1-benzylpiperazin-2-one

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 1-benzylpiperazin-2-one (0.29 g, 1.54 mmol) and diethyl ethoxymethylenemalonate (0.35 g, 1.63 mmol) in toluene was heated in a sealed tube at 80° C. for 4 hours. The resultant mixture was concentrated under vacuum. The residue was dissolved in anhydrous DMF (10 mL), cooled to 0° C. under an atmosphere of nitrogen, and treated with a solution of lithium bis(trimethylsilyl)amide in THF (1 M, 2.0 mL, 2.0 mmol). The reaction mixture was stirred at room temperature overnight and concentrated under vacuum. The residue was partitioned between ethyl acetate and dilute aqueous HCl. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was triturated with diethyl ether, and the solid precipitated was filtered to provide the title compound. The resultant mixture was concentrated under vacuum The residue was dissolved in anhydrous DMF (10 mL) cooled to 0° C. under an atmosphere of nitrogen concentrated under vacuum The residue was partitioned between ethyl acetate and dilute aqueous HCl The organic extract was washed with brine dried over anhydrous magnesium sulfate filtered concentrated under vacuum The residue was triturated with diethyl ether the solid precipitated was filtered

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 1-benzylpiperazin-2-one (0.29 g, 1.54 mmol) and diethyl ethoxymethylenemalonate (0.35 g, 1.63 mmol) in toluene was heated in a sealed tube at 80° C. for 4 hours. The resultant mixture was concentrated under vacuum. The residue was dissolved in anhydrous DMF (10 mL), cooled to 0° C. under an atmosphere of nitrogen, and treated with a solution of lithium bis(trimethylsilyl)amide in THF (1 M, 2.0 mL, 2.0 mmol). The reaction mixture was stirred at room temperature overnight and concentrated under vacuum. The residue was partitioned between ethyl acetate and dilute aqueous HCl. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was triturated with diethyl ether, and the solid precipitated was filtered to provide the title compound. The resultant mixture was concentrated under vacuum The residue was dissolved in anhydrous DMF (10 mL) cooled to 0° C. under an atmosphere of nitrogen concentrated under vacuum The residue was partitioned between ethyl acetate and dilute aqueous HCl The organic extract was washed with brine dried over anhydrous magnesium sulfate filtered concentrated under vacuum The residue was triturated with diethyl ether the solid precipitated was filtered

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of benzyl 4-benzyl-3-oxopiperazine-1-carboxylate (4.7 g, 14.5 mmol) and 10% Pd/C (0.47 g) in ethanol (150 mL) was stirred under an atmosphere of hydrogen (1 atm) at room temperature overnight. The product mixture was filtered through a pad of Celite, and concentrated under vacuum to provide 1-benzylpiperazin-2-one. The product mixture was filtered through a pad of Celite concentrated under vacuum

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of benzyl 4-benzyl-3-oxopiperazine-1-carboxylate (4.7 g, 14.5 mmol) and 10% Pd/C (0.47 g) in ethanol (150 mL) was stirred under an atmosphere of hydrogen (1 atm) at room temperature overnight. The product mixture was filtered through a pad of Celite, and concentrated under vacuum to provide 1-benzylpiperazin-2-one. A portion of the resultant oil (1.06 g, 5.5 mmol) was treated with a mixture of N,N-diisopropylethylamine (1.46 mL, 8.3 mmol), DMAP (68 mg, 0.55 mmol), and acetic anhydride (0.73 mL, 7.8 mmol) in methylene chloride (30 mL) at 0° C. After stirring at room temperature overnight, the resultant mixture was concentrated and the residue was subjected to column chromatography on silica gel eluting with a 10-90 mixture of methanol and ethyl acetate. Collection and concentration of appropriate fractions provided the title piperazinone. The product mixture was filtered through a pad of Celite concentrated under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1,4-dichlorophthalazine (500 mg, 2.51 mmol), 1-benzylpiperazin-2-one (526 mg, 2.76 mmol), potassium carbonate (521 mg, 3.01 mmol), and N-methylpyrrolidinone (3 mL) were heated at 110° for 8 hours. The reaction was taken up in ethyl acetate (80 mL) and washed with aqueous K2CO3 (10%), water, and saturated sodium chloride. The organics were dried (MgSO4) and evaporated to give an orange oil. Chromatography over silica gel with a gradient of hexanes/0-40% ethyl acetate gave an off-white solid. MS (M+H)+=353.9. washed with aqueous K2CO3 (10%), water, and saturated sodium chloride The organics were dried (MgSO4) evaporated to give an orange oil

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 35 mL of TFA in dichloromethane was added 4-benzyl-3-oxo-piperazine-1-carboxylic acid tert-butyl ester (10.39 g, 35.8 mmol) in portions. After 18 hours the solution was concentrated via rotary evaporator and H20 was added. The pH was adjusted to 12 with 4M NaOH. The mixture was extracted with dichloromethane. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give 1-benzyl-piperazin-2-one (6.29 g, 92%) as an oil. After 18 hours the solution was concentrated via rotary evaporator and H20 was added The mixture was extracted with dichloromethane The combined organic layers were dried over sodium sulfate filtered concentrated in vacuo