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【结 构 式】 
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【分子编号】58291 【品名】{(2R,3R,5R)-3-(acetyloxy)-4-bromo-5-[5-fluoro-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl}methyl acetate 【CA登记号】 |
【 分 子 式 】C13H14BrFN2O7 【 分 子 量 】409.1658432 【元素组成】C 38.16% H 3.45% Br 19.53% F 4.64% N 6.85% O 27.37% |
合成路线1
该中间体在本合成路线中的序号：(V)The bromoacetylation of 5-fluorouridine (I) with 2-acetoxyisobutyryl bromide (II) in acetonitrile, ethyl acetate or dichloromethane gives a mixture of four bromoacylated compounds (III), (IV), (V) and (VI). This mixture, without separation, is treated with Zn/Ac-OH in DMF or methanol/ethyl acetate to yield two unsaturated uridine derivatives (VII) and (VIII), which are easily separated. The major isomer (VIII) is condensed with 1,2,4-triazole (IX) by means of POCl3 and TEA in acetonitrile to afford the triazolyl derivative (X), which is treated with ammonia in methanol to provide the cytidine derivative (XI). Finally, this compound is deacylated by means of NaOMe in methanol to afford the target fluorocytidine derivative.
| 【1】 Confalone, P.N.; Jin, F. (Pharmasset, Inc.); Method for the synthesis of 2',3'-dideoxy-2',3'-didehydronucleosides. WO 0270533 . |
| 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) | 32205 | 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-fluoro-2,4(1H,3H)-pyrimidinedione; 5-Fluorouridine | 316-46-1 | C9H11FN2O6 | 详情 | 详情 |
| (II) | 12806 | 2-bromo-1,1-dimethyl-2-oxoethyl acetate; alpha-Acetoxy-isobutyryl bromide | 40635-67-4 | C6H9BrO3 | 详情 | 详情 |
| (III) | 58289 | {(2R,3R,5R)-3-(acetyloxy)-4-bromo-5-[5-fluoro-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl}methyl 2-(acetyloxy)-2-methylpropanoate | C17H20BrFN2O9 | 详情 | 详情 | |
| (IV) | 58290 | {(2R,4S,5R)-4-(acetyloxy)-3-bromo-5-[5-fluoro-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl}methyl 2-(acetyloxy)-2-methylpropanoate | C17H20BrFN2O9 | 详情 | 详情 | |
| (V) | 58291 | {(2R,3R,5R)-3-(acetyloxy)-4-bromo-5-[5-fluoro-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl}methyl acetate | C13H14BrFN2O7 | 详情 | 详情 | |
| (VI) | 58292 | {(2R,5R)-4-(acetyloxy)-3-bromo-5-[5-fluoro-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl}methyl acetate | C13H14BrFN2O7 | 详情 | 详情 | |
| (VII) | 58293 | {(2S,5R)-5-[5-fluoro-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-2,5-dihydro-2-furanyl}methyl acetate | C11H11FN2O5 | 详情 | 详情 | |
| (VIII) | 58294 | {(2S,5R)-5-[5-fluoro-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-2,5-dihydro-2-furanyl}methyl 2-(acetyloxy)-2-methylpropanoate | C15H17FN2O7 | 详情 | 详情 | |
| (IX) | 13135 | 1H-1,2,4-Triazole; 1,2,4-Triazole | 288-88-0 | C2H3N3 | 详情 | 详情 |
| (X) | 58295 | 2-({(2S,5R)-5-[5-fluoro-2-oxo-4-(1H-1,2,4-triazol-1-yl)-1(2H)-pyrimidinyl]-2,5-dihydro-2-furanyl}methoxy)-1,1-dimethyl-2-propenyl acetate | C18H20FN5O5 | 详情 | 详情 | |
| (XI) | 58296 | 2-({(2S,5R)-5-[4-amino-5-fluoro-2-oxo-1(2H)-pyrimidinyl]-2,5-dihydro-2-furanyl}methoxy)-1,1-dimethyl-2-propenyl acetate | C16H20FN3O5 | 详情 | 详情 |