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【结 构 式】 
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【分子编号】10866 【品名】11-beta-[4-(Dimethylamino)phenyl]-5-alpha-hydroxy-5',5'-dimethyl-19-epi-spiro[9-estrene-3,2'-1,3-dioxan]-17-one 【CA登记号】 |
【 分 子 式 】C31H43NO4 【 分 子 量 】493.68676 【元素组成】C 75.42% H 8.78% N 2.84% O 12.96% |
合成路线1
该中间体在本合成路线中的序号：(V)The Grignard reaction of the protected epoxide (I) with 4-(dimethylamino)phenylmagnesium bromide (II) gives the 11-substituted compound (III), which is submitted to an Oppenhauer oxidation with cyclohexanone and aluminum isopropoxide yielding the 17-keto derivative (IV). The photochemical epimerization of the 13beta-methyl of (IV) with a high pressure mercury lamp in dioxane affords the epimer (V), which is condensed with 1-tetrahydropyranyloxy-2-propyne (VI) by means of butyllithium in THF to give the acetylenic alcohol (VII). Finally, this compound is reduced with hydrogen over Pd/C in ethanol and deprotected and dehydrated by treatment with hot aqueous acetic acid.
| 【1】 Wiechert, R.; Neef, G.; Synthesis of antiprogestational steroids. J Steroid Biochem 1987, 27, 4-6, 851. |
| 【2】 Pento, J.; Castaner, J.; Onapristone. Drugs Fut 1995, 20, 8, 784. |
| 【3】 Shiokawa, Y.; Akahane, A.; Katayama, H.; Mitsunaga, T. (Fujisawa Pharmaceutical Co., Ltd.); Pyrazolopyridine cpds. and processes for preparation thereof. AU 8817602; EP 0299209; JP 1989045385; US 4925849; US 4994453; US 5087629; US 5102878; US 5179103; US 5296490 . |
| 【4】 Henderson, D.; Neef, G.; Elger, W.; Wiechert, R.; Beier, S.; New steroids with antiprogestational and antiglucocorticoid activities. Steroids 1984, 44, 4, 349-72. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 10862 | 5-alpha,10-alpha-Epoxy-5',5'-dimethylspiro[9(11)-estrene-3,2'-1,3-diaxan]-17-beta-ol | C23H34O4 | 详情 | 详情 | |
| (II) | 10863 | Bromo[4-(dimethylamino)phenyl]magnesium | 7353-91-5 | C8H10BrMgN | 详情 | 详情 |
| (III) | 10864 | 11-beta-[4-(Dimethylamino)phenyl]-5',5'-dimethylspiro[9-estrene-3,2'-1,3-dioxane]-5-alpha,17-beta-diol | C31H45NO4 | 详情 | 详情 | |
| (IV) | 10865 | 11-beta-[4-(Dimethylamino)phenyl]-5-alpha-hydroxy-5',5'-dimethylspiro[9-estrene-3,2'-1,3-dioxan]-17-one | C31H43NO4 | 详情 | 详情 | |
| (V) | 10866 | 11-beta-[4-(Dimethylamino)phenyl]-5-alpha-hydroxy-5',5'-dimethyl-19-epi-spiro[9-estrene-3,2'-1,3-dioxan]-17-one | C31H43NO4 | 详情 | 详情 | |
| (VI) | 10867 | 2-(2-Propynyl)tetrahydro-2H-pyran | C8H12O | 详情 | 详情 | |
| (VII) | 10868 | 11beta-[4-(Dimethylamino)phenyl]-5alpha,17alpha-dihydroxy-13alpha-methyl-17beta-[3-(tetrahydropyran-2-yl)-1-propynyl]gonan-3-one propyleneketal | C37H51NO5 | 详情 | 详情 |