CN108752415A - A kind of Finasteride chiral impurity（5 β-Finasterides）Synthesis and purification process - Google Patents
A kind of Finasteride chiral impurity（5 β-Finasterides）Synthesis and purification process Download PDFInfo
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Abstract
The invention discloses a kind of Finasteride chiral impurity (5 β-Finasterides) synthesis and purification process, bisamidate (formula 1) is used to obtain target product formula 3 by catalytic hydrogenation, refined, dehydrogenation and purifying for raw material, synthetic route is：
Description
Technical field
The invention belongs to steroid drugs the field of chemical synthesis, and in particular to a kind of 5 β-Fei Na of Finasteride chiral impurity are male
The preparation method of amine.
Background technology
Finasteride, chemistry entitled Finasteride, molecular formula C23H36N2O, molecular weight 372.54, CAS registration numbers
98319-26-7, structural formula are as follows.
Finasteride is a kind of 4- aza steroids, it is testosterone metabolism as during stronger dihydrotestosterone
5 alpha-reductase of desmoenzyme-II types specific inhibitor.And it benign prostatic hyperplasis or is depended on as hypertrophy of the prostate
Conversion of the testosterone to dihydrotestosterone in prostate.This medicine can effectively reduce blood and intraprostatic dihydro testis
Ketone.Finasteride does not have affinity to androgen receptor.Finasteride belongs to 5 alpha reductase inhibitors, is made by its hormone
With mechanism, that is, inhibit testosterone to be converted to protona (DHT), so that prostate volume is reduced and improve symptom, increase uroflow rate,
Preventing benign prostatic hyperplasia (BPH) is in progress.
In the bulk pharmaceutical chemicals process exploitation of the drug, usually use bisamidate for the synthetic route of starting material, route
As follows：
We have found that there are a chiral impurity, 5 β-non-in the Finasteride product prepared using this route under study for action
That male amine, structural formula is shown in as follows：
Its production quantity 0.1% or so, and be difficult obtained by the method that isolates and purifies of routine active compound impurity it is pure
Reference substance.By literature search, the synthetic method of the impurity is had not been reported.Therefore, the present invention is developed with bisamidate
For the Finasteride chiral impurity synthetic method of starting material.
Invention content
The purpose of the present invention is：5 β of Finasteride chiral impurity-Finasteride synthetic method is without correlation in the prior art
Report, in order to solve the above-mentioned technical problem, the present invention develops Finasteride chiral impurity synthetic method.
Scheme provided by the invention is：In the method that bisamidate prepares 5 β-Finasterides as starting material, including such as
Lower step：
(1) catalytic hydrogenation：Bisamidate formula 1, palladium carbon, sulfonic acid catalyst and glacial acetic acid are passed through hydrogen reaction, obtain hydrogen
Compound formula 2A and hydride formula 2B,
The specific steps are：Under nitrogen protection, bisamidate (formula 1), palladium carbon, sulfonic acid catalyst and glacial acetic acid are heated to
40~80 DEG C, it is passed through hydrogen, the reaction was continued 6~12h, nitrogen terminates reaction, filters out palladium carbon while hot, filtrate decompression is concentrated to give hydrogenation
Object (formula 2A and formula 2B), reaction equation is；
In the Finasteride synthetic route reported, the production quantity of 5 β-chiral hydrides object (formula 2B) exists in hydrogenation
5% or so, content is relatively low, it is difficult to obtain the higher 5 β-chiral hydrides object (formula of purity by the conventional separation means such as recrystallization
2B).This case finds that for the content important role of 5 β-chiral hydride objects, different proportion is then added in the dosage of catalyst
Sulphonic acids catalyst, catalytic hydrogenation is optimized, such as following table, the results show that after using sulphonic acids catalyst, mesh
5 β of mark compound-chiral hydride object can be increased to 30% or so by 5% highest.
(2) it refines：After hydride stirs dissolved clarification in 20 times of volume of solvent A, sodium carbonate liquor, water washing are used successively, are received
Collection organic phase is concentrated under reduced pressure into paste；10 times of volume of solvent B are added, continue to be concentrated into 3~6 times of volumes, in -5 DEG C~5 DEG C coolings
1~4h is filtered for the first time；Mother liquor concentrations are obtained to 0.5~1 times of volume, in 5~15 DEG C of cooling 1~4h, secondary suction filtration, filter cake
For 5 β-chiral hydride objects (formula 2B), process is：
Different solvents influence obviously, as shown in the table the concentration effect of 5 β-chiral hydride objects (formula 2B)：
| Serial number | Solvent | 5 β-chiral hydride object purity | Mass yield |
| 1 | Dichloromethane | 52.4% | 36.2% |
| 2 | Ethyl alcohol | 58.8% | 48.6% |
| 3 | Acetone | 77.4% | 20.4% |
| 4 | Toluene | 87.3% | 17.8% |
| 5 | Acetonitrile | 89.1% | 21.4% |
| 6 | Ethyl acetate | 94.2% | 22.7% |
| 7 | Ethyl formate | 93.5% | 21.3% |
| 8 | Isopropyl acetate | 94.7% | 21.5% |
Experiment shows that can the purity for 5 β of product-chiral hydride object that this step obtains be the mesh for determining obtain high-purity
Mark the committed step of 5 β of compound-Finasteride.When 5 β of gained second step product-chiral hydride object purity be less than 90%, after
The target product purity that continuous dehydrogenation is obtained with purifying will be 98% hereinafter, therefore, the range of choice of the refining solvent B of the step is
Ethyl acetate, Ethyl formate and isopropyl acetate.
(3) dehydrogenation reaction：5 β-chiral hydride objects are dissolved in organic solvent, DDQ is added under nitrogen protection, and (2,3- bis- is chloro-
5,6- dicyanos-Isosorbide-5-Nitrae-benzoquinones) and BSTFA (bis- (trimethylsilyl) trifluoroacetamides of N, O-) reactions, obtain 5 β-Finasterides
3 crude product of formula,
The specific steps are：5 β-chiral hydride objects are dissolved in dioxane, DDQ is added under nitrogen protection, and (2,3- bis- is chloro-
5,6- dicyanos-Isosorbide-5-Nitrae-benzoquinones), BSTFA (bis- (trimethylsilyl) trifluoroacetamides of N, O-), in 110 DEG C react 8h, reaction
After, it is down to room temperature, reaction is quenched in solution of sodium bisulfite, and toluene extraction is added, and gained toluene layer uses sodium carbonate molten successively
Liquid, solution of sodium bisulfite, sodium carbonate liquor, saturated common salt water washing；Toluene layer is collected, activated carbon, anhydrous sodium sulfate is added,
It is heated to reflux 1 hour, filters, filtrate decompression is concentrated on a small quantity；Solvent C is added, continues to be concentrated into a small amount of；Solvent C is added, after
It is continuous to be concentrated into about 5 times of volumes.Cooling, suction filtration, it is dry that 5 β-Finasterides formula, 3 crude product, reaction equation are：
Optionally include the purification step of step (4)：It is 1 metering with 5 β-Finasteride quality by 5 β-Finasteride crude products,
The solvent D of 100 times of volumes is added, is heated to reflux dissolved clarification, is concentrated into about 20 times of volumes, in -5 DEG C~5 DEG C cooling 1~4h, filters,
Filter cake decompression drying obtains 5 β-Finasteride fine work.
Further, the one kind of sulfonic acid catalyst in p-methyl benzenesulfonic acid, methanesulfonic acid, dosage described in step (1)
It is 0.01-0.5 times of 1 weight of bisamidate formula.
Further, the effective content of palladium carbon described in step (1) is 5%~10%.
Further, bisamidate described in step (1), glacial acetic acid, sulfonic acid catalyst, palladium carbon mass ratio be 1:5:
0.05:0.25~1:10:0.5:0.5.
Further, step (2) described solvent A is one kind in dichloromethane or chloroform, and solvent B is selected from formic acid second
One kind in ester, ethyl acetate, isopropyl acetate.
Further, solvent C described in step (3) is one kind in ethyl acetate, isopropyl acetate.
Further, solvent D described in step (4) is one kind in ethyl acetate, isopropyl acetate.
The beneficial effects of the invention are as follows：5 β-the Fei Na that the process conditions designed using the present invention can prepare high-purity are male
Amine.Suitable sulfonic acid catalyst is added in first step catalytic hydrogenation, makes HPLC of the 5 β-chiral hydride objects in hydride
Content is improved from 5% to 30%, and refining solvent chooses one kind in ethyl acetate, Ethyl formate and isopropyl acetate, can obtain
5 βs-chiral hydride object refined substance of the yield 20% or so and HPLC contents arrived 94% or more；5 β-chiral hydride object refined substances
5 β-the Finasterides of purity 99.5% can be obtained through follow-up dehydrogenation reaction and purifying again.5 β-the Fei Na obtained using the present invention are male
Amine can be used as Finasteride quality for impurity reference substance.
