二亚乙基三胺

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

实验步骤: 113.3 g (790 mmol) of trifluoroacetic acid ethyl ester is added in drops to a solution consisting of 41.14 g (390 mmol) of 1,4,7-triazaheptane in 350 ml of tetrahydrofuran at 80° C. and under nitrogen. It is allowed to stir overnight at room temperature, concentrated by evaporation in a vacuum. The remaining oil is crystallized from hexane. concentrated by evaporation in a vacuum The remaining oil is crystallized from hexane

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

实验步骤: 51.5 g (500 mmol) of diethylenetriamine and 139 ml (1 mol) of triethylamine are dissolved in dichloromethane and mixed at -20° C. with 161 g of benzyl cyanoformate (Fluka) in dichloromethane and then stirred overnight at room temperature. After the reaction is completed, concentration by evaporation is performed during draw-off, the residue is taken up in diethyl ether, the organic phase is washed with sodium carbonate solution and dried with sodium sulfate. The filtrate is mixed with hexane, the precipitate is filtered out and dried. concentration by evaporation the organic phase is washed with sodium carbonate solution dried with sodium sulfate The filtrate is mixed with hexane the precipitate is filtered out dried

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

实验步骤: A mixture of 155 g of triacetone amine, 113 g of diethylene triamine, and 2.5 g of conc. sulfuric acid in 2.5 liters of methanol is hydrogenated in the presence of 7 g of 5% palladium on carbon in the manner described in Example 1. In addition to yielding 1,7-bis(2,2,6,6-tetramethyl-4-piperidyl)-1,4,7-triazaheptane, distillation of the hydrogenation mixture yields at 115°-118° C./0.09 mm Hg 1-(2,2,6,6-tetramethyl-4-piperidyl)-1,4,7-triazaheptane as main product. In addition to yielding 1,7-bis(2,2,6,6-tetramethyl-4-piperidyl)-1,4,7-triazaheptane, distillation of the hydrogenation mixture

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

实验步骤: This compound was synthesized following the procedure of Atkins, T. J.; Richman, J. E.; and Oettle, W. F.; Org. synth., 58, 86-98 (1978). To a stirred solution of p-toluenesulfonyl chloride (618 g, 3.24 mole) in pyridine (1500 ml) at 0° C. was added a solution of 1,4,7-triazaheptane (95.5 g, 0.926 mole) in pyridine (150 ml) under a dry argon atmosphere, maintaining the temperature ≤50° C. The addition required 30 minutes. After the mixture was allowed to cool to room temperature slowly while stirring for 3 h, H2O (2 l) was slowly added to the cooled (ice bath) mixture. The heavy white precipitate which formed was filtered and washed thoroughly with H2O. The pale yellow solid was dissolved in DMF (3 l) and 0.1N HCl (4 l) was slowly added at 5° C. The slurry was filtered and the pale yellow solid was washed thoroughly with H2O and dried in vacuo to give 486 g (93% yield) of the product: mp 180°-1° C.; 1H NMR(DMSO-d6) δ 2.39 (s,3 H), 2.40 (s, 6 H), 2.84 (m, 4 H), 3.04 (t, J=6.9 Hz, 4 H) 7.40 (d, J=8.1 Hz, 4 H), 7.59 (d, J=8.3 Hz, 2 H), 7.67 (m, 6 H). This compound was synthesized maintaining the temperature ≤50° C The addition required 30 minutes cooled (ice bath) mixture The heavy white precipitate which formed was filtered washed thoroughly with H2O The pale yellow solid was dissolved in DMF (3 l) 0.1N HCl (4 l) was slowly added at 5° C The slurry was filtered the pale yellow solid was washed thoroughly with H2O dried in vacuo

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

实验步骤: 51.5 g (500 mmol) of diethylenetriamine and 139 ml (1 mol) of triethylamine are dissolved in dichloromethane and mixed at -20° C. with 161 g of benzyl cyanoformate (Fluka) in dichloromethane and then stirred overnight at room temperature. After the reaction is completed, concentration by evaporation is performed during draw-off, the residue is taken up in diethyl ether, the organic phase is washed with sodium carbonate solution and dried with sodium sulfate. The filtrate is mixed with hexane, the precipitate is filtered out and dried. concentration by evaporation the organic phase is washed with sodium carbonate solution dried with sodium sulfate The filtrate is mixed with hexane the precipitate is filtered out dried

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

实验步骤: 0.71 ml of diethylenetriamine and 0.9 g of NaOH, dissolved in 3 ml of water, are added to 10.6 g of the monochloro derivative from Example 70, dissolved in 50 ml of toluene. After warming to 100°, the solvent begins to distill off. A further 50 ml of toluene and 1 g of polyethylene glycol 1000 and 0.9 g of NaOH are added and the mixture is heated with stirring for 14 h under reflux. After cooling, the reaction mixture is diluted using 100 ml of ethyl acetate and the solution is washed four times with water. The organic solution is dried over Na2SO4 and evaporated. The residue is dissolved in 50 ml of methanol, filtered through 200 g of silica gel and washed with 500 ml of methanol. The methanol solution is evaporated, the residue being a nearly colorless resin. After warming to 100° to distill off A further 50 ml of toluene and 1 g of polyethylene glycol 1000 and 0.9 g of NaOH are added the mixture is heated under reflux After cooling the reaction mixture is diluted the solution is washed four times with water The organic solution is dried over Na2SO4 evaporated The residue is dissolved in 50 ml of methanol filtered through 200 g of silica gel washed with 500 ml of methanol The methanol solution is evaporated

