2-(2-氨基乙基二硫基)乙胺;盐酸盐

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 9.30 g of 6-chloro-1H,3H-benzo[de]isochromene-1,3-dione and 4.46 g of cystamine hydrochloride were suspended in 50 ml of N-methylpyrrolidone (NMP). 5.5 g of diisopropylethylamine were added and the mixture was heated, with stirring, at 120° C. After 2 hours, 50 ml of NMP were added and the mixture continued to be stirred at 120° C. for 3 h. After cooling, the precipitated product was recovered, the filtered solution was extended by addition of 200 ml of water and a second precipitate was recovered. The precipitates were washed in water and dried. 11.46 g of white powder were recovered. The analyses showed that the product conformed to the expected structure. the mixture was heated to be stirred at 120° C. for 3 h After cooling the precipitated product was recovered the filtered solution was extended by addition of 200 ml of water a second precipitate was recovered The precipitates were washed in water dried 11.46 g of white powder were recovered

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 9.30 g of 6-chloro-1H,3H-benzo[de]isochromene-1,3-dione and 4.46 g of hydrochlorided cystamine hydrochloride are suspended in 50 ml of N-methylpyrrolidone (NMP). 5.5 g of diisopropylethylamine are added and the mixture is heated with stirring at 120° C. After two hours, 50 ml of NMP are added and the mixture is kept with stirring at 120° C. for 3 hours. After cooling, the precipitated product is recovered and the filtered solution is extended by addition of 200 ml of water, and a second precipitate is recovered. The precipitates are washed with water and dried. 11.46 g of white powder are recovered. The analyses show that the product is in accordance with the expected product. the mixture is heated with stirring at 120° C. for 3 hours After cooling the precipitated product is recovered the filtered solution is extended by addition of 200 ml of water a second precipitate is recovered The precipitates are washed with water dried 11.46 g of white powder are recovered

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 9.30 g of 6-chloro-1H,3H-benzo[de]isochromene-1,3-dione and 4.46 g of cystamine hydrochloride were suspended in 50 ml of N-methylpyrrolidone (NMP). 5.5 g of diisopropylethylamine were added and the mixture was heated, with stirring, at 120° C. After 2 hours, 50 ml of NMP were added and the mixture continued to be stirred at 120° C. for 3 h. After cooling, the precipitated product was recovered, the filtered solution was extended by addition of 200 ml of water and a second precipitate was recovered. The precipitates were washed in water and dried. 11.46 g of white powder were recovered. The analyses showed that the product conformed to the expected structure. the mixture was heated to be stirred at 120° C. for 3 h After cooling the precipitated product was recovered the filtered solution was extended by addition of 200 ml of water a second precipitate was recovered The precipitates were washed in water dried 11.46 g of white powder were recovered

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 9.30 g of 6-chloro-1H,3H-benzo[de]isochromene-1,3-dione and 4.46 g of cystamine hydrochloride were suspended in 50 ml of N-methylpyrrolidone (NMP). 5.5 g of diisopropylethylamine were added and the mixture was heated, with stirring, at 120° C. After 2 hours, 50 ml of NMP were added and the mixture continued to be stirred at 120° C. for 3 h. After cooling, the precipitated product was recovered, the filtered solution was extended by addition of 200 ml of water and a second precipitate was recovered. The precipitates were washed in water and dried. 11.46 g of white powder were recovered. The analyses showed that the product conformed to the expected structure. the mixture was heated to be stirred at 120° C. for 3 h After cooling the precipitated product was recovered the filtered solution was extended by addition of 200 ml of water a second precipitate was recovered The precipitates were washed in water dried 11.46 g of white powder were recovered

