An Improved and Efficient Synthesis of Panobinostat. (September 2018)

• Record Type: Journal Article
• Authors: Chen, Shanwen; Zhang, Peiming; Chen, Huali; Zhang, Pu; Yu, Yu; Gan, Zongjie
• Is Part Of: Journal of chemical research. Volume 42:Number 9(2018)
• Page Start: 471
• Page End: 473
• Publication Date: 2018-09
• Subjects: panobinostat -- histone deacetylase inhibitor -- synthesis -- Wittig–Horner reaction; Chemistry -- Research -- Periodicals; Chemistry -- Periodicals; 540.5
• DOI: 10.3184/174751918X15357309308931
• Languages: English
• ISSNs: 1747-5198

Abstract

An improved and efficient method for the synthesis of panobinostat was developed. The commercially available starting material 4-(chloromethyl)benzaldehyde was converted to ( E )-methyl 3-[4-(chloromethyl)phenyl]acrylate via the Wittig–Horner reaction and was then directly condensed with 2-(2-methyl-1 H -indol-3-yl)ethanamine to afford the key intermediate ( E )-methyl 3-[4-({[2-(2-methyl-1 H -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, 1 H NMR and 13 C NMR. This procedure is operationally simple and would be more suitable for industrial production.