CN108358817A - A kind of preparation method of Mo Fanselin intermediate and Mo Fanselin - Google Patents
A kind of preparation method of Mo Fanselin intermediate and Mo Fanselin Download PDFInfo
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- CN108358817A CN108358817A CN201810180553.8A CN201810180553A CN108358817A CN 108358817 A CN108358817 A CN 108358817A CN 201810180553 A CN201810180553 A CN 201810180553A CN 108358817 A CN108358817 A CN 108358817A
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- 0 CC(C)C*c1ccc(CI(C)C([U]C)=*)cc1 Chemical compound CC(C)C*c1ccc(CI(C)C([U]C)=*)cc1 0.000 description 2
- TVSMLBGFGKLKOO-UHFFFAOYSA-N CC1CCN(C)CC1 Chemical compound CC1CCN(C)CC1 TVSMLBGFGKLKOO-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/06—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups by reactions not involving the formation of carbamate groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
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Abstract
General structure the invention discloses the preparation method of a kind of Mo Fanselin intermediate and Mo Fanselin, Mo Fanselin intermediates isIt is obtained by 4 isobutoxy benzaldehydes and carbamate reduction amination, synthetic route is
Description
Technical field
The present invention relates to the synthesis fields of pharmaceutical molecules, the more particularly to synthesis technology of medicine intermediate, and in particular to one
Kind prepares a Mo Fanselin intermediates and the method for Mo Fanselin.
Background technology
Whole world parkinsonian about 7 million to one 10,000,000 at present, China just have 2,600,000, rank first in the world, often
Year will also increase by 100,000 neopathy patients.50% or more parkinsonian once had mental symptom (PDP).These spirit
Symptom is mainly shown as illusion and vain hope, and the treatment and tourniquet to parkinsonian carry out bigger challenge.Parkinson's disease essence
Refreshing disease is the main cause that Parkinsonian enters old nurse apartment.Parkinson's disease psychosis is now in addition to low at present
Without approval other drugs except dose clozapine (clozapine, Clozaril), and Clozapine has serious security risk,
It can lead to dangerous quantity of leucocyte decline and drowsiness side effect.
The tartaric acid Mo Fanselin (Pimavanserin, Nuolazid) of company of Acadia research and development is for treating pa gold
Sen Shi disease mental symptoms are non-dopamine neurotransmitter similar to object, can be more without influencing with selective exclusion five hydroxytryptamine 2A receptors
The effect of bar amine.
So far, less about the synthesis patent of Mo Fanselin synthesis, the following synthesis road of US7790899B2 reports
Line：
The shortcomings that route：(1) it participates in reaction using hydrogen to need to carry out under high pressure, security risk is high；Reaction needs
Palladium catalyst charcoal, it is expensive.(2) virose phosgene is arrived involved in reaction, it is larger to the health effect of operator, it is unfavorable for
Environmental protection, security risk is high, is unfavorable for industrialized production.
Another synthetic route, as follows described in US7601740B2：
The DPPA that the route uses is expensive, and azido compound intermediate, the nitrine of generation will be passed through in reaction process
There are the security risks such as explosion, severe toxicity in compound.
CN105111135A reports following route：
The route tries although avoiding using severe toxicity is dangerous using carbonyl dimidazoles as active urea intermediate source is obtained
Agent, but route steps are long, intermediate is not purified, and the purifying of finished product is relatively difficult.
CN105418460A discloses following preparation methods：
Though this method has used chloro-formate instead of the phosgene of severe toxicity, chloro-formate toxicity is still huge, environment
It is seriously polluted, and reaction step is more, yield is low.
How to develop that a kind of reaction condition is mild, the preparation methods of the few Mo Fanselin intermediates of reaction step goes forward side by side one
A step synthesis Mo Fanselin is a challenging job.
Invention content
It is an object of the invention to overcome the deficiencies of the prior art and provide a kind of reaction condition is mild, high income not
Preparation among Fan Selin.
On the preparation method based on above-mentioned intermediate, one kind Mo Fanselin is provided
Preparation method.
