反应详情

温度

150 °C

6-chloro-N-(2-(4-fluorophenyl)-2-methylpropyl)pyridazin-3-amine (300 mg, 1.1 mmol, 1.0 equiv) and dioxane (5 mL) were added to a microwave vial and sonication was applied until the mixture was homogeneous. Tributyl(1-ethoxyvinyl)stannane (475 μL, 1.4 mmol, 1.3 equiv) and trans-dichlorobis(triphenylphosphine)palladium (30 mg, 0.04 mmol, 0.03 equiv) were then added, and the reaction was heated in a microwave reactor at 150° C. for 20 min. The reaction was concentrated, dissolved in EtOAc (25 mL), and mixed with 2.0 M potassium fluoride (5 mL). The mixture was filtered through celite, and then washed with water, dried over Na2SO4, filtered, and concentrated. The crude solid was redissolved in 50% THF/water (4 mL), followed by the addition of NBS (300 mg, 1.7 mmol, 1.5 equiv). The reaction mixture was stirred for 1 h and then diluted with brine (20 mL) and ethyl acetate (20 mL). After transferring to a separatory funnel and shaking, the organic layer was separated from the aqueous layer. The organic layer was then dried over Na2SO4, filtered, and concentrated to give a brown oil that was purified by silica gel chromatography (0-100% EtOAC/hexanes) to afford 270 mg of 2-bromo-1-(6-(2-(4-fluorophenyl)-2-methylpropylamino)pyridazin-3-yl)ethanone as an orange oil.

1. customsonication
2. concentrationThe reaction was concentrated
3. dissolutiondissolved in EtOAc (25 mL)
4. additionmixed with 2.0 M potassium fluoride (5 mL)
5. filtrationThe mixture was filtered through celite
6. washwashed with water
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. dissolutionThe crude solid was redissolved in 50% THF/water (4 mL)
11. customAfter transferring to a separatory funnel
12. stirringshaking
13. customthe organic layer was separated from the aqueous layer
14. dry with materialThe organic layer was then dried over Na2SO4
15. filtrationfiltered
16. concentrationconcentrated
17. customto give a brown oil that
18. customwas purified by silica gel chromatography (0-100% EtOAC/hexanes)