Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction
Lukáš Marek1, Lukáš Kolman1, Jiří Váňa1
1Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentská 573, CZ532 10 Pardubice, Czech Republic.
Abstract:
A highly modular method for the synthesis of (Z)-3-[amino(phenyl/methyl)methylidene]-1,3-dihydro-2H-indol-2-ones starting from easily available 3-bromooxindoles or (2-oxoindolin-3-yl)triflate and thioacetamides or thiobenzamides is described. A series of 49 compounds, several of which have previously been shown to possess significant tyrosin kinase inhibiting activity, was prepared in yields varying mostly from 70 to 97% and always surpassing those obtained by other published methods. The method includes an Eschenmoser coupling reaction, which is very feasible (even without using a thiophile except tertiary amides) and scalable. The (Z)-configuration of all products was confirmed by NMR techniques.
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