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

HRID 871631Notes

Reaction equation

HRID 871631 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:7][C:8]1[CH:9]=[C:10]([SH: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>[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[S:14][C:10]1[CH:9]=[C:8]([CH:13]=[CH:12][CH:11]=1)[NH2:7])[CH3:28]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 315773-AminothiophenolHCID 109226204-Chloro-6-ethoxy-7-methoxyquinazoline

Product 1

HCID 668767623-(6-Ethoxy-7-methoxyquinazolin-4-ylthio)anilineYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred suspension of cesium carbonate (3.60 g, 11.06 mmol) in THF (60 mL) was added 3-aminobenzenethiol (1.00 g, 7.99 mmol). After stirring for 30 minutes at rt, 4-chloro-6-ethoxy-7-methoxyquinazoline described in Example 11A (1.91 g, 7.99 mmol) was added and the reaction mixture was heated at rt for 15 h. The reaction mixture was cooled to rt and concentrated under reduced pressure to give a solid. Purification by silica gel column chromatography (eluting with 2% methanol in dichloromethane) afforded 3-(6-ethoxy-7-methoxyquinazolin-4-ylthio)aniline (1.20 g, 46%) as a cream solid, which did not require further purification. 1H NMR (400 MHz, DMSO-d6) δ 8.69 (s, 1H), 7.33 (s, 1H), 7.30 (s, 1H), 7.12 (dd, J=8, 8 Hz, 1H), 6.79 (s, 1H), 6.66-6.73 (m, 2H), 5.33 (brs, 2H), 4.21 (q, J=7 Hz, 2H), 3.98 (s, 3H), 1.43 (t, J=7 Hz, 3H); LC-MS (ESI) m/z 328 (M+H)+.

Workup

  1. additionwas added
  2. temperaturethe reaction mixture was heated at rt for 15 h
  3. temperatureThe reaction mixture was cooled to rt
  4. concentrationconcentrated under reduced pressure
  5. customto give a solid
  6. customPurification
  7. washby silica gel column chromatography (eluting with 2% methanol in dichloromethane)

Sources & evidence

ORD record
ord-2d76e16832b64c2e842808aeabdbce36
Source dataset
uspto-grants-2015_03
Patent number
US08969587B2

Reaction notes

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