Cesium carbonate → 3-(6,7-Bis(2-methoxyethoxy)quinazolin-4-ylthio)aniline

HRID 1918013Notes

Reaction equation

HRID 1918013 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([SH:8])[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:16]1[C:25]2[C:20](=[CH:21][C:22]([O:31][CH2:32][CH2:33][O:34][CH3:35])=[C:23]([O:26][CH2:27][CH2:28][O:29][CH3:30])[CH:24]=2)[N:19]=[CH:18][N:17]=1>O1CCCC1.C(Cl)(Cl)Cl.O.[Cl-].[Na+].O>[CH3:30][O:29][CH2:28][CH2:27][O:26][C:23]1[CH:24]=[C:25]2[C:20](=[CH:21][C:22]=1[O:31][CH2:32][CH2:33][O:34][CH3:35])[N:19]=[CH:18][N:17]=[C:16]2[S:8][C:4]1[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=1)[NH2:1]

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 315773-AminothiophenolHCID 112899424-Chloro-6,7-bis(2-methoxyethoxy)quinazoline

Product 1

HCID 668768743-(6,7-Bis(2-methoxyethoxy)quinazolin-4-ylthio)anilineYield 77.5%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

3-Aminothiophenol (56 mg, 0.45 mmol) was treated with cesium carbonate (193 g, 0.59 mmol) in anhydrous tetrahydrofuran (22 mL) and the mixture stirred at room temperature for 30 minutes. 4-chloro-6,7-bis(2-methoxyethoxy)quinazoline (142 mg, 0.45 mmol) from Example 12A was added and the mixture stirred at 60° C. overnight. After cooling to room temperature the mixture was diluted with chloroform, water and brine were added and the organic phase separated. The water phase was extracted three times with chloroform, dried (MgSO4) and concentrated under reduced pressure. The residue was purified by silica gel chromatography (dichloromethane/methanol 9:1) to afford 3-(6,7-bis(2-methoxyethoxy)quinazolin-4-ylthio)aniline (140 mg, 77%) as a solid. 1H NMR (300 MHz, CDCl3) δ 8.75 (s, 1H), 7.41 (s, 1H), 7:26 (t, 2H), 6.99-6.94 (m, 2H), 6.74 (d, 1H), 4.30 (s, 4H), 3.99 (bs, 6H), 3.87 (s, 6H); LC-MS (ESI) m/z 402 (M+H)+.

Workup

  1. stirringthe mixture stirred at 60° C. overnight
  2. temperatureAfter cooling to room temperature the mixture
  3. additionwere added
  4. customthe organic phase separated
  5. extractionThe water phase was extracted three times with chloroform
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography (dichloromethane/methanol 9:1)

Sources & evidence

ORD record
ord-7c994ce37b2a4bc8add8a9ba55c75464
Source dataset
uspto-grants-2013_12
Patent number
US08618289B2

Reaction notes

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