CN107417753A - A kind of preparation method of Mestanlone - Google Patents
A kind of preparation method of Mestanlone Download PDFInfo
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- CN107417753A CN107417753A CN201710434760.7A CN201710434760A CN107417753A CN 107417753 A CN107417753 A CN 107417753A CN 201710434760 A CN201710434760 A CN 201710434760A CN 107417753 A CN107417753 A CN 107417753A
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- mestanlone
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0003—Androstane derivatives
- C07J1/0033—Androstane derivatives substituted in position 17 alfa and 17 beta
- C07J1/0037—Androstane derivatives substituted in position 17 alfa and 17 beta the substituent in position 17 alfa being a saturated hydrocarbon group
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- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a kind of preparation method of Mestanlone, the structural formula of the Mestanlone are as follows：Its specific preparation method is as follows：(1) chemical compounds I carries the compound ii of cyano group with acetone cyanohydrin or Cymag generation；(2) solution of Compound Compound II is first adjusted to acidity, with ethylene glycol, triethyl orthoformate return into ketal；Then solution is tuned into strong basicity again, forms compound III；(3) catalyst and hydrogen are added into the solution of compound III, generates compounds Ⅳ；(4) compounds Ⅳ is inserted into container and dissolved with tetrahydrofuran, then instilled the grignard reagent of methyl-magnesium-chloride or methyl-magnesium-bromide, obtain compound V；(5) elutriation under acid condition, obtains 3 ketals and obtains Mestanlone compound V again in same container.The present invention realizes the Chemical Manufacture of Mestanlone using simplest technique, and required raw material is few, and pollutant is few, while the Mestanlone purity of production department is high, fractional yield increase.
Description
Technical field
The present invention relates to pharmaceutical field, specifically a kind of preparation method of Mestanlone.
Background technology
Mestanlone alias mesterolone, mesterolone, androstanolone, for treating male hypogonadism and essence
Son reduction property sterility.With the development of society, the demand of Mestanlone is increasing, the production technology of Mestanlone at present
Complexity, while the product purity produced is low, causes product price height.
The content of the invention
It is an object of the invention to provide a kind of preparation method of Mestanlone, to solve what is proposed in above-mentioned background technology
Problem.
To achieve the above object, the present invention provides following technical scheme：
A kind of preparation method of Mestanlone, the structural formula of the Mestanlone are as follows：
Its specific preparation method is as follows：
(1) chemical compounds I carries the compound ii of cyano group with acetone cyanohydrin or Cymag generation, and this reaction is usually in alkalescence
Under the conditions of；
(2) solution of Compound Compound II is first adjusted to acidity, with ethylene glycol, triethyl orthoformate return into contracting
Ketone；Then solution is tuned into strong basicity, pH >=13, to take off the compound III that cyano group forms the ketone group of 3- ketals -17 again；
(3) catalyst and hydrogen are added into the solution of compound III, while controlling reaction temperature is to 35-45 degrees Celsius, it is raw
Into compounds Ⅳ, and compounds Ⅳ is taken out in neutral conditions；
(4) compounds Ⅳ is inserted into container and dissolved with tetrahydrofuran, then instill methyl-magnesium-chloride or methyl bromide
The grignard reagent of magnesium, backflow, obtains methyl compound V on 17-；
(5) under acid condition, then hydrolysis obtains 3- ketals and obtains U.S. male promise elutriation compound V again in same container
Dragon.
As the further scheme of the present invention：Potassium carbonate, sodium carbonate, triethylamine or hydroxide are utilized in the step (1)
Sodium makes pH value of solution=8-10 of chemical compounds I, 30-40 degrees Celsius of reaction temperature, by stirring, ensures the reaction time in 2-3 hours
It is interior.
As the further scheme of the present invention：The regulation reagent of acid condition is PTS in the step (2).
As the further scheme of the present invention：The regulation reagent of step (2) the neutral and alkali condition is sodium hydroxide.
As the further scheme of the present invention：The solvent of step (2) compound ii is boron trifluoride acetic acid solution.
As the further scheme of the present invention：Step (3) catalyst is palladium charcoal.
As the further scheme of the present invention：Carry out needing to heat during addition reaction in the step (4), control solution temperature
Degree is at 40-60 degrees Celsius.
As the further scheme of the present invention：Acid regulation is controlled with hydrochloric acid in the step (5).
Compared with prior art, the beneficial effects of the invention are as follows：
The present invention realizes the Chemical Manufacture of Mestanlone using simplest technique, and required raw material is few, and pollutant is few, simultaneously
The Mestanlone purity of production department is high, fractional yield increase.
Embodiment
Below in conjunction with the embodiment of the present invention, the technical scheme in the embodiment of the present invention is clearly and completely described,
Obviously, described embodiment is only part of the embodiment of the present invention, rather than whole embodiments.Based in the present invention
Embodiment, the every other embodiment that those of ordinary skill in the art are obtained under the premise of creative work is not made, all
Belong to the scope of protection of the invention.
Embodiment 1
In the embodiment of the present invention, a kind of preparation method of Mestanlone, the structural formula of the Mestanlone is as follows：
Its specific preparation method is as follows：
(1) chemical compounds I carries the compound ii of cyano group with acetone cyanohydrin or Cymag generation, and this reaction is usually in alkalescence
Under the conditions of, pH value of solution=8 of chemical compounds I, 30 degrees Celsius of temperature are made using potassium carbonate, sodium carbonate, triethylamine or sodium hydroxide；
(2) solution of Compound Compound II is first adjusted to acidity, with ethylene glycol, triethyl orthoformate return into contracting
Ketone, the regulation reagent of acid condition is PTS etc., and the solvent of compound ii is boron trifluoride acetic acid solution etc.；Then again by solution
It is tuned into strong basicity, pH >=13, to take off the compound III that cyano group forms the ketone group of 3- ketals -17；
(3) catalyst and hydrogen are added into the solution of compound III, catalyst is palladium charcoal, while controlling reaction temperature is to 35
Degree Celsius, compounds Ⅳ is generated, and compounds Ⅳ is taken out in neutral conditions；
(4) compounds Ⅳ is inserted into container and dissolved with tetrahydrofuran, then instill methyl-magnesium-chloride or methyl bromide
The grignard reagent of magnesium, backflow, obtains methyl compound V on 17-；
(5) elutriation is under acid condition again in same container for compound V, with the acidity of solution in hydrochloric acid control container,
Then hydrolysis 3- ketals obtain Mestanlone；
Embodiment 2
In the embodiment of the present invention, a kind of preparation method of Mestanlone, the structural formula of the Mestanlone is as follows：
Its specific preparation method is as follows：
(1) chemical compounds I carries the compound ii of cyano group with acetone cyanohydrin or Cymag generation, and this reaction is usually in alkalescence
Under the conditions of, pH value of solution=9 of chemical compounds I, 35 degrees Celsius of temperature are made using potassium carbonate, sodium carbonate, triethylamine or sodium hydroxide；
(2) solution of Compound Compound II is first adjusted to acidity, with ethylene glycol, triethyl orthoformate return into contracting
Ketone, the regulation reagent of acid condition is PTS etc., and the solvent of compound ii is boron trifluoride acetic acid solution etc.；Then again by solution
It is tuned into strong basicity, pH >=13, to take off the compound III that cyano group forms the ketone group of 3- ketals -17；
(3) catalyst and hydrogen are added into the solution of compound III, catalyst is palladium charcoal, while controlling reaction temperature is to 40
Degree Celsius, compounds Ⅳ is generated, and compounds Ⅳ is taken out in neutral conditions；
(4) compounds Ⅳ is inserted into container and dissolved with tetrahydrofuran, then instill methyl-magnesium-chloride or methyl bromide
The grignard reagent of magnesium, backflow, obtains methyl compound V on 17-；
(5) elutriation is under acid condition again in same container for compound V, with the acidity of solution in hydrochloric acid control container,
Then hydrolysis 3- ketals obtain Mestanlone；
Embodiment 3
In the embodiment of the present invention, a kind of preparation method of Mestanlone, the structural formula of the Mestanlone is as follows：
Its specific preparation method is as follows：
(1) chemical compounds I carries the compound ii of cyano group with acetone cyanohydrin or Cymag generation, and this reaction is usually in alkalescence
Under the conditions of, pH value of solution=10 of chemical compounds I, 40 degrees Celsius of temperature are made using potassium carbonate, sodium carbonate, triethylamine or sodium hydroxide；
(2) solution of Compound Compound II is first adjusted to acidity, with ethylene glycol, triethyl orthoformate return into contracting
Ketone, the regulation reagent of acid condition is PTS etc., and the solvent of compound ii is boron trifluoride acetic acid solution etc.；Then again by solution
It is tuned into strong basicity, pH >=13, to take off the compound III that cyano group forms the ketone group of 3- ketals -17；
(3) catalyst and hydrogen are added into the solution of compound III, catalyst is palladium charcoal, while controlling reaction temperature is to 45
Degree Celsius, compounds Ⅳ is generated, and compounds Ⅳ is taken out in neutral conditions；
(4) compounds Ⅳ is inserted into container and dissolved with tetrahydrofuran, then instill methyl-magnesium-chloride or methyl bromide
The grignard reagent of magnesium, backflow, obtains methyl compound V on 17-；
(5) elutriation is under acid condition again in same container for compound V, with the acidity of solution in hydrochloric acid control container,
Then hydrolysis 3- ketals obtain Mestanlone；
It is obvious to a person skilled in the art that the invention is not restricted to the details of above-mentioned one exemplary embodiment, Er Qie
In the case of without departing substantially from spirit or essential attributes of the invention, the present invention can be realized in other specific forms.Therefore, no matter
From the point of view of which point, embodiment all should be regarded as exemplary, and be nonrestrictive, the scope of the present invention is by appended power
Profit requires rather than described above limits, it is intended that all in the implication and scope of the equivalency of claim by falling
Change is included in the present invention.
