CN107698561A - A kind of preparation method of pazopanib - Google Patents
A kind of preparation method of pazopanib Download PDFInfo
- Publication number
- CN107698561A CN107698561A CN201711256726.1A CN201711256726A CN107698561A CN 107698561 A CN107698561 A CN 107698561A CN 201711256726 A CN201711256726 A CN 201711256726A CN 107698561 A CN107698561 A CN 107698561A
- Authority
- CN
- China
- Prior art keywords
- pazopanib
- ethanol
- preparation
- added dropwise
- present
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Abstract
The present invention relates to a kind of pazopanib process for purification, belong to bulk drug preparing technical field.The preparation method of pazopanib of the present invention, comprises the following steps：Pazopanib dissolving crude product adds the activated carbon of Axitinib weight 5%, stirred, filter in the in the mixed solvent of acetone and ethanol；Under stirring, 95% ethanol of 0.6 1.2 times of first step liquor capacity is slowly added dropwise into first step filtrate, is added dropwise, system is quickly cooled to 8 DEG C to 3 DEG C, continues to stir；3rd step filters, and obtains product of the present invention.The invention provides the pazopanib bulk drug that a kind of D90 of high-purity is 100 120 microns, present invention process is simple to operation, is adapted to industrialized production, and product purity of the present invention can reach more than 99.95%.
Description
Technical field
The present invention relates to a kind of pazopanib process for purification, belong to bulk drug preparing technical field.
Background technology
Pazopanib（Axitinib）, alias Axitinib, chemical name：N- methyl -2- [3- ((E) -2- pyridines -2-
Base-vinyl) -1H- indoles -6- bases sulphonyl]-benzamide.Pazopanib is antineoplastic, is clinically mainly used in previously connecing
A kind of progressive stage clear-cell carcinoma of tyrosine kinase inhibitor or cytokine therapy failure is received（RCC）Adult patient.Ah
West is developed for Buddhist nun by Pfizer companies, and on January 27th, 2012, FDA approvals listing, there is 2 specifications of 1 mg pieces and 5 mg pieces.
Pazopanib is white powder, 218.4 DEG C of fusing point, is slightly soluble in polyethylene glycol 400, is slightly soluble in methanol or ethanol, pole
Acetonitrile is slightly soluble in, is practically insoluble in water.Solubility is 0.8mg/ml in 20 DEG C of pH1.2 hydrochloric acid solutions, pH6.8 phosphate-buffereds
Solubility is 0.2 microgram/ml in solution, is typical pH dependent forms medicine.
Chinese patent application 201310322548.3,201310543901.0 provides the preparation method of Axitinib,
201310165500.6,201710156853.8 crystal formations and preparation method for disclosing Axitinib.Because Axitinib belongs to
Slightly solubility small dose drug, when preparation of preparation, it will usually Axitinib is crushed to certain granules degree, to improve its piece
The dissolution rate of agent.But granularity is too thin, Electrostatic Absorption can be produced, causes uniformity of dosage units exceeded, Axitinib content in preparation
After fluctuation can cause human body to be taken, the fluctuation of Axitinib concentration in blood, cause various adverse reactions.
Therefore, in the needs to having produced preparation, it is desirable to provide a kind of granularity is moderate, and the bulk drug that purity is high.
The content of the invention
【Goal of the invention】
It is an object of the invention to provide a kind of granularity is moderate, and the Axitinib bulk drug that purity is high.
【Technical scheme】
The technical scheme is that：A kind of preparation method of pazopanib, comprises the following steps
First step pazopanib dissolving crude product is in the in the mixed solvent of acetone and ethanol, the activity of addition Axitinib weight 5%
Charcoal, stir 1 hour, filtering；
The volume ratio of mixed solvent described in this step, acetone and ethanol is 1：（0.3-0.6）；
This step resulting solution, the concentration of pazopanib is 8-16%（Mass volume ratio）；
Under second step stirring, 95% ethanol of 0.6-1.2 times of first step liquor capacity is slowly added dropwise into first step filtrate, is added dropwise
Finish, system is quickly cooled to -8 DEG C to -3 DEG C, continue to stir 1-3 hours；
This step mixing speed can directly affect the granularity of product, preferably 300-380r/min, more preferably 340-360 r/min
The speed that 95% ethanol is added dropwise in this step is 4-8ml/min；It is preferred that 5-6ml/min；
The preferable technical scheme of this step, the volume that 95% ethanol is added dropwise is 0.7-1.0 times of first step liquor capacity；
3rd step is filtered, and filter cake is washed with the mixed solution of first step acetone and ethanol, obtains product of the present invention.
