ER-35794

Chemical Name: (E,E,E)-7-Ethyl-6-fluoro-7-(1-isopropyl-1,2,3,4-tetrahydroquinolin-6-yl)-3-methyl-2,4,6-heptatrienoic acid
项目整合开发状态: Biological Testing
项目研究机构: Eisai (Originator)
合成路线:Formylation of tetrahydroquinoline (I) with N,N-dimethylformamide and POCl3 afforded aldehyde (II),which was condensed with ethylmagnesium bromide to give alcohol (III),and then oxidized to ketone (IV) with activated MnO2 in acetone.Coupling with triethyl 2-fluoro-2-phosphonoacetate (V) in the presence of NaH in DMF produced a mixture of olefins,from which the desired E isomer (VI) was separated by column chromatography.Ester reduction with DIBAL-H at -70 C provided the E-alcohol (VII),which was oxidized to aldehyde (VIII) with MnO2 in acetone.Horner-Emmons condensation with phosphonate (IX) afforded heptatrienoic ester (X),which was finally hydrolyzed with NaOH to the target heptatrienoic acid.