新产品编号:106503
Chemical Name: 1-Deoxy-1-[2-[2-(1H-imidazol-4-yl)ethylamino]-6-(2,2-diphenylethylamino)-9H-purin-9-yl]-N-ethyl-beta-D-ribofuranuronamide trifluoroacetate
CAS No. 167465-88-5 (as hydrochloride), 167298-03-5 (free base)
项目整合开发状态: Biological Testing
项目研究机构: GlaxoSmithKline (Originator)
合成路线:Guanosine (I) was protected as the triacetate ester (II) and then chlorinated with POCl3 in the presence of dimethylaniline and tetraethylammonium chloride to give the 6-chloro derivative (III).Diazotization of (III) with tert-butyl nitrite,followed by a modified Sandmeyer reaction provided dichloro purine (IV).Substitution of the 6-chloro of (IV) by 2,2-diphenylethylamine (V) in the presence of diisopropylethylamine in refluxing isopropanol furnished the chloroadenosine derivative (VI),and subsequent removal of the acetate protecting groups of (VI) by hydrolysis with Na2CO3 in aqueous MeOH yielded the adenosine derivative (VII).
合成路线:Alternatively,condensation of 2,6-dichloropurine (VIII) with protected ribose (IX) at 140 C gave the ribofuranosyl purine (X).Subsequent displacement of the 6-chloro of (V) by amine (V),followed by hydrolysis of the benzoate esters afforded the intermediate (VII).
合成路线:Protection of the 2',3'-diol group of adenosine (VII) as the corresponding acetonide (XII) was effected by treatment with 2,2-dimethoxypropane and p-toluenesulfonic acid.The primary alcohol group of (XII) was then oxidized to carboxylic acid (XIII) using KMnO4.After conversion of (XIII) to acid chloride by means of refluxing SOCl2,coupling with ethylamine furnished amide (XIV).Displacement of the 2-chloro of (XIV) by histamine (XV) in hot DMSO produced adduct (XVI).The acetonide group of (XVI) was finally deprotected using aqueous trifluoroacetic acid.
📌 参考资料/链接：
参考文献标题:2,6-Diaminopurine derivs.
文献作者:Gregson,M.; Ayres,B.E.; Ewan,G.B.; Ellis,F.; Knight,J.(Glaxo Wellcome plc)
参考来源:EP 0680488; JP 1996505864; US 5925624; WO 9417090
📄 详细内容
合成路线:Guanosine (I) was protected as the triacetate ester (II) and then chlorinated with POCl3 in the presence of dimethylaniline and tetraethylammonium chloride to give the 6-chloro derivative (III).Diazotization of (III) with tert-butyl nitrite,followed by a modified Sandmeyer reaction provided dichloro purine (IV).Substitution of the 6-chloro of (IV) by 2,2-diphenylethylamine (V) in the presence of diisopropylethylamine in refluxing isopropanol furnished the chloroadenosine derivative (VI),and subsequent removal of the acetate protecting groups of (VI) by hydrolysis with Na2CO3 in aqueous MeOH yielded the adenosine derivative (VII).
合成路线:Alternatively,condensation of 2,6-dichloropurine (VIII) with protected ribose (IX) at 140 C gave the ribofuranosyl purine (X).Subsequent displacement of the 6-chloro of (V) by amine (V),followed by hydrolysis of the benzoate esters afforded the intermediate (VII).
合成路线:Protection of the 2',3'-diol group of adenosine (VII) as the corresponding acetonide (XII) was effected by treatment with 2,2-dimethoxypropane and p-toluenesulfonic acid.The primary alcohol group of (XII) was then oxidized to carboxylic acid (XIII) using KMnO4.After conversion of (XIII) to acid chloride by means of refluxing SOCl2,coupling with ethylamine furnished amide (XIV).Displacement of the 2-chloro of (XIV) by histamine (XV) in hot DMSO produced adduct (XVI).The acetonide group of (XVI) was finally deprotected using aqueous trifluoroacetic acid.
参考文献标题:The discovery and synthesis of highly potent,A2A receptor agonists
文献作者:Keeling,S.E.; Albinson,F.D.; Ayres,B.E.; Butchers,P.R.; Chambers,C.L.; Cherry,P.C.; Ellis,F.; Ewan,G.B.; Gregson,M.; Knight,J.; Mills,K.; Ravenscroft,P.; Reynolds,L.H.; Sanjar,S.; Sheehan,M.J.
参考来源:Bioorg Med Chem Lett 2000,10(4),403