Study On Synthesis Of A New Intermediate For Antidepressant Drug Vilazodone

5-(1-Piperazinyl)benzofuran-2-carboxamide is a intermediate of antidepressant Viibry. This paper shows study feasible and reasonable synthetic route of5-(1-Piperazinyl) benzofuran-2-carboxamide. The synthetic route contains four steps. The structure of produce of each step was certified by1H-NMR、13C-NMR、FI-IR、MS. Study on synthesis process of every step by means of changing different amount of catalyst, reaction pressure, temperature, solvent, base and reaction time in single factor experiment and orthogonal experiment.Firstly,5-Nitrosalicylaldehyde reacts with Ethyl bromoacetate to5-nitro-benzofuran-2-carboxylic acid methyl ester. The better reaction conditions are gained, which are reaction temperature105℃, base K2CO3, solvent NMP, reaction time7hs, the mole ratio of materials is1.2. The reaction yield is93.5%. Off-white solid is gained, whose purity is94.4%.Secondly,5-amino-benzofuran-2-carboxylic acid methyl ester is prepared by catalytic hydrogenation. The better reaction conditions are gained, which are the mass ratio of catalyst and material0.1, reaction pressure0.3MPa, reaction temperature25℃and time7hs. The reaction yield is96.9%.Thirdly,5-amino-benzofuran-2-carboxylic acid methyl ester reacts with bis(2-chlorolthyl) amine hydrochloride to5-(1-Piperazinyl)benzofuran-2-carboxylic acid methyl ester. The better reaction conditions are gained, which are the mole ratio of materials1.5, solvent is n-butyl alcohol, reaction temperature110℃and time8hs. The reaction yield is42.9%.Lastly,5-(1-Piperazinyl)benzofuran-2-carboxamide is produced by ammonolysis. The better reaction conditions are gained, which are the mole ratio of ammonia water and material30.0, reaction temperature45℃and time5hs. The reaction yield is42.9%.