DOTA SYNTHESIS Russian patent published in 2020 - IPC C07D257/02 C07B41/06 

FIELD: chemical or physical processes.

SUBSTANCE: invention relates to a synthesis method of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), comprising (a) reacting 1,4,7,10-tetraazacyclicododecane (cyclen) with haloacetic acid and excess base; (b) crystallizing the reaction mixture obtained in step (a) by adding an organic solvent thereto, wherein said crystallisation is carried out at pH more than 3 and less than 3.5; (c) filtering the aqueous solution of the product crystallized at step (b) by nanofiltration; (d) crystallizing the filtered solution obtained in step (c), by adding organic solvent thereto. Invention also relates to a method of producing a metal-DOTA chelate complex and a method of producing meglumine gadoterate.

EFFECT: disclosed is a method of synthesis of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid applicable in industrial production, at which organic and inorganic impurities from the DOTA crude reaction mixture are better removed.

27 cl, 1 tbl, 2 ex