SB-334867A

1-(2-甲基-1,3-苯并恶唑-6-基)-3-(1,5-萘啶-4-基)脲Chemical Name: N-(2-Methylbenzoxazol-6-yl)-N'-(1,5-naphthyridin-4-yl)urea hydrochloride
CAS No. 249889-64-3
项目整合开发状态: Preclinical
项目研究机构: GlaxoSmithKline (Originator)
合成路线:The known 4-hydroxy-1,5-naphthyridine-3-carboxylic acid (I) was decarboxylated to (II) upon refluxing in quinoline.Heating of (II) with POCl3 furnished 4-chloro-1,5-naphthyridine (III),which was converted to amine (IV) by reaction with n-propylamine in pyridine.Curtius rearrangement of 2-methyl-6-benzoxazolecarboxylic acid (V) in the presence of diphenylphosphoryl azide gave isocyanate (VI).Finally,coupling between isocyanate (VI) and amine (IV) provided the title urea.
📌 参考资料/链接:
参考文献标题:Phenylurea and phenylthio urea derivs.
文献作者:Johns,A.; Porter,R.A.(SmithKline Beecham plc)
参考来源:EP 1075478; WO 9958533

📄 详细内容


合成路线:The cyclization of 3aminopyridine (I) with diethyl ethoxymethylenemalonate (II) in refluxing Dowtherm gives 4-hydroxy-1,5-naphthyridine-3-carboxylic acid ethyl ester (III),which is hydrolyzed with NaOH in refluxing water to yield the corresponding hydroxyacid (IV).The decarboxylation of (IV) by heating at 320 C in mineral oil affords 4-hydroxy-1,5-naphthyridine (V),which is acylated with trifluoromethanesulfonic anhydride to provide the triflate (VI).The reaction of (VI) with propylamine in pyridine affords 4-amino-1,5-naphthyridine (VII),which is condensed with 2-methylbenzoxazole-6-ylcarbonyl azide (VIII) (obtained by reaction of the corresponding acid (IX) with DPPA) in refluxing toluene to provide the target urea.

参考文献标题:1,3-Biarylureas as selective non-peptide antagonists of the orexin-1 receptor
文献作者:Porter,R.A.; Chan,W.N.; Coulton,S.; Johns,A.; Hadley,M.S.; Widdowson,K.; Jerman,J.C.; Brough,S.J.; Coldwell,M.C.; Smart,D.; Jewitt,F.; Jeffrey,P.; Austin,N.
参考来源:Bioorg Med Chem Lett 2001,11(14),1907


合成路线:The cyclization of 3aminopyridine (I) with diethyl ethoxymethylenemalonate (II) in refluxing Dowtherm gives 4-hydroxy-1,5-naphthyridine-3-carboxylic acid ethyl ester (III),which is hydrolyzed with NaOH in refluxing water to yield the corresponding hydroxyacid (IV).The decarboxylation of (IV) by heating at 320 C in mineral oil affords 4-hydroxy-1,5-naphthyridine (V),which is acylated with trifluoromethanesulfonic anhydride to provide the triflate (VI).The reaction of (VI) with propylamine in pyridine affords 4-amino-1,5-naphthyridine (VII),which is condensed with 2-methylbenzoxazole-6-ylcarbonyl azide (VIII) (obtained by reaction of the corresponding acid (IX) with DPPA) in refluxing toluene to provide the target urea.
参考文献标题:Synthesis of antimalarials.VI.Synthesis of certain 1,5- and 1,8-naphthyridine derivatives
文献作者:Adams,J.T.; et al.
参考来源:J Am Chem Soc 1946,681317


产品链接: CAS No. 249889-64-3››