METHOD FOR PREPARATION OF POLYMORPHOUS FORM IN TREPROSTINIL DIETHANOLAMINE SALT Russian patent published in 2022 - IPC C07C59/72 C07C59/90 C07C51/41 C07C213/08 

FIELD: chemistry.

SUBSTANCE: invention relates to a method for the production of a polymorphous form B of Treprostinil diethanolamine salt, including following stages: a. dissolution of Treprostinil in methanol at 25-50°C, b. addition to the solution obtained at the stage a) of diethanolamine or its solution in methanol, c. mixing of the reaction mixture obtained at the stage b) until its complete dissolution, d. after the completion of salt formation at the stage c), addition to the solution of the first portion of an aprotic solvent, e. filtration of the solution obtained at the stage d), f. introduction to the filtrate obtained at the stage e) of a seed from the polymorphous form B of Treprostinil diethanolamine salt, g. addition to the suspension of crystals obtained at the stage f) of the second portion of the aprotic solvent, h. mixing of the suspension obtained at the stage g) until crystallization completion, i. isolation, flushing, and drying of crystals, where the aprotic solvent is selected from esters, ketones, composite esters, and acetonitrile. The invention also relates to the conversion of a polymorphous form A or a mixture of polymorphous forms A and B of Treprostinil diethanolamine salt into a polymorphous form B.

EFFECT: new stable reproducible method for the production of a polymorphous form B of Treprostinil diethanolamine salt is developed.

9 cl, 2 tbl, 17 ex, 21 dwg