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【结 构 式】 
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【药物名称】CB-1267 【化学名称】1(S),3(R)-Dihydroxy-20(R)-[5,5,5-trifluoro-4-hydroxy-4-(trifluoromethyl)-2-pentynyloxymethyl]-9,10-secopregna-5(Z),7(E),10(19)-triene 【CA登记号】139174-97-3 【 分 子 式 】C28H36F6O4 【 分 子 量 】550.58712 |
【开发单位】Leo (Originator) 【药理作用】Oncolytic Drugs, Vitamin D Analogs |
合成路线1
Reduction of vitamin D derivative (I) with NaBH4 in ethanol-THF affords alcohol (II), which is alkylated with propargyl bromide (III) and potassium tert-butoxide in the presence of a crown ether. The resulting propargyl ether (IV) is condensed with hexafluoroacetone, by means of butyl litium, to provide tertiary alcohol (V). This compound is then photochemically isomerized in the presence of anthracene as a sensitizer to give (VI). Final deprotection of TBDMS groups with tetrabutylammonium fluoride in THF yields the title compound.
| 【1】 Calverley, M.J.; Grue-Sorensen, G.; Binderup, E.T. (Leo Pharmaceutical Products Ltd. A/S); Novel vitamin D analogues. EP 0522013; JP 1993505613; US 5374629; WO 9115475 . |
| 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) | 27521 | (2R)-2-[(1R,3aS,7aR)-4-[(E)-2-((3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethylidene]-7a-methyloctahydro-1H-inden-1-yl]propanal | C34H60O3Si2 | 详情 | 详情 | |
| (II) | 27522 | (2R)-2-[(1R,3aS,7aR)-4-[(E)-2-((3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethylidene]-7a-methyloctahydro-1H-inden-1-yl]-1-propanol | C34H62O3Si2 | 详情 | 详情 | |
| (III) | 11176 | 3-Bromopropyne; 3-Bromo-1-propyne | 106-96-7 | C3H3Br | 详情 | 详情 |
| (IV) | 27523 | (1R,5S)-3-((E)-2-[(1R,3aS,7aR)-7a-methyl-1-[(1R)-1-methyl-2-(2-propynyloxy)ethyl]octahydro-4H-inden-4-ylidene]ethylidene)-5-[[tert-butyl(dimethyl)silyl]oxy]-4-methylenecyclohexyl tert-butyl(dimethyl)silyl ether | C37H64O3Si2 | 详情 | 详情 | |
| (V) | 27524 | 5-[((2R)-2-[(1R,3aS,7aR)-4-[(E)-2-((3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethylidene]-7a-methyloctahydro-1H-inden-1-yl]propyl)oxy]-1,1,1-trifluoro-2-(trifluoromethyl)-3-pentyn-2-ol | C40H64F6O4Si2 | 详情 | 详情 | |
| (VI) | 27525 | 5-[((2R)-2-[(1R,3aS,7aR)-4-[(Z)-2-((3S,5R)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-2-methylenecyclohexylidene)ethylidene]-7a-methyloctahydro-1H-inden-1-yl]propyl)oxy]-1,1,1-trifluoro-2-(trifluoromethyl)-3-pentyn-2-ol | C40H64F6O4Si2 | 详情 | 详情 |