CN109369424A - A kind of purification process of dapoxetine hydrochloride - Google Patents
A kind of purification process of dapoxetine hydrochloride Download PDFInfo
- Publication number
- CN109369424A CN109369424A CN201810746519.2A CN201810746519A CN109369424A CN 109369424 A CN109369424 A CN 109369424A CN 201810746519 A CN201810746519 A CN 201810746519A CN 109369424 A CN109369424 A CN 109369424A
- Authority
- CN
- China
- Prior art keywords
- dapoxetine hydrochloride
- filtrate
- purification process
- added
- dapoxetine
- 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
- 229960005217 dapoxetine Drugs 0.000 title claims abstract description 57
- USRHYDPUVLEVMC-FQEVSTJZSA-N dapoxetine Chemical compound C1([C@H](CCOC=2C3=CC=CC=C3C=CC=2)N(C)C)=CC=CC=C1 USRHYDPUVLEVMC-FQEVSTJZSA-N 0.000 title claims abstract description 55
- 238000000746 purification Methods 0.000 title claims abstract description 16
- 239000000706 filtrate Substances 0.000 claims abstract description 28
- 239000000126 substance Substances 0.000 claims abstract description 17
- 239000012043 crude product Substances 0.000 claims abstract description 7
- 239000012535 impurity Substances 0.000 claims abstract description 7
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 238000003756 stirring Methods 0.000 claims abstract description 7
- 238000010792 warming Methods 0.000 claims abstract description 7
- 239000013078 crystal Substances 0.000 claims abstract description 6
- 239000002904 solvent Substances 0.000 claims abstract description 6
- 239000000203 mixture Substances 0.000 claims abstract description 4
- 238000001816 cooling Methods 0.000 claims abstract description 3
- 238000001556 precipitation Methods 0.000 claims abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 28
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 239000002808 molecular sieve Substances 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 6
- 235000019441 ethanol Nutrition 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- 238000012545 processing Methods 0.000 claims description 3
- 239000000243 solution Substances 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 18
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 239000000047 product Substances 0.000 abstract description 6
- 238000004128 high performance liquid chromatography Methods 0.000 abstract description 5
- 231100000331 toxic Toxicity 0.000 abstract description 4
- 230000002588 toxic effect Effects 0.000 abstract description 4
- -1 comprising: step 1 Chemical compound 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 3
- 238000005516 engineering process Methods 0.000 abstract description 3
- 238000009472 formulation Methods 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 239000012046 mixed solvent Substances 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000009849 deactivation Effects 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000007670 refining Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 206010054949 Metaplasia Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000008676 import Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000015689 metaplastic ossification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000000697 serotonin reuptake Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/10—Separation; Purification; Stabilisation; Use of additives
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to pharmaceutical technology fields, and in particular to a kind of purification process of dapoxetine hydrochloride, comprising: step 1, dapoxetine hydrochloride crude product is dissolved in organic solvent, is filtered to remove insoluble impurities, obtains first-time filtrate；Step 2, sorptive inorganic substance is added into first-time filtrate, is vigorously stirred, sorptive inorganic substance is filtered to remove after standing, obtain secondary filtrate, is concentrated under reduced pressure；Step 3, secondary filtrate is warming up to not higher than 80 DEG C, is kept for certain time be concentrated, is added with stirring solvent, then cooling is recrystallized, and the crystal of precipitation is separated, and is washed, and it is dry, obtain the dapoxetine hydrochloride of purification.The product purity that the method for the present invention obtains is high, high performance liquid chromatography discovery substantially only one chromatographic peak.The method of the present invention solves the problems, such as that crude dapoxetine hydrochloride and dapoxetine hydrochloride bulk pharmaceutical chemicals face, and has the characteristics that easy, easily controllable and industrialized production, improves formulation products quality, reduce toxic side effect.
Description
Technical field
The invention belongs to field of pharmaceutical chemistry technology.More particularly to the purification process of dapoxetine hydrochloride.
Background technique
Dapoxetine hydrochloride, chemical structural formula are as follows: (S)-N, N- dimethyl -3- (naphthalene -1- oxygroup)-phenylpropyl alcohol ammonia hydrochloric acid
Salt is white powder.
