CN100389114C - Ampiroxicam refining method - Google Patents
Ampiroxicam refining method Download PDFInfo
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- CN100389114C CN100389114C CNB2006100378275A CN200610037827A CN100389114C CN 100389114 C CN100389114 C CN 100389114C CN B2006100378275 A CNB2006100378275 A CN B2006100378275A CN 200610037827 A CN200610037827 A CN 200610037827A CN 100389114 C CN100389114 C CN 100389114C
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- ampiroxicam
- crude product
- haloalkane
- purification
- refining method
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to an ampiroxicam refining method. The purity of raw medicinal materials of ampiroxicam is greatly influenced by recrystal solvents. The present invention provides a new refining method which comprises the following steps: ampiroxicam crude products are dissolved in haloalkane and concentrated to be dried after the ampiroxicam crude products are washed and dried, then, the ampiroxicam crude products are recrystallized, and finally, ampiroxicam white crystals are obtained. Ampiroxicam refined with the method has the advantages of favorable stability, high purity, simple and convenient operation, and low cost, and the ampiroxicam is suitable for industrial production.
Description
Technical field
The present invention relates to a kind of process for purification of Ampiroxicam.
Background technology
Ampiroxicam (Ampiroxicam) is 4-[1-(Ethoxycarbonyloxy) ethoxy]-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide (CAS Registry Number:99464-64-9), be to be long-acting type NSAID (non-steroidal anti-inflammatory drug) of new generation, be mainly used in analgesia and anti-inflammatory after rheumatoid arthritis, osteoarthritis, pain in the back, scapulohumeral periarthritis, neck shoulder wrist syndrome, wound, operation and the exodontia clinically.As day clothes non_steroidal anti_inflammatory drug of new generation once, it is strong that Ampiroxicam has effect, longer duration, and distinguishing feature such as safe, gastrointestinal tolerance is good is quite paid close attention on medical market.EP 147177 has reported the process for purification of Ampiroxicam: the reaction solution that will contain the Ampiroxicam crude product is used the toluene recrystallization again behind column chromatography.This method will use the toluene of strong carinogenicity to do recrystallization solvent, easily produces dissolvent residual, and impurity is difficult to remove, and influences quality product, is difficult to reach people's clinical application requirement.In addition, the column chromatography spended time is long, and used eluent is a mixed solvent, and is not easy to recovery of applied, and the cost height is difficult for realizing suitability for industrialized production.
Summary of the invention
The objective of the invention is to avoid the weak point that above-mentioned prior art exists and provide a kind of solvent toxicity little, safety coefficient is big, and is easy and simple to handle, saves cost, is easy to realize the process for purification of the Ampiroxicam of suitability for industrialized production.Gained elaboration outward appearance is good, the purity height, and quality product meets people's clinical application requirement.
Purpose of the present invention can reach by following measure:
A kind of process for purification of Ampiroxicam, it is characterized in that the Ampiroxicam crude product is dissolved in the haloalkane of 10～30 times of Ampiroxicam crude product amounts, clean with distilled water, saturated nacl aqueous solution respectively, dry, concentrate, add 5～15 times of organic solvent recrystallizations of Ampiroxicam crude product amount again, obtain the Ampiroxicam white crystals.
Purpose of the present invention can also reach by following measure:
The Ampiroxicam crude product is dissolved in the haloalkane of 25～28 times of Ampiroxicam crude product amounts.
Wherein said haloalkane is each halides of alkane of C1～C10.
Alkyl alcohol, ketone or ester that wherein said recrystallization organic solvent is C1～C8.
Elaboration outward appearance with the refining gained of the inventive method is good, the purity height, and quality product meets people's clinical application requirement, and Ampiroxicam crystallization HPLC purity can reach more than 99%.
Embodiment
Embodiment 1
In the 1000ml four-necked bottle of reflux exchanger and stirring rod is housed; under the nitrogen protection; add Ampiroxicam crude product (12.3g) respectively; add 246ml methylene dichloride stirring and dissolving; use 125ml water and the water washing of 125ml saturated common salt respectively, anhydrous sodium sulfate drying steams and removes methylene dichloride; residue adds the 123ml ethyl formate; 1.0g gac refluxed 30 minutes, the heat filter; cooling crystallization; filter, vacuum-drying below 100 ℃ gets Ampiroxicam white crystals 9.4g; 157～159 ℃ of mp, yield 76.4%.