Moreover, it will be appreciated that although the present specification is described in terms of embodiments, not each embodiment is only wrapped
Containing an independent technical scheme, this narrating mode of specification is only that those skilled in the art should for clarity
Using specification as an entirety, the technical solutions in the various embodiments may also be suitably combined, forms those skilled in the art
It is appreciated that other embodiment.
Claims (8)
1. a kind of preparation method of Mestanlone, it is characterised in that the structural formula of the Mestanlone is as follows：
Its specific preparation method is as follows：
(1) chemical compounds I carries the compound ii of cyano group with acetone cyanohydrin or Cymag generation；
(2) solution of Compound Compound II is first adjusted to acidity, reacted with ethylene glycol, triethyl orthoformate into ketal；So
Solution is tuned into strong basicity, pH >=13, to take off the compound III that cyano group forms the ketone group of 3- ketals -17 again afterwards；
(3) catalyst and hydrogen are added into the solution of compound III, while controlling reaction temperature is to 35-45 degrees Celsius, generationization
Compound IV, and compounds Ⅳ is taken out in neutral conditions；
(4) compounds Ⅳ is inserted into container and dissolved with tetrahydrofuran, then instill methyl-magnesium-chloride or methyl-magnesium-bromide
Grignard reagent, backflow, obtains methyl compound V on 17-；
(5) elutriation obtains Mestanlone under acid condition, then hydrolyzing 3- ketals to compound V again in same container；
2. the preparation method of Mestanlone according to claim 1, it is characterised in that utilize carbonic acid in the step (1)
Potassium, sodium carbonate, triethylamine or sodium hydroxide make pH value of solution=8-10 of chemical compounds I, 30-40 degrees Celsius of reaction temperature, by stirring
Mix, ensure the reaction time within 2-3 hours.
3. the preparation method of Mestanlone according to claim 1, it is characterised in that acid condition in the step (2)
Regulation reagent be PTS.
4. the preparation method of Mestanlone according to claim 1, it is characterised in that step (2) the neutral and alkali condition
Regulation reagent be sodium hydroxide.
5. the preparation method of the Mestanlone according to claim 1 or 4, it is characterised in that step (2) compound ii
Solvent be boron trifluoride acetic acid solution.
6. the preparation method of Mestanlone according to claim 1, it is characterised in that step (3) catalyst is palladium
Charcoal.
7. the preparation method of Mestanlone according to claim 1, it is characterised in that addition is carried out in the step (4)
Need to heat during reaction, control solution temperature is at 40-60 degrees Celsius.
8. the preparation method of Mestanlone according to claim 1, it is characterised in that acid regulation in the step (5)
Controlled with hydrochloric acid.
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| CN201710434760.7A CN107417753A (en) | 2017-06-10 | 2017-06-10 | A kind of preparation method of Mestanlone |
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| CN201710434760.7A CN107417753A (en) | 2017-06-10 | 2017-06-10 | A kind of preparation method of Mestanlone |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109627273A (en) * | 2018-12-05 | 2019-04-16 | 华中药业股份有限公司 | A kind of synthetic method of -17 beta-hydroxy -3- ketone of -17 Alpha-Methyl of furazabol intermediate androstane |
| CN109627274A (en) * | 2018-12-05 | 2019-04-16 | 华中药业股份有限公司 | The preparation method of -17 beta-hydroxy -3- ketone of -17 Alpha-Methyl of androstane |
| CN110862430A (en) * | 2019-12-06 | 2020-03-06 | 华中药业股份有限公司 | Preparation method of 5 α -androstane-3, 17-dione |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004064722A2 (en) * | 2001-12-11 | 2004-08-05 | Endeavor Pharmaceuticals, Incorporated | Process for the production of oxandrolone |
| CN106436297A (en) * | 2015-08-10 | 2017-02-22 | 王娟 | Polyester fiber fabric treating solution |
-
2017
- 2017-06-10 CN CN201710434760.7A patent/CN107417753A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004064722A2 (en) * | 2001-12-11 | 2004-08-05 | Endeavor Pharmaceuticals, Incorporated | Process for the production of oxandrolone |
| CN106436297A (en) * | 2015-08-10 | 2017-02-22 | 王娟 | Polyester fiber fabric treating solution |
Non-Patent Citations (1)
| Title |
|---|
| 刘泺: ""甲睾酮的合成"", 《中国医药工业杂志》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109627273A (en) * | 2018-12-05 | 2019-04-16 | 华中药业股份有限公司 | A kind of synthetic method of -17 beta-hydroxy -3- ketone of -17 Alpha-Methyl of furazabol intermediate androstane |
| CN109627274A (en) * | 2018-12-05 | 2019-04-16 | 华中药业股份有限公司 | The preparation method of -17 beta-hydroxy -3- ketone of -17 Alpha-Methyl of androstane |
| CN110862430A (en) * | 2019-12-06 | 2020-03-06 | 华中药业股份有限公司 | Preparation method of 5 α -androstane-3, 17-dione |
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Application publication date: 20171201 |
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