CN108059647A - A kind of synthetic method of alclometasone diproionate intermediate 11- β monohydric pregnants - Google Patents
A kind of synthetic method of alclometasone diproionate intermediate 11- β monohydric pregnants Download PDFInfo
- Publication number
- CN108059647A CN108059647A CN201810068164.6A CN201810068164A CN108059647A CN 108059647 A CN108059647 A CN 108059647A CN 201810068164 A CN201810068164 A CN 201810068164A CN 108059647 A CN108059647 A CN 108059647A
- Authority
- CN
- China
- Prior art keywords
- formula
- reaction
- compound
- monohydric
- pregnants
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/008—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms substituted in position 21
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to field of pharmaceutical preparations, and in particular to a kind of synthetic method of 11 β monohydric pregnants of alclometasone diproionate intermediate.It is using II compound of formula as raw material, and progress radical reaction obtains 11 β monohydric pregnants under the effect of zinc powder, chromium chloride hexahydrate and thioacetic acid.Method provided by the invention is easy to operate, and yield is higher, is suitble to industrial production.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, and in particular to a kind of alclometasone diproionate intermediate 11- β monohydric pregnants
Synthetic method.
Background technology
Alclometasone diproionate be low middle effect corticosteroid medication, pharmacological testing research show its with it is anti-inflammatory,
The effect of antiallergy, anti-proliferate.Clinically alclometasone diproionate has anti-inflammatory, antipruritic and pressor effect.Usually recognize
Be corticosteroid by inducing lipocortin class, inhibition of phospholipase A 2 hydrolyses membrane phospholipids release arachidonic acid, before controlling
The biosynthesis of the inflammatory mediators such as row parathyrine and leukotriene plays anti-inflammatory effect, and 11- β monohydric pregnants are as dipropionic acid Ah chlorine's rice
A loose very crucial intermediate, structural formula are：
The method of prior art synthesis 11- β monohydric pregnants has：
United States Patent (USP) US5426198 is using zinc powder, thioacetic acid, chromium trichloride in N, N-dimethylformamide and tetrahydrochysene furan
Mixed solvent of muttering is reacted, and is reacted in room temperature and reflux having groped temperature respectively, and room temperature needs reacted for 2.5 days,
When back flow reaction needs 1.1 are small, the method purity is 80~95%, and the higher production cost of reaction time long energy consumption is high, is not suitable for
Industrialized production.
11- α hydroxyls are introduced with microbe transformation method, then 11- α hydroxyls are converted into the side of 11- β hydroxyls with chemical synthesis
Method is to introduce 11- β in steroidal synthesis both at home and abroad at present, and the most common method of hydroxyl, party's law technology is immature, synthetic route
Long, the production cycle is long, and production cost is high, is not suitable for industrial industrialization.
Therefore a kind of reaction condition of personnel of the present invention's exploitation is mild, and easy to operate, the used time is short and product purity is high
11- β monohydric pregnants preparation method.
The content of the invention
In view of this, it is an object of the invention to provide a kind of method for preparing 11- β monohydric pregnants, there is reaction item
The advantages of part is mild, and reaction required time is short and easy to operate.
To achieve the above object, the technical scheme is that：
11- β monohydric pregnants are occurred by II compound represented of formula under the effect of zinc powder, chromium chloride hexahydrate and thioacetic acid
Radical reaction generates, and the solvent of reaction is n,N dimethylformamide, acetone, N, the one or more of N dimethyl acetamide,
Reaction equation is as follows：
As preferred scheme, the reaction temperature of above-mentioned radical reaction is -50~50 DEG C.
It is further preferred that the reaction temperature of radical reaction is -10~10 DEG C.
As preferred scheme, the molar ratio of above-mentioned II compound of formula and solvent is 1:1.0~20.0, it is preferably 1.0:
1.0~10.0, further preferably 1.0:5.0~10.0.
As preferred scheme, the molar ratio of above-mentioned II compound of formula and zinc powder is 1:1.0~10.0.
It is further preferred that above-mentioned II compound of formula and the molar ratio of zinc powder are 1.0:1.0~5.0, further preferably
1.0:1.0~3.0.
As preferred scheme, the molar ratio of above-mentioned II compound of formula and thioacetic acid is 1:1.0~10.0.
