Acetic Acid → 4-[(1-Ethyl-1H-pyrazol-5-yl)amino]-6,7-dimethoxy-3-quinolinecarboxamide

HRID 1822842Notes

Reaction equation

HRID 1822842 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].[CH2:19]([N:21]1[C:25]([NH2:26])=[CH:24][CH:23]=[N:22]1)[CH3:20].C(O)(=O)C>CN(C=O)C>[CH2:19]([N:21]1[C:25]([NH:26][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][C:3]=2[C:16]([NH2:18])=[O:17])=[CH:24][CH:23]=[N:22]1)[CH3:20]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 3373101-Ethyl-1H-pyrazol-5-amineHCID 221702044-Chloro-6,7-dimethoxyquinoline-3-carboxamide

Product 1

HCID 221703004-[(1-Ethyl-1H-pyrazol-5-yl)amino]-6,7-dimethoxy-3-quinolinecarboxamideYield 32.7%

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), 1-ethyl-5-aminopyrazol (0.030 g, 0.27 mmol) and acetic acid (40 μl) in DMF (0.8 ml) was heated at 100° C. for 7.5 h. The DMF was evaporated under reduced pressure and the residue was dissolved in a mixture of MeCN and water (1:7) containing 0.1% trifluoroacetic acid. 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 and absorbed on a short SPE column [ISOLUTE™ C18 (EC)] pre-conditioned subsequently with methanol and water. The column was washed extensively with water until the pH of the eluent was neutral. The product was then eluted with methanol, the solvent evaporated and the residue crystallized from ethanol to give the title compound (19 mg, 32%).

Workup

  1. customThe DMF was evaporated under reduced pressure
  2. dissolutionthe residue was dissolved in a mixture of MeCN and water (1:7)
  3. additioncontaining 0.1% trifluoroacetic acid
  4. additiona gradient (containing 0.1% trifluoroacetic acid) of 10→40% MeCN in water as eluent
  5. customgave
  6. customafter evaporation
  7. customabsorbed on a short SPE column [ISOLUTE™ C18 (EC)] pre-conditioned subsequently with methanol and water
  8. washThe column was washed extensively with water until the pH of the eluent
  9. washThe product was then eluted with methanol
  10. customthe solvent evaporated
  11. customthe residue crystallized from ethanol

Sources & evidence

ORD record
ord-dc6855be52ab42649af2e4ce58435a2f
Source dataset
uspto-grants-2006_05
Patent number
US07037925B2

Reaction notes

Loading…