1-acetyl-3-benzylidenepiperazine-2,5-dione

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution containing 6.36. g (26.00 mmol) of 1-Acetyl-3-benzylidene piperazine-2,5-dione described by D. Villemn, et al. (Synthetic Communications, 20:3325 (1990)), in 100 mL of DMF under nitrogen atmosphere was added 9.62 mL (65.10 mmol) of t-butyl bromoacetate and 7.55 g (32.60 mmol) of silver oxide. The reaction was heated to 45° C. overnight. The reaction was filtered through a plug of celite and the filtrate concentration under reduced pressure. The residue was diluted with ethyl acetate and washed with water. The organic phase was dried over magnesium sulfate. Filtration, removal of solvent under reduced pressure and column chromatography of the residue on silica gel with 1% methanol/dichloromethane gave 5.37 g of a tan solid. Further purification via preparative HPLC gave 2.5 g (27%) of the title compound. FAB MS [M+H] m/z: Calcd: 359, Found: 359. To a solution containing 6.36 The reaction was filtered through a plug of celite the filtrate concentration under reduced pressure The residue was diluted with ethyl acetate washed with water The organic phase was dried over magnesium sulfate Filtration, removal of solvent under reduced pressure and column chromatography of the residue on silica gel with 1% methanol/dichloromethane

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

実験手順: 1,4-Diacetyl-2,5-piperazinedione (25.0 g, 126 mmol), which is compound (8) mentioned in Reference Example 1, was heated at 120°-130° C. in DMF (200 ml) with triethylamine (17.6 ml, 126 mmol) and benzaldehyde (13.0 ml, 126 mmol). After 4 h the mixture was cooled to room temperature and poured into EtOAc (1000 ml), and washed three times with brine. Any solid formed at this stage was filtered off. The filtrate was dried (MgSO4) and the solvent removed in vacuo. The residue was recrystallised from EtOAc:Hexane to give 11.78 g (38%) of the title compound as a yellow solid. washed three times with brine Any solid formed at this stage was filtered off The filtrate was dried (MgSO4) the solvent removed in vacuo The residue was recrystallised from EtOAc

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

実験手順: 1,4-Diacetyl-2,5-piperazinedione (25.0 g, 126 mmol), which is compound (8) mentioned in Reference Example 1 was heated at 120-130° C. in DMF (200 ml) with triethylamine (17.6 ml, 126 mmol) and benzaldehyde (13.0 ml, 126 mmol). After 4 h the mixture was cooled to room temperature and poured into EtOAc (1000 ml), and washed three times with brine. Any solid formed at this stage was filtered off. The filtrate was dried (MgSO4) and the solvent removed in vacuo. The residue was recrystallised from EtOAc:Hexane to give 11.78 g (38%) of the title compound as a yellow solid. washed three times with brine Any solid formed at this stage was filtered off The filtrate was dried (MgSO4) the solvent removed in vacuo The residue was recrystallised from EtOAc

反応条件: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution containing 6.36. g (26.00 mmol) of 1-Acetyl-3-benzylidene piperazine-2,5-dione described by D. Villemn, et al. (Synthetic Communications, 20:3325 (1990)), in 100 mL of DMF under nitrogen atmosphere was added 9.62 mL (65.10 mmol) of t-butyl bromoacetate and 7.55 g (32.60 mmol) of silver oxide. The reaction was heated to 45° C. overnight. The reaction was filtered through a plug of celite and the filtrate concentration under reduced pressure. The residue was diluted with ethyl acetate and washed with water. The organic phase was dried over magnesium sulfate. Filtration, removal of solvent under reduced pressure and column chromatography of the residue on silica gel with 1% methanol/dichloromethane gave 5.37 g of a tan solid. Further purification via preparative HPLC gave 2.5 g (27%) of the title compound. FAB MS [M+H] m/z: Calcd: 359, Found: 359. To a solution containing 6.36 The reaction was filtered through a plug of celite the filtrate concentration under reduced pressure The residue was diluted with ethyl acetate washed with water The organic phase was dried over magnesium sulfate Filtration, removal of solvent under reduced pressure and column chromatography of the residue on silica gel with 1% methanol/dichloromethane

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

実験手順: 1,4-Diacetyl-2,5-piperazinedione (25.0 g, 126 mmol), which is compound (8) mentioned in Reference Example 1, was heated at 120°-130° C. in DMF (200 ml) with triethylamine (17.6 ml, 126 mmol) and benzaldehyde (13.0 ml, 126 mmol). After 4 h the mixture was cooled to room temperature and poured into EtOAc (1000 ml), and washed three times with brine. Any solid formed at this stage was filtered off. The filtrate was dried (MgSO4) and the solvent removed in vacuo. The residue was recrystallised from EtOAc:Hexane to give 11.78 g (38%) of the title compound as a yellow solid. washed three times with brine Any solid formed at this stage was filtered off The filtrate was dried (MgSO4) the solvent removed in vacuo The residue was recrystallised from EtOAc

