2,2,2-Trifluoroethanol → HCID 10113164, compound

HRID 2215045Notes

Reaction equation

HRID 2215045 reaction equation
[CH2:1]([OH:6])[C:2]([F:5])([F:4])[F:3].[H-].[Na+].[NH:9]([C:16]1[N:17]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:18]2[C:23]([C:24](=[O:26])[CH:25]=1)=[C:22](Cl)[N:21]=[C:20]([CH3:28])[CH:19]=2)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>CS(C)=O>[NH:9]([C:16]1[N:17]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:18]2[C:23]([C:24](=[O:26])[CH:25]=1)=[C:22]([O:6][CH2:1][C:2]([F:5])([F:4])[F:3])[N:21]=[C:20]([CH3:28])[CH:19]=2)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 24758Sodium hydrideHCID 10269984HCID 10269984, compound

Product 1

HCID 10113164HCID 10113164, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Conditions

Temperature
60 °C

Procedure

Trifluoroethanol (0.08 mL, 1.1 mmol) was added to a suspension of NaH (60% oil dispersion, 44 mg, 1.1 mmol) in DMSO (4 mL) at 0° C., and the mixture was heated at 60° C. for 1 h. The mixture was cooled to room temperature and a solution of 2-anilino-5-chloro-7-methyl-1-phenyl-1,6-naphthyridin-4(1H)-one (200 mg, 0.55 mmol) in DMSO (2 mL) was added. The resulting mixture was stirred at 50° C. for 16 h. The reaction mixture was cooled, poured into ice water and extracted with CH2Cl2. The organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by a Biotage silica gel chromatography (2:1 EtOAc:Hex) to provide 2-anilino-7-methyl-1-phenyl-5-(2,2,2-trifluoroethoxy)-1,6-naphthyridin-4(1H)-one (159 mg, 68%): LCMS RT: 2.65 min, MH+: 426.4. This transformation can be accomplished by using other aprotic solvents such as DMF, THF and dioxane with temperatures appropriate for these solvents. Commercially available alkoxides can also be used in the absence of base.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. temperatureThe reaction mixture was cooled
  3. extractionextracted with CH2Cl2
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by a Biotage silica gel chromatography (2:1 EtOAc:Hex)

Sources & evidence

ORD record
ord-4bd79bf17fb64b11b949f1f91ab7d605
Source dataset
uspto-grants-2006_09
Patent number
US07109196B2

Reaction notes

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