It is further preferred that the molar ratio of above-mentioned II compound of formula and thioacetic acid is 1:1.0~5.0, further preferably
For 1.0:1.0~3.0.
As preferred scheme, the molar ratio of above-mentioned II compound of formula and chromium chloride hexahydrate is 1:0.1~5.0.
It is further preferred that above-mentioned II compound of formula and the molar ratio of chromium chloride hexahydrate are 1:0.1~2.0, further
Preferably 1.0:0.1~1.0.
As preferred scheme, when the reaction time of above-mentioned radical reaction is 0.5~5 small.
The above-mentioned method for preparing 11- β monohydric pregnants, comprises the following steps：
1) chromium trichloride, II compound of zinc powder, thioacetic acid and formula are added under oxygen free condition in a solvent, free radical occurs
Reaction, obtains solution 1；
2) solution 1 is poured into ice water, centrifuged, precipitation after tetrahydrofuran dissolved clarification with filtering to get filtrate；
3) filtrate is concentrated, ethyl acetate is added in and petroleum ether is refining to obtain product 11- β monohydric pregnants.
As preferred scheme, the step of above-mentioned preparation method, is：
1) solvent and chromium trichloride are added under nitrogen protection deoxygenation conditions in a kettle, cooled down after stirring dissolved clarification；It adds in
Thioacetic acid is added dropwise in zinc powder, heat preservation, and II compound of formula and solvent mixed solution is added dropwise.
2) reaction solution is poured into ice water after the completion of reacting, is filtered, filter cake after tetrahydrofuran dissolved clarification with adding in anhydrous slufuric acid
Sodium is dried.
3) add in ethyl acetate after filtrate concentration and petroleum ether refines and can obtain 11- β monohydric pregnants.
The second object of the present invention is to provide the 11- β monohydric pregnants that a kind of method by purpose one is prepared have
There is the advantages of product purity is high, the reaction time is short, substantially increase production efficiency.
To achieve the above object, the technical scheme is that：
11- β monohydric pregnants are occurred by II compound represented of formula under the effect of zinc powder, chromium chloride hexahydrate and thioacetic acid
Radical reaction generates, and reaction equation is as follows：
As preferred scheme, the solvent of reaction is n,N dimethylformamide, acetone, N, one kind of N dimethyl acetamide
It is or a variety of.
The above-mentioned method for preparing 11- β monohydric pregnants, comprises the following steps：
1) chromium trichloride, II compound of zinc powder, thioacetic acid and formula, -50~50 DEG C of generation free radicals are added in a solvent
Reaction, obtains solution 1；
2) solution 1 is poured into ice water, centrifuged, precipitation after tetrahydrofuran dissolved clarification with filtering to get filtrate；
3) filtrate is concentrated, ethyl acetate is added in and petroleum ether is refining to obtain product 11- β monohydric pregnants.
The third object of the present invention is that providing a kind of 11- β monohydric pregnants of purpose two is being used to prepare dipropionic acid Ah chlorine
The purposes of meter Song, key intermediate 11- β monohydric pregnants to be prepared by the method for purpose one, have product purity it is high,
The advantages of reaction time is short.
The beneficial effects of the present invention are：It is provided by the invention to prepare alclometasone diproionate intermediate 11- β monohydric pregnants
Method, has the following advantages：
1. reaction condition is mild, easy to operate, without solvent extraction；
2. shortening preparation time, when the entire process time is 6.0~10 small, lower production cost, greatly improve production effect
Rate, more conducively production industrialization；
3. process stabilizing, impurity is no more than 1%, 11- β monohydric pregnants high purity more than 99% in product.
Description of the drawings
Fig. 1 is the chromatogram of 1 product of embodiment
Fig. 2 is the chromatogram of 2 product of embodiment
Specific embodiment
The preferred embodiment of the present invention will be described in detail (referring to the drawings) below.Tool is not specified in preferred embodiment
The experimental method of concrete conditions in the establishment of a specific crime, usually according to normal condition, illustrated embodiment is to preferably be said to present disclosure
It is bright, but be not that present disclosure is only limitted to illustrated embodiment.So those skilled in the art are according to foregoing invention
Content carries out nonessential modifications and adaptations to embodiment, still falls within protection scope of the present invention.
