ethyl (E)-3-(3,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-6-quinolinyl)-2-propenoate -Drug Synthesis Database

【结构式】

【分子编号】43475

【品名】ethyl (E)-3-(3,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-6-quinolinyl)-2-propenoate

【CA登记号】

【分子式】C₁₆H₁₇NO₄

【分子量】287.31532

【元素组成】C 66.89% H 5.96% N 4.88% O 22.27%

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：(XXVII)

An alternative procedure for the preparation of tetrahydroquinoline (XXIII) consisted in the acylation of ethyl 4-aminocinnamate (XXV) with the in situ prepared dimethylmalonyl chloride (to give (XXVI)), followed by cyclization to the quinoline dione (XXVII) by means of phosphorus pentoxide and methanesulfonic acid. The hydrogenation of the double bond of (XXVII) and simultaneous reduction of the keto group produced quinolinone (XXVIII). Further reduction of the lactam carbonyl group of (XXVIII) to provide (XXIII) was carried out via conversion to thiolactam (XXIX), which was alkylated with iodomethane to the S-methyl thioimidate (XXX) and then reduced with NaBH3CN.

参考文献中间体

合成目标

【1】 Hayler, J.; LeGrand, D.; Kane, P.D.; et al.; The design and synthesis of thrombin inhibitors: The introduction of in vivo efficacy and oral bioavailability into benzthiazolylalanine inhibitors. Bioorg Med Chem Lett 2000, 10, 14, 1567.
【2】 Smith, G.P.; Brundish, D.E.; Menear, K.A.; Walker, C.V.; Herold, P.; Fullerton, J.D.; Allen, M.C.; Le Grand, D.M.; Kane, P.D.; Cockcroft, X.-L.; Wathey, W.B.; Butler, P.I.; Hatto, J.D.I.; Hayler, J.D. (Novartis AG); Tetrahydroquinoline inhibitors of trypsin and thrombin. GB 2312674 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIX)	43477	ethyl 3-(3,3-dimethyl-2-thioxo-1,2,3,4-tetrahydro-6-quinolinyl)propanoate		C₁₆H₂₁NO₂S	详情	详情
(XXIII)	43471	ethyl 3-(3,3-dimethyl-1,2,3,4-tetrahydro-6-quinolinyl)propanoate		C₁₆H₂₃NO₂	详情	详情
(XXV)	43473	ethyl (E)-3-(4-aminophenyl)-2-propenoate	5048-82-8	C₁₁H₁₃NO₂	详情	详情
(XXVI)	43474	3-[4-[(E)-3-ethoxy-3-oxo-1-propenyl]anilino]-2,2-dimethyl-3-oxopropionic acid		C₁₆H₁₉NO₅	详情	详情
(XXVII)	43475	ethyl (E)-3-(3,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydro-6-quinolinyl)-2-propenoate		C₁₆H₁₇NO₄	详情	详情
(XXVIII)	43476	ethyl 3-(3,3-dimethyl-2-oxo-1,2,3,4-tetrahydro-6-quinolinyl)propanoate		C₁₆H₂₁NO₃	详情	详情
(XXX)	43478	ethyl 3-[3,3-dimethyl-2-(methylsulfanyl)-3,4-dihydro-6-quinolinyl]propanoate		C₁₇H₂₃NO₂S	详情	详情

Extended Information