1-(4-Fluorophenyl)piperazine → Ethyl 9-fluoro-8-[4-(4-fluorophenyl)piperazin-1-yl]-4-methyl-1-oxo-1,4-dihydrobenzo[f] [1,7]naphthyridine-2-carboxylate

HRID 413061Notes

Reaction equation

HRID 413061 reaction equation
F[C:2]1[C:22]([F:23])=[CH:21][C:5]2[C:6]3[C:7](=[O:20])[C:8]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:9][N:10]([CH3:14])[C:11]=3[CH:12]=[N:13][C:4]=2[CH:3]=1.[F:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)=[CH:27][CH:26]=1>CS(C)=O>[F:23][C:22]1[C:2]([N:34]2[CH2:33][CH2:32][N:31]([C:28]3[CH:27]=[CH:26][C:25]([F:24])=[CH:30][CH:29]=3)[CH2:36][CH2:35]2)=[CH:3][C:4]2[N:13]=[CH:12][C:11]3[N:10]([CH3:14])[CH:9]=[C:8]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:7](=[O:20])[C:6]=3[C:5]=2[CH:21]=1

Participants

4

Reactant 2

HCID 752601-(4-Fluorophenyl)piperazineHCID 18523355Ethyl 8,9-difluoro-4-methyl-1-oxo-1,4-dihydrobenzo[f][1,7]naphthyridine-2-carboxylate

Product 1

HCID 18523292Ethyl 9-fluoro-8-[4-(4-fluorophenyl)piperazin-1-yl]-4-methyl-1-oxo-1,4-dihydrobenzo[f] [1,7]naphthyridine-2-carboxylateYield 34.1%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of 1.5 g of ethyl 8,9-difluoro-4-methyl-1-oxo-1,4-dihydrobenzo[f][1,7]naphthyridine-2-carboxylate and 1.7 g of 1-(4-fluorophenyl)piperazine in 30 cm3 of dimethyl sulphoxide was heated, with stirring, at a temperature of 90° C. for 4 days. After cooling to 20° C., the mixture was poured into 150 cm3 of ice-cold water. The medium was extracted 3 times with 150 cm3 of dichloromethane. The organic extracts were washed 3 times with 100 cm3 of water and dried over sodium sulphate. After filtration and concentration under reduced pressure (5.2 kPa), the compound obtained was purified by chromatography on silica gel (0.06-0.20 mm). Elution was carried out with 7.8 liters of a dichloromethane-ethanol mixture (97-3 by volume), and 200 cm3 fractions were collected. The fractions between 5.6 and 7.8 liters were concentrated under reduced pressure (5.2 kPa). 0.77 g of ethyl 9-fluoro-8-[4-(4-fluorophenyl)piperazin-1-yl]-4-methyl-1-oxo-1,4-dihydrobenzo[f][1,7]naphthyridine-2-carboxylate was obtained in the form of yellow crystals, which melted at 300° C.

Workup

  1. temperaturewas heated
  2. temperatureAfter cooling to 20° C.
  3. extractionThe medium was extracted 3 times with 150 cm3 of dichloromethane
  4. washThe organic extracts were washed 3 times with 100 cm3 of water
  5. dry with materialdried over sodium sulphate
  6. filtrationAfter filtration and concentration under reduced pressure (5.2 kPa)
  7. customthe compound obtained
  8. customwas purified by chromatography on silica gel (0.06-0.20 mm)
  9. washElution
  10. customwere collected
  11. concentrationThe fractions between 5.6 and 7.8 liters were concentrated under reduced pressure (5.2 kPa)

Sources & evidence

ORD record
ord-68d0855bb8814b7a89a89d27df99c7d8
Source dataset
uspto-grants-2003_05
Patent number
US06566362B2

Reaction notes

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