Loading patent…
AssigneeRichter Gedeon Nyrt.
InventorsJózsef Bódi, György Visky, János Széles, Sándor Mahó, Csaba Sánta, János Csörgei, Zoltán Tuba, László Terdy, Csaba Molnár, Antal Aranyi, Zoltán Horváth, Gábor Balogh
Estimating the term…
The present invention relates to a process for the synthesis of the known 17-acetoxy-11-β-[4-(dimethyl amino)-phenyl]-21-methoxy-19-norpregna-4,9-dien-3,20-dione (further on CDB-4124) of formula (I) from 3,3-[1,2-ethandiyl-bis(oxy)]-oestr-5(10),9(11)-dien-17-one of formula (II). Compound CDB-4124 belongs to the group of anti-hormones. The process has the following steps: i) formation of an epoxide; ii) addition of hydrogen cyanide; iii) silylation of a hydroxyl group; iv) reaction with 4-(dimethylamino)-phenyl magnesium bromide Grignard reagent in the presence of CuCl (Teutsch reaction); v) silylation of a hydroxyl group with trimethyl chlorosilane; vi) reaction with diisobutyl aluminum hydride and after addition of acid to the reaction mixture; vii) methoxy-methylation with methoxy-methyl Grignard reagent formed in situ, while hydrolyzing the trimethylsilyl protective groups; viii) oxidation of a hydroxyl group with dicyclohexyl carbodiimide in the presence of dimethyl sulfoxide and a strong organic acid (Swern oxidation), and in given case after purification by chromatography; ix) acetylation of a hydroxyl group with acetic anhydride in the presence of perchloric acid, and in given case, purification by chromatography. The invention also relates to new intermediates of the process.
An industrial process for the synthesis of 17-acetoxy-11β-[4-(dimethylamino)-phenyl]-21-methoxy-19-norpregna-4,9-dien-3,20-dione of formula (I)
11β-[4-(dimethylamino)-phenyl]-3,3-[1,2-ethandiyl-bis(oxy)]-5,17α-bis-[trimethyl-silyl-(oxy)]-5α-oestr-9-en-17β-carbonitrile of formula (VII)
11β-[4-(dimethylamino)-phenyl]-3,3-[1,2-ethandiyl-bis(oxy)]-5,17α-bis-[trimethyl-silyl-(oxy)]-5α-oestr-9-en-17β-carbaldehide of formula (VIII).
Dependencies are inferred from the claim text.