CN105949259A - Preparation technology for 6-methylene-17a-hydroxy progesterone acetate - Google Patents
Preparation technology for 6-methylene-17a-hydroxy progesterone acetate Download PDFInfo
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- CN105949259A CN105949259A CN201610284563.7A CN201610284563A CN105949259A CN 105949259 A CN105949259 A CN 105949259A CN 201610284563 A CN201610284563 A CN 201610284563A CN 105949259 A CN105949259 A CN 105949259A
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- methine
- progesterone acetate
- hydroxyl progesterone
- molfraction
- methanol
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/0005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21
- C07J7/001—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group
- C07J7/004—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group substituted in position 17 alfa
- C07J7/0045—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by a keto group substituted in position 17 alfa not substituted in position 16
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Abstract
The invention discloses the preparation technology for 6-methylene-17a-hydroxy progesterone acetate. According to the technology, the p-toluenesulfonic acid is added in batches, and both the reaction rate and the by-product formation are controlled. The product yield and the product purity are improved. During the refining process, the dichloromethane is added to dissolve materials, and an obtained product is subjected to layered washing in water and concentrating. After that, the dichloromethane remaining in the product are removed in batches by using methanol. Compared with the conventional decolorizing and refining process by using activated carbon, zinc dust and glacial acetic acid to remove impurities in the product and correct the dark color of a solution, not only the quality and the yield of the product are improved, but also the production cost is saved at the same time. Meanwhile, the process time is shortened.
Description
Technical field
The present invention relates to the synthesis of 17a-hydroxyl progesterone acetate derivative, be specifically related to a kind of 6-methine
The preparation technology of-17a-hydroxyl progesterone acetate.
Background technology
6-methine-17a-hydroxyl progesterone acetate, has another name called megestrol acetate, chemical formula C24H32O4,
Molecular weight is 384.51, for white or slightly yellow crystalline powder, odorless tasteless, fusing point 214-216 DEG C,
It is dissolved in acetone, is slightly soluble in ethanol, ether, water insoluble.Intermediate for synthesis medroxyprogestetone acetate is commonly used for raw
Changing reagent, biochemical test is studied, and megestrol acetate is semi-synthetic progestin derivative, swells hormonal dependent
Tumor has certain inhibitory action.Its mechanism of action is identical with medroxyprogesterone, it may be possible to by dividing pituitary gonadotropic hormone
The impact secreted, controls growth and the growth of ovary follicle, thus reduces the generation of estrogen.Act on estrogen
Receptor, stops its synthesis and re-uses, disturbing the combination of itself and estrogen, suppressing tumor cell growth.Additionally,
Also can antagonism glucocorticoid receptor (GR), the interference steroid hormone receptor regulation albumen relevant to cell Growth and Differentiation
Between interaction.
At present, for the preparation technology of 6-methine-17a-hydroxyl progesterone acetate, recovery rate is relatively low, produces
Product purity is the most not high enough.
Summary of the invention
For reaching object above, the present invention adopts the technical scheme that: a kind of high recovery rate, highly purified 6-
The preparation technology of methine-17a-hydroxyl progesterone acetate, comprises the following steps:
S1, adds triethyl orthoformate and anhydrous with 17a-hydroxyl progesterone acetate after being mixed by oxolane
Ethanol, mix homogeneously under inert protective atmosphere；
S2, is warmed up to 30～40 DEG C, adds p-methyl benzenesulfonic acid, is continuously heating to 35～45 DEG C, question response
After liquid clarification, start calculating reacting time, insulation reaction 1 hour；
S3, adds p-methyl benzenesulfonic acid again, continues reaction, and TLC detection is done in sampling, until reaction is completely；
S4, is cooled to 30～40 DEG C, is separately added into methylphenylamine and formaldehyde, is warming up to 35～45 DEG C,
It is incubated 2 hours；
S5, is cooled to 10～20 DEG C, adds hydrochloric acid, insulation reaction 1.5～2 hours at 20～30 DEG C；
S6, adds water and is cooled to 0～5 DEG C of precipitation crystal, centrifugal, obtains 6-methine-17a-hydroxyl progesterone vinegar
Acid esters crude product.
