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【结 构 式】 
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【分子编号】61585 【品名】N-{1-[(2R,3S,5R)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-(hydroxymethyl)-4-oxotetrahydro-2-furanyl]-2-oxo-1,2-dihydro-4-pyrimidinyl}benzamide 【CA登记号】 |
【 分 子 式 】C22H29N3O6Si 【 分 子 量 】459.57438 【元素组成】C 57.5% H 6.36% N 9.14% O 20.89% Si 6.11% |
合成路线1
该中间体在本合成路线中的序号：(VII)The reaction of cytidine (I) with benzoyl anhydride in dioxane gives N-benzoylcytidine (II), which is selectively monoprotected at the primary OH group by means of 4-methoxytrityl chloride and pyridine to yield N-benzoyl-5'O-(monomethoxytrityl)cytidine (III). The monosilylation of (III) by means of Tbdms-Cl and AgNO3 in pyridine/THF affords a mixture of the 3'-O-silyl (IV) and the desired 2'-O-silyl (V) derivative which is easily separated by flash chromatography. (The yield of the desired 2'-O-silyl isomer (V) can be improved by isomerization of the 3'-O-silyl isomer (IV) by means of pyridine in methanol at 70 C). The oxidation of (V) by means of CrO3 and Ac2O provides the 3'-oxonucleoside (VI), which is selectively deprotected by means of TsOH in chloroform/methanol to give compound (VII). The reaction of (VII) with trimethylsilylacetylene (VIII) by means of BuLi and CeCl3 in THF yields the protected ethynyl nucleoside (IX), which is debenzoylated by means of NH3 in methanol to afford the silylated nucleoside (X). Finally, this compound is treated with TBAF in THF to obtain the target ethynyl cytidine.
| 【1】 Ludwig, P.S.; Schwender, R.A.; Schott, H.; A new laboratory scale synthesis for the anticancer drug 3'-C.ethynylcytidine. Synthesis (Stuttgart) 2002, 16, 2387. |
| 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) | 27920 | Cytidine; 4-amino-1-((2S,3S,4S,5S)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one;4-amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2(1H)-pyrimidinone | 65-46-3 | C9H13N3O5 | 详情 | 详情 |
| (II) | 61580 | N-Benzoylcytidine;N-[1-[3,4-Dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]benzamide;N-{1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-2-oxo-1,2-dihydro-4-pyrimidinyl}benzamide | 13089-48-0 | C16H17N3O6 | 详情 | 详情 |
| (III) | 61581 | N-[1-((2R,3R,4S,5R)-3,4-dihydroxy-5-{[tris(4-methoxyphenyl)methoxy]methyl}tetrahydro-2-furanyl)-2-oxo-1,2-dihydro-4-pyrimidinyl]benzamide | C38H37N3O9 | 详情 | 详情 | |
| (IV) | 61582 | N-[1-((2R,3R,4S,5R)-4-{[tert-butyl(dimethyl)silyl]oxy}-3-hydroxy-5-{[tris(4-methoxyphenyl)methoxy]methyl}tetrahydro-2-furanyl)-2-oxo-1,2-dihydro-4-pyrimidinyl]benzamide | C44H51N3O9Si | 详情 | 详情 | |
| (V) | 61583 | N-[1-((2R,3R,4R,5R)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-hydroxy-5-{[tris(4-methoxyphenyl)methoxy]methyl}tetrahydro-2-furanyl)-2-oxo-1,2-dihydro-4-pyrimidinyl]benzamide | C44H51N3O9Si | 详情 | 详情 | |
| (VI) | 61584 | N-[1-((2R,3S,5R)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-oxo-5-{[tris(4-methoxyphenyl)methoxy]methyl}tetrahydro-2-furanyl)-2-oxo-1,2-dihydro-4-pyrimidinyl]benzamide | C44H49N3O9Si | 详情 | 详情 | |
| (VII) | 61585 | N-{1-[(2R,3S,5R)-3-{[tert-butyl(dimethyl)silyl]oxy}-5-(hydroxymethyl)-4-oxotetrahydro-2-furanyl]-2-oxo-1,2-dihydro-4-pyrimidinyl}benzamide | C22H29N3O6Si | 详情 | 详情 | |
| (VIII) | 23897 | ethynyl(trimethyl)silane；trimethylsilyl acetylene | 1066-54-2 | C5H10Si | 详情 | 详情 |
| (IX) | 61586 | N-(1-{(2R,3R,4R,5R)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-hydroxy-5-(hydroxymethyl)-4-[2-(trimethylsilyl)ethynyl]tetrahydro-2-furanyl}-2-oxo-1,2-dihydro-4-pyrimidinyl)benzamide | C27H39N3O6Si2 | 详情 | 详情 | |
| (X) | 61587 | 4-amino-1-{(2R,3R,4R,5R)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-hydroxy-5-(hydroxymethyl)-4-[2-(trimethylsilyl)ethynyl]tetrahydro-2-furanyl}-2(1H)-pyrimidinone | C20H35N3O5Si2 | 详情 | 详情 |