新产品编号:1046211
Chemical Name: 6-Chloro-5-(methylsulfanyl)-N-(3-pyridyl)indoline-1-carboxamide
项目整合开发状态: Biological Testing
项目研究机构: GlaxoSmithKline (Originator)
合成路线:The heating of nicotinoyl azide (I) in refluxing toluene gives the corresponding isocyanate (II),which without isolation is condensed with 6-chloro-5-(methylsulfanyl)indoline (IV) to afford the target compound.Intermediate indoline (IV) is obtained by reduction of 6-chloro-5-(methylsulfanyl)indole (III) with NaBH3CN in HOAc.
合成路线:Alkylation of 3-chloro-4-methylaniline (I) with bromoacetaldehyde diethyl acetal (II) afforded secondary amine (III).Subsequent cyclization of (III) in boiling trifluoroacetic acid/trifluoroacetic anhydride provided a (3:2) mixture of indoles (IV) and (V),from which the desired 6-chloro isomer (IV) was isolated by column chromatography,and then reduced to indoline (VI) using NaBH3CN in AcOH.5-Aminoquinoline (VII) was treated with carbonyl diimidazole to give intermediate (VIII).This was finally coupled with indoline (VI) in DMF at 100 C to yield the corresponding urea.
📌 参考资料/链接：
参考文献标题:Indoline derivs.as 5HT2C antagonists
文献作者:Ham,P.; Jones,G.E.; Forbes,I.T.(SmithKline Beecham plc)
参考来源:EP 0707581; JP 1996512299; US 5834494; WO 9501976
📄 详细内容
合成路线:The heating of nicotinoyl azide (I) in refluxing toluene gives the corresponding isocyanate (II),which without isolation is condensed with 6-chloro-5-(methylsulfanyl)indoline (IV) to afford the target compound.Intermediate indoline (IV) is obtained by reduction of 6-chloro-5-(methylsulfanyl)indole (III) with NaBH3CN in HOAc.
参考文献标题:Model studies on a synthetically facile series of N-substituted phenyl-N'-pyridin-3-yl ureas leading to 1-(3-pyridylcarbamoyl)indolines that are potent and selective 5-HT2C/2B receptor antagonists
文献作者:Bromidge,S.M.; Dabbs,S.; Davies,D.T.; Davies,S.; Duckworth,D.M.; Forbes,I.T.; Gadre,A.; Ham,P.; Jones,G.E.; King,F.D.; Saunders,D.V.; Thewlis,K.M.; Vyas,D.; Blackburn,T.P.; Holland,V.; Kennett,G.A.; Riley,G.J.; Wood,M.D.
参考来源:Bioorg Med Chem 1999,7(12),2767