Sodium hydride → HCID 21717263, compound

HRID 1386332Notes

Reaction equation

HRID 1386332 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].[Cl:14][C:15]1[C:24]2[C:19](=[CH:20][C:21]([O:27][CH2:28][CH2:29][N:30]3[CH:34]=[CH:33][N:32]=[CH:31]3)=[C:22]([O:25][CH3:26])[CH:23]=2)[N:18]=[CH:17][N:16]=1>CN(C=O)C>[ClH:14].[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]([C:15]3[C:24]4[C:19](=[CH:20][C:21]([O:27][CH2:28][CH2:29][N:30]5[CH:34]=[CH:33][N:32]=[CH:31]5)=[C:22]([O:25][CH3:26])[CH:23]=4)[N:18]=[CH:17][N:16]=3)[C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 37310136-fluoro-2,3-dihydro-1H-indol-2-oneHCID 111412614-Chloro-6-methoxy-7-(2-(imidazol-1-yl)ethoxy)quinazoline

Product 1

HCID 21717263HCID 21717263, compoundYield 42.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 6-fluorooxindole (407 mg, 2.7 mmol), (Synthesis 1993, 51), in DMF (6 ml) was added dropwise to sodium hydride (108 mg, 2.7 mmol, prewashed with hexane) in DMF (6 ml). The mixture was stirred for 30 minutes at ambient temperature and 4-chloro-7-(2-(imidazol-1-yl)ethoxy)-6-methoxyquinazoline (274 mg, 0.9 mmol), (prepared as described for the starting material in Example 22), was added as a solid. The mixture was heated at 65° C. for 30 minutes, allowed to cool and was partitioned between saturated aqueous ammonium chloride solution and methylene chloride. The organic layer was separated, dried (MgSO4), and the solvent removed by evaporation. The residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum. The solid was dissolved in methylene chloride/methanol and 5M ethereal hydrogen chloride (4 ml) was added. The mixture was concentrated by evaporation to 5 ml total volume and the resulting solid was collected by filtration, washed with ether and dried under vacuum to give 4-(6-fluorooxindol-3-yl)-7-(2-(imidazol-1-yl)ethoxy)-6-methoxyquinazoline hydrochloride (175 mg, 40%).

Workup

  1. additionwas added as a solid
  2. temperatureThe mixture was heated at 65° C. for 30 minutes
  3. temperatureto cool
  4. customwas partitioned between saturated aqueous ammonium chloride solution and methylene chloride
  5. customThe organic layer was separated
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed by evaporation
  8. customThe residue was triturated with ether
  9. filtrationcollected by filtration
  10. washwashed with ether
  11. customdried under vacuum
  12. dissolutionThe solid was dissolved in methylene chloride/methanol
  13. addition5M ethereal hydrogen chloride (4 ml) was added
  14. concentrationThe mixture was concentrated by evaporation to 5 ml total volume
  15. filtrationthe resulting solid was collected by filtration
  16. washwashed with ether
  17. customdried under vacuum

Sources & evidence

ORD record
ord-e3ff95e8f0814625afb3b2a7ac300d24
Source dataset
uspto-grants-2001_07
Patent number
US06265411B1

Reaction notes

Loading…