Specific implementation mode
Presently in connection with embodiment, the present invention is described in further detail, and application of the invention is not limited to following
Embodiment, the accommodation in any form done to the present invention fall within protection scope of the present invention.
In following embodiments, the reaction equation of the catalytic hydrogenation of the first step is：
The subtractive process of second step is：
The reaction equation of dehydrogenation reaction of third step is：
Comparative example：Zhongguo Xinyao Zazhi,20(22),2248-2250；2011
The first step, catalytic hydrogenation：Bisamidate (20g, 1W), 5% palladium carbon (10g, 0.5W), ice are added in reaction bulb
60 DEG C of reaction 8h of hydrogen heat-insulation are led in acetic acid (140g, 7W), nitrogen protection, hydrogen displacement three times, and nitrogen displacement terminates hydrogenation.
80 DEG C are warming up to, filters off palladium carbon while hot；Filtrate decompression is concentrated to dryness, and obtains hydride, sample detection.5 β-chirality in hydride
Hydride main peak content 5.2%.
Embodiment 1：
The first step, catalytic hydrogenation：Bisamidate (20g, 1W), 5% palladium carbon (10g, 0.5W), right is added in reaction bulb
60 DEG C of reaction 8h of hydrogen heat-insulation are led in toluenesulfonic acid (4g, 0.2W) and glacial acetic acid (140g, 7W), nitrogen protection, hydrogen displacement three times,
Nitrogen displacement terminates hydrogenation.80 DEG C are warming up to, filters off palladium carbon while hot；Filtrate decompression is concentrated to dryness, and obtains hydride, sampling
Detection.5 β-chiral hydrides owner peak content 28.8% in hydride.
Second step refines：Dichloromethane (400ml, 20V) is added in hydride, stirs dissolved clarification；Successively with 10% carbonic acid
Sodium solution (180ml, 9V), water (100ml, 5V), water (100ml, 5V) wash liquid separation.It collects dichloromethane layer and is concentrated under reduced pressure into paste
Shape pours ethyl acetate (200ml, 10V) and is concentrated into about (80ml, 4V), 0~5 DEG C of cooling 2h filtering；Mother liquor concentrations are obtained to about
(10ml, 0.5V), 5~10 DEG C of cooling 3h filterings, filtration product decompression drying 12h at 60 DEG C.Obtain 5 β-chiral hydride objects
(4.54g, mass yield 22.7%), main peak content 94.2%.
Third walks, dehydrogenation reaction：5 β-chiral hydrides object (3g, 1W), DDQ (3g, 1W), BSTFA are added in reaction bulb
(15ml, 5V), dioxane (60ml, 20V), nitrogen protection keep the temperature 110 DEG C of reaction 8h.30 DEG C are cooled to hereinafter, being added 10%
Solution of sodium bisulfite (60ml, 20V) stirs 15 minutes；Toluene (180ml, 60V) is added, stirs 10 minutes；Liquid separation, gained
Toluene layer is successively with 10% sodium carbonate liquor (30ml, 10V), 10% solution of sodium bisulfite (30ml, 10V), 10% sodium carbonate
Solution (30ml, 10V), saturated salt solution (30ml, 10V) wash liquid separation.Obtain toluene layer be added activated carbon (0.75g,
0.25W), anhydrous sodium sulfate (3g, 1W), 110 DEG C are heated to reflux 1h, filtering.Filtrate decompression is concentrated on a small quantity；Pour acetic acid isopropyl
Ester (60ml, 20V) continues to be concentrated into about a small amount of；Isopropyl acetate (60ml, 20V) is poured, continues to be concentrated into about (15ml, 5V).
0~5 DEG C of cooling 1h filtering, product decompression drying 12h at 90 DEG C obtain 5 β-Finasterides crude product (1.44g, mass yield
48%), main peak content 98.7%.
4th step, purifying：5 β-Finasterides crude product (1g, 1W) is taken, isopropyl acetate (100ml, 100V), heating is added
Flow back dissolved clarification, is concentrated into about (20ml, 20V), and 0~5 DEG C of cooling 2h filtering, product decompression drying 12h at 90 DEG C obtains 5 β-
Finasteride fine work (0.81g, mass yield 81%), main peak content 99.5%.
