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Method for preparing trimetazidine dihydrochloride

A technology of trimetazidine hydrochloride and piperazine, which is applied in the field of drug synthesis, can solve the problems of dangerous lithium tetrahydrogen aluminum and 2-piperazinone, which are difficult to obtain and low yield, and achieve simple operation and mild reaction conditions Safe, high yield effect

Active Publication Date: 2017-02-15
SUZHOU JINGYE MEDICINE & CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0015] The method has a low yield, 2-piperazinone is not easy to obtain, and needs to use dangerous lithium tetrahydrogen aluminum

Method used

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  • Method for preparing trimetazidine dihydrochloride
  • Method for preparing trimetazidine dihydrochloride
  • Method for preparing trimetazidine dihydrochloride

Examples

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Embodiment 1

[0038] Example 1: Put 300 g of methanol into the hydrogenation kettle, add 52 g (0.6 mol) of piperazine, add 36 g (0.6 mol) of acetic acid under mechanical stirring, heat to 40 ° C, keep for 30 min; cool to 35 ° C, add 2,3 , 130g (0.66mol) of 4-trimethoxybenzaldehyde, 1g (0.0027mol) of hexadecyltrimethylammonium bromide, 2g of nickel catalyst, airtight, nitrogen replacement in the system, keeping the hydrogen pressure at 0.5~0.8MPa, The system temperature was 50-60°C, and the reaction was stirred for 4 hours. Cool, release the pressure, filter to remove the catalyst, add toluene after the filtrate is concentrated, add 50g of 5% sodium hydroxide water, stir for 15min, stand still and separate layers, add 20g of water to the toluene layer to wash once, add 300g of ethanol after concentrating under reduced pressure, and add activated carbon 1 g, stirred for 30 minutes to decolorize, filtered, slowly added hydrochloric acid to the filtrate to adjust the pH to 2, stirred for 30 min...

Embodiment 2

[0042] Put 280g of methanol into the hydrogenation kettle, add 52g (0.6mol) of piperazine, add 36g (0.6mol) of acetic acid under mechanical stirring, heat to 40°C, keep for 30 min; cool to 35°C, add 2,3,4-trimethyl Oxybenzaldehyde 120g (0.61mol), hexadecyltrimethylammonium bromide 0.75g (0.002mol), nickel catalyst 2g, airtight, system nitrogen replacement, keep hydrogen pressure at 0.5~0.8MPa, system temperature at Stir and react for 4 hours at 50~60°C. Cool, release the pressure, filter to remove the catalyst, add toluene after the filtrate is concentrated, add 50g of 5% sodium hydroxide water, stir for 15min, stand still and separate layers, add 20g of water to the toluene layer to wash once, add 300g of ethanol after concentrating under reduced pressure, and add activated carbon 1g, stirred for 30 minutes to decolorize, filtered, slowly added hydrochloric acid to the filtrate to adjust the pH to 2, stirred for 30 minutes, filtered, washed with ethanol, dried to obtain 189.7...

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Abstract

The invention discloses a method for preparing trimetazidine dihydrochloride. The method includes steps of (1), dissolving piperazine into solvents and adding acid into the solvents to obtain piperazine salt; (2), adding 2, 3, 4-trimethoxy benzaldehyde, cetyl trimethyl ammonium bromide and nickel catalysts into the product obtained at the step (1) and carrying out catalytic hydrogenation reaction; (3), separating reaction products to obtain oily substances after the reaction is completely carried out, acidifying the oily substances by the aid of hydrochloric acid and crystallizing the oily substances to obtain the trimetazidine dihydrochloride. The method has the advantage of mild and safe reaction conditions and simplicity and convenience in operation. Besides, the usage of the piperazine can be reduced, the trimetazidine dihydrochloride prepared by the aid of the method is high in purity and yield, and the production cost can be reduced.

Description

technical field [0001] The invention relates to a preparation method of trimetazidine hydrochloride, which belongs to the technical field of medicine synthesis. Background technique [0002] Trimetazidine hydrochloride, chemical name is 1-[(2,3,4-trimethoxyphenyl)methyl]-piperazine hydrochloride, English name is Trimetazidine dihydrochloride; CAS: 13171-25-0; [0003] Its structural formula is: [0004] Molecular weight 339.3, white crystalline powder. [0005] Trimetazidine hydrochloride is a piperazine derivative, which is clinically used to treat angina pectoris. By improving myocardial energy metabolism without producing positive or negative inotropic effects, the symptoms of myocardial ischemia are relieved, coronary blood flow and peripheral blood flow are increased, and myocardial metabolism and myocardial energy production are promoted; it can reduce cardiac workload and reduce myocardial Oxygen consumption and myocardial energy consumption, thereby improving th...

Claims

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Application Information

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IPC IPC(8): C07D295/096
CPCC07D295/096
Inventor 沈建伟
Owner SUZHOU JINGYE MEDICINE & CHEM
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