Bis(2-bromoethyl)amine hydrobromide

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

実験手順: To a mixture of 6.08 g of 2-chloro-3-methylaniline, 9 g of di(2-bromoethyl)amine hydrobromide and 4 ml of water was added a solution of 0.8 g of potassium hydorxide and 2.5 ml of water 3 times of 1 hour interval at 100° C., then the reaction mixture was stirred at the same temperature for 9 hours. To the resultant reaction mixture was added potassium hydroxide to make the mixture alkaline, and the mixture was extracted with diethyl ether, washed with water, dried with anhydrous magnesium sulfate. The solvent was removed by evaporation and the residue thus obtained was purified by means of a silica gel column chromatography (eluent: 5%-methanol/chloroform), and obtained 3.41 g of 4-(2-chloro-3-methylphenyl)piperazine. To the resultant reaction mixture the mixture was extracted with diethyl ether washed with water dried with anhydrous magnesium sulfate The solvent was removed by evaporation the residue thus obtained was purified by means of a silica gel column chromatography (eluent: 5%-methanol/chloroform)

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

実験手順: To a mixture of 6.08 g of 2-chloro-3-methylaniline, 9 g of di(2-bromoethyl)amine hydrobromide and 4 ml of water was added a solution of 0.8 g of potassium hydorxide and 2.5 ml of water 3 times of 1 hour interval at 100° C., then the reaction mixture was stirred at the same temperature for 9 hours. To the resultant reaction mixture was added potassium hydroxide to make the mixture alkaline, and the mixture was extracted with diethyl ether, washed with water, dried with anhydrous magnesium sulfate. The solvent was removed by evaporation and the residue thus obtained was purified by means of a silica gel column chromatography (eluent: 5%-methanol/chloroform), and obtained 3.41 g of 4-(2-chloro-3-methylphenyl)piperazine. To the resultant reaction mixture the mixture was extracted with diethyl ether washed with water dried with anhydrous magnesium sulfate The solvent was removed by evaporation the residue thus obtained was purified by means of a silica gel column chromatography (eluent: 5%-methanol/chloroform)

反応条件: temp:64.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 6-amino-8-methyl-3,4-dihydro-2(1H)-quinolinone (19.4 g), bis(2-bromoethyl)amine hydrobromide (41 g) and methanol (140 ml) was stirred for 13 hours at 64° C. After cooling, sodium carbonate (5.83 g) was added thereto and the mixture was stirred for 9 hours at 70° C. After cooling, the resulting precipitate was collected by filtration and the residue was washed with methanol to give 3,4-dihydro-8-methyl-6-(1-piperazinyl)-2(1H)-quinolinone hydrobromide (21.6 g). After cooling the mixture was stirred for 9 hours at 70° C After cooling the resulting precipitate was collected by filtration the residue was washed with methanol

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

実験手順: A mixture of 5-aminooxindol (14 g), 29 g of bis(β-bromoethyl)amine.hydrobromide in 250 ml of ethanol was stirred under reflux for 8 hours and allowed to stand overnight at room temperature. To the mixture was added sodium carbonate (10.1 g) and the mixture was stirred further for 8 hours under reflux. After cooling to room temperature, crystals which precipitated were collected by filtration and recrystallized from a mixture of water and ethanol to give 16 g of 5-(1-piperazinyl)oxindol.hydrobromide. under reflux for 8 hours the mixture was stirred further for 8 hours under reflux crystals which precipitated were collected by filtration recrystallized from a mixture of water and ethanol

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

実験手順: A mixture of 5-aminooxindol (14 g), 29 g of bis(β-bromoethyl)amine.hydrobromide in 250 ml of ethanol was stirred under reflux for 8 hours and allowed to stand overnight at room temperature. To the mixture was added sodium carbonate (10.1 g) and the mixture was stirred further for 8 hours under reflux. After cooling to room temperature, crystals which precipitated were collected by filtration and recrystallized from a mixture of water and ethanol to give 16 g of 5-(1-piperazinyl)oxindol.hydrobromide. under reflux for 8 hours the mixture was stirred further for 8 hours under reflux crystals which precipitated were collected by filtration recrystallized from a mixture of water and ethanol

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

実験手順: 18.3 grams of 3,4,5-trimethoxyaniline and 31.2 g of bis(β-bromoethyl)amine monohydrobromide are mixed with 170 ml of methanol and refluxed by heating under a nitrogen gas stream for 10 hours. After cooling the reaction mixture, 5.3 g of anhydrous sodium carbonate are added to the mixture and refluxed by heating for additional 10 hours. Under reduced pressure, about 70 ml of methanol are removed off by distillation, and the mixture is allowed to staand to cool at room temperature. The crystals thus precipitated are collected by filtration and washed with a small amount of ethanol. Recrystallization from ethanol obtains 38 g of 4-(3,4,5-trimethoxyphenyl)piperazine monohydrobromide in the form of colorless plate-like crystals with a melting point of 227°-228° C. refluxed by heating under a nitrogen gas stream for 10 hours are added to the mixture refluxed by heating for additional 10 hours Under reduced pressure, about 70 ml of methanol are removed off by distillation The crystals thus precipitated are collected by filtration washed with a small amount of ethanol Recrystallization from ethanol

