新产品编号:1060449
Chemical Name: 3-[2-(2-Phenylethyl)morpholin-4-ylmethyl]-1H-indole oxalate
项目整合开发状态: Biological Testing
项目研究机构: Merck Sharp & Dohme (Originator)
合成路线:Condensation of 2,6-diamino-4-hydroxypyrimidine (I) with chloroacetone (II) produced a mixture of pyrrolopyrimidine (III) and furopyrimidine (IV).After treatment of this mixture with pivalic anhydride,the insoluble pivaloyl amide of pyrrolopyrimidine (V) was separated from the soluble dipivaloyl furopyrimidine with boiling EtOAc.Subsequent Mannich reaction of (V) with dimethylamine and formaldehyde afforded the (dimethylamino)methyl derivative (VI).The dimethylamino group of (VI) was then displaced with 4-mercaptopyridine (VII) to give thioether (VIII).Finally,the pivaloyl amide group of (VIII) was hydrolyzed with NaOH to yield the target compound.
📌 参考资料/链接：
参考文献标题:Synthesis of classical and a nonclassical 2-amino-4-oxo-6-methyl-5-substituted Pyrrolo[2,3-d]pyrimidine antifolate inhibitors of thymidylate synthase1
文献作者:Gangjee,A.; Mavandadi,F.; Kisliuk,R.L.; Queener,S.F.
参考来源:J Med Chem 1999,42(12),2272
📄 详细内容
合成路线:Condensation of 2,6-diamino-4-hydroxypyrimidine (I) with chloroacetone (II) produced a mixture of pyrrolopyrimidine (III) and furopyrimidine (IV).After treatment of this mixture with pivalic anhydride,the insoluble pivaloyl amide of pyrrolopyrimidine (V) was separated from the soluble dipivaloyl furopyrimidine with boiling EtOAc.Subsequent Mannich reaction of (V) with dimethylamine and formaldehyde afforded the (dimethylamino)methyl derivative (VI).The dimethylamino group of (VI) was then displaced with 4-mercaptopyridine (VII) to give thioether (VIII).Finally,the pivaloyl amide group of (VIII) was hydrolyzed with NaOH to yield the target compound.
参考文献标题:2-Amino-4-oxo-5-substituted-pyrrolo[2,3-d.]pyrimidines as nonclassical antifolate inhibitors of thymidylate synthase
文献作者:Gangjee,A.; Mavandadi,F.; Kisliuk,R.L.; Mcguire,J.J.; Queener,S.F.
参考来源:J Med Chem 1996,39(23),4563-4568