On the basis of technique scheme, it is preferred that in described step S6, centrifugal process includes, first by thing
Material is centrifugal, drying, rinses with the water of 45～55 DEG C, then dries, is pulled an oar by material with the water of 45～55 DEG C,
It is centrifuged again, rinses with the water of 45～55 DEG C, then dry, obtain 6-methine-17a-hydroxyl progesterone acetate thick
Product.
On the basis of technique scheme, it is preferred that the 17a-of each molfraction in described step S1
Hydroxyl progesterone acetate, the corresponding triethyl orthoformate adding 0.83 molfraction and 0.6 molfraction
Dehydrated alcohol.
On the basis of technique scheme, the 17a-hydroxyl progesterone acetate of each molfraction, described
The corresponding p-methyl benzenesulfonic acid adding 0.2 molfraction in step S2, corresponding addition 0.1 in described step S3
The p-methyl benzenesulfonic acid of molfraction.
On the basis of technique scheme, it is preferred that the 17a-of each molfraction in described step S4
Hydroxyl progesterone acetate, the corresponding methylphenylamine adding 0.35 molfraction and 0.33 molfraction
Formaldehyde.
On the basis of technique scheme, it is preferred that also include step S7, by step S6 gained 6-time
Methyl-17 a-hydroxyl progesterone acetate crude product in dichloromethane molten clearly, add water stirring after stratification, take
Lower floor's solution is concentrated to dryness.It is further preferred that also include step S8, material step S7 obtained adds
Enter methanol to be evaporated to do, add methanol and be evaporated to do, then add methanol, at 62～64 DEG C
Lower backflow 30～40 minutes, be cooled to 5～10 DEG C, centrifugal, dry, and methanol rinses and dries, again with methanol
Being pulled an oar by material, then be centrifuged, again with methanol is rinsed, and dries and obtains refined 6-methine-17a-hydroxyl progesterone
Acetate.
Compared with prior art, it is an advantage of the current invention that:
(1) preparation technology of the 6-methine-17a-hydroxyl progesterone acetate of the present invention, uses and adds by several times
The method of p-methyl benzenesulfonic acid, controls response speed and by-product generates, and improves product recovery rate and purity；
(2) divide with methanol after adding water stratification washing after subtractive process using the molten clear material of dichloromethane and concentrating
The method of secondary removing dichloromethane, produces relative to using activated carbon, zinc powder and glacial acetic acid method of decolorizing and refining to remove
The partially deep problem of individual impurities and solution color in product, the quality and the yield that not only increase product also a saving simultaneously
Production cost, shortens the process time.
Accompanying drawing explanation
Fig. 1 is the flow chart of the preparation technology of the 6-methine-17a-hydroxyl progesterone acetate of the present invention.
Detailed description of the invention
Shown in Figure 1, the preparation technology of the 6-methine-17a-hydroxyl progesterone acetate of the present invention, bag
Include following steps:
First, add p-methyl benzenesulfonic acid by several times, react.
S1, adds triethyl orthoformate and anhydrous with 17a-hydroxyl progesterone acetate after being mixed by oxolane
Ethanol, mix homogeneously under inert protective atmosphere；
S2, is warmed up to 30～40 DEG C, adds p-methyl benzenesulfonic acid, is continuously heating to 35～45 DEG C, question response
After liquid clarification, start calculating reacting time, insulation reaction 1 hour；
S3, adds p-methyl benzenesulfonic acid again, continues reaction, and TLC detection is done in sampling, until reaction is completely；
Secondly, put into methylphenylamine, formaldehyde and hydrochloric acid, react.
S4, is cooled to 30～40 DEG C, is separately added into methylphenylamine and formaldehyde, is warming up to 35～45 DEG C,
It is incubated 2 hours；
S5, is cooled to 10～20 DEG C, adds hydrochloric acid, insulation reaction 1.5～2 hours at 20～30 DEG C；
Then, elutriation, centrifugal obtain crude product.
S6, adds water and is cooled to 0～5 DEG C of precipitation crystal, centrifugal, obtains 6-methine-17a-hydroxyl progesterone vinegar
Acid esters crude product.
