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

HRID 1918187Notes

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-f688a949260d436695a1c85b5e5386c5
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08618289B2

Reaction notes

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