CN110835349A - Method for preparing α -arteether bulk drug by one-pot method - Google Patents
Method for preparing α -arteether bulk drug by one-pot method Download PDFInfo
- Publication number
- CN110835349A CN110835349A CN201911102258.1A CN201911102258A CN110835349A CN 110835349 A CN110835349 A CN 110835349A CN 201911102258 A CN201911102258 A CN 201911102258A CN 110835349 A CN110835349 A CN 110835349A
- Authority
- CN
- China
- Prior art keywords
- arteether
- bulk drug
- preparing
- reaction
- pot method
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
- C07D493/20—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of α -arteether bulk drug preparation, and particularly relates to a method for preparing α -arteether bulk drug by a one-pot method, which comprises the following steps of S1 artemisinin is subjected to reduction reaction under the catalytic action of a catalyst to prepare dihydroartemisinin, S2 dihydroartemisinin is subjected to etherification reaction under the condition of using original low carbonate or borate as a catalyst to obtain a α -arteether bulk drug mixture, the solvent of the etherification reaction is a combination of a nonpolar organic solvent and ethanol, the pH value of a reaction system is 1-4, the one-pot method provided by the invention directly prepares α -arteether bulk drug from artemisinin without producing a dihydroartemisinin intermediate, so that qualified α -arteether bulk drug is directly obtained, and the recovery rate of the reaction system is more than 98%.
Description
Technical Field
The invention belongs to the technical field of α -arteether bulk drug preparation, and particularly relates to a method for preparing α -arteether bulk drug by a one-pot method.
Background
Arteether is an antimalarial compound derived from artemisia annua. The molecular formula is as follows: c17H28O5White crystals or crystalline powders. Arteether is an ether derivative of dihydroartemisinin, which has been extensively preclinical, animal and toxicological studies and for drug regulation, currently demonstrated promising activity, and can treat uncomplicated malaria, as well as severe complicated malaria, cerebral malaria andmultidrug malaria. And arteether is more effective than artemisinin, shows faster effect of killing schizophrenic organisms, short fever clearing time without side effect and low recurrence rate, has stronger effect of killing plasmodium aneuploidy, and can rapidly control symptoms. The World Health Organization (WHO) has also used arteether as an antimalarial drug to treat life. Arteether is more potent than artemisinin and is an ideal antimalarial drug, especially a multidrug resistant and concurrent strain (complexed strains) for the treatment of Plasmodium falciparum. Arteether exhibits faster schizonticidal action with a faster clearance, short fever clearance without side effects and a low recurrence rate.
At present, two common arteether bulk drugs are available, namely, a mixture of β -arteether and α/β -arteether, and researches show that the efficacy of α/β arteether and a single β arteether preparation are safe and effective in reducing the clinical symptoms of acute malignant malaria, and the two preparations can also rapidly eliminate parasitic diseases.
For example, patent CN1694887 discloses a process for the preparation of β -arteether starting from artemisinin by reduction to dihydroartemisinin at room temperature with a small amount of sodium borohydride in ethanol in the presence of a new polyhydroxy catalyst, acylation of the dihydroartemisinin in the presence of an acid catalyst, extraction of arteether from the aqueous reaction mixture with 1% ethyl acetate in n-hexane followed by workup and purification of the impure arteether to obtain 80-86% (w/w) pure α and β arteether.
The patent CN102887907A discloses a method for semi-synthesizing β -arteether by a single-reaction kettle method by using artemisinin as a raw material, which is characterized in that borohydride such as potassium borohydride and the like is used as a reducing agent in a medium-polarity ether solvent system such as absolute ethyl alcohol or tetrahydrofuran and the like, dihydroartemisinin is obtained by reduction, without separation and purification, methanesulfonic acid or phosphoric acid and the like are added to adjust the pH value to be neutral, Lewis acid ZnBr2 and other catalysts are further added to react to prepare arteether, and after the reaction is finished, β -arteether (β -arteether 0.85k is prepared from 1kg of artemisinin) is directly separated and purified in an extraction and crystallization recrystallization mode to obtain high-yield β -arteether (the content of the refined arteether is more than 99.0 percent), related substances α -arteether is less than 0.2 percent, the dihydroartemisinin is less than 0.1 percent, and total impurities are less than 0.5 percent.
