Acetic Acid → 4-[2-(Aminocarbonyl)anilino]-6,7-dimethoxy-3-quinolinecarboxamide

HRID 1822849

Reaction equation

HRID 1822849 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:16]([NH2:18])=[O:17].[NH2:19][C:20]1[CH:28]=[CH:27][CH:26]=[CH:25][C:21]=1[C:22]([NH2:24])=[O:23].C(O)(=O)C>CN(C=O)C>[NH2:24][C:22]([C:21]1[CH:25]=[CH:26][CH:27]=[CH:28][C:20]=1[NH:19][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:16]([NH2:18])=[O:17])=[O:23]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 6942AnthranilamideHCID 221702044-Chloro-6,7-dimethoxyquinoline-3-carboxamide

Product 1

HCID 221702664-[2-(Aminocarbonyl)anilino]-6,7-dimethoxy-3-quinolinecarboxamideYield 41.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-chloro-6,7-dimethoxy-3-quinolinecarboxamide (0.046 g, 0.17 mmol), 2-aminobenzamide (0.029 g, 0.21 mmol) and acetic acid (40 μl) in DMF (0.8 ml) was heated at 100° C. for 6 h. After cooling the reaction mixture was evaporated. The residue was dissolved in a mixture of MeCN and water (1:3) containing 0.1% trifluoroacetic acid and the turbid solution was filtered through a plug of glass wool. Preparative HPLC using a gradient (containing 0.1% trifluoroacetic acid) of 10→40% MeCN in water as eluent gave, after evaporation, the title compound as the trifluoroacetic acid salt. The product was suspended in saturated aqueous NaHCO3 an absorbed on a short SPE column [ISOLUTE™ C18 (EC)] pre-conditioned subsequently with methanol and then water. The column was washed extensively with water until the pH of the eluent was neutral. The product was then eluted with methanol. After evaporation, the residue was crystallized from ethanol to give the title compound (26 mg, 41%).

Workup

  1. temperatureAfter cooling the reaction mixture
  2. customwas evaporated
  3. dissolutionThe residue was dissolved in a mixture of MeCN and water (1:3)
  4. additioncontaining 0.1% trifluoroacetic acid
  5. filtrationthe turbid solution was filtered through a plug of glass wool
  6. additiona gradient (containing 0.1% trifluoroacetic acid) of 10→40% MeCN in water as eluent
  7. customgave
  8. customafter evaporation
  9. customan absorbed on a short SPE column [ISOLUTE™ C18 (EC)] pre-conditioned subsequently with methanol
  10. washThe column was washed extensively with water until the pH of the eluent
  11. washThe product was then eluted with methanol
  12. customAfter evaporation
  13. customthe residue was crystallized from ethanol

Sources & evidence

ORD record
ord-de1bf3d214084f2aa382fa73e4cc257b
Source dataset
uspto-grants-2006_05
Patent number
US07037925B2

Linked notes

Loading…