Potassium Carbonate → HCID 21701559, compound

HRID 1596245Notes

Reaction equation

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

Participants

Conditions

Temperature: 60 °C

Procedure

2-Bromoethyl methyl ether (712 μl, 7.56 mmol) was added dropwise to a solution of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (2.2 g, 6.88 mmol) and potassium carbonate (2.84 g, 20.6 mmol) in DMF (110 ml). The mixture was stirred for 10 hours at 60° C. then for 2 days at ambient temperature, the solvent was removed by evaporation and the crude product purified by flash chromatography eluting with ethyl acetate/petroleum ether (4/1). The resulting solid was dissolved in hot ethanol and ethanolic hydrogen chloride was added. After cooling, the resulting solid was collected by filtration, washed with ethanol and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-methoxyethoxy)quinazoline hydrochloride (1.74 g, 62%).

Workup

waitfor 2 days at ambient temperature
customthe solvent was removed by evaporation
customthe crude product purified by flash chromatography
washeluting with ethyl acetate/petroleum ether (4/1)
dissolutionThe resulting solid was dissolved in hot ethanol
additionethanolic hydrogen chloride was added
temperatureAfter cooling
filtrationthe resulting solid was collected by filtration
washwashed with ethanol
customdried under vacuum

Sources & evidence

ORD record: ord-e33fd2b1d0704cfbafd0cf8eb7a1f5aa
Source dataset: uspto-grants-2001_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06291455B1

Reaction notes

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