合成路线:This compound has been obtained by two similar ways:1) The reaction of 6-chloropurine-2-amine (I) with 6,6-dimethyl-5,7-dioxaspiro[2.5]octane-4,8-dione (II) by means of K2CO3 in DMF gives the expected condensation product (III),which is methanolized with HCl/methanol yielding 2-[2-(2-amino-6-methoxypurin-9-yl)ethyl]malonic acid dimethyl ester (IV).The reduction of (IV) with NaBH4 in tert-butanol/methanol affords the corresponding diol (V),which is finally converted into pecnciclovir by hydrolysis with 2N NaOH.2) The reaction of purine (I) with 3-bromopropane-1,1,1-tricarboxylic acid triethyl ester (VI) by means ofK2CO3 in DMF gives the expected condensation product (VII),which is partially decarboxylated with sodium methoxide in methanol yielding 2-[2-(2-amino-6-chloropurin-9-yl)ethyl]malonic acid diethyl ester (VIII).The reduction of (VIII) with NaBH4 in tert-butanol/methanol followed by acetylation with acetic anhydride affords the corresponding diol diacetate (IX),which is finally converted into penciclovir by hydrlysis with 2N HCl.
合成路线: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.
合成路线:The reaction of purine (I) with 3-bromopropane-1,1,1-tricarboxylic acid triethyl ester (II) by means ofK2CO3 in DMF gives the expected condensation product (III),which is partially decarboxylated with sodium methoxide in methanol yielding 2-[2-(2-amino-6-chloropurin-9-yl)ethyl]malonic acid diethyl ester (IV).The reduction of (IV) with NaBH4 in tert-butanol/methanol followed by acetylation with acetic anhydride affords the corresponding diol diacetate (V),which is finally converted into famciclovir by reductive dechlorination with H2 over Pd/C in ethyl acetate/triethylamine.
参考文献标题:A direct approach to the synthesis of famciclovir and penciclovir
文献作者: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.
参考来源:Nucleosides Nucleotides 1996,15(5),981
合成路线: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 癈 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.
参考文献标题:A new route to famciclovir via palladium catalysed allylation
文献作者:Geen,G.R.; Share,A.C.; Slater,G.R.; Ramsay,T.W.; Smith,N.M.; Freer,R.
参考来源:Tetrahedron 2000,56(26),4589
产品链接: CAS No. 104227-87-4››