合成路线1

A modification of Leimgruber-Batcho synthesis of indoles was employed to convert 3-methyl-4-nitrobenzoic acid (I) to the 3,5-disubstituted indole (V)). In this process, the intermediate enamine (II) was alkylated with the bromobenzoate (III) prior to hydrolysis and reductive cyclization to the indole nucleus. Alkylation of (V) with iodomethane under basic conditions, followed by amide formation using (R)-4,4,4-trifluoro-2-methylbutylamine (VII) afforded the key intermediate amidoester (VIII). Hydrolysis of the methyl ester moiety of (VIII) with aqueous lithium hydroxide, followed by sulfonimide formation gave ZD 3523).