2-[2-(oxiran-2-yl)ethyl]isoindole-1,3-dione

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 sample of 2.1 g (9.0 mmol) 1-(2,3-dichlorophenyl)-piperazine in 40 mL 2-PrOH was reacted in the microwave (pressure vessel, Pmax 150 W, cooling, 90° C., 20 min) with 2.0 g (9.0 mmol) 25. The solvent was removed in vacuo and the foamy residue was washed with 10 mL 2-PrOH. Yield: 2.96 g (73%). 1H NMR (CDCl3): δ 1.79 (m, 2H), 2.42 (m, 2H), 2.56 (s, 2H), 2.79 (m, 2H), 3.02 (s, 4H), 3.60 (s, 1H), 3.74-3.83 (m, 3H), 6.90 (m, 1H), 7.06-7.11 (m, 2H), 7.67 (m, 2H), 7.81 (m, 2H). 13C NMR (CDCl3): δ 33.9, 35.3, 51.4, 53.4, 63.8, 64.5, 118.2, 122.7, 124.1, 127.0, 131.6, 133.4, 133.4, 150.4, 167.7. The solvent was removed in vacuo the foamy residue was washed with 10 mL 2-PrOH

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

実験手順: 5 g (˜25 mmol) 2-(3,4-epoxybutyl)-isoindolin-1,3-dione, 7.5 g (30 mmol) benzhydrylpiperazine and 3.5 g (25 mmol) potassium carbonate are stirred in DMF for 6 hours 80° C. After cooling, the reaction mixture is filtered and concentrated under vacuum. The residue is taken up in 300 ml acetic acid ethyl ester and washed three times each with 20 ml water. The organic phase is dried over sodium sulfate and the solvent is removed under vacuum. The residue is chromatographically purified over silica gel with CHCl3/CH3OH. After cooling the reaction mixture is filtered concentrated under vacuum washed three times each with 20 ml water The organic phase is dried over sodium sulfate the solvent is removed under vacuum The residue is chromatographically purified over silica gel with CHCl3/CH3OH

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 70 g (350 mmol) 2-(but-3-enyl)-isoindolin-1,3-dione are dissolved in dichloromethane. The solution is cooled to ca. 0° C. and a suspension of 120.8 g (350 mmol) 50% 3-chloro-peroxy-benzoic acid in dichloromethane is added under cooling. The mixture is left standing without further cooling at room temperature for two days. After addition of 250 ml saturated NaHCO3 solution the organic phase is separated and washed three times each with 200 ml saturated NaHCO3 solution and once with water. The organic phase is dried over sodium sulfate and the solvent is removed under vacuum: yield 80 g. is added under cooling The mixture is left without further cooling at room temperature for two days is separated washed three times each with 200 ml saturated NaHCO3 solution The organic phase is dried over sodium sulfate the solvent is removed under vacuum

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

実験手順: A sample of 2.1 g (9.0 mmol) 1-(2,3-dichlorophenyl)-piperazine in 40 mL 2-PrOH was reacted in the microwave (pressure vessel, Pmax 150 W, cooling, 90° C., 20 min) with 2.0 g (9.0 mmol) 25. The solvent was removed in vacuo and the foamy residue was washed with 10 mL 2-PrOH. Yield: 2.96 g (73%). 1H NMR (CDCl3): δ 1.79 (m, 2H), 2.42 (m, 2H), 2.56 (s, 2H), 2.79 (m, 2H), 3.02 (s, 4H), 3.60 (s, 1H), 3.74-3.83 (m, 3H), 6.90 (m, 1H), 7.06-7.11 (m, 2H), 7.67 (m, 2H), 7.81 (m, 2H). 13C NMR (CDCl3): δ 33.9, 35.3, 51.4, 53.4, 63.8, 64.5, 118.2, 122.7, 124.1, 127.0, 131.6, 133.4, 133.4, 150.4, 167.7. The solvent was removed in vacuo the foamy residue was washed with 10 mL 2-PrOH

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

実験手順: A sample of 2.1 g (9.0 mmol) 1-(2,3-dichlorophenyl)-piperazine in 40 mL 2-PrOH was reacted in the microwave (pressure vessel, Pmax 150 W, cooling, 90° C., 20 min) with 2.0 g (9.0 mmol) 25. The solvent was removed in vacuo and the foamy residue was washed with 10 mL 2-PrOH. Yield: 2.96 g (73%). 1H NMR (CDCl3): δ 1.79 (m, 2H), 2.42 (m, 2H), 2.56 (s, 2H), 2.79 (m, 2H), 3.02 (s, 4H), 3.60 (s, 1H), 3.74-3.83 (m, 3H), 6.90 (m, 1H), 7.06-7.11 (m, 2H), 7.67 (m, 2H), 7.81 (m, 2H). 13C NMR (CDCl3): δ 33.9, 35.3, 51.4, 53.4, 63.8, 64.5, 118.2, 122.7, 124.1, 127.0, 131.6, 133.4, 133.4, 150.4, 167.7. The solvent was removed in vacuo the foamy residue was washed with 10 mL 2-PrOH

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 2-(2-(oxiran-2-yl)ethyl)isoindoline-1,3-dione obtained in step 2 (0.30 g, 1.38 mmol) and potassium carbonate (0.48 g, 3.45 mmol) in N,N-dimethylformamide (3.0 ml), was added 1-(2,3-dimethylphenyl)piperazine hydrochloride (0.31 g, 1.38 mmol) at room temperature. The resulting reaction mixture was stirred at 110° C. for 18 hours. After the reaction complete, the reaction mixture thus obtained was filtered through a plug of Celite. The filtrate was concentrated under reduced pressure to obtain the title compound (0.26 g). The compound was used for the next step without further purification. The resulting reaction mixture After the reaction complete, the reaction mixture thus obtained was filtered through a plug of Celite The filtrate was concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4-(3,4-dichlorophenoxy)piperidine (WO 0058305, WO 0177101) (4.40 g) and 2-(2-oxiran-2-ylethyl)-1H-isoindole-1,3(2H)-dione (J. Med. Chem. 1979, 22(6), 631-9. 5.00 g) in ethanol (50 ml) was stirred at 60° C. for 12 h. The mixture was cooled down and left overnight. The formed crystals were collected by filtration, washed with cold ethanol and dried under vacuum to afford the sub-title compound as a white solid (3.0 g). The mixture was cooled down left overnight The formed crystals were collected by filtration washed with cold ethanol dried under vacuum

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4-(3,4-dichlorophenoxy)piperidine (WO 0058305, WO 0177101) (4.40 g) and 2-(2-oxiran-2-ylethyl)-1H-isoindole-1,3(2H)-dione (J. Med. Chem. 1979, 22(6), 631-9. 5.00 g) in ethanol (50 ml) was stirred at 60° C. for 12 h. The mixture was cooled down and left overnight. The formed crystals were collected by filtration, washed with cold ethanol and dried under vacuum to afford the sub-title compound as a white solid (3.0 g). The mixture was cooled down left overnight The formed crystals were collected by filtration washed with cold ethanol dried under vacuum