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

HRID 1918033Notes

Reaction equation

HRID 1918033 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-bb4c0c9da0fc45ac97a0defa7db890f3
Source dataset
uspto-grants-2013_12
Patent number
US08618289B2

Reaction notes

Loading…