Dapoxetine hydrochloride is a kind of selective serotonin reuptake inhibithors, half-life short, for treating male's morning
It lets out, is developed by companies such as Johnson & Johnson's pharmacy, listed in European a few countries.The medicine absorbs fastly, can quickly reach effective blood concentration,
The blood Cmax of 1.4~2.0h of peak time, single dose dapoxetine hydrochloride 30 and 60mg are respectively 297 and 498ng/mL, are in
Dosage correlation, distribution volume 21L/kg, Tissue distribution is wide, and the drug concentration and blood concentration of nerve fiber are close, absolutely
Bioavilability is 42%, protein binding rate 9%；It is metabolized through number of ways, and up to 40 kinds or so of metabolite, main generation
Thanking to product is demethyl Dapoxetine hydrochloride and Dapoxetine hydrochloride-N oxide.The characteristics of pharmacokinetics of dapoxetine hydrochloride is shown as dosage phase
Closing property and time invariance, while not influenced by multi-dose, main metabolites are not influenced similarly by multi-dose.It grinds
Study carefully the C for showing young and old peoplemaxSimilar with AUC, food can reduce the absorption rate of dapoxetine hydrochloride, but AUC is not
It is impacted.
About the preparation of Dapoxetine hydrochloride, it is as follows to have method report:
1.W.Jand P.D.B digest
Synthetic route:
1)
2)
2. United States Patent (USP): US5292962
Synthetic route:
3. Chinese patent CN88102018A
Synthetic route:
1)
2)
4. Chinese patent CN1821212A
Synthetic route
The starting material prepared in the above-mentioned methods is although different, but there are severe reaction conditions, raw material is not easy to adopt
Purchase, reaction step are cumbersome.
General recrystallization purifying technology is difficult to obtain the dapoxetine hydrochloride of high-purity, thus the method for the prior art is not
It is easy to get the dapoxetine hydrochloride of high yield high-purity, causes with high costs and drug toxic residue, affects preparation production
Quality.
In addition, will lead to the reduction of active pharmaceutical ingredient content, color when the compound storage improper or resting period is too long
Reinforce, the content in relation to substance increases.In some cases, since controlling of production process is improper, pharmaceutical purity is caused also not to be inconsistent
It closes and requires.The prior art does not disclose this special purification process, it is therefore necessary to underproof product or crude product into one
Step is purified, and provides the compound of high-purity with high yield.There is an urgent need in the art to develop a kind of low cost, high income,
The refining methd of dapoxetine hydrochloride suitable for mass production, to overcome disadvantages mentioned above.
Summary of the invention
For the defect for overcoming the dapoxetine hydrochloride purity of prior art preparation low, the present invention provides a kind of purified salts
The method of sour Dapoxetine hydrochloride compound reduces the residual of toxic solvents to improve dapoxetine hydrochloride purity, and passes through this
The purification process of invention also contributes to formulation products quality, reduces toxic side effect, is suitable for industrialized production.
The targeted dapoxetine hydrochloride of refining methd provided by the invention is obtained by the synthetic method that is currently known
Dapoxetine hydrochloride crude product or commercially available or import dapoxetine hydrochloride bulk pharmaceutical chemicals, the hereafter referred to collectively as present invention use
Raw material dapoxetine hydrochloride, it is however generally that, the purity of dapoxetine hydrochloride crude product is lower than 98%, even lower than 92%.
The present inventor, by the experiment largely screened, has found above-mentioned document and one on the basis of a large amount of existing literatures
As method for purifying and separating be difficult to the compound that high productivity obtains high-purity, and other various isolation and purification methods and a variety of
There may be diversified associativity and unpredictabilities again for conditional parameter.The present inventor is by long-term conscientious research, warp
After crossing the specific method of combined application and Optimal Parameters, a kind of dapoxetine hydrochloride including following processing step has been had been surprisingly found that
The purification process of compound can increase substantially the purity of raw material dapoxetine hydrochloride:
Specifically, the present invention provides:
A kind of purification process of dapoxetine hydrochloride, including following processing step:
Dapoxetine hydrochloride crude product is dissolved in organic solvent by step 1), is filtered to remove insoluble impurities, is obtained primary
Filtrate, the organic solvent is in methanol, ethyl alcohol, propyl alcohol, acetone, acetonitrile, sulfolane, chloroform, ethyl acetate, ethylene glycol
One or more of mixtures；
Step 2), into first-time filtrate be added sorptive inorganic substance, be vigorously stirred, be filtered to remove after standing adsorptivity without
Machine substance obtains secondary filtrate, is concentrated under reduced pressure, the sorptive inorganic substance is active carbon or molecular sieve；
Secondary filtrate is warming up to not higher than 80 DEG C, is kept for certain time be concentrated, be added with stirring molten by step 3)
Agent, the solvent are ethyl acetate, methylene chloride, hexamethylene, hexane, toluene and methanol, and then cooling is recrystallized, and will be analysed
Crystal separation out, is washed, dry, obtains the dapoxetine hydrochloride of purification.
