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【结 构 式】 
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【分子编号】35325 【品名】2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]-3-(benzyloxy)propyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-methylbutanoate 【CA登记号】 |
【 分 子 式 】C29H34N6O7 【 分 子 量 】578.6252 【元素组成】C 60.2% H 5.92% N 14.52% O 19.36% |
合成路线1
该中间体在本合成路线中的序号：(XX)The condensation of 2-(acetoxymethoxy)-1,3-bis(benzyloxy)propane (XIV) with N2-acetylguanine (XV) by means of hexamethyldisilazane (HMDS) and trifluoromethanesulfonic acid gives the N2-acetyl-O,O'-dibenzylganciclovir (XVI), which is selectively monodebenzylated with either H2 over Pd/C in methanol or cyclohexene and Pd(OH)2 in refluxing ethanol, yielding intermediate (XVII), which by deacetylation with NH4OH in methanol affords mono-O-benzylganciclovir (XVIII). The condensation of (XVIII) with N-benzyloxycarbonyl-L-valine (XIX) by means of DCC in dichloromethane gives the expected valine ester (XX), which is finally debenzylated with H2 over Pd/C in methanol as before.
| 【1】 Nestor, J.J.; Womble, S.W.; Maag, H. (F. Hoffmann-La Roche AG); 2-(2-Amino-1,6-dihydro-6-oxo-purin-9-yl)methoxy-1,3-propanediol deriv.. CA 2154721; EP 0694547; ES 2083348; JP 1996041061; US 5840891; US 6083953 . |
| 【2】 Sorbera, L.A.; Castañer, J.; Castañer, R.M.; Valganciclovir Hydrochloride. Drugs Fut 2000, 25, 5, 474. |
| 【3】 Dvorak, C.A.; Beard, C.C.; Wren, D.L.; Axt, S.D.; Han, Y.-K.; Fatheree, P.R.; Nguyen, S.L.; Lund, J.P.; Fisher, L.E.; Arzeno, H.B.; Humphreys, E.R. (F. Hoffmann-La Roche AG); Process for preparing purine derivs.. US 6040446; WO 9727198 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIV) | 29160 | [2-(benzyloxy)-1-[(benzyloxy)methyl]ethoxy]methyl acetate | C20H24O5 | 详情 | 详情 | |
| (XV) | 29163 | N-(6-oxo-6,9-dihydro-1H-purin-2-yl)acetamide | C7H7N5O2 | 详情 | 详情 | |
| (XVI) | 29162 | N-[9-([2-(benzyloxy)-1-[(benzyloxy)methyl]ethoxy]methyl)-6-oxo-6,9-dihydro-1H-purin-2-yl]acetamide | C25H27N5O5 | 详情 | 详情 | |
| (XVII) | 35323 | N-(9-[[2-(benzyloxy)-1-(hydroxymethyl)ethoxy]methyl]-6-oxo-6,9-dihydro-1H-purin-2-yl)acetamide | C18H21N5O5 | 详情 | 详情 | |
| (XVIII) | 35324 | 2-amino-9-[[2-(benzyloxy)-1-(hydroxymethyl)ethoxy]methyl]-1,9-dihydro-6H-purin-6-one | C16H19N5O4 | 详情 | 详情 | |
| (XIX) | 18092 | (2S)-2-[[(benzyloxy)carbonyl]amino]-3-methylbutyric acid | C13H17NO4 | 详情 | 详情 | |
| (XX) | 35325 | 2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]-3-(benzyloxy)propyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-methylbutanoate | C29H34N6O7 | 详情 | 详情 |