Finally, wash by adding water stratification and after concentration, remove dichloromethane with methanol by several times, obtaining refined 6-
Methine-17a-hydroxyl progesterone acetate.
S7, by step S6 gained 6-methine-17a-hydroxyl progesterone acetate crude product in dichloromethane molten
Clearly, stratification after the stirring that adds water, takes off layer solution and is concentrated to dryness.
S8, material step S7 obtained adds methanol and is evaporated to do, adds methanol and be evaporated to
Dry, then add methanol, reflux 30～40 minutes at 62～64 DEG C, be cooled to 5～10 DEG C, centrifugal,
Drying, methanol rinses and dries, and material is pulled an oar by again with methanol, then is centrifuged, and again with methanol is rinsed, and drying obtains
Refined 6-methine-17a-hydroxyl progesterone acetate.
Below in conjunction with specific embodiment, the present invention is described in further detail.
Embodiment 1
S1, by the oxolane suction retort of 7.2 moles, puts into the 17a-hydroxyl progesterone of 1 mole
Acetate, starts stirring 10 minutes, by the triethyl orthoformate of 0.83 mole and the dehydrated alcohol of 0.6 mole
Respectively in suction retort, it is passed through nitrogen protection；
S2, stirring, warming-in-water, during temperature to 35 DEG C, add the p-methyl benzenesulfonic acid of 0.2 mole for the first time,
It is continuously heating to 40 DEG C, after liquid clarification, starts calculating reacting time, insulation reaction 1 hour；
S3, opens the p-methyl benzenesulfonic acid that dog-house second time adds 0.1 mole, after reacting 1 hour, starts
Sampling TLC detection, until reaction is completely；
S4, is cooled to 35 DEG C, the methylphenylamine of 0.35 mole and 0.33 moles of formaldehyde is put into respectively instead
Answer in tank, be warming up to 40 DEG C, be incubated 2 hours；
S5, when being cooled to 15 DEG C, closes nitrogen valve, starts to be slowly added dropwise hydrochloric acid, drip in 30 minutes,
Insulation reaction 1.8 hours under the conditions of 20～30 DEG C；
S6, is pumped into the material reacted in elutriation tank, and opens chilled brine valve, is cooled to 3 DEG C, stirs
Mix 1 hour, stand more than 1 hour, elutriation retort material is slowly put into centrifugal in centrifuge, drying,
After rinsing 30 minutes with the water of 50 DEG C, centrifuge dripping, with the water of 50 DEG C, material is pulled an oar, then be centrifuged, use
The water of 50 DEG C rinses 45 minutes, and centrifuge dripping 45 minutes obtains crude product；
S7, with the molten clear material of the dichloromethane of 10 times of crude product volumes in bleacher, add water stirring 10 points
Clock, then stands 10 minutes, and lower floor's solution passes through filter suction treatment tank, is added by remaining for bleacher water
The most molten clear material of dichloromethane of 0.5 times of volume, stirs 10 minutes, then stands 10 minutes, and lower floor is molten
Liquid passes through filter suction treatment tank, is concentrated to dryness by treatment tank material normal pressure, is separately added into the decompression of secondary methanol
It is concentrated to dryness, adds the methanol of 1 times of volume, reflux 30 minutes, be cooled to 8 DEG C, material is slowly put
Enter centrifugal in centrifuge, drying.Rinse with the methanol of 0.5 times of volume after drying, stop being centrifuged.With 0.5 times of body
Material is pulled an oar by long-pending methanol, restarts centrifuge, then rinses with the methanol of 0.2 times of volume, dries 45 points
Clock obtains refined 6-methine-17a-hydroxyl progesterone acetate.
Products obtained therefrom is carried out chromatography detection, and gained refines 6-methine-17a-hydroxyl progesterone acetate
Purity is >=99%.
Calculating gained and refine 6-methine-17a-hydroxyl progesterone acetate, product recovery rate is 92%.
