Sodium hydride → 2-Chloro-4-((6,7-dimethoxyquinazolin-4-yl)oxy)aniline

HRID 1008335Notes

Reaction equation

HRID 1008335 reaction equation
[H-].[Na+].Cl.[NH2:4][C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[CH:7][C:6]=1[Cl:12].Cl[C:14]1[C:23]2[C:18](=[CH:19][C:20]([O:26][CH3:27])=[C:21]([O:24][CH3:25])[CH:22]=2)[N:17]=[CH:16][N:15]=1.ClC1N=CC2C(=CC=CC=2)N=1>O.CS(C)=O>[Cl:12][C:6]1[CH:7]=[C:8]([O:11][C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:26][CH3:27])=[C:21]([O:24][CH3:25])[CH:22]=3)[N:17]=[CH:16][N:15]=2)[CH:9]=[CH:10][C:5]=1[NH2:4]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 740542-ChloroquinazolineHCID 27693644-Chloro-6,7-dimethoxyquinazolineHCID 125981904-Amino-3-chlorophenol hydrochloride

Product 1

HCID 218898992-Chloro-4-((6,7-dimethoxyquinazolin-4-yl)oxy)anilineYield 76%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

Sodium hydride (60 wt %, 5.80 g) was added to dimethyl sulfoxide (40 ml). The mixture was stirred at 60° C. for 30 min and was then cooled to room temperature. Next, 4-amino-3-chlorophenol hydrochloride (13.05 g) was added thereto. The mixture was stirred at room temperature for 10 min. 4-Chloro-6,7-dimethoxyquinazoline (8.14 g), which is a chloroquinazoline derivative synthesized by a conventional method as described, for example, in J. Am. Chem. Soc., 68, 1299 (1946) or J. Am. Chem. Soc., 68, 1305 (1946), was then added thereto. The mixture was stirred at 110° C. for 30 min. Water was then added to the reaction solution, followed by extraction with chloroform. The chloroform layer was then washed with a saturated aqueous sodium hydrogencarbonate solution and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and methanol was added to the residue to prepare a suspension. The precipitated crystal was collected by suction filtration to give 9.13 g (yield 76%) of the title compound.

Workup

  1. temperaturewas then cooled to room temperature
  2. stirringThe mixture was stirred at room temperature for 10 min
  3. customsynthesized by a conventional method
  4. addition, 68, 1305 (1946), was then added
  5. stirringThe mixture was stirred at 110° C. for 30 min
  6. extractionfollowed by extraction with chloroform
  7. washThe chloroform layer was then washed with a saturated aqueous sodium hydrogencarbonate solution
  8. dry with materialwas dried over anhydrous sodium sulfate
  9. customThe solvent was removed by distillation under the reduced pressure, and methanol
  10. additionwas added to the residue
  11. customto prepare a suspension
  12. filtrationThe precipitated crystal was collected by suction filtration

Sources & evidence

ORD record
ord-a84fa358114a47809a19c3443e5796d8
Source dataset
uspto-grants-2004_09
Patent number
US06797823B1

Reaction notes

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