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【结 构 式】 
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【分子编号】32209 【品名】5'-Deoxy-2',3'-isopropylidene-5-fluorouridine; 5-Fluoro-1-[(4R,6R)-2,2,6-trimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-2,4(1H,3H)-pyrimidinedione 【CA登记号】 |
【 分 子 式 】C12H15FN2O5 【 分 子 量 】286.2599832 【元素组成】C 50.35% H 5.28% F 6.64% N 9.79% O 27.95% |
合成路线1
该中间体在本合成路线中的序号：(V)This compound can be prepared by several different ways: 1) The reaction of 5-fluorouridine (I) with 2,2-dimethoxypropane (A) by means of p-toluenesulfonic acid gives 2',3'-isopropylidene-5-fluorouridine (III), which is treated with triphenylphosphite methiodide in DMF to afford 5'-deoxy-5'-iodo-2',3'-isopropylidene-5-fluorouridine (IV). The reduction of (IV) with H2 over Pd/C in methanol-triethyl-amine yields 5'-deoxy-2',3'-isopropylidene-5-fluorouridine (V), which is finally hydrolyzed with aqueous trifluoroacetic acid. 2) The hydrolysis of compound (IV) with aqueous trifluoroacetic acid as before gives 5'-deoxy-5'-iodouridine (II), which is finally reduced with H2 over Pd/C as before. 3) Compound (II) can also be obtained by reaction of (I) with triphenyl phosphite methiodide as before. 4) It can also be prepared via reduction of the 5'-chloro intermediate with tributyltin hydride.
| 【1】 Beranek, J.; Hrebabecky, H.; Analogs of nucleosides. XVI. 5'-Halo-2',3'-sulfites in the synthesis of 2',5'-dideoxy-5-fluorouridine and related analogs. Coll Czech Chem Commun 1978, 43, 15, 3268-78. |
| 【2】 Cook, A.F.; et al.; Fluorinated pyrimidine nucleosides. 3. Synthesis and antitumor activity of a series of 5'-deoxy-5-fluoropyrimidine nucleosides. J Med Chem 1979, 22, 11, 1330-35. |
| 【3】 Cook, A.F. (Hoffmann-La Roche, Inc.); 5'-Deoxy-5-fluoropyrimidine nucleosides. DE 2756653; ES 471584; FR 2374334; GB 1589688; JP 53095982; US 4071680 . |
| 【4】 Castaner, J.; Albonico, S.M.; Serradell, M.N.; Blancafort, P.; Doxifluridine. Drugs Fut 1981, 6, 2, 80. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 10722 | 1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane | 77-76-9 | C5H12O2 | 详情 | 详情 |
| (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) | 32206 | 1-[(2R,3R,4S,5S)-3,4-dihydroxy-5-(iodomethyl)tetrahydro-2-furanyl]-5-fluoro-2,4(1H,3H)-pyrimidinedione | C9H10FIN2O5 | 详情 | 详情 | |
| (III) | 32207 | 2',3'-Isopropylidene-5-fluorouridine; 5-Fluoro-1-[(4R,6R)-6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-2,4(1H,3H)-pyrimidinedione | C12H15FN2O6 | 详情 | 详情 | |
| (IV) | 32208 | 5-Fluoro-1-[(4R,6S)-6-(iodomethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-2,4(1H,3H)-pyrimidinedione; 5'-Deoxy-5'-iodo-2',3'-isopropylidene-5-fluorouridine | C12H14FIN2O5 | 详情 | 详情 | |
| (V) | 32209 | 5'-Deoxy-2',3'-isopropylidene-5-fluorouridine; 5-Fluoro-1-[(4R,6R)-2,2,6-trimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-2,4(1H,3H)-pyrimidinedione | C12H15FN2O5 | 详情 | 详情 |