METHOD FOR OBTAINING CRYSTALLINE FORM 8 SOPHOSBUVIR (VERSIONS) Russian patent published in 2021 - IPC A61K31/7072 C07H19/10 

FIELD: chemistry.

SUBSTANCE: invention relates to variants of a method for producing crystalline form 8 of sofosbuvir. One of the variants of the method includes mashing a mixture of a known form of sofosbuvir, selected from crystalline forms 1, 6, 7, and amorphous form, and an organic solvent in which it is soluble or moderately soluble, selected from isopropanol, ethanol, ethyl acetate, with a precipitating agent, selected from the group consisting of diethyl ether, diisopropyl ether, dimethyl ether, methyl tert-butyl ether, petroleum ether, n-hexane, n-heptane, n-octane and mixtures thereof, the amount of organic solvent in the mixture being from 5 to 60% of the mass of a mixture of a known form of sofosbuvir and an organic solvent. In this case, a mixture of a known form of sofosbuvir and an organic solvent, in which it is soluble or moderately soluble, is obtained by dissolving the known form of sofosbuvir in an amount of organic solvent sufficient to dissolve the form, followed by evaporation of the organic solvent to the specified amount in the mixture of the organic solvent. Another variant of the method includes ultrasonic treatment of a known form of sofosbuvir, selected from crystalline forms 1, 6, 7, α and an amorphous form suspended in an organic solvent, in which it is very little soluble or practically insoluble, selected from the group including n-heptane, n-hexane, n-octane, their isomers or mixtures thereof, petroleum ether. Also, the ultrasound treatment is carried out until the known form of sofosbuvir passes into an amorphous oily state, and then again into a solid crystalline state.

EFFECT: proposed variants of the method make it possible to obtain the crystalline form 8 of sofosbuvir with high yield and purity.

2 cl, 3 dwg, 5 tbl, 12 ex