Synthesis of (<i>Z</i>)-3-[amino(phenyl)methylidene]-1,3-dihydro-2<i>H</i>-indol-2-ones using an Eschenmoser coupling reaction
Lukáš Marek, Lukáš Kolman, Jiří Váňa, Jan Svoboda, Jiří Hanusek
Abstract
A highly modular method for the synthesis of ( Z )-3-[amino(phenyl/methyl)methylidene]-1,3-dihydro-2 H -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.