新产品编号:566865
Chemical Name: 2-(1-Methyl-1H-imidazol-2-yl)-N-(2-methyl-1H-indol-5-yl)thieno[3,2-b]pyridin-7-amine
CAS No. 225382-65-0
项目整合开发状态: Biological Testing
项目研究机构: Pfizer (Originator)
合成路线:Decarboxylation of methyl 3-aminothiophene-2-carboxylate (I) in 2 N NaOH leads to 3-aminothiophene (II).Meldrum's acid (III) is condensed with triethyl orthoformate to produce the ethoxymethylene derivative (IV).Subsequent reaction of enol ether (IV) with 3-aminothiophene (II) gives rise to enamine (V),which is further cyclized to thienopyridinone (VI) upon heating in dowtherm A at 260 C.This is then chlorinated by means of oxalyl chloride to furnish 4-chlorothieno[3,2-b]pyridine (VII).Metalation of (VII) with butyllithium in cold THF,followed by treatment with I2 affords the aryl iodide (VIII).Palladium-catalyzed coupling of (VIII) with the lithiated derivative of 1-methylimidazole (IX) yields (X).Finally,displacement of the chloride group of (X) with 5-amino-2-methylindole (XI) provides the title compound.
📌 参考资料/链接：
参考文献标题:Thienopyrimidine and thienopyridine derivs.useful as anticancer agents
文献作者:Sobolov-Jaynes,S.B.; Munchhof,M.J.(Pfizer Products Inc.)
参考来源:EP 1028964; JP 2001522853; WO 9924440
📄 详细内容
合成路线:Decarboxylation of methyl 3-aminothiophene-2-carboxylate (I) in 2 N NaOH leads to 3-aminothiophene (II).Meldrum's acid (III) is condensed with triethyl orthoformate to produce the ethoxymethylene derivative (IV).Subsequent reaction of enol ether (IV) with 3-aminothiophene (II) gives rise to enamine (V),which is further cyclized to thienopyridinone (VI) upon heating in dowtherm A at 260 C.This is then chlorinated by means of oxalyl chloride to furnish 4-chlorothieno[3,2-b]pyridine (VII).Metalation of (VII) with butyllithium in cold THF,followed by treatment with I2 affords the aryl iodide (VIII).Palladium-catalyzed coupling of (VIII) with the lithiated derivative of 1-methylimidazole (IX) yields (X).Finally,displacement of the chloride group of (X) with 5-amino-2-methylindole (XI) provides the title compound.
参考文献标题:Development of thienopyridines as VEGFR-2 kinase inhibitors
文献作者:Munchhof,M.J.; Adams,M.A.; Atherton,J.A.; et al.
参考来源:225th ACS Natl Meet (March 23 2003,New Orleans) 2003,Abst MEDI 129