反应详情

To a solution of 7,8-bis(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (100 mg, 0.28 mmol), prepared as described in Example 1, Ph3P (220 mg, 0.84 mmol) and (5-trifluoromethyl-pyridin-2-yl)methanol (50 mg, 0.28 mmol) in THF (2.0 mL) was added 40 wt % diethyl azodicarboxylate (DEAD) solution in toluene (0.33 mL, 0.84 mmol) at RT under argon. The reaction was stirred at RT for 30 min. Water (5.0 mL) was then added and the resulting mixture was extracted with EtOAc (3×5 mL). The combined organic layers were washed with water (2×5 mL) followed by saturated aqueous NaCl (2×5 mL). The combined organic layers were concentrated under reduced pressure to obtain the crude product. This crude product was purified using reverse phase preparative HPLC to give the title compound 7,8-bis(4-chlorophenyl)-2-((5-(trifluoromethyl)pyridin-2-yl)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (69.2 mg, 48%) as a yellow solid. MS (M+H)=516; 1H NMR (CDCl3): δ 8.83 (1H, s), 8.20 (1H, s), 7.93 (1H, d, J=8.2 Hz), 7.40 (1H, d, J=10.0 Hz), 7.26-7.34 (6H, m), 7.11 (2H, d, J=10.0 Hz), 5.47 (2H, s).

1. extractionthe resulting mixture was extracted with EtOAc (3×5 mL)
2. washThe combined organic layers were washed with water (2×5 mL)
3. concentrationThe combined organic layers were concentrated under reduced pressure
4. customto obtain the crude product
5. customThis crude product was purified