FR-180102
Chemical Name: N-[2,4-Dichloro-3-(isoquinolin-5-yloxymethyl)phenyl]acetamide
项目整合开发状态: Biological Testing
项目研究机构: Fujisawa (Originator)
合成路线:Nitration of 2,6-dichlorobenzaldehyde (I) with 70% HNO3 in concentrated H2SO4 at ice-bath temperature provided the 3-nitro derivative (II).This was reduced with NaBH4 in MeOH at 10 C to the alcohol (III),which was treated with mesyl chloride and triethylamine in dichloromethane to give mesylate (IV).Alkylation of 5-hydroxyisoquinoline (V) with mesylate (IV) in the presence of NaH in DMF yielded ether (VI).Subsequent reduction of the nitro group of (VI) with hydrazine and FeCl3 provided amine (VII),which was finally acylated with Ac2O in dichloroethane at 70 C to furnish the target acetamide.
📌 参考资料/链接：
参考文献标题:A novel class of orally active non-peptide bradykinin B2 receptor antagonists.1.Construction of the basic framework
文献作者:Abe,Y.; Kayakiri,H.; Satoh,S.; Inoue,T.; Sawada,Y.; Imai,K.; Inamura,N.; Asano,M.; Hatori,C.; Katayama,A.; Oku,T.; Tanaka,H.
参考来源:J Med Chem 1998,41(4),564
📄 详细内容
合成路线:Nitration of 2,6-dichlorobenzaldehyde (I) with 70% HNO3 in concentrated H2SO4 at ice-bath temperature provided the 3-nitro derivative (II).This was reduced with NaBH4 in MeOH at 10 C to the alcohol (III),which was treated with mesyl chloride and triethylamine in dichloromethane to give mesylate (IV).Alkylation of 5-hydroxyisoquinoline (V) with mesylate (IV) in the presence of NaH in DMF yielded ether (VI).Subsequent reduction of the nitro group of (VI) with hydrazine and FeCl3 provided amine (VII),which was finally acylated with Ac2O in dichloroethane at 70 C to furnish the target acetamide.
参考文献标题:Discovery of a novel benzyloxyisoquinoline derivative with potent anti-Helicobacter pylori activity
文献作者:Yoshida,Y.; Barrett,D.; Azami,H.; Morinaga,C.; Matsumoto,Y.; Takasugi,H.
参考来源:Bioorg Med Chem Lett 1998,8(14),1897