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

実験手順: 1,4-Diacetyl-2,5-piperazinedione (25.0 g, 126 mmol), which is compound (8) mentioned in Reference Example 1, was heated at 120°-130° C. in DMF (200 ml) with triethylamine (17.6 ml, 126 mmol) and benzaldehyde (13.0 ml, 126 mmol). After 4 h the mixture was cooled to room temperature and poured into EtOAc (1000 ml), and washed three times with brine. Any solid formed at this stage was filtered off. The filtrate was dried (MgSO4) and the solvent removed in vacuo. The residue was recrystallised from EtOAc:Hexane to give 11.78 g (38%) of the title compound as a yellow solid. washed three times with brine Any solid formed at this stage was filtered off The filtrate was dried (MgSO4) the solvent removed in vacuo The residue was recrystallised from EtOAc

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

実験手順: 1,4-Diacetyl-2,5-piperazinedione (25.0 g, 126 mmol), which is compound (8) mentioned in Example 3, was heated at 120°-130° C. in DMF (200 ml) with triethylamine (17.6 ml, 126 mmol) and benzaldehyde (13.0 ml, 126 mmol). After 4 h the mixture was cooled to room temperature and poured into EtOAc (1000 ml), and washed three times with brine. Any solid formed at this stage was filtered off. The filtrate was dried (MgSO4) and the solvent removed in vacuo. The residue was recrystallised from EtOAc:Hexane to give 11.78 g (38%) of the title compound as a yellow solid. washed three times with brine Any solid formed at this stage was filtered off The filtrate was dried (MgSO4) the solvent removed in vacuo The residue was recrystallised from EtOAc

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

実験手順: 1,4-Diacetyl-2,5-piperazinedione (described by Marcuccio and Elix in Aust. J. Chem, 1984, 37, 1791) (25.0 g, 126 mmol) was treated at 130° C. in DMF (200 ml) with triethylamine (17.6 ml, 126 mmol) and benzaldehyde (13.0 ml, 126 mmol). After 4 hours the mixture was cooled to room temperature and poured into EtOAc (1000 ml) and washed 3 times with brine. Any solid formed at this stage was filtered off. The filtrate was dried (MgSO4) and the solvent removed in vacuo. The residue was recrystallised from EtOAc:Hexane to give 11.78 g (38%) of 1-acetyl-3-benzylidene-2,5-piperazinedione. washed 3 times with brine Any solid formed at this stage was filtered off The filtrate was dried (MgSO4) the solvent removed in vacuo The residue was recrystallised from EtOAc

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

実験手順: 1-Acetyl-3-benzylidene-2,5-piperazinedione (compound 18 prepared in Reference Example 2) was N-methylated by treatment with methyl iodide (2.0 equivalents) in the presence of Na2CO3 (1.0 equivalents) in DMF at room temperature for 24 hours. The solvent was removed and the residue purified by flash chromatography. The product 1-acetyl-3-benzylidene-4-methyl-2,5-piperazinedione, obtained in 45% yield, was treated with 4-methoxybenzaldehyde (1.0-1.1 equivalents) in the presence of Cs2CO3 in DMF at 80° C. for 206 hours to give compound 121, which is (3Z,6Z)-6-benzylidene-3-(4-methoxybenzylidene)-1-methyl-2,5-piperazinedione, in 35% yield. The solvent was removed the residue purified by flash chromatography

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

実験手順: 1,4-Diacetyl-2,5-piperazinedione (25.0 g, 126 mmol), which is compound (8) mentioned in Reference Example 1, was heated at 120°-130° C. in DMF (200 ml) with triethylamine (17.6 ml, 126 mmol) and benzaldehyde (13.0 ml, 126 mmol). After 4 h the mixture was cooled to room temperature and poured into EtOAc (1000 ml), and washed three times with brine. Any solid formed at this stage was filtered off. The filtrate was dried (MgSO4) and the solvent removed in vacuo. The residue was recrystallised from EtOAc:Hexane to give 11.78 g (38%) of the title compound as a yellow solid. washed three times with brine Any solid formed at this stage was filtered off The filtrate was dried (MgSO4) the solvent removed in vacuo The residue was recrystallised from EtOAc

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

実験手順: 1,4-Diacetyl-2,5-piperazinedione (25.0 g, 126 mmol) was heated at 120°-130° C. in DMF (200 ml) with triethylamine (17.6 ml, 126 mmol) and benzaldehyde (13.0 ml, 126 mmol). After 4 h the mixture was cooled to room temperature and poured into EtOAc (1000 ml), and washed three times with brine. Any solid formed at this stage was filtered off. The filtrate was dried (MgSO4) and the solvent removed in vacuo. The residue was recrystallised from EtOAc:Hexane to give 11.78 g (38%) of the title compound as a yellow solid. washed three times with brine Any solid formed at this stage was filtered off The filtrate was dried (MgSO4) the solvent removed in vacuo The residue was recrystallised from EtOAc

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

実験手順: 1,4-Diacetyl-2,5-piperazinedione (25.0 g, 126 mmol), which is compound (8) mentioned in Reference Example 1 was heated at 120-130° C. in DMF (200 ml) with triethylamine (17.6 ml, 126 mmol) and benzaldehyde (13.0 ml, 126 mmol). After 4 h the mixture was cooled to room temperature and poured into EtOAc (1000 ml), and washed three times with brine. Any solid formed at this stage was filtered off. The filtrate was dried (MgSO4) and the solvent removed in vacuo. The residue was recrystallised from EtOAc:Hexane to give 11.78 g (38%) of the title compound as a yellow solid. washed three times with brine Any solid formed at this stage was filtered off The filtrate was dried (MgSO4) the solvent removed in vacuo The residue was recrystallised from EtOAc