Embodiment 1
1) in the case where vacuumizing logical nitrogen deoxygenation conditions, dried and clean 50L reaction kettles add in chromium trichloride 1.2kg and
21.5L dimethylformamides stir dissolved clarification, are cooled to -5~5 DEG C of addition zinc powder 1.2kg, then 1.4kg thioacetic acid is added dropwise, and keep
II compound of 3.4kg formulas dissolved with 17.2L dimethylformamides is slowly added dropwise at -10~0 DEG C, mixed liquor has been taken out very
The logical nitrogen deoxidation of sky；
2) when constant temperature -10~0 DEG C reaction 0.5~1.0 is small, (acetone=4: 1) thin-layered chromatography monitors TLC chloroform:
Raw material disappears；
3) reaction solution is poured into the ice water of 0~5 DEG C of 164L, stirring 10~centrifuge after twenty minutes, filter cake 40.0L tetra-
When addition anhydrous sodium sulfate drying 1 is small after hydrogen furans stirring dissolved clarification, filtering；
4) filtrate is concentrated until cutout, and addition petroleum ether and stirring crystallization 1~2 is small after residue adds in ethyl acetate dissolved clarification
When, centrifugation, filter cake is put into vacuum drying chamber in vacuum degree≤- 0.08MPa, 40~50 DEG C be dried under reduced pressure 1.5~2.5 it is small when, obtain
To product 3.24kg, yield 90%, purity 99.2%.Product chromatogram is shown in Fig. 1, and product chromatography testing result is shown in Table 1.
1 product chromatography testing result of table
| Peak # | Retention time | Area | Highly | Area % | Theoretical tray # | Tailing factor | Separating degree |
| 1 | 9.529 | 39542 | 2012 | 0.113 | 5121 | 1.035 | 0.000 |
| 2 | 11.466 | 151549 | 6067 | 0.435 | 5363 | 0.869 | 3.342 |
| 3 | 15.658 | 34597379 | 1092036 | 99.238 | 5956 | 1.222 | 5.831 |
| 4 | 21.866 | 74734 | 1613 | 0.214 | 6358 | 0.835 | 6.505 |
| It amounts to | 34863204 | 1101729 | 100.000 |
Embodiment 2
1) in the case where vacuumizing logical nitrogen deoxygenation conditions, dried and clean 10L reaction kettles add in chromium trichloride 161.5g and
3.0L dimethyl acetamides stir dissolved clarification, are cooled to -5~5 DEG C of addition zinc powder 157.5g, then 161.5g thioacetic acid is added dropwise, and protect
The 600g Formula II compounds being slowly added dropwise at -10~0 DEG C with 2.4L dimethylacetamide amine solvents are held, mixed liquor has been taken out very
The logical nitrogen deoxidation of sky；
2) when constant temperature -10~0 DEG C reaction 0.5~1.0 is small, (acetone=4: 1) thin-layered chromatography monitors TLC chloroform:
Raw material disappears；
3) reaction solution is poured into the ice water of 0~5 DEG C of 24L, stirring 10~centrifuge after twenty minutes, filter cake 8.0L tetrahydrochysenes
When addition anhydrous sodium sulfate drying 1 is small after furans stirring dissolved clarification, filtering；
4) filtrate is concentrated until cutout, and addition petroleum ether and stirring crystallization 1~2 is small after residue adds in ethyl acetate dissolved clarification
When, centrifugation, filter cake is put into vacuum drying chamber in vacuum degree≤- 0.08MPa, 40~50 DEG C be dried under reduced pressure 1.5~2.5 it is small when, obtain
To product 464.6g, yield 92.0%, purity 99.1%.Product chromatogram is shown in Fig. 2, and product chromatography testing result is shown in Table 2.