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

实验步骤: Cystamine hydrochloride (400 mg excess) and triethylamine (1.0 ml, excess) were dissolved in 20 ml methanol, and HPMA copolymer with p-nitrophenyl active ester (Mn=18,300 Da and Mw=22,500 Da, ONp %=9.6 mol-%) (420 mg) in 5 ml methanol was added dropwise to above solution with stirring. The mixture was stirred overnight at room temperature. The solution was concentrated under vacuum and applied to Sephadex LH-20 column to separate the polymer conjugate, eluted with methanol. The polymer fraction was collected and solvent was removed under vacuum giving HPMA copolymer-cystamine conjugates. The product was dissolved in water, and DTPA dianhydride (300 mg, excess) was added to the solution. The mixture was stirred for 30 minutes, and pH was adjusted to 7.0 with NaHCO3. The mixture was stirred at room temperature overnight. The polymer was separated from excess DTPA by passing through a Sephadex G-25 column, eluted with water. GdCl3 was added with xylene orange as an indicator. The solution was neutralized with NaOH to pH 5.0. The resulting solution was passed through a Sephadex G-25 column to remove excess GdCl3 and salt. Finally, the product was lyophilized giving a colorless product, HPMA copolymer-[DTPA-Gd] conjugate, indicated as (C) below. The yield was 340 mg, or 85%. The mixture was stirred overnight at room temperature The solution was concentrated under vacuum to separate the polymer conjugate eluted with methanol The polymer fraction was collected solvent was removed under vacuum

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

实验步骤: Cystamine hydrochloride (400 mg excess) and triethylamine (1.0 ml, excess) were dissolved in 20 ml methanol, and HPMA copolymer with p-nitrophenyl active ester (Mn=18,300 Da and Mw=22,500 Da, ONp %=9.6 mol-%) (420 mg) in 5 ml methanol was added dropwise to above solution with stirring. The mixture was stirred overnight at room temperature. The solution was concentrated under vacuum and applied to Sephadex LH-20 column to separate the polymer conjugate, eluted with methanol. The polymer fraction was collected and solvent was removed under vacuum giving HPMA copolymer-cystamine conjugates. The product was dissolved in water, and DTPA dianhydride (300 mg, excess) was added to the solution. The mixture was stirred for 30 minutes, and pH was adjusted to 7.0 with NaHCO3. The mixture was stirred at room temperature overnight. The polymer was separated from excess DTPA by passing through a Sephadex G-25 column, eluted with water. GdCl3 was added with xylene orange as an indicator. The solution was neutralized with NaOH to pH 5.0. The resulting solution was passed through a Sephadex G-25 column to remove excess GdCl3 and salt. Finally, the product was lyophilized giving a colorless product, HPMA copolymer-[DTPA-Gd] conjugate, indicated as (C) below. The yield was 340 mg, or 85%. The mixture was stirred overnight at room temperature The solution was concentrated under vacuum to separate the polymer conjugate eluted with methanol The polymer fraction was collected solvent was removed under vacuum

反应条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 60 g of cystamine hydrochloride are solubilized in 500 mL and cooled to 5° C. pH is raised to 10 by addition of aq. NaOH (30%). A solution of 4-chlorobutanoyl chloride (105 g) in anhydrous THF (500 mL), is added dropwise, while pH is maintained above 7 by addition of aq. NaOH (30%). After completion of the addition and stabilization of pH at 7, the mixture is kept mixing for 3 d. The aqueous layer is extracted with 3×500 mL dichloromethane, combined with THF layer and dried over Na2SO4. After drying under vacuum, 41 g of a white powder are collected. Analyses are in accordance with the expected structure. After completion of the addition and stabilization of pH at 7 the mixture is kept mixing for 3 d The aqueous layer is extracted with 3×500 mL dichloromethane dried over Na2SO4 After drying under vacuum, 41 g of a white powder are collected

