Sodium hydride → 4-(4-Chloro-2-fluoroanilino)-7-(2-(2,6-dioxopiperidino)ethoxy)-6-methoxyquinazoline

HRID 1838565Notes

Reaction equation

HRID 1838565 reaction equation
[H-].[Na+].[C:3]1(=[O:10])[NH:8][C:7](=[O:9])[CH2:6][CH2:5][CH2:4]1.Br[CH2:12][CH2:13][O:14][C:15]1[CH:24]=[C:23]2[C:18]([C:19]([NH:25][C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][C:27]=3[F:33])=[N:20][CH:21]=[N:22]2)=[CH:17][C:16]=1[O:34][CH3:35]>CN(C=O)C>[Cl:32][C:29]1[CH:30]=[CH:31][C:26]([NH:25][C:19]2[C:18]3[C:23](=[CH:24][C:15]([O:14][CH2:13][CH2:12][N:8]4[C:7](=[O:9])[CH2:6][CH2:5][CH2:4][C:3]4=[O:10])=[C:16]([O:34][CH3:35])[CH:17]=3)[N:22]=[CH:21][N:20]=2)=[C:27]([F:33])[CH:28]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 70726GlutarimideHCID 187534227-(2-Bromoethoxy)-4-(4-chloro-2-fluoroanilino)6-methoxyquinazoline

Product 1

HCID 224782274-(4-Chloro-2-fluoroanilino)-7-(2-(2,6-dioxopiperidino)ethoxy)-6-methoxyquinazolineYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (55 mg of a 60% dispersion in mineral oil. 1.1 mmol) was added to a solution of glutarimide (120 mg, 1.06 mmol) in DMF (5 ml) at ambient temperature under argon and the mixture stirred for 30 minutes. 7-(2-Bromoethoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline (428 mg, 1 mmol), (prepared as described for the starting material in Example 62), in DMF (2 ml) was added and the resulting pale green solution was stirred for 18 hours and then quenched with water. The volatiles were removed by evaporation, and the residue was partitioned between water and ethyl acetate. The organic phase was separated and washed with water and then dried (MgSO4). The solvent was removed by evaporation, and the residue was purified by column chromatography eluting with ethyl acetate then ethyl acetate/methanol (9/1). The purified product was recrystallised from ethyl acetate and hexane, collected by filtration and washed with ether to give 4-(4-chloro-2-fluoroanilino)-7-(2-(2,6-dioxopiperidino)ethoxy)-6-methoxyquinazoline (252 mg, 55%).

Workup

  1. additionwas added
  2. stirringthe resulting pale green solution was stirred for 18 hours
  3. customquenched with water
  4. customThe volatiles were removed by evaporation
  5. customthe residue was partitioned between water and ethyl acetate
  6. customThe organic phase was separated
  7. washwashed with water
  8. dry with materialdried (MgSO4)
  9. customThe solvent was removed by evaporation
  10. customthe residue was purified by column chromatography
  11. washeluting with ethyl acetate
  12. customThe purified product was recrystallised from ethyl acetate and hexane
  13. filtrationcollected by filtration
  14. washwashed with ether

Sources & evidence

ORD record
ord-79ff2895d009484aacfb38dd24969eaa
Source dataset
uspto-grants-2004_01
Patent number
US06673803B2

Reaction notes

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