Ethyl Acetate → N6-Ethyl-4-(4-amino-3-chlorophenoxy)-7-benzyloxy-6-quinolinecarboxamide

HRID 388074Notes

Reaction equation

HRID 388074 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[Cl:9].[H-].[Na+].[CH2:12]([NH:14][C:15]([C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][C:26]=1[O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[N:23]=[CH:22][CH:21]=[C:20]2Cl)=[O:16])[CH3:13].C(OCC)(=O)C>CS(C)=O.O>[CH2:12]([NH:14][C:15]([C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][C:26]=1[O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[N:23]=[CH:22][CH:21]=[C:20]2[O:8][C:5]1[CH:6]=[CH:7][C:2]([NH2:1])=[C:3]([Cl:9])[CH:4]=1)=[O:16])[CH3:13]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 871844-Amino-3-chlorophenolHCID 22936981N6-Ethyl-7-benzyloxy-4-chloro-6-quinolinecarboxamide

Product 1

HCID 22936317N6-Ethyl-4-(4-amino-3-chlorophenoxy)-7-benzyloxy-6-quinolinecarboxamideYield 92%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

After dissolving 4-amino-3-chlorophenol (379 mg, 2.64 mmol) in dimethylsulfoxide (10 ml), sodium hydride (106 mg, 2.64 mmol) was gradually added at room temperature and the mixture was stirred for 30 minutes. N6-Ethyl-7-benzyloxy-4-chloro-6-quinolinecarboxamide (720 mg, 2.11 mmol) was added, and the mixture was heated at 100° C. for 2 hours while stirring. Upon cooling to room temperature, the reaction solution was distributed between ethyl acetate and water, and the organic layer was washed with ammonia water, water and saturated saline and dried over anhydrous sodium sulfate. The solvent was distilled off, suspended in ethyl acetate and diluted with hexane, and the crystals were filtered out and blow-dried to obtain the title compound (870 mg, 1.94 mmol, 92%) as brown crystals.

Workup

  1. additionwas gradually added at room temperature
  2. stirringwhile stirring
  3. temperatureUpon cooling to room temperature
  4. washthe organic layer was washed with ammonia water, water and saturated saline
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled off
  7. additiondiluted with hexane
  8. filtrationthe crystals were filtered out and
  9. customblow-dried

Sources & evidence

ORD record
ord-c5eafd406c8046d0a1e4313d99e0b8bc
Source dataset
uspto-grants-2013_02
Patent number
US08372981B2

Reaction notes

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