CN102690281A - Synthetic method of 1-methyl 4-pyrazole pinacol ester - Google Patents
Synthetic method of 1-methyl 4-pyrazole pinacol ester Download PDFInfo
- Publication number
- CN102690281A CN102690281A CN2011100677831A CN201110067783A CN102690281A CN 102690281 A CN102690281 A CN 102690281A CN 2011100677831 A CN2011100677831 A CN 2011100677831A CN 201110067783 A CN201110067783 A CN 201110067783A CN 102690281 A CN102690281 A CN 102690281A
- Authority
- CN
- China
- Prior art keywords
- methyl
- pinacol ester
- reaction
- pyrazoles
- compound 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
- 0 C*1C(*OC)=CC=*1 Chemical compound C*1C(*OC)=CC=*1 0.000 description 2
Abstract
The invention relates to a synthetic method of 1-methyl 4-pyrazole pinacol ester. The biggest advantage of the invention is that the technology is greatly improved; and the problem that the preparation technology of 1-methyl 4-pyrazole pinacol ester is limited in a laboratory and there is no large-scale production is solved. The technical scheme provided by the invention is as follows: the synthetic method of 1-methyl 4-pyrazole pinacol ester comprises The following steps of: Step 1, performing a reaction between 1-methyl 4-pyrazole and triisopropyl borate under the action of n-butyllithium to obtain an intermediate A; and Step 2, performing a reaction between the intermediate A and pinacol under the action of magnesium sulfate to obtain the target product 1-methyl 4-pyrazole pinacol ester. The obtained 1-methyl 4-pyrazole pinacol ester is an important intermediate commonly-used in pharmaceutical chemistry.
Description
Technical field
The present invention relates to 1-methyl 4-pyrazoles pinacol ester preparation method.
Background technology
At present 1-methyl 4-pyrazoles pinacol ester preparation method has following two kinds, method one: with 1-methylpyrazole and Virahol tetramethyl ethylene ketone boric acid ester is starting raw material, with n-Butyl Lithium-78
oC reaction, cancellation be after washing, dichloromethane extraction, obtain after concentrating thick product 1-methyl 4-pyrazoles pinacol ester (
Ref:WO2009158376).Synthetic route is as follows:
This synthetic route is inappropriate for technical scale and produces in batches, and reason is following: the dichloromethane solution that extraction obtains directly concentrates the dried bullion that obtains, and is not suitable for suitability for industrialized production.Thick product does not pass through purifying, directly is used for a following step.
Method two: with 1-methylpyrazole and tetramethyl ethylene ketone borine is starting raw material, reaction at normal temperatures, through pentane washing, obtain after concentrating thick product 1-methyl 4-pyrazoles pinacol ester (
Ref:US2008091027).Synthetic route is as follows:
This synthetic route is inappropriate for technical scale and produces in batches, and reason is following: raw materials used tetramethyl ethylene ketone borine is somewhat expensive, and cost is high.The pentane solution that extraction obtains directly concentrates the dried bullion that obtains, and is not suitable for suitability for industrialized production.Thick product does not pass through purifying, directly is used for a following step.
More than the major defect of these two kinds of technologies be that aftertreatment is difficult for amplifying, product does not have purifying, is not suitable for large-scale production.Therefore, find a kind of compound method of high yield, make this technology large-scale application on producing, just become the key issue that the present invention need solve.
Summary of the invention
The object of the invention is to provide the compound method of a kind of industriallization, whole yield is higher, preparation cost is low 1-methyl 4-pyrazoles pinacol ester.Effectively prepare the method for 1-methyl 4-pyrazoles pinacol ester, the preparation that has solved existing 1-methyl 4-pyrazoles pinacol ester is confined to prepared in laboratory, problem that can't large-scale production.
