1,2-Dichloroethane → Ethyl 7-chloro-1-(2,4-difluoro-5-methylaminophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate

HRID 1415936Notes

Reaction equation

HRID 1415936 reaction equation
[NH2:1][C:2]1[C:3]([F:27])=[CH:4][C:5]([F:26])=[C:6]([N:8]2[C:17]3[C:12](=[CH:13][C:14]([F:19])=[C:15]([Cl:18])[N:16]=3)[C:11](=[O:20])[C:10]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:9]2)[CH:7]=1.Cl[CH2:29]CCl.CO.C=O>[Pd].C(O)(=O)C>[Cl:18][C:15]1[N:16]=[C:17]2[C:12]([C:11](=[O:20])[C:10]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[CH:9][N:8]2[C:6]2[CH:7]=[C:2]([NH:1][CH3:29])[C:3]([F:27])=[CH:4][C:5]=2[F:26])=[CH:13][C:14]=1[F:19]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 712FormaldehydeHCID 887MethanolHCID 53833255Ethyl 1-(3-amino-4,6-difluorophenyl)-7-chloro-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate

Product 1

HCID 54102467Ethyl 7-chloro-1-(2,4-difluoro-5-methylaminophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolvent

Procedure

Ethyl 1-(5-amino-2,4-difluorophenyl)-7-chloro-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate (500 mg) was added to a mixture of 10 ml of 1,2-dichloroethane, 5 ml of methanol and 0.5 ml of acetic acid together with 100 mg of 37% formalin. Using 0.08 g of 10% palladium on carbon, hydrogenation was carried out for 16 hours. After the catalyst was filtered off, the filtrate was concentrated in vacua. The residue was dissolved in 50 ml of chloroform, washed with an aqueous solution of 50% sodium carbonate, dried over anhydrous magnesium sulfate, and then concentrated in vacua. The residue was subject to chromatography using 20 g of silica gel (eluting solution: chloroform) to give 150 mg of the title compound.

Workup

  1. filtrationAfter the catalyst was filtered off
  2. concentrationthe filtrate was concentrated in vacua
  3. dissolutionThe residue was dissolved in 50 ml of chloroform
  4. washwashed with an aqueous solution of 50% sodium carbonate
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacua

Sources & evidence

ORD record
ord-4039d01e4f784e4caa8c82d93150cfef
Source dataset
uspto-grants-1999_06
Patent number
US05910498

Reaction notes

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