The methods disclosed above are all methods for preparing β -arteether, and based on the use and advantages of α/β arteether, α/β arteether has great demand in China, but no report about α/β arteether bulk drug is found at present.
Disclosure of Invention
In order to solve the problems in the prior art, the invention provides a method for preparing α -arteether bulk drug by using artemisinin as a raw material through a one-pot method.
In order to achieve the above purpose, the invention provides the following technical scheme:
the method for preparing α -arteether bulk drug by one-pot method comprises the following steps:
s1, the artemisinin undergoes a reduction reaction under the catalytic action of a catalyst to prepare dihydroartemisinin;
s2 the dihydroartemisinin is etherified with original low carbonate or borate as catalyst to obtain α -arteether bulk drug mixture, the solvent of the etherification is the combination of non-polar organic solvent and ethanol, and the pH value of the reaction system is 1-4.
Preferably, the temperature of the reduction reaction in step S1 is-5 to 10 ℃, and the reaction time is 2 to 3 hours.
Preferably, the catalyst for the reduction reaction is sodium borohydride or potassium borohydride.
Preferably, the amount of the catalyst used in step S1 is 15% -30% of the mass of artemisinin.
Preferably, the reaction solvent in step S1 is absolute ethyl alcohol, and the mass ratio of the artemisinin to the absolute ethyl alcohol is 1: 4-10.
Preferably, the reaction pressure of step S1 is an atmospheric reaction.
Preferably, the nonpolar organic solvent in step S2 is selected from n-hexane, cyclohexane, n-heptane or cycloheptane.
Preferably, the volume ratio of the non-polar organic solvent to ethanol is 2-4: 1.
Preferably, the orthooligocarbonate or borate catalyst of step S2 is selected from triethyl orthoformate, triethyl orthoacetate, diethyl carbonate or triethyl borate.
Further preferably, the orthocarbonate or borate catalyst is used in an amount of 0.2 to 0.5 times the mass of artemisinin.
Preferably, the reaction time of the etherification reaction in the step S2 is 2 to 4 hours.
Preferably, after the etherification reaction in step S2, the step S3 of post-treatment and purification is performed, i.e., the pH is adjusted to be neutral, water is added for extraction, and the organic phase is dried, fine filtered, and concentrated under reduced pressure until no solvent is evaporated to obtain the target α -arteether bulk drug mixture.
Preferably, step S2 further performs the following operations before adding the catalyst: slowly adding acid to adjust the pH value to 2-3, and stirring and reacting for 1-10h at room temperature.
The operation is carried out before the catalyst is added for etherification reaction, the proportion of α -arteether and β -arteether can be adjusted to obtain a mixture of α -arteether and β -arteether which meets the requirements of pharmacopoeia.
As a preferred embodiment, step S2 includes the following operations: removing part of ethanol from the reaction system after the reaction in the step S1, adding a nonpolar organic solvent, simultaneously stirring and cooling to below 30 ℃, adding an acid solution to adjust the pH value to 2-3, stirring and reacting at room temperature for 1-10h, adding an original low carbonate or borate catalyst, continuously keeping the temperature and reacting for 2-4h until the spot content of dihydroartemisinin is less than 1 per thousand, and finishing the reaction.
Preferably, the acid solution is ethanol hydrochloride solution, boron trifluoride diethyl etherate, trimethylchlorosilane solution or acetyl chloride.