Technical scheme of the present invention: a kind of compound method of 1-methyl 4-pyrazoles pinacol ester may further comprise the steps: the first step, 1-methyl 4-pyrazoles obtain midbody with the triisopropyl borate ester reaction under the n-Butyl Lithium effect
ASecond step, midbody
AAnd tetramethyl ethylene ketone (pinacol) reacts under the sal epsom effect and obtains title product 1-methyl 4-pyrazoles boric acid pinacol ester
B
Concrete synthesis route of the present invention is following:
Concrete reaction conditions is following: described the first step reaction: raw material 1-methyl 4-pyrazoles and anhydrous tetrahydro furan are added in the reaction flask, and solution cools to-60 ~-70
oC slowly drips 1.1 ~ 1.2 equivalent n-Butyl Lithiums (2.5M hexane solution), and the control dropping temperature is no more than-60
oC is-60 ~-70
oC reacts 2 ~ 3h, slowly drips triisopropyl borate ester again, continues-60 ~-70
oC reacts 2 ~ 3h, rises to room temperature (20 ~ 30 ℃, the back together) reaction 8 ~ 12h afterwards, and reaction is cooled to 0 ~ 10 after finishing
oC with saturated ammonium chloride solution cancellation reaction solution, regulates pH to 5 ~ 6, standing demix with the hydrochloric acid soln of 2N.Water layer concentrates organic layer with ethyl acetate extraction three times, adds normal heptane displacement anhydrous tetrahydro furan, and organic layer is concentrated into about 4 times of volumes, and spissated solution is crystallization 3h at room temperature.Filter, filter cake is used the normal heptane rinsing, and drying obtains midbody
A
Described second step reaction: successively with midbody
A, tetramethyl ethylene ketone, anhydrous tetrahydro furan adds in the reaction flask, and stirring at normal temperature to solid dissolves; Add anhydrous magnesium sulfate afterwards, react 8 ~ 12h under the room temperature, reaction finishes after-filtration; Mother liquor is with 10 times of volume washings twice, and organic layer is concentrated into 1 ~ 2 times of volume, and solution is cooled to-10 ~ 0
oC stirs 4 ~ 6h.Filter, drying obtains title product 1-methyl 4-pyrazoles pinacol ester
B
Beneficial effect of the present invention: sharpest edges of the present invention are that technology has been done bigger improvement, have optimized aftertreatment technology, filter twice organic layer of after washing, make solvent with normal heptane then, are cooled to-10 ~ 0
oThe C crystallization obtains the high purity final product.The present invention obtains title product through two-step reaction, and two step total recoverys are about 72%, obtain purity greater than 98% final product.Avoid original process that solvent directly is concentrated into and done the shortcoming that can't realize suitability for industrialized production.This technical process raw material is cheap, easy handling, and the required PT is shorter, has reduced production cost; Both be fit to laboratory short run preparation, be fit to carry out large-scale industrial production again.
Embodiment
Following embodiment is explained content of the present invention better, but the present invention is not limited to following instance.Reaction formula is following:
Embodiment 1
The first step: under mechanical stirring, will (1.22mol, 100g)
SMAdd in the there-necked flask with the 2L anhydrous tetrahydro furan, solution cools to-60 ~-70
oC, (the control dropping temperature is no more than-60 for 1.34 mol, 535mL) n-Butyl Lithium (2.5M hexane solution) in slowly dropping
oC dropwises-60 ~-70
oC reacts 3h, and (the control dropping temperature is no more than-60 for 1.34 mol, 252g) triisopropyl borate ester in slowly dropping in reaction solution
oC continues-60 ~-70
oC reacts 3h, slowly is warming up to room temperature, reacts 12h under the room temperature, and the sampling detection reaction is qualified.Be cooled to 0 ~ 10
oC is added drop-wise to the saturated aqueous ammonium chloride of 2L in the reaction solution, with the hydrochloric acid soln of 2N pH is transferred to 5, standing demix.Water layer merges organic layer with 2L ethyl acetate extraction three times, and organic layer is concentrated into 300mL.Add 2L normal heptane displacement anhydrous tetrahydro furan, be concentrated into 400mL, spissated solution is stirring and crystallizing 3h at room temperature.Filter, with 100mL normal heptane rinsing filter cake once, drying obtains the white solid midbody
A(136g ，>99% HPLC purity, productive rate 89%).
