-药物合成数据库

【药物名称】

化学结构式(Chemical Structure):

参考文献No.	44377
标题:	3-Methylidenyl-2-indolinone modulators of protein kinase
作者:	Miller, T.A.; Tang, P.C.; Sun, L.; Tran, N.M.; Liang, C.; Nguyen, A.T.; Nematalla, A. (Sugen, Inc.)
来源:	WO 0008202

合成路线图解说明: 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No.	587645
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
作者:	Sun, L.; Tran, N.; Liang, C.; Hubbard, S.; Tang, F.; Lipson, K.; Schreck, R.; Zhou, Y.; McMahon, G.; Tang, C.
来源:	J Med Chem 2000,43(14),2655

合成路线图解说明: 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.