Preparation method of the present invention, prepared pazopanib D90For 100-120 microns.
【Beneficial effect】
The invention provides the pazopanib bulk drug that a kind of D90 of high-purity is 100-120 microns, product of the present invention need not
Crush, be used directly for the preparation of preparation, reduce the loss of material in crushing process, the pollution to environment, and because hitting
Relevant material rise caused by hitting caused by heat.Present invention process is simple to operation, is adapted to industrialized production, product of the present invention
Purity can reach more than 99.95%.
【Embodiment and reference examples】
The embodiment of the present invention is prepared with pazopanib crude product with prior art, and high performance liquid chromatography detection purity is 97.02%.
Embodiment 1, first step 8g pazopanibs dissolving crude product add in the in the mixed solvent of 100ml acetone and ethanol
0.4g activated carbons, stir 1 hour, filtering；The volume ratio of mixed solvent described in this step, acetone and ethanol is 1：0.3；
Under second step stirring, 60ml95% ethanol is slowly added dropwise into first step filtrate, rate of addition 4ml/min, drips
Finish, system is quickly cooled to -8 DEG C, continue stirring 1 hour；Mixing speed is 300r/min
3rd step is filtered, and filter cake is washed 3 times with the mixed solution of first step acetone and ethanol, every time with 10ml, obtains pazopanib
D90 is 100 microns, and high performance liquid chromatography detection purity is 99.97%, yield 94.02%.
Embodiment 2, first step 16g pazopanibs dissolving crude product add in the in the mixed solvent of 100ml acetone and ethanol
0.8g activated carbons, stir 1 hour, filtering；The volume ratio of mixed solvent described in this step, acetone and ethanol is 1：0.6；
Under second step stirring, 120ml 95% ethanol is slowly added dropwise into first step filtrate, rate of addition 8ml/min, is added dropwise
Finish, system is quickly cooled to -3 DEG C, continue stirring 3 hours；Mixing speed is 380r/min；
3rd step is filtered, and filter cake is washed 3 times with the mixed solution of first step acetone and ethanol, every time with 12ml, obtains pazopanib
D90 is 120 microns, and high performance liquid chromatography detection purity is 99.99%, yield 93.96%.
Embodiment 3, first step 14g pazopanibs dissolving crude product add in the in the mixed solvent of 100ml acetone and ethanol
0.7g activated carbons, stir 1 hour, filtering；The volume ratio of acetone and ethanol is 1：0.5；
Under second step stirring, 90ml95% ethanol is slowly added dropwise into first step filtrate, rate of addition 5ml/min, drips
Finish, system is quickly cooled to -5 DEG C, continue stirring 2 hours；Mixing speed is 350r/min；
3rd step is filtered, and filter cake is washed 3 times with the mixed solution of first step acetone and ethanol, every time with 10ml, obtains pazopanib
D90For 112 microns, high performance liquid chromatography detection purity is 99.99%, yield 94.16%.
Claims (8)
1. a kind of preparation method of pazopanib, it is characterised in that comprise the following steps：
First step pazopanib dissolving crude product is in the in the mixed solvent of acetone and ethanol, the activity of addition Axitinib weight 5%
Charcoal, stir 1 hour, filtering；
Under second step stirring, 95% ethanol of 0.6-1.2 times of first step liquor capacity is slowly added dropwise into first step filtrate, is added dropwise
Finish, system is quickly cooled to -8 DEG C to -3 DEG C, continue to stir 1-3 hours；
3rd step is filtered, and filter cake is washed with the mixed solution of first step acetone and ethanol, obtains product of the present invention.
2. according to the preparation method of pazopanib described in claim 1, it is characterised in that mixed solvent described in the first step, acetone
Volume ratio with ethanol is 1：（0.3-0.6）.
3. according to the preparation method of pazopanib described in claim 1, it is characterised in that the first step obtains the dense of pazopanib
Spend for 8-16%（Mass volume ratio）.
