2-[2-(2-Amino-9H-purin-9-yl)ethyl]-1,3-propanediol -Drug Synthesis Database

【结构式】

【分子编号】11643

【品名】2-[2-(2-Amino-9H-purin-9-yl)ethyl]-1,3-propanediol

【CA登记号】

【分子式】C₁₀H₁₅N₅O₂

【分子量】237.2616

【元素组成】C 50.62% H 6.37% N 29.52% O 13.49%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(VIII)

A synthesis of famciclovir that corresponds to that previously published and studies on its oral bioavailability in rats and mice, identifying famciclovir as the preferred prodrug of BRL-39123 (penciclovir), have been published.

参考文献中间体

合成目标

【1】 Choudary, B.M.; Geen, G.R.; Kincey, P.M.; Parratt, M.J.; Dales, J.R.M.; Johnson, G.P.; O'Donnell, S.; Tudor, D.W.; Woods, N.; A direct approach to the synthesis of famciclovir and penciclovir. Nucleosides Nucleotides 1996, 15, 5, 981.
【2】 Harnden, M.R.; Boyd, M.R.; Vere Hodge, R.A.; Jarvest, R.L.; Sutton, D.; Prodrugs of the selective antiherpesvirus agent 9-[4-hydroxy-3-(hydroxy methyl)but-1-yl]guanine (BRL 39123) with improved gastrointestinal absorption properties. J Med Chem 1989, 32, 1738-43.

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)	11636	6,8-Dichloro-9H-purin-2-ylamine; 6,8-Dichloro-9H-purin-2-amine		C₅H₃Cl₂N₅	详情	详情
(II)	11637	dimethyl 3-(2-iodoethyl)pentanedioate		C₉H₁₅IO₄	详情	详情
(III)	11638	2-[(acetoxy)methyl]-4-(2-amino-6,8-dichloro-9H-purin-9-yl)butyl acetate		C₁₄H₁₇Cl₂N₅O₄	详情	详情
(IV)	11639	6,6-Dimethyl-5,7-dioxaspiro[2.5]octane-4,8-dione	5617-70-9	C₈H₁₀O₄	详情	详情
(V)	11640	5-[2-(2-amino-6,8-dichloro-9H-purin-9-yl)ethyl]-2,2-dimethyl-1,3-dioxane-4,6-dione		C₁₃H₁₃Cl₂N₅O₄	详情	详情
(VI)	11641	5-[2-(2-amino-9H-purin-9-yl)ethyl]-2,2-dimethyl-1,3-dioxane-4,6-dione		C₁₃H₁₅N₅O₄	详情	详情
(VII)	11642	dimethyl 2-[2-(2-amino-9H-purin-9-yl)ethyl]malonate		C₁₂H₁₅N₅O₄	详情	详情
(VIII)	11643	2-[2-(2-Amino-9H-purin-9-yl)ethyl]-1,3-propanediol		C₁₀H₁₅N₅O₂	详情	详情
(IX)	11644	6-Chloro-9H-purin-2-amine; 6-Chloro-9H-purin-2-ylamine; 2-Amino-6-chloropurine	10310-21-1	C₅H₄ClN₅	详情	详情
(X)	11645	5-[2-(2-Amino-6-chloro-9H-purin-9-yl)ethyl]-2,2-dimethyl-1,3-dioxane-4,6-dione		C₁₃H₁₄ClN₅O₄	详情	详情
(XI)	11646	triethyl 3-bromo-1,1,1-propanetricarboxylate		C₁₂H₁₉BrO₆	详情	详情
(XII)	11647	triethyl 3-(2-amino-6-chloro-9H-purin-9-yl)-1,1,1-propanetricarboxylate		C₁₇H₂₂ClN₅O₆	详情	详情
(XIII)	11648	triethyl 3-(2-amino-9H-purin-9-yl)-1,1,1-propanetricarboxylate		C₁₇H₂₃N₅O₆	详情	详情
(XIV)	11649	diethyl 2-[2-(2-amino-9H-purin-9-yl)ethyl]malonate		C₁₄H₁₉N₅O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

