Hydrochloric Acid → Ethyl 1-(2,4-difluorophenyl)-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxylate

HRID 246977Notes

Reaction equation

HRID 246977 reaction equation
[NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.N([C:10]1[N:19]=[C:18]2[C:13]([C:14](=[O:33])[C:15]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:16][N:17]2[C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])=[CH:12][C:11]=1[F:34])=[N+]=[N-].C(OCC)(=O)C.Cl>C(O)C.CN(C)C=O.C(OCC)C.O>[F:27][C:21]1[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=1[N:17]1[C:18]2[C:13](=[CH:12][C:11]([F:34])=[C:10]([N:1]3[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]3)[N:19]=2)[C:14](=[O:33])[C:15]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[CH:16]1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 4837PiperazineHCID 8857Ethyl AcetateHCID 13849345Ethyl 7-azido-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate

Product 1

HCID 13849334Ethyl 1-(2,4-difluorophenyl)-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxylateYield 84%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

In a mixture of 4.5 ml of ethanol and 4.5 ml of N,N-dimethylformamide was dissolved 400 mg of anhydrous piperazine, and 450 mg of ethyl 7-azido-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate was added to the resulting solution, after which the resulting mixture was subjected to reaction at 80° C. for 1 hour. The solvent was removed by distillation under reduced pressure, and to the residue thus obtained were added 30 ml of ethyl acetate and 30 ml of water, after which the pH thereof was adjusted to 1.0 with 2N hydrochloric acid. The aqueous layer was separated, and 15 ml of chloroform was added to the aqueous layer, after which the pH thereof was adjusted to 8.5 with 1N aqueous sodium hydroxide solution. The organic layer was separated, washed successively with 10 ml of water and 10 ml of saturated aqueous sodium chloride solution, and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and to the residue thus obtained was added 5 ml of diethyl ether, after which the crystals thus deposited were collected by filtration to obtain 420 mg (yield 84.0%) of ethyl 1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthyridine-3-carboxylate. The physical properties of this compound were identical with those of the compound obtained in Example 65.

Workup

  1. additionwas added to the resulting solution
  2. customafter which the resulting mixture was subjected to reaction at 80° C. for 1 hour
  3. customThe solvent was removed by distillation under reduced pressure
  4. customto the residue thus obtained
  5. customThe aqueous layer was separated
  6. addition15 ml of chloroform was added to the aqueous layer
  7. customThe organic layer was separated
  8. washwashed successively with 10 ml of water and 10 ml of saturated aqueous sodium chloride solution
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customThe solvent was removed by distillation under reduced pressure
  11. customto the residue thus obtained
  12. filtrationafter which the crystals thus deposited were collected by filtration

Sources & evidence

ORD record
ord-af0641548a274c819001e0b7fb1632b5
Source dataset
uspto-grants-1987_11
Patent number
US04704459

Reaction notes

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