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

HRID 2101327Notes

Reaction equation

HRID 2101327 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:24][C:25]1[C:30]([CH2:31]Cl)=[CH:29][CH:28]=[C:27]([C:33]([F:36])([F:35])[F:34])[N:26]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:24][C:25]1[C:30]([CH2:31][N:15]2[C:14](=[O:17])[N:11]3[CH:12]=[CH:13][C:8]([C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)=[C:9]([C:18]4[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=4)[C:10]3=[N:16]2)=[CH:29][CH:28]=[C:27]([C:33]([F:34])([F:35])[F:36])[N:26]=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 598347962-Chloro-3-(chloromethyl)-6-(trifluoromethyl)pyridine

Product 1

HCID 160048102-((2-chloro-6-(trifluoromethyl)pyridin-3-yl)methyl)-7-(4-chlorophenyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-oneYield 81%

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 (200 mg, 0.62 mmol) and 2-chloro-3-(chloromethyl)-6-(trifluoromethyl)pyridine in anhydrous DMF (4.0 mL) at room temperature was added anhydrous K2CO3 (1.8 g, 13 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 to afford 260 mg (81%) of the title compound as a yellow foam. This product (25 mg) was further purified using preparative reverse phase HPLC (Phenomenex Luna 5 μm C-18 21.2×100 mm column eluted with a linear gradient of 40% to 80% B over 8 min (A=0.1% trifluoroacetic acid, 90% water, 10% methanol and B=0.1% trifluoroacetic acid, 90% methanol, 10% water) with flow rate at 20 mL/min and UV detection at 220 nm). The desired fractions were concentrated under reduced pressure. The residue was dissolved in EtOAc, washed with saturated aqueous NaHCO3 once, water twice, then saturated aqueous NaCl, dried over Na2SO4 and evaporated. The residue was dissolved in acetonitrile, frozen and lyophilized to afford 21 mg of the title compound as a light yellow powder. HPLC/MS: retention time=2.96 min, [M+H]+=516.1.

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

Sources & evidence

ORD record
ord-e4446f73c05e433eba833764dab13f4a
Source dataset
uspto-grants-2009_08
Patent number
US07572808B2

Reaction notes

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