GB1457802A - - Google Patents

Abstract

1457802 21-Fluoro-19-norpregnadiene compounds CIBA-GEIGY AG 26 Feb 1974 [28 Feb 1973 20 Dec 1973] 8619/74 Heading C2U Novel steroids of the formula (wherein X is H, C 1-7 alkyl, Cl or F and R 1 and R 2 are each H or an acyclic, carbocyclic-acyclic or carbocyclic hydrocarbon radical or both, together with the adjacent carbon atom, form a cycloaliphatic ring) are prepared (1) by introduction of a double bond into the corresponding 6,7-saturated steroids; (2) by converting the starting materials of (1) into 3-enol ethers, adding on the elements of a hypohalous acid and dehydrohalogenating the product; (3) by converting the aforementioned 3-enol ethers unsubstituted in the 6-position into 6-formyl derivatives and converting these to required 6- methyl #<SP>4,6</SP>-3-ones via 6-methyl-#<SP>4</SP>-3-ones; (4) by eliminating CO or CO 2 from corresponding 19-als or 19-oic acids; (5) by converting corresponding steroids containing in the 17(3-position the side chain -C(OM) = CHY in which Y is H, CHO or esterified oxalyl and M is an alkali metal or, if Y is CHO or esterified oxalyl, may also be H into the required products, possibly with temporary protection of the 3-oxo group; (6) by exchanging a 21-bromo or -organic sulphonyloxy substituent for F in corresponding steroids containing such a 21-substituent; or (7) by converting corresponding 16α,17α-diols or their 16-alkanoates into the required 16,17- acetals or -ketals by reaction with R 1 -CO-R 2 or a reactive derivative thereof. Products unsubstituted in the 6-position may be converted into 6-halo compounds by conversion to 6α,7α- epoxy-#<SP>4</SP>-3-ones and reaction of these with HCl or HF or a donor thereof. 21 - Fluoro - 16α,17α - isopropylidenedioxy- 3,20 - dioxo - 4,6 - pregnadienoic -19 - acid is prepared from 16α,17α - epoxy - 21 - fluoro- 3# - hydroxy - 5 - pregnen - 20 - one via 3#- acetoxy - 16# - bromo - 21 - fluoro - 17α - hydroxy- 5 - pregnen - 20 - one; the corresponding 17α- acetoxy compound; 3#,16α - diacetoxy - 21- fluoro - 17α - hydroxy - 5 - pregnen - 20 - one; 3# - acetoxy - 21 - fluoro - 16α,17α - isopropylidenedioxy - 5 - pregnen - 20 - one; the corresponding saturated 5α - bromo - 6# - ol; 3# - acetoxy - 5α- bromo - 6#,19 - epoxy - 21 - fluoro - 16α,17α- isopropylidenedioxy - 5α - pregnan - 20 - one; the corresponding 3#-ol; the corresponding #<SP>4</SP>- 3-one; 19 - acetoxy - 21 - fluoro - 16α,17α- isopropylidenedioxy - 4,6 - pregnadiene - 3,20- dione (a by-product here is 3-acetoxy-21-fluoro- 16α,17α - isopropylidenedioxy - 19 - nor- 1,3,5(10) - pregnatrien- 20 - one); and the corresponding 19-ol. 21-Fluoro - 16α,17α-isopropylidenedioxy - 6# - methyl - 19 - pregn - 4- ene-3,20-dione is prepared by reduction of the corresponding 6-methylene steroid. The novel steroids display a pronounced gestagenic and ovulation-inhibiting action and may be made up into pharmaceutical preparations with suitable carriers.