Water → N6-Methoxy-4-(4-amino-3-chlorophenoxy)-7-benzyloxy-6-quinolinecarboxamide

HRID 388078Notes

Reaction equation

HRID 388078 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[Cl:9].[H-].[Na+].[CH3:12][O:13][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].O>CS(C)=O.C(OCC)(=O)C.CCCCCC>[CH3:12][O:13][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]

Participants

8

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 871844-Amino-3-chlorophenolHCID 22936829N6-Methoxy-7-benzyloxy-4-chloro-6-quinolinecarboxamide

Product 1

HCID 22936373N6-Methoxy-4-(4-amino-3-chlorophenoxy)-7-benzyloxy-6-quinolinecarboxamideYield 16%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
100 °C

Procedure

After dissolving 4-amino-3-chlorophenol (408 mg, 2.84 mmol) in dimethylsulfoxide (10 ml), sodium hydride (114 mg, 2.84 mmol) was gradually added at room temperature and the mixture was stirred for 30 minutes. N6-Methoxy-7-benzyloxy-4-chloro-6-quinolinecarboxamide (388 mg, 1.14 mmol) was added, and the mixture was heated at 100° C. for 18 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 water and saturated saline and dried over anhydrous magnesium sulfate. After distilling off the solvent, it was subjected to silica gel column chromatography, the target fraction was concentrated under reduced pressure, the obtained crude product was suspended in ethyl acetate, the suspension was diluted with hexane, and the crystals were filtered out, washed with hexane and blow-dried to obtain the title compound (81.0 mg, 0.180 mmol, 16%) as light red 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 water and saturated saline
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationAfter distilling off the solvent, it
  7. concentrationthe target fraction was concentrated under reduced pressure
  8. customthe obtained crude product
  9. filtrationthe crystals were filtered out
  10. washwashed with hexane
  11. customblow-dried

Sources & evidence

ORD record
ord-2124dd8887ef4eb2b229ad53649d4139
Source dataset
uspto-grants-2013_02
Patent number
US08372981B2

Reaction notes

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