3-(甲氨基)-2,3-二氢异吲哚-1-one

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

实验步骤: A solution of 3-methylamino-1-isoindolinone (6.8 g) in anhydrous dimethylformamide (200 cc) is added to a suspension of sodium hydride (as a 50% suspension in oil) (2.2 g) in anhydrous dimethylformamide (100 cc) at a temperature close to 20° C. in the course of 15 minutes and agitation is continued for 1 hour. Then, a solution of 3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)-1-bromopropane (13 g) in dimethylformamide (100 cc) is added in the course of 10 minutes, and agitation is continued for a further 20 hours. The solution obtained is evaporated to dryness under reduced pressure (1 mm Hg; 0.1 kPa). The residue obtained is dissolved in methylene chloride (500 cc) and washed with distilled water (3×500 cc). The organic phase is dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C. The residue obtained is dissolved in methylene chloride (20 cc) and poured onto silica (750 g ) contained in a column of 8 cm diameter. Elution is carried out with a mixture of methylene chloride and methanol (92-8 by volume). The first 3750 cc are eliminated and the eluate corresponding to the next 600 cc is concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa). The residue obtained is dissolved in methyl ethyl ketone (50 cc). A solution of oxalic acid (1.2 g) in methyl ethyl ketone (20 cc) is added and agitation continued for 1 hour at a temperature close to 20° C. The precipitate formed is separated by filtration. 5 g of 3-methylamino-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate are thus obtained, melting at 122° C. close to 20° C. in the course of 15 minutes and agitation is continued for a further 20 hours The solution obtained is evaporated to dryness under reduced pressure (1 mm Hg; 0.1 kPa) The residue obtained washed with distilled water (3×500 cc) The organic phase is dried over anhydrous magnesium sulphate filtered concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C The residue obtained poured onto silica (750 g ) Elution is carried out with a mixture of methylene chloride and methanol (92-8 by volume) the eluate corresponding to the next 600 cc is concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) The residue obtained agitation continued for 1 hour at a temperature close to 20° C The precipitate formed is separated by filtration

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

实验步骤: A solution of 3-methylamino-1-isoindolinone (6.8 g) in anhydrous dimethylformamide (200 cc) is added to a suspension of sodium hydride (as a 50% suspension in oil) (2.2 g) in anhydrous dimethylformamide (100 cc) at a temperature close to 20° C. in the course of 15 minutes and agitation is continued for 1 hour. Then, a solution of 3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)-1-bromopropane (13 g) in dimethylformamide (100 cc) is added in the course of 10 minutes, and agitation is continued for a further 20 hours. The solution obtained is evaporated to dryness under reduced pressure (1 mm Hg; 0.1 kPa). The residue obtained is dissolved in methylene chloride (500 cc) and washed with distilled water (3×500 cc). The organic phase is dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C. The residue obtained is dissolved in methylene chloride (20 cc) and poured onto silica (750 g ) contained in a column of 8 cm diameter. Elution is carried out with a mixture of methylene chloride and methanol (92-8 by volume). The first 3750 cc are eliminated and the eluate corresponding to the next 600 cc is concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa). The residue obtained is dissolved in methyl ethyl ketone (50 cc). A solution of oxalic acid (1.2 g) in methyl ethyl ketone (20 cc) is added and agitation continued for 1 hour at a temperature close to 20° C. The precipitate formed is separated by filtration. 5 g of 3-methylamino-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate are thus obtained, melting at 122° C. close to 20° C. in the course of 15 minutes and agitation is continued for a further 20 hours The solution obtained is evaporated to dryness under reduced pressure (1 mm Hg; 0.1 kPa) The residue obtained washed with distilled water (3×500 cc) The organic phase is dried over anhydrous magnesium sulphate filtered concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C The residue obtained poured onto silica (750 g ) Elution is carried out with a mixture of methylene chloride and methanol (92-8 by volume) the eluate corresponding to the next 600 cc is concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) The residue obtained agitation continued for 1 hour at a temperature close to 20° C The precipitate formed is separated by filtration

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

实验步骤: A solution of 3-methylamino-1-isoindolinone (6.8 g) in anhydrous dimethylformamide (200 cc) is added to a suspension of sodium hydride (as a 50% suspension in oil) (2.2 g) in anhydrous dimethylformamide (100 cc) at a temperature close to 20° C. in the course of 15 minutes and agitation is continued for 1 hour. Then, a solution of 3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)-1-bromopropane (13 g) in dimethylformamide (100 cc) is added in the course of 10 minutes, and agitation is continued for a further 20 hours. The solution obtained is evaporated to dryness under reduced pressure (1 mm Hg; 0.1 kPa). The residue obtained is dissolved in methylene chloride (500 cc) and washed with distilled water (3×500 cc). The organic phase is dried over anhydrous magnesium sulphate, filtered and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C. The residue obtained is dissolved in methylene chloride (20 cc) and poured onto silica (750 g ) contained in a column of 8 cm diameter. Elution is carried out with a mixture of methylene chloride and methanol (92-8 by volume). The first 3750 cc are eliminated and the eluate corresponding to the next 600 cc is concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa). The residue obtained is dissolved in methyl ethyl ketone (50 cc). A solution of oxalic acid (1.2 g) in methyl ethyl ketone (20 cc) is added and agitation continued for 1 hour at a temperature close to 20° C. The precipitate formed is separated by filtration. 5 g of 3-methylamino-2-[3-(4-phenyl-1,2,3,6-tetrahydro-1-pyridyl)propyl]-1-isoindolinone oxalate are thus obtained, melting at 122° C. close to 20° C. in the course of 15 minutes and agitation is continued for a further 20 hours The solution obtained is evaporated to dryness under reduced pressure (1 mm Hg; 0.1 kPa) The residue obtained washed with distilled water (3×500 cc) The organic phase is dried over anhydrous magnesium sulphate filtered concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C The residue obtained poured onto silica (750 g ) Elution is carried out with a mixture of methylene chloride and methanol (92-8 by volume) the eluate corresponding to the next 600 cc is concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) The residue obtained agitation continued for 1 hour at a temperature close to 20° C The precipitate formed is separated by filtration