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【结 构 式】 
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【分子编号】35316 【品名】9-([2-hydroxy-1-[(trityloxy)methyl]ethoxy]methyl)-2-(tritylamino)-1,9-dihydro-6H-purin-6-one 【CA登记号】 |
【 分 子 式 】C47H41N5O4 【 分 子 量 】739.87384 【元素组成】C 76.3% H 5.59% N 9.47% O 8.65% |
合成路线1
该中间体在本合成路线中的序号：(VI)The reaction of ganciclovir (I) with trityl chloride in DMF in the presence of triethylamine and DMAP gives the N,O-bis(trityl) compound (VI), which is condensed with the activated L-valine derivative (III) by means of triethylamine in DMF/toluene to yield the expected valine ester (VII). Finally, the trityl groups of (VII) are removed with TFA in trifluoroethanol to afford the previously reported monoprotected compound (IV). The condensation of the tritylated ganciclovir (VI) with N-(tert-butoxycarbonyl)-L-valine (VIII) by means of DCC in dichloromethane gives the expected valine ester (IX), which is finally deprotected with TFA in dichloromethane. The valine ester (IX) can also be obtained by condensation of tritylated ganciclovir (VI) with N-(tert-butoxycarbonyl)-L-valine-N-carboxyanhydride (X) by means of triethylamine in DMF.
| 【1】 Sorbera, L.A.; Castañer, J.; Castañer, R.M.; Valganciclovir Hydrochloride. Drugs Fut 2000, 25, 5, 474. |
| 【2】 Arzeno, H.B.; Humphreys, E.R. (F. Hoffmann-La Roche AG); Process for preparing purine derivs.. US 5756736; WO 9727196 . |
| 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) | 35312 | 2-amino-9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]-1,9-dihydro-6H-purin-6-one | C9H13N5O4 | 详情 | 详情 | |
| (III) | 29555 | benzyl (4S)-4-isopropyl-2,5-dioxo-1,3-oxazolidine-3-carboxylate | 158257-41-1 | C14H15NO5 | 详情 | 详情 |
| (IV) | 35314 | 2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]-3-hydroxypropyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-methylbutanoate | C22H28N6O7 | 详情 | 详情 | |
| (VI) | 35316 | 9-([2-hydroxy-1-[(trityloxy)methyl]ethoxy]methyl)-2-(tritylamino)-1,9-dihydro-6H-purin-6-one | C47H41N5O4 | 详情 | 详情 | |
| (VII) | 35319 | 2-[[6-oxo-2-(tritylamino)-1,6-dihydro-9H-purin-9-yl]methoxy]-3-(trityloxy)propyl (2S)-2-[[(benzyloxy)carbonyl]amino]-3-methylbutanoate | C60H56N6O7 | 详情 | 详情 | |
| (VIII) | 19733 | (2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid | C10H19NO4 | 详情 | 详情 | |
| (IX) | 35317 | 2-[[6-oxo-2-(tritylamino)-1,6-dihydro-9H-purin-9-yl]methoxy]-3-(trityloxy)propyl (2S)-2-[(tert-butoxycarbonyl)amino]-3-methylbutanoate | C57H58N6O7 | 详情 | 详情 | |
| (X) | 35318 | tert-butyl (4S)-4-isopropyl-2,5-dioxo-1,3-oxazolidine-3-carboxylate | 141468-55-5 | C11H17NO5 | 详情 | 详情 |