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【结 构 式】 
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【药物名称】AdThd 【化学名称】5'-Amino-5'-deoxythymidine 【CA登记号】25152-20-9, 67883-75-4 (monoacetate salt), 67883-74-3 (monoHCl) 【 分 子 式 】C10H15N3O4 【 分 子 量 】241.24875 |
【开发单位】Research Corporation Technologies (Originator) 【药理作用】ANTIINFECTIVE THERAPY, Antiviral Drugs |
合成路线1
The condensation of aniline (I) with diethyl ethoxymethylenemalonate (II) by heating at 90 C gives diethyl anilinomethylenemalonate (III), which is cyclized to ethyl 4-hydroxyquinoline-3-carboxylate (IV) by heating at 240 C in diphenyl ether-biphenyl. The reaction of (IV) with hot POCl3 affords ethyl 4-chloro-quinoline-3-carboxylate (V), which is finally cyclized with phenylhydrazine (VI) by heating at 105 C in xylene. (VI) is prepared in the usual way starting from aniline (I) by diazotation with NaNO2-HCl to phenyldiazonium chloride (VII), and reduction with SnCl2-HCl.
| 【1】 Urbanski, J.A.; Chua, J.; Tomson, A.J.; Horwitz, J.P.; Nucleosides. I. 5'-Amino-5'-deoxyuridine and 5'-amino-5'-deoxythymidine. J Org Chem 1962, 27, 3045-48. |
| 【2】 Prusoff, W.H.; Lin, T.S.; Synthesis and biological activity of several amino analogues of thymidine. J Med Chem 1978, 21, 1, 109-112. |
| 【3】 Blancafort, P.; Hopkins, S.J.; Castaner, J.; Serradell, M.N.; AdThd. Drugs Fut 1983, 8, 3, 179. |
| 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) | 12161 | Thymidine; 1-[(2R,4S,5R)-4-Hydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione | 50-89-5 | C10H14N2O5 | 详情 | 详情 |
| (II) | 35959 | [(2R,3S,5R)-3-hydroxy-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methyl 4-methylbenzenesulfonate | C17H20N2O7S | 详情 | 详情 | |
| (III) | 35960 | 1-[(2R,4S,5R)-5-(azidomethyl)-4-hydroxytetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione | C10H13N5O4 | 详情 | 详情 |