4-苄基哌嗪-2-酮

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-benzylpiperazin-2-one (0.56 g, 2.95 mmol) in DMF (10 mL) was added 60% sodium hydride (0.12 g, 2.95 mmol), and this solution was stirred at room temperature for 30 minutes. 2-(4-chloromethylphenoxy)-5-nitropyridine (0.78 g, 2.95 mmol) was added to the reaction mixture, and the mixture was stirred for 1 hour at room temperature. To this mixture was added brine (50 mL), and extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The remaining oil was dissolved in ethyl acetate (5 mL), and to the resulting solution was added iron powder (0.33 g, 5.89 mmol). This solution was stirred for 2 hours at room temperature. The resulting reaction solution was concentrated under reduced pressure, and a saturated sodium bicarbonate solution (50 mL) was added to the residue. The obtained mixture was extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated. The remaining oil was dissolved in THF (10 mL). To the resulting solution were added triethylamine (0.21 mL, 1.47 mmol) and 3,4-dichlorobenzoyl chloride (0.31 mL, 1.47 mmol), and this solution was stirred at room temperature for 2 hours. A saturated sodium bicarbonate solution (50 mL) was added to the solution, and extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=40:1). The obtained oil was dissolved in ethyl acetate (5 mL), and to the resulting solution was added a solution of 4 N hydrogen chloride in ethyl acetate (1.5 mL, 6 mmol). The formed white powder was collected by suction filtration, to thereby yield 0.045 g of the title compound. the mixture was stirred for 1 hour at room temperature extracted with ethyl acetate (50 mL) The ethyl acetate layer was washed with brine dried over anhydrous magnesium sulfate evaporated under reduced pressure The remaining oil was dissolved in ethyl acetate (5 mL) This solution was stirred for 2 hours at room temperature The resulting reaction solution was concentrated under reduced pressure a saturated sodium bicarbonate solution (50 mL) was added to the residue The obtained mixture was extracted with ethyl acetate (50 mL) The ethyl acetate layer was washed with brine dried over anhydrous sodium sulfate evaporated The remaining oil was dissolved in THF (10 mL) this solution was stirred at room temperature for 2 hours extracted with ethyl acetate (50 mL) The ethyl acetate layer was washed with brine dried over anhydrous magnesium sulfate evaporated under reduced pressure The residue was purified by silica gel column chromatography (chloroform:methanol=40:1) The obtained oil was dissolved in ethyl acetate (5 mL) The formed white powder was collected by suction filtration

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Sodium hydride (50% in oil, 10.4 g., 0.22 mole) is added to a stirred solution of 4-(phenylmethyl)piperazinone (Example 45, 38.0 g., 0.20 mole) in THF (2.0 l.). After 1 hour methyl iodide (80.0 g., 0.75 mole) is added and the reaction solution is refluxed for 2.5 hours. The THF is removed under reduced pressure and the residual oil is partitioned between chloroform and water. Evaporation of the chloroform gives an oil which is chromatographed on silica gel to give the title compound, which is converted to the p-ISA salt, m.p. 138°-140°. the reaction solution is refluxed for 2.5 hours The THF is removed under reduced pressure the residual oil is partitioned between chloroform and water Evaporation of the chloroform gives an oil which is chromatographed on silica gel

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Sodium hydride (50% in oil, 10.4 g., 0.22 mole) is added to a stirred solution of 4-(phenylmethyl)piperazinone (Example 45, 38.0 g., 0.20 mole) in THF (2.0 l.). After 1 hour methyl iodide (80.0 g., 0.75 mole) is added and the reaction solution is refluxed for 2.5 hours. The THF is removed under reduced pressure and the residual oil is partitioned between chloroform and water. Evaporation of the chloroform gives an oil which is chromatographed on silica gel to give the title compound, which is converted to the p-ISA salt, m.p. 138°-140°. the reaction solution is refluxed for 2.5 hours The THF is removed under reduced pressure the residual oil is partitioned between chloroform and water Evaporation of the chloroform gives an oil which is chromatographed on silica gel

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of ethyl chloroacetate (204 g., 1.67 mole) in ethanol (500 ml.) is added to a stirred solution of ethylenediamine (600 g., 10 mole) in ethanol (3 l.) at 0°. After addition is complete the solution is allowed to warm to 20°-25°. After 5 hours a solution of sodium methoxide (90.0 g., 1.67 mole) in methanol (200 ml.) is added and the solution is stirred overnight, filtered to remove inorganic salts and evaporated to remove solvent and unreacted ethylenediamine. The residual oil (189 g.) is added to a mixture of benzyl chloride (241 g., 1.9 mole) anhydrous sodium carbonate (191 g., 2.28 mole) in ethanol (2.3 l.) and the solution is stirred under reflux for 3 hours. The ethanol is removed under reduced pressure and the residue is partitioned between chloroform and water. Evaporation of the chloroform gave a crystalline product which was recrystallized from ethyl acetate to give the title compound, m.p. 154°- 156°. After addition to warm to 20°-25° filtered to remove inorganic salts evaporated to remove solvent and unreacted ethylenediamine the solution is stirred under reflux for 3 hours The ethanol is removed under reduced pressure the residue is partitioned between chloroform and water Evaporation of the chloroform gave a crystalline product which was recrystallized from ethyl acetate

