反应详情

温度

-10 °C

In a 500 ml flask, 10.0 g (46.3 mmol) of 5-methyl-3-phenyl-isoxazole-4-carboxylic acid methylamide is suspended in 150 ml of tetrahydrofuran (THF) under argon. At −70° C. a solution of butyl lithium (63 ml, 1.6M in hexane, 101 mmol, 2.2 eq.) is slowly added. After 1 h at this temperature, the solution is warmed to −10° C. and a solution of 11.9 g (55.5 mmol, 1.2 eq.) of 4-(4-methyl-piperazin-1-ylmethyl)-benzonitrile in 80 ml of THF is slowly added. Under warming to room temperature, the red solution is stirred for another hour, then quenched with 2 ml of water and concentrated. The yellow residue is then taken up in 75 ml of dioxane and kept at 5° C. Then, 230 ml of a 4M solution of HCl in dioxane is carefully added and the suspension stirred for 20 h at room temperature. Then, the solvent is removed and the residue dissolved in ethyl acetate and carefully neutralised with sat. NaHCO3-solution. The phases are separated and the organic phases washed with brine, dried over Na2SO4 and concentrated. Chromatographic purification (CH2Cl2/MeOH 95:5 to 90:10) yields 7.9 g (41%) of 5-methyl-6-[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-3-phenyl-5H-isoxazolo[4,5-c]pyridin-4-one as a white solid. Mass spectrum: m/z (M+H)+: 415.0

1. temperatureUnder warming to room temperature
2. customquenched with 2 ml of water
3. concentrationconcentrated
4. customkept at 5° C
5. additionThen, 230 ml of a 4M solution of HCl in dioxane is carefully added
6. stirringthe suspension stirred for 20 h at room temperature
7. customThen, the solvent is removed
8. dissolutionthe residue dissolved in ethyl acetate
9. customThe phases are separated
10. washthe organic phases washed with brine
11. dry with materialdried over Na2SO4
12. concentrationconcentrated
13. customChromatographic purification (CH2Cl2/MeOH 95:5 to 90:10)