新产品编号:1117401
Chemical Name: 2,4-Diamino-6-[N-(3,4,5-trimethoxyphenyl)-N-methylaminomethyl]pyrido[2,3-d]pyrimidine
项目整合开发状态: Biological Testing
项目研究机构: Duquesne University (Originator), Indiana University (Originator)
合成路线:The title compound has been prepared by two synthetic procedures.Condensation of 2-aminopyridine-3,5-dicarbonitrile (I) with guanidine (II) in refluxing EtOH produced the pyridopyrimidine (III).Subsequent reductive condensation of (III) with 3,4,5-trimethoxyaniline (IV) by hydrogenation over Raney Nickel provided the (arylamino)methyl derivative (V).Final reductive alkylation of (V) by means of formaldehyde and sodium cyanoborohydride then gave the target methylated amine.
📌 参考资料/链接：
参考文献标题:Derivs.of pyrido [2,3-d] and [3,2-d] pyrimidine and methods of using these derivs.
文献作者:Gangjee,A.(Duquesne University)
参考来源:US 5508281
📄 详细内容
合成路线:In an alternative synthesis,2,4,6-triaminopyrimidine (VI) was condensed with bromomalonaldehyde (VII) under acidic conditions to give pyridopyrimidine (VIII),which was protected with pivaloyl anhydride in pyridine,yielding the bispivaloylamide (IX).Palladium-catalyzed Heck coupling of (IX) with styrene (X) afforded (XI).Subsequent ozonolysis of the styryl derivative (XI),followed by reductive workup with dimethyl sulfide gave aldehyde (XII).Reduction of (XII) to the corresponding alcohol with NaBH4,followed by bromination with PPh3 and Br2 provided bromide (XIII).The N-methyl aniline (XIV) was synthesized by direct alkylation of 3,4,5-trimethoxyaniline (IV) with methyl iodide.Nucleophilic displacement of the bromide (XIII) with aniline (XIV) afforded the tertiary amine (XV).The pivaloyl protecting groups of (XV) were finally removed by treatment with methanolic NaOMe.
参考文献标题:Synthesis and dihydrofolate reductase inhibitory activities of 2,4-diamino-5-deaza and 2,4-diamino-5,10-dideaza lipophilic antifolates
文献作者:Gangjee,A.; Devraj,R.; Queener,S.F.
参考来源:J Med Chem 1997,40(4),470