ethyl 4-[2-(4-morpholinyl)-1-cyclohexen-1-yl]-4-oxobutanoate -Drug Synthesis Database

【结构式】

【分子编号】44737

【品名】ethyl 4-[2-(4-morpholinyl)-1-cyclohexen-1-yl]-4-oxobutanoate

【CA登记号】

【分子式】C₁₆H₂₅NO₄

【分子量】295.37884

【元素组成】C 65.06% H 8.53% N 4.74% O 21.67%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(III)

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.

参考文献中间体

合成目标

【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

Extended Information