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【结 构 式】

【分子编号】11731

【品名】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

【CA登记号】

【 分 子 式 】C38H71NO4Si2

【 分 子 量 】662.15708

【元素组成】C 68.93% H 10.81% N 2.12% O 9.67% Si 8.48%

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:(XIX)

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
Extended Information