In step 1), the organic solvent is ethyl acetate.
In step 2), the active carbon or 0.1- for accounting for overall solution volume 0.05-0.8%g/ml are added into first-time filtrate
The molecular sieve of 1%g/ml.
In step 3), the solvent is the methanol that volume ratio is 1:15: the mixed solution of ethyl acetate.
Compared with the prior art, the present invention has the following advantages and good effect:
1, the product purity that the method for the present invention obtains is high, when by high effective liquid chromatography for measuring dapoxetine hydrochloride purity,
It was found that substantially only one chromatographic peak, the purity of dapoxetine hydrochloride are not less than 99.6%.
The present invention fundamentally changes the domestic and international lower status of dapoxetine hydrochloride material purity, solves crude salt
The problem that sour Dapoxetine hydrochloride and dapoxetine hydrochloride bulk pharmaceutical chemicals face.The method of the present invention also has easy, easily controllable and industrial
The characteristics of metaplasia produces.
Specific embodiment
The following describes the present invention further through the description of specific embodiments, but it is to limit of the invention that this, which is not,
System, those skilled in the art's basic thought according to the present invention can make various modifications or improvements, but without departing from this
The basic thought of invention, is all within the scope of the present invention.
The purity of HPLC measurement dapoxetine hydrochloride:
Method: referring to Chinese patent application 201310619658.6, the efficient liquid phase in relation to substance in a kind of Dapoxetine hydrochloride
Chromatography determination method uses chromatographic column for C18 column, and mobile phase is phosphate buffer (being 3.2 with phosphorus acid for adjusting pH value)-second
Nitrile-methanol solution (40:30:30).
Embodiment 1
Take 10g date of manufacture longer dapoxetine hydrochloride bulk pharmaceutical chemicals (Ke Bangte Chemical Co., Ltd. of manufacturer, lot number
20140501), high performance liquid chromatography measures purity 94.48%.By the dapoxetine hydrochloride dissolution of raw material in 40ml acetone,
It is sufficiently stirred, makes it completely dissolved, be filtered to remove insoluble impurities, collect first-time filtrate.
Into the first-time filtrate be added 0.2g active carbon, 40 DEG C stirring and adsorbing 15 minutes, filter deactivation charcoal, collect two
Secondary filtrate, 60 DEG C of reduced pressures.
Secondary filtrate is warming up to 70-75 DEG C of temperature, is kept for half an hour, the first for accounting for liquor capacity 300% is then added
The mixed solvent of alcohol and ethyl acetate (volume ratio 1:15).4 DEG C are cooled to 5 DEG C/h of speed, there is crystalline substance in the process
Body is slowly precipitated, and after placing 8-10 hours, completely, 500rpm centrifugation, with pure water washing 3 times, anhydrous calcium chloride is dry for crystallization.
Obtain dapoxetine hydrochloride 9.21g, purity 99.72%.
Embodiment 2
The expired dapoxetine hydrochloride bulk pharmaceutical chemicals of 10g (Ke Bangte Chemical Co., Ltd. of manufacturer, lot number 20141201) is taken,
High performance liquid chromatography measures purity 92.24%.By the dapoxetine hydrochloride dissolution of raw material in 50ml ethyl alcohol, it is sufficiently stirred,
It makes it completely dissolved, is filtered to remove insoluble impurities, collect first-time filtrate.
Into the first-time filtrate be added 0.3g active carbon, 35 DEG C stirring and adsorbing 10 minutes, filter deactivation charcoal, collect two
Secondary filtrate, 55 DEG C of reduced pressures.
Secondary filtrate is warming up to 72-78 DEG C of temperature, is kept for 1 hour, the methanol for accounting for liquor capacity 300% is then added
With the mixed solvent of ethyl acetate (volume ratio 1:20), it is cooled to 0 DEG C with 5 DEG C/h of speed, there is crystal in the process
It is slowly precipitated, after placing 6 hours, completely, filtering, with pure water washing 3 times, air dries, and obtains dapoxetine hydrochloride for crystallization
9.02g, purity 99.68%.
Embodiment 3
The dapoxetine hydrochloride crude product for taking 10g to prepare according to US5292962, high performance liquid chromatography measure purity
93.28%.It by the dapoxetine hydrochloride dissolution of raw material in the in the mixed solvent of 60ml ethyl alcohol and methanol, is sufficiently stirred, keeps its complete
Fully dissolved is filtered to remove insoluble impurities, collects first-time filtrate.
