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Eniluracil, GW-776, 5-EU, 776C85

5-乙炔基尿嘧啶Chemical Name: 5-Ethynyluracil; 5-Ethynyl-2,4(1H,3H)-pyrimidinedione
CAS No. 59989-18-3
项目整合开发状态: Phase III
项目研究机构: GlaxoSmithKline (Originator)
合成路线:This compound has been obtained by two similar ways:1.The reaction of 5-iodouracil (I) with trimethylsilylacetylene (II) by means of PdCl2(PPh3)2 and CuI2 in TEA/DMF gives 5-(trimethylsilylethynyl)uracil (III),which is then desilylated with sodium methoxide or NaOH in methanol.2.The reaction of 5-iodouracil (I) with POCl3 at 120 C catalyzed by N,N-diethylaniline gives 2,4-dichloro-5-iodopyrimidine (IV),which by reaction with NaOMe in methanol is converted into 2,4-dimethoxy-5-iodopyrimidine (V).The condensation of (V) with trimethylsilylacetylene by means of PdCl2(PPh3)2 and CuI2 in TEA/DMF yields 2,4-dimethoxy-5-(trimethylsilylethynyl)pyrimidine (VI),which is treated with NaI and Tms-Cl in refluxing acetonitrile to afford 5-(trimethylsilylethynyl)uracil (III).
📌 参考资料/链接:
参考文献标题:Enzyme inactivators
文献作者:Spector,T.; Porter,D.J.T.; Rahim,S.G.(Glaxo Wellcome plc)
参考来源:EP 0539442; EP 0711555; JP 1994502619; JP 2000297076; WO 9201452

📄 详细内容


合成路线:This compound has been obtained by two similar ways:1.The reaction of 5-iodouracil (I) with trimethylsilylacetylene (II) by means of PdCl2(PPh3)2 and CuI2 in TEA/DMF gives 5-(trimethylsilylethynyl)uracil (III),which is then desilylated with sodium methoxide or NaOH in methanol.2.The reaction of 5-iodouracil (I) with POCl3 at 120 C catalyzed by N,N-diethylaniline gives 2,4-dichloro-5-iodopyrimidine (IV),which by reaction with NaOMe in methanol is converted into 2,4-dimethoxy-5-iodopyrimidine (V).The condensation of (V) with trimethylsilylacetylene by means of PdCl2(PPh3)2 and CuI2 in TEA/DMF yields 2,4-dimethoxy-5-(trimethylsilylethynyl)pyrimidine (VI),which is treated with NaI and Tms-Cl in refluxing acetonitrile to afford 5-(trimethylsilylethynyl)uracil (III).

参考文献标题:Uracil reductase inactivators
文献作者:Spector,T.; Porter,D.J.T.; Rahim,S.G.(Glaxo Wellcome plc)
参考来源:EP 0550580; JP 1994504263; JP 1998045623; WO 9204901


合成路线:This compound has been obtained by two similar ways:1.The reaction of 5-iodouracil (I) with trimethylsilylacetylene (II) by means of PdCl2(PPh3)2 and CuI2 in TEA/DMF gives 5-(trimethylsilylethynyl)uracil (III),which is then desilylated with sodium methoxide or NaOH in methanol.2.The reaction of 5-iodouracil (I) with POCl3 at 120 C catalyzed by N,N-diethylaniline gives 2,4-dichloro-5-iodopyrimidine (IV),which by reaction with NaOMe in methanol is converted into 2,4-dimethoxy-5-iodopyrimidine (V).The condensation of (V) with trimethylsilylacetylene by means of PdCl2(PPh3)2 and CuI2 in TEA/DMF yields 2,4-dimethoxy-5-(trimethylsilylethynyl)pyrimidine (VI),which is treated with NaI and Tms-Cl in refluxing acetonitrile to afford 5-(trimethylsilylethynyl)uracil (III).
参考文献标题:Process research and development of a dihydropyrimidine dehydrogenase inactivator: Large-scale preparation of eniluracil using a Sonogashira coupling
文献作者:Cooke,J.W.B.; et al.
参考来源:Org Process Res Dev 2001,5(4),383


产品链接: CAS No. 59989-18-3››