4. according to the preparation method of pazopanib described in claim 1, it is characterised in that second step mixing speed is 300-
380r/min。
5. according to the preparation method of pazopanib described in claim 1, it is characterised in that second step mixing speed is 340-360
r/min。
6. according to the preparation method of pazopanib described in claim 1, it is characterised in that the speed of 95% ethanol is added dropwise in second step
For 4-8ml/min.
7. according to the preparation method of pazopanib described in claim 1, it is characterised in that the speed of 95% ethanol is added dropwise in second step
For 5-6ml/min.
8. according to the preparation method of pazopanib described in claim 1, it is characterised in that the volume of 95% ethanol is added dropwise in second step
For 0.7-1.0 times of first step liquor capacity.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711256726.1A CN107698561A (en) | 2017-12-04 | 2017-12-04 | A kind of preparation method of pazopanib |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711256726.1A CN107698561A (en) | 2017-12-04 | 2017-12-04 | A kind of preparation method of pazopanib |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107698561A true CN107698561A (en) | 2018-02-16 |
Family
ID=61181199
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711256726.1A Withdrawn CN107698561A (en) | 2017-12-04 | 2017-12-04 | A kind of preparation method of pazopanib |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107698561A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113943271A (en) * | 2020-07-15 | 2022-01-18 | 鲁南制药集团股份有限公司 | Acixtinib crystal form and preparation method thereof |
-
2017
- 2017-12-04 CN CN201711256726.1A patent/CN107698561A/en not_active Withdrawn
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113943271A (en) * | 2020-07-15 | 2022-01-18 | 鲁南制药集团股份有限公司 | Acixtinib crystal form and preparation method thereof |
| CN113943271B (en) * | 2020-07-15 | 2023-11-14 | 鲁南制药集团股份有限公司 | Acetinib crystal form and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102387789A (en) | Delayed release, oral dosage compositions that contain amorphous cddo-me | |
| CN102256984A (en) | Method for producing diamine derivative | |
| CN107698561A (en) | A kind of preparation method of pazopanib | |
| CN107721978A (en) | A kind of preparation method of pazopanib | |
| CN107216409A (en) | A kind of preparation method of chitosan L malic acid rare earth compoundings | |
| CN102276447B (en) | Naproxen hydrate crystal, preparation method thereof and medicinal composition containing naproxen hydrate crystal and sumatriptan | |
| CN109111426A (en) | A kind of fused bicyclic heteroaryl group or aryl compound, and application thereof | |
| CN101723857B (en) | Contain lipid prodrug and the pharmacome thereof of the medicine of guanidine radicals | |
| CN101575340B (en) | Preparation method of ketorolac tromethamine | |
| CN105193803A (en) | Ilepcimide sustained release preparation and preparation method thereof | |
| CN104672210B (en) | The preparation method of Egelieting and alogliptin benzoate | |
| CN109925287A (en) | A kind of Pyrochep and preparation method thereof | |
| CN103159651B (en) | Sulfonylurea guanidine and preparation method and application thereof | |
| WO2021258851A1 (en) | Pharmaceutical composition for treating diabetes and preparation method therefor | |
| CN104016942B (en) | Thiazolinone analog derivative and pharmaceutical composition thereof and application | |
| CN108129486B (en) | Pyrimidone derivatives and uses thereof | |
| CN114524769B (en) | Celecoxib-carbamazepine eutectic, preparation method, pharmaceutical composition and application | |
| CN104530054A (en) | Polymorphic substance of yonkenafil hydrochloride and preparation method thereof | |
| CN110204493A (en) | Tricyclic antidepressants XOR inhibitor and its preparation method and application | |
| KR20200098992A (en) | Methods for preparing aceclofenac and pharmaceutical composition comprising the same | |
| CN102688250A (en) | Synthesis and application of azo derivatives as inhibitor of RSK2 | |
| CN112679370B (en) | Preparation method of medicinal arginine glutamic acid | |
| CN103588653B (en) | Polymorph of 4-methylbenzoate-4-[2-dimethylamino-1-(1-hydroxycyclohexyl) ethyl]phenyl-ester hydrochloride, and preparation method and application thereof | |
| CN101985438A (en) | Substituted phenyl piperazinyl aralkylone derivatives and application thereof to preparation of analgesics | |
| CN101418001B (en) | Dipeptidase-IV inhibitor sulfonyl urea derivates |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20180216 |
|
| WW01 | Invention patent application withdrawn after publication |