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

実験手順: 18.3 grams of 3,4,5-trimethoxyaniline and 31.2 g of bis(β-bromoethyl)amine monohydrobromide are mixed with 170 ml of methanol and refluxed by heating under a nitrogen gas stream for 10 hours. After cooling the reaction mixture, 5.3 g of anhydrous sodium carbonate are added to the mixture and refluxed by heating for additional 10 hours. Under reduced pressure, about 70 ml of methanol are removed off by distillation, and the mixture is allowed to staand to cool at room temperature. The crystals thus precipitated are collected by filtration and washed with a small amount of ethanol. Recrystallization from ethanol obtains 38 g of 4-(3,4,5-trimethoxyphenyl)piperazine monohydrobromide in the form of colorless plate-like crystals with a melting point of 227°-228° C. refluxed by heating under a nitrogen gas stream for 10 hours are added to the mixture refluxed by heating for additional 10 hours Under reduced pressure, about 70 ml of methanol are removed off by distillation The crystals thus precipitated are collected by filtration washed with a small amount of ethanol Recrystallization from ethanol

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

実験手順: 18.3 Grams of 3,4,5-trimethoxyaniline and 31.2 g of bis(β-bromoethyl)amine monohydrobromide are mixed with 170 ml of methanol and refluxed by heating under a nitrogen gas stream for 10 hours. After cooling the reaction mixture, 5.3 g of anhydrous sodium carbonate are added to the mixture and refluxed by heating for and additional 10 hours. Under reduced pressure, about 70 ml of methanol are removed off by distillation, and the mixture is allowed to stand to cool at room temperature. The crystals thus precipitated are collected by filtration and washed with a small amount of ethanol. Recrystallization from ethanol obtains 38 g of 4-(3,4,5-trimethoxyphenyl)piperazine monohydrobromide in the form of colorless plate-like crystals with a melting point of 227°-228° C. refluxed by heating under a nitrogen gas stream for 10 hours are added to the mixture refluxed by heating for and additional 10 hours Under reduced pressure, about 70 ml of methanol are removed off by distillation The crystals thus precipitated are collected by filtration washed with a small amount of ethanol Recrystallization from ethanol

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

実験手順: 18.3 Grams of 3,4,5-trimethoxyaniline and 31.2 g of bis(β-bromoethyl)amine monohydrobromide are mixed with 170 ml of methanol and refluxed by heating under a nitrogen gas stream for 10 hours. After cooling the reaction mixture, 5.3 g of anhydrous sodium carbonate are added to the mixture and refluxed by heating for and additional 10 hours. Under reduced pressure, about 70 ml of methanol are removed off by distillation, and the mixture is allowed to stand to cool at room temperature. The crystals thus precipitated are collected by filtration and washed with a small amount of ethanol. Recrystallization from ethanol obtains 38 g of 4-(3,4,5-trimethoxyphenyl)piperazine monohydrobromide in the form of colorless plate-like crystals with a melting point of 227°-228° C. refluxed by heating under a nitrogen gas stream for 10 hours are added to the mixture refluxed by heating for and additional 10 hours Under reduced pressure, about 70 ml of methanol are removed off by distillation The crystals thus precipitated are collected by filtration washed with a small amount of ethanol Recrystallization from ethanol

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

実験手順: TEA (7.12 g, 70 mmol) was added dropwise to a stirred solution of bis(2-bromoethyl)amine hydrobromide (10.00 g, 32 mmol) and phosphorus oxychloride (4.91 g, 32 mmol) in CH2Cl2 (50 ml) at 0° C. under N2. The mixture was allowed to stir overnight and then poured over ice. The layers were separated, and the aqueous layer was extracted with CH2Cl2 (3×50 ml). The organic layers were combined and dried (MgSO4). The filtrate was concentrated under reduced pressure and the residue purified by chromatography (1:4 EtOAc: hexanes) to give 29 as an oil (3.86 g, 35%); 1H NMR (CDCl3) 3.70 (t, 4H, 6.73 Hz), 3.55 (t, 4H, 6.75 Hz)ppm. poured over ice The layers were separated the aqueous layer was extracted with CH2Cl2 (3×50 ml) dried (MgSO4) The filtrate was concentrated under reduced pressure the residue purified by chromatography (1:4 EtOAc: hexanes)

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

実験手順: 2-Fluoro-6-methoxyaniline (7.80 g) and 17.23 g of di-(2-bromoethyl)amine hydrobromide were dissolved in 5 ml of water and, by heating at about 110° C. on a bath, 10 ml of 30% potassium hydroxide solution was added thereto (each about 3.5 ml once an hour). Heating was further continued (7 hours in total). After cooled, the reaction solution was made alkaline with aqueous solution of sodium hydroxide to salt out and extracted with chloroform twice. The extract was washed with saturated sodium chloride solution, dried over sodium sulfate, the solvent was evaporated therefrom, and the residue was purified by a column chromatography to give 8.95 g of oily 1-(2-fluoro-6-methoxyphenyl)piperazine in 34.94 g yield or 94%. each about 3.5 ml once an hour Heating (7 hours in total) After cooled extracted with chloroform twice The extract was washed with saturated sodium chloride solution dried over sodium sulfate the solvent was evaporated the residue was purified by a column chromatography

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

実験手順: 8-Aminocarbostyril (15.47 g, 96.6 mmols) and bis(β-bromoethyl)amine hydrobromide (33 g, 106 mmols) were suspended in DMF and the suspension was stirred at 70° to 80° C. for 10 hours. After adding 5.1 g of sodium carbonate the reaction mixture was stirred at the same temperature as above for 7 hours. After distilling off the solvent under reduced pressure, methanol was added to the residue to crystallize. The crude crystals thus obtained were recrystallized from methanol-ether to give 5.1 g of 8-(1-piperazinyl)carbostyril hydrobromide, m.p. above 300° C., colorless scales. was stirred at the same temperature as above for 7 hours After distilling off the solvent under reduced pressure, methanol was added to the residue to crystallize The crude crystals thus obtained were recrystallized from methanol-ether