A new synthetic route to famciclovir has been described: The alkylation of 2,2-dimethyl-1,3-dioxan-5-one (I) with vinylmagnesium bromide (II) in THF gives the 2,2-dimethyl-5-vinyl-1,3-dioxan-5-ol derivative (II), which is treated with methyl chloroformate in the same solvent to yield the mixed carbonate (IV). Condensation of (IV) with 6-chloropurine-2-amine (V) by means of 1,2-bis(diphenylphosphino)ethane (dppe) and tris(dibenzylideneacetone)dipalladium(0) [Pd2(dba)3] in DMF at 80 °C for 7.5 h affords a 5:95 mixture of the N-7 (VI) and N-9 (VII) regioisomers, respectively. Hydrogenation of regioisomer (VII) with H2 over Pd/C in THF eliminates the 6-chlorine atom and reduces the exocyclic double bond giving the 2-aminopurine derivative (VIII), which is treated with HCl in methanol to remove the acetonide group affording diol (IX). Finally, this compound is acylated with acetic anhydride and DMAP/TEA in dichloromethane.

参考文献中间体

合成目标

【1】 Geen, G.R.; Share, A.C.; Slater, G.R.; Ramsay, T.W.; Smith, N.M.; Freer, R.; A new route to famciclovir via palladium catalysed allylation. Tetrahedron 2000, 56, 26, 4589.

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)	46538	2,2-dimethyl-1,3-dioxan-5-one		C₆H₁₀O₃	详情	详情
(II)	16524	bromo(vinyl)magnesium	1826-67-1	C₂H₃BrMg	详情	详情
(III)	46539			C₈H₁₃BrMgO₃	详情	详情
(IV)	46540	2,2-dimethyl-5-vinyl-1,3-dioxan-5-yl methyl carbonate		C₁₀H₁₆O₅	详情	详情
(V)	11644	6-Chloro-9H-purin-2-amine; 6-Chloro-9H-purin-2-ylamine; 2-Amino-6-chloropurine	10310-21-1	C₅H₄ClN₅	详情	详情
(VI)	46541	6-chloro-7-[2-(2,2-dimethyl-1,3-dioxan-5-ylidene)ethyl]-7H-purin-2-ylamine; 6-chloro-7-[2-(2,2-dimethyl-1,3-dioxan-5-ylidene)ethyl]-7H-purin-2-amine		C₁₃H₁₆ClN₅O₂	详情	详情
(VII)	46542	6-chloro-9-[2-(2,2-dimethyl-1,3-dioxan-5-ylidene)ethyl]-9H-purin-2-ylamine; 6-chloro-9-[2-(2,2-dimethyl-1,3-dioxan-5-ylidene)ethyl]-9H-purin-2-amine		C₁₃H₁₆ClN₅O₂	详情	详情
(VIII)	46543	9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]-9H-purin-2-amine; 9-[2-(2,2-dimethyl-1,3-dioxan-5-yl)ethyl]-9H-purin-2-ylamine		C₁₃H₁₉N₅O₂	详情	详情
(IX)	11643	2-[2-(2-Amino-9H-purin-9-yl)ethyl]-1,3-propanediol		C₁₀H₁₅N₅O₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

6-Deoxypenciclovir (I) was reacted with trimethyl orthoacetate in the presence of p-toluenesulfonic acid to give the cyclic orthoacetate intermediate (II) which, after aqueous quenching, afforded monoacetate ester (III). Subsequent treatment of (III) with isopropyl p-nitrophenyl carbonate (IV) using a catalytic amount of dimethylaminopyridine provided the target carbonate ester.

参考文献中间体

合成目标

【1】 Kim, D.-K.; et al.; Synthesis and evaluation of 2-amino-9-(3-acyloxymethyl-4-alkoxycarbonyloxybut-1-yl)purines and 2-amino-9-(3-alkoxycarbonyloxymethyl-4-alkoxycarbonyloxybut-1-yl)purines as potential prodrugs of penciclovir. Bioorg Med Chem 1999, 7, 8, 1715.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	11643	2-[2-(2-Amino-9H-purin-9-yl)ethyl]-1,3-propanediol	C₁₀H₁₅N₅O₂	详情	详情
(II)	35792	9-[2-(2-methoxy-2-methyl-1,3-dioxan-5-yl)ethyl]-9H-purin-2-ylamine; 9-[2-(2-methoxy-2-methyl-1,3-dioxan-5-yl)ethyl]-9H-purin-2-amine	C₁₃H₁₉N₅O₃	详情	详情
(III)	35793	4-(2-amino-9H-purin-9-yl)-2-(hydroxymethyl)butyl acetate	C₁₂H₁₇N₅O₃	详情	详情
(IV)	35794	isopropyl 4-nitrophenyl carbonate	C₁₀H₁₁NO₅	详情	详情

Extended Information