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:220.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a 25 mL microwave vessel was added 4-bromobenzene (6.1 g, 39.0 mmol), 4-benzylpiperazin-2-one (5.0 g, 36.3 mmol), potassium carbonate (3.6 g, 26.3 mmol), and copper(I) iodide (500 mg, 2.6 mmol). The reaction vessel was sealed and purged with nitrogen. Anhydrous NMP (8.0 mL) was added via syringe. The vessel was heated via microwave at 220° C. for 40 minutes. The mixture was filtered through a bed of celite followed by CH2Cl2 (20 mL). The filtrate was purified via silica gel chromatography using 2% MeOH in CH2Cl2 to obtain the desired piperazinone as a white solid (3.4 g, 12.7 mmol, 50% yield). 1H NMR (400 MHz, CDCl3) δ 7.42-7.24 (m, 10H), 3.69 (t, J=5.4 Hz, 1H), 3.63 (s, 1H), 3.40-3.31 (m, 2H), 2.84 (s, 1H), 2.81 (t, J=5.2 Hz, 1H). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=267.3; tR=1.63 min. The reaction vessel was sealed purged with nitrogen Anhydrous NMP (8.0 mL) was added via syringe The mixture was filtered through a bed of celite The filtrate was purified via silica gel chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Sodium hydride (50% in oil, 10.4 g., 0.22 mole) is added to a stirred solution of 4-(phenylmethyl)piperazinone (Example 45, 38.0 g., 0.20 mole) in THF (2.0 l.). After 1 hour methyl iodide (80.0 g., 0.75 mole) is added and the reaction solution is refluxed for 2.5 hours. The THF is removed under reduced pressure and the residual oil is partitioned between chloroform and water. Evaporation of the chloroform gives an oil which is chromatographed on silica gel to give the title compound, which is converted to the p-TSA salt, m.p. 138°-140°. the reaction solution is refluxed for 2.5 hours The THF is removed under reduced pressure the residual oil is partitioned between chloroform and water Evaporation of the chloroform gives an oil which is chromatographed on silica gel

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of ethyl chloroacetate (204 g., 1.67 mole) in ethanol (500 ml.) is added to a stirred solution of ethylenediamine (600 g., 10 mole) in ethanol (3 l.) at 0°. After addition is complete the solution is allowed to warm to 20°-25°. After 5 hours a solution of sodium methoxide (90.0 g., 1.67 mole) in methanol (200 ml.) is added and the solution is stirred overnight, filtered to remove inorganic salts and evaporated to remove solvent and unreacted ethylenediamine. The residual oil (189 g.) is added to a mixture of benzyl chloride (241 g., 1.9 mole) anhydrous sodium carbonate (191 g., 2.28 mole) in ethanol (2.3 l.) and the solution is stirred under reflux for 3 hours. The ethanol is removed under reduced pressure and the residue is partitioned between chloroform and water. Evaporation of the chloroform gave a crystalline product which was recrystallized from ethyl acetate to give the title compound, m.p. 154°- 156°. After addition to warm to 20°-25° filtered to remove inorganic salts evaporated to remove solvent and unreacted ethylenediamine the solution is stirred under reflux for 3 hours The ethanol is removed under reduced pressure the residue is partitioned between chloroform and water Evaporation of the chloroform gave a crystalline product which was recrystallized from ethyl acetate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 4-benzylpiperazin-2-one (0.56 g, 2.95 mmol) in DMF (10 mL) was added 60% sodium hydride (0.12 g, 2.95 mmol), and this solution was stirred at room temperature for 30 minutes. 2-(4-chloromethylphenoxy)-5-nitropyridine (0.78 g, 2.95 mmol) was added to the reaction mixture, and the mixture was stirred for 1 hour at room temperature. To this mixture was added brine (50 mL), and extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The remaining oil was dissolved in ethyl acetate (5 mL), and to the resulting solution was added iron powder (0.33 g, 5.89 mmol). This solution was stirred for 2 hours at room temperature. The resulting reaction solution was concentrated under reduced pressure, and a saturated sodium bicarbonate solution (50 mL) was added to the residue. The obtained mixture was extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated. The remaining oil was dissolved in THF (10 mL). To the resulting solution were added triethylamine (0.21 mL, 1.47 mmol) and 3,4-dichlorobenzoyl chloride (0.31 mL, 1.47 mmol), and this solution was stirred at room temperature for 2 hours. A saturated sodium bicarbonate solution (50 mL) was added to the solution, and extracted with ethyl acetate (50 mL). The ethyl acetate layer was washed with brine, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=40:1). The obtained oil was dissolved in ethyl acetate (5 mL), and to the resulting solution was added a solution of 4 N hydrogen chloride in ethyl acetate (1.5 mL, 6 mmol). The formed white powder was collected by suction filtration, to thereby yield 0.045 g of the title compound. the mixture was stirred for 1 hour at room temperature extracted with ethyl acetate (50 mL) The ethyl acetate layer was washed with brine dried over anhydrous magnesium sulfate evaporated under reduced pressure The remaining oil was dissolved in ethyl acetate (5 mL) This solution was stirred for 2 hours at room temperature The resulting reaction solution was concentrated under reduced pressure a saturated sodium bicarbonate solution (50 mL) was added to the residue The obtained mixture was extracted with ethyl acetate (50 mL) The ethyl acetate layer was washed with brine dried over anhydrous sodium sulfate evaporated The remaining oil was dissolved in THF (10 mL) this solution was stirred at room temperature for 2 hours extracted with ethyl acetate (50 mL) The ethyl acetate layer was washed with brine dried over anhydrous magnesium sulfate evaporated under reduced pressure The residue was purified by silica gel column chromatography (chloroform:methanol=40:1) The obtained oil was dissolved in ethyl acetate (5 mL) The formed white powder was collected by suction filtration