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

HRID 871780Notes

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-16ad77817b4a42778632c698f83ad0ed
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969587B2

Reaction notes

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