Refinement method of lercanidipine hydrochloride

A technology of lercanidipine hydrochloride and a purification method, applied in the field of medicine, can solve the problems of unstable yield and poor process reproducibility, and achieve the effects of short purification period, good stability and high yield

Active Publication Date: 2013-01-02
CHINA RESOURCES SAIKE PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to provide a refining method of lercanidipine hydrochloride, so as to overcome the shortcomings of poor process reproducibility and unstable yield in the existing lercanidipine hydrochloride post-treatment process

Method used

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  • Refinement method of lercanidipine hydrochloride

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] Embodiment 1, the preparation of lercanidipine hydrochloride crude product

[0017] Add 64g (0.193mol) lercanidipine hydrochloride core, 500mlDCM, 500mlDMF to the dry reaction flask, 2 Under protection, add 21ml (0.075mol) of thionyl chloride dropwise at 15°C~25°C, stir and react at 15°C~25°C for 2 hours, add dropwise dichloromethane solution of 57g (0.192mol) of lercanidipine hydrochloride side chain , stirred and reacted for 5 hours, after TLC showed that the reaction was complete, add 700ml saturated aqueous sodium bicarbonate solution to adjust PH=8, separate liquids, add 500ml of 4M dilute hydrochloric acid to the organic phase and stir to form a salt, evaporate to dryness under reduced pressure to obtain an oil, add 3000ml of isopropyl acetate was stirred for 10 hours for crystallization, and then filtered to obtain a light gray solid with a purity of 94.27%.

Embodiment 2

[0018] Embodiment 2, the volume determination contrast experiment of organic solvent

[0019] In a 250ml three-necked flask equipped with a thermometer and a stirring paddle, add 32 g of crude lercanidipine hydrochloride, and a mixed solvent of 48 ml of ethanol and 48 ml of isopropyl acetate, start stirring, raise the temperature to 30~35°C, soak and wash 2 hours, then lowered to room temperature (25°C), continued to stir for 6 hours, filtered, and air-dried at 60°C to obtain 28.2 g, yield 88.1%, HPLC purity 99.87%.

Embodiment 3

[0020] Embodiment 3, the volume determination contrast experiment of organic solvent

[0021] In a 250 ml three-necked flask equipped with a thermometer and a stirring paddle, respectively add 32 g of crude lercanidipine hydrochloride, add a mixed solvent of 24 ml of ethanol and 72 ml of isopropyl acetate, start stirring, heat up to 30~35 °C, soak Wash for 2 hours, then lower to room temperature (25°C), continue to stir for 6 hours, filter, and blow dry at 60°C to obtain 29.8 g, yield 93.1%, HPLC purity 99.91%.

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Abstract

The invention discloses a refinement method of lercanidipine hydrochloride, which comprises the following steps: dissolving a lercanidipine hydrochloride crude product in mixed organic solvent of C1-3 alkyl alcohol and C1-3 alkyl acetate, wherein the volume mass ratio of the mixed organic solvent is 2-6 times, preferably 3-4 times; heating to 0-40 DEG C, and stirring, wherein the preferable temperature is 30-35 DEG C; soaking and washing for 2 hours, and cooling to 0-25 DEG C, preferably 18-25 DEG C; and continuing stirring the obtained solution for 6 hours, filtering the precipitated solid, washing the filter cake with absolute ethanol to obtain a yellow solid, and carrying out forced air drying to obtain the high-purity lercanidipine hydrochloride. The method further refines the lercanidipine hydrochloride crude product, is simple and convenient for operation, has the advantages of high purification rate, high speed, high stability in the whole operation, short refinement period, high yield and cost saving, and finally obtains the high-purity lercanidipine hydrochloride.

Description

technical field [0001] The invention relates to the technical field of medicines, in particular to a method for refining lercanidipine hydrochloride. Background technique [0002] Lercanidipine hydrochloride is 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-[(3,3-diphenylpropane Base) methylamino] -1,1-dimethylethyl methyl ester hydrochloride, is a new type of 1,4-dihydropyridine derivatives with calcium ion pathway blocking activity, strong effective action, and Long time, high blood vessel selectivity, etc., is the third generation of CCB products, its antihypertensive mechanism is to block the calcium channel of arterial smooth muscle and directly relax the vascular smooth muscle, thereby reducing the total peripheral vascular resistance, The negative inotropic effect caused by the selective vasodilator effect of lercanidipine hydrochloride is weaker than that of nifedipine, nitrendipine and felodipine, and the vascular selectivity is stronger...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D211/90
Inventor 陆骁骏李东徐承环邹江杨琰
Owner CHINA RESOURCES SAIKE PHARMA
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