A 500 mL three-neck round bottom flask was charged with 100 mL of dry DMF and the flask flushed with nitrogen. Two syringes were charged separately with solutions of diethylenetriaminepentaacetic acid dianhydride (2.00 g, 5.60 mmol) in 175 mL of DMF and 1,3-diaminopropane (0.415 g, 5.60 mmol) in DMF/DBN (172 mL/3 mL). The two syringes, mounted on a syringe pump were connected to the flask via two long needles passing through rubber septa. These solutions were added dropwise at ambient temperature at a rate of 40 mL/hour to a vigorously stirred solution. A syringe filled with DBN remained positioned in the flask such that additional DBN could be added dropwise to the reaction mixture when cloudiness was seen. A total of 2.5 mL of additional DBN was required to maintain a homogeneous reaction mixture. After the addition was complete, the reaction mixture was allowed to stir overnight, stripped to dryness, and 1N HCl added to adjust the pH to 10.5. This solution was then applied to AG1-X8 (100-200 MESH, OAc-) resin and eluted with 0.5N acetic acid to yield 0.428 g (18%) of the title product, as a white solid after removal of acetic acid followed by lyophilization.
