Potassium Carbonate → 7-(4-chlorophenyl)-2-((2-methoxy-6-(trifluoromethyl)pyridin-3-yl)methyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

HRID 2101325Notes

Reaction equation

HRID 2101325 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]3[C:14](=[O:17])[NH:15][N:16]=[C:10]3[C:9]=2[C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[CH:4][CH:3]=1.Cl[CH2:25][C:26]1[C:27]([O:36][CH3:37])=[N:28][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:30][CH:31]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]3[C:14](=[O:17])[N:15]([CH2:25][C:26]4[C:27]([O:36][CH3:37])=[N:28][C:29]([C:32]([F:35])([F:33])[F:34])=[CH:30][CH:31]=4)[N:16]=[C:10]3[C:9]=2[C:18]2[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 577993927-(4-chlorophenyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one2×HCID 598348193-(Chloromethyl)-2-methoxy-6-(trifluoromethyl)pyridine

Product 1

HCID 160048077-(4-chlorophenyl)-2-((2-methoxy-6-(trifluoromethyl)pyridin-3-yl)methyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-oneYield 82.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of 7-(4-chlorophenyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (161.4 mg, 0.50 mmol) and 3-(chloromethyl)-2-methoxy-6-(trifluoromethyl)pyridine (169 mg, 0.75 mmol) in anhydrous DMF (3.0 mL) at room temperature was added anhydrous K2CO3 (138 mg, 1.0 mmol). The resulting yellow suspension was stirred at 70° C. for 3 h. Analysis by HPLC/MS indicated that starting 7-(4-chlorophenyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one had been consumed. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EtOAc (20 mL×2). The combined EtOAc extracts were washed with water, then saturated aqueous NaCl, dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified using a silica gel cartridge (12 g) eluted with a gradient of ethyl acetate (30-100%) in hexanes to afford 210 mg (82%) of the title compound as a yellow solid. HPLC/MS: retention time=3.11 min, [M+H]+=512.2.

Workup

  1. customhad been consumed
  2. temperatureAfter cooling to room temperature
  3. additionthe reaction mixture was diluted with water
  4. extractionextracted with EtOAc (20 mL×2)
  5. washThe combined EtOAc extracts were washed with water
  6. dry with materialsaturated aqueous NaCl, dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified
  10. washeluted with a gradient of ethyl acetate (30-100%) in hexanes

Sources & evidence

ORD record
ord-150fe015970d45b7a4f20ff953113fe8
Source dataset
uspto-grants-2009_08
Patent number
US07572808B2

Reaction notes

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