CN101993469A - Method for preparing medicinal dienogest - Google Patents
Method for preparing medicinal dienogest Download PDFInfo
- Publication number
- CN101993469A CN101993469A CN2009101846628A CN200910184662A CN101993469A CN 101993469 A CN101993469 A CN 101993469A CN 2009101846628 A CN2009101846628 A CN 2009101846628A CN 200910184662 A CN200910184662 A CN 200910184662A CN 101993469 A CN101993469 A CN 101993469A
- Authority
- CN
- China
- Prior art keywords
- dienogest
- preparation
- organic solvent
- medicinal
- methylene dichloride
- 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.)
- Pending
Links
Abstract
The invention provides a method for preparing medicinal dienogest. The method comprises the following steps of: performing column purification on a dienogest coarse product, and then re-crystallizing, so that the standard of the expected medicinal dienogest is met.
Description
Technical field
The present invention relates to a kind of contraceptive bian---the preparation method of medicinal dienogest belongs to chemistry and chemical and medicine industry field.
Background technology
(Dienogest is the contraception new drug of nineteen ninety-five in Germany's listing STS-557) to dienogest, is a kind of mixed type progestogen, and it has the double properties of 19-norepinephrine testosterone derivative and derivatives of progesterone, and has unique pharmacodynamics and pharmacokinetics character concurrently.
The chemistry of dienogest is called 17 alfa-cyanomethyls-17 beta-hydroxy-4,9-estradiene-3-ketone, and structural formula is as follows:
PCT patent WO2007066158A discloses the method for preparing high purity dienogest, and this patent is defined as high purity dienogest: the total amount of impurity is less than 0.1%, and the amount of 4-bromo-dienogest is under detection limit (0.02%) simultaneously.
According to the relevant regulations of ICH, our purpose is to prepare the medicinal dienogest that directly can be used for preparation, and total weight range of this dienogest impurity is less than 0.5%.
Summary of the invention
A kind of total weight range of medicinal dienogest impurity is less than 0.5%, such medicinal dienogest enough can use in preparation, and the people is injured very little, the more important thing is and produce such dienogest, its cost is low, make that the medicine valency is low, so purpose of the present invention prepares a kind of like this medicinal dienogest exactly.
For solving the object of the invention, the technology that the present invention adopts is:
A kind of preparation method of medicinal dienogest comprises: after the dienogest crude product was dissolved in organic solvent, the silica gel of packing in the silicagel column adopted gradient elution method, collects sample, concentrates, and obtains solid and obtains the medicinal dienogest through recrystallization again.
The weight ratio of described dienogest and silica gel is 1: (30～60).
The dissolution solvent of described dienogest is a methylene dichloride.
Described gradient elution method is an organic solvent A: organic solvent B=100: 1～10: 1 gradient elutions.
Described organic solvent A is a methylene dichloride, and organic solvent B is selected from acetone or ethyl acetate.
Described recrystallization solvent is an acetonitrile, if needed, can carry out secondary recrystallization with acetonitrile and ethyl acetate again.
The gradient elution of described employing is organic solvent A in proper order: organic solvent B=100: 1,50: 1,20: 1,10: 1 wash-outs successively.
The present invention has following advantage compared to existing technology:
The silicagel column that the present invention adopts is common silicagel column, rather than disclosed preparation HPLC among the WO2007066158A, and the advantage of common silicagel column is its low price, and is easy to operate, and production output is far above preparation HPLC.
Embodiment
The present invention is further illustrated below in conjunction with embodiment.
Embodiment 1: the preparation of medicinal dienogest
After dienogest crude product 60 grams add the dissolving of 250mL methylene dichloride, toward simple glass silicagel column (diameter 12cm, length 100cm) dress 200-300 purpose silica gel 3000 grams, cross silicagel column, methylene dichloride: methylene dichloride again behind acetone=100: 1 wash-out: acetone=50: 1 wash-outs once, methylene dichloride again: acetone=20: 1 wash-outs, last methylene dichloride: acetone=10: 1 wash-outs, collect concentrating sample liquid, dense doing gets faint yellow solid 57.8 grams, with the acetonitrile reflux molten clear 30 minutes, stirring is cooled to normal temperature, and suction filtration is dried to such an extent that white solid 54 restrains.Yield 90%.Total impurities is 0.35% (HPLC).
Embodiment 2: the preparation of medicinal dienogest
After dienogest crude product 60 grams add the dissolving of 250mL methylene dichloride, toward simple glass silicagel column (diameter 12cm, length 100cm) dress 200-300 purpose silica gel 3600 grams, cross silicagel column, methylene dichloride: methylene dichloride again behind ethyl acetate=100: 1 wash-out: ethyl acetate=50: 1 wash-outs once, methylene dichloride again: ethyl acetate=20: 1 wash-outs, last methylene dichloride: ethyl acetate=10: 1 wash-outs, collect concentrating sample liquid, dense doing gets faint yellow solid 58.8 grams, with the acetonitrile reflux molten clear 30 minutes, stirring is cooled to normal temperature, and suction filtration is dried to such an extent that white solid 54.6 restrains.Yield 91%.Total impurities is 0.22% (HPLC).
Embodiment 3: the preparation of medicinal dienogest
After dienogest crude product 60 grams add the dissolving of 250mL methylene dichloride, toward simple glass silicagel column (diameter 12cm, length 100cm) dress 200-300 purpose silica gel 1800 grams, cross silicagel column, methylene dichloride: methylene dichloride again behind acetone=100: 1 wash-out: acetone=50: 1 wash-outs once, methylene dichloride again: acetone=20: 1 wash-outs, last methylene dichloride: acetone=10: 1 wash-outs, collect concentrating sample liquid, dense doing gets faint yellow solid 52.8 grams, with the acetonitrile reflux molten clear 30 minutes, stirring is cooled to normal temperature, and suction filtration is dried to such an extent that white solid 49.2 restrains.Yield 82%.Total impurities is 0.42% (HPLC).