Compared with the prior art, the invention has the following beneficial effects:
(1) the invention provides a preparation method of arteether bulk drug with 25-35% of α -arteether and 65-75% of β -arteether, which uses artemisinin as raw material, directly obtains qualified α -arteether bulk drug without producing dihydroartemisinin intermediate in one-pot method, and has the advantages of few reaction steps, high product yield and purity, arteether purity up to more than 98%, and purity requirement specified in pharmacopoeia.
(2) The method provided by the invention does not need complex purification means such as chromatography column, crystallization and recrystallization and the like; only adopts liquid-liquid extraction mode to purify, and has simple operation.
(3) The one-pot synthesis of arteether has higher efficiency, the single process from artemisinin feeding to α -arteether raw material product can be completed in 8-10 hours, 2 batches can be produced in 24 hours every day, and compared with the process for producing intermediate dihydroartemisinin, the time consumption can be shortened by at least half.
(4) The weight yield of the process is 1:1-1.05(α -arteether 25-35%, β -arteether 65-75%) calculated by artemisinin, and the recovery rate of the reaction system is more than 98%;
(5) after-treatment, by means of simple extraction, drying and other forms, impurities such as byproducts, salt, moisture and the like can be well removed, so that the content and the purity of the final arteether can stably meet the requirements of the pharmacopoeia of α -arteether bulk drug.
(6) The invention has the advantages of single solvent, recovery and treatment in each step, low solvent consumption and low cost.
Detailed Description
Example 1
The method for preparing α -arteether bulk drug by one-pot method comprises the following steps:
s1, weighing 100g of artemisinin, adding into a reaction bottle, adding 600mL of absolute ethyl alcohol, stirring and refrigerating, adding 20g of solid sodium borohydride in batches when the temperature in the reaction bottle reaches-5 ℃, finishing adding within about 1 hour, and controlling the reaction temperature to be not more than 10 ℃; after sodium borohydride is added and the reaction is continued for 30min, thin-layer chromatography is carried out, artemisinin spots are completely disappeared, 28mL of acetic acid is added to stop the reaction, and the pH value of the reaction system is 6.5; distilling under reduced pressure to remove 400mL of ethanol, and stopping distillation;
s2, stirring and cooling, adding 400mL of n-hexane while stirring, heating to the internal temperature of 20 ℃, starting to dropwise add 8mL of 20% hydrochloric acid ethanol solution until the pH value of a reaction system is 2, keeping the temperature at 20 ℃ for reaction for 1 hour, adding 22.5mL of triethyl orthoformate serving as a catalyst, continuously keeping the temperature for reaction for 2 hours, carrying out thin layer chromatography, and finishing the reaction when the spot of dihydroartemisinin is less than 1 per thousand;
s3, adding 40mL of 10% sodium bicarbonate solution to reach pH7, continuously adding 250mL, 200mL and 200mL of purified water respectively, extracting for three times, separating liquid, collecting an organic phase, adding 5g of anhydrous sodium sulfate, stirring, drying, standing for 2 hours, finely filtering to obtain an arteether-containing organic phase, concentrating under reduced pressure until the solvent is slowly evaporated, continuously distilling under high vacuum degree and reduced pressure by using an oil pump until no solvent is evaporated, discharging the product while the product is hot, and weighing to obtain 102.5g of light yellow oily matter, namely the target α -arteether bulk drug.
The high performance liquid chromatography determination shows that α -arteether 31.5%, β -arteether 68.5%, arteether total content 101.3%, weight yield 102.5%.
Referring to the specification of α -arteether bulk drug in Indian pharmacopoeia, the pharmaceutical composition has the following physicochemical properties:
1. the characteristics are as follows: a pale yellow oily semisolid;
2. solubility: dissolving in n-hexane, acetone, dichloromethane and ethyl acetate, and dissolving in methanol easily;
3. the contents of the components are 95-105%, α -arteether 25-35% and β -arteether 65-75%.
