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【结 构 式】

【分子编号】36070

【品名】1-[(3S,8S,9S,10R,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-1-ethanone

【CA登记号】145-13-1

【 分 子 式 】C21H32O2

【 分 子 量 】316.48388

【元素组成】C 79.7% H 10.19% O 10.11%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(I)

The reaction of pregnenolone (I) with I2 and pyridine at 90 C gives (3beta-hydroxypregn-5-en-20-one-21-yl)pyridinium iodide (II), which by treatment with sodium methoxide in refluxing methanol is converted into methyl 5-androsten-3beta-ol-17beta-carboxylate (III). The Meerwein-Poundorf oxidation of (III) with cyclohexanone (A) and aluminum isopropoxide in refluxing toluene yields methyl 4-androsten-3-one-17beta-carboxylate (IV), which is hydrolyzed with KOH in refluxing methanol - water to the corresponding free acid (3-oxo-4-etienic acid) (V). The reaction of (V) with oxalyl chloride (B) and diethylamine in refluxing toluene affords 17beta-(N,N-diethylcarbamoyl)-4-androstene-3-one (VI), which is oxidized with O3 or with NaIO4 and KMnO4 giving 17beta-(N,N-diethylcarbamoyl)-5-oxo-3,5-secoandrostan-3-oic acid (VII). The cyclization of (VII) with methylamine ethylene glycol at 180 C in a pressure vessel affords 17beta-(N,N-diethylcarbamoyl)-4-methyl-4-aza-5-androsten-3-one (VIII), which is finally reduced with H2 over Pt in acetic acid. The cyclization of the acid (VII) with NH3 in ethanol at 180 C in a pressure vessel gives 17beta-(N,N-diethylcarbamoyl)-4-aza-5-androsten-3-one (IX), which is reduced with H2 over Pt in acetic acid yielding 17beta-(N,N-diethylcarbamoyl)-4-aza-5alpha-androstan-3-one (X). Finally, this compound is methylated with CH3I by means of NaH in toluene.

1 Hillier, K.; Blancafort, P.; Serradell, M.N.; Castaner, J.; 4-MA. Drugs Fut 1983, 8, 4, 323.
2 Jobson, R.B.; Johnston, D.B.R.; Rasmusson, G.H.; Reinhold, D.F.; Utne, T. (Merck & Co., Inc.); Preparation of 4-aza-17-substituted-5 alpha -androstan-3-ones useful as 5 alpha -reductase inhibitors. US 4220775 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(A) 11059 Cyclohexanone 108-94-1 C6H10O 详情 详情
(B) 29841 Oxalyl chloride; 2-Chloro-2-oxoacetyl chloride 79-37-8 C2Cl2O2 详情 详情
(I) 36070 1-[(3S,8S,9S,10R,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-1-ethanone 145-13-1 C21H32O2 详情 详情
(II) 36071 1-[2-[(3S,8S,9S,10R,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl]pyridinium iodide C26H36INO2 详情 详情
(III) 36072 Methyl 3[beta]-hydroxyandrost-5-ene- 17[beta]carboxylate; methyl (3S,8S,9S,10R,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-carboxylate 7254-03-7 C21H32O3 详情 详情
(IV) 14899 methyl (8S,9S,10R,13S,14S,17S)-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-carboxylate C21H30O3 详情 详情
(V) 14892 (8S,9S,10R,13S,14S,17S)-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-carboxylic acid; 4-Androstene-3-oxo-17-beta-carboxylic acid 7385-78-6 C20H28O3 详情 详情
(VI) 36073 (8S,9S,10R,13S,14S,17S)-N,N-diethyl-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-carboxamide C24H37NO2 详情 详情
(VII) 36074 3-[(3S,3aS,5aS,6R,9aS,9bS)-3-[(diethylamino)carbonyl]-3a,6-dimethyl-7-oxododecahydro-1H-cyclopenta[a]naphthalen-6-yl]propionic acid C23H37NO4 详情 详情
(VIII) 36075 (4aR,4bS,6aS,7S,9aS,9bS)-N,N-diethyl-1,4a,6a-trimethyl-2-oxo-2,3,4,4a,4b,5,6,6a,7,8,9,9a,9b,10-tetradecahydro-1H-indeno[5,4-f]quinoline-7-carboxamide C24H38N2O2 详情 详情
(IX) 36076 (4aR,4bS,6aS,7S,9aS,9bS)-N,N-diethyl-4a,6a-dimethyl-2-oxo-2,3,4,4a,4b,5,6,6a,7,8,9,9a,9b,10-tetradecahydro-1H-indeno[5,4-f]quinoline-7-carboxamide C23H36N2O2 详情 详情
(X) 36077 (4aR,4bS,6aS,7S,9aS,9bS,11aR)-N,N-diethyl-4a,6a-dimethyl-2-oxohexadecahydro-1H-indeno[5,4-f]quinoline-7-carboxamide C23H38N2O2 详情 详情
Extended Information