Cesium carbonate → 3-(6-(Benzyloxy)-7-methoxyquinazolin-4-yloxy)aniline

HRID 631376Notes

Reaction equation

[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[N:15]=[CH:14][N:13]=[C:12]2Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:22][C:23]1[CH:24]=[C:25]([OH:29])[CH:26]=[CH:27][CH:28]=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][C:18]=1[O:19][CH3:20])[N:15]=[CH:14][N:13]=[C:12]2[O:29][C:25]1[CH:24]=[C:23]([CH:28]=[CH:27][CH:26]=1)[NH2:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 75 °C

Procedure

To a solution of 6-(benzyloxy)-4-chloro-7-methoxyquinazoline (3.3 g, 0.01097 mol) and 3-aminophenol (1.2 g, 0.01097 mol) in THF (70 mL), Cs2CO3 (5.36 g, 0.0164 mol) was added at room temperature. The reaction mixture was stirred at 75° C. for 25 hr. The mixture was filtered and the solid was washed with ethyl acetate (100 mL). The organic phase was washed with water, brine and dried over MgSO4. The solvent was evaporated under vacuum and the solid was triturated with ethyl ether (20 mL). The solid was filtered and washed with ethyl ether to afford 3-(6-(benzyloxy)-7-methoxyquinazolin-4-yloxy)aniline (3.72 g, 90% yield). 1HNMR (DMSO-d6): δ 8.55 (s, 1H), 7.66 (s, 1H,), 7.46 (m, 8H), 7.08 (t, 1H), 6.49 (d, 1H), 6.40 (m, 2H), 5.30 (s, 2H), 4.02 (s, 3H). LC-MS (ESI) m/z 508 (M+H)+.

Workup

filtrationThe mixture was filtered
washthe solid was washed with ethyl acetate (100 mL)
washThe organic phase was washed with water, brine
dry with materialdried over MgSO4
customThe solvent was evaporated under vacuum
customthe solid was triturated with ethyl ether (20 mL)
filtrationThe solid was filtered
washwashed with ethyl ether

Sources & evidence

ORD record: ord-fa9a52df1e4342068b5cb0d81d1b6abe
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09320739B2

Reaction notes

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