Example 2
The method for preparing α -arteether bulk drug by one-pot method comprises the following steps:
s1, weighing 100g of artemisinin, adding into a reaction bottle, adding 600mL of absolute ethyl alcohol, stirring and refrigerating, adding 20g of solid sodium borohydride in batches when the temperature in the reaction bottle reaches-5 ℃, finishing adding within about 1 hour, and controlling the reaction temperature to be not more than 10 ℃; after sodium borohydride is added and the reaction is continued for 30min, thin-layer chromatography is carried out, artemisinin spots are completely disappeared, 25mL of acetyl chloride is added to stop the reaction, and the pH value of the reaction system is 6.5; distilling under reduced pressure to remove 400mL of ethanol, and stopping distillation;
s2, stirring and cooling, adding 400mL of cyclohexane while cooling, heating to 20 ℃ of internal temperature, starting to dropwise add 20mL of 50% boron trifluoride diethyl etherate until the pH value of a reaction system is 2, keeping the temperature at 20 ℃ for reaction for 1 hour, adding 22.5mL of catalyst triethyl orthoacetate, keeping the temperature for reaction for 3 hours, carrying out thin layer chromatography, and ending the reaction when the spot of dihydroartemisinin is less than 1 per thousand;
s3, adding 40mL of 10% sodium bicarbonate solution to reach pH7, continuously adding 250mL, 200mL and 200mL of purified water respectively, extracting for three times, separating liquid, collecting an organic phase, adding 5g of anhydrous sodium sulfate, stirring, drying, standing for 2 hours, finely filtering to obtain an arteether-containing organic phase, concentrating under reduced pressure until the solvent is slowly evaporated, continuously distilling under high vacuum degree and reduced pressure by using an oil pump until no solvent is evaporated, discharging the product while the product is hot, and weighing to obtain 104.5g of light yellow oily substance, namely the target α -arteether bulk drug.
The high performance liquid chromatography determination shows that α -arteether 28.5%, β -arteether 71.5%, arteether total content 102.0%, and weight yield 104.5%.
Example 3
The method for preparing α -arteether bulk drug by one-pot method comprises the following steps:
s1, weighing 100g of artemisinin, adding into a reaction bottle, adding 600mL of absolute ethyl alcohol, stirring and refrigerating, adding 18g of solid sodium borohydride in batches when the temperature in the reaction bottle reaches-5 ℃, finishing adding within about 1 hour, and controlling the reaction temperature to be not more than 10 ℃; after sodium borohydride is added and the reaction is continued for 30min, thin-layer chromatography is carried out, artemisinin spots are completely disappeared, 100mL of sulfuric acid ethanol solution containing 12.5mL of concentrated sulfuric acid is added to stop the reaction, and the pH value of the reaction system is 6.5; distilling under reduced pressure to remove 500mL of ethanol (namely 200mL of residual ethanol), and stopping distillation;
s2, stirring and cooling, adding 400mL of n-heptane while cooling, heating to 20 ℃ of internal temperature, starting dropwise adding 9mL of trimethylchlorosilane solution until the pH value of a reaction system is 2, keeping the temperature at 20 ℃ for reaction for 1 hour, adding 22mL of triethyl borate serving as a catalyst, continuing to keep the temperature for reaction for 3 hours, carrying out thin layer chromatography, and finishing the reaction when the spot of dihydroartemisinin is less than 1 per thousand;
s3, adding 40mL of 10% sodium bicarbonate solution to reach pH7, continuously adding 250mL, 200mL and 200mL of purified water respectively, extracting for three times, separating liquid, collecting an organic phase, adding 5g of anhydrous sodium sulfate, stirring, drying, standing for 2 hours, finely filtering to obtain an arteether-containing organic phase, concentrating under reduced pressure until the solvent is slowly evaporated, continuously distilling under high vacuum degree and reduced pressure by using an oil pump until no solvent is evaporated, discharging the product while the product is hot, and weighing to obtain 101.7g of light yellow oily matter, namely the target α -arteether bulk drug.
The content of α -arteether 25.5%, β -arteether 74.5%, arteether total content 101.3%, and weight yield 101.7% were determined by high performance liquid chromatography.
Example 4
The method for preparing α -arteether bulk drug by one-pot method comprises the following steps:
s1, weighing 100g of artemisinin, adding into a reaction bottle, adding 800mL of absolute ethyl alcohol, stirring and refrigerating, adding 27g of solid potassium borohydride in batches when the temperature in the reaction bottle reaches-5 ℃, finishing adding within about 1 hour, and controlling the reaction temperature to be not more than 10 ℃; after the potassium borohydride is added and the reaction is continued for 30min, thin-layer chromatography is carried out, artemisinin spots are completely disappeared, 26mL of acetic acid is added to stop the reaction, and the pH value of the reaction system is 6.5; distilling under reduced pressure to remove 600mL of ethanol, and stopping distillation;
s2, stirring and cooling, adding 400mL of normal hexane while stirring, heating to 20 ℃ of internal temperature, starting to dropwise add 7mL of acetyl chloride until the pH value of a reaction system is 2, keeping the temperature at 20 ℃ for reaction for 1 hour, adding 24.5mL of diethyl carbonate serving as a catalyst, continuing to keep the temperature for reaction for 6 hours, carrying out thin layer chromatography, and ending the reaction when the spot size of dihydroartemisinin is less than 1 per thousand;
s3, adding 40mL of 10% sodium bicarbonate solution to reach pH7, continuously adding 250mL, 200mL and 200mL of purified water respectively, extracting for three times, separating liquid, collecting an organic phase, adding 5g of anhydrous sodium sulfate, stirring, drying, standing for 2 hours, finely filtering to obtain an arteether-containing organic phase, concentrating under reduced pressure until the solvent is slowly evaporated, continuously distilling under high vacuum degree and reduced pressure by using an oil pump until no solvent is evaporated, discharging the product while the product is hot, and weighing to obtain 100.2g of light yellow oily matter, namely the target α -arteether bulk drug.
The high performance liquid chromatography determination shows that α -arteether 31.6%, β -arteether 68.4%, arteether total content 99.8%, and weight yield 100.2%.
Example 5
The method for preparing α -arteether bulk drug by one-pot method comprises the following steps:
s1, weighing 100g of artemisinin, adding into a reaction bottle, adding 800mL of absolute ethyl alcohol, stirring and refrigerating, adding 30g of solid potassium borohydride in batches when the temperature in the reaction bottle reaches-5 ℃, finishing adding within about 1 hour, and controlling the reaction temperature to be not more than 10 ℃; after the potassium borohydride is added and the reaction is continued for 30min, thin-layer chromatography is carried out, artemisinin spots are completely disappeared, 30mL of acetic acid is added to stop the reaction, and the pH value of the reaction system is 6.5; distilling under reduced pressure to remove 600mL of ethanol, and stopping distillation;
s2, stirring and cooling, adding 400mL of normal hexane while stirring, heating to 20 ℃ of internal temperature, starting dropwise adding 18mL of 50% boron trifluoride diethyl ether until the pH value of a reaction system is 2, adding 21.5mL of catalyst triethyl orthoformate, continuously keeping the temperature for reaction for 4 hours, carrying out thin layer chromatography, and finishing the reaction when the spot of dihydroartemisinin is less than 1 per thousand;
s3, adding 40mL of 10% sodium bicarbonate solution to reach pH7, continuously adding 250mL, 200mL and 200mL of purified water respectively, extracting for three times, separating liquid, collecting an organic phase, adding 5g of anhydrous sodium sulfate, stirring, drying, standing for 2 hours, finely filtering to obtain an arteether-containing organic phase, concentrating under reduced pressure until the solvent is slowly evaporated, continuously distilling under high vacuum degree and reduced pressure by using an oil pump until no solvent is evaporated, discharging the product while the product is hot, and weighing to obtain 102.7g of light yellow oily matter, namely the target α -arteether bulk drug.
