Preparation of 17 beta-substituted 4-aza-androst-1-en-3-one compounds, e.g. finasteride, by 3-stage dehydrogenation of corresponding 1,2-saturated compound

摘要

Production of 17beta -substituted 4-aza-androst-1-en-3-one compounds (I) involves: (1) protecting 3-keto-4-aza (lactam) group of 4-aza-androstan-3-one (II); (2) contacting product with dehydrogenation catalyst in presence of optionally substituted benzoquinone, allyl methyl carbonate, allyl ethyl carbonate and/or allyl propyl carbonate, to introduce 1(2)-double bond; and (3) removing protecting(s) groups. Production of 17beta -substituted 4-aza-androst-1-en-3-one compounds of formula (I) (or their salts if R = OH) involves: (1) introducing protecting groups into the 3-keto-4-aza (lactam) group of a corresponding 4-aza-androstan-3-one compound of formula (II) to give a product of formula (III) (and optionally also protecting R if R = OH); (2) contacting the product with a dehydrogenation catalyst in presence of optionally substituted benzoquinone, allyl methyl carbonate, allyl ethyl carbonate and/or allyl propyl carbonate, to introduce a 1(2)-double bond; and (3) removing the protection introduced in step (1). [Image] R : OH; 1-12C alkyl or 2-12C alkenyl (both optionally substituted); or phenyl, benzyl, OR 1, NHR 1or NR 1R 2; R 1H; or 1-12C alkyl, 2-12C alkenyl or phenyl (all optionally substituted); R 2H, Me, Et or propyl; or NR 1R 25- or 6-membered heterocycle; R 3trialkylsilyl; R 4alkoxycarbonyl (preferably tert. butoxycarbonyl (Boc)), phenoxycarbonyl or trialkylsilyl; or R 3+ R 4-CO-CO- or -CO-Y-CO-; Y : (CR 5R 6) n, C(R 5)=C(R 6) or o-phenylene; R 5, R 6H, 1-8C alkyl or alkenyl, optionally substituted phenyl or benzyl; n : 1-4. ACTIVITY : Cytostatic; Antialopecia. MECHANISM OF ACTION : 5alpha -Reductase Inhibitor.