Embodiment 2
S1, by the oxolane suction retort of 7.2 moles, puts into the 17a-hydroxyl progesterone of 1 mole
Acetate, starts stirring 10 minutes, by the triethyl orthoformate of 0.83 mole and the dehydrated alcohol of 0.6 mole
Respectively in suction retort, it is passed through nitrogen protection；
S2, stirring, warming-in-water, during temperature to 30 DEG C, add the p-methyl benzenesulfonic acid of 0.2 mole for the first time,
It is continuously heating to 35 DEG C, after liquid clarification, starts calculating reacting time, insulation reaction 1 hour；
S3, opens the p-methyl benzenesulfonic acid that dog-house second time adds 0.1 mole, after reacting 1 hour, starts
Sampling TLC detection, until reaction is completely；
S4, is cooled to 30 DEG C, is put into respectively by the formaldehyde of the methylphenylamine of 0.35 mole and 0.33 mole
In retort, it is warming up to 35 DEG C, is incubated 2 hours；
S5, when being cooled to 10 DEG C, closes nitrogen valve, starts to be slowly added dropwise hydrochloric acid, drip in 30 minutes,
Insulation reaction 1.5 hours under the conditions of 20 DEG C；
S6, is pumped into the material reacted in elutriation tank, and opens chilled brine valve, is cooled to 0 DEG C, stirs
Mix 1 hour, stand more than 1 hour, elutriation retort material is slowly put into centrifugal in centrifuge, drying,
After rinsing 30 minutes with the water of 45 DEG C, centrifuge dripping, with the water of 45 DEG C, material is pulled an oar, then be centrifuged, use
The water of 45 DEG C rinses 45 minutes, and centrifuge dripping 45 minutes obtains crude product；
S7, with the molten clear material of the dichloromethane of 10 times of crude product volumes in bleacher, add water stirring 10 points
Clock, then stands 10 minutes, and lower floor's solution passes through filter suction treatment tank, is added by remaining for bleacher water
The most molten clear material of dichloromethane of 0.5 times of volume, stirs 10 minutes, then stands 10 minutes, and lower floor is molten
Liquid passes through filter suction treatment tank, is concentrated to dryness by treatment tank material normal pressure, is separately added into the decompression of secondary methanol
It is concentrated to dryness, adds the methanol of 1 times of volume, reflux 30 minutes, be cooled to 5 DEG C, material is slowly put
Enter centrifugal in centrifuge, drying.Rinse with the methanol of 0.5 times of volume after drying, stop being centrifuged.With 0.5 times of body
Material is pulled an oar by long-pending methanol, restarts centrifuge, then rinses with the methanol of 0.2 times of volume, dries 45 points
Clock obtains refined 6-methine-17a-hydroxyl progesterone acetate.
Products obtained therefrom is carried out chromatography detection, and gained refines 6-methine-17a-hydroxyl progesterone acetate
Purity is >=99%.
Calculating gained and refine 6-methine-17a-hydroxyl progesterone acetate, product recovery rate is 90%.
Embodiment 3
S1, by the oxolane suction retort of 7.2 moles, puts into the 17a-hydroxyl progesterone of 1 mole
Acetate, starts stirring 10 minutes, by the triethyl orthoformate of 0.83 mole and the dehydrated alcohol of 0.6 mole
Respectively in suction retort, it is passed through nitrogen protection；
S2, stirring, warming-in-water, during temperature to 40 DEG C, add the p-methyl benzenesulfonic acid of 0.2 mole for the first time,
It is continuously heating to 45 DEG C, after liquid clarification, starts calculating reacting time, insulation reaction 1 hour；
S3, opens the p-methyl benzenesulfonic acid that dog-house second time adds 0.1 mole, after reacting 1 hour, starts
Sampling TLC detection, until reaction is completely；
S4, is cooled to 40 DEG C, load weighted methylphenylamine and formaldehyde is put into respectively in retort, heats up
To 45 DEG C, it is incubated 2 hours；
S5, when being cooled to 20 DEG C, closes nitrogen valve, starts to be slowly added dropwise hydrochloric acid, drip in 30 minutes,
Insulation reaction 2 hours under the conditions of 30 DEG C；
S6, is pumped into the material reacted in elutriation tank, and opens chilled brine valve, is cooled to 5 DEG C, stirs
Mix 1 hour, stand more than 1 hour, elutriation retort material is slowly put into centrifugal in centrifuge, drying,
After rinsing 30 minutes with the water of 55 DEG C, centrifuge dripping, with the water of 55 DEG C, material is pulled an oar, then be centrifuged, use
The water of 55 DEG C rinses 45 minutes, and centrifuge dripping 45 minutes obtains crude product；
S7, with the molten clear material of the dichloromethane of 10 times of crude product volumes in bleacher, add water stirring 10 points
Clock, then stands 10 minutes, and lower floor's solution passes through filter suction treatment tank, is added by remaining for bleacher water
The most molten clear material of dichloromethane of 0.5 times of volume, stirs 10 minutes, then stands 10 minutes, and lower floor is molten
Liquid passes through filter suction treatment tank, is concentrated to dryness by treatment tank material normal pressure, is separately added into the decompression of secondary methanol
It is concentrated to dryness, adds the methanol of 1 times of volume, reflux 30 minutes, be cooled to 10 DEG C, material is slowly put
Enter centrifugal in centrifuge, drying.Rinse with the methanol of 0.5 times of volume after drying, stop being centrifuged.With 0.5 times of body
Material is pulled an oar by long-pending methanol, restarts centrifuge, then rinses with the methanol of 0.2 times of volume, dries 45 points
Clock obtains refined 6-methine-17a-hydroxyl progesterone acetate.
Products obtained therefrom is carried out chromatography detection, and gained refines 6-methine-17a-hydroxyl progesterone acetate
Purity is >=99%.
Calculating gained and refine 6-methine-17a-hydroxyl progesterone acetate, product recovery rate is 91%.
The present invention is not limited to above-mentioned embodiment, for those skilled in the art, not
On the premise of departing from the principle of the invention, it is also possible to making some improvements and modifications, these improvements and modifications are also considered as
Within protection scope of the present invention.The content not being described in detail in this specification belongs to this area professional technique people
The known prior art of member.
Claims (7)
1. the preparation technology of a 6-methine-17a-hydroxyl progesterone acetate, it is characterised in that include with
Lower step:
S1, adds triethyl orthoformate and anhydrous with 17a-hydroxyl progesterone acetate after being mixed by oxolane
Ethanol, mix homogeneously under inert protective atmosphere；
S2, is warmed up to 30～40 DEG C, adds p-methyl benzenesulfonic acid, is continuously heating to 35～45 DEG C, question response
After liquid clarification, start calculating reacting time, insulation reaction 1 hour；
S3, adds p-methyl benzenesulfonic acid again, continues reaction, and TLC detection is done in sampling, until reaction is completely；
S4, is cooled to 30～40 DEG C, is separately added into methylphenylamine and formaldehyde, is warming up to 35～45 DEG C,
It is incubated 2 hours；
S5, is cooled to 10～20 DEG C, adds hydrochloric acid, insulation reaction 1.5～2 hours at 20～30 DEG C；
S6, adds water and is cooled to 0～5 DEG C of precipitation crystal, centrifugal, obtains 6-methine-17a-hydroxyl progesterone vinegar
Acid esters crude product.
2. the preparation technology of 6-methine-17a-hydroxyl progesterone acetate as claimed in claim 1, it is special
Levy and be: in described step S6, centrifugal process includes, first material is centrifugal, drying, with 45～55 DEG C
Water rinses and dries, is pulled an oar by material with the water of 45～55 DEG C, then is centrifuged, and rinses with the water of 45～55 DEG C,
Dry again, obtain 6-methine-17a-hydroxyl progesterone acetate crude product.
3. the preparation technology of 6-methine-17a-hydroxyl progesterone acetate as claimed in claim 1, it is special
Levy and be: the 17a-hydroxyl progesterone acetate of each molfraction in described step S1, corresponding addition 0.83
The triethyl orthoformate of molfraction and the dehydrated alcohol of 0.6 molfraction.