Second step: successively with (1.03mol, 130g) midbody
A, (1.13 mol, 134g) tetramethyl ethylene ketone, 1.3L anhydrous tetrahydro furan add in the there-necked flask; Stirring at normal temperature 10min dissolves to solid, and (0.52mol, 62.4g) anhydrous magnesium sulfate react 12h under the room temperature in adding; The sampling detection reaction finishes, and filters, and mother liquor is concentrated into about 150mL, adds the 1.3L normal heptane; With 1.4L washing twice, organic layer is concentrated into about 130mL, and solution is cooled to-10 ~-5
oC stirs 6h.Filter, drying obtains white solid 1-methyl 4-pyrazoles pinacol ester (171g,>98% HPLC purity, productive rate 80%).
Embodiment 2
The first step: under mechanical stirring, will (1.22mol, 100g)
SMAdd in the there-necked flask with the 2L anhydrous tetrahydro furan, solution cools to-60 ~-70
oC, (the control dropping temperature is no more than-60 for 1.46mol, 585mL) n-Butyl Lithium (2.5M) in slowly dropping
oC dropwises-60 ~-70
oC reacts 2.5h, and (the control dropping temperature is no more than-60 for 1.34 mol, 252g) triisopropyl borate ester in slowly dropping in reaction solution
oC continues-60 ~-70
oC reacts 2.5h, slowly is warming up to room temperature, and normal temperature is reaction 10h down, and the sampling detection reaction is qualified.Be cooled to 0 ~ 10
oC is added drop-wise to the saturated aqueous ammonium chloride of 2L in the reaction solution, with the hydrochloric acid soln of 2N pH is transferred to 5, standing demix.Water layer merges organic layer with 2L ethyl acetate extraction three times, and organic layer is concentrated into 300mL.Add 2L normal heptane displacement anhydrous tetrahydro furan, be concentrated into 400mL, spissated solution is stirring and crystallizing 3h at room temperature.Filter, with 100mL normal heptane rinsing filter cake once, drying obtains white solid
A(131g ，>99 %HPLC purity, productive rate 86%).
Second step: incite somebody to action successively (1.03mol, 130g)
A, (1.13 mol, 134g) tetramethyl ethylene ketone, the anhydrous tetrahydro furan of 1.3L add in the there-necked flask; Stirring at normal temperature 10min dissolves to solid, and (0.52mol, 62.4g) anhydrous magnesium sulfate react 10h under the room temperature in adding; The sampling detection reaction finishes, and filters, and mother liquor is concentrated into about 150mL, adds the 1.3L normal heptane; With 1.4L washing twice, organic layer is concentrated into about 130mL, and solution is cooled to-10 ~-5
oC stirs 5h.Filter, drying obtains white solid 1-methyl 4-pyrazoles pinacol ester (171g,>98% HPLC purity, productive rate 80%).
Embodiment 3
The first step: under mechanical stirring, will (1.22mol, 100g)
SMAdd in the there-necked flask with the 2L anhydrous tetrahydro furan, solution cools to-60 ~-70
oC, (the control dropping temperature is no more than-60 for 1.34 mol, 535mL) n-Butyl Lithium (2.5M) in slowly dropping
oC dropwises-60 ~-70
oC reacts 3h, and (the control dropping temperature is no more than-60 for 1.34 mol, 252g) triisopropyl borate ester in slowly dropping in reaction solution
oC continues-60 ~-70
oC reacts 3h, slowly is warming up to room temperature, and normal temperature is reaction 12h down, and the sampling detection reaction is qualified.Be cooled to 0 ~ 10
oC is added drop-wise to the saturated aqueous ammonium chloride of 2L in the reaction solution, with the hydrochloric acid soln of 2N pH is transferred to 6, standing demix.Water layer merges organic layer with 2L ethyl acetate extraction three times, and organic layer is concentrated into 300mL.Add 2L normal heptane displacement anhydrous tetrahydro furan, be concentrated into 400mL, spissated solution is stirring and crystallizing 3h at room temperature.Filter, with 100mL normal heptane rinsing filter cake once, drying obtains white solid
A(130g ，>99% HPLC purity, productive rate 85.5%).
Second step: incite somebody to action successively (1.03mol, 130g)
A, (1.13 mol, 134g) tetramethyl ethylene ketone, the anhydrous tetrahydro furan of 1.3L add in the there-necked flask; Stirring at normal temperature 10min dissolves to solid, and (0.52mol, 62.4g) anhydrous magnesium sulfate react 8h under the room temperature in adding; The sampling detection reaction finishes, and filters, and mother liquor is concentrated into about 150mL, adds the 1.3L normal heptane; With 1.4L washing twice, organic layer is concentrated into about 130mL, and solution is cooled to-10 ~-5
oC stirs 6h.Filter, drying obtains white solid 1-methyl 4-pyrazoles pinacol ester (171g,>98 %HPLC purity, productive rate 80%).
