CN109694373A - A kind of preparation method of the beautiful Wei of high-purity department - Google Patents
A kind of preparation method of the beautiful Wei of high-purity department Download PDFInfo
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- CN109694373A CN109694373A CN201710989311.9A CN201710989311A CN109694373A CN 109694373 A CN109694373 A CN 109694373A CN 201710989311 A CN201710989311 A CN 201710989311A CN 109694373 A CN109694373 A CN 109694373A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Abstract
The present invention relates to a kind of beautiful Weis (simeprevir) of high-purity department, belong to bulk pharmaceutical chemicals preparation technical field.Preparation method of the present invention, comprising the following steps: a beautiful Wei crude product will be taken charge of and be dissolved in n,N-Dimethylformamide solvent, stirring and dissolving continues stirring 40 minutes to visually without solid particle, solution solid-to-liquid ratio is 0.08g/ml-0.18g/ml；Be added first step solution total amount 1.0-1.5%(volume mass ratio) active carbon, stir 30 minutes, filtering；95% ethyl alcohol of filtrate volume 1-3% is added into filtrate, adds the acetone of filtrate volume 1-2.6%, with sodium hydrate regulator solution pH between 6.8-8.0, stirs 30 minutes；- 8 DEG C to 0 DEG C are cooled to, stirring and crystallizing filters, 95% ethanol washing of filter cake, obtains the beautiful Wei of high-purity department.
Description
Technical field
The present invention relates to a kind of beautiful Weis (simeprevir) of high-purity department, belong to bulk pharmaceutical chemicals preparation technical field.
Background technique
Hepatitis C (HCV) is a kind of haematogenous infectiousness liver diseases, if being not treated in time, weight may be caused to liver
Big damage.In the U.S., there are about 3,200,000 hepatitis C patients, and there are about 1.5 ten thousand people to die of the disease every year, dies of hepatitis C mostly
Related disease, such as cirrhosis and liver cancer.
Take charge of beautiful Wei, alias: western miaow Wei, English name: simeprevir.FDA in November, 2013 approval listing, commercially available rule
Lattice: 150mg capsule.Taking charge of a beautiful Wei is NS3/4A protease inhibitors of new generation, is oral drugs once a day, by
Medivir company and Johnson & Johnson (Janssen) develop jointly, for treating the compensatory hepatopathy of chronic hepatitis C adult patients,
Liver fibrosis including each stage, its working principle is that by blocks protein enzyme, to inhibit HCV answering in liver cell
System.
Chinese patent 20141025388.9 and 201410284733.2, which discloses, takes charge of the beautiful Wei of beautiful Wei intermediate and department
Preparation method, but due to taking charge of a beautiful Wei, structure is complicated, and preparation process is more and complicated, and not soluble in water and alcoholic solvent, reaction gained
Product is not easily purified, and causes clinical application adverse reaction more.
Summary of the invention
Goal of the invention: a kind of beautiful Wei of high-purity department is provided, quality raw materials medicine is provided for preparation, reduces clinical adverse
Generation.
The technical scheme is that
A kind of preparation method of the beautiful Wei of high-purity department, comprising the following steps:
The first step will be taken charge of a beautiful Wei crude product and is dissolved in n,N-Dimethylformamide solvent, and stirring and dissolving is to visually without solid
Grain, solution solid-to-liquid ratio are 0.08g/ml-0.18g/ml, continue stirring 40 minutes；
Second step be added first step solution total amount 1.0-1.5%(volume mass ratio) active carbon, stir 30 minutes, filtering；
95% ethyl alcohol of filtrate volume 1-3% is added into filtrate for third step, and stirring adds the acetone of filtrate volume 1-2.6%,
Stirring is stirred 30 minutes with sodium hydrate regulator solution pH between 6.8-8.0；
4th step is cooled to -8 DEG C to 0 DEG C, stirs 1-3 hours, crystallization, filtering, 95% ethanol washing of filter cake.Obtain high-purity department
Beautiful Wei.
Currently preferred technical solution, the solid-to-liquid ratio of first step acquired solution are 0.10g/ml -0.15g/ml.
Currently preferred technical solution, the amount that 95% ethyl alcohol is added in third step is the 2% of filtrate volume.
Currently preferred technical solution, the amount that acetone is added in third step is the 2% of filtrate volume.
Currently preferred technical solution, third step between 7.0-7.5, stir 30 points with sodium hydrate regulator solution pH
Clock
Temperature is reduced to -6 DEG C to -2 DEG C crystallizations by currently preferred technical solution, the 4th step.
The utility model has the advantages that in technical solution of the present invention on the one hand active carbon, which is added, can decolourize, it on the other hand can be by crude product
In impurity absorption.The beautiful Wei of the department of technical solution preparation through the invention, high-efficient liquid phase technique detection purity can achieve 99.6%
More than.
