Method for preparing nitrendipine impurities

A technology for nitrendipine and impurities, applied in the field of nitrendipine impurity preparation

CN110305059APending Publication Date: 2019-10-08深圳振强生物技术有限公司
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Publication Date
2019-10-08

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Abstract

The invention discloses a method for preparing nitrendipine impurities. The method comprises the following steps that 2-(benzyl(methyl)amino)ethanol, diketene and base are heated in a first solvent to40DEG C-70DEG C for reaction for 30 minute-2 hour, and an intermediate acetoacetate 2-(N-methyl-N-benzylamino)ethyl ester is obtained after reaction concentration; and the intermediate acetoacetate 2-(N-methyl-N-benzylamino)ethyl ester and m-nitrobenzaldehyde are added to a second solvent, ammonia water is added, a heating reflux reaction is performed for 1 hour-16 hour, cooling and then concentration are performed, and the nitrendipine impurities are obtained by a predetermined method. According to the method for preparing the nitrendipine impurities, convenience is provided for impurity analysis and research of nitrendipine bulk drugs and a preparation thereof, and a detection method and a determination basis are provided for the production and drug safety of nitrendipine.
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Description

technical field

[0001] The invention relates to the technical field of nitrendipine detection, in particular to a method for preparing nitrendipine impurities. Background technique

[0002] Nitrendipine is a dihydropyridine drug, the chemical name is 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate ethyl ester A Esters belong to calcium antagonists, their pharmacological effects are similar to nifedipine, and their effect on vascular relaxation is stronger than that of nifedipine, and their antihypertensive effect lasts for a long time. The temperature is 10~20, and the half-life is 10~22h. Clinically, it is mainly used for the treatment of various types of hypertension and angina pectoris. Impurities in drugs refer to substances in drugs that have no therapeutic effect or affect the stability and curative effect of drugs, and are even harmful to human health. In the research, production, storage and clinical application of drugs, it is necessary to ma...

Examples

Embodiment approach

[0027] As another embodiment, it is also possible to heat 2-(benzyl(methyl)amino)ethanol, diketene and triethylamine in a mass ratio of 5:3:1 to 70°C in tetrahydrofuran as a solvent, and react for 30 Minutes, the reaction was concentrated to give the intermediate 2-(N-methyl-N-benzylamino)ethyl acetoacetate.

[0028] As another embodiment, it is also possible to heat 2-(benzyl(methyl)amino)ethanol, diketene and triethylamine in a solvent tetrahydrofuran to 55°C in a mass ratio of 5:3:1, and react for 75 Minutes, the reaction was concentrated to give the intermediate 2-(N-methyl-N-benzylamino)ethyl acetoacetate.

[0029] Wherein, the raw material quality of described 2-(benzyl (methyl) amino) ethanol, diketene and triethylamine can be 0.1 gram~100 gram, for example, and the volume of described solvent tetrahydrofuran can be 2-( 5 to 10 times that of benzyl (methyl) amino) ethanol, diketene and triethylamine.

[0030] Step S20, adding the intermediate 2-(N-methyl-N-benzylamino...