反应详情

温度

-30 °C

In a 100 mL round-bottomed flask, ethyl 6-(6-(2,4-difluorophenyl)imidazo[2,1-b]oxazol-5-yl)-[1,2,4]triazolo[4,3-b]pyridazine-3-carboxylate (2.00 g, 4.87 mmol, Example #37, Step D) was suspended in THF (30 mL) and cooled to about −30° C. Methylmagnesium chloride (3.0 M in THF, 6.50 mL, 19.5 mmol) was added over about 10 min to the suspension. The mixture was stirred for about 25 min at about −30° C., followed by slow addition of a saturated solution of ammonium chloride (15 mL). The suspension was diluted with the addition of water (20 mL) and then DCM (20 mL). The layers were separated and the aqueous layer was extracted DCM (2×50 mL). The combined organic extracts were washed with water and brine, dried over MgSO4, filtered, and the solvents were removed under reduced pressure to give a solid that was triturated with Et2O (15 mL) and collected by vacuum filtration as a powder (1.50 g, 81%): LC/MS (Table 1, Method g) Rt=2.06 min; MS m/z: 380.9 (M+H)+.

1. customThe layers were separated
2. extractionthe aqueous layer was extracted DCM (2×50 mL)
3. washThe combined organic extracts were washed with water and brine
4. dry with materialdried over MgSO4
5. filtrationfiltered
6. customthe solvents were removed under reduced pressure
7. customto give a solid
8. customthat was triturated with Et2O (15 mL)
9. filtrationcollected by vacuum filtration as a powder (1.50 g, 81%)