An improved and efficient synthesis of panobinostat

An improved and efficient method for the synthesis of panobinostat was developed. The commercially available starting material 4-(chloromethyl)benzaldehyde was converted to (E)-methyl3-[4-(chloromethyl)phenyl]acrylate via the Wittig-Horner reaction and was then directly condensed with 2-(2-methyl-1H-indol-3-yl)ethanamine to afford the key intermediate (E)-methyl 3-[4-({[2-(2-methyl-1H-indol-3-yl) ethyl] amino} methyl) phenyl] acrylate in a one-pot synthesis reactor. Subsequently a nucleophilic substitution reaction was carried out smoothly to generate the desired compound. The key intermediate and target compound were characterised by HRMS, H-1 NMR and C-13 NMR. This procedure is operationally simple and would be more suitable for industrial production.