2 product chromatography testing result of table
| Peak # | Retention time | Area | Highly | Area % | Theoretical tray # | Tailing factor | Separating degree |
| 1 | 4.752 | 22332 | 1411 | 0.063 | 2225 | 1.340 | 0.000 |
| 2 | 8.027 | 9161 | 442 | 0.026 | 3241 | 1.022 | 6.776 |
| 3 | 11.391 | 42289 | 1612 | 0.119 | 4078 | 0.989 | 5.266 |
| 4 | 12.179 | 5932 | 265 | 0.017 | 6510 | 1.245 | 1.196 |
| 5 | 13.990 | 170235 | 4581 | 0.478 | 3679 | 0.815 | 2.373 |
| 6 | 19.987 | 35295179 | 774453 | 99.100 | 4649 | 1.191 | 5.724 |
| 7 | 29.422 | 70556 | 1191 | 0.198 | 5411 | 1.074 | 6.806 |
| It amounts to | 35615683 | 783954 | 100.000 |
Embodiment 3
1) in the case where vacuumizing logical nitrogen deoxygenation conditions, dried and clean 10L reaction kettles add in chromium trichloride 113.0g and
1.0L dimethylformamides and 1.1L acetone stirring dissolved clarification, are cooled to -5~5 DEG C of addition zinc powder 110.2gg, then 140.6g are added dropwise
Thioacetic acid holds the 420g Formula II compounds of the dropwise addition 1.7L dimethylacetamides amine solvent slowly at -10~0 DEG C, mixed liquor
Evacuated logical nitrogen deoxidation；
2) when constant temperature -10~0 DEG C reaction 0.5~1.0 is small, (acetone=4: 1) thin-layered chromatography monitors TLC chloroform:
Raw material disappears；
3) reaction solution is poured into the ice water of 0~5 DEG C of 20L, stirring 10~centrifuge after twenty minutes, filter cake 7.0L tetrahydrochysenes
When addition anhydrous sodium sulfate drying 1 is small after furans stirring dissolved clarification, filtering；
4) filtrate is concentrated until cutout, and addition petroleum ether and stirring crystallization 1~2 is small after residue adds in ethyl acetate dissolved clarification
When, centrifugation, filter cake is put into vacuum drying chamber in vacuum degree≤- 0.08MPa, 40~50 DEG C be dried under reduced pressure 1.5~2.5 it is small when, obtain
To product 300.0g, yield 85%, purity 99.2%.
By above example can when 6~10 is small it is interior react and purify obtain 11- β monohydric pregnants, 11- β in product
Monohydric pregnant high purity more than 99%.The reaction condition for preparing 11- β monohydric pregnants provided by the invention is mild, operation letter
It is single, production cost is greatly reduced, improves production efficiency, suitable for industrialized production.
Finally illustrate, the above embodiments are merely illustrative of the technical solutions of the present invention and it is unrestricted, although with reference to compared with
The present invention is described in detail in good embodiment, it will be understood by those of ordinary skill in the art that, it can be to the skill of the present invention
Art scheme is modified or replaced equivalently, and without departing from the objective and scope of technical solution of the present invention, should all be covered at this
Among the right of invention.
Claims (10)
- A kind of 1. method for preparing 11- β monohydric pregnants, which is characterized in that using II compound represented of formula as raw material, with N, N bis- Methylformamide, acetone, N, the one or more of N dimethyl acetamide are solvent, in zinc powder, chromium chloride hexahydrate and sulfydryl second Acid effect issues raw radical reaction generation 11- β monohydric pregnants, and reaction equation is as follows：
- 2. according to the method described in claim 1, it is characterized in that, the temperature of the radical reaction is -50~50 DEG C.
- 3. according to the method described in claim 2, it is characterized in that, the temperature of the radical reaction is -10~10 DEG C.
- 4. according to the method described in claim 1, it is characterized in that, when the reaction time of the reaction is 0.5~5 small.
- 5. according to the method described in claim 1, it is characterized in that, II compound of the formula and the molar ratio of zinc powder are 1:1.0 ~10.0.
- 6. according to the method described in claim 1, it is characterized in that, the molar ratio of II compound of the formula and thioacetic acid is 1: 1.0~10.0.
- 7. according to the method described in claim 1, it is characterized in that, II compound of the formula and the molar ratio of chromium chloride hexahydrate For 1:0.1~5.0.
