Piritrexim, 301U74, NSC-351521, BW-301U
吡曲克辛Chemical Name: 6-(2,5-Dimethoxyphenylmethyl)-5-methylpyrido[2,3-d]pyrimidine-2,4-diamine; 2,4-Diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidine
CAS No. 72732-56-0, 79483-69-5 (isethionate)
项目整合开发状态: Phase III
项目研究机构: GlaxoSmithKline (Originator), Ilex Oncology (Licensee)
合成路线:The reaction of 2,5-dimethoxybenzaldehyde (I) with ethyl acetoacetate (II) in a mixture of piperidine and glacial acetic acid in refluxing benzene gives ethyl alpha-acetyl-beta-(2,5-dimethoxyphenyl)acrylate (III),which is hydrogenated in a Parr low-pressure apparatus using 5% palladium on charcoal catalyst in ethyl acetate to yield ethyl alpha-acetyl-(2,5-dimethoxyphenyl)propionate (IV).The condensation of the propionate (IV) with 2,4.6-triaminopyrimidine in diphenylether at 195-230 C provides 2,4-diamino-7,8-dihydro-6-(2,5-dimethoxybenzyl)-5-methyl-7-oxopyrido[2,3-d]pyrimidine (VI).The key intermediate (VI) is converted to the 7-chloro compound (VII) by treatment with a 1:1 complex of N,N-dimethylformamide thionyl chloride,and finally (VII) is hydrogenolyzed with palladium on charcoal in the presence of potassium hydroxide to yield BW-301 U.
📌 参考资料/链接：
参考文献标题:BW-301 U
文献作者:Sigel,C.W.
参考来源:Drugs Fut 1985,10(2),108
📄 详细内容
合成路线:The synthesis of [14C]-labeled piritrexim has been described:The condensation of 2,5-dimethoxybenzaldehyde (I) with acetone in aqueous NaOH gives 4-(2,5-dimethoxyphenyl)-3-(E)-buten-2-one (II),which is hydrogenated with H2 over Pd/C in methanol to give 4-(2,5-dimethoxyphenyl)-2-butanone (III).The condensation of (III) with malononitrile (IV) by means of acetic acid-sodium acetate in refluxing toluene yields 2-cyano-5-(2,5-dimethoxyphenyl)-3-methyl-2-pentenenitrile (V),which is condensed with acetic acid diethoxymethyl ester (VI) at 105 C to afford the corresponding diethoxymethyl derivative (VII).The cyclization of (VII) with 32% HBr in acetic acid affords 2-bromo-5-(2,5-dimethoxybenzyl)-4-methylpyridine-3-carbonitrile (VIII),which is finally cyclized again with [14C]-labeled guanidine (IX) by means of NaH in refluxing tert-butyl alcohol.
参考文献标题:Synthesis of carbon-14 labelled piritrexim - A potential anticanceragent
文献作者:Wisowaty,J.C.; Darnofall,M.E.; Hill,J.A.
参考来源:J Label Compd Radiopharm 1993,33(12),1119
合成路线:The reaction of 2,5-dimethoxybenzaldehyde (I) with ethyl acetoacetate (II) in a mixture of piperidine and glacial acetic acid in refluxing benzene gives ethyl alpha-acetyl-beta-(2,5-dimethoxyphenyl)acrylate (III),which is hydrogenated in a Parr low-pressure apparatus using 5% palladium on charcoal catalyst in ethyl acetate to yield ethyl alpha-acetyl-(2,5-dimethoxyphenyl)propionate (IV).The condensation of the propionate (IV) with 2,4.6-triaminopyrimidine in diphenylether at 195-230 C provides 2,4-diamino-7,8-dihydro-6-(2,5-dimethoxybenzyl)-5-methyl-7-oxopyrido[2,3-d]pyrimidine (VI).The key intermediate (VI) is converted to the 7-chloro compound (VII) by treatment with a 1:1 complex of N,N-dimethylformamide thionyl chloride,and finally (VII) is hydrogenolyzed with palladium on charcoal in the presence of potassium hydroxide to yield BW-301 U.
参考文献标题:Synthesis and antitumor activity of 2,4-diamino-6-(2,5-dimethoxybenzyl)-5-methylpyrido[2,3-d]pyrimidine
文献作者:Grivsky,E.M.; Lee,S.; Sigel,C.W.; Duch,D.S.; Nichol,C.A.
参考来源:J Med Chem 1980,23(3),327-329
产品链接: CAS No. 72732-56-0›› 产品链接: CAS No.79483-69-5››