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Turosteride((-)-enantiomer), FCE-26073

妥罗雄脲Chemical Name: 17beta-[N-Isopropyl-N-(isopropylcarbamoyl)carbamoyl]-4-methyl-4-aza-5alpha-androstan-3-one; N-Isopropyl-N-(N-isopropylcarbamoyl)-4-methyl-3-oxo-4-aza-5alpha-androstane-17beta-carboxamide; 1,3-Diisopropyl-1-(4-methyl-3-oxo-4-aza-5alpha-androstan-17beta-carbonyl)urea
CAS No. 137099-09-3
项目整合开发状态: Phase II
项目研究机构: Pfizer (Originator)
合成路线:1) By the reaction of 4-methyl-3-oxo-4-aza-5alpha-androstane-17beta-carboxylic acid (I) with diisopropylcarbodiimide (II) in methylene chloride at room temperature.

合成路线:2) By the reaction of 3-oxoandrost-4-ene-17beta-carboxylic acid (III) with diisopropylcarbodiimide (II) in refluxing ethyl acetate and subsequent A-ring opening of compound (IV) by treatment with the Lamieux-von Rudloff reagent (permanganate-periodate) in isopropanol.The cyclization of the secoacid (V) so obtained,with methylamine in dioxane under pressure,followed by the hydrogenation under pressure,on 10% Pd/C in ethanol,affords turosteride.This method is used for the large scale production of turosteride.
📌 参考资料/链接:
参考文献标题:17beta-Substd.-4-aza-5alpha-androstan-3-one derivs.and process for their preparation
文献作者:Panzeri,A.; Di Salle,E.; Nesi,M.(Pharmacia Corp.)
参考来源:EP 0468012; JP 1992505462; US 5155107; WO 9112261

📄 详细内容


合成路线:1) By the reaction of 4-methyl-3-oxo-4-aza-5alpha-androstane-17beta-carboxylic acid (I) with diisopropylcarbodiimide (II) in methylene chloride at room temperature.

合成路线:2) By the reaction of 3-oxoandrost-4-ene-17beta-carboxylic acid (III) with diisopropylcarbodiimide (II) in refluxing ethyl acetate and subsequent A-ring opening of compound (IV) by treatment with the Lamieux-von Rudloff reagent (permanganate-periodate) in isopropanol.The cyclization of the secoacid (V) so obtained,with methylamine in dioxane under pressure,followed by the hydrogenation under pressure,on 10% Pd/C in ethanol,affords turosteride.This method is used for the large scale production of turosteride.

参考文献标题:Turosteride
文献作者:Di Sale,E.; Panzeri,A.
参考来源:Drugs Fut 1993,18(5),436


合成路线:The synthesis of [14C]-turosteride has been reported:The reaction of 20-[14C]-3-hydroxy-5-pregnen-20-one (I) with iodine and pyridine gives the pyridinium derivative (II),which is treated with sodium methoxide and methanol yielding 3-hydroxy-5-androstene-17beta-carboxylic acid methyl ester (III).The oxidation of (III) with cyclohexanone and aluminum isopropoxide affords 3-oxo-5-androstene-17beta-carboxylic acid methyl ester (IV),which is oxidized with potassium permanganate and sodium periodate to the propionic acid derivative (V).The cyclization of (V) with methylamine in diglyme at 180 C affords 4-methyl-3-oxo-4-aza-5-androstene-17beta-carboxylic acid methyl ester (VI),which is hydrogenated with H2 over PtO2 in acetic acid to the corresponding saturated compound (VII).The saponification of (VII) with KOH in refluxing methanol/water gives the 4-methyl-3-oxo-4-aza-5alpha-androstane-17beta-carboxylic acid (VIII),which is finally condensed with diisopropylcarbodiimide (IX) in refluxing dichloromethane.

参考文献标题:Synthesis of carbon-14 labelled 1-[4-methyl-3-oxo-4-aza-5alpha-androstane-17beta-carbonyl]-1,3-diisopropylurea (turosteride),a new 5alpha-reductase inhibitor
文献作者:Panzeri,A.; Dostert,P.; Angiuli,P.; Fontana,E.; Pignatti,A.
参考来源:J Label Compd Radiopharm 1996,38(7),667


合成路线:1) By the reaction of 4-methyl-3-oxo-4-aza-5alpha-androstane-17beta-carboxylic acid (I) with diisopropylcarbodiimide (II) in methylene chloride at room temperature.
参考文献标题:Azasteroids as inhibitors of rat prostatic 5alpha-reductase
文献作者:Rasmusson,H.G.; Reynolds,G.F.; Utne,T.; Jobson,R.B.; Primka,R.L.; Berman,C.; Brooks,J.R.
参考来源:J Med Chem 1984,27(12),1690-701


产品链接: CAS No. 137099-09-3››