- 8. according to claim 1~7 any one of them method, which is characterized in that comprise the following steps：1) chromium trichloride, zinc powder, thioacetic acid and II compound of formula are added under oxygen free condition in a solvent, radical reaction occur, Obtain solution 1；2) solution 1 is poured into ice water, centrifuged, precipitation obtains filtrate with being filtered after tetrahydrofuran dissolved clarification；3) filtrate is concentrated, ethyl acetate is added in and petroleum ether is refining to obtain product 11- β monohydric pregnants.
- 9. the 11- β monohydric pregnants prepared by claim 1~8 any one of them method.
- 10. the 11- β monohydric pregnants described in claim 9 are being used to prepare the application of alclometasone diproionate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810068164.6A CN108059647B (en) | 2018-01-24 | 2018-01-24 | Synthesis method of alclometasone dipropionate intermediate 11-beta hydroxy pregna |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810068164.6A CN108059647B (en) | 2018-01-24 | 2018-01-24 | Synthesis method of alclometasone dipropionate intermediate 11-beta hydroxy pregna |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108059647A true CN108059647A (en) | 2018-05-22 |
| CN108059647B CN108059647B (en) | 2020-10-20 |
Family
ID=62141795
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810068164.6A Active CN108059647B (en) | 2018-01-24 | 2018-01-24 | Synthesis method of alclometasone dipropionate intermediate 11-beta hydroxy pregna |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108059647B (en) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109651477A (en) * | 2019-02-21 | 2019-04-19 | 湖南科瑞生物制药股份有限公司 | A method of preparing the dehydrogenation rear center body product of Aclovate |
| CN109651476A (en) * | 2019-02-21 | 2019-04-19 | 湖南科瑞生物制药股份有限公司 | A method of preparing the reduction rear center body product of Aclovate |
| CN109651478A (en) * | 2019-02-21 | 2019-04-19 | 湖南科瑞生物制药股份有限公司 | A method of preparing the dehydrogenation rear center body of Aclovate |
| CN109666054A (en) * | 2019-02-21 | 2019-04-23 | 湖南科瑞生物制药股份有限公司 | A method of preparing Aclovate product |
| CN109678920A (en) * | 2019-02-21 | 2019-04-26 | 湖南科瑞生物制药股份有限公司 | A method of preparing Aclovate |
| CN109776643A (en) * | 2019-02-21 | 2019-05-21 | 湖南科瑞生物制药股份有限公司 | A method of preparing the etherificate rear center body of Aclovate |
| CN109796515A (en) * | 2019-02-21 | 2019-05-24 | 湖南科瑞生物制药股份有限公司 | A method of preparing the reduction rear center body of Aclovate |
| CN109796514A (en) * | 2019-02-21 | 2019-05-24 | 湖南科瑞生物制药股份有限公司 | A method of Aclovate is prepared by etherificate rear center body |
| CN112375114A (en) * | 2020-11-12 | 2021-02-19 | 湖南新合新生物医药有限公司 | Preparation method of prednisolone acetate |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5426198A (en) * | 1987-08-14 | 1995-06-20 | The Upjohn Company | 9α-dehalogenation process |
| CN102746357A (en) * | 2011-04-22 | 2012-10-24 | 天津金耀集团有限公司 | Technology for synthesizing reduced steroid |
| CN107400153A (en) * | 2017-04-23 | 2017-11-28 | 浙江仙琚制药股份有限公司 | A kind of preparation method of hydrocortisone acetate |
-
2018
- 2018-01-24 CN CN201810068164.6A patent/CN108059647B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5426198A (en) * | 1987-08-14 | 1995-06-20 | The Upjohn Company | 9α-dehalogenation process |
| CN102746357A (en) * | 2011-04-22 | 2012-10-24 | 天津金耀集团有限公司 | Technology for synthesizing reduced steroid |
| CN107400153A (en) * | 2017-04-23 | 2017-11-28 | 浙江仙琚制药股份有限公司 | A kind of preparation method of hydrocortisone acetate |
Non-Patent Citations (1)
| Title |
|---|
| HO-JANE SHUE等: "Synthesis and structure-activity studies in a series of 7.alpha.-halogeno corticosteroids", 《JOURNAL OF MEDICINAL CHEMISTRY》 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109651477A (en) * | 2019-02-21 | 2019-04-19 | 湖南科瑞生物制药股份有限公司 | A method of preparing the dehydrogenation rear center body product of Aclovate |
