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Eschenmoser reaction applied in the synthesis of kinase inhibitors

Authors: Marek Lukáš | Váňa Jiří | Svoboda Jan | Kocúrik Martin | Vrbický Martin | Pochobradský Jaroslav | Hanusek Jiří

Year: 2021

Type of publication: ostatní - přednáška nebo poster

Page from-to: nestránkováno

Titles:

Language	Name	Abstract	Keywords
eng	Eschenmoser reaction applied in the synthesis of kinase inhibitors	Current medicinal chemistry recognize several compounds with 3-[amino(aryl)methylidene]indol-2-one (1) pharmacophore as potent inhibitors of human kinases. This attribute predisposed them to be used in the treatment of autoimmune and oncological diseases. Despite significant pharmaceutical interest, synthetic accesibility of this structure scaffold is somewhat limited. In our group, we recently prooved2 that thiophile-free Eschenmoser coupling reaction of 3-bromoindol-2-ones with thioamides can serve as a powerful tool in preparation of 3-[amino(aryl)methylidene]indol-2-ones. In this work, we would like to further demonstrate versatility of this method by implementing it in novel synthetic approach (Scheme 1)3 of well-known tyrosine and Aurora A/B kinase inhibitors – Nintedanib, Hesperadin and their analogues Key thiobenzanilide derivatives (2a, 2b), were prepared first using thiobenzoylation or thionation reaction, and then they were reacted with substituted 3-bromoindol-2-ones (3a-f) in polar aprotic solvents (ACN, DMF) without action of a base or a thiophile. Desired Eschenmoser coupling products were obtained in good yields from 60 to 95%.	Eschenmoser reaction; kinase inhibitors; 3-bromoindol-2-ones