Ethyl 3-(3-chloro-2,4,5-trifluorophenyl)-3-oxopropanoate → Ethyl 1-(6-amino-5-fluoro-3-methylpyridin-2-yl)-8-chloro-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate

HRID 368469Notes

Reaction equation

HRID 368469 reaction equation
C(O[CH:4]=[C:5]([C:11](=[O:22])[C:12]1[CH:17]=[C:16]([F:18])[C:15]([F:19])=[C:14]([Cl:20])[C:13]=1F)[C:6]([O:8][CH2:9][CH3:10])=[O:7])C.ClC1C(F)=C(C=C(F)C=1F)C(CC(OCC)=O)=O.[NH2:41][C:42]1[C:47]([F:48])=[CH:46][C:45]([CH3:49])=[C:44]([NH2:50])[N:43]=1>C(Cl)(Cl)Cl.CO>[NH2:41][C:42]1[N:43]=[C:44]([N:50]2[C:13]3[C:12](=[CH:17][C:16]([F:18])=[C:15]([F:19])[C:14]=3[Cl:20])[C:11](=[O:22])[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4]2)[C:45]([CH3:49])=[CH:46][C:47]=1[F:48]

Participants

6

Reactant 3

HCID 10934859Ethyl 3-(3-chloro-2,4,5-trifluorophenyl)-3-oxopropanoateHCID 221211783-Fluoro-5-methylpyridine-2,6-diamineHCID 54402571Ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate

Product 1

HCID 22121228Ethyl 1-(6-amino-5-fluoro-3-methylpyridin-2-yl)-8-chloro-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6212ChloroformSolvent2×

Conditions

Temperature
85 °C

Procedure

To 1 ml chloroform solution of ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate prepared from 280 mg of ethyl 3-chloro-2,4,5-trifluorobenzoylacetate by normal process was added all of 2,6-diamino-3-fluoro-5-methylpyridine as described above together with 2 ml of methanol and 4 ml of chloroform. After allowing to stand at room temperature for 40 minutes, the solution was concentrated under reduced pressure. To the residue were added 600 mg of anhydrous potassium carbonate and 1 ml of N,N-dimethylformamide, and the mixture was stirred at 85° C. for 15 minutes and allowed to cool. The solution was separated by adding 30 ml of chloroform and 300 ml of distilled water, and the chloroform layer was washed twice with 300 ml of distilled water. The chloroform layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. To the residue was added 0.5 ml of ethanol, and the mixture was allowed to stand overnight. The precipitate was dispersed in ethanol, collected by filtration, and washed with ethanol and diisopropylether successively to obtain 171 mg of the title compound as a colorless powder.

Workup

  1. concentrationthe solution was concentrated under reduced pressure
  2. additionTo the residue were added 600 mg of anhydrous potassium carbonate and 1 ml of N,N-dimethylformamide
  3. temperatureto cool
  4. customThe solution was separated
  5. additionby adding 30 ml of chloroform and 300 ml of distilled water
  6. washthe chloroform layer was washed twice with 300 ml of distilled water
  7. dry with materialThe chloroform layer was dried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. additionTo the residue was added 0.5 ml of ethanol
  10. waitto stand overnight
  11. additionThe precipitate was dispersed in ethanol
  12. filtrationcollected by filtration
  13. washwashed with ethanol and diisopropylether successively

Sources & evidence

ORD record
ord-70743b92ec834c2d9fcbf94ffb781b51
Source dataset
uspto-grants-2000_10
Patent number
US06133284

Reaction notes

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