| CN109651476A (en) * | 2019-02-21 | 2019-04-19 | 湖南科瑞生物制药股份有限公司 | A method of preparing the reduction rear center body product of Aclovate |
| CN109651478A (en) * | 2019-02-21 | 2019-04-19 | 湖南科瑞生物制药股份有限公司 | A method of preparing the dehydrogenation rear center body of Aclovate |
| CN109666054A (en) * | 2019-02-21 | 2019-04-23 | 湖南科瑞生物制药股份有限公司 | A method of preparing Aclovate product |
| CN109678920A (en) * | 2019-02-21 | 2019-04-26 | 湖南科瑞生物制药股份有限公司 | A method of preparing Aclovate |
| CN109776643A (en) * | 2019-02-21 | 2019-05-21 | 湖南科瑞生物制药股份有限公司 | A method of preparing the etherificate rear center body of Aclovate |
| CN109796515A (en) * | 2019-02-21 | 2019-05-24 | 湖南科瑞生物制药股份有限公司 | A method of preparing the reduction rear center body of Aclovate |
| CN109796514A (en) * | 2019-02-21 | 2019-05-24 | 湖南科瑞生物制药股份有限公司 | A method of Aclovate is prepared by etherificate rear center body |
| CN112375114A (en) * | 2020-11-12 | 2021-02-19 | 湖南新合新生物医药有限公司 | Preparation method of prednisolone acetate |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108059647B (en) | 2020-10-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108059647A (en) | A kind of synthetic method of alclometasone diproionate intermediate 11- β monohydric pregnants | |
| CN106256824B (en) | Preparation method of high-purity delafloxacin meglumine salt | |
| CN101648957B (en) | Preparation method of sesamin phenol | |
| CN103319548A (en) | Purification method for cane sugar-6-acetate | |
| CN103665084A (en) | Method for preparing abiraterone acetate | |
| CN107304186B (en) | Refining method of olaparib | |
| CN106146403B (en) | A kind of purification process of the miscellaneous Shandong amine of grace | |
| CN107827911B (en) | 7-phenylacetylaminocephalosporanic acid composite crystal and preparation method thereof | |
| CN108726539B (en) | Preparation process of high-purity anhydrous sodium iodide powder | |
| CN108440521B (en) | Method for preparing fibrauretine from salting-out waste liquid in fibrauretine production | |
| CN108822062A (en) | A kind of refining methd of docetaxel | |
| CN112645906A (en) | Method for separating and purifying paclitaxel by high-efficiency chromatography | |
| CN111410632A (en) | Regorafenib refining method | |
| CN107709313B (en) | Method for preparing trityl candesartan | |
| CN111484458B (en) | Preparation method of 2-hydroxy-5-sulfonic pyrimidine | |
| CN111377840A (en) | Preparation method of R- (+) -dihydrolipoic acid | |
| CN114573467B (en) | Synthesis process of 2, 4-dimethyl-3-aminobenzoic acid | |
| CN112409420B (en) | Purification method of 2 '-fluoro-2' -deoxyuridine | |
| CN112979706A (en) | Refining method of disodium levoornidazole phosphate impurity | |
| CN110386928B (en) | Azilsartan synthesis process | |
| CN114369073B (en) | Method for preparing high-purity hydrochlorothiazide | |
| US11208419B2 (en) | Phenylbenzofuran compound, preparation method therefor, composition containing the same and medical application thereof | |
| CN110372605B (en) | Synthesis method of 2-methylthio-4, 6-dichloro-5-nitropyrimidine | |
| CN107459537B (en) | Method for extracting, separating and purifying mannose oligosaccharide from yeast | |
| CN109734762B (en) | Method for synthesizing 16- β methyl steroid compound by one-pot method |
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 | ||
| TA01 | Transfer of patent application right | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20190307 Address after: 401520 No. 666 Rongjun Road, Nanjin Street Subdistrict Office, Hechuan District, Chongqing Applicant after: Chongqing Huapont Pharm. Co., Ltd. Address before: 401121 No. 69 Ren Xingguang Avenue, Yubei District, Chongqing Applicant before: Chongqing Huapont Pharm. Co., Ltd. |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant |