CN109675624A - A kind of no copper Click catalytic reaction system and its application - Google Patents
A kind of no copper Click catalytic reaction system and its application Download PDFInfo
- Publication number
- CN109675624A CN109675624A CN201811428695.8A CN201811428695A CN109675624A CN 109675624 A CN109675624 A CN 109675624A CN 201811428695 A CN201811428695 A CN 201811428695A CN 109675624 A CN109675624 A CN 109675624A
- Authority
- CN
- China
- Prior art keywords
- reaction system
- copper click
- catalytic reaction
- click
- ionic liquid
- 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0277—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature
- B01J31/0278—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature containing nitrogen as cationic centre
- B01J31/0279—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature containing nitrogen as cationic centre the cationic portion being acyclic or nitrogen being a substituent on a ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention discloses a kind of no copper Click catalytic reaction system and its applications, belong to Click catalytic reaction system technical field.Technical solution of the present invention main points are as follows: no copper Click catalytic reaction system is ionic liquid, cation in the ionic liquid are as follows:Anion in ionic liquid are as follows:
Description
Technical field
The invention belongs to Click catalytic reaction system technical fields, and in particular to a kind of no copper Click catalytic reaction system
And its application.
Background technique
In the past few years, contain 1,2,3- triazole structures molecule be found to have the antiviral of wide spectrum, antibacterial,
Antimycotic and anticancer bioactive inhibits to live as 1,2,3- 3-triazole compounds of Fourth Ring show good serine protease
Property；The thio dioxide of nucleoside derivates t-butyldimethylsilyl spiral shell amino oxygen is accredited as effective non-nucleosides and reverses
Transcriptase inhibitors.In addition, the application of 1,2,3- triazole is not limited only to drug discovery, but also it is widely used in many other grind
Field is studied carefully, such as bioconjugate, macromolecular chemistry and polymer science.
Classical Huisgen 1,3- Dipolar Cycloaddition is using end alkynes and nitrine as raw material, in the condition of high-temperature heating
Under obtain 1,4- replace and 1,5- replace 1,2,3- triazole mixture.The discovery of Sharpless and Medal group, copper catalysis
End alkynes and nitrine Dipolar Cycloaddition (CuAAC reaction) can efficiently prepare under mild conditions 1,4- substitution
1,2,3- triazole, but Isosorbide-5-Nitrae, 5- polysubstituted 1,2,3- triazoles cannot be prepared.Further, since the biology poison of metallic copper
Property, make it is copper-promoted into CuAAC react in bio-orthogonal reaction application be restricted.In recent years, ionic liquid zwitterion
Synergistic effect make it show good catalytic activity in many organic reactions, but it is in no metal catalytic
There is not been reported for application in Click reaction.
Summary of the invention
The technical problem to be solved by the present invention is to provide a kind of efficiently without copper Click catalytic reaction system, the catalytic body
System can promote the efficient progress of Click reaction under mild conditions.
The present invention adopts the following technical scheme that solve above-mentioned technical problem, a kind of no copper Click catalytic reaction system,
It is characterized in that this without copper Click catalytic reaction system is ionic liquid, cation in ionic liquid are as follows:
Anion in ionic liquid are as follows:
No copper Click catalytic reaction system of the present invention is promoting without the application in copper Click reaction.
No copper Click catalytic reaction system of the present invention is promoting to react preparation 1,4,5- substitution -1 without copper Click,
Application in 2,3- triazole compounds, it is characterised in that detailed process are as follows: with azide compounds and dicarbapentaborane class chemical combination
Object is reaction substrate, reacts under the facilitation of no copper Click catalytic reaction system in 50 DEG C and target product Isosorbide-5-Nitrae, 5- is made
Replace -1,2,3- triazole compounds, wherein azide compounds are Dicarbapentaborane class compound is Synthesis process
In reaction equation:
No copper Click catalytic reaction system of the present invention is promoting to react preparation 1,4,5- substitution -1 without copper Click,
Application in 2,3- triazole compounds, it is characterised in that specific steps are as follows: sequentially add nitrine class in the reaction vessel
It closes object, dicarbapentaborane class compound and without copper Click catalytic reaction system, 2h is stirred to react in 50 DEG C, is examined in reaction process with TLC
It surveys, uses the mixed extractant solvent of ethyl acetate and distilled water after reaction, organic phase extracted is dry with anhydrous sodium sulfate,
Crude product is obtained after being spin-dried for, then obtains target product Isosorbide-5-Nitrae through column chromatography separating purification, and 5- replaces -1,2,3- triazole chemical combination
Object, water phase extracted divide water to be spin-dried for, then at 40 DEG C of vacuum drying recycling are without copper Click catalytic reaction system and repetitive cycling makes
With.
Further preferably, the molar ratio of the azide compounds, dicarbapentaborane class compound and ionic liquid is 1:
1:1。
Further preferably, the volume ratio of the in the mixed solvent ethyl acetate and distilled water of the ethyl acetate and distilled water is
1:1。
Compared with the prior art, the present invention has the following advantages:
1, the catalyst system ionic liquid used in the present invention is prepared easy, cheap and easy to get, and has mild acid-base property；
2, the reaction system carries out under solvent-free conditions, efficiently avoids the use of toxic solvent；
3, the present invention is not necessarily to the use of metallic copper in the process of reaction；
4, catalyst system good substrate applicability of the invention, the substrate of different substituents have good yield and selection
Property；
5, catalyst system of the invention has good chemo-selective, and conversion zone is selectively generating Isosorbide-5-Nitrae, and 5- takes
Generation -1,2,3- triazole compound；
6, catalyst system of the invention can be recycled repeatedly, and its catalytic activity is held essentially constant.
Specific embodiment
Above content of the invention is described in further details by the following examples, but this should not be interpreted as to this
The range for inventing above-mentioned theme is only limitted to embodiment below, and all technologies realized based on above content of the present invention belong to this hair
Bright range.
Embodiment 1
Meta-methoxy benzyl azide 0.20mmol, ethyl acetoacetate 0.20mmol is taken to be placed in dry reaction flask, so
Ionic liquid A2B5 0.20mmol is added afterwards, is stirred to react 2h in 50 DEG C, reaction process is detected with TLC, uses body after reaction
Product is than being that the ethyl acetate of 1:1 and the mixed extractant solvent of distilled water are spin-dried for obtaining crude product, and the crude product is through silica gel column chromatography
Isolated target product, separation yield are 91%.
Embodiment 2
It takes and methoxy-benzyl nitrine 0.20mmol, ethyl acetoacetate 0.20mmol is placed in dry reaction flask, so
Ionic liquid A2B5 0.20mmol is added afterwards, is stirred to react 2h in 50 DEG C, reaction process is detected with TLC, uses body after reaction
Product is than being that the ethyl acetate of 1:1 and the mixed extractant solvent of distilled water are spin-dried for obtaining crude product, and the crude product is through silica gel column chromatography
Isolated target product, separation yield are 92%.
Embodiment 3
O-methoxy benzyl azide 0.20mmol, ethyl acetoacetate 0.20mmol is taken to be placed in dry reaction flask, so
Ionic liquid A1B3 0.20mmol is added afterwards, is stirred to react 2h in 50 DEG C, reaction process is detected with TLC, uses body after reaction
Product is than being that the ethyl acetate of 1:1 and the mixed extractant solvent of distilled water are spin-dried for obtaining crude product, and the crude product is through silica gel column chromatography
Isolated target product, separation yield are 85%.
Embodiment 4
Take and luorobenzyl nitrine 0.20mmol, ethyl acetoacetate 0.20mmol be placed in dry reaction flask, then plus
Enter ionic liquid A1B2 0.20mmol, be stirred to react 2h in 50 DEG C, reaction process is detected with TLC, uses volume ratio after reaction
It is spin-dried for obtaining crude product for the ethyl acetate of 1:1 and the mixed extractant solvent of distilled water, which separates through silica gel column chromatography
Target product is obtained, separation yield is 93%.
