2-amino-9-[[2-(benzyloxy)-1-(hydroxymethyl)ethoxy]methyl]-1,9-dihydro-6H-purin-6-one -Drug Synthesis Database

【结构式】

【分子编号】35324

【品名】2-amino-9-[[2-(benzyloxy)-1-(hydroxymethyl)ethoxy]methyl]-1,9-dihydro-6H-purin-6-one

【CA登记号】

【分子式】C₁₆H₁₉N₅O₄

【分子量】345.35816

【元素组成】C 55.65% H 5.55% N 20.28% O 18.53%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XVIII)

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.

参考文献中间体

合成目标

【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	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

合成路线2

该中间体在本合成路线中的序号：(XVIII)

The condensation of 1-acetoxy-2-(acetoxymethoxy)-3-(benzyloxy) propane (XXI) with guanine (XXII) by means of HMDS and trifluoromethanesulfonic acid gives O-acetyl-O'-benzylganciclovir (XXIII), which is deacetylated with NaOH in methanol to yield the previously reported mono-O-benzylganciclovir (XVIII). The preceding reaction sequence can also be performed by using 1-(benzyloxy)-2-(propionyloxymethoxy)-3-(propionyloxy)propane (XXIV) instead of compound (XXI), yielding intermediate (XXV) and finally the previously reported mono-O-benzylganciclovir (XVIII).

参考文献中间体

合成目标

【1】 Sorbera, L.A.; Castañer, J.; Castañer, R.M.; Valganciclovir Hydrochloride. Drugs Fut 2000, 25, 5, 474.
【2】 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
(XVIII)	35324	2-amino-9-[[2-(benzyloxy)-1-(hydroxymethyl)ethoxy]methyl]-1,9-dihydro-6H-purin-6-one		C₁₆H₁₉N₅O₄	详情	详情
(XXI)	35326	[2-(acetoxy)-1-[(benzyloxy)methyl]ethoxy]methyl acetate		C₁₅H₂₀O₆	详情	详情
(XXII)	10352	2-Amino-1,9-dihydro-6H-purin-6-one; Guanine	73-40-5	C₅H₅N₅O	详情	详情
(XXIII)	35327	2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]-3-(benzyloxy)propyl acetate		C₁₈H₂₁N₅O₅	详情	详情
(XXIV)	35328	3-(benzyloxy)-2-[(propionyloxy)methoxy]propyl propionate		C₁₇H₂₄O₆	详情	详情
(XXV)	35329	2-[(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)methoxy]-3-(benzyloxy)propyl propionate		C₁₉H₂₃N₅O₅	详情	详情

Extended Information