Sodium hydride → 6-Methoxy-4-(oxindol-3-yl)-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline hydrochloride

HRID 1386306Notes

Reaction equation

HRID 1386306 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:26][CH2:27][CH2:28][N:29]3[CH2:33][CH2:32][CH2:31][CH2:30]3)=[C:21]([O:24][CH3:25])[CH:22]=2)[N:17]=[CH:16][N:15]=1>C1COCC1.CN(C=O)C>[ClH:13].[CH3:25][O:24][C:21]1[CH:22]=[C:23]2[C:18](=[CH:19][C:20]=1[O:26][CH2:27][CH2:28][N:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1)[N:17]=[CH:16][N:15]=[C:14]2[CH:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][C:2]1=[O:10]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 321710OxindoleHCID 109357264-Chloro-6-methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline

Product 1

HCID 217172726-Methoxy-4-(oxindol-3-yl)-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline hydrochlorideYield 19.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of oxindole (259 mg, 1.95 mmol) in THF (3 ml) was added dropwise to a suspension of sodium hydride (78 mg, 1.95 mmol, prewashed with hexane) in THF (3 ml). The mixture was stirred for 30 minutes at ambient temperature and a solution of 4-chloro-6-methoxy-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline (200 mg, 0.65 mmol) in DMF (3 ml) was added dropwise. The mixture was heated at 60° C. for 30 minutes, the THF was removed by evaporation and the residue was partitioned between methylene chloride and water. The organic layer was separated, washed with brine, dried (MgSO4) and the solvent removed by evaporation. The solid residue was purified by chromatography on neutral aluminium oxide eluting with methylene chloride/methanol (80/20). The purified solid was dissolved in methylene chloride containing methanol and 3M ethereal hydrogen chloride was added. The volatiles were removed by evaporation and the residue was suspended in ether. The solid was collected by filtration, washed with ether and dried under vacuum to give 6-methoxy-4-(oxindol-3-yl)-7-(2-(pyrrolidin-1-yl)ethoxy)quinazoline hydrochloride (55 mg, 18%).

Workup

  1. temperatureThe mixture was heated at 60° C. for 30 minutes
  2. customthe THF was removed by evaporation
  3. customthe residue was partitioned between methylene chloride and water
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed by evaporation
  8. customThe solid residue was purified by chromatography on neutral aluminium oxide eluting with methylene chloride/methanol (80/20)
  9. dissolutionThe purified solid was dissolved in methylene chloride
  10. additioncontaining methanol and 3M ethereal hydrogen chloride
  11. additionwas added
  12. customThe volatiles were removed by evaporation
  13. filtrationThe solid was collected by filtration
  14. washwashed with ether
  15. customdried under vacuum

Sources & evidence

ORD record
ord-503e740d1895472d8bbe632608761ec6
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

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