Water → HCID 18523425, compound

HRID 413054Notes

Reaction equation

HRID 413054 reaction equation
[F:1][C:2]1[C:15]2[N:14]=[CH:13][C:12]3[N:11]([CH3:16])[CH:10]=[C:9]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:8](=[O:22])[C:7]=3[C:6]=2[CH:5]=[CH:4][C:3]=1F.[F:24][C:25]1[CH:26]=[C:27]([N:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)[CH:28]=[CH:29][C:30]=1[CH3:31].O>CS(C)=O.ClCCl>[F:1][C:2]1[C:15]2[N:14]=[CH:13][C:12]3[N:11]([CH3:16])[CH:10]=[C:9]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:8](=[O:22])[C:7]=3[C:6]=2[CH:5]=[CH:4][C:3]=1[N:35]1[CH2:34][CH2:33][N:32]([C:27]2[CH:28]=[CH:29][C:30]([CH3:31])=[C:25]([F:24])[CH:26]=2)[CH2:37][CH2:36]1

Participants

6

Reactant 3

HCID 962WaterHCID 47388061-(3-fluoro-4-methylphenyl)piperazineHCID 18523248HCID 18523248, compound

Product 1

HCID 18523425HCID 18523425, compoundYield 23.7%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A stirred suspension of 3 g of ethyl 7,8-difluoro-4-methyl-1-oxo-1,4-dihydrobenzo[f][1,7]naphthyridine-2-carboxylate and 3.9 g of 1-(3-fluoro-4-methylphenyl)piperazine in 30 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 150 cm3 of water in the region of 10° C. and the precipitate was taken up in 100 cm3 of dichloromethane, dried with 10 g of magnesium sulphate and concentrated to dryness under reduced pressure (20 kPa). The yellow powder obtained was chromatographed on a Merck silica gel column (particle size 0.04-0.06 mm, diameter 3 cm, height 80 cm), eluted at an argon pressure of 1 bar with a mixture of dichloromethane and methanol (98/2 mixture by volume), and 200 cm3 fractions were collected. Fractions 16 to 23 were combined and then concentrated to dryness under reduced pressure (2.7 kPa). The yellow solid obtained was washed with 10 cm3 of diethyl ether, filtered and dried. 1.1 g of ethyl 7-fluoro-8-[4-(3-fluoro-4-methylphenyl)piperazin-1-yl]-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 a temperature in the region of 290° C.

Workup

  1. dry with materialdried with 10 g of magnesium sulphate
  2. concentrationconcentrated to dryness under reduced pressure (20 kPa)
  3. customThe yellow powder obtained
  4. customwas chromatographed on a Merck silica gel column (particle size 0.04-0.06 mm, diameter 3 cm, height 80 cm)
  5. washeluted at an argon pressure of 1 bar with a mixture of dichloromethane and methanol (98/2 mixture by volume), and 200 cm3 fractions
  6. customwere collected
  7. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  8. customThe yellow solid obtained
  9. washwas washed with 10 cm3 of diethyl ether
  10. filtrationfiltered
  11. customdried

Sources & evidence

ORD record
ord-ca344a65730f4f7f9729acb3694a74fd
Source dataset
uspto-grants-2003_05
Patent number
US06566362B2

Reaction notes

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