The technical solution used in the present invention is：
A method of a Mo Fanselin intermediates being prepared, the general structure of described Mo Fanselin intermediate isIt is obtained by 4- isobutoxies benzaldehyde and carbamate reduction amination, synthesizes road
Line is as follows
In structure above, R is electroneutral or electron-withdrawing group.
As being further improved for the above method, R is selected from alkane, the halogenated alkane of C1~C6；Phenyl or by halogen, ester
One or more substituted phenyl in base, nitro, cyano.
As being further improved for the above method, the go back original reagent of reductive amination process is selected from sodium borohydride, acetic acid boron hydrogen
Change at least one of sodium, sodium cyanoborohydride.
As being further improved for the above method, the temperature of reductive amination process is 0~50 DEG C.
A method of a Mo Fanselin is prepared, is included the following steps：
1) a Mo Fanselin intermediates are prepared by above-mentioned method
2) by Mo Fanselin intermediatesIt is anti-by ammonolysis
It should obtain a Mo Fanselin.
As being further improved for the above method, carried out under the conditions of ammonolysis reaction is existing for alkaline medium.
As being further improved for the above method, alkaline medium be selected from potassium carbonate, ammonium carbonate, potassium hydroxide, sodium hydroxide,
At least one of potassium tert-butoxide, sodium hydride, triethylamine, diisopropylethylamine.
As being further improved for the above method, the solvent of ammonolysis reaction is selected from methanol, ethyl alcohol, isopropanol, the tert-butyl alcohol, just
Butanol, benzene, toluene, dichloromethane, chloroform, methyl acetate, ethyl acetate, isopropyl acetate, ether, methyl tertiary butyl ether(MTBE), four
At least one of hydrogen furans, isopropyl ether, acetonitrile, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, dimethyl sulfoxide (DMSO).
As being further improved for the above method, the temperature of ammonolysis reaction is 10~100 DEG C.
The beneficial effects of the invention are as follows：
Preparation among the Mo Fanselin of the present invention, by reductive amination process, a step just obtains among target
Body greatly simplifies the reaction step of a Mo Fanselin, reduces the synthesis cost of a Mo Fanselin.
The materials safety that the method for the present invention uses, it is of low cost, effectively reduce production cost.
The reaction condition of the method for the present invention is mild, avoids that toxicity is big and the use of not easy-operating phosgene, it is industrial easily
In realization.
It is easy that the intermediate and product of the method for the present invention isolate and purify, in this embodiment it is not even necessary to pass through separation of intermediates, you can straight
Tapping into row, reaction prepares a Mo Fanselin in next step, and easy to operate, yield is than prior art higher.
Specific implementation mode
A method of a Mo Fanselin intermediates being prepared, the general structure of described Mo Fanselin intermediate isIt is obtained by 4- isobutoxies benzaldehyde and carbamate reduction amination, synthesizes road
Line is as follows
In structure above, R is electroneutral or electron-withdrawing group.
Its reaction principle is that 4- isobutoxies benzaldehyde generates carbon-to-nitrogen double bon i.e. imines (Schiff with urethane reaction
Alkali), using obtaining aminated compounds after reducing agent such as sodium borohydride reduction.
As being further improved for the above method, R is selected from alkane, the halogenated alkane of C1~C6；Phenyl or by halogen, ester
One or more substituted phenyl in base, nitro, cyano.The skeleton of alkane or halogenated alkane can be linear chain or branched chain.
Halogen is preferably chlorine, fluorine.
As being further improved for the above method, the go back original reagent of reductive amination process is selected from sodium borohydride, acetic acid boron hydrogen
Change at least one of sodium, sodium cyanoborohydride.
As being further improved for the above method, the temperature of reductive amination process is 0~50 DEG C.
A method of a Mo Fanselin is prepared, is included the following steps：
1) a Mo Fanselin intermediates are prepared by above-mentioned method
2) by Mo Fanselin intermediatesIt is anti-by ammonolysis
It should obtain a Mo Fanselin.
