Ethanol → Ethyl 7-anilino-3-fluoro-5-oxo-8-phenyl-5,8-dihydro-1,8-naphthyridine-2-carboxylate

HRID 1839391Notes

Reaction equation

HRID 1839391 reaction equation
[NH:1]([C:8]1[N:9]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:10]2[C:15]([C:16](=[O:18])[CH:17]=1)=[CH:14][C:13]([F:19])=[C:12](Cl)[N:11]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:27]([O-:30])([O-])=[O:28].[Cs+].[Cs+].[CH3:33][CH2:34]O>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH:1]([C:8]1[N:9]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:10]2[N:11]=[C:12]([C:27]([O:30][CH2:33][CH3:34])=[O:28])[C:13]([F:19])=[CH:14][C:15]=2[C:16](=[O:18])[CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 702EthanolHCID 10796Cesium carbonateHCID 219481862-anilino-7-chloro-6-fluoro-1-phenyl-1,8-naphthyridin-4(1H)-one

Product 1

HCID 21948195Ethyl 7-anilino-3-fluoro-5-oxo-8-phenyl-5,8-dihydro-1,8-naphthyridine-2-carboxylateYield 81%

Reagents, catalysts & solvents 3

HCID 812191,3-Bis(diphenylphosphino)propaneCatalystHCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

2-anilino-7-chloro-6-fluoro-1-phenyl-1,8-naphthyridin-4(1H)-one (200 mg, 0.55 mmol), DPPP (12 mg, 0.030 mmol), Pd(OAc)2 (6.0 mg, 0.028 mmol), and Cs2CO3 (114 mg, 0.42 mmol) was dissolved in a 1:1 mixture of EtOH (3 mL)/DMF (3 mL). A balloon filled with CO was attached to the flask and the solution was stirred vigorously. The solution was saturated with CO by evacuating the flask followed by back filling the flask with CO. This was repeated 3 times before heating the solution to 70° C. After 4 h of stirring all of the starting material had been consumed and the reaction was cooled to room temperature. The solution was diluted with EtOAc and was washed with water. The organic layer was collected, dried over Na2SO4, and concentrated in vacuo. The crude solid was triturated with Et2O, filtered and dried to give ethyl 7-anilino-3-fluoro-5-oxo-8-phenyl-5,8-dihydro-1,8-naphthyridine-2-carboxylate as a light brown solid (900 mg, 81%): LCMS RT: 2.63 min, MH+: 404.4

Workup

  1. additionA balloon filled with CO
  2. customby evacuating the flask
  3. stirringAfter 4 h of stirring all of the starting material
  4. customhad been consumed
  5. temperaturethe reaction was cooled to room temperature
  6. additionThe solution was diluted with EtOAc
  7. washwas washed with water
  8. customThe organic layer was collected
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated in vacuo
  11. customThe crude solid was triturated with Et2O
  12. filtrationfiltered
  13. customdried

Sources & evidence

ORD record
ord-4837f282993d4c10a982af62b0934e73
Source dataset
uspto-grants-2004_01
Patent number
US06677352B1

Reaction notes

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