Beilstein J. Org. Chem.2021,17, 2765–2772, doi:10.3762/bjoc.17.186
achieved by treating 2-(2-oxo-2-phenylethyl)benzonitriles with amines in the presence of Me3Al. The reaction proceeds via a domino nucleophilic addition with subsequent intramolecular cyclisation. This method provides a wide variety of substituted 1-aminoisoquinolines with good functional group tolerance
. Furthermore, the synthetic utility of this protocol was demonstrated in the successful synthesis of the antitumor agent CWJ-a-5 in gram scale.
Keywords: 1-aminoisoquinolines; CWJ-a-5; intramolecular cyclisation; 2-(2-oxo-2-phenylethyl)benzonitriles; nucleophilic addition; Introduction
Heterocyclic compounds
-phenylethyl)benzonitriles was also examined. Scheme 3 summarizes the scope of 2-(2-oxo-2-phenylethyl)benzonitriles (3b–e) towards the domino nucleophilic addition followed by an intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines under optimal reaction conditions. Accordingly, 2-(2
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Graphical Abstract
Figure 1:
Biologically active 1-aminoisoquinolines.