Embodiment 5
It takes and nitrobenzyl nitrine 0.20mmol, ethyl acetoacetate 0.20mmol is placed in dry reaction flask, then
Ionic liquid A3B4 0.20mmol is added, is stirred to react 2h in 50 DEG C, reaction process is detected with TLC, uses volume after reaction
Mixed extractant solvent than ethyl acetate and distilled water for 1:1 is spin-dried for obtaining crude product, and the crude product is through silica gel column chromatography point
From target product is obtained, separation yield is 90%.
Embodiment 6
Take and bromobenzyl nitrine 0.20mmol, ethyl acetoacetate 0.20mmol be placed in dry reaction flask, then plus
Enter ionic liquid A1B5 0.20mmol, be stirred to react 2h in 50 DEG C, reaction process is detected with TLC, uses volume ratio after reaction
It is spin-dried for obtaining crude product for the ethyl acetate of 1:1 and the mixed extractant solvent of distilled water, which separates through silica gel column chromatography
Target product is obtained, separation yield is 93%.
Embodiment 7
Take o-chlorobenzyl nitrine 0.20mmol, ethyl acetoacetate 0.20mmol to be placed in dry reaction flask, then plus
Enter ionic liquid A2B5 0.20mmol, be stirred to react 2h in 50 DEG C, reaction process is detected with TLC, uses volume ratio after reaction
It is spin-dried for obtaining crude product for the ethyl acetate of 1:1 and the mixed extractant solvent of distilled water, which separates through silica gel column chromatography
Target product is obtained, separation yield is 91%.
Embodiment 8
M-trifluoromethyl benzyl azide 0.20mmol, ethyl acetoacetate 0.20mmol is taken to be placed in dry reaction flask,
Then ionic liquid A2B4 0.20mmol is added, is stirred to react 2h in 50 DEG C, reaction process is detected with TLC, is used after reaction
Volume ratio is that the ethyl acetate of 1:1 and the mixed extractant solvent of distilled water are spin-dried for obtaining crude product, and the crude product is through silicagel column color
Isolated target product is composed, separation yield is 95%.
Embodiment 9
3,5- dimethyl benzyl nitrine 0.20mmol, ethyl acetoacetate 0.20mmol is taken to be placed in dry reaction flask,
Then ionic liquid A4B3 0.20mmol is added, is stirred to react 2h in 50 DEG C, reaction process is detected with TLC, is used after reaction
Volume ratio is that the ethyl acetate of 1:1 and the mixed extractant solvent of distilled water are spin-dried for obtaining crude product, and the crude product is through silicagel column color
Isolated target product is composed, separation yield is 92%.
Embodiment 10
Isosorbide-5-Nitrae-dimethyl benzyl nitrine 0.20mmol, ethyl acetoacetate 0.20mmol is taken to be placed in dry reaction flask,
Then ionic liquid A4B1 0.20mmol is added, is stirred to react 2h in 50 DEG C, reaction process is detected with TLC, is used after reaction
Volume ratio is that the ethyl acetate of 1:1 and the mixed extractant solvent of distilled water are spin-dried for obtaining crude product, and the crude product is through silicagel column color
Isolated target product is composed, separation yield is 90%.
Embodiment 11
Meta-methoxy benzyl azide 0.20mmol, trifluoroacetic ethyl acetoacetate 0.20mmol is taken to be placed in dry reaction flask
In, ionic liquid A3B5 0.20mmol is then added, is stirred to react 2h in 50 DEG C, reaction process is detected with TLC, and reaction terminates
The mixed extractant solvent of the ethyl acetate and distilled water that are afterwards 1:1 with volume ratio is spin-dried for obtaining crude product, and the crude product is through silica gel
Pillar layer separation obtains target product, and separation yield is 90%.
Embodiment 12
Meta-methoxy benzyl azide 0.20mmol, isobutyl acetoacetate 0.20mmol is taken to be placed in dry reaction flask,
Then ionic liquid A2B5 0.20mmol is added, is stirred to react 2h in 50 DEG C, reaction process is detected with TLC, is used after reaction
Volume ratio is that the ethyl acetate of 1:1 and the mixed extractant solvent of distilled water are spin-dried for obtaining crude product, and the crude product is through silicagel column color
Isolated target product is composed, separation yield is 91%.
Embodiment 13
Meta-methoxy benzyl azide 0.20mmol, tert-butyl acetoacetate 0.20mmol is taken to be placed in dry reaction flask,
Then ionic liquid A3B1 0.20mmol is added, is stirred to react 2h in 50 DEG C, reaction process is detected with TLC, is used after reaction
Volume ratio is that the ethyl acetate of 1:1 and the mixed extractant solvent of distilled water are spin-dried for obtaining crude product, and the crude product is through silicagel column color
Isolated target product is composed, separation yield is 90%.
Embodiment 14
Meta-methoxy benzyl azide 0.20mmol, acetoacetate acrylic ester 0.20mmol is taken to be placed in dry reaction flask,
Then ionic liquid A4B4 0.20mmol is added, is stirred to react 2h in 50 DEG C, reaction process is detected with TLC, is used after reaction
Volume ratio is that the ethyl acetate of 1:1 and the mixed extractant solvent of distilled water are spin-dried for obtaining crude product, and the crude product is through silicagel column color
Isolated target product is composed, separation yield is 89%.
Embodiment 15
It takes and methoxy-benzyl nitrine 0.20mmol, ethyl benzoylacetate 0.20mmol is placed in dry reaction flask,
Then ionic liquid A5B2 0.20mmol is added, is stirred to react 2h in 50 DEG C, reaction process is detected with TLC, is used after reaction
Volume ratio is that the ethyl acetate of 1:1 and the mixed extractant solvent of distilled water are spin-dried for obtaining crude product, and the crude product is through silicagel column color
Isolated target product is composed, separation yield is 91%.
Embodiment 16
Take and methoxyl group nitrine 0.20mmol, ethyl butyrylacetate 0.20mmol be placed in dry reaction flask, then plus
Enter ionic liquid A4B1 0.20mmol, be stirred to react 2h in 50 DEG C, reaction process is detected with TLC, uses volume ratio after reaction
It is spin-dried for obtaining crude product for the ethyl acetate of 1:1 and the mixed extractant solvent of distilled water, which separates through silica gel column chromatography
Target product is obtained, separation yield is 90%.
Embodiment 17
Meta-methoxy benzyl azide 0.20mmol, dibenzoyl methane 0.20mmol is taken to be placed in dry reaction flask,
Then ionic liquid choline A2B3 0.20mmol is added, is stirred to react 2h in 50 DEG C, reaction process is detected with TLC, and reaction terminates
The mixed extractant solvent of the ethyl acetate and distilled water that are afterwards 1:1 with volume ratio is spin-dried for obtaining crude product, and the crude product is through silica gel
Pillar layer separation obtains target product, and separation yield is 91%.
Embodiment 18
It takes and methylbenzyl nitrine 0.20mmol, ethyl acetoacetate 0.20mmol is placed in dry reaction flask, then
Ionic liquid A3B3 0.20mmol is added, is stirred to react 2h in 50 DEG C, reaction process is detected with TLC, uses volume after reaction
Mixed extractant solvent than ethyl acetate and distilled water for 1:1 is spin-dried for obtaining crude product, and the crude product is through silica gel column chromatography point
From target product is obtained, separation yield is 93%.
Embodiment 19
It takes and dry reaction is placed in methoxy-benzyl nitrine 0.20mmol, 4- methoxyl group methyl acetoacetate 0.20mmol
In bottle, ionic liquid A2B2 0.20mmol is then added, is stirred to react 2h in 50 DEG C, reaction process is detected with TLC, reaction knot
Shu Houyong volume ratio is that the ethyl acetate of 1:1 and the mixed extractant solvent of distilled water are spin-dried for obtaining crude product, and the crude product is through silicon
Rubber column gel column chromatographic isolation obtains target product, and separation yield is 90%.
Embodiment 20
Situation is recycled in catalyst system
Using aziminobenzene and ethyl acetoacetate as reaction model, under 50 DEG C of reaction conditions, using A2B5 as catalyst.
