Sodium hydride → 1-phenyl-1,8-naphthyridin-4(1H)-one

HRID 1063537Notes

Reaction equation

HRID 1063537 reaction equation
[NH:1](/[C:8](/NC(C)C)=[CH:9]\[C:10]([C:12]1[C:13](Cl)=[N:14][C:15](Cl)=[C:16](F)[CH:17]=1)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+]>CN(C=O)C.O>[C:2]1([N:1]2[C:13]3[C:12](=[CH:17][CH:16]=[CH:15][N:14]=3)[C:10](=[O:11])[CH:9]=[CH:8]2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 24758Sodium hydrideHCID 60061202(2Z)-3-anilino-1-(2,6-dichloro-5-fluoro-3-pyridinyl)-3-(isopropylamino)-2-propen-1-one

Product 1

HCID 222789461-phenyl-1,8-naphthyridin-4(1H)-oneYield 86.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

(2Z)-3-Anilino-1-(2,6-dichloro-5-fluoro-3-pyridinyl)-3-(isopropylamino)-2-propen-1-one (40.0 mg, 0.109 mmol) was dissolved in 4 mL of DMF. NaH (8.70 mg, 0.217 mmol, 60% dispersion in oil) was added and the reaction was heated to 85° C. under argon for 2 h. The reaction mixture was cooled to room temperature and diluted with water and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue using Biotage silica gel chromatography eluting with 100% EtOAc to 95:5 EtOAc:MeOH provided 7-chloro-6-fluoro-2-isopropylamino)-1-phenyl-1,8-naphthyridin-4(1H)-one (21 mg, 64%) as a white solid: LCMS RT: 2.57 min, MH+: 332.2.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionthe aqueous layer was extracted with EtOAc
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue
  7. washeluting with 100% EtOAc to 95:5 EtOAc

Sources & evidence

ORD record
ord-2742a6b035694b5ea1c5bbdc9ef1228d
Source dataset
uspto-grants-2005_11
Patent number
US06964971B2

Reaction notes

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