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【结 构 式】

【药物名称】

【化学名称】3-[6-Oxo-9-(trifluoromethyl)-5,6,7,12-tetrahydroindolo[3,2-d][1]benzazepin-2-yl]propanenitrile

【CA登记号】252894-30-7

【 分 子 式 】C20H14F3N3O

【 分 子 量 】369.34928

【开发单位】CNRS (Originator), National Cancer Institute (Originator), Universität Hamburg (Originator)

【药理作用】Oncolytic Drugs, CDK1/Cyclin B Inhibitors, Inhibitors of Signal Transduction Pathways

合成路线1

5-Iodoanthranilic acid (I) was converted to ethyl ester (II) (1), which was subsequently reacted with ethoxysuccinyl chloride (III) to furnish the amide (IV). Dieckmann cyclization of (IV) using KH produced ketoester (V), and further dealkoxycarbonylation by heating in wet DMSO gave rise to benzazepinedione (VI). After formation of the corresponding hydrazone (VIII) with 4-(trifluoromethyl)phenylhydrazine (VII), Fisher indole synthesis yielded the paulone system (IX). The Heck reaction of (IX) with acrylonitrile in the presence of palladium catalyst gave adduct (X). The target saturated analogue was finally prepared by refluxing the acrylonitrile derivative (X) with Mg in MeOH.

1 Kunick, C.; Jalluri, R.K.; Sausville, E.A.; Gussio, R.; Zaharevitz, D.W.; Meijer, L.; Lemdke, T.; schultz, C.; Leost, M.; 2-Substituted paullones: CDK1/cyclin B-inhibiting property and in vitro antiproliferative activity. Bioorg Med Chem Lett 2000, 10, 6, 567.
2 Gussio, R.; Zaharevitz, D.W.; Sausville, E.A.; Jalluri, R.K. (US Department of Health & Human Services); Fused azepinone cyclin dependent kinase inhibitors. WO 9965910 .
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) 19964 5-Iodoanthranilic acid; 2-amino-5-iodobenzoic acid 5326-47-6 C7H6INO2 详情 详情
(II) 40683 ethyl 2-amino-5-iodobenzoate C9H10INO2 详情 详情
(III) 40684 ethyl 4-chloro-4-oxobutanoate; Ethyl succinyl chloride 14794-31-1 C6H9ClO3 详情 详情
(IV) 40685 ethyl 2-[(4-ethoxy-4-oxobutanoyl)amino]-5-iodobenzoate C15H18INO5 详情 详情
(V) 40686 ethyl 5-hydroxy-7-iodo-2-oxo-2,3-dihydro-1H-1-benzazepine-4-carboxylate C13H12INO4 详情 详情
(VI) 40687 7-iodo-3,4-dihydro-1H-1-benzazepine-2,5-dione C10H8INO2 详情 详情
(VII) 40688 1-[4-(trifluoromethyl)phenyl]hydrazine 368-90-1 C7H7F3N2 详情 详情
(VIII) 40689 7-iodo-3,4-dihydro-1H-1-benzazepine-2,5-dione 5-[N-[4-(trifluoromethyl)phenyl]hydrazone] C17H13F3IN3O 详情 详情
(IX) 40690 2-iodo-9-(trifluoromethyl)-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one C17H10F3IN2O 详情 详情
(X) 40691 (E)-3-[6-oxo-9-(trifluoromethyl)-5,6,7,12-tetrahydroindolo[3,2-d][1]benzazepin-2-yl]-2-propenenitrile C20H12F3N3O 详情 详情
Extended Information