反应详情

温度

60 °C

A solution of 3,6-dichloro-4-isopropyl pyridazine (7) (5.54 g, 29.0 mmol) in tetrahydrofuran (116 mL) in a 500 mL round bottom flask (caution: use an extra large flask) was treated with (4-amino-2,6-dichloro-phenyl)-acetonitrile (44) (5.81 g, 28.9 mmol). The reaction mixture was equipped with a cold water condenser and heated to 60° C. The flask was then raised out of the oil bath and potassium tert-butoxide (6.85 g, 57.99 mmol) was added. The mixture was heated to 60° C. for 45 min. The reaction was cooled to room temperature, transferred to a separatory funnel, diluted with ethyl acetate (500 mL) and was washed with a saturated aqueous sodium chloride solution (2×250 mL). The organic layer was separated, dried with magnesium sulfate, and was filtered. Silica gel 60 (70-230 mesh) was added to the filtrate and the solvent was concentrated under vacuum. The resulting mixture was purified by flash chromatography (Biotage 75L) using silica gel eluted with 15%-30% ethyl acetate in hexanes. The desired fractions were collected and concentrated under vacuum to afford a solid which was dried under high vacuum to afford (4-amino-2,6-dichloro-phenyl)-(6-chloro-5-isopropyl-pyridazin-3-yl)-acetonitrile (45) (7.87 g, 77%) as an orange foam; LRMS for C15H13Cl3N4 (M+H) m/z=355. This compound was used without further purification. Molecular Weight=355.6567; Exact Mass=354.0206

1. customThe reaction mixture was equipped with a cold water condenser
2. additionwas added
3. temperatureThe mixture was heated to 60° C. for 45 min
4. temperatureThe reaction was cooled to room temperature
5. customtransferred to a separatory funnel
6. washwas washed with a saturated aqueous sodium chloride solution (2×250 mL)
7. customThe organic layer was separated
8. dry with materialdried with magnesium sulfate
9. filtrationwas filtered
10. additionSilica gel 60 (70-230 mesh) was added to the filtrate
11. concentrationthe solvent was concentrated under vacuum
12. customThe resulting mixture was purified by flash chromatography (Biotage 75L)
13. washeluted with 15%-30% ethyl acetate in hexanes
14. customThe desired fractions were collected
15. concentrationconcentrated under vacuum
16. customto afford a solid which
17. customwas dried under high vacuum