| CPC A61K 49/106 (2013.01) | 42 Claims |
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1. A process for the manufacturing of a dimeric complex compound 5 of formula
 which comprises:
1) Preparing a solution of DO3A tri-tert-butyl ester of formula 1A
 in an organic solvent;
2) Preparing a solution of a compound of formula 2
 in an organic solvent;
3) Admixing the solutions prepared according to steps 1) and 2) to obtain a solution of a compound of formula 3
 4) Without isolating the compound from the solution of step 3), removing the tert-butyl protecting groups from the compound of formula 3 to obtain a solution of a respective free ligand of formula 4
 5) Without isolating the free ligand of formula 4, adding a molar excess of gadolinium metal ions to the solution of step 4) in an amount of 2.05 moles or more with respect to 1 mole of deprotected dimeric ligand of formula 4 to obtain a solution of the respective dimeric complex of formula 5;
6) Adding to the solution of the dimeric complex of formula 5 a precipitating agent to precipitate a portion of free gadolinium metal ions; and
7) isolating the dimeric complex of formula 5 as a white solid by spray drying of the solution directly collected from step 6),
wherein a reaction solvent in all the steps following the preparation of the compound of formula 3 is an aqueous solvent.
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