Be added the A type molecular sieve of 0.2g into the first-time filtrate, 35 DEG C stirring and adsorbing 15 minutes, filter de- molecular sieve, receive
Collect secondary filtrate, 60 DEG C of reduced pressures.
Secondary filtrate is warming up to 70-75 DEG C of temperature, is kept for half an hour, the ring for accounting for liquor capacity 300% is then added
Hexane is cooled to 2 DEG C with 5.5 DEG C/h of speed, has crystal to be slowly precipitated in the process, after placing 8-12 hours, crystallization
Completely, 500rpm is centrifuged, and with a little washing, anhydrous calcium chloride is dry, obtains dapoxetine hydrochloride 9.05g, purity 99.75%.
Embodiment 4
10g dapoxetine hydrochloride bulk pharmaceutical chemicals (Ke Bangte Chemical Co., Ltd. of manufacturer, lot number 20140702) is taken, efficiently
Liquid chromatography measures purity 96.25%.By the dapoxetine hydrochloride dissolution of raw material in 50ml acetonitrile, it is sufficiently stirred, makes it
It is completely dissolved, is filtered to remove insoluble impurities, collect first-time filtrate.
Be added the X-type molecular sieve of 0.3g into the first-time filtrate, 35 DEG C stirring and adsorbing 18 minutes, filter de- molecular sieve, receive
Collect secondary filtrate, 55 DEG C of reduced pressures.
Eluent is warming up to 65-70 DEG C of temperature, is kept for half an hour, the methanol for accounting for liquor capacity 400% is then added
With the mixed solvent of ethyl acetate (volume ratio 1:10), it is cooled to 1 DEG C with 6 DEG C/h of speed, there is crystal in the process
It is slowly precipitated, after placing 8 hours, completely, filtering, with pure water washing 3 times, air dries, and obtains dapoxetine hydrochloride for crystallization
9.45g, purity 99.80%.
Claims (4)
1. a kind of purification process of dapoxetine hydrochloride, including following processing step:
Dapoxetine hydrochloride crude product is dissolved in organic solvent by step 1), is filtered to remove insoluble impurities, obtains primary filter
Liquid, the organic solvent in methanol, ethyl alcohol, propyl alcohol, acetone, acetonitrile, sulfolane, chloroform, ethyl acetate, ethylene glycol one
Kind or several mixtures；
Sorptive inorganic substance is added into first-time filtrate, is vigorously stirred, sorptive inorganic object is filtered to remove after standing for step 2)
Matter obtains secondary filtrate, is concentrated under reduced pressure, the sorptive inorganic substance is active carbon or molecular sieve；
Secondary filtrate is warming up to not higher than 80 DEG C, is kept for certain time be concentrated, be added with stirring solvent, institute by step 3)
Stating solvent is ethyl acetate, methylene chloride, hexamethylene, hexane, toluene and methanol, and then cooling is recrystallized, by precipitation
Crystal separation, is washed, dry, obtains the dapoxetine hydrochloride of purification.
2. the purification process of dapoxetine hydrochloride according to claim 1, which is characterized in that in step 1), the organic solvent
For ethyl acetate.
3. the purification process of dapoxetine hydrochloride according to claim 1, which is characterized in that in step 2), into first-time filtrate
The molecular sieve of the active carbon or 0.1-1%g/ml that account for overall solution volume 0.05-0.8%g/ml is added.
