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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence