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A kind of preparation method of perindopril

A technology of perindopril and solvent, applied in the field of medicine, can solve the problems of difficult operation and high risk factor, and achieve the effect of improving safety and operability

Active Publication Date: 2022-06-24
北京鑫开元医药科技有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The purpose of the present invention is to overcome the above-mentioned deficiencies of the prior art and provide a method for preparing perindopril, which aims to solve the problem of high risk factor and difficult operation in the production process due to the need to use hydrogen in the existing perindopril preparation process. technical issues

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  • A kind of preparation method of perindopril
  • A kind of preparation method of perindopril
  • A kind of preparation method of perindopril

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preparation example Construction

[0040] The embodiment of the present invention provides a preparation method of perindopril, comprising the following steps:

[0041] Step S11 : adding the first solvent, benzyl ester perindopril and ammonium formate into the reaction vessel, and stirring to raise the temperature to the first preset temperature.

[0042] In this embodiment, the type and specification of the reaction vessel can be selected according to needs, for example, it can be a three-necked bottle with a volume of 500ml. The first solvent is used for dissolving benzyl ester perindopril and ammonium formate, which can be a protic solvent or an aprotic solvent, which can be selected according to needs. For example, when the first solvent is a protic solvent, it includes at least one of water, methanol, ethanol, isopropanol, formic acid, and acetic acid, and can be selected from water, methanol, ethanol, etc.; when the first solvent is aprotic In the case of solvents, it includes ethyl acetate, acetone, dim...

Embodiment 1

[0082] The preparation method of perindopril provided in this embodiment comprises the following steps:

[0083] Step S311: add ethanol (100ml), benzyl ester perindopril (10.0g) and ammonium formate (2.6g) to a 500ml three-necked flask, stir and heat up to 65°C;

[0084] Step S312: adding 10% anhydrous palladium carbon (1.0 g) to the there-necked flask, after adding, controlling the temperature of the solution in the there-necked flask to perform a reflux reaction at 75°C to 80°C, and the reflux reaction time is 2h;

[0085] Step S313: cooling the solution subjected to the reflux reaction to 20°C to 30°C, then filtering at 20°C to 30°C, concentrating under reduced pressure, and evaporating ethanol to dryness to obtain an intermediate, which is the residue after evaporating ethanol to dryness ;

[0086] Step S314: add 100ml of ethyl acetate and 50ml of purified water to the intermediate, stir for 10min and then stand for stratification to obtain an organic phase and an inorgan...

Embodiment 2

[0098] The preparation method of perindopril provided in this embodiment comprises the following steps:

[0099] Step S321: add ethanol (100ml), benzyl ester perindopril (10.0g) and ammonium formate (5.2g) to a 500ml three-necked bottle, stir and heat up to 65°C;

[0100] Step S322: add 10% anhydrous palladium carbon (1.0 g) to the there-necked flask, and after the addition, control the temperature of the solution in the there-necked flask to perform a reflux reaction at 75°C to 80°C, and the reflux reaction time is 2h;

[0101] Step S323: cooling the solution subjected to the reflux reaction to 20°C to 30°C, then filtering at 20°C to 30°C, concentrating under reduced pressure, and evaporating ethanol to dryness to obtain an intermediate, which is the residue after evaporating ethanol to dryness ;

[0102] Step S324: add 100ml of ethyl acetate and 50ml of purified water to the intermediate, stir for 10min and then stand for stratification to obtain an organic phase and an ino...

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Abstract

The invention belongs to the field of medicines, and in particular relates to a method for preparing perindopril, which comprises the following steps: adding a first solvent, perindopril benzyl ester and ammonium formate into a reaction vessel, stirring and raising the temperature to a first preset temperature; Water palladium carbon is added into the reaction vessel, and the temperature of the solution in the reaction vessel is controlled to carry out a reflux reaction at a second preset temperature; the solution after the reflux reaction is cooled and filtered to obtain an intermediate; the second solvent is added to the intermediate , stirred and left to stand for separation to obtain an organic phase and an inorganic phase; the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure to obtain perindopril. The present invention uses perindopril benzyl ester as raw material, adopts palladium carbon and ammonium formate to reduce perindopril benzyl ester to prepare perindopril, and the whole process can be realized without using hydrogen or high pressure The industrialized production of perindopril greatly improves the safety and operability of the production process.

Description

technical field [0001] The invention belongs to the field of medicine, in particular to a preparation method of perindopril. Background technique [0002] The chemical name for perindopril is (2S, 3aS, 7As)-1-[2-[l-(ethoxycarbonyl)-(S)-butylamino]-(S)-oxopropyl]-octahydro Indole-2-carboxylic acid, its chemical structural formula is shown below: [0003] [0004] The main property of perindopril is the inhibition of angiotensin I converting enzyme (or kininase II), on the one hand it can prevent the conversion of decapeptide angiotensin I to octapeptide angiotensin II (vasoconstrictor), on the other hand It also prevents degradation of bradykinin (vasodilator) to inactive peptides. These two effects contribute to the beneficial effects of perindopril in cardiovascular disease, especially arterial hypertension, heart failure and stable coronary heart disease. [0005] At present, the method for preparing perindopril by benzyl ester perindopril is usually the reductive de...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K5/062C07K1/34C07K1/02
CPCC07K5/06026
Inventor 柴国举孙天宇邓桂兴刘毅蒋娟艳戴信敏
Owner 北京鑫开元医药科技有限公司