4. according to claim 1 to one of 3 dapoxetine hydrochloride purification process, which is characterized in that it is described molten in step 3)
Agent is the methanol that volume ratio is 1:15: the mixed solution of ethyl acetate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810746519.2A CN109369424A (en) | 2018-07-09 | 2018-07-09 | A kind of purification process of dapoxetine hydrochloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810746519.2A CN109369424A (en) | 2018-07-09 | 2018-07-09 | A kind of purification process of dapoxetine hydrochloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109369424A true CN109369424A (en) | 2019-02-22 |
Family
ID=65404218
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810746519.2A Pending CN109369424A (en) | 2018-07-09 | 2018-07-09 | A kind of purification process of dapoxetine hydrochloride |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109369424A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114621107A (en) * | 2022-04-01 | 2022-06-14 | 广药白云山化学制药(珠海)有限公司 | Method for recycling product from dapoxetine hydrochloride mother liquor |
| CN115385807A (en) * | 2022-08-25 | 2022-11-25 | 天方药业有限公司 | Recovery method of dapoxetine hydrochloride acetonitrile and isopropanol mother liquor |
| CN115554731A (en) * | 2022-10-24 | 2023-01-03 | 连云港贵科药业有限公司 | Preparation method of gemcitabine |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011161690A1 (en) * | 2010-06-23 | 2011-12-29 | Symed Labs Limited | Processes for the preparation of (+)-n,n-dimethyl-2-[1-(naphthalenyloxy) ethyl] benzene methanamine and intermediates thereof |
| CN106883133A (en) * | 2017-03-10 | 2017-06-23 | 南京斯贝源医药科技有限公司 | A kind of preparation method of dapoxetine hydrochloride |
| CN107473977A (en) * | 2017-09-21 | 2017-12-15 | 成都海杰亚医药科技有限公司 | Intermediate and the preparation method of Dapoxetine hydrochloride prepared by a kind of Dapoxetine hydrochloride |
-
2018
- 2018-07-09 CN CN201810746519.2A patent/CN109369424A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011161690A1 (en) * | 2010-06-23 | 2011-12-29 | Symed Labs Limited | Processes for the preparation of (+)-n,n-dimethyl-2-[1-(naphthalenyloxy) ethyl] benzene methanamine and intermediates thereof |
| CN106883133A (en) * | 2017-03-10 | 2017-06-23 | 南京斯贝源医药科技有限公司 | A kind of preparation method of dapoxetine hydrochloride |
| CN107473977A (en) * | 2017-09-21 | 2017-12-15 | 成都海杰亚医药科技有限公司 | Intermediate and the preparation method of Dapoxetine hydrochloride prepared by a kind of Dapoxetine hydrochloride |
Non-Patent Citations (1)
| Title |
|---|
| 郭佳: "盐酸达泊西汀的合成工艺及质量标准", 《中国优秀硕士论文全文数据库医药卫生科技辑》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114621107A (en) * | 2022-04-01 | 2022-06-14 | 广药白云山化学制药(珠海)有限公司 | Method for recycling product from dapoxetine hydrochloride mother liquor |
| CN115385807A (en) * | 2022-08-25 | 2022-11-25 | 天方药业有限公司 | Recovery method of dapoxetine hydrochloride acetonitrile and isopropanol mother liquor |
| CN115554731A (en) * | 2022-10-24 | 2023-01-03 | 连云港贵科药业有限公司 | Preparation method of gemcitabine |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN113292533B (en) | Method for purifying polymer impurities in lipoic acid | |
| CN109369424A (en) | A kind of purification process of dapoxetine hydrochloride | |
| EP1927586B1 (en) | Process for producing 5-aminolevulinic acid hydrochloride | |
| CN103502203A (en) | Methods of making L-ornithine phenyl acetate | |
| CN110590587A (en) | Synthetic method of 3-chloro-L-alanine methyl ester hydrochloride | |
| CN102093236B (en) | Ornithine aspartate compound and new preparation method thereof | |
| CN105348262B (en) | A kind of improved method preparing dabigatran etcxilate | |
| CN101863948A (en) | High-purity (2 beta, 3 alpha, 5 alpha, 16 beta, 17 beta)-2-(4-morpholinyl)-16-(1-pyrrolidinyl)-androstane-3,17-diol or composition thereof and preparation method thereof | |
| CN114008023B (en) | Crystal form of Sofos-piramide and preparation method thereof | |
| US20130060049A1 (en) | Method for preparing (s)-4-hydroxy-2-oxo-1-pyrrolidine acetamide | |
| CN102924311B (en) | L-ornithine-L-aspartate preparation method | |
| CN110467580B (en) | Resolution method of Raxinard axis chiral enantiomer | |
| CN101270074A (en) | Method for preparing high purity mitiglinide calcium | |
| CN102702181A (en) | Lafutidine compound and novel preparation method of lafutidine compound | |
| CN110872251A (en) | N-ethylpyridine methylamine trifluoroacetate and crystal, preparation process and application thereof | |
| CN105461573A (en) | Preparation method of (S)-N-demethyl dapoxetine | |
| CN105198905A (en) | Method for preparing ultrapure marbofloxacin through purification | |
| CN114213306A (en) | Preparation method of brivaracetam acid impurity | |
| CN109400606B (en) | Method for refining apixaban from apixaban crude product | |
| CN102617327A (en) | Dexibuprofen compound and preparation method thereof | |
| CN102363621B (en) | Cefminox sodium hexahydrate, preparation method thereof and pharmaceutical composition containing hexahydrate | |
| CN101768164B (en) | Naloxone hydrochloride compound with high purity | |
| CN100383114C (en) | Nateglinide preparing process | |
| CN105646284A (en) | Lacosamide synthesis method | |
| CN113354581A (en) | Preparation method and application of chiral chloroquine and phosphate thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20190222 |