Dimethylformamide → N6-Methoxy-7-benzyloxy-4-chloro-6-quinolinecarboxamide

HRID 853604Notes

Reaction equation

HRID 853604 reaction equation
S(Cl)(Cl)=O.CN(C)C=O.[CH2:10]([O:17][C:18]1[CH:27]=[C:26]2[C:21]([C:22](=O)[CH:23]=[CH:24][NH:25]2)=[CH:20][C:19]=1[C:29]([O:31]C1C=CC=CC=1)=O)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[ClH:38].[O:39]([NH2:41])[CH3:40]>C(OCC)(=O)C.CCCCCC.O>[CH3:40][O:39][NH:41][C:29]([C:19]1[CH:20]=[C:21]2[C:26](=[CH:27][C:18]=1[O:17][CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[N:25]=[CH:24][CH:23]=[C:22]2[Cl:38])=[O:31]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 521874O-Methylhydroxylamine hydrochlorideHCID 22936353Phenyl 7-benzyloxy-4-oxo-1,4-dihydro-6-quinolinecarboxylate

Product 1

HCID 22936829N6-Methoxy-7-benzyloxy-4-chloro-6-quinolinecarboxamideYield 18.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

After adding thionyl chloride (10 ml) and a catalytic amount of dimethylformamide to phenyl 7-benzyloxy-4-oxo-1,4-dihydro-6-quinolinecarboxylate (2.32 g, 6.25 mmol), the mixture was heated to reflux for 2 hours while stirring. The reaction solution was concentrated under reduced pressure and azeotropically distilled twice with toluene, the residue was dissolved in a dimethylformamide (20 ml) and triethylamine (20 ml) mixed solvent, methoxylamine hydrochloride (10.4 g, 125 mmol) was added thereto while cooling in an ice water bath, and the mixture was stirred at room temperature for 18 hours. The reaction solution was distributed between ethyl acetate and water, and then the organic layer was washed with water and saturated brine 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 (392 mg, 1.14 mmol, 18%) as white crystals.

Workup

  1. temperatureto reflux for 2 hours
  2. concentrationThe reaction solution was concentrated under reduced pressure
  3. distillationazeotropically distilled twice with toluene
  4. dissolutionthe residue was dissolved in a dimethylformamide (20 ml) and triethylamine (20 ml)
  5. additionwas added
  6. temperaturewhile cooling in an ice water bath
  7. stirringthe mixture was stirred at room temperature for 18 hours
  8. washthe organic layer was washed with water and saturated brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. distillationAfter distilling off the solvent, it
  11. concentrationthe target fraction was concentrated under reduced pressure
  12. customthe obtained crude product
  13. filtrationthe crystals were filtered out
  14. washwashed with hexane
  15. customblow-dried

Sources & evidence

ORD record
ord-6ef6e1a0a3594ce7bde6ed4c9de9e77f
Source dataset
uspto-grants-2007_08
Patent number
US07253286B2

Reaction notes

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