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【结 构 式】 
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【分子编号】44739 【品名】ethyl 3-(3-ethoxy-3-oxopropyl)-4,5,6,7-tetrahydro-1H-indole-2-carboxylate 【CA登记号】 |
【 分 子 式 】C16H23NO4 【 分 子 量 】293.36296 【元素组成】C 65.51% H 7.9% N 4.77% O 21.82% |
合成路线1
该中间体在本合成路线中的序号：(V)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.
| 【2】 Miller, T.A.; Tang, P.C.; Sun, L.; Tran, N.M.; Liang, C.; Nguyen, A.T.; Nematalla, A. (Sugen, Inc.); 3-Methylidenyl-2-indolinone modulators of protein kinase. WO 0008202 . |
| 【1】 Liang, C.; Sun, L.; Tran, N.; et al.; 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. J Med Chem 2000, 43, 14, 2655. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 44735 | 4-(1-cyclohexen-1-yl)morpholine | 670-80-4 | C10H17NO | 详情 | 详情 |
| (II) | 40684 | ethyl 4-chloro-4-oxobutanoate; Ethyl succinyl chloride | 14794-31-1 | C6H9ClO3 | 详情 | 详情 |
| (III) | 44737 | ethyl 4-[2-(4-morpholinyl)-1-cyclohexen-1-yl]-4-oxobutanoate | C16H25NO4 | 详情 | 详情 | |
| (IV) | 44738 | Diethyl aminomalonate; diethyl 2-aminomalonate | C7H13NO4 | 详情 | 详情 | |
| (V) | 44739 | ethyl 3-(3-ethoxy-3-oxopropyl)-4,5,6,7-tetrahydro-1H-indole-2-carboxylate | C16H23NO4 | 详情 | 详情 | |
| (VI) | 44740 | 3-(4,5,6,7-tetrahydro-1H-indol-3-yl)propionic acid | C11H15NO2 | 详情 | 详情 | |
| (VII) | 44741 | 3-(2-formyl-4,5,6,7-tetrahydro-1H-indol-3-yl)propionic acid | C12H15NO3 | 详情 | 详情 | |
| (VIII) | 18699 | 1,3-dihydro-2H-indol-2-one | 59-48-3 | C8H7NO | 详情 | 详情 |
| (IX) | 44743 | 5-bromo-1,3-dihydro-2H-indol-2-one | C8H6BrNO | 详情 | 详情 |