Embodiment 2
The first step, catalytic hydrogenation：Bisamidate (20g, 1W), 5% palladium carbon (10g, 0.5W) are added in reaction bulb, it is right
40 DEG C of reactions of hydrogen heat-insulation are led in toluenesulfonic acid (10g, 0.5W) and glacial acetic acid (200g, 10W), nitrogen protection, hydrogen displacement three times
12h, nitrogen displacement terminate hydrogenation.80 DEG C are warming up to, filters off palladium carbon while hot；Filtrate decompression is concentrated to dryness, and obtains hydride,
Sample detection.5 β-chiral hydrides owner peak content 30.2% in hydride.
Second step refines：Chloroform (400ml, 20V) is added in hydride, stirs dissolved clarification；Successively with 10% carbonic acid
Sodium solution (180ml, 9V), water (100ml, 5V), water (100ml, 5V) wash liquid separation.It collects chloroform layer and is concentrated under reduced pressure into paste
Shape pours Ethyl formate (200ml, 10V) and is concentrated into about (60ml, 3V), -5 DEG C~0 DEG C cooling 1h filtering；Obtain mother liquor concentrations
To about (10ml, 0.5V), 5~10 DEG C of cooling 1h filterings, filtration product decompression drying 12h at 60 DEG C.Obtain 5 β-chiral hydrides
Object (4.26g, mass yield 21.3%), main peak content 93.5%.
Third walks, dehydrogenation reaction：5 β-chiral hydrides object (3g, 1W), DDQ (3g, 1W), BSTFA are added in reaction bulb
(15ml, 5V), dioxane (60ml, 20V), nitrogen protection keep the temperature 110 DEG C of reaction 8h.30 DEG C are cooled to hereinafter, being added 10%
Solution of sodium bisulfite (60ml, 20V) stirs 15 minutes；Toluene (180ml, 60V) is added, stirs 10 minutes；Liquid separation, gained
Toluene layer is successively with 10% sodium carbonate liquor (30ml, 10V), 10% solution of sodium bisulfite (30ml, 10V), 10% sodium carbonate
Solution (30ml, 10V), saturated salt solution (30ml, 10V) wash liquid separation.Obtain toluene layer be added activated carbon (0.25g,
0.75W), anhydrous sodium sulfate (3g, 1W), 110 DEG C are heated to reflux 1h, filtering.Filtrate decompression is concentrated on a small quantity；Pour ethyl acetate
(60ml, 20V) continues to be concentrated into about a small amount of；Ethyl acetate (60ml, 20V) is poured, continues to be concentrated into about (15ml, 5V).0~5
DEG C cooling 1h filterings, product decompression drying 12h at 90 DEG C.5 β-Finasterides crude product (1.38g, mass yield 46%) is obtained, it is main
Peak content 97.8%.
4th step, purifying：5 β-Finasterides crude product (1g, 1W) is taken, ethyl acetate (100ml, 100V) is added, heats back
Dissolved clarification is flowed, is concentrated into about (20ml, 20V), -5~0 DEG C of cooling 1h filtering, product decompression drying 12h at 90 DEG C.It is non-to obtain 5 β-
That male amine fine work (0.83g, mass yield 83%), main peak content 99.0%.
Embodiment 3
The first step, catalytic hydrogenation：In reaction bulb be added bisamidate (20g, 1W), 10% palladium carbon (5g, 0.25W),
80 DEG C of reaction 6h of hydrogen heat-insulation, nitrogen are led in methanesulfonic acid (1g, 0.05W), glacial acetic acid (100g, 5W), nitrogen protection, hydrogen displacement three times
Gas displacement terminates hydrogenation.Palladium carbon is filtered off while hot；Filtrate decompression is concentrated to dryness, and obtains hydride, sample detection.In hydride
5 β-chiral hydride owners peak content 26.1%.
Second step refines：Dichloromethane (400ml, 20V) is added in hydride, stirs dissolved clarification；Successively with 10% carbonic acid
Sodium solution (180ml, 9V), water (100ml, 5V), water (100ml, 5V) wash liquid separation.It collects dichloromethane layer and is concentrated under reduced pressure into paste
Shape pours isopropyl acetate (200ml, 10V) and is concentrated into about (120ml, 6V), 0~5 DEG C of cooling 4h filtering；Obtain mother liquor concentrations
To about (20ml, 1V), 10~15 DEG C of cooling 4h filterings, filtration product decompression drying 12h at 60 DEG C.Obtain 5 β-chiral hydrides
Object (4.08g, mass yield 20.4%), main peak content 92.8%.
Third walks, dehydrogenation reaction：5 β-chiral hydrides object (3g, 1W), DDQ (3g, 1W), BSTFA are added in reaction bulb
(15ml, 5V), dioxane (60ml, 20V), nitrogen protection keep the temperature 110 DEG C of reaction 8h.30 DEG C are cooled to hereinafter, being added 10%
Solution of sodium bisulfite (60ml, 20V) stirs 15 minutes；Toluene (180ml, 60V) is added, stirs 10 minutes；Liquid separation, gained
Toluene layer is successively with 10% sodium carbonate liquor (30ml, 10V), 10% solution of sodium bisulfite (30ml, 10V), 10% sodium carbonate
Solution (30ml, 10V), saturated salt solution (30ml, 10V) wash liquid separation.Obtain toluene layer be added activated carbon (0.75g,
0.25W), anhydrous sodium sulfate (3g, 1W), 110 DEG C are heated to reflux 1h, filtering.Filtrate decompression is concentrated on a small quantity；Pour acetic acid isopropyl
Ester (60ml, 20V) continues to be concentrated into about a small amount of；Isopropyl acetate (60ml, 20V) is poured, continues to be concentrated into about (15ml, 5V).
0~5 DEG C of cooling 1h filtering, product decompression drying 12h at 90 DEG C.Obtain 5 β-Finasterides crude product (1.29g, mass yield
43%), main peak content 98.4%.
4th step, purifying：5 β-Finasterides crude product (1g, 1W) is taken, isopropyl acetate (100ml, 100V), heating is added
Flow back dissolved clarification, is concentrated into about (20ml, 20V), 0~5 DEG C of cooling 4h filtering, product decompression drying 12h at 90 DEG C.Obtain 5 β-
Finasteride fine work (0.77g, mass yield 77%), main peak content 99.4%.
5 β-Finasterides obtained in the above various embodiments are detected, mass spectrum：M/z373 (M+H+), with that non-hero
Amine reference substance carries out HPLC (EP8.5) and demarcates, and RRT is 1.17 (with Finasteride RRT for 1).With 5 β-Finasteride reference substances
It is compareed, complies fully with the characteristic of 5 β-Finasterides.
It is enlightenment with above-mentioned desirable embodiment according to the present invention, through the above description, relevant staff is complete
Various changes and amendments can be carried out without departing from the scope of the technological thought of the present invention' entirely.The technology of this invention
Property range is not limited to the contents of the specification, it is necessary to determine its technical scope according to right.
Claims (10)
1. a kind of preparation method of 5 β of Finasteride chiral impurity-Finasteride, structure is 3 compound of formula, and feature includes
Following steps：
(1) catalytic hydrogenation：Bisamidate formula 1, palladium carbon, sulfonic acid catalyst and glacial acetic acid are passed through hydrogen reaction, obtain hydride
Formula 2A and hydride formula 2B, reaction equation are：
(2) it refines：After hydride stirs dissolved clarification in 20 times of volume of solvent A, sodium carbonate liquor, water washing, collection is used to have successively
Machine is mutually concentrated under reduced pressure into paste；Be added 10 times of volume of solvent B, continue to be concentrated into 3~6 times of volumes, in -5 DEG C~5 DEG C coolings 1~
4h is filtered for the first time；Mother liquor concentrations are obtained to 0.5~1 times of volume, in 5~15 DEG C of cooling 1~4h, secondary suction filtration, filter cake 5
β-chiral hydride object formula 2B, process are：
(3) dehydrogenation reaction：5 β-chiral hydride objects are dissolved in organic solvent, DDQ (2,3- bis- chloro- 5,6- is added under nitrogen protection
Dicyano-Isosorbide-5-Nitrae-benzoquinones) and BSTFA (bis- (trimethylsilyl) trifluoroacetamides of N, O-) reactions, obtain 5 β-Finasterides formula 3
Crude product, reaction equation are：
2. the preparation method of 5 β-Finasterides according to claim 1, which is characterized in that sulfonic acid described in step (1) is catalyzed
Agent is p-methyl benzenesulfonic acid or methanesulfonic acid, and dosage is 0.01-0.5 times of 1 weight of bisamidate formula.
