FIELD: chemistry of technological processes.
SUBSTANCE: method for producing tofacitinib of formula (I). The method includes the following steps: (a) adding cyanoacetic acid in a molar equivalent of 0.2-1.2 to the compound of formula (II-S); (b) causing a reaction of the reaction mixture with the carbodiimide of formula (III) at 0-40°C in presence of a coupling agent, where R represents cyclohexyl or isopropyl. The invention is also related to a method for obtaining an intermediate compound of formula (II-S), including the following stages: (ia) interaction of a compound of formula (VI) with a compound of formula (VII) in the presence of an inorganic base at 80-100°C to form a compound of formula (V); (iia) reacting a compound of formula (V) with an alkali metal hydroxide, where the reaction is carried out at 30-65°C in the solvent system of methanol:water at a ratio of 4:1 vol. to form a compound of formula (IV); (iiia) hydrogenation of a compound of formula (IV) at pH 3-5 using a metal catalyst at 25-60°C to form a compound of formula (II); (iva) adjusting the pH of the reaction mass using an organic base; (va) extracting the compound of formula (II) with a solvent from the reaction mass; (via) adding cyanoacetic acid to form a compound of formula (II-S).
EFFECT: provision of a method that reduces formation of N-methyl impurities during the preparation of tofacitinib of formula (I).
18 cl, 1 tbl, 8 ex
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