Method for preparing ivabradine hydrochloride alpha crystal form

A technology of ivabradine hydrochloride and its crystal form, which is applied in the fields of organic chemistry and organic chemistry, and can solve problems such as difficult removal of residual solvents and low product purity

Active Publication Date: 2017-08-18
JIANGSU HENGRUI MEDICINE CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, according to the existing public technology, the preparation of the α crystal form is to dissolve in a mixed solvent of toluene and N-methylpyrrolidone, and then cool and crystallize. Due to the high boiling point of N-methylpyrrolidone (about 203 ° C), the product is dry. At this time, the residual solvent is not easy to remove. In order to meet the quality requirements of the solvent residue, a higher temperature and a longer drying time are required, and the long-term high temperature effect will easily reduce the purity of the product.

Method used

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  • Method for preparing ivabradine hydrochloride alpha crystal form
  • Method for preparing ivabradine hydrochloride alpha crystal form
  • Method for preparing ivabradine hydrochloride alpha crystal form

Examples

Experimental program
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Effect test

Embodiment 1

[0044]In 100mL (10 times, V / W) toluene, add 10.0g ivabradine hydrochloride (δ crystal form) obtained according to the method described in the patent specification EP0534859, heat up to reflux, stir for 0.5h, cool to room temperature, reduce Pressure filtration, and then drying at 60° C. under vacuum for 6 h, yielded 9.7 g of white solid powder, with a yield of 97.0%.

[0045] Analyzing assay results

[0046]

Embodiment 2

[0048] In 100mL (10 times, V / W) toluene, add 10.0g ivabradine hydrochloride (δd crystal form) obtained according to the method described in the patent specification EP0534859, heat up to reflux, stir for 0.5h, cool to room temperature, reduce Press filter, and then dry at 60°C under vacuum for 6 hours to obtain 9.8 g of white solid powder with a yield of 98.0%.

[0049] Analyzing assay results

[0050]

Embodiment 3

[0052] In 100mL (10 times, V / W) toluene, add 10.0g ivabradine hydrochloride (beta crystal form) obtained according to the method described in the patent specification CN1827600B, heat up to reflux, stir for 1.5h, cool to room temperature, reduce Press filter, and then dry at 60°C under vacuum for 6 hours to obtain 9.8 g of white solid powder with a yield of 98.0%.

[0053] Analyzing assay results

[0054]

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Abstract

The present invention relates to a method for preparing an ivabradine hydrochloride alpha crystal form, particularly to a preparation method of an ivabradine hydrochloride alpha crystal form represented by a formula I, wherein the amorphous crystal form or other crystal forms of the ivabradine hydrochloride are subjected to high temperature stirring crystal transformation in toluene, butyl acetate or 4-methyl-2-pentanone and other high boiling point poor solvents. According to the present invention, with the application of the method to prepare the ivabradine hydrochloride alpha crystal form, the operation process is simple, the product yield is high, and the product is easy to dry. The formula I is defined in the specification.

Description

technical field [0001] The invention relates to a method for preparing α crystal form of ivabradine hydrochloride. The ivabradine hydrochloride prepared by the method can be used as an active ingredient in the production of pharmaceutical preparations. Background technique [0002] Ivabradine hydrochloride (Ivabradine hydrochloride), chemical name 3-[3-[[[(7S)-3,4-dimethoxybicyclo[4.2.0]oct-1,3,5-triene- 7-yl]methyl]methylamino]propyl]-1,3,4,5-tetrahydro-7,8-dimethoxy-2H-3-benzazepine-2-one hydrochloride , the structural formula is as shown in formula (I): [0003] [0004] Ivabradine hydrochloride has highly valuable pharmacological properties and therapeutic effects, especially on heart rate slowing properties, making it useful for the treatment or prevention of various clinical symptoms of myocardial ischemia, such as angina pectoris, myocardial infarction and associated Rhythm disorders, and can be used for the treatment or prevention of various conditions involving...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D223/16
CPCC07B2200/13C07D223/16
Inventor 贺建峰尹超刘凯
Owner JIANGSU HENGRUI MEDICINE CO LTD
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