The high performance liquid chromatography determination shows that α -arteether 30.1%, β -arteether 69.9%, arteether total content 100.1%, weight yield 102.7%.
Finally, it should be noted that the above-mentioned contents are only used for illustrating the technical solutions of the present invention, and not for limiting the protection scope of the present invention, and that the simple modifications or equivalent substitutions of the technical solutions of the present invention by those of ordinary skill in the art can be made without departing from the spirit and scope of the technical solutions of the present invention.
Claims (10)
1. A method for preparing α -arteether bulk drug by a one-pot method comprises the following steps:
s1, the artemisinin undergoes a reduction reaction under the catalytic action of a catalyst to prepare dihydroartemisinin;
s2 the dihydroartemisinin is etherified with original low carbonate or borate as catalyst to obtain α -arteether bulk drug mixture, the solvent of the etherification is the combination of non-polar organic solvent and ethanol, and the pH value of the reaction system is 1-4.
2. The one-pot method for preparing α -arteether bulk drug according to claim 1,
the temperature of the reduction reaction in the step S1 is-5 to 10 ℃, and the reaction time is 2 to 3 hours.
3. The one-pot method for preparing α -arteether bulk drug according to claim 1,
the catalyst for the reduction reaction is sodium borohydride or potassium borohydride.
4. The one-pot method for preparing α -arteether bulk drug according to claim 1,
the nonpolar organic solvent in step S2 is selected from n-hexane, cyclohexane, n-heptane, or cycloheptane.
5. The one-pot method for preparing α -arteether bulk drug according to claim 1,
step S2 the orthooligocarbonate or boronate catalyst is selected from triethyl orthoformate, triethyl orthoacetate, diethyl carbonate or triethyl borate.
6. The one-pot method of preparing α -arteether bulk drug according to claim 5,
the dosage of the original low carbonate or borate catalyst is 0.2-0.5 times of the mass of the artemisinin.
7. The one-pot method for preparing α -arteether bulk drug according to claim 1,
the reaction time of the etherification reaction in the step S2 is 2 to 4 hours.
8. The one-pot method of preparing α -arteether bulk drug according to any one of claims 1-7,
and (S2) after the etherification reaction is finished, carrying out post-treatment and purification in the step S3, namely adjusting the pH to be neutral, adding water for extraction, drying an organic phase, carrying out fine filtration, and carrying out reduced pressure concentration until no solvent is evaporated to obtain a target α -arteether bulk drug mixture.
9. The one-pot method of preparing α -arteether bulk drug according to any one of claims 1-7,
step S2 also performs the following operations before adding the catalyst: slowly adding acid to adjust the pH value to 2-3, and stirring and reacting for 1-10h at room temperature.