R is electroneutral or electron-withdrawing group, can make cloud density on the O being directly connected relatively low in this way,
It is generated convenient for ammonolysis reaction.Meanwhile particularly, when R group has stronger electron attraction, the by-product of the reaction is in one
Fixed acidity, is easily consumed under alkaline condition, is more advantageous to the progress of ammonolysis reaction.Preferably, R is selected from the alkane of C1~C6
Hydrocarbon, halogenated alkane；Phenyl or by one or more substituted phenyl in halogen, ester group, nitro, cyano.Alkane or alkyl halide
The skeleton of hydrocarbon can be linear chain or branched chain.Halogen is preferably chlorine, fluorine.
As being further improved for the above method, carried out under the conditions of ammonolysis reaction is existing for alkaline medium.
As being further improved for the above method, alkaline medium be selected from potassium carbonate, ammonium carbonate, potassium hydroxide, sodium hydroxide,
At least one of potassium tert-butoxide, sodium hydride, triethylamine, diisopropylethylamine.
As being further improved for the above method, the solvent of ammonolysis reaction is selected from methanol, ethyl alcohol, isopropanol, the tert-butyl alcohol, just
Butanol, benzene, toluene, dichloromethane, chloroform, methyl acetate, ethyl acetate, isopropyl acetate, ether, methyl tertiary butyl ether(MTBE), four
At least one of hydrogen furans, isopropyl ether, acetonitrile, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, dimethyl sulfoxide (DMSO).
As being further improved for the above method, the temperature of ammonolysis reaction is 10~100 DEG C.
It elaborates below to the embodiment of the present invention, the present embodiment is carried out lower based on the technical solution of the present invention
Implement, gives detailed embodiment and specific operating process, but protection scope of the present invention is not limited to following implementation
Example.
The part material used in following embodiment can be prepared or be commercially available by existing method, or pressed
Following method synthesizes to obtain.
By 1 prepare compound 3 of compound
Addition parahydroxyben-zaldehyde (15.0g, 122.8mmo1) in 250mL there-necked flasks, Anhydrous potassium carbonate (25.4g,
184.2mmoL), potassium iodide (1.4g, 12.3mmoL) and 75mL DMF, are heated to 85 DEG C, are slowly added into reaction system
Isobutane bromide (50.5g, 368.4mmo1), finishes, and system reacts 6h under the conditions of 85 DEG C.Stop reaction, system is cooled to room
Temperature, filtering, filter cake 90mL ethyl acetate rinses 2 times.Filtrate is poured into 250mL water, organic phase is separated, water phase is used respectively
90mL ethyl acetate extracts three times, merges organic phase, is washed once with 150mL saturated common salts, and anhydrous sodium sulfate drying has been dried
Finish, filtering, filtrate is spin-dried for obtaining 20.8g compounds, weak yellow liquid, yield 95%.
MS(m/z)：[M+H]+=179.3；3 nuclear magnetic data of compound is as follows：'H NMR(400MHz,CDCl3)(ppm):
9.84(s,1H),7.85(d,2H),7.08(d,2H),3.84(d,2H),2.05-1.87(m,1H),0.98(d,6H)。
By compound 6 and 7 prepare compound 8 of compound
Compound 6 (5.0g, 44.2mmoLl), compound 7 (6.1g, 48.6mmoL), acetic acid are added in 250mL there-necked flasks
(3.2g, 53.04mmoL), 30mL dichloromethane, system are cooled to 0 DEG C, and or so half an hour, Xiang Qi was slowly added to triacetoxyl group
Sodium borohydride (7.6g, 36mmoL), system reacts 12h at room temperature.30mL 10%NaOH solution, stirring are added dropwise into system
Liquid separation, water phase are extracted twice time (30mL*2) with dichloromethane, merge organic phase, and 30mL saturation NaCl solutions washed once, nothing
Aqueous sodium persulfate is dried, filtering, and filtrate concentrates yellow solid, and solid is recrystallized by dichloromethane/normal heptane=1/10, obtains chemical combination
Object 8, yellow solid, 8.3g, yield 85%.
