METHOD OF OBTAINING SGLT2 BENZYLENBENZOLE INHIBITORS Russian patent published in 2017 - IPC C07H7/04 C07C39/15 C07C43/225 C07C41/16 A61K31/7034 A61P3/10 

FIELD: chemistry.

SUBSTANCE: invention relates to a process of obtaining SGLT2 benzylenbenzole inhibitors, producing an inhibitory effect on sodium-dependent glucose transporter of compound of formula , comprising (a) production of the first reaction mixture, containg formula : alkyl magnesium complex selected from groups, consisting of C₁-C₄ alkyl magnesium chloride, C₁-C₄ alkyl magnesium bromide, (C₁-C₄ alkyl) dimagnesium, C₃-C₇ cycloalkylmagnesium chloride, C₃-C₇ cycloalkylmagnesium bromide and (C₃-C₇ cycloalkyl) dimagnesium and the first organic solvent, where proportion of alkil magnesium complex and the compound of formula IIa is selected from 0.9, 0.91, 0.92, 0.93, 0.94, 0.95, 0.96 and 0.97 (mmol/mmol), where the first reaction mixture is at a temperature of -50°C or lower, with formation of an intermediate compound; and (b) production of the second reaction mixture containing an intermediate compound, a second organic solvent and a compound of formula IIIa: with formation of compound of formula Ia where R⁴ is OH and each R^a is R^b; (C) obtaining the third reaction mixture containing C₁-C₃ alkyl hydroxy, a strong acid and a compound of formula Ia where R⁴ is OH and each R^a is R^b, with formation of a compound of formula Ia where R₄ is C₁-C₃ alkoxy, and each R^a is independently seleted from the group, containg H and R^b; and (d) obtaining of the fourth reaction mixture, comprising a reducing agent and a compound of formula Ia where R⁴ is C¹-C³ alkoxy and where the reaction mixture contains less than 0.1 magnesium equivalents in relation to quantity of compound of formula Ia with formation of a compound of formula Ia, where R⁴ is H, where X is iodine, R¹ is chlorine, R² is H, R³ is (C₃-C₆ cycloalkoxy) C₁-C₃ alkoxy, R⁴ is selected from the group consisting of H, OH and C₁-C₃ alkoxy, each R⁴ is independently selected from the group, consisting of H, C₁-C₃ alkyl and R^b. R^b is a protection group, where alkyl, alkoxy and cycloalkyl groups or their parts can optionally be completely or partially fluorinated and one or more hydrogen atoms may optionally be replaced with deuterium atoms and synthetic intermediates which can be used for obtaining such compounds. .

EFFECT: increase the output of desired product and decrease the amount of by-products.

38 cl, 2 tbl, 7 dwg, 25 ex