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

实验步骤: A 988 g (1:04 mole) portion of polyisobutyl-24 chloroformate prepared according to the procedure outlined in Example 2, which had been diluted to 1800 ml with toluene was combined with 1800 ml of a solution containing 870 ml (8.05 moles) of diethylenetriamine in toluene using a Kenics static mixer (11 inches×3/8 inch); the reaction mixture was discharged into a 5 liter receiver. The reaction mixture was stripped, and then diluted with 8 1 hexane. A lower layer containing excess diethylene triamine was removed. The upper layer was washed twice with 3 l 5% aqueous sodium hydroxide; phase separation was assisted by the addition of salt, NaCl (to give brine in situ). After a final wash with basic brine, the organic layer was dried (over Na2SO4 ), filtered and stripped to give the above-identified product as a viscous yellow liquid (AV=64). was removed The upper layer was washed twice with 3 l 5% aqueous sodium hydroxide phase separation was assisted by the addition of salt, NaCl (to give brine in situ) After a final wash with basic brine the organic layer was dried (over Na2SO4 ) filtered

反应条件: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 14 g of t-butyl 2-bromo-3-[(4-nitrophenyl)methoxy]propanoate (prepared according to the procedure described by P. L. Rings et al., Synth. Commun., 1993, 23, 2639) (0.0389 mol), in 30 ml of acetonitrile was added to a solution of 20 g of diethylenetriamine (0.19 mol) in 20 ml of acetonitrile kept at 0°-5° C. and under inert atmosphere. The solution was then heated to 35° C. for 4 h. The solvent was evaporated under vacuum and 100 ml of a NaCl saturated solution were added to the residue. The solution was extracted with Et2O; the organic phase was washed with H2O, dried and concentrated under vacuum to obtain 12 g of the desired product (0.031 mol). kept at 0°-5° C. and under inert atmosphere The solvent was evaporated under vacuum and 100 ml of a NaCl saturated solution were added to the residue The solution was extracted with Et2O the organic phase was washed with H2O dried concentrated under vacuum

反应条件: temp:35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 14 g of t-butyl 2-bromo-3-[(4-nitrophenyl)methoxy]propanoate (prepared according to the procedure described by P. L. Rings et al., Synth. Commun., 1993, 23, 2639) (0.0389 mol), in 30 ml of acetonitrile was added to a solution of 20 g of diethylenetriamine (0.19 mol) in 20 ml of acetonitrile kept at 0°-5° C. and under inert atmosphere. The solution was then heated to 35° C. for 4 h. The solvent was evaporated under vacuum and 100 ml of a NaCl saturated solution were added to the residue. The solution was extracted with Et2O; the organic phase was washed with H2O, dried and concentrated under vacuum to obtain 12 g of the desired product (0.031 mol). kept at 0°-5° C. and under inert atmosphere The solvent was evaporated under vacuum and 100 ml of a NaCl saturated solution were added to the residue The solution was extracted with Et2O the organic phase was washed with H2O dried concentrated under vacuum

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

实验步骤: Employing the reaction equipment and general procedures described in Example I, a solution of 229.0 g. (3.75 moles) monoethanolamine and 225.0 g. (3.75 moles) ethylenediamine was admixed with 6.25 g. (0.054 mole; 2.3wt.% and 1.44 mole%, basis MEA) 85% phosphoric acid and heated at 250° C. under 225 - 225 psig pressure for 2.0 hours. Analysis of the reaction product by gas-liquid chromatography (GLC Area %) showed a total conversion of reactants of only 4.7% was obtained. The reaction products were 95.0 diethylenetriamine, 2.5 piperazine and 2.5 Area % N-(2-aminoethyl)-ethanolamine. No higher polyethylene polyamines, e.g., triethylenetetramine, tetraethylenepentamine, etc. were formed. was obtained

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

实验步骤: Employing the reaction equipment and general procedures described in Example I, a solution of 229.0 g. (3.75 moles) monoethanolamine and 225.0 g. (3.75 moles) ethylenediamine was admixed with 6.25 g. (0.054 mole; 2.3wt.% and 1.44 mole%, basis MEA) 85% phosphoric acid and heated at 250° C. under 225 - 225 psig pressure for 2.0 hours. Analysis of the reaction product by gas-liquid chromatography (GLC Area %) showed a total conversion of reactants of only 4.7% was obtained. The reaction products were 95.0 diethylenetriamine, 2.5 piperazine and 2.5 Area % N-(2-aminoethyl)-ethanolamine. No higher polyethylene polyamines, e.g., triethylenetetramine, tetraethylenepentamine, etc. were formed. was obtained

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

实验步骤: DOTA-alkyl-biotin was synthesized following the procedure of Takenouchi et al. (J. Organic Chem. 58:1955-1958, 1993) starting with the compound H-Lys(Boc)-OMe (Bachem, E-1620). H-Lys(Boc)-OMe was treated stepwise with methyl bromoacetate and diethylenetriamine to obtain tert-butyl 4-(3,12-dioxo-1,4,7,10-tetraazacyclododecan-2-yl)butylcarbamate. Borane-THF complex was used to reduce the carboxylic amides followed by trifluoroacetic acid Boc deprotection to obtain 4-(1,4,7,10-tetraazacyclododecan-2-yl)butan-1-amine. This compound was subsequently reacted with biotin-xx, SSE (Invitrogen, B-6352) in DMSO with a 10 fold molar excess of triethylamine for 3 hours vortexing at room temperature. In all synthesis steps compounds were purified by HPLC and confirmed by mass spectrometry with a Waters (Milford, Mass.) LCT electrospray time-of-flight (ES-TOF) liquid chromatography mass spectrometry (LC/MS) or by MALDI-TOF as described above.