1-Methylpyrrolidine → HCID 178471955, compound

HRID 1274728Notes

Reaction equation

HRID 1274728 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]=1[F:21])[C:6]([O:8][CH2:9][CH3:10])=[O:7])C.ClC1C(F)=C(C=C(F)C=1F)C(CC(OCC)=O)=O.Cl.[NH2:42][C:43]1[CH:48]=[C:47]([NH2:49])[C:46]([F:50])=[CH:45][N:44]=1.CN1CCCC1>C(Cl)(Cl)Cl>[NH2:42][C:43]1[CH:48]=[C:47]([NH:49][CH:4]=[C:5]([C:11](=[O:22])[C:12]2[CH:17]=[C:16]([F:18])[C:15]([F:19])=[C:14]([Cl:20])[C:13]=2[F:21])[C:6]([O:8][CH2:9][CH3:10])=[O:7])[C:46]([F:50])=[CH:45][N:44]=1

Participants

6

Reactant 4

HCID 84541-MethylpyrrolidineHCID 10934859Ethyl 3-(3-chloro-2,4,5-trifluorophenyl)-3-oxopropanoateHCID 221212585-Fluoropyridine-2,4-diaminehydrochlorideHCID 54402571Ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate

Product 1

HCID 178471955HCID 178471955, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
90 °C

Procedure

To 1.2 ml chloroform solution of ethyl 3-ethoxy-2-(3-chloro-2,4,5-trifluorobenzoyl)acrylate prepared from 0.34 g of ethyl 3-chloro-2,4,5-trifluorobenzoylacetate by normal process was added 0.25 g of 2,4-diamino-5-fluoropyridine hydrochloride together with 0.28 g of N-methylpyrrolidine. The solution was concentrated under reduced pressure, and to the residue were added 0.52 g of anhydrous potassium carbonate and 0.8 ml of N,N-dimethylformamide, and the mixture was stirred at 90° C. for 15 minutes and allowed to cool. The solution was separated by adding 20 ml of chloroform and 100 ml of distilled water, and the chloroform layer was washed with 100 ml of distilled water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to column chromatography (silica gel, 14 g; eluent: chloroform:methanol, 1:0, and then, 100:1), and the fraction containing the main product was concentrated under reduced pressure. The precipitate was dispersed in ethanol, collected by filtration, and washed with ethanol and diisopropylether successively to obtain 1.06 g of the title mixture (1:1 in NMR) as a pale brown powder.

Workup

  1. concentrationThe solution was concentrated under reduced pressure
  2. additionto the residue were added 0.52 g of anhydrous potassium carbonate and 0.8 ml of N,N-dimethylformamide
  3. temperatureto cool
  4. customThe solution was separated
  5. additionby adding 20 ml of chloroform and 100 ml of distilled water
  6. washthe chloroform layer was washed with 100 ml of distilled water
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. additioneluent: chloroform:methanol, 1:0, and then, 100:1), and the fraction containing the main product
  10. concentrationwas concentrated under reduced pressure
  11. additionThe precipitate was dispersed in ethanol
  12. filtrationcollected by filtration
  13. washwashed with ethanol and diisopropylether successively

Sources & evidence

ORD record
ord-a435a6a05f374d07b87ca105291ee5d1
Source dataset
uspto-grants-2000_12
Patent number
US06156903

Reaction notes

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