新产品编号:691843
Chemical Name: (Z)-3-[2-(5-Bromo-2-oxo-2,3-dihydro-1H-indol-3-ylidenemethyl)-4,5,6,7-tetrahydro-1H-indol-3-yl]propionic acid
CAS No. 258830-93-2
项目整合开发状态: Biological Testing
项目研究机构: Sugen (Originator)
合成路线:Condensation of ethyl succinyl chloride (II) with 4-(1-cyclohexenyl)morpholine (I) in the presence of Et3N produced enamino ketoester (III).Cyclization of (III) with diethyl aminomalonate (IV) gave the tetrahydroindole (V).Hydrolysis of the ester functions of (V) with NaOH,followed by acidic decarboxylation,afforded the tetrahydroindolylpropionic acid (VI).Vilsmeier formylation of (VI) with DMF and POCl3 furnished aldehyde (VII).This was then condensed with 5-bromo-2-oxindole (IX) (obtained by treatment of (VIII) with N-bromosuccinimide),using either pyrrolidine or piperidine in refluxing EtOH to yield the title compound.
📌 参考资料/链接：
参考文献标题:3-Methylidenyl-2-indolinone modulators of protein kinase
文献作者:Miller,T.A.; Tang,P.C.; Sun,L.; Tran,N.M.; Liang,C.; Nguyen,A.T.; Nematalla,A.(Sugen,Inc.)
参考来源:WO 0008202
📄 详细内容
合成路线:Condensation of ethyl succinyl chloride (II) with 4-(1-cyclohexenyl)morpholine (I) in the presence of Et3N produced enamino ketoester (III).Cyclization of (III) with diethyl aminomalonate (IV) gave the tetrahydroindole (V).Hydrolysis of the ester functions of (V) with NaOH,followed by acidic decarboxylation,afforded the tetrahydroindolylpropionic acid (VI).Vilsmeier formylation of (VI) with DMF and POCl3 furnished aldehyde (VII).This was then condensed with 5-bromo-2-oxindole (IX) (obtained by treatment of (VIII) with N-bromosuccinimide),using either pyrrolidine or piperidine in refluxing EtOH to yield the title compound.
参考文献标题:Identification of substituted 3-[(4,5,6,7-tetrahydro-1H-indol-2-yl)methylene]-1,3-dihydroindol-2-ones as growth factor receptor inhibitors for VEGF-R2 (F1k-1/KDR),FGF-R1,and PDGF-Rbeta tyrosine kinases
文献作者:Sun,L.; Tran,N.; Liang,C.; Hubbard,S.; Tang,F.; Lipson,K.; Schreck,R.; Zhou,Y.; McMahon,G.; Tang,C.
参考来源:J Med Chem 2000,43(14),2655