反应条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 60 g of cystamine hydrochloride are solubilized in 500 mL and cooled to 5° C. pH is raised to 10 by addition of aq. NaOH (30%). A solution of 4-chlorobutanoyl chloride (105 g) in anhydrous THF (500 mL), is added dropwise, while pH is maintained above 7 by addition of aq. NaOH (30%). After completion of the addition and stabilization of pH at 7, the mixture is kept mixing for 3 d. The aqueous layer is extracted with 3×500 mL dichloromethane, combined with THF layer and dried over Na2SO4. After drying under vacuum, 41 g of a white powder are collected. Analyses are in accordance with the expected structure. After completion of the addition and stabilization of pH at 7 the mixture is kept mixing for 3 d The aqueous layer is extracted with 3×500 mL dichloromethane dried over Na2SO4 After drying under vacuum, 41 g of a white powder are collected

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 9.30 g of 6-chloro-1H,3H-benzo[de]isochromene-1,3-dione and 4.46 g of hydrochlorided cystamine hydrochloride are suspended in 50 ml of N-methylpyrrolidone (NMP). 5.5 g of diisopropylethylamine are added and the mixture is heated with stirring at 120° C. After two hours, 50 ml of NMP are added and the mixture is kept with stirring at 120° C. for 3 hours. After cooling, the precipitated product is recovered and the filtered solution is extended by addition of 200 ml of water, and a second precipitate is recovered. The precipitates are washed with water and dried. 11.46 g of white powder are recovered. The analyses show that the product is in accordance with the expected product. the mixture is heated with stirring at 120° C. for 3 hours After cooling the precipitated product is recovered the filtered solution is extended by addition of 200 ml of water a second precipitate is recovered The precipitates are washed with water dried 11.46 g of white powder are recovered

反应条件: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 9.30 g of 6-chloro-1H,3H-benzo[de]isochromene-1,3-dione and 4.46 g of hydrochlorided cystamine hydrochloride are suspended in 50 ml of N-methylpyrrolidone (NMP). 5.5 g of diisopropylethylamine are added and the mixture is heated with stirring at 120° C. After two hours, 50 ml of NMP are added and the mixture is kept with stirring at 120° C. for 3 hours. After cooling, the precipitated product is recovered and the filtered solution is extended by addition of 200 ml of water, and a second precipitate is recovered. The precipitates are washed with water and dried. 11.46 g of white powder are recovered. The analyses show that the product is in accordance with the expected product. the mixture is heated with stirring at 120° C. for 3 hours After cooling the precipitated product is recovered the filtered solution is extended by addition of 200 ml of water a second precipitate is recovered The precipitates are washed with water dried 11.46 g of white powder are recovered

反应条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 60 g of cystamine hydrochloride was solubilized in 500 mL and cooled to 5° C. The pH was raised to 10 by addition of aq. NaOH (30%). A solution of 4-chlorobutanoyl chloride (105 g) in anhydrous THF (500 mL), was added dropwise, while the pH was maintained above 7 by addition of aq. NaOH (30%). After completion of the addition and stabilization of pH at 7, the mixture mixed for 3 days. The aqueous layer was extracted with 3×500 mL dichloromethane, combined with THF layer and dried over Na2SO4. After drying under vacuum, 41 g of a white powder were collected. Analyses were in accordance with the expected structure. After completion of the addition and stabilization of pH at 7 the mixture mixed for 3 days The aqueous layer was extracted with 3×500 mL dichloromethane dried over Na2SO4 After drying under vacuum, 41 g of a white powder were collected

反应条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 60 g of cystamine hydrochloride was solubilized in 500 mL and cooled to 5° C. The pH was raised to 10 by addition of aq. NaOH (30%). A solution of 4-chlorobutanoyl chloride (105 g) in anhydrous THF (500 mL), was added dropwise, while the pH was maintained above 7 by addition of aq. NaOH (30%). After completion of the addition and stabilization of pH at 7, the mixture mixed for 3 days. The aqueous layer was extracted with 3×500 mL dichloromethane, combined with THF layer and dried over Na2SO4. After drying under vacuum, 41 g of a white powder were collected. Analyses were in accordance with the expected structure. After completion of the addition and stabilization of pH at 7 the mixture mixed for 3 days The aqueous layer was extracted with 3×500 mL dichloromethane dried over Na2SO4 After drying under vacuum, 41 g of a white powder were collected