新产品编号:998751
Chemical Name: 7-Benzylamino-6-chloro-2-(1-piperazinyl)-4-(1-pyrrolidinyl)pteridine
项目整合开发状态: Biological Testing
项目研究机构: Boehringer Ingelheim (Originator)
合成路线:The cyclization of ethyl cyanoacetate (I) with urea (II) in ethanolic NaOEt provided 6-aminouracil (III).Nitrosation of (III) with NaNO2 in aqueous AcOH,followed by reduction of the resulting nitroso compound (IV) using sodium hydrosulfite gave 5,6-diaminouracil,which was purified by conversion to its hydrochloride salt (V).Condensation of this diamine with melted oxalic acid produced tetrahydroxypteridine (VI).Subsequent reaction of (VI) with PCl5 and POCl3 afforded tetrachlorocompound (VII).The reaction of (VII) with pyrrolidine (VIII) in aqueous KHCO3/CHCl3 resulted in a mixture of 2-,4-,7- and 4,7-substituted compounds,from which the desired 4-pyrrolidino-2,6,7-trichloropteridine (IX) was isolated by column chromatography.Further treatment of (IX) with benzylamine (X) in dioxan at r.t.provided diamine (XI).Finally,substitution of the third chlorine atom for piperazine (XII) was accomplished in boiling dioxan.
📌 参考资料/链接：
参考文献标题:Synthesis of 7-benzylamino-6-chloro-2-piperazino-4-pyrrolidinopteridine and novel derivatives free of positional isomers.Potent inhibitors of cAMP-specific phosphodiesterase and of malignant tumor cell growth
文献作者:Merz,K.-H.; Marko,D.; Regiert,T.; Reiss,G.; Frank,W.; Eisenbrand,G.
参考来源:J Med Chem 1998,41(24),4733
📄 详细内容
合成路线:The cyclization of ethyl cyanoacetate (I) with urea (II) in ethanolic NaOEt provided 6-aminouracil (III).Nitrosation of (III) with NaNO2 in aqueous AcOH,followed by reduction of the resulting nitroso compound (IV) using sodium hydrosulfite gave 5,6-diaminouracil,which was purified by conversion to its hydrochloride salt (V).Condensation of this diamine with melted oxalic acid produced tetrahydroxypteridine (VI).Subsequent reaction of (VI) with PCl5 and POCl3 afforded tetrachlorocompound (VII).The reaction of (VII) with pyrrolidine (VIII) in aqueous KHCO3/CHCl3 resulted in a mixture of 2-,4-,7- and 4,7-substituted compounds,from which the desired 4-pyrrolidino-2,6,7-trichloropteridine (IX) was isolated by column chromatography.Further treatment of (IX) with benzylamine (X) in dioxan at r.t.provided diamine (XI).Finally,substitution of the third chlorine atom for piperazine (XII) was accomplished in boiling dioxan.
参考文献标题:Zur kenntnis des leukopterins
文献作者:Sch鰌f,C.; Reichert,R.
参考来源:Liebigs Ann Chem 1941,54882
合成路线:The cyclization of ethyl cyanoacetate (I) with urea (II) in ethanolic NaOEt provided 6-aminouracil (III).Nitrosation of (III) with NaNO2 in aqueous AcOH,followed by reduction of the resulting nitroso compound (IV) using sodium hydrosulfite gave 5,6-diaminouracil,which was purified by conversion to its hydrochloride salt (V).Condensation of this diamine with melted oxalic acid produced tetrahydroxypteridine (VI).Subsequent reaction of (VI) with PCl5 and POCl3 afforded tetrachlorocompound (VII).The reaction of (VII) with pyrrolidine (VIII) in aqueous KHCO3/CHCl3 resulted in a mixture of 2-,4-,7- and 4,7-substituted compounds,from which the desired 4-pyrrolidino-2,6,7-trichloropteridine (IX) was isolated by column chromatography.Further treatment of (IX) with benzylamine (X) in dioxan at r.t.provided diamine (XI).Finally,substitution of the third chlorine atom for piperazine (XII) was accomplished in boiling dioxan.
参考文献标题:Diaminouracil hydrochloride
文献作者:Taylor,E.C.Jr.; Sherman,W.R.
参考来源:Org Synth Coll 1957,3715