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 → HCID 178517477, compound

HRID 2101326Notes

Reaction equation

HRID 2101326 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]([O:28]C)=[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>Br>[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]([OH:28])=[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

3

Reactant 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)-one

Product 1

HCID 178517477HCID 178517477, compound

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Conditions

Temperature
85 °C

Procedure

To aqueous HBr solution (48%, 10 mL) was added 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 (210 mg, 0.41 mmol). The resulting solution was stirred at 85° C. for 4 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure to remove most of the solvent. The remaining liquid was stirred at 0° C., and neutralized to pH 7-8 by careful addition of 1.0 N aqueous NaOH. Yellow precipitate formed, and this was collected by filtration, washed with water (20 mL×2), and dried in a vacuum oven at 45° C. for 16 h to afford 200 mg (93% pure) of the title compound as a yellow solid. The product was purified by preparative reverse phase HPLC (Phenomenex Luna 5 μm C-18 21.2×100 mm column eluted with a linear gradient of 50% to 90% B over 18 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 product was dissolved in acetonitrile, frozen and lyophilized to afford 150 mg (74%) of the title compound as a light yellow powder. HPLC/MS: retention time=2.50 min, [M+H]+=498.2.

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. customto remove most of the solvent
  4. stirringThe remaining liquid was stirred at 0° C.
  5. additionneutralized to pH 7-8 by careful addition of 1.0 N aqueous NaOH
  6. customYellow precipitate formed
  7. filtrationthis was collected by filtration
  8. washwashed with water (20 mL×2)
  9. customdried in a vacuum oven at 45° C. for 16 h

Sources & evidence

ORD record
ord-850b409687754b978315843eb9449951
Source dataset
uspto-grants-2009_08
Patent number
US07572808B2

Reaction notes

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