Dimethylformamide → N6-Methyl-7-(benzyloxy)-4-chloro-6-quinolinecarboxamide

HRID 1433697Notes

Reaction equation

HRID 1433697 reaction equation
S(Cl)([Cl:3])=O.[CH2:5]([O:12][C:13]1[CH:22]=[C:21]2[C:16]([C:17](=O)[CH:18]=[CH:19][NH:20]2)=[CH:15][C:14]=1[C:24]([O:26]C1C=CC=CC=1)=O)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C[N:34]([CH3:37])C=O>>[CH3:37][NH:34][C:24]([C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][C:13]=1[O:12][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[N:20]=[CH:19][CH:18]=[C:17]2[Cl:3])=[O:26]

Participants

4

Reactant 3

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

Product 1

HCID 22936745N6-Methyl-7-(benzyloxy)-4-chloro-6-quinolinecarboxamideYield 89.7%

Procedure

After adding thionyl chloride (12 ml) and a catalytic amount of dimethylformamide to phenyl 7-(benzyloxy)-4-oxo-1,4-dihydro-6-quinolinecarboxylate (1.20 g, 3.23 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 suspended in dimethylformamide (20 ml), a 40% methylamine-methanol solution (5 ml) was gradually added while cooling in an ice water bath, and the mixture was stirred for 1 hour. The reaction solution was distributed between ethyl acetate-tetrahydrofuran (1:1) and water, and the organic layer was washed with saturated aqueous ammonium chloride solution, water and saturated brine and then dried over anhydrous sodium sulfate. The solvent was distilled off, diethyl ether and then hexane were added for crystallization, and the crystals were filtered out and blow-dried to obtain the title compound (947 mg, 2.90 mmol, 89.7%) as light yellow crystals.

Workup

  1. temperatureto reflux for 2 hours
  2. concentrationThe reaction solution was concentrated under reduced pressure
  3. distillationazeotropically distilled twice with toluene
  4. additiona 40% methylamine-methanol solution (5 ml) was gradually added
  5. temperaturewhile cooling in an ice water bath
  6. stirringthe mixture was stirred for 1 hour
  7. washthe organic layer was washed with saturated aqueous ammonium chloride solution, water and saturated brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. distillationThe solvent was distilled off
  10. additiondiethyl ether and then hexane were added for crystallization
  11. filtrationthe crystals were filtered out and
  12. customblow-dried

Sources & evidence

ORD record
ord-e3048acb9cf249d0b123763e1d634b60
Source dataset
uspto-grants-2009_11
Patent number
US07612092B2

Reaction notes

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