反应详情

温度

120 °C

A vial containing 2-(4-iodo-6-oxo-6H-pyridazin-1-yl)-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide (Intermediate 94, 51.5 mg, 0.10 mmol), potassium carbonate (23.5 mg, 0.170 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (6.9 mg, 0.01 mmol), and palladium (II) acetate (2.7 mg, 0.0120 mmol) was evacuated, charged with a nitrogen atmosphere, and treated with toluene (1 mL) and 2-chloroaniline (12.6 μL, 0.12 mmol). The vial was sealed, and the reaction was warmed to 120° C., where it stirred for 3.5 h, followed by stirring at 25° C. overnight. At this point, the reaction was partitioned between ethyl acetate (5 mL) and water (5 mL). The organic layer was washed with a 10% aqueous ammonium chloride solution (5 mL) and a saturated aqueous sodium chloride solution (5 mL). The organics were dried over sodium sulfate, filtered, and concentrated in vacuo onto silica gel. Chromatography (20-90% ethyl acetate/hexanes) afforded 2-[4-(2-chloro-phenylamino)-6-oxo-6H-pyridazin-1-yl]-4-methyl-pentanoic acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-1H-pyrazol-3-yl]-amide as a white/yellow solid (41.2 mg, 80%).

1. customwas evacuated
2. additioncharged with a nitrogen atmosphere
3. customThe vial was sealed
4. stirringby stirring at 25° C. overnight
5. customAt this point, the reaction was partitioned between ethyl acetate (5 mL) and water (5 mL)
6. washThe organic layer was washed with a 10% aqueous ammonium chloride solution (5 mL)
7. dry with materialThe organics were dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo onto silica gel