10. The one-pot method for preparing α -arteether bulk drug according to claim 1,
the mass ratio of the two isomers in the arteether bulk drug is α -arteether 25-35%, β -arteether 65-75%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911102258.1A CN110835349A (en) | 2019-11-12 | 2019-11-12 | Method for preparing α -arteether bulk drug by one-pot method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911102258.1A CN110835349A (en) | 2019-11-12 | 2019-11-12 | Method for preparing α -arteether bulk drug by one-pot method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110835349A true CN110835349A (en) | 2020-02-25 |
Family
ID=69575096
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911102258.1A Pending CN110835349A (en) | 2019-11-12 | 2019-11-12 | Method for preparing α -arteether bulk drug by one-pot method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110835349A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114524824A (en) * | 2022-02-25 | 2022-05-24 | 张家港威胜生物医药有限公司 | Green production process for preparing arteether |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6346631B1 (en) * | 2000-03-24 | 2002-02-12 | Council Of Scientific And Industrial Research | Process for the preparation of arteethers from dihydroartemisinin |
| CN1694887A (en) * | 2002-11-29 | 2005-11-09 | 科学与工业研究委员会 | Single pot conversion of artemisinin into arteether |
| CN103570740A (en) * | 2013-11-12 | 2014-02-12 | 重庆华方武陵山制药有限公司 | Preparation process of artemether |
| CN104557965A (en) * | 2013-11-12 | 2015-04-29 | 上海佰纳医药科技有限公司 | Preparation technology for beta-artemether |
| CN104725395A (en) * | 2013-12-20 | 2015-06-24 | 上海迪赛诺化学制药有限公司 | Technology for preparing beta-artemether |
-
2019
- 2019-11-12 CN CN201911102258.1A patent/CN110835349A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6346631B1 (en) * | 2000-03-24 | 2002-02-12 | Council Of Scientific And Industrial Research | Process for the preparation of arteethers from dihydroartemisinin |
| CN1694887A (en) * | 2002-11-29 | 2005-11-09 | 科学与工业研究委员会 | Single pot conversion of artemisinin into arteether |
| CN103570740A (en) * | 2013-11-12 | 2014-02-12 | 重庆华方武陵山制药有限公司 | Preparation process of artemether |
| CN104557965A (en) * | 2013-11-12 | 2015-04-29 | 上海佰纳医药科技有限公司 | Preparation technology for beta-artemether |
| CN104725395A (en) * | 2013-12-20 | 2015-06-24 | 上海迪赛诺化学制药有限公司 | Technology for preparing beta-artemether |
Non-Patent Citations (1)
| Title |
|---|
| A. BROSSI ET AL.: "Arteether, a New Antimalarial Drug: Synthesis and Antimalarial Properties", 《J.MED.CHEM.》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114524824A (en) * | 2022-02-25 | 2022-05-24 | 张家港威胜生物医药有限公司 | Green production process for preparing arteether |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20190144414A1 (en) | Method for purifying cannabinoid compounds | |
| EP1414775B1 (en) | Bicyclic cannabinoid | |
| WO2006093745A1 (en) | Purification of rapamycin | |
| CN105061414B (en) | One kettle way prepares Brexpiprazole | |
| CN101146809A (en) | Process for preparing quinoline compounds and products obtained therefrom | |
| US6346631B1 (en) | Process for the preparation of arteethers from dihydroartemisinin | |
| CN110835349A (en) | Method for preparing α -arteether bulk drug by one-pot method | |
| CN114292236A (en) | Preparation method of etomidate intermediate | |
| CN102050714B (en) | Method for synthesizing Teprenone | |
| CN102993135B (en) | A kind of purification process of orlistat | |
| KR101676512B1 (en) | Method for producing olmesartan medoxomil | |
| CN104725395A (en) | Technology for preparing beta-artemether | |
| CN111116490A (en) | Preparation and purification method of oxalagogri intermediate salicylate | |
| CN1687025A (en) | New technique for synthesizing aglycon of soybean | |
| CN102516233B (en) | Method for producing voriconazole | |
| CN112047815B (en) | Preparation method of cannabidiol compound | |
| CN113354647A (en) | Ganciclovir sodium synthesis process | |
| AU2002236753B2 (en) | An improved process for preparing pure ondansetron hydrochloride dihydrate | |
| CN112409182A (en) | Synthesis, purification and separation method of menthyl lactate | |
| CN111440181A (en) | Dipyrazolo seven-membered oxygen heterocyclic compound containing quinoline structure and synthetic method thereof | |
| CN108084049B (en) | Preparation method of posaconazole intermediate | |
| CN115785057B (en) | Preparation method of ticagrelor intermediate compound and salt thereof | |
| CN112898306B (en) | Preparation method of barretinib | |
| CN113801089B (en) | Preparation method of clenbuterol intermediate | |
| CN101570564B (en) | Method for refining tanshinone II A acrylic acid |
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 | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20200225 |