Potassium Carbonate → 4-(3-Acetoxy-4-methylanilino)-6-methoxy-7-(2-methoxyethoxy)quinazoline

HRID 1596260Notes

Reaction equation

HRID 1596260 reaction equation
C(=O)([O-])[O-].[K+].[K+].[C:7]([O:10][C:11]1[CH:12]=[C:13]([CH:28]=[CH:29][C:30]=1[CH3:31])[NH:14][C:15]1[C:24]2[C:19](=[CH:20][C:21]([OH:27])=[C:22]([O:25][CH3:26])[CH:23]=2)[N:18]=[CH:17][N:16]=1)(=[O:9])[CH3:8].[CH3:32][O:33][CH2:34][CH2:35]Br>CN(C=O)C>[C:7]([O:10][C:11]1[CH:12]=[C:13]([CH:28]=[CH:29][C:30]=1[CH3:31])[NH:14][C:15]1[C:24]2[C:19](=[CH:20][C:21]([O:27][CH2:35][CH2:34][O:33][CH3:32])=[C:22]([O:25][CH3:26])[CH:23]=2)[N:18]=[CH:17][N:16]=1)(=[O:9])[CH3:8]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 809722-Bromoethyl methyl etherHCID 1354508044-(3-Acetoxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 224782334-(3-Acetoxy-4-methylanilino)-6-methoxy-7-(2-methoxyethoxy)quinazolineYield 84.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

Potassium carbonate (2.2 g, 16 mmol) was added to a solution of 4-(3-acetoxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline (1.51 g, 4 mmol) in DMF (30 ml) and the mixture stirred for 15 minutes. 2-Bromoethyl methyl ether (667 mg, 4.8 mmol) was then added dropwise. The mixture was stirred for 1 hour at ambient temperature, then heated at 60° C. for 17 hours and finally allowed to cool. The insoluble material was removed by filtration and the filter pad washed with DMF. The filtrate was partitioned between ethyl acetate and water, the organic layer was separated, washed with brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5 followed by 93/7). The purified product was triturated with ether to give 4-(3-acetoxy-4-methylanilino)-6-methoxy-7-(2-methoxyethoxy)quinazoline (1.34 g, 84%) as a white powder.

Workup

  1. stirringThe mixture was stirred for 1 hour at ambient temperature
  2. temperatureto cool
  3. customThe insoluble material was removed by filtration
  4. washthe filter pad washed with DMF
  5. customThe filtrate was partitioned between ethyl acetate and water
  6. customthe organic layer was separated
  7. washwashed with brine
  8. dry with materialdried (MgSO4)
  9. customthe solvent removed by evaporation
  10. customThe residue was purified by column chromatography
  11. washeluting with methylene chloride/methanol (95/5 followed by 93/7)
  12. customThe purified product was triturated with ether

Sources & evidence

ORD record
ord-b237e2251cc0420a8ced25ae405fa862
Source dataset
uspto-grants-2001_09
Patent number
US06291455B1

Reaction notes

Loading…