Embodiment 4
The first step: under mechanical stirring, will (1.22mol, 100g)
SMAdd in the there-necked flask with the 2L anhydrous tetrahydro furan, solution cools to-60 ~-70
oC, (the control dropping temperature is no more than-60 for 1.34 mol, 535mL) n-Butyl Lithium (2.5M) in slowly dropping
oC dropwises-60 ~-70
oC reacts 3h, and (the control dropping temperature is no more than-60 for 1.34 mol, 252g) triisopropyl borate ester in slowly dropping in reaction solution
oC continues-60 ~-70
oC reacts 3h, slowly is warming up to room temperature, and normal temperature is reaction 8h down, and the sampling detection reaction is qualified.Be cooled to 0 ~ 10
oC is added drop-wise to the saturated aqueous ammonium chloride of 2L in the reaction solution, with the hydrochloric acid soln of 2N pH is transferred to 5, standing demix.Water layer merges organic layer with 2L ethyl acetate extraction three times, and organic layer is concentrated into 300mL.Add 2L normal heptane displacement anhydrous tetrahydro furan, be concentrated into 400mL, spissated solution is stirring and crystallizing 3h at room temperature.Filter, with 100mL normal heptane rinsing filter cake once, drying obtains white solid
A(136g ，>99 HPLC purity, productive rate 89%).
Second step: incite somebody to action successively (1.03mol, 130g)
A, (1.13 mol, 134g) tetramethyl ethylene ketone, the anhydrous tetrahydro furan of 1.3L add in the there-necked flask; Stirring at normal temperature 10min dissolves to solid, and (0.52mol, 62.4g) anhydrous magnesium sulfate react 12h under the room temperature in adding; The sampling detection reaction finishes, and filters, and mother liquor is concentrated into about 150mL, adds the 1.3L normal heptane; With 1.4L washing twice, organic layer is concentrated into about 260mL, and solution is cooled to-10 ~-5
oC stirs 6h.Filter, drying obtains white solid 1-methyl 4-pyrazoles pinacol ester (167g,>98% HPLC purity, productive rate 78%).
Embodiment 5
The first step: under mechanical stirring, will (1.22mol, 100g)
SMAdd in the there-necked flask with the 2L anhydrous tetrahydro furan, solution cools to-60 ~-70
oC, (the control dropping temperature is no more than-60 for 1.34 mol, 535mL) n-Butyl Lithium (2.5M) in slowly dropping
oC dropwises-60 ~-70
oC reacts 3h, and (the control dropping temperature is no more than-60 for 1.34 mol, 252g) triisopropyl borate ester in slowly dropping in reaction solution
oC continues-60 ~-70
oC reacts 3h, slowly is warming up to room temperature, and normal temperature is reaction 8h down, and the sampling detection reaction is qualified.Be cooled to 0 ~ 10
oC is added drop-wise to the saturated aqueous ammonium chloride of 2L in the reaction solution, with the hydrochloric acid soln of 2N pH is transferred to 5, standing demix.Water layer merges organic layer with 2L ethyl acetate extraction three times, and organic layer is concentrated into 300mL.Add 2L normal heptane displacement anhydrous tetrahydro furan, be concentrated into 400mL, spissated solution is stirring and crystallizing 3h at room temperature.Filter, with 100mL normal heptane rinsing filter cake once, drying obtains white solid
A(136g ，>99%HPLC purity, productive rate 89%).
Second step: incite somebody to action successively (1.03mol, 130g)
A, (1.13 mol, 134g) tetramethyl ethylene ketone, the anhydrous tetrahydro furan of 1.3L add in the there-necked flask; Stirring at normal temperature 10min dissolves to solid, and (0.52mol, 62.4g) anhydrous magnesium sulfate react 8h under the room temperature in adding; The sampling detection reaction finishes, and filters, and mother liquor is concentrated into about 150mL, adds the 1.3L normal heptane; With 1.4L washing twice, organic layer is concentrated into about 130mL, and solution is cooled to-5 ~ 0
oC stirs 4h.Filter, drying obtains white solid 1-methyl 4-pyrazoles pinacol ester (160g,>98% HPLC purity, productive rate 75%).
