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METHOD OF OBTAINING SGLT2 BENZYLENBENZOLE INHIBITORS
专利权人:
Terakos Sab; LLK
发明人:
SYUJ Bajkhua (US),СЮЙ Байхуа (US),LV Binkhua (CN),ЛВ Бинхуа (CN),SYUJ Ge (CN),СЮЙ Гэ (CN),SID Brajan (US),СИД Брайан (US),ROBERZH Zhak (US),РОБЭРЖ Жак (US),SYUJ Bajkhua,СЮЙ Байхуа,LV Binkhua,ЛВ Бинхуа,SYUJ Ge,СЮЙ Гэ,SID Brajan,СИД Брайан,ROBERZH Zhak,РОБЭРЖ Жак
申请号:
RU2014144944
公开号:
RU0002625795C2
申请日:
2013.03.14
申请国别(地区):
RU
年份:
2017
代理人:
摘要:
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 Ra is Rb; (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 Ra is Rb, with formation of a compound of formula Ia where R4 is C1-C3 alkoxy, and each Ra is independently seleted from the group, containg H and Rb; 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 Rb. Rb is a protection group, where alkyl, alkoxy and cycloalkyl groups or their parts can optionally b
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