MS(m/z)：[M+H]+=223.3；8 nuclear magnetic data of compound is as follows：'H NMR(400MHz,CDCl3)(ppm):
7.45-7.31(m,2H),7.11-7.02(m,2H),3.95(s,1H),3.69(s,2H),2.55-2.49(m,1H),2.40-
2.29(m,4H),2.19(s,3H),1.87-1.69(m,2H),1.41-1.29(m,2H)。
Embodiment 1：
By compound 3 and compound 4-a prepare compounds 5-a
Compound 3 (5g, 28.05mmoL), compound 4-a (2.3g, 30.86mmoL), acetic acid is added in 100mL there-necked flasks
(2.0g, 33.66mmoL), 30mL dichloromethane, system are cooled to 0 DEG C, and or so half an hour, rear its was slowly added to triacetoxyl group
Sodium borohydride (8.9g, 42.1mmoL), system reacts 12h at room temperature.30mL 10%NaOH solution is added dropwise into system, stirs
Liquid separation is mixed, water phase is extracted twice (30mL*2) with dichloromethane, merges organic phase, and 30mL saturation NaCl solutions washed once, nothing
Aqueous sodium persulfate is dried, filtering, and filtrate is concentrated to give off-white powder, and solid is recrystallized by ethyl acetate/normal heptane=1/10, obtained
Compound 5-a, white solid, 5.73g, yield 86%.
MS(m/z)：[M+H]+=228.3；Compound 5-a nuclear magnetic datas are as follows：'H NMR(400MHz,CDCl3)(ppm):
7.82(d,2H),7.13(d,2H),6.85(s,1H),4.26(s,2H),4.01(d,2H),3.74(s,3H),2.10-1.95
(m,1H),1.03(d,6H)。
Mo Fanselin is prepared by compound 5-a and compound 8
Compound 5-a (5.0g, 21.07mmoL), triethylamine (4.3g, 42.14mmoL), toluene is added in 250mL there-necked flasks
(30mL), system are cooled to 0-10 DEG C, and after stirring 0.5h, the toluene solution of compound 8 (5.2g, 23.18mmoL) is added dropwise
(30mL), is added dropwise.After system is warming up to 80 DEG C of stirring 12h, it is cooled to 0-5 DEG C, water 60mL is added, after 1h is stirred at room temperature,
Liquid separation, organic phase 60mL saturated common salt water washings are stood, the drying of anhydrous slufuric acid is concentrated to dryness, obtains off-white powder.Solid
It is recrystallized, is filtered with 95% ethyl alcohol (50mL), eluted with 95% ethyl alcohol (10mL), obtain off-white powder 6.4g, as not model
Color woods, yield 71%.
Mo Fanselin MS (m/z)：[M+H]+=428.6；Nuclear magnetic data is as follows:'H NMR(400MHz,CDCl3)
(ppm):7.35-7.24(m,2H),7.13-7.01(m,4H),6.85(d,2H),5.94(s,1H),4.77(s,1H),4.25
(s,2H),3.71(d,2H),3.17-3.05(m,2H),2.41-2.34(m,4H),2.7(s,3H),1.86-1.54(m,4H),
0.95(d,6H)。
Embodiment 2：
By compound 3 and compound 4-b prepare compounds 5-b
Compound 3 (5g, 28.05mmoL), compound 4-b (2.75g, 30.86mmoL), acetic acid is added in 100mL there-necked flasks
(2.0g, 33.66mmoL), 30mL dichloromethane, system are cooled to 0 DEG C, and or so half an hour, Xiang Qi was slowly added to triacetoxyl group
Sodium borohydride (8.9g, 42.1mmoL), system reacts 12h at room temperature.30mL 10%NaOH solution is added dropwise into system, stirs
Liquid separation is mixed, water phase is extracted twice (30mL*2) with dichloromethane, merges organic phase, and 30mL saturation NaCl solutions washed once, nothing
Aqueous sodium persulfate is dried, filtering, and filtrate is concentrated to give off-white powder, and solid is recrystallized by ethyl acetate/normal heptane=1/10, obtained
Compound 5-b, white solid, 6.2g, yield 88%.
