OBTAINING SECURE DO3A Russian patent published in 2024 - IPC C07D257/02 

FIELD: chemistry.

SUBSTANCE: invention relates to a single-step method of producing a salt of protected DO3A of formula (I)

where X is an anion of chlorine, iodine or bromine; y is integer from 1 to 3; and R is C₁-C₆ alkyl or aryl group; wherein said method includes: 1) reaction of cyclene with activated acetic ester of formula XCH₂COOR in an organic solvent selected from the group consisting of DMF (N,N-dimethylformamide), DMSO (dimethylsulfoxide), MeCN (acetonitrile) and DMAC (dimethylacetamide) and in the presence of an auxiliary base selected from the group consisting of NaOAc, NaHCO₃, Na₂CO₃, KHCO₃, K₂CO₃, DIPEA (N,N-diisopropylethylamine), and triethylamine to obtain a mixture; 2) adding water to the mixture of step 1), in which the water added at step 2) is in amount of 2.0–10 times (wt./wt.) greater than the amount of cyclene at step 1), to obtain a suspension containing the protected DO3A in the form of a solid salt of formula (I); and 3) collecting and washing salt of protected DO3A.

EFFECT: novel method of producing a salt of protected DO3A of formula (I) is developed, which provides convenient production on a larger, for example, industrial scale and enables to isolate the corresponding triester of DO3A in form of a solid salt directly from the crude reaction mixture.

17 cl, 1 tbl, 8 ex