Pyridine → 3-(2,4-Difluorophenyl)-4-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-1,2,5-oxadiazole

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Reaction Conditions

Reaction Steps

A 50 mL round bottomed flask was charged with 1-(2,4-difluorophenyl)-2-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)ethane-1,2-dione (0.300 g, 0.908 mmol, Preparation #M.1), hydroxylamine hydrochloride (0.631 g, 9.08 mmol) and EtOH (5 mL). The resulting mixture was treated with pyridine (3.67 mL, 45.4 mmol) and was then heated to about 90° C. for about 7 h. The mixture was cooled to ambient temperature, diluted with EtOAc (10 mL), washed with 1N HCl (10 mL) and water (10 mL). The organics were separated, dried over MgSO4, filtered and concentrated in vacuo to afford a yellow residue. To the residue was added triphenylphosphine (0.328 g, 1.25 mmol) and toluene (5 mL). The mixture was cooled to about 0° C. and DIAD (0.243 mL, 1.25 mmol) was added to give a solution which was heated to about reflux for about 1 h. The solution was cooled to ambient temperature, diluted with EtOAc (10 mL) and washed with saturated aqueous NaHCO3 (10 mL). The organics were separated, dried over MgSO4, filtered and concentrated to dryness. The residue was purified by flash chromatography on silica gel with MeOH/DCM (0-5% gradient) followed by RP-HPLC (Table 1, Method n) to afford the title compound (0.056 g, 20%) as a yellow solid. LC/MS (Table 1, Method g) Rt=2.83 min; MS m/z 343 (M+H)+.

Provenance & Evidence