CN104557979A - Preparation method of levamisole hydrochloride - Google Patents
Preparation method of levamisole hydrochloride Download PDFInfo
- Publication number
- CN104557979A CN104557979A CN201310500876.8A CN201310500876A CN104557979A CN 104557979 A CN104557979 A CN 104557979A CN 201310500876 A CN201310500876 A CN 201310500876A CN 104557979 A CN104557979 A CN 104557979A
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- CN
- China
- Prior art keywords
- preparation
- levamisole hydrochloride
- tetramisole
- quality
- acetone
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a preparation method of helminthic levamisole hydrochloride. The preparation method comprises the following steps: dissolving a raw material L-tetramisole into an acetone, and adding sodium selenite; after decolorizing and filtering by using activated carbon, inflating dry hydrogen chloride gas while stirring till the pH value is 3-5; after reaction, separating and purifying to obtain the levamisole hydrochloride finished product. The levamisole hydrochloride prepared by the preparation method has the advantages of high quality, and no agglomerate, less impurity and no yellow spots in the storage process, and the like, so that the quality of the prepared levamisole hydrochloride is ensured; the levamisole hydrochloride is high in yield and environment-friendly and has a very bright industrial application prospect.
Description
Technical field
The invention belongs to field of medicine and chemical technology, particularly a kind of preparation method of insect repellent R-12564, belongs to field of chemical preparation.
Background technology
This product is the levo form of tetramisole, optionally suppresses the succinodehydrogenase in polypide muscle, makes fumaric acid not be reduced to succsinic acid, thus affect the anaerobic metabolism of polypide muscle, reduces energy and produces.When polypide contacts with it, neuromuscular depolarize can be made, muscle generation contracts last and cause paralysis; The plan choline effect of medicine is conducive to the discharge of polypide.Its activity is about 1 ~ 2 times of tetramisole (raceme), but toxic side effect is then lower.In addition, medicine may have restraining effect to the micro-tubular structure of polypide.LEVAMISOLE HCL also has immunomodulatory and the excited function of immunity.Good therapeutic effect is had to roundworm, hookworm, pinworm and strongyloidiasis.Because this product single dose is efficient higher, therefore be suitable for group therapy.To the activity of bancroft's filaria, Wuchereria malayi and filaria volvulus adult and microfilaria comparatively diethylcarbamazine be high, but late result is poor.
In prior art, usually L-tetramisole is dissolved in acetone, pass into dry hydrogen chloride gas, generate white precipitate, the R-12564 prepared by above technique existed that oxidizable and quality stability in high-temperature drying procedures is poor, storage can be lumpd for more than 1 year, turn yellow, the problem such as impurity increase.
Summary of the invention
The object of the present invention is to provide the preparation method of the R-12564 that a kind of steady quality, yield are high.
Reaction mechanism of the present invention is as follows:
Principle of the present invention is:
By liquid phase and mass spectrum and nuclear magnetic resonance spectroscopy research, the impurity of R-12564 mainly product generation slow oxidative reaction and being formed, because its molecular structure there being an Imidazothiazole ring, and oxidation open loop formation sulfoxide easily occurs the element sulphur on thiazole ring, so R-12564 there will be the problems such as caking, flavescence, impurity increase for more than 1 year in storage.
The technical solution realizing the object of the invention is:
A preparation method for R-12564, is dissolved in acetone by raw material L-tetramisole, adds Sodium Selenite, after activated carbon decolorizing filters, pass into dry hydrogen chloride gas under stirring until pH value is 3-5, reaction terminates rear separating-purifying, namely obtains R-12564 finished product.
In step of the present invention, the quality that feeds intake of described acetone is 2 ~ 4 times of raw material.
In step of the present invention, described hydrogenchloride intake is 1.0 ~ 2.0 times of feed molar amount.
In step of the present invention, described Sodium Selenite add-on is 0.02 ~ 0.05 times of raw materials quality.
The present invention compared with prior art, its remarkable advantage: the product obtained by preparation method of the present invention has that quality is high and in storage process, product does not lump, impurity is few, without advantages such as macula luteas, ensure that the quality preparing R-12564; Simultaneously high, the environmental friendliness of yield of the present invention, has good prospects for commercial application.
Embodiment
Embodiment 1:
Acetone 200g is dropped in the container filling 100gL-tetramisole, dissolve after being warming up to 50 DEG C, add gac 4-6g, Sodium Selenite 2g, stir decolouring 30 minutes, filter, filtrate passes into dry hydrogen chloride gas 25g and controls between 3-5 to pH value under stirring, filter after purifying, R-12564 108.3g is obtained after drying, yield 92.1%, target product stores and within more than 1 year, does not all lump, produces without yellow block, standing storage steady quality.
Embodiment 2:
Acetone 400g is dropped in the container filling 100gL-tetramisole, dissolve after being warming up to 50 DEG C, add gac 4-6g, Sodium Selenite 5g, stir decolouring 30 minutes, filter, filtrate passes into dry hydrogen chloride gas 25g and controls between 3-5 to pH value under stirring, filter after purifying, R-12564 110.5g is obtained after drying, yield 94.3%, target product stores and within more than 1 year, does not all lump, produces without yellow block, standing storage steady quality.
