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

HRID 631749Notes

Reaction equation

C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:7][C:8]1[CH:9]=[C:10]([OH:14])[CH:11]=[CH:12][CH:13]=1.Cl[C:16]1[C:25]2[C:20](=[CH:21][C:22]([O:28][CH2:29][CH3:30])=[C:23]([O:26][CH3:27])[CH:24]=2)[N:19]=[CH:18][N:17]=1>C1COCC1>[CH2:29]([O:28][C:22]1[CH:21]=[C:20]2[C:25]([C:16]([O:14][C:10]3[CH:9]=[C:8]([CH:13]=[CH:12][CH:11]=3)[NH2:7])=[N:17][CH:18]=[N:19]2)=[CH:24][C:23]=1[O:26][CH3:27])[CH3:30]

Participants

Conditions

Temperature: 50 °C

Procedure

To a stirred slurry of cesium carbonate (2.99 g, 9.20 mmol) in anhydrous THF (50 mL) at rt, was added 3-aminophenol (1.00 g, 9.17 mmol). After stirring for 30 mins, 4-chloro-7-ethoxy-6-methoxyquinazoline (prepared as described in Example 6A Steps 1 through 5) (2.19 g, 9.20 mmol) was added and the reaction mixture was heated at 50° C. for 18 h. The mixture was cooled to rt and concentrated under reduced pressure and the resulting solid was washed with water (three times) then ethyl acetate (three times) to afford 3-(7-ethoxy-6-methoxyquinazolin-4-yloxy)aniline (1.75 g, 61%) as yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 8.54 (s, 1H), 7.51 (s, 1H), 7.35 (s, 1H), 7.09 (m, 1H), 6.37-6.50 (m, 3H), 5.31 (brs, 2H), 4.25 (q, J=7 Hz, 2H), 3.97 (s, 3H), 1.44 (t, J=7 Hz, 3H); LC-MS (ESI) m/z 312 (M+H)+.

Workup

temperatureThe mixture was cooled to rt
concentrationconcentrated under reduced pressure
washthe resulting solid was washed with water (three times)

Sources & evidence

ORD record: ord-e066f8e13bd04d4194dbb3bf6691cfd8
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09320739B2

Reaction notes

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