新产品编号:185603
Chemical Name: 4-(4-Amino-6-chloropyrimidin-2-ylsulfanyl)-N,N-diethyl-2(E)-butenamide
CAS No. 185219-02-7
项目整合开发状态: Biological Testing
项目研究机构: Pfizer (Originator)
合成路线:Alkylation of 4,6-dihydroxy-2-mercaptopyrimidine (I) with 4-methoxybenzyl chloride (II) provided methoxybenzyl sulfide (III).This was treated with POCl3 and 2-picoline to give dichloropyrimidine (IV).Then,ammonolysis with NH4OH in acetonitrile produced aminopyrimidine (V).Removal of the methoxybenzyl protecting group orf (V) was accomplished by treatment with methanesulfonic acid in CH2Cl2 to provide (VI).4-Chlorocrotonyl chloride (VII) was condensed with diethylamine to yield chloro amide (VIII) (1).The title compound was then obtained by alkylation of mercaptopyrimidine (VI) with chloro amide (VIII) in the presence of NaOH in aqueous ethanol.
📌 参考资料/链接：
参考文献标题:Alpha-substituted pyrimidine-thioalkyl and alkylester compounds as inhibitors of viral reverse transcriptase
文献作者:Nugent,R.A.; et al.(Pharmacia & Upjohn AB)
参考来源:EP 0824524; WO 9635678
📄 详细内容
合成路线:Alkylation of 4,6-dihydroxy-2-mercaptopyrimidine (I) with 4-methoxybenzyl chloride (II) provided methoxybenzyl sulfide (III).This was treated with POCl3 and 2-picoline to give dichloropyrimidine (IV).Then,ammonolysis with NH4OH in acetonitrile produced aminopyrimidine (V).Removal of the methoxybenzyl protecting group orf (V) was accomplished by treatment with methanesulfonic acid in CH2Cl2 to provide (VI).4-Chlorocrotonyl chloride (VII) was condensed with diethylamine to yield chloro amide (VIII) (1).The title compound was then obtained by alkylation of mercaptopyrimidine (VI) with chloro amide (VIII) in the presence of NaOH in aqueous ethanol.
参考文献标题:Pyrimidine thioethers: A novel class of HIV-1 reverse transcriptase inhibitors with activity against BHAP-resistant HIV
文献作者:Nugent,R.A.; Schlachter,S.T.; Murphy,M.J.; Cleek,G.J.; Poel,T.J.; Wishka,D.G.; Graber,D.R.; Yagi,Y.; Keiser,B.J.; Olmsted,R.A.; Kopta,L.A.; Swaney,S.M.; Poppe,S.M.; Morris,J.; Tarpley,W.G.; Thomas,R.C.
参考来源:J Med Chem 1998,41(20),3793