441741-66-8

Usage

Chemical Properties

Pale Yellow Solid

Uses

Intermediate in the preparation of Panobinostat

Upstream product

• 2731-06-8 2-methyltryptamine 
• 1067-74-9 Methyl diethylphosphonoacetate 
• 73291-09-5 4-chloromethylbenzaldehyde 
• 7560-50-1 methyl (2E)-3-(4-formylphenyl)acrylate 
• 441741-65-7 (E)-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]acrylic acid methyl ester 

Downstream Products

• 404950-80-7 panobinostat 

Relevant academic research and scientific papers

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)-methyl 3-[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, 1H NMR and 13C NMR. This procedure is operationally simple and would be more suitable for industrial production.

Synthesis method of panobinostat key intermediate

The invention belongs to the field of medicine synthesis, and particularly relates to a synthesis method of a panobinostat key intermediate. The key intermediate is (E)-3-[4-[[[2-(2-methyl-1H-indole-3-yl)ethyl] amino] methyl] phenyl] methyl acrylate hydrochloride. The method has the advantages that the yield is as high as 85 percent or higher; the impurities are few; the purity is 99.5 percent orhigher; meanwhile, the operation is simple and convenient.

Synthesis method of panobinostat

The invention discloses a synthesis method of panobinostat. The synthesis method comprises a step of synthesizing 2-methyl tryptamine or hydrochloride thereof, namely taking 2-methylindole as a raw material, conducting reaction with chloroacetyl chloride or bromoacetyl bromide, and conducting reaction with potassium phthalimide to obtain the 2-methyl tryptamine. According to the technical scheme adopted by the invention, influence of toxic raw materials on the safety of a panobinostat product is avoided; meanwhile, the invention provides the synthesis method applicable to industrial production.

PROCESS FOR MAKING SALTS OF N-HYDROXY-3-[4-[[[2-(2-METHYL-1H-INDOL-3-YL)ETHYL]AMINO]METHYL]PHENYL]-2E-2-PROPENAMIDE

Salts of N-hydroxy-3-[4-[[[2-(2-methyl-1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2E-2-propenamide are prepared by various methods.

METHOD OF USE OF DEACETYLASE INHIBITORS

The present invention provides methods of treating and/or preventing pathologic cardiac hypertrophy and heart failure comprising administering hydroxamate compounds which are deacetylase inhibitors.

Deacetylase inhibitors

The present invention provides hydroxamate compounds which are deacetylase inhibitors. The compounds are suitable for pharmaceutical compositions having anti-proliferative properties.