MS(m/z)：[M+H]+=252.3；Compound 5-b nuclear magnetic datas are as follows：'H NMR(400MHz,CDCl3)(ppm):
7.88(d,2H),7.11(d,2H),6.89(s,1H),4.23(s,2H),3.92-3.79(m,4H),3.74(s,3H),1.91-
1.83(m,1H),1.33(m,3H),0.95(d,6H)。
Mo Fanselin is prepared by compound 5-b and compound 8
Compound 5-b (5.0g, 19.9mmoL), triethylamine (4.03g, 39.8mmoL), toluene is added in 250mL there-necked flasks
(30mL), system are cooled to 0-10 DEG C, and after stirring 0.5h, the toluene solution of compound 8 (4.9g, 21.9mmoL) is added dropwise
(30mL), is added dropwise.After system is warming up to 80 DEG C of stirring 12h, it is cooled to 0-5 DEG C, water 60mL is added, after 1h is stirred at room temperature,
Liquid separation, organic phase 60mL saturated common salt water washings are stood, the drying of anhydrous slufuric acid is concentrated to dryness, obtains off-white powder.Solid
It is recrystallized, is filtered with 95% ethyl alcohol (50mL), eluted with 95% ethyl alcohol (10mL), obtain off-white powder 5.8g, as not model
Color woods, yield 68%.
Embodiment 3：
By compound 3 and compound 4-c prepare compounds 5-c
Compound 3 (5g, 28.05mmoL), compound 4-c (4.2g, 30.86mmoL), acetic acid is added in 100mL there-necked flasks
(2.0g, 33.66mmoL), 30mL dichloromethane, system are cooled to 0 DEG C, and or so half an hour, Xiang Qi was slowly added to triacetoxyl group
Sodium borohydride (8.9g, 42.1mmoL), system reacts 12h at room temperature.30mL 10%NaOH solution is added dropwise into system, stirs
Liquid separation is mixed, water phase is extracted twice (30mL*2) with dichloromethane, merges organic phase, and 30mL saturation NaCl solutions washed once, nothing
Aqueous sodium persulfate is dried, filtering, and filtrate is concentrated to give off-white powder, and solid is recrystallized by ethyl acetate/normal heptane=1/8, obtained
Compound 5-c, white solid, 7.3g, yield 87%.
MS(m/z)：[M+H]+=300.4；Compound 5-c nuclear magnetic datas are as follows：'H NMR(400MHz,CDCl3)(ppm):
7.87-7.75(m,2H),7.45-7.37(m,3H),7.33(d,2H),7.03(d,2H),4.25(s,2H),3.92(d,2H),
1.87-1.73(m,1H),0.98(d,6H)。
Mo Fanselin is prepared by compound 5-c and compound 8
Compound 5-c (5.0g, 16.7mmoL), triethylamine (3.4g, 33.4mmoL) toluene is added in 250mL there-necked flasks
(30mL), system are cooled to 0-10 DEG C, and after stirring 0.5h, the toluene solution of compound 8 (4.1g, 18.4mmoL) is added dropwise
(30mL), is added dropwise.After system is warming up to 80 DEG C of stirring 12h, it is cooled to 0-5 DEG C, water 60mL is added, 1h is stirred at room temperature, it is quiet
Liquid separation, organic phase 60mL saturated common salt water washings are set, the drying of anhydrous slufuric acid is concentrated to dryness, obtains off-white powder.Solid is used
95% ethyl alcohol (50mL) recrystallizes, and filters, and is eluted with 95% ethyl alcohol (10mL), obtains off-white powder 5.3g, as Mo Fanse
Woods, yield 74%.