After reaction, after the mixed extractant solvent of the ethyl acetate and distilled water that are 1:1 with volume ratio, target product is dissolved in organic phase
In, during ionic liquid is soluble in the aqueous phase, most of water in water phase is spin-dried for, it is sufficiently dry in 40 DEG C of vacuum ovens, it obtains
Ionic liquid as catalyst be directly used in next step react.After ionic-liquid catalyst repetitive cycling uses 5 times, ionic liquid
The catalytic activity of body is not substantially reduced.
Embodiment above describes basic principles and main features of the invention and advantage, the technical staff of the industry should
Understand, the present invention is not limited to the above embodiments, and the above embodiments and description only describe originals of the invention
Reason, under the range for not departing from the principle of the invention, various changes and improvements may be made to the invention, these changes and improvements are each fallen within
In the scope of protection of the invention.
Claims (6)
1. a kind of no copper Click catalytic reaction system, it is characterised in that this is ionic liquid without copper Click catalytic reaction system,
It is cationic in ionic liquid are as follows:
Anion in ionic liquid are as follows:
2. no copper Click catalytic reaction system described in claim 1 is promoting without the application in copper Click reaction.
3. no copper Click catalytic reaction system described in claim 1 is promoting to react preparation 1,4,5- substitution-without copper Click
Application in 1,2,3- triazole compound, it is characterised in that detailed process are as follows: with azide compounds and dicarbapentaborane class
Conjunction object is reaction substrate, reacts under the facilitation of no copper Click catalytic reaction system in 50 DEG C and target product Isosorbide-5-Nitrae is made,
5- replaces -1,2,3- triazole compounds, and wherein azide compounds are Dicarbapentaborane class compound is Synthesis process
In reaction equation:
4. no copper Click catalytic reaction system according to claim 3 is promoting to take without copper Click reaction preparation 1,4,5-
Application in -1,2,3- triazole compounds of generation, it is characterised in that specific steps are as follows: sequentially add nitrine in the reaction vessel
Class compound, dicarbapentaborane class compound and without copper Click catalytic reaction system, 2h is stirred to react in 50 DEG C, is used in reaction process
TLC detection, uses the mixed extractant solvent of ethyl acetate and distilled water, organic phase anhydrous sodium sulfate extracted after reaction
Drying obtains crude product, then obtains target product Isosorbide-5-Nitrae through column chromatography separating purification after being spin-dried for, 5- replaces -1,2,3- triazoles
Compound, water phase extracted divide water to be spin-dried for, and without copper Click catalytic reaction system and repeat to follow then at 40 DEG C of vacuum drying recycling
Ring uses.
5. no copper Click catalytic reaction system according to claim 4 is promoting to take without copper Click reaction preparation 1,4,5-
Generation -1,2,3- triazole compounds in application, it is characterised in that: the azide compounds, dicarbapentaborane class compound with
The molar ratio of ionic liquid is 1:1:1.
6. no copper Click catalytic reaction system according to claim 4 is promoting to take without copper Click reaction preparation 1,4,5-
Application in -1,2,3- triazole compounds of generation, it is characterised in that: the in the mixed solvent second of the ethyl acetate and distilled water
The volume ratio of acetoacetic ester and distilled water is 1:1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811428695.8A CN109675624A (en) | 2018-11-27 | 2018-11-27 | A kind of no copper Click catalytic reaction system and its application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811428695.8A CN109675624A (en) | 2018-11-27 | 2018-11-27 | A kind of no copper Click catalytic reaction system and its application |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN109675624A true CN109675624A (en) | 2019-04-26 |
Family
ID=66185059
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811428695.8A Pending CN109675624A (en) | 2018-11-27 | 2018-11-27 | A kind of no copper Click catalytic reaction system and its application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109675624A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130310569A1 (en) * | 2012-05-21 | 2013-11-21 | Hunaid Nulwala | Triazolide based ionic liquids |
| CN105061340A (en) * | 2015-08-31 | 2015-11-18 | 河南师范大学 | Method for preparing 1,2,3-triazoie compound through active-carbon-carried nano-copper catalyst in catalyzed synthesis mode |
| CN105949136A (en) * | 2016-05-13 | 2016-09-21 | 河南师范大学 | Synthetic method of 1,5-substituted-1,2,3-triazole compounds |
| CN105949240A (en) * | 2016-05-13 | 2016-09-21 | 河南师范大学 | Method for synthesizing 4-phosphonic acid-1,5-substituted-1,2,3 triazole compounds through catalysis of ionic liquid |
| CN108440503A (en) * | 2018-04-10 | 2018-08-24 | 张海英 | The preparation method of the disubstituted quinazoline medicinal compound of the parent nucleus containing triazole |
-
2018
- 2018-11-27 CN CN201811428695.8A patent/CN109675624A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130310569A1 (en) * | 2012-05-21 | 2013-11-21 | Hunaid Nulwala | Triazolide based ionic liquids |
| CN105061340A (en) * | 2015-08-31 | 2015-11-18 | 河南师范大学 | Method for preparing 1,2,3-triazoie compound through active-carbon-carried nano-copper catalyst in catalyzed synthesis mode |
| CN105949136A (en) * | 2016-05-13 | 2016-09-21 | 河南师范大学 | Synthetic method of 1,5-substituted-1,2,3-triazole compounds |
| CN105949240A (en) * | 2016-05-13 | 2016-09-21 | 河南师范大学 | Method for synthesizing 4-phosphonic acid-1,5-substituted-1,2,3 triazole compounds through catalysis of ionic liquid |
| CN108440503A (en) * | 2018-04-10 | 2018-08-24 | 张海英 | The preparation method of the disubstituted quinazoline medicinal compound of the parent nucleus containing triazole |
Non-Patent Citations (1)
| Title |
|---|
| 王景梅 等: "1,2,3-三唑化合物的合成研究进展", 《有机化学》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9598425B2 (en) | Method for preparing Ibrutinib | |
| KR101333620B1 (en) | Crystals of morphinan derivative and process for producing the same | |
| CN105107545A (en) | Application of ionic liquid catalyst | |
| CN105085373A (en) | Purification method of apremilast product | |
| CN101381389B (en) | Chemical synthesis method of 5,7-diene steroids compounds | |
| CN108484536B (en) | Synthetic method of orlistat intermediate of weight-reducing drug | |
| CN109675624A (en) | A kind of no copper Click catalytic reaction system and its application | |
| CN104945341A (en) | Method for synthesizing 1,2,3-triazole compound through three components in one pot | |
| CN108047138A (en) | Preparation method without hydrazine N-BETA-Alanyl-L-histidine | |
| CN104356069A (en) | Preparation method and application of high-purity olmesartan medoxomil intermediate ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazolyl-5-carboxylate | |
| CN105949136B (en) | A kind of synthetic method of 1,5- substitution -1,2,3- triazole compound | |
| CN112979552A (en) | Preparation method of high-purity dexmedetomidine hydrochloride | |
| CN102775450A (en) | Method for preparing 1,6-Anhydro-2-azido-2-deoxy-beta-D-glucopyranose | |
| CN107353256A (en) | The method of the triazole compounds of 4 acetyl group of one pot process 1,2,3 | |
| CN106905177A (en) | A kind of preparation method of the biphenyl propionic acid ethyl ester derivative hydrochloride of 2 amino 3 | |
| CN103193712B (en) | A kind of preparation method of N-BETA-Alanyl-L-histidine | |
| CN104072577A (en) | Method for preparing S-acetyl-L-glutathione | |
| CN104387327A (en) | Synthetic method of 3, 4-dihydropyrimidinone medicine intermediates | |
| CN109503501A (en) | DBU class ionic liquid is promoting without the application in copper Click reaction | |
| CN105968065B (en) | A kind of preparation method of COX-2 inhibitors SC 69124 intermediate | |
| CN103288764A (en) | Quinhydroxy ketone glycine ester hydrochloride and preparation method thereof | |
| CN103130702A (en) | Method for synthesizing 3-substituted indole and 2,3-disubstituted indole | |
| CN108033906A (en) | A kind of preparation method of Silodosin intermediate | |
| WO2019153453A1 (en) | Method for preparing d-borneol | |
| RU2268877C1 (en) | Method for preparing 2-chloro-4-nitrophenol |
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: 20190426 |