Water → Ethyl 9-[3-(3,4-dimethylphenyl)piperazin-1-yl]-8-fluoro-4-methyl-1-oxo-1,4-dihydrobenzo[f] [1,7]naphthyridine-2-carboxylate

HRID 413059Notes

Reaction equation

HRID 413059 reaction equation
[F:1][C:2]1[C:22](F)=[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.[CH3:24][C:25]1[CH:26]=[C:27]([CH:32]2[CH2:37][NH:36][CH2:35][CH2:34][NH:33]2)[CH:28]=[CH:29][C:30]=1[CH3:31].O>CS(C)=O>[CH3:24][C:25]1[CH:26]=[C:27]([CH:32]2[NH:33][CH2:34][CH2:35][N:36]([C:22]3[C:2]([F:1])=[CH:3][C:4]4[N:13]=[CH:12][C:11]5[N:10]([CH3:14])[CH:9]=[C:8]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:7](=[O:20])[C:6]=5[C:5]=4[CH:21]=3)[CH2:37]2)[CH:28]=[CH:29][C:30]=1[CH3:31]

Participants

5

Reactant 3

HCID 962WaterHCID 18523355Ethyl 8,9-difluoro-4-methyl-1-oxo-1,4-dihydrobenzo[f][1,7]naphthyridine-2-carboxylateHCID 185234042-(3,4-Dimethylphenyl)piperazine

Product 1

HCID 18523411Ethyl 9-[3-(3,4-dimethylphenyl)piperazin-1-yl]-8-fluoro-4-methyl-1-oxo-1,4-dihydrobenzo[f] [1,7]naphthyridine-2-carboxylateYield 42%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

A stirred suspension of 2.5 g of ethyl 8,9-difluoro-4-methyl-1-oxo-1,4-dihydrobenzo[f][1,7]naphthyridine-2-carboxylate and 2.6 g of 2-(3,4-dimethylphenyl)piperazine in 45 cm3 of dimethyl sulphoxide was heated at a temperature in the region of 100° C. for about 100 hours. The reaction mixture was treated with 400 cm3 of water and filtered. The residue obtained was chromatographed on a Merck silica gel column (particle size 0.04-0.06 mm, diameter 5.5 cm, height 45 cm), eluted at an argon pressure of 120 kPa with a mixture of dichloromethane and ethanol (92/8 mixture by volume) and 50 cm3 fractions were collected. Fractions 37 to 80 were combined and then concentrated to dryness under reduced pressure (2.7 kPa). 1.61 g of ethyl 9-[3-(3,4-dimethylphenyl)piperazin-1-yl]-8-fluoro-4-methyl-1-oxo-1,4-dihydrobenzo[f][1,7]naphthyridine-2-carboxylate was obtained in the form of a yellow solid, which melted at 290° C.

Workup

  1. filtrationfiltered
  2. customThe residue obtained
  3. customwas chromatographed on a Merck silica gel column (particle size 0.04-0.06 mm, diameter 5.5 cm, height 45 cm)
  4. washeluted at an argon pressure of 120 kPa with a mixture of dichloromethane and ethanol (92/8 mixture by volume) and 50 cm3 fractions
  5. customwere collected
  6. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-8a7cc7eba9454ddbacf43ffb1414f060
Source dataset
uspto-grants-2003_05
Patent number
US06566362B2

Reaction notes

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