Potassium Carbonate → 4-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(2-(2-pyridyloxy)ethoxy)quinazoline

HRID 1384538Notes

Reaction equation

[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([OH:19])=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1.Cl.Cl[CH2:25][CH2:26][O:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:25][CH2:26][O:27][C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=4)=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:22])[CH:3]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (200 mg, 0.63 mmol), 2-(2-chloroethoxy)pyridine hydrochloride (120 mg, 0.61 mmol) and potassium carbonate (260 mg, 1.9 mmol) in DMF (25 ml) was heated at 90° C. for 16 hours. The mixture was diluted with water and extracted with ethyl acetate. The extract was dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with ethyl acetate/methanol mixtures (100/0 increasing to 90/10) to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(2-pyridyloxy)ethoxy)quinazoline (20 mg, 7%) as an off-white solid. 1H NMR Spectrum: (DMSOd6) 3.99(s, 3H); 4.35(t, 2H); 4.42(t, 2H); 6.22(t, 1H); 6.40(d, 1H); 7.42(s, 1H); 7.55(d, 2H); 7.71(d, 1H); 7.85(t, 1H); 8.55(d, 1H); 9.62(s, 1H) MS-ESI: 441 [MH]+

Workup

extractionextracted with ethyl acetate
dry with materialThe extract was dried (MgSO4)
customthe solvent removed by evaporation
customThe residue was purified by column chromatography
washeluting with ethyl acetate/methanol mixtures (100/0 increasing to 90/10)

Sources & evidence

ORD record: ord-51643dffe89748d3b9b182bbe60f67e3
Source dataset: uspto-grants-2001_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06258951B1

Reaction notes

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