Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

Beilstein Journal of Organic Chemistry

Felix Bacher¹  Irina Kuznetcova¹  Vladimir B. Arion¹  Hsiang-Yu Chuang²  Daniel Vegh³ 

[1] Institute of Inorganic Chemistry of the University of Vienna, Währinger Strasse 42, 1090 Vienna, Austria;Institute of Organic Chemistry of the University of Vienna, Währinger Strasse 38, 1090 Vienna, Austria;Institute of Organic Chemistry, Catalysis and Petrochemistry, Department of Organic Chemistry, Slovak Techmical University of Technology in Bratislava, Radlinského 9, SK-81237 Bratislava, Slovak Republic;

关键词: anticancer;    fischer indole synthesis;    heck reaction;    heterocyclic compounds;    indolobenzazepines;    latonduines;    paullones;   

DOI  :  10.3762/bjoc.18.15

来源: DOAJ

【 摘 要 】

Paullone isomers are known as inhibitors of tubulin polymerase and cyclin dependent kinases (Cdks), which are potential targets for cancer chemotherapy. Herein we report an efficient and clean pathway to the fourth isomer, which remained elusive so far, namely 7,8-dihydroindolo[2,3-d][1]benzazepin-6(5H)-one. Moreover, we demonstrate the generality of our pathway by synthesizing two closely related analogues, one containing a bromo substituent and the other one incorporating an 8-membered instead of a 7-membered ring. The key transformation in this four-step synthesis, with an overall yield of 29%, is the Fischer indole reaction of 2-nitrophenylacetyl acetoacetate with 1-benzyl-1-phenylhydrazine in acetic acid that delivers methyl 2-(1-benzyl-3-(2-nitrophenyl)-1H-indol-2-yl)acetate in 55% yield.

【 授权许可】

Unknown