反应详情

温度

90 °C

To a round bottom flask was added 6-((2,4-difluorophenyl)ethynyl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine (19.5 g, 65.4 mmol, Preparation #J.1) and concentrated H2SO4 (145 mL, 1630 mmol). The reaction mixture was heated to about 90° C. for about 15 min. The reaction mixture was diluted with ice water (1000 mL) and partitioned with DCM (500 mL). The aqueous layer was neutralized with 50% aqueous NaOH (about 350 mL) to about pH 7. The organic layer was isolated and the aqueous layer was extracted with DCM (3×500 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo to give 19.5 g of crude material. The crude material was purified by silica gel chromatography using EtOAc/acetone (gradient, 1:0 to 0:1) to give title compound (17.1 g, 83%) as a brown solid. LC/MS (Table 1, Method a) Rt=2.41 min; MS m/z: 317.2 (M+H)+.

1. custompartitioned with DCM (500 mL)
2. customThe organic layer was isolated
3. extractionthe aqueous layer was extracted with DCM (3×500 mL)
4. dry with materialThe combined organic extracts were dried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customto give 19.5 g of crude material
8. customThe crude material was purified by silica gel chromatography