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【结 构 式】 
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【分子编号】11729 【品名】tert-Butyl([(1S,3R,8S,9S,10R,13S,14S)-3-[[tert-butyl(dimethyl)silyl]oxy]-17-[(E)ethylidene]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-1-yl]oxy)dimethylsilane; tert-Butyl(dimethyl)silyl (1S,3R,8S,9S,10R,13S,14S)-1-[[tert-butyl(dimethyl)silyl]oxy]-17-[(E)ethylidene]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl ether 【CA登记号】 |
【 分 子 式 】C33H60O2Si2 【 分 子 量 】545.0092 【元素组成】C 72.73% H 11.1% O 5.87% Si 10.31% |
合成路线1
该中间体在本合成路线中的序号：(XVII)4) The Wittig condensation of the previously reported 1alpha,3beta-bis(tert-butyldimethylsilyloxy)androst-5-en-17-one (III) with ethyltriphenylphosphonium bromide and potassium tert-butoxide gives the corresponding 17-ethylidene derivative (XVII), which is treated first with 9-borabicyclo[3.3.1]nonane (9-BBN) and then with H2O2 and NaOH in THF yielding a mixture of the 20(S)- and 20(R)-isomers of the 1alpha,3beta-bis(tert-butyldimethylsilyloxy)pregn-5-en-20-ol that was separated by preparative TLC. The 20(S)-isomer (XVIII) was condensed with N,N-dimethylacrylamide (XV) by means of NaH affording the propionamide derivative (XIX), which by a Grignard condensation with methylmagnesium bromide catalyzed by CeCl3 is converted into 1alpha,3beta-bis(tert-butyldimethylsilyloxy)-20(S)-(3-hydroxy-3-methylbutoxy)pregn-5-ene (XX). Finally, this compound is dehydrogenated as before by bromination with N-bromosuccinimide (NBS) and dehydrobromination with 2,4,6-trimethylpyridine (TMPyr) to afford the 3-hydroxy-3-methylbutoxy derivative (XI), already obtained.
| 【1】 Kubodera, N.; Active vitamin D analogs. Important and various roles by medicinal chemists during the course of development of promising candidates as useful medicines. Jpn J Org Chem 1996, 54, 2, 139-45. |
| 【2】 Leeson, P.A.; Martel, A.M.; Castaner, J.; 22-Oxacalcitriol. Drugs Fut 1996, 21, 12, 1229. |
| 【3】 Kato, M.; Mikami, T.; Ochi, K.; Watanabe, H.; Kubodera, N. (Chugai Pharmaceutical Co. Ltd.); 22-Oxacalciferol deriv. and production thereof. WO 9312083 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 11715 | (1S,8R,9S,10R,13S,14S)-1,3-Bis[[tert-butyl(dimethyl)silyl]oxy]-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one | C31H56O3Si2 | 详情 | 详情 | |
| (V) | 11717 | Ethyl(triphenyl)phosphonium bromide; (Ethyl)triphenylphosphonium bromide | 1530-32-1 | C20H20BrP | 详情 | 详情 |
| (XI) | 11723 | 4-[[(1S)-1-((1S,3R,9S,10R,13S,14S,17S)-1,3-Bis[[tert-butyl(dimethyl)silyl]oxy]-10,13-dimethyl-2,3,4,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethyl]oxy]-2-methyl-2-butanol | C38H70O4Si2 | 详情 | 详情 | |
| (XV) | 11727 | N,N-Dimethylacrylamide; N,N-Dimethyl-2-propenamide | 2680-03-7 | C5H9NO | 详情 | 详情 |
| (XVII) | 11729 | tert-Butyl([(1S,3R,8S,9S,10R,13S,14S)-3-[[tert-butyl(dimethyl)silyl]oxy]-17-[(E)ethylidene]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-1-yl]oxy)dimethylsilane; tert-Butyl(dimethyl)silyl (1S,3R,8S,9S,10R,13S,14S)-1-[[tert-butyl(dimethyl)silyl]oxy]-17-[(E)ethylidene]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl ether | C33H60O2Si2 | 详情 | 详情 | |
| (XVIII) | 11730 | (1S)-1-((1S,3R,8S,9S,10R,13S,14S,17S)-1,3-Bis[[tert-butyl(dimethyl)silyl]oxy]-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-ethanol | C33H62O3Si2 | 详情 | 详情 | |
| (XIX) | 11731 | 3-[[(1S)-1-((1S,3R,8S,9S,10R,13S,14S,17S)-1,3-Bis[[tert-butyl(dimethyl)silyl]oxy]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethyl]oxy]-N,N-dimethylpropanamide | C38H71NO4Si2 | 详情 | 详情 | |
| (XX) | 11732 | 4-[[(1S)-1-((1S,3R,8S,9S,10R,13S,14S,17S)-1,3-Bis[[tert-butyl(dimethyl)silyl]oxy]-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethyl]oxy]-2-methyl-2-butanol | C38H72O4Si2 | 详情 | 详情 |