METHOD FOR PRODUCTION OF CRYSTAL FORM OF CALCOBUTROL A MODIFICATION Russian patent published in 2022 - IPC C07D257/02 A61K49/10 

FIELD: chemistry.

SUBSTANCE: invention relates to a method for the production of a compound of the formula (I) in a crystal form of A modification, which is monohydrate with 2.0-2.5 wt.% of ethanol, and X-ray powder diffractometry diagram of the compound shows the maximum peak of 2 theta angle at 7.6°, 9.1°, 11.1°, 11.3°, 11.9°, and 12.3°. The method consists in that a gadolinium complex of dihydroxy-hydroxy-methylpropyl-tetraazacyclododecane-triacetic acid (gadobutrol) is subjected to decomposition, precipitated salt of gadolinium is removed, then, a solution with free ligands is bound to acidic ion-exchange resin, then, it is eluted with an aqueous main solution, then, it is bound into a complex to calcium²⁺ ions, then Ca:butrol stoichiometry is brought up to 1:1, then, crystallization from aqueous ethanol is carried out at a water content of 9-11 wt.%, and then, the product is dried and, thus, the compound of the formula (I) is isolated.

EFFECT: method for the production of a crystal form of A modification of a compound of the formula (I) with high purity, which is used in the production of Gadovist, is developed.

4 cl, 6 dwg, 9 tbl, 7 ex