Methyl iodide → 7-(4-chlorophenyl)-2-((2-(methoxymethyl)-6-(trifluoromethyl)pyridin-3-yl)methyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

HRID 2101340Notes

Reaction equation

HRID 2101340 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:30])[N:15]([CH2:17][C:18]4[C:19]([CH2:28][OH:29])=[N:20][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:22][CH:23]=4)[N:16]=[C:10]3[C:9]=2[C:31]2[CH:36]=[CH:35][N:34]=[CH:33][CH:32]=2)=[CH:4][CH:3]=1.[H-].[Na+].I[CH3:40]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][N:11]3[C:14](=[O:30])[N:15]([CH2:17][C:18]4[C:19]([CH2:28][O:29][CH3:40])=[N:20][C:21]([C:24]([F:26])([F:27])[F:25])=[CH:22][CH:23]=4)[N:16]=[C:10]3[C:9]=2[C:31]2[CH:32]=[CH:33][N:34]=[CH:35][CH:36]=2)=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 160048747-(4-chlorophenyl)-2-((2-(hydroxymethyl)-6-(trifluoromethyl)pyridin-3-yl)methyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

Product 1

HCID 160048757-(4-chlorophenyl)-2-((2-(methoxymethyl)-6-(trifluoromethyl)pyridin-3-yl)methyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-oneYield 45.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 7-(4-chlorophenyl)-2-((2-(hydroxymethyl)-6-(trifluoromethyl)pyridin-3-yl)methyl)-8-(pyridin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (26 mg, 0.05 mmol) in anhydrous DMF (0.5 mL) cooled at 0° C. was added sodium hydride (60% in oil, 4.0 mg, 0.1 mmol). The resulting mixture was stirred at 0° C. for 30 min, then iodomethane (20 μL, 0.25 mmol) was added. The reaction mixture was stirred at 0° C. for 30 min, then quenched by addition of water. The mixture was extracted with EtOAc (10 mL×2), and the combined EtOAc extracts were washed with saturated aqueous NaCl, dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified using a silica gel cartridge (4 g) eluted with a gradient of ethyl acetate (50-100%) in hexanes to afford 12 mg of the title compound as a yellow foam. HPLC/MS: retention time=2.93 min, [M+H]+=526.1.

Workup

  1. stirringThe reaction mixture was stirred at 0° C. for 30 min
  2. customquenched by addition of water
  3. extractionThe mixture was extracted with EtOAc (10 mL×2)
  4. washthe combined EtOAc extracts were washed with saturated aqueous NaCl
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified
  8. washeluted with a gradient of ethyl acetate (50-100%) in hexanes

Sources & evidence

ORD record
ord-a4c6d1f5d3aa4133907a5f1d184509c5
Source dataset
uspto-grants-2009_08
Patent number
US07572808B2

Reaction notes

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