Embodiment 2
In the 1000ml four-necked bottle of reflux exchanger and stirring rod is housed, under the nitrogen protection, add Ampiroxicam crude product (12.3g) respectively; add 123ml n-butyl bromide stirring and dissolving, use 230ml water and the water washing of 230ml saturated common salt respectively, anhydrous sodium sulfate drying; steam and remove n-butyl bromide, residue adds 62ml butanone, 1.0g gac; refluxed 25 minutes, and filtered cooling crystallization; filter, vacuum-drying below 100 ℃ gets Ampiroxicam white crystals 9.0g; mp156～159 ℃, yield 73.2%.
Embodiment 3
In the 1000ml four-necked bottle of reflux exchanger and stirring rod is housed, under the nitrogen protection, add Ampiroxicam crude product (12.3g) respectively; add 369ml bromo-decane stirring and dissolving, use 320ml water and the water washing of 320ml saturated common salt respectively, anhydrous sodium sulfate drying; steam and remove bromo-decane, residue adds 185ml Virahol, 1.0g gac; refluxed 20 minutes, and filtered cooling crystallization; filter, vacuum-drying below 100 ℃ gets Ampiroxicam white crystals 8.9g; 155～158 ℃ of mp, yield 69.7%.
Claims (3)
1. the process for purification of an Ampiroxicam, it is characterized in that the Ampiroxicam crude product is dissolved in the haloalkane of 10～30 times of Ampiroxicam crude product amounts, clean with distilled water, saturated nacl aqueous solution respectively, dry, concentrate, add 5～15 times of organic solvent recrystallizations of Ampiroxicam crude product amount again, obtain the Ampiroxicam white crystals; Wherein the recrystallization organic solvent is alkyl alcohol, ketone or the ester of C1～C8.
2. the process for purification of Ampiroxicam according to claim 1 is characterized in that the Ampiroxicam crude product is dissolved in the haloalkane of 25～28 times of Ampiroxicam crude product amounts.
3. the process for purification of Ampiroxicam according to claim 1 is characterized in that wherein said haloalkane is each halides of alkane of C1～C10.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100378275A CN100389114C (en) | 2006-01-17 | 2006-01-17 | Ampiroxicam refining method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100378275A CN100389114C (en) | 2006-01-17 | 2006-01-17 | Ampiroxicam refining method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1800180A CN1800180A (en) | 2006-07-12 |
| CN100389114C true CN100389114C (en) | 2008-05-21 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006100378275A Expired - Fee Related CN100389114C (en) | 2006-01-17 | 2006-01-17 | Ampiroxicam refining method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100389114C (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4551452A (en) * | 1983-12-21 | 1985-11-05 | Pfizer Inc. | Anti-inflammatory 2-methyl-2H-1,2-benzo-(or -thieno-)thiazine-3-carboxamide 1,1-dioxide derivatives, compositions, and method of use therefor |
-
2006
- 2006-01-17 CN CNB2006100378275A patent/CN100389114C/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4551452A (en) * | 1983-12-21 | 1985-11-05 | Pfizer Inc. | Anti-inflammatory 2-methyl-2H-1,2-benzo-(or -thieno-)thiazine-3-carboxamide 1,1-dioxide derivatives, compositions, and method of use therefor |
Non-Patent Citations (4)
| Title |
|---|
| 《安吡昔康的合成及中间体的优化》. 梅之南等.《中国药物化学杂志》，第10卷第1期. 2000 |
| 《安吡昔康的合成及中间体的优化》. 梅之南等.《中国药物化学杂志》，第10卷第1期. 2000 * |
| 1-氯乙基碳酸酯. 王荣耕.《精细与专用化学品》，第23期. 2002 |
| 1-氯乙基碳酸酯. 王荣耕.《精细与专用化学品》，第23期. 2002 * |
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| Publication number | Publication date |
|---|---|
| CN1800180A (en) | 2006-07-12 |
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| C14 | Grant of patent or utility model | ||
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| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20080521 Termination date: 20130117 |