Potassium Carbonate → 7-(2-(2-Bromoethoxy)ethoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline

HRID 1838597Notes

Reaction equation

HRID 1838597 reaction equation
Br[CH2:2][CH2:3][O:4][CH2:5][CH2:6][Br:7].[Cl:8][C:9]1[CH:28]=[CH:27][C:12]([NH:13][C:14]2[C:23]3[C:18](=[CH:19][C:20]([OH:26])=[C:21]([O:24][CH3:25])[CH:22]=3)[N:17]=[CH:16][N:15]=2)=[C:11]([F:29])[CH:10]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Br:7][CH2:6][CH2:5][O:4][CH2:3][CH2:2][O:26][C:20]1[CH:19]=[C:18]2[C:23]([C:14]([NH:13][C:12]3[CH:27]=[CH:28][C:9]([Cl:8])=[CH:10][C:11]=3[F:29])=[N:15][CH:16]=[N:17]2)=[CH:22][C:21]=1[O:24][CH3:25]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 21521Bis(2-bromoethyl) etherHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 187534287-(2-(2-Bromoethoxy)ethoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazolineYield 52.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Bromoethyl ether (1.57 ml, 12 mmol) was added to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (1 g, 3.1 mmol), (prepared as described for the starting material in Example 2), and potassium carbonate (1.73 g, 12 mmol) in DMF (10 ml). The mixture was stirred for 18 hours at ambient temperature and was partitioned between ethyl acetate and water. The organic layer was separated, washed with water and then brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography on silica eluting with methylene chloride/acetonitrile/methanol (60/38/2). The purified product was triturated with ether, collected by filtration, washed with ether and dried under vacuum to give 7-(2-(2-bromoethoxy)ethoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline (763 mg, 52%).

Workup

  1. custom(prepared
  2. customwas partitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. washwashed with water
  5. dry with materialbrine, dried (MgSO4)
  6. customthe solvent removed by evaporation
  7. customThe residue was purified by column chromatography on silica eluting with methylene chloride/acetonitrile/methanol (60/38/2)
  8. customThe purified product was triturated with ether
  9. filtrationcollected by filtration
  10. washwashed with ether
  11. customdried under vacuum

Sources & evidence

ORD record
ord-609a3dee64464910ac715d023ebe8517
Source dataset
uspto-grants-2004_01
Patent number
US06673803B2

Reaction notes

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