33]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 321710OxindoleHCID 226492214-Chloro-7-methoxy-6-(3-(4-morpholinyl)propoxy)quinazoline

Product 1

HCID 21717186HCID 21717186, compoundYield 74.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of oxindole (200 mg, 1.5 mmol) in THF (3 ml) was added dropwise under nitrogen to sodium hydride (60 mg, 1.5 mmol, prewashed with hexane) in THF (3 ml). After stirring for 20 minutes at ambient temperature, a solution of 4-chloro-6(3-morpholinopropoxy)-7-methoxyquinazoline (169 mg, 0.5 mmol) in DMF (3 ml) was added. The mixture was heated at 75° C. for 1 hour, allowed to cool and the volatiles removed by evaporation. The mixture was partitioned between water and ether. The aqueous layer was adjusted to pH8 with 2M hydrochloric acid. The resulting precipitate was collected by filtration, washed with water, and dried under vacuum. The solid was dissolved in methylene chloride/methanol and 3M ethereal hydrogen chloride (0.5 ml) was added. The mixture was diluted with ether, the solid was collected by filtration and dried under vacuum to give 7-methoxy-6-(3-morpholinopropoxy)-4-(oxindol-3-yl)quinazoline hydrochloride (175 mg, 69%).

Workup

  1. temperatureThe mixture was heated at 75° C. for 1 hour
  2. temperatureto cool
  3. customthe volatiles removed by evaporation
  4. customThe mixture was partitioned between water and ether
  5. filtrationThe resulting precipitate was collected by filtration
  6. washwashed with water
  7. customdried under vacuum
  8. dissolutionThe solid was dissolved in methylene chloride/methanol
  9. addition3M ethereal hydrogen chloride (0.5 ml) was added
  10. additionThe mixture was diluted with ether
  11. filtrationthe solid was collected by filtration
  12. customdried under vacuum

Sources & evidence

ORD record
ord-37a2d28cac4c46578d175c83ca60b054
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

Loading…