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【结 构 式】 
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【分子编号】56604 【品名】(8S,10R,13S,14S,17S)-17-(2-chloroethynyl)-10,13-dimethyl-17-(nitrooxy)-1,2,6,7,8,10,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one 【CA登记号】 |
【 分 子 式 】C21H24ClNO4 【 分 子 量 】389.8786 【元素组成】C 64.69% H 6.2% Cl 9.09% N 3.59% O 16.41% |
合成路线1
该中间体在本合成路线中的序号：(XIV)Reaction of 4,9(11)-androstadien-3,17-dione (III) with trimethyl orthoformate and TsOH in dioxane gives 3-methoxy-3,5,9(11)-androstatrien-17-one (XI), which is condensed with 1,2-dichloroethylene (XII) by means of MeLi in ethyl ether/THF to yield 17a-(chloroethynyl)-17b-hydroxy-4,9(11)-androstadien-3-one (XIII). Esterification of the OH group of (XIII) with fuming HNO3 and acetic anhydride affords the 17b-(nitrooxy) derivative (XIV), which is treated with formic acid and AgNO3 in N-methylpyrrolidone to provide 21-chloro-17a-(formyloxy)-4,9(11)-pregnadien-3,20-dione (XV). Hydrolysis of the formyloxy group of (XV) by means of KHCO3 in methanol/water gives 21-chloro-17a-hydroxy-4,9(11)-pregnadien-3,20-dione (XVI), which is finally acetylated by means of AcOK and KI in hot DMF.
| 【1】 Castaner, J.; Sorbera, L.A.; Leeson, P.A.; Bayes, M.; Anecortave Acetate. Drugs Fut 2002, 27, 11, 1039. |
| 【2】 Annen, K.; Laurent, H.; Wiechert, R.; Hofmeister, H. (Schering AG); Process for the preparation of pregnane deriv.. DE 3434448; EP 0181442; US 4708823 . |
| 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) | 56595 | (8S,10R,13S,14S)-10,13-dimethyl-7,8,10,12,13,14,15,16-octahydro-1H-cyclopenta[a]phenanthrene-3,17(2H,6H)-dione | C19H24O2 | 详情 | 详情 | |
| (XI) | 18040 | (8S,10R,13S,14S)-3-methoxy-10,13-dimethyl-1,2,7,8,10,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one | C20H26O2 | 详情 | 详情 | |
| (XII) | 28793 | (Z)-1,2-dichloroethene | 156-59-2 | C2H2Cl2 | 详情 | 详情 |
| (XIII) | 56603 | (8S,10R,13S,14S,17S)-17-(2-chloroethynyl)-17-hydroxy-10,13-dimethyl-1,2,6,7,8,10,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one | C21H25ClO2 | 详情 | 详情 | |
| (XIV) | 56604 | (8S,10R,13S,14S,17S)-17-(2-chloroethynyl)-10,13-dimethyl-17-(nitrooxy)-1,2,6,7,8,10,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one | C21H24ClNO4 | 详情 | 详情 | |
| (XV) | 50605 | allyl (2S,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-[(E)-3-[(methylsulfonyl)amino]-1-propenyl]-1-pyrrolidinecarboxylate | C18H34N2O5SSi | 详情 | 详情 | |
| (XVI) | 56606 | (8S,10R,13S,14S,17R)-17-(2-chloroacetyl)-17-hydroxy-10,13-dimethyl-1,2,6,7,8,10,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one | C21H27ClO3 | 详情 | 详情 |