Embodiment 4: the preparation of medicinal dienogest
To prepare dienogest 60 grams by embodiment 2 and use 1000mL acetonitrile reflux molten clear, and add the 1000mL ethyl acetate under stirring, and be cooled to normal temperature, suction filtration is dried to such an extent that white solid 58 restrains.Yield 95%.Total impurities is 0.10% (HPLC).
Embodiment 5: the preparation of medicinal dienogest
To prepare dienogest 60 grams by embodiment 3 and use 1000mL acetonitrile reflux molten clear, and add the 1000mL ethyl acetate under stirring, and be cooled to normal temperature, suction filtration is dried to such an extent that white solid 58 restrains.Yield 95%.Total impurities is 0.15% (HPLC).
Claims (8)
1. the preparation method of a medicinal dienogest comprises: after the dienogest crude product was dissolved in organic solvent, the silica gel of packing in the silicagel column adopted gradient elution method, collects sample, concentrates, and obtains solid and obtains the medicinal dienogest through recrystallization again.
2. preparation method according to claim 1, the weight ratio that it is characterized in that described dienogest and silica gel is 1: (30～60).
3. preparation method according to claim 1, the dissolution solvent that it is characterized in that described dienogest is a methylene dichloride.
4. preparation method according to claim 1 is characterized in that described gradient elution method is an organic solvent A: organic solvent B=100: 1～10: 1 gradient elutions.
5. preparation method according to claim 4 is characterized in that described organic solvent A is a methylene dichloride, and organic solvent B is selected from acetone, ethyl acetate.
6. preparation method according to claim 1 is characterized in that described recrystallization solvent is an acetonitrile.
7. preparation method according to claim 6, it is characterized in that the acetonitrile recrystallization after, can carry out recrystallization once more with acetonitrile and ethyl acetate again.
8. according to the arbitrary described preparation method of claim 1 to 7, it is characterized in that the gradient elution that adopts is organic solvent A in proper order: organic solvent B=100: 1,50: 1,20: 1,10: 1 wash-outs successively.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101846628A CN101993469A (en) | 2009-08-27 | 2009-08-27 | Method for preparing medicinal dienogest |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101846628A CN101993469A (en) | 2009-08-27 | 2009-08-27 | Method for preparing medicinal dienogest |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101993469A true CN101993469A (en) | 2011-03-30 |
Family
ID=43784279
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009101846628A Pending CN101993469A (en) | 2009-08-27 | 2009-08-27 | Method for preparing medicinal dienogest |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101993469A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110357937A (en) * | 2018-03-26 | 2019-10-22 | 华润紫竹药业有限公司 | A kind of Dienogest compound |
| CN110655551A (en) * | 2019-09-23 | 2020-01-07 | 华润紫竹药业有限公司 | Dienogest drug single new crystal form and preparation method thereof |
-
2009
- 2009-08-27 CN CN2009101846628A patent/CN101993469A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110357937A (en) * | 2018-03-26 | 2019-10-22 | 华润紫竹药业有限公司 | A kind of Dienogest compound |
| CN110655551A (en) * | 2019-09-23 | 2020-01-07 | 华润紫竹药业有限公司 | Dienogest drug single new crystal form and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112638873A (en) | Refining method of indocyanine green | |
| CN102617575A (en) | Preparation process of high-purity oxymatrine | |
| CN102408318B (en) | Method for extracting and purifying sequoyitol | |
| CN101973864A (en) | Method for extracting shikonin from lithospermum | |
| CN101993469A (en) | Method for preparing medicinal dienogest | |
| CN102675395B (en) | Polycrystal forms of ulipristal acetate and preparation method thereof | |
| CN101891740A (en) | Method for extracting laburnine from upper part of thermopsis lanceolate | |
| CN104557576A (en) | Method for preparing high-purity pregabalin | |
| CN107722005B (en) | A kind of refining methd of pa Berkeley | |
| CN107033114B (en) | Method for separating and purifying dihydromyricetin | |
| CN104231025A (en) | Estrone raw material medicine impurity, preparation method of estrone raw material medicine impurity, and application of estrone raw material medicine impurity being used as standard substance | |
| CN106632380A (en) | Process for producing high-purity ellagic acid by desolvation crystallization method | |
| CN106316935B (en) | A kind of preparation method of Abemaciclib intermediate | |
| CN104844681B (en) | The process for purification of the brilliant type eplerenone of a kind of L | |
| CN104945364A (en) | Icaritin compound and application of compound | |
| CN102351828A (en) | Novel technology for extracting genistein | |
| CN106632145B (en) | Novel preparation method of vortioxetine hydrobromide crystal form alpha | |
| CN105085540B (en) | A kind of method for preparing high content nimoctin | |
| CN106543082B (en) | Preparation method of 5, 11-dihydro-6H-dibenzo [ b, e ] azepine-6 ketone | |
| CN112159448A (en) | Ethinylestradiol pharmaceutical co-crystal and preparation method and application thereof | |
| CN103848847B (en) | A kind of method that improvement prepares Olanzapine and its crystal formation II | |
| CN104650048B (en) | Purification method of olmesartan medoxomil condensation compound | |
| CN102070554B (en) | Method for preparing (5-thiazolyl) methyl-(4'-nitryl) phenyl carbonic ether hydrochloride | |
| CN105541756B (en) | The method that one kind prepares 1 (3,7 pairs of bases of dimethylamino phenthazine 10) ethyl ketone | |
| CN103755765B (en) | Polymorphic of CDB-2914 and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20110330 |