Potassium Carbonate → 4-(4-Chloro-2-fluorophenoxy)-6-methoxy-7-((4-pyridyl)methoxy)quinazoline

HRID 1384587Notes

Reaction equation

[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([O: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.C(=O)([O-])[O-].[K+].[K+].Cl.Cl[CH2:31][C:32]1[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=1>CN(C=O)C>[Cl:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:31][C:32]4[CH:37]=[CH:36][N:35]=[CH:34][CH:33]=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: 80 °C

Procedure

A mixture of 4-(4-chloro-2-fluorophenoxy)-7-hydroxy-6-methoxyquinazoline (112 mg, 0.35 mmol), potassium carbonate (138 mg, 1 mmol) and 4-(chloromethyl)pyridine hydrochloride (59 mg, 0.36 mmol) in DMF (2 ml) was heated at 80° C. for 1 hour. The mixture was allowed to cool and partitioned between ethyl acetate and water. The organic layer was separated, washed with water and brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5) to give 4-(4-chloro-2-fluorophenoxy)-6-methoxy-7-((4-pyridyl)methoxy)quinazoline (115 mg, 80%). m.p. 197-198° C. 1H NMR Spectrum: (DMSOd6) 4.03(s, 3H); 5.46(s, 2H); 7.45(d, 1H); 7.49(s, 1H); 7.5(d, 2H); 7.58(t, 1H); 7.62(s, 1H); 7.72(dd, 1H); 8.58(s, 1H); 8.65(d, 2H) MS-ESI: 412 [MH]+

Workup

temperatureto cool
custompartitioned between ethyl acetate and water
customThe organic layer was separated
washwashed with water and brine
dry with materialdried (MgSO4)
customthe solvent removed by evaporation
customThe residue was purified by column chromatography
washeluting with methylene chloride/methanol (95/5)

Sources & evidence

ORD record: ord-c51f1601eb9c4be2a63d5fc79054f6ce
Source dataset: uspto-grants-2001_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06258951B1

Reaction notes

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