Patent GB-1235742-A (GB)
Title: 01beta-METHYL-19-NORPREGNENE COMPOUNDS
IPC: A61K31/57
Filed: 1968-12-06
Abstract: 1,235,742. 11# - Methyl - 19 - norpregnene compounds. G. D. SEARLE & CO. 6 Dec., 1968 [8 Dec., 1967], No. 58044/68. Heading C2U. Novel steroids of the formula (wherein R is H, CHO or C 2-7  alkanoyl; R<SP>1</SP> is C 1-7  alkyl; R<SP>11</SP> is O or H (#-OH or #-Oacyl), where acyl is C 2-7  alkanoyl; Y is H, Cl or CH 3 ; X is H 2  or, when ring B is saturated and contains no substituent, =CH 2 ; and the #<SP>6</SP> double bond is optional) are prepared from 3-alkoxy- 13#-alkyl - 17α - ethyl - 17# - hydroxy - 11#- methylgona - 1,3,5(10) - trienes by known methods. Thus, dehydration to the 17(20)- dehydro compounds, hydroxylation to the 17α,20-diols, Birch reduction to the 2,5(10)- dien-3-enol ethers, hydrolysis to the #<SP>4</SP>-3-ones and 20-oxidation gives the 17α-hydroxy-#<SP>4</SP>-3,20- diones which may then be acylated, either by conventional processes which may necessitate hydrolysis of any #<SP>3</SP>'<SP>5</SP>-3-enol acylate formed or directly using as acylating agent the complex formed from a metalloid halide, an organic acid halide and a halogenated aliphatic solvent and conducting the reaction in the presence of a lower nitroparaffin of high dielectric constant and under anhydrous conditions. In another process the 20-hydroxy group of the abovementioned 17α,20-diols is oxidized and the resulting 20-ones are ketalized before Birch reduction, after which they may be hydrolysed directly to product 17α-hydroxy-#<SP>4</SP>-3,20-diones or acylated and then hydrolysed to 17α-acyloxy- #<SP>4</SP>-3,20-diones. The 16-methylene derivatives are prepared from 3-alkoxy-11#-methyl-19- norpregna - 1,3,5(10),16 - tetraen - 20 - ones by conversion to 16α,17#-pyrazolines, pyrolysis of these to 16-methyl-#<SP>16</SP>-compounds, peroxidation of these, cleavage of the 16α,17α-epoxides with strong acids to give 16-methylene-17α-ols, and then Birch reducing and hydrolysing these and oxidizing the 20-ol products which may then be 17-acylated. 6-Dehydro compounds are prepared by conversion of the #<SP>4</SP>-3-ones to #<SP>3,5</SP>-3- enol ethers and then oxidation of these, e.g. with manganese dioxide reagent or dichlorodicyanobenzoquinone; while 6α-methyl derivatives are prepared by subjecting these enol ethers to the Vilsmeier reagent to afford the corresponding 6-iminium intermediates, hydrolysing these to the 6-formyl compounds, reducing these to the 6-hydroxymethyl compounds, hydrolysing and dehydrogenating to the 6- methylene - #<SP>4</SP> - 3 - ones, hydrogenating these to the 6#-methyl compounds and epimerizing these; alternatively the 6-formyl derivatives may be converted directly to the 6α-methyl-#<SP>4</SP>- 3-ones by reduction and acid treatment. The 6 - methyl - #<SP>6</SP> - compounds are prepared from the 6-methylene compounds by isomerization. The 6α-chloro compounds are prepared from the above-mentioned enol ethers by treatment with HOCl or an agent liberating it and epimerization of the 6#-chloro-#<SP>4</SP>-3-ones thus-produced. The 6 - chloro - #<SP>4,6</SP> compounds are prepared (a) by direct dehydrogenation of the 6α-chloro-#<SP>4</SP>- compounds; or (b) via the 3-enol ethers as described above for the 6-methyl compounds; or (c) by converting the 3-keto-#<SP>4,6</SP>-compounds to 6α,7α-epoxides, adding on HCl to give the the 6# - chloro - 7α - hydroxy compounds, and dehydrating these. The 3#-ols are prepared by reduction of the 3-ones; they may subsequently be acylated. Starting materials which are racemates may be resolved by standard procedures.