Embodiment following embodiment beauty Wei crude product purity used of taking charge of is 95.6%, high-efficient liquid phase technique detection.
Embodiment 1, the beautiful Wei crude product of 8g department are dissolved in 100ml n,N-Dimethylformamide solvent, stirring and dissolving to mesh
Depending on no solid particle, continue stirring 40 minutes；Active carbon 1g is added, stirs 30 minutes, filtering；The 95% of 3ml is added into filtrate
Ethyl alcohol, stirring, adds 1ml acetone, stirs, and is 6.8 with sodium hydrate regulator solution pH, stirs 30 minutes；- 8 DEG C are cooled to,
Stirring 1 hour, crystallization, filtering, filter cake 95% ethanol washing of 15ml.40 DEG C of vacuum drying, vacuum degree 0.06MPa, when dry
Between 6 hours, high performance liquid chromatography detection department beauty Wei Hanliang be 99.86%, yield 92.23%.
Embodiment 2, the beautiful Wei crude product of 18g department are dissolved in 100ml n,N-Dimethylformamide solvent, and stirring and dissolving is extremely
Visually without solid particle, continue stirring 40 minutes；Active carbon 1.5g is added, stirs 30 minutes, filtering；1ml is added into filtrate
95% ethyl alcohol, stirring, add 2.6ml acetone, stir, with sodium hydrate regulator solution pH be 8, stir 30 minutes；It is cooled to
It 0 DEG C, stirs 1 hour, crystallization, filtering, filter cake 95% ethanol washing of 15ml.40 DEG C of vacuum drying, vacuum degree 0.06MPa are done
6 hours dry time, high performance liquid chromatography detection department beauty Wei Hanliang are 99.95%, yield 91.89%.
Embodiment 3, the beautiful Wei crude product of 15g department are dissolved in 100ml n,N-Dimethylformamide solvent, and stirring and dissolving is extremely
Visually without solid particle, continue stirring 40 minutes；Active carbon 1.2g is added, stirs 30 minutes, filtering；2ml is added into filtrate
95% ethyl alcohol, stirring, add 2ml acetone, stir, with sodium hydrate regulator solution pH be 7.5, stir 30 minutes；Cooling
It to -5 DEG C, stirs 1 hour, crystallization, filtering, filter cake 95% ethanol washing of 15ml.40 DEG C of vacuum drying, vacuum degree 0.06MPa,
Drying time 6 hours, high performance liquid chromatography detection department beauty Wei Hanliang was 99.97%, yield 91.93%.
Claims (6)
1. a kind of preparation method of the beautiful Wei of high-purity department, which comprises the following steps:
The first step will be taken charge of a beautiful Wei crude product and is dissolved in n,N-Dimethylformamide solvent, and stirring and dissolving is to visually without solid
Grain, solution solid-to-liquid ratio are 0.08g/ml-0.18g/ml, continue stirring 40 minutes；
Second step be added first step solution total amount 1.0-1.5%(volume mass ratio) active carbon, stir 30 minutes, filtering；
95% ethyl alcohol of filtrate volume 1-3% is added into filtrate for third step, and stirring adds the acetone of filtrate volume 1-2.6%,
Stirring is stirred 30 minutes with sodium hydrate regulator solution pH between 6.8-8.0；
4th step is cooled to -8 DEG C to 0 DEG C, stirs 1-3 hours, crystallization, and filtering, 95% ethanol washing of filter cake obtains production of the present invention
Product.
2. according to preparation method described in claim 1, which is characterized in that the solid-to-liquid ratio of first step acquired solution is 0.10g/ml-
0.15g/ml。
3. according to preparation method described in claim 1, which is characterized in that the amount that 95% ethyl alcohol is added in third step is filtrate volume
2%。
4. according to preparation method described in claim 1, which is characterized in that the amount that acetone is added in third step is the 2% of filtrate volume.
5. according to preparation method described in claim 1, which is characterized in that third step is with sodium hydrate regulator solution pH in 7.0-
Between 7.5, stir 30 minutes.
6. according to preparation method described in claim 1, which is characterized in that temperature is reduced to -6 DEG C to -2 DEG C crystallizations by the 4th step.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710989311.9A CN109694373A (en) | 2017-10-23 | 2017-10-23 | A kind of preparation method of the beautiful Wei of high-purity department |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710989311.9A CN109694373A (en) | 2017-10-23 | 2017-10-23 | A kind of preparation method of the beautiful Wei of high-purity department |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109694373A true CN109694373A (en) | 2019-04-30 |
Family
ID=66226604
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710989311.9A Pending CN109694373A (en) | 2017-10-23 | 2017-10-23 | A kind of preparation method of the beautiful Wei of high-purity department |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109694373A (en) |
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2017
- 2017-10-23 CN CN201710989311.9A patent/CN109694373A/en active Pending
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20190430 |
|
| WD01 | Invention patent application deemed withdrawn after publication |