I-type crystallization of N-n-propyl-3-(4-methylphenyl)-4-(4-mesylphenyl)-2,5-dihydropyrrole-2-ketone and manufacturing method thereof

A technology of methanesulfonyl phenyl and methyl phenyl, which is applied in the field of crystal form of antibacterial drugs, can solve the problems of fine crystallization, difficult filtration, poor fluidity, etc. The effect of crystal stability

Active Publication Date: 2010-07-14
JIANGSU HENGRUI MEDICINE CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Generally speaking, amorphous pharmaceutical products have no regular crystal structure and often have other defects, such as fine crystallization of the product, difficult filtration, easy agglomeration, poor fluidity, etc.

Method used

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  • I-type crystallization of N-n-propyl-3-(4-methylphenyl)-4-(4-mesylphenyl)-2,5-dihydropyrrole-2-ketone and manufacturing method thereof
  • I-type crystallization of N-n-propyl-3-(4-methylphenyl)-4-(4-mesylphenyl)-2,5-dihydropyrrole-2-ketone and manufacturing method thereof
  • I-type crystallization of N-n-propyl-3-(4-methylphenyl)-4-(4-mesylphenyl)-2,5-dihydropyrrole-2-ketone and manufacturing method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0036] N-n-propyl-3-(4-methylphenyl)-4-(4-methylsulfonylphenyl)-2,5-dihydropyrrol-2-one 10.0g (according to patent CN1318541A ​​disclosed method) was added into ethanol (150ml), heated to reflux to dissolve, slowly cooled to crystallize, and continued to crystallize to room temperature, and the precipitated crystals were collected by filtration. The obtained crystals were dried under reduced pressure at room temperature overnight to obtain 8.86 g of crystals with a yield of 88.6%. The residual ethanol solvent in the obtained sample is 100ppm, and the melting point measured by capillary method is 181.0~182.0°C; the X-ray diffraction spectrum of the crystalline sample is shown in figure 1 , is a type I crystal. See DSC Spectrum figure 2 , with a sharp melting endothermic peak of 183.87°C. The sample was dried under reduced pressure at 80° C. for 4 hours. The melting point of the dried sample was measured by capillary method to be 181.5-183.0° C., and the X-ray diffraction pa...

Embodiment 2

[0038] Add 10.0 g of N-n-propyl-3-(4-methylphenyl)-4-(4-methylsulfonylphenyl)-2,5-dihydropyrrol-2-one into methanol (150ml), Heat to reflux to dissolve, slowly cool to 35°C to start crystallization, continue to crystallize to room temperature, and collect the precipitated crystals by filtration. The obtained crystals were dried under reduced pressure at room temperature overnight to obtain 8.3 g of crystals, with a yield of 83%. Gained sample methanol solvent residual 200ppm, capillary method measures melting point 181.0~183.0 ℃; The characteristic peak of the X-ray diffraction spectrum of this crystalline sample is the same as figure 1 , is a type I crystal. The DSC spectrum has a sharp melting endothermic peak at 184.0°C. Then the sample was dried under reduced pressure at 80° C. for 4 hours. The melting point of the dried sample was measured by capillary method to be 181.5-183.0° C., and the X-ray diffraction spectrum was type I crystal. The DSC spectrum has a sharp melt...

Embodiment 3

[0040] Add 10.0 g of N-n-propyl-3-(4-methylphenyl)-4-(4-methylsulfonylphenyl)-2,5-dihydropyrrol-2-one to 50% ethanol (200ml) , heated to reflux to dissolve, slowly cooled to crystallize, crystals began to precipitate at 65°C, a large amount of crystals precipitated at 60°C, continued to crystallize to room temperature, and the precipitated crystals were collected by filtration. The obtained crystals were dried under reduced pressure at 60° C. overnight to obtain 9.1 g of crystals with a yield of 91%. The resulting sample has 500ppm ethanol solvent residue, contains 0.45% water, and has a melting point of 181.0-182.0°C measured by capillary method; the X-ray diffraction spectrum of the crystal sample is type I crystal. The DSC spectrum has a sharp melting endothermic peak at 184.42°C. Then the sample was vacuum-dried at 80°C for 4 hours, the moisture content of the dried sample was 0.20%, the melting point was 181.0-182.5°C measured by capillary method, and the X-ray diffracti...

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Abstract

The invention relates to I-type crystallization of N-n-propyl-3-(4-methylphenyl)-4-(4-mesylphenyl)-2,5-dihydropyrrole-2-ketone and a manufacturing method thereof. The method comprises the step of crystallizing any crystal form of or amorphous N-n-propyl-3-(4-methylphenyl)-4-(4-mesylphenyl)-2,5-dihydropyrrole-2-ketone solid with a polar organic solvent or aqueous solution thereof to obtain the I-type crystallization of N-n-propyl-3-(4-methylphenyl)-4-(4-mesylphenyl)-2,5-dihydropyrrole-2-ketone. The obtained I-type crystallization of N-n-propyl-3-(4-methylphenyl)-4-(4-mesylphenyl)-2,5-dihydropyrrole-2-ketone has favorable crystal form stability and chemical stability, and the utilized crystallization solvent has low toxicity and less residue, thereby the invention can be better used for clinical treatment.

Description

technical field [0001] The present invention relates to a crystal form of antibacterial drugs, especially N-n-propyl-3-(4-methylphenyl)-4-(4-methylsulfonylphenyl)-2,5-dihydropyrrole- 2-keto type I crystal and its preparation method. Background technique [0002] Two isoforms of cyclooxygenase isozymes are known so far: cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). Cyclooxygenase 1 is a structural enzyme that exists in normal tissues. Its physiological function is to catalyze the oxidation of arachidonic acid into prostaglandins, maintain the protective function of the gastrointestinal mucosa and the normal function of the kidney; cyclooxygenase 2 is Inducible enzyme, which is produced by stimulating cells such as endotoxins, cytokines or hormones, and can catalyze the production of prostaglandins that cause inflammation. At present, the effects of most non-steroidal anti-inflammatory drugs on the above two enzymes are known, and they inhibit cyclooxygenase 1 as we...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D207/38A61K31/4015A61P31/04
CPCC07D207/38A61P31/04
Inventor 孙飘扬陈永江刘全文
Owner JIANGSU HENGRUI MEDICINE CO LTD
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