Preparation method of agomelatine I type crystal

A crystal, type I technology, applied in the field of preparation of agomelatine type I crystal, can solve problems such as weight change, withdrawal syndrome, sexual dysfunction and the like

Inactive Publication Date: 2010-05-12
TIANJIN TAIPU PHARMA SCI & TECH DEV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Its unique mechanism of action is completely different from commonly used antidepressants such as selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI): SSRI and SNRI Antidepressants achieve antidepressant efficacy by increasing the concentration of serotonin, but this also brings many side effects, such as weight change, sexual dysfunction, withdrawal syndrome, etc.

Method used

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  • Preparation method of agomelatine I type crystal
  • Preparation method of agomelatine I type crystal
  • Preparation method of agomelatine I type crystal

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 3

[0027] Preparation of 7-methoxy-1-naphthylacetic acid

[0028] Dissolve 40 g of sodium hydroxide in 1000 ml of water, add 1000 ml of 95% ethanol, and mix well. Then, 50 g of (7-methoxy-1-naphthyl)-ethyl acetate was added to the above mixed solution and stirred at room temperature for 3 hours. The reaction was stopped and the ethanol was evaporated under reduced pressure to obtain a brownish red liquid. After washing with ethyl acetate 300ml X 2, 30ml of 95% ethanol was added to the water layer. Under stirring, concentrated hydrochloric acid was added dropwise to adjust the pH to 2, and a large amount of light brown was precipitated. solid. The product was filtered and dried to obtain 32 g, mp154-156°C, the content determined by HPLC was 98.48%, and the yield was 72%.

[0029] Reference Example 4: Preparation of 7-methoxy-1-naphthylacetamide

[0030] Add 50 g of 7-methoxy-1-naphthyl acetic acid to 750 ml of dichloromethane, heat to dissolve, and slowly add thionyl chloride dropwise...

Embodiment 7

[0038] Preparation of N-[2-(7-methoxy-1-naphthyl)ethyl]acetamide (agomelatine)

[0039] Dissolve 40g of 2-(7-methoxy-1-naphthyl)ethylamine in 250ml of pyridine, and heat to 40°C to dissolve it. Under ice-bath cooling and stirring, 21.9 g of acetyl chloride was slowly added dropwise. After dripping, remove the ice bath and stir at room temperature for 30 minutes. Then the reaction solution was poured into 300ml ice water, while vigorously stirring, a large amount of white precipitate was precipitated, stirring was continued for 1 hour, filtered, and the filter cake was washed with 200ml×2 water to obtain 48g of crude product (the obtained crude product was used in the following preparation examples).

[0040] 1 H NMR(400MHZ, CDCl 3 ): δ7.77-7.15(m 6H,); δ5.61(s, 1H,); δ3.99(s, 3H,); δ3.62(m, 2H,); δ3.25(t, 2H ,); δ 1.95 (s, 3H,) is consistent with literature reports (J. Med. Chem, 1994, 37(20), 3231-3239.

[0041] Preparation examples

Embodiment 1

[0043] Add 2g of agomelatine phase product to 10ml of absolute ethanol to dissolve, filter, and slowly drip the filtrate into 200ml of distilled water with stirring at room temperature. After the addition is complete, stir at room temperature for 30 minutes, filter, wash the filter cake with distilled water, and vacuum dry for 10 hours. The yield is 88.5% and the content is 99.4%. The single crystal data is consistent with the type I data described in the literature (ActaCryst, 1994, C50, 907-910.); see the X-ray powder diffraction pattern figure 1 .

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Abstract

The invention discloses a preparation method of an agomelatine I type crystal which is an anti-depressant. The preparation method comprises the following steps of: dissolving crude agomelatine in a hydrophily organic solvent, filtering, dropping the filtrate into water under stirring, separating out solids and drying; wherein the weight part ratio of the hydrophily organic solvent to the water is 1:2-50. The agomelatine I type crystal prepared by the invention has excellent quality, good reproducibility, and high purity of HPLC normalization method to be above 99 percent, and is more suitable for large-scale industrialization production.

Description

Technical field [0001] The invention belongs to the technical field of pharmaceutical chemical synthesis, and relates to a method for preparing agomelatine type I crystals. Background technique [0002] Agomelatine is the first and only melatonin 1, 2 (MT1MT2) receptor agonist developed by the French company Servier, and it is also an antagonist of serotonin 2c (5HT2c) receptor. Mainly used to treat the onset of depression. Its unique mechanism of action is completely different from commonly used antidepressants such as selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI): SSRI and SNRI Antidepressants achieve antidepressant effects by increasing the concentration of serotonin, but this also brings many side effects, such as weight change, sexual dysfunction, and withdrawal syndrome. The molecular structure of agomelatine directly binds to the serotonin 2c (5HT2c) receptor of the postsynaptic membrane of nerves, thereby exerting...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C233/18C07C231/24
Inventor 赵健朱建强
Owner TIANJIN TAIPU PHARMA SCI & TECH DEV
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