1,2-Dibromoethane → 2-(2-bromoethyl)-6-(4-(trifluoromethoxy)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

HRID 2368024Notes

Reaction equation

HRID 2368024 reaction equation
[F:1][C:2]([F:21])([F:20])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:11]=[CH:12][C:13]3[N:14]([C:16](=[O:19])[NH:17][N:18]=3)[CH:15]=2)=[CH:6][CH:5]=1.[Br:22][CH2:23][CH2:24]Br>CN(C=O)C.O>[Br:22][CH2:23][CH2:24][N:17]1[C:16](=[O:19])[N:14]2[CH:15]=[C:10]([C:7]3[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:20])[F:21])=[CH:9][CH:8]=3)[CH:11]=[CH:12][C:13]2=[N:18]1

Participants

5

Reactant 2

HCID 78391,2-DibromoethaneHCID 58044589HCID 58044589, compound

Product 1

HCID 580446052-(2-bromoethyl)-6-(4-(trifluoromethoxy)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
95 °C

Procedure

6-(4-(trifluoromethoxy)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (synthesized according to Example 1, 500 mg, 1.69 mmol) was dissolved in 5 ml DMF and 1,2 dibromoethane (1.0 mL, 11.8 mmol) was added. The reaction was heated to 95° C. overnight. The reaction was cooled, diluted with water/EtOAC and the layers were separated. The organic layer was washed with NaHCO3. The organics were dried (MgSO4), filtered, concentrated and purified by flash chromatography (Rf=0.46, 1:1 hexanes:EtOAc) to afford 2-(2-bromoethyl)-6-(4-(trifluoromethoxy)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one. To a solution of 2-(2-bromoethyl)-6-(4-(trifluoromethoxy)phenyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (50 mg, 0.124 mmol) in 1 mL DMF was added K2CO3 (51 mg, 0.372 mmol) and 4-phenyl-1H-imidazole (36 mg, 0.249 mmol) and the reaction was heated to 85° C. for 24-72 hours until the SM was consumed. The reaction was concentrated and purified by reverse phase HPLC to afford compound 100 (24 mg, 41%). GS-490257. C24H18F3N5O2, m/z (ESI)=466.2 [M+H]+.

Workup

  1. temperatureThe reaction was cooled
  2. customthe layers were separated
  3. washThe organic layer was washed with NaHCO3
  4. dry with materialThe organics were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by flash chromatography (Rf=0.46, 1:1 hexanes:EtOAc)

Sources & evidence

ORD record
ord-5e912fbd23b046249414ac0a299207f3
Source dataset
uspto-grants-2014_04
Patent number
US08703759B2

Reaction notes

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