Chinese name: Finasteride
English name: Finasteride
CAS: 98319-26-7
Molecular formula: C23H36N2O2
MDL number: MFCD00869737
Molecular weight: 372.54
Appearance: white or white crystalline solid. Soluble in chloroform, dimethyl sulfoxide, ethanol, methanol or n-propanol, insoluble in propylene glycol or polyethylene glycol 400, very slightly soluble in 0.1mol/L hydrochloric acid, 0.1mol/L sodium hydroxide solution or water. Melting point about 257℃; There is also a melting point of 252 ~ 254℃. [α]D-59°(C=l, methanol).
Melting point :253 °C
Specific rotation: 405-59 ° (c = 1 in methanol)
Boiling point :576.6±50.0 °C(Predicted)
Density :1.065± 0.06g /cm3(Predicted)
Storage condition: room temp
Solubility: DMSO: 32 mg/mL, soluble
Solubility: DMSO: 32 mg/mL, soluble
Acidity coefficient (pKa) : 14.17±0.70(Predicted)
Form: solid
Color: White to beige
Water solubility: insoluble
Merck: 14,4082
Merck: 4082
BCS Class: 1
InChIKey: DBEPLOCGEIEOCV-WSBQPABSSA -n
LogP: 3.030
Use 1
It is used to treat the diseases of male prostatic hypertrophy and baldness
Use 2
5α-reductase inhibitors, which inhibit the conversion of testosterone to DHT. For the treatment of benign prostatic hyperplasia.
Preparation method
Method one
Using pregnenolone as raw material. It reacts with pyridine and then with sodium methanol to obtain 3-hydroxy-5-androstene-17β-carboxylate methyl ester (Ⅲ). And aluminum isopropyl alcohol in toluene and cyclohexanone, reflux. Filter, wash, dry, concentrate under reduced pressure. Petroleum ether was added, stirred at 5℃, and the oxidation product (Ⅳ) was extracted and filtered with yield of 74.6%. The oxidation product and 95% ethanol and 10% potassium hydroxide solution were reflux under nitrogen protection. After the ethanol is steamed under reduced pressure, the Ph value is about 3 with 6mol of hydrochloric acid. The cake was washed with water until neutral, and the hydrolysate (V) was obtained by drying. The yield was 96.4%. The hydrolyzed products were dissolved in tert-butanol, and the aqueous solution of anhydrous sodium carbonate was added under stirring, and the aqueous solution of sodium periodate and potassium permanganate was added under reflux, and the reflux was added. Cool, strain. After the filtrate is decompressed and most of the tert-butanol is steamed away, the Ph value is about 2 under the ice bath with 6mol/L hydrochloric acid. Extract with ethyl acetate, wash with saturated sodium chloride and dry. The ring-opening product (Ⅵ) was obtained by recrystallization of ethyl acetate with a yield of 66%. Under the cooling of the ice bath, ammonia gas was added to the glycol, the ring-opening product was added, and the reaction was slowly raised to 180℃. Let it cool, add water, and use 6 moles per second. The hydrochloric acid is adjusted to a Ph of about 2. The solid was filtered, washed to neutral, recrystallized with dimethylformamide to obtain a ring product (Ⅶ) with yield of 62.1%. The cycled product was hydrogenated with platinum dioxide, acetic acid and a small amount of perchloric acid at 85℃ and atmospheric pressure. After the catalyst is filtered, concentration is reduced to dry. The residue was recrystallized with dimethylformamide to obtain a hydrogenated product (Ⅷ) with a yield of 92.9%. The hydrogenated product was mixed with triphenylphosphine, toluene and 2,2 '-dipyridine disulfide (DPDS) and stirred at room temperature. Pyridine sulfide (Ⅸ) was isolated by column chromatography with a yield of 79.0%. The sulfide and anhydrous tetrahydrofuran and tert-butylamine were stirred overnight at room temperature, dichloromethane was added, washed with 2mol/L hydrochloric acid and saturated sodium chloride, dried and concentrated under reduced pressure. The residue was recrystallized with ethyl acetate to obtain the amide product (X) in 77.1% yield. The amide, together with benzene-selenite anhydride and chlorobenzene, backflows and slowly steam out the solvent and the resulting water. The crude product was recrystallized with ethyl acetate to obtain white finasteride crystal with yield of 52.3% and melting point of 253-255 ℃.
China
