Synthesis of amino-terminated hexethylene glycol (HEG) linked DOTA ligand 4.
Reagents and conditions: (a) 1.0 eq. MsCl, Et3N, DCM, 0 °C-RT, 3 h; (b) Potassium phthalimide, DMF, 110 °C, 15 h, 44% in two steps; (c) 1.5 eq. MsCl, Et3N, DCM, 0 °C-RT, 3 h; (d) NaI, acetone, 65 °C, 15 h, 95% in two steps; (e) DO3A-t-Bu-ester, KHCO3, DMF, 12 h, RT, 96%; (f) Hydrazine, ethanol, 65 °C, 4 h, 96%.