The basic principles and main features and advantages of the present invention of the present invention have been shown and described above.The skill of the industry
Art personnel it should be appreciated that the present invention is not limited to the above embodiments, the above embodiments and description only describe
The principle of the present invention, without departing from the spirit and scope of the present invention, various changes and improvements may be made to the invention, these
Changes and improvements all fall within the protetion scope of the claimed invention.The claimed scope of the invention by appended claims and
Its equivalent thereof.
Claims (10)
1. a kind of preparing a method for Mo Fanselin intermediates, the general structure of described Mo Fanselin intermediate isIt is obtained by 4- isobutoxies benzaldehyde and carbamate reduction amination, synthesizes road
Line is as follows
In structure above, R is electroneutral or electron-withdrawing group.
2. according to the method described in claim 1, it is characterized in that：R is selected from alkane, the halogenated alkane of C1~C6；Phenyl or by
One or more substituted phenyl in halogen, ester group, nitro, cyano.
3. according to the method described in claim 1, it is characterized in that：The go back original reagent of reductive amination process be selected from sodium borohydride,
At least one of acetic acid sodium borohydride, sodium cyanoborohydride.
4. according to the method described in claim 1, it is characterized in that：The solvent of reductive amination process is selected from dichloromethane, tetrahydrochysene
Furans, 1,4- dioxane, toluene, methanol.
5. according to the method described in claim 1, it is characterized in that：The temperature of reductive amination process is 0~50 DEG C.
6. a kind of method preparing a Mo Fanselin, includes the following steps：
1) a Mo Fanselin intermediates are prepared by Claims 1 to 5 any one of them method
2) by Mo Fanselin intermediatesIt is obtained by ammonolysis reaction
Mo Fanselin.
7. according to the method described in claim 6, it is characterized in that：It is carried out under the conditions of ammonolysis reaction is existing for alkaline medium.
8. according to the method described in claim 6, it is characterized in that：The solvent of ammonolysis reaction be selected from methanol, ethyl alcohol, isopropanol,
The tert-butyl alcohol, n-butanol, benzene, toluene, dichloromethane, chloroform, methyl acetate, ethyl acetate, isopropyl acetate, ether, methyl- tert
In butyl ether, tetrahydrofuran, isopropyl ether, acetonitrile, N,N-dimethylformamide, DMAC N,N' dimethyl acetamide, dimethyl sulfoxide (DMSO)
It is at least one.
9. according to the method described in claim 6, it is characterized in that：The temperature of ammonolysis reaction is 10~100 DEG C.
10. according to the method described in claim 7, it is characterized in that：Alkaline medium be selected from potassium carbonate, ammonium carbonate, potassium hydroxide,
At least one of sodium hydroxide, potassium tert-butoxide, sodium hydride, triethylamine, diisopropylethylamine.
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| CN110894186A (en) * | 2018-09-12 | 2020-03-20 | 浙江京新药业股份有限公司 | Preparation method of pimavanserin and intermediate thereof |
| CN111320569A (en) * | 2018-12-17 | 2020-06-23 | 江苏艾立康药业股份有限公司 | Preparation method of pimavanserin solid intermediate |
| WO2020234383A1 (en) * | 2019-05-22 | 2020-11-26 | Zaklady Farmaceutyczne Polpharma S.A. | A pharmaceutical intermediate |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110894186A (en) * | 2018-09-12 | 2020-03-20 | 浙江京新药业股份有限公司 | Preparation method of pimavanserin and intermediate thereof |
| CN110894186B (en) * | 2018-09-12 | 2022-05-24 | 浙江京新药业股份有限公司 | Preparation method of pimavanserin and intermediate thereof |
| CN111320569A (en) * | 2018-12-17 | 2020-06-23 | 江苏艾立康药业股份有限公司 | Preparation method of pimavanserin solid intermediate |
| CN111320569B (en) * | 2018-12-17 | 2022-03-08 | 江苏艾立康医药科技有限公司 | Preparation method of pimavanserin solid intermediate |
| WO2020234383A1 (en) * | 2019-05-22 | 2020-11-26 | Zaklady Farmaceutyczne Polpharma S.A. | A pharmaceutical intermediate |
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