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

HRID 631578Notes

Reaction equation

HRID 631578 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:29][CH3:30])=[C:23]([O:26][CH2:27][CH3:28])[CH:24]=2)[N:19]=[CH:18][N:17]=1>C1COCC1.C(OCC)(=O)C>[CH2:27]([O:26][C:23]1[CH:24]=[C:25]2[C:20](=[CH:21][C:22]=1[O:29][CH3:30])[N:19]=[CH:18][N:17]=[C:16]2[O:14][C:10]1[CH:9]=[C:8]([CH:13]=[CH:12][CH:11]=1)[NH2:7])[CH3:28]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 115683-AminophenolHCID 109226204-Chloro-6-ethoxy-7-methoxyquinazoline

Product 1

HCID 668762473-(6-Ethoxy-7-methoxyquinazolin-4-yloxy)anilineYield 50%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred suspension of cesium carbonate (3.60 g, 11.06 mmol) in THF (50 mL) was added 3-aminophenol (0.91 g, 8.38 mmol). After stirring for 30 minutes at rt, 4-chloro-6-ethoxy-7-methoxyquinazoline described in Example 11A (2.00 g, 8.38 mmol) was added and the reaction mixture was heated at 50° C. for 15 h. The reaction mixture was cooled to rt and diluted with ethyl acetate. The solution was washed with aqueous 1 M NaOH solution, then brine, and dried over MgSO4. Filtration and concentrated under reduced pressure, gave a solid that was triturated with ethyl acetate. Filtration and drying afforded 3-(6-ethoxy-7-methoxyquinazolin-4-yloxy)aniline (1.30 g, 50%) as a cream solid, which did not require further purification. 1H NMR (400 MHz, DMSO-d6) δ 8.54 (s, 1H), 7.48 (s, 1H), 7.36 (s, 1H), 7.08 (dd, J=8, 8 Hz, 1H), 6.36-6.49 (m, 3H), 5.30 (brs, 2H), 4.21 (q, J=7 Hz, 2H), 3.98 (s, 3H), 1.41 (t, J=7 Hz, 3H); LC-MS (ESI) m/z 312 (M+H)+.

Workup

  1. additionwas added
  2. temperaturethe reaction mixture was heated at 50° C. for 15 h
  3. temperatureThe reaction mixture was cooled to rt
  4. washThe solution was washed with aqueous 1 M NaOH solution
  5. dry with materialbrine, and dried over MgSO4
  6. filtrationFiltration
  7. concentrationconcentrated under reduced pressure
  8. customgave a solid
  9. customthat was triturated with ethyl acetate
  10. filtrationFiltration
  11. customdrying

Sources & evidence

ORD record
ord-7e3ed9dd1a9544399eefbedd090edb28
Source dataset
uspto-grants-2016_04
Patent number
US09320739B2

Reaction notes

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