Embodiment 3
Acetone 300g is dropped in the container filling 100gL-tetramisole, dissolve after being warming up to 50 DEG C, add gac 4-6g, Sodium Selenite 3g, stir decolouring 30 minutes, filter, filtrate passes into dry hydrogen chloride gas 25g and controls between 3-5 to pH value under stirring, filter after purifying, R-12564 109.8g is obtained after drying, yield 93.2%, target product stores and within more than 1 year, does not all lump, produces without yellow block, standing storage steady quality.
Claims (4)
1. a preparation method for R-12564, is characterized in that raw material L-tetramisole to be dissolved in acetone, adds Sodium Selenite, after activated carbon decolorizing filters, pass into dry hydrogen chloride gas under stirring until pH value is 3-5, reaction terminates rear separating-purifying, namely obtains R-12564 finished product.
2. the preparation method of R-12564 according to claim 1, is characterized in that the quality that feeds intake of described acetone is 2 ~ 4 times of raw material.
3. the preparation method of R-12564 according to claim 1, is characterized in that the intake of described hydrogenchloride is 1.0-2.0 times of L-tetramisole molar weight.
4. the preparation method of R-12564 according to claim 1, is characterized in that described Sodium Selenite add-on is 0.02 ~ 0.05 times of raw materials quality.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310500876.8A CN104557979A (en) | 2013-10-23 | 2013-10-23 | Preparation method of levamisole hydrochloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310500876.8A CN104557979A (en) | 2013-10-23 | 2013-10-23 | Preparation method of levamisole hydrochloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104557979A true CN104557979A (en) | 2015-04-29 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310500876.8A Pending CN104557979A (en) | 2013-10-23 | 2013-10-23 | Preparation method of levamisole hydrochloride |
Country Status (1)
| Country | Link |
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| CN (1) | CN104557979A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110840888A (en) * | 2018-08-20 | 2020-02-28 | 山西医科大学 | The anthelmintic tetramizole can be used as novel antiarrhythmic drug |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3463786A (en) * | 1967-12-19 | 1969-08-26 | American Cyanamid Co | Method of resolving dl 6 - phenyl - 2,3,5,6-tetrahydroimidazo(2,1-b) - thiazole and novel compounds resulting therefrom |
| US3579530A (en) * | 1967-08-24 | 1971-05-18 | Ici Australia Ltd | Process for the resolution of racemic tetramisole |
| US3580923A (en) * | 1968-02-14 | 1971-05-25 | Ici Ltd | Resolution process |
| US3646051A (en) * | 1969-04-24 | 1972-02-29 | Rhone Poulenc Sa | Process for the resolution of a substituted imidazothiazole |
| CN1052117A (en) * | 1989-11-24 | 1991-06-12 | 詹森药业有限公司 | Immunostimulating 6-aryl-5,6-glyoxalidine be the preparation method of [2,1-b] thiazole derivative also |
| CN103242347A (en) * | 2013-05-20 | 2013-08-14 | 黑龙江大学 | Preparation method of tetramisole hydrochloride |
-
2013
- 2013-10-23 CN CN201310500876.8A patent/CN104557979A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3579530A (en) * | 1967-08-24 | 1971-05-18 | Ici Australia Ltd | Process for the resolution of racemic tetramisole |
| US3463786A (en) * | 1967-12-19 | 1969-08-26 | American Cyanamid Co | Method of resolving dl 6 - phenyl - 2,3,5,6-tetrahydroimidazo(2,1-b) - thiazole and novel compounds resulting therefrom |
| US3580923A (en) * | 1968-02-14 | 1971-05-25 | Ici Ltd | Resolution process |
| US3646051A (en) * | 1969-04-24 | 1972-02-29 | Rhone Poulenc Sa | Process for the resolution of a substituted imidazothiazole |
| CN1052117A (en) * | 1989-11-24 | 1991-06-12 | 詹森药业有限公司 | Immunostimulating 6-aryl-5,6-glyoxalidine be the preparation method of [2,1-b] thiazole derivative also |
| CN103242347A (en) * | 2013-05-20 | 2013-08-14 | 黑龙江大学 | Preparation method of tetramisole hydrochloride |
Non-Patent Citations (3)
| Title |
|---|
| SÁNDOR KESZEI，等: "Supercritical fluid extraction: a novel method for the resolution of tetramisole", 《TETRAHEDRON: ASYMMETRY》 * |
| 刘来利，等: "肉鸡肌注亚硒酸钠后血液中总抗氧能力变化的研究", 《畜牧兽医杂志》 * |
| 黄胜民: "四咪唑盐酸盐成盐母液回收新工艺", 《华夏医学》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110840888A (en) * | 2018-08-20 | 2020-02-28 | 山西医科大学 | The anthelmintic tetramizole can be used as novel antiarrhythmic drug |
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| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
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| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20150429 |