4. the preparation technology of 6-methine-17a-hydroxyl progesterone acetate as claimed in claim 1, it is special
Levy and be: the 17a-hydroxyl progesterone acetate of each molfraction, corresponding addition 0.2 in described step S2
The p-methyl benzenesulfonic acid of molfraction, the corresponding p-methyl benzenesulfonic acid adding 0.1 molfraction in described step S3.
5. the preparation technology of 6-methine-17a-hydroxyl progesterone acetate as claimed in claim 1, it is special
Levy and be: the 17a-hydroxyl progesterone acetate of each molfraction in described step S4, corresponding addition 0.35
The methylphenylamine of molfraction and the formaldehyde of 0.33 molfraction.
6. the preparation technology of 6-methine-17a-hydroxyl progesterone acetate as claimed in claim 1, it is special
Levy and be: also include step S7, by step S6 gained 6-methine-17a-hydroxyl progesterone acetate crude product
In dichloromethane molten clearly, add water stirring after stratification, take off layer solution and be concentrated to dryness.
7. the preparation technology of 6-methine-17a-hydroxyl progesterone acetate as claimed in claim 6, it is special
Levying and be: also include step S8, material step S7 obtained adds methanol and is evaporated to do, then adds
Enter methanol to be evaporated to do, then add methanol, reflux 30～40 minutes at 62～64 DEG C, cooling
To 5～10 DEG C, centrifugal, drying, methanol rinses and dries, and material is pulled an oar by again with methanol, then is centrifuged, then uses
Methanol rinses, and dries and obtains refined 6-methine-17a-hydroxyl progesterone acetate.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106866766A (en) * | 2017-02-14 | 2017-06-20 | 岳阳环宇药业有限公司 | The preparation method and preparation system of a kind of medroxyprogesterone acetate |
| CN106977569A (en) * | 2017-04-12 | 2017-07-25 | 杭州弘任医药科技有限公司 | The preparation method of the α hydroxyprogesterone acetates of 6 methylene 17 |
| CN110590890A (en) * | 2019-09-27 | 2019-12-20 | 台州仙琚药业有限公司 | Preparation method of 17 alpha-acetoxyl group-6-methylene pregn-4-ene-3, 20-diketone |
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| US20090012321A1 (en) * | 2007-06-06 | 2009-01-08 | Klaus Annen | Process for preparing 17alpha-acetoxy-6-methylenepregn-4-ene-3,20-dione, medroxyprogesterone acetate and megestrol acetate |
| CN102153609A (en) * | 2011-01-20 | 2011-08-17 | 城固县振华生物科技有限责任公司 | Chemical synthesis method for 6-methylene monoester |
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2016
- 2016-04-29 CN CN201610284563.7A patent/CN105949259A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090012321A1 (en) * | 2007-06-06 | 2009-01-08 | Klaus Annen | Process for preparing 17alpha-acetoxy-6-methylenepregn-4-ene-3,20-dione, medroxyprogesterone acetate and megestrol acetate |
| CN102153609A (en) * | 2011-01-20 | 2011-08-17 | 城固县振华生物科技有限责任公司 | Chemical synthesis method for 6-methylene monoester |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106866766A (en) * | 2017-02-14 | 2017-06-20 | 岳阳环宇药业有限公司 | The preparation method and preparation system of a kind of medroxyprogesterone acetate |
| CN106866766B (en) * | 2017-02-14 | 2018-03-20 | 岳阳环宇药业有限公司 | The preparation method and preparation system of a kind of medroxyprogesterone acetate |
| CN106977569A (en) * | 2017-04-12 | 2017-07-25 | 杭州弘任医药科技有限公司 | The preparation method of the α hydroxyprogesterone acetates of 6 methylene 17 |
| CN106977569B (en) * | 2017-04-12 | 2020-06-23 | 杭州弘任医药科技有限公司 | Preparation method of 6-methylene-17 α -hydroxyprogesterone acetate |
| CN110590890A (en) * | 2019-09-27 | 2019-12-20 | 台州仙琚药业有限公司 | Preparation method of 17 alpha-acetoxyl group-6-methylene pregn-4-ene-3, 20-diketone |
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Application publication date: 20160921 |
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