Synthesis of the Kinase Inhibitors Nintedanib, Hesperadin, and Their Analogues Using the Eschenmoser Coupling Reaction.
J Org Chem
; 86(15): 10621-10629, 2021 08 06.
Article
em En
| MEDLINE
| ID: mdl-34269051
A novel synthetic approach involving an Eschenmoser coupling reaction of substituted 3-bromooxindoles (H, 6-Cl, 6-COOMe, 5-NO2) with two substituted thiobenzanilides in dimethylformamide or acetonitrile was used for the synthesis of eight kinase inhibitors including Nintedanib and Hesperadin in yields exceeding 76%. Starting compounds for the synthesis are also easily available in good yields. 3-Bromooxindoles were prepared either from corresponding isatins using a three-step synthesis in an average overall yield of 65% or by direct bromination of oxindoles (yield of 65-86%). Starting N-(4-piperidin-1-ylmethyl-phenyl)-thiobenzamide was prepared by thionation of the corresponding benzanilide in an 86% yield and N-methyl-N-(4-thiobenzoylaminophenyl)-2-(4-methylpiperazin-1-yl)acetamide was prepared by thioacylation of the corresponding aniline with methyl dithiobenzoate in an 86% yield.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
/
Indóis
Idioma:
En
Revista:
J Org Chem
Ano de publicação:
2021
Tipo de documento:
Article
País de publicação:
Estados Unidos