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【结 构 式】 
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【分子编号】10860 【品名】1-[[(dicyclohexylamino)sulfonyl]methyl]-7,7-dimethylbicyclo[2.2.1]hept-2-yl (2R)-4-cyano-2-ethyl-2-(4-pyridinyl)butanoate 【CA登记号】 |
【 分 子 式 】C34H51N3O4S 【 分 子 量 】597.86276 【元素组成】C 68.31% H 8.6% N 7.03% O 10.7% S 5.36% |
合成路线1
该中间体在本合成路线中的序号：(XVI-S)4) The (R)- and (S)-enantiomers of title product are obtained as follows: the trans-esterification of 2-(4-pyridyl)acetic acid methyl ester (XII) with the chiral alcohol (Oppolzer's camphor) (XIII) by means of butyllithium in THF gives the corresponding ester (XIV), which is alkylated with ethyl iodide and potassium hydride in THF yielding a mixture of the corresponding alkylated esters (XVR) and (XVS). The condensation of this mixture with acrylonitrile (IV) by means of potassium tert-butoxide in tert-butanol affords a mixture of the two diastereomeric nitriles (XVIR) and (XVIS), which are easily separable by column chromatography in silica gel. Both isolated compounds are then cyclized with sulfuric acid in refluxing acetic acid.
| 【1】 Webster, G.; Thickitt, C.P.; Rowlands, M.G.; Neidle, S.; Jarman, M.; Clissold, D.W.; McCague, R.; Mann, J.; Synthesis of the aromatase inhibitor 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione and its enantiomers. J Chem Soc - Perkins Trans I 1989, 196. |
| 【2】 Prous, J.; Castaner, J.; Rogletimide. Drugs Fut 1992, 17, 9, 791. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XV-S) | 10858 | 1-[[(dicyclohexylamino)sulfonyl]methyl]-7,7-dimethylbicyclo[2.2.1]hept-2-yl (2S)-2-(4-pyridinyl)butanoate | C31H48N2O4S | 详情 | 详情 | |
| (XV-R) | 10859 | 1-[[(dicyclohexylamino)sulfonyl]methyl]-7,7-dimethylbicyclo[2.2.1]hept-2-yl (2R)-2-(4-pyridinyl)butanoate | C31H48N2O4S | 详情 | 详情 | |
| (XVI-S) | 10860 | 1-[[(dicyclohexylamino)sulfonyl]methyl]-7,7-dimethylbicyclo[2.2.1]hept-2-yl (2R)-4-cyano-2-ethyl-2-(4-pyridinyl)butanoate | C34H51N3O4S | 详情 | 详情 | |
| (XVI-R) | 10861 | 1-[[(dicyclohexylamino)sulfonyl]methyl]-7,7-dimethylbicyclo[2.2.1]hept-2-yl (2R)-4-cyano-2-ethyl-2-(4-pyridinyl)butanoate | C34H51N3O4S | 详情 | 详情 | |
| (IV) | 10847 | Acrylonitrile | 107-13-1 | C3H3N | 详情 | 详情 |
| (XII) | 10855 | methyl 2-(4-pyridinyl)acetate | C8H9NO2 | 详情 | 详情 | |
| (XIII) | 10856 | N,N-Dicyclohexyl(2-hydroxy-7,7-dimethylbicyclo[2.2.1]hept-1-yl)methanesulfonamide; (-)-10-Dicyclohexylsulfamoyl-d-isoborneol | C22H39NO3S | 详情 | 详情 | |
| (XIV) | 10857 | 1-[[(dicyclohexylamino)sulfonyl]methyl]-7,7-dimethylbicyclo[2.2.1]hept-2-yl 2-(4-pyridinyl)acetate | C29H44N2O4S | 详情 | 详情 |