Dimethylformamide → HCID 22478196, compound

HRID 2182548Notes

Reaction equation

[Cl:1][N:2]([C:10]1C2C(=CC(O)=C(OC)C=2)N=CN=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[F:9].Br[CH2:24][CH2:25][CH2:26][O:27][CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][O:29]1.[C:34](=[O:37])([O-])[O-].[K+].[K+].[CH3:40][N:41]([CH:43]=[O:44])C>O>[Cl:1][N:2]([CH2:10][O:44][C:43]1[C:4]2[C:3](=[CH:8][C:34]([O:37][CH2:24][CH2:25][CH2:26][O:27][CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][O:29]3)=[CH:6][CH:5]=2)[N:2]=[CH:40][N:41]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[F:9]

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 4-(chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (3.28 g, 10 mmol), (prepared as described for the starting material in Example 2), 1-bromo-3-tetrahydropyranyloxypropane (2.5 g, 11 mmol) and potassium carbonate (5.0 g, 36 mmol) in DMF (50 ml) was stirred and heated at 90° C. for 3 hours. The reaction mixture was allowed to cool, was diluted with water (500 ml) and extracted with ethyl acetate (3×100 ml). The extracts were combined, washed with water (×3), and then brine, and dried (MgSO4). The solvent was removed by evaporation and the residue was purified by column chromatography eluting with ethyl acetate. The purified product was recrystallised from ethyl acetate/hexane to give 4-(chloro-2-fluoroanilino)methoxy-7-(3-tetrahydropyran-2-yloxypropoxy)quinazoline (2.25 g, 49%).

Workup

custom(prepared
temperatureto cool
extractionextracted with ethyl acetate (3×100 ml)
washwashed with water (×3)
dry with materialbrine, and dried (MgSO4)
customThe solvent was removed by evaporation
customthe residue was purified by column chromatography
washeluting with ethyl acetate
customThe purified product was recrystallised from ethyl acetate/hexane

Sources & evidence

ORD record: ord-ce530470a468441592258919911f65a8
Source dataset: uspto-grants-2005_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06897210B2

Reaction notes

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