Synthesis method of itopride hydrochloride

Abstract

The invention discloses a synthesis method of itopride hydrochloride, and relates to the technical field of organic synthesis. Hydroxybenzylamine is taken as starting material, in non-polar solvent, in the presence of an acid-binding agent, the Hydroxybenzylamine and 3,4-dimethoxybenzoyl chloride are subjected to amidation to obtain an intermediate N-(4-hydroxyl) benzyl-3,4-dimenthoxybenzamide, and in polar solvent, in the presence of a catalyst, the intermediate N-(4-hydroxyl) benzyl-3,4-dimenthoxybenzamide and 2-chlorine-N,N-dimethylethylamine are subjected to etherification to obtain the itopride hydrochloride. According to the method, the raw materials are easy to obtain, the route is short, only two steps of synthetic reactions are needed, the high yield of 85-97% can be achieved in each step, by means of amidation and etherification with high product purity, a dangerous process of high-pressure hydrogenation is avoided successfully, and meanwhile, the production and raw materialcosts are greatly reduced.

Description

Technical field: [0001] The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing itopride hydrochloride. Background technique: [0002] Itopride hydrochloride is a new type of drug developed by Hokuriku Pharmaceutical Co., Ltd. to promote gastrointestinal motility. It is mainly used clinically to treat various dyspeptic symptoms caused by non-ulcer dyspepsia and chronic gastritis, with low side effects It is a real gastrointestinal motility agent without serious reactions of similar drugs. [0003] At present, the synthetic methods of itopride hydrochloride are based on 4-(2-dimethylamino)ethoxy)benzylamine and 3,4-dimethoxybenzoyl chloride as key intermediates, which occur in a solvent. Amidation reaction. However, the preparation of the key intermediate 4-{2-(dimethylamino)} ethoxybenzylamine is relatively cumbersome, the steps are longer, and the dangerous process of pressure hydrogenation of Ranisin must be carried out. The...

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Problems solved by technology

However, the preparation of the key intermediate 4-{2-(dimethylamino)}ethoxybenzylamine is cumbersome, and the steps are long, and the dangerous process of pressurized hydrogenation of Raney gold must be carried out, and the purity of the obtained product is 95 %, it is more difficult to purify, and then also leads to the decrease of the target product yield in the next step, the difficulty of purification increases, the total yield of the current synthesis process is low, the steps are long, and the hydrogenation step needs to be completed under the pressure of 5-10atm, which does not meet the current advocacy The concept of green and safe pharmaceutical production

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