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

HRID 1274763Notes

Reaction equation

HRID 1274763 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]([F:49])=[C:44]([NH:50][CH:51]([CH3:53])[CH3:52])[N:43]=1>C(Cl)(Cl)Cl>[Cl:20][C:14]1[C:15]([F:19])=[C:16]([F:18])[CH:17]=[C:12]2[C:13]=1[N:41]([C:42]1[C:47]([F:48])=[CH:46][C:45]([F:49])=[C:44]([NH:50][CH:51]([CH3:53])[CH3:52])[N:43]=1)[CH:4]=[C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[C:11]2=[O:22]

Participants

5

Reactant 3

HCID 10934859Ethyl 3-(3-chloro-2,4,5-trifluorophenyl)-3-oxopropanoateHCID 221212742-Amino-3,5-difluoro-6-isopropylaminopyridineHCID 54402571Ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate

Product 1

HCID 22121250Ethyl 8-chloro-6,7-difluoro-1-(3,5-difluoro-6-isopropylamino-pyridine-2-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
90 °C

Procedure

To 2.5 ml of chloroform solution of ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate prepared from 0.70 g of ethyl 3-chloro-2,4,5-trifluorobenzoylacetate by normal process was added 600 mg of 2-amino-3,5-difluoro-6-isopropylaminopyridine. The solution was concentrated under reduced pressure. To the residue were added 600 mg of anhydrous potassium carbonate and 2 ml of N,N-dimethylformamide, and the mixture was stirred at 90° C. for 20 minutes and allowed to cool. The solution was separated by adding 30 ml of chloroform and 400 ml of distilled water, and the chloroform layer was washed twice with 400 ml of distilled water, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and allowed to stand. The precipitate was collected by filtration, washed with ethanol and diisopropylether successively to obtain 620 mg of the title compound as a pale yellow powder.

Workup

  1. concentrationThe solution was concentrated under reduced pressure
  2. additionTo the residue were added 600 mg of anhydrous potassium carbonate and 2 ml of N,N-dimethylformamide
  3. temperatureto cool
  4. customThe solution was separated
  5. additionby adding 30 ml of chloroform and 400 ml of distilled water
  6. washthe chloroform layer was washed twice with 400 ml of distilled water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. filtrationThe precipitate was collected by filtration
  10. washwashed with ethanol and diisopropylether successively

Sources & evidence

ORD record
ord-f8e5f291833545098bd93ab6d589f4ff
Source dataset
uspto-grants-2000_12
Patent number
US06156903

Reaction notes

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