3. the preparation method of 5 β-Finasterides according to claim 1, which is characterized in that palladium carbon has described in step (1)
It is 5%~10% to imitate content.
4. the preparation method of 5 β-Finasterides according to claim 1, which is characterized in that bisamide described in step (1)
Object, glacial acetic acid, sulfonic acid catalyst, palladium carbon mass ratio be 1:5:0.05:0.25~1:10:0.5:0.5.
5. the preparation method of 5 β-Finasterides according to claim 1, which is characterized in that step (2) described solvent A is two
One kind in chloromethanes or chloroform, the one kind of solvent B in Ethyl formate, ethyl acetate, isopropyl acetate.
6. the preparation method of 5 β-Finasterides according to claim 1, which is characterized in that step (1) is specially：Nitrogen is protected
Under shield, bisamidate formula 1, palladium carbon, sulfonic acid catalyst and glacial acetic acid are heated to 40~80 DEG C, are passed through hydrogen, the reaction was continued 6
~12h, nitrogen terminate reaction, filter out palladium carbon while hot, filtrate decompression is concentrated to give hydride formula 2A and hydride formula 2B.
7. the preparation method of 5 β-Finasterides according to claim 1, which is characterized in that step (3) is specially：By 5 β-hands
Property hydride be dissolved in dioxane, under nitrogen protection be added DDQ (2,3-Dichloro-5,6-dicyano-1,4-benzoquinone), BSTFA
(bis- (trimethylsilyl) trifluoroacetamides of N, O-) react 8h in 110 DEG C and are down to room temperature, sodium hydrogensulfite after reaction
Reaction is quenched in solution, and toluene extraction is added, and gained toluene layer uses sodium carbonate liquor, solution of sodium bisulfite, sodium carbonate molten successively
Liquid, saturated common salt water washing；Toluene layer is collected, activated carbon, anhydrous sodium sulfate is added, is heated to reflux 1 hour, is filtered, filtrate subtracts
Pressure is concentrated into a small amount of；Solvent C is added, continues to be concentrated into a small amount of；Solvent C is added, continues to be concentrated into about 5 times of volumes.Cooling, pumping
Filter, dry 5 β-Finasterides formula, 3 crude product.
8. the preparation method of 5 β-Finasterides according to claim 1, which is characterized in that further include the purifying step of step (4)
Suddenly, specially：By 5 β-Finasteride crude products, the solvent D of 100 times of volumes is added, is heated to reflux dissolved clarification, is concentrated into about 20 times of bodies
Product, in -5 DEG C~5 DEG C cooling 1~4h, filtering, filter cake decompression drying obtains 5 β-Finasteride fine work.
9. the preparation method of 5 β-Finasterides according to claim 7, which is characterized in that solvent C is described in step (3)
One kind in ethyl acetate, isopropyl acetate.
10. the preparation method of 5 β-Finasterides according to claim 8, which is characterized in that solvent D is described in step (4)
One kind in ethyl acetate, isopropyl acetate.
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| CN110229211A (en) * | 2018-12-13 | 2019-09-13 | 湖北葛店人福药业有限责任公司 | A kind of refinery decolorization method of Finasteride |
| CN111484542A (en) * | 2020-04-30 | 2020-08-04 | 湖北葛店人福药业有限责任公司 | Method for treating finasteride mother liquor |
| CN111896658A (en) * | 2020-08-10 | 2020-11-06 | 扬子江药业集团四川海蓉药业有限公司 | Method for detecting isomer impurities in finasteride by using high performance liquid chromatograph |
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| CN110229211A (en) * | 2018-12-13 | 2019-09-13 | 湖北葛店人福药业有限责任公司 | A kind of refinery decolorization method of Finasteride |
| CN110229211B (en) * | 2018-12-13 | 2022-04-01 | 湖北葛店人福药业有限责任公司 | Refining and decoloring method of finasteride |
| CN111484542A (en) * | 2020-04-30 | 2020-08-04 | 湖北葛店人福药业有限责任公司 | Method for treating finasteride mother liquor |
| CN111484542B (en) * | 2020-04-30 | 2024-01-30 | 湖北葛店人福药业有限责任公司 | Treatment method of finasteride mother liquor |
| CN111896658A (en) * | 2020-08-10 | 2020-11-06 | 扬子江药业集团四川海蓉药业有限公司 | Method for detecting isomer impurities in finasteride by using high performance liquid chromatograph |
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