17a-fluoroalkyl steroids method for producing the same and pharmaceutical compositions containing said compounds
A technology of fluoroalkyl steroids and drugs, which is applied in the field of 17-fluoromethyl steroids and can solve the problems of ignorance of 17-pentafluoroethyl-alkylated steroids
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Embodiment 1
[0172] 17β-Hydroxy-17α-trifluoromethyl-androst-4-en-3-one
[0173] 10 g of 3β-acetoxy-DHEA was dissolved in 300 ml of THF, and mixed with 0.5 g of tetrabutylammonium fluoride. While stirring at room temperature, 15 ml of trifluoromethyltrimethylsilane was slowly added dropwise, followed by stirring for 3 hours. Next, 200 ml of semi-concentrated sodium bicarbonate solution was added, and THF was distilled off in vacuo. The residue was extracted three times with 100 ml of ethyl acetate. The combined organic extracts are dried, concentrated by evaporation and chromatographed on silica gel. 12 g of 3β-acetoxy-17β-trimethylsilyloxy-17α-trifluoromethyl-androst-5-ene are obtained.
[0174]Dissolve 12 g of 3β-acetoxy-17β-trimethylsilyloxy-17α-trifluoromethyl-androst-5-ene in 100 ml of THF, then mix with 20 ml of 30% hydrofluoric acid at room temperature mix. After 3 hours, it is poured into 200 ml of 12% ammonia solution, extracted with ethyl acetate (3*100 ml), the organic extra...
Embodiment 2
[0178] 17β-Hydroxy-17α-trifluoromethyl-7α-methyl-androst-4-en-3-one
[0179] 7 g of 17β-hydroxy-17α-trifluoromethyl-androst-4-en-3-one were refluxed with 8.5 g of chloranil in 200 ml of tert-butanol for 30 minutes. Allow to cool, then evaporate to dryness. The residue is chromatographed on silica gel. For further purification, recrystallize from dichloromethane / hexane. 17β-Hydroxy-17α-trifluoromethyl-androst-4,6-dien-3-one is obtained.
[0180] 1 H-NMR: 1.04(s, 3H, H-18), 1.13(s, 3H, H-19), 5.69(s, 1H, H-4), 6.11(m, 2H, H-6, H-7 )
[0181] 19 F-NMR: -75.3
[0182] Add 80ml of THF to a methylmagnesium iodide solution (prepared from 2.5g of magnesium and 6.4ml of iodomethane in 80ml of ether), cool to -5°C, and then add 1 g copper acetate monohydrate. After cooling to -20°C, a solution of 5 g of 17β-hydroxy-17α-trifluoromethyl-androst-4,6-dien-3-one in 80 ml of THF was added dropwise. After 2 hours it was poured into ice water / 2N sulfuric acid and extracted with ethyl ...
Embodiment 3
[0186] 17β-Hydroxy-17α-trifluoromethyl-4-chloro-androst-4-en-3-one
[0187] step 1
[0188] 17β-Hydroxy-17α-trifluoromethyl-4ξ,5ξ-epoxy-androstan-3-one
[0189] 2 g of 17β-hydroxy-17α-trifluoromethyl-androst-4-en-3-one were dissolved in 120 ml of methanol and 70 ml of THF and mixed with 20 ml of hydrogen peroxide solution (35%) at 10°C. While stirring, 5 ml of 10% sodium hydroxide solution was added, followed by stirring for 3 hours. The reaction solution was concentrated by evaporation to 50 ml, then mixed with 50 ml of dichloromethane and 25 ml of water, and the organic phase was separated. Washed with semi-concentrated thiosulfate, dried and evaporated to dryness. The resulting residue consisted of a mixture of 4α,5α- or 4β,5β-epoxides and was used in the next step without further purification.
[0190] step 2
[0191] 17β-Hydroxy-17α-trifluoromethyl-4-chloro-androst-4-en-3-one
[0192] 2 g of the epoxide mixture (step 1) were dissolved in 200 ml of acetone and mixed ...
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