Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2 H-indol-2-ones using an Eschenmoser coupling reaction

Lukáš Marek; Lukáš Kolman; Jiří Váňa; Jan Svoboda; Jiří Hanusek

doi:10.3762/bjoc.17.47

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2 H-indol-2-ones using an Eschenmoser coupling reaction

Beilstein J Org Chem. 2021 Feb 23:17:527-539. doi: 10.3762/bjoc.17.47. eCollection 2021.

Authors

Lukáš Marek¹, Lukáš Kolman¹, Jiří Váňa¹, Jan Svoboda¹, Jiří Hanusek¹

Affiliation

¹ Institute 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.

Keywords: (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones; 3-bromooxindoles; Eschenmoser coupling reaction; thioamides; tyrosin kinase inhibitors.