Amadinone

A solution of 250.0 mg of δ4-3,20-dioxo-6α,7α-oxido-17α-acetoxy-19- norpregnene in 15 ml of 1 N hydrochloric acid in dioxan is kept for 1 h at 25°C, then poured into water and neutralized with sodium bicarbonate solution. The precipitated crude product is dissolved in a 5:1 mixture of ether and methylene chloride, washed with water until the washings run neutral, and the solution is dried and evaporated under vacuum to give the δ4-3,20- dioxo-6-chloro-7α-hydroxy-17α-acetoxy-19-nor-pregnene. The crude δ4-3,20-dioxo-6-chloro-7α-hydroxy-17α-acetoxy-19-nor-pregnene is dissolved in 3 ml of pyridine, mixed at 5°-0°C with 0.3 ml of methanesulphonyl chloride while being stirred, and the mixture is kept for 2 days at 10°C. The reaction product is then poured into dilute sodium bicarbonate solution, dissolved in ether, and the ethereal solution is washed until the washings run neutral, dried and evaporated under vacuum and the δ4-3,20-dioxo-6-chloro-7α-mesyloxy-17α-acetoxy-19-norpregnene is obtained. The δ4-3,20-dioxo-6-chloro-7α-mesyloxy-17α-acetoxy-19-norpregnene is dissolved in 25 ml of dimethyl formamide, mixed with 4.5 g of anhydrous sodium acetate, and the whole is heated for 75 min at 85°C under nitrogen while being stirred. The cooled reaction mixture is diluted with water, extracted with a 5:1-mixture of ether and methylene chloride, and the organic layer is washed with 100 ml of water, dried and evaporated. The resulting crude product is dissolved in benzene and chromatographed on 15 times its own weight of alumina (activity II). The afore-mentioned solvent elates 105.0 mg of pure δ4,6-3,20-dioxo-6-chloro-17α-acetoxy-19-norpregnadiene, melting point 159°-161°C (recrystallized from methylene chloride:hexane). The δ4,6-3,20-dioxo-6-chloro-17-hydroxy-19-norpregnadien, melting point 159°-161°C, may be produced by hydrolysis of δ4,6-3,20-dioxo-6-chloro-17α- acetoxy-19-norpregnadiene.

Progestin.