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Example 7
The synthesis of the methotrexate conjugates is described in (
Example 6
For the synthesis of platinum based anti cancer prodrugs, two approaches may be followed. The first approach (
A second approach (
Example 111
A mixture of N-Boc-ethylenediamine (5.6 mL, 35.4 mmol, 1.1 eq.) and saturated NaHCO3 (60 mL) was cooled to 0° C., to which compound 509 (5.00 g, 32.2 mmol, 1.0 eq.) was added in portions. After stirring at 0° C. for 30 min, the reaction was warmed to r.t. and stirred for 1 h. The precipitate was collected by filtration and washed with cold water, then dissolved in EtOAc and washed with brine, dried over anhydrous Na2SO4 and concentrated to give a white solid (6.69 g, 87% yield).
Example 4
Paclitaxel prodrug was synthesized following a five-step synthesis process and purified by column chromatography (