Claims (8)
1. the compound method of a 1-methyl 4-pyrazoles boric acid pinacol ester comprises following two steps: the first step, 1-methyl 4-pyrazoles obtain midbody with the triisopropyl borate ester reaction under the n-Butyl Lithium effect
ASecond step, midbody
AReact under the sal epsom effect with tetramethyl ethylene ketone and to obtain title product 1-methyl 4-pyrazoles boric acid pinacol ester
B, reaction scheme is following:
2. the compound method of 1-methyl 4-pyrazoles pinacol ester according to claim 1, it is characterized in that: the consumption of n-Butyl Lithium is 1.1 ~ 1.2 equivalents in the reaction.
3. the compound method of 1-methyl 4-pyrazoles pinacol ester according to claim 1 is characterized in that: the first step reaction for 1-methyl 4-pyrazoles and n-Butyl Lithium-60 ~-70
oC reacts 2 ~ 3h, drips triisopropyl borate ester, continues-60 ~-70
oC reacts 2 ~ 3h, rises to room temperature reaction 8 ~ 12h afterwards; The reaction of second step is for reacting 8 ~ 12h under the room temperature.
4. the compound method of 1-methyl 4-pyrazoles pinacol ester according to claim 1 is characterized in that with 2N hydrochloric acid the pH value being adjusted to 5 ~ 6 after the first step reaction cancellation.
5. the compound method of 1-methyl 4-pyrazoles pinacol ester according to claim 1 is characterized in that will replacing anhydrous tetrahydro furan with normal heptane in the first step post-reaction treatment process.
6. the compound method of 1-methyl 4-pyrazoles pinacol ester according to claim 5, it is characterized in that normal heptane displacement anhydrous tetrahydro furan after organic layer be concentrated into 4 times of volumes, crystallization at room temperature then.
7. the compound method of 1-methyl 4-pyrazoles pinacol ester according to claim 1 is characterized in that washing organic layer twice with the water of 10 times of volumes in the second step post-reaction treatment.
8. the compound method of 1-methyl 4-pyrazoles pinacol ester according to claim 7 is characterized in that after the washing organic layer being concentrated into 1 ~ 2 times of volume, then-10 ~ 0
oThe C crystallization.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011100677831A CN102690281A (en) | 2011-03-22 | 2011-03-22 | Synthetic method of 1-methyl 4-pyrazole pinacol ester |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011100677831A CN102690281A (en) | 2011-03-22 | 2011-03-22 | Synthetic method of 1-methyl 4-pyrazole pinacol ester |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102690281A true CN102690281A (en) | 2012-09-26 |
Family
ID=46856032
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011100677831A Pending CN102690281A (en) | 2011-03-22 | 2011-03-22 | Synthetic method of 1-methyl 4-pyrazole pinacol ester |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102690281A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103145746A (en) * | 2012-12-20 | 2013-06-12 | 大连联化化学有限公司 | Process method for synthesizing cyclopentene/ hexene-1-boronic acid pinacol cyclic ester |
| CN105440067B (en) * | 2016-01-10 | 2017-03-29 | 沧州普瑞东方科技有限公司 | A kind of technique of 4 borate of synthesis N substituted pyrazolecarboxylics |
| CN109053788A (en) * | 2018-09-20 | 2018-12-21 | 山东谛爱生物技术有限公司 | A kind of preparation method of pyrazole compound |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101466676A (en) * | 2006-04-12 | 2009-06-24 | 默克公司 | Pyridyl amide T-type calcium channel antagonists |
| WO2010083283A2 (en) * | 2009-01-15 | 2010-07-22 | Incyte Corporation | Processes for preparing jak inhibitors and related intermediate compounds |
-
2011
- 2011-03-22 CN CN2011100677831A patent/CN102690281A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101466676A (en) * | 2006-04-12 | 2009-06-24 | 默克公司 | Pyridyl amide T-type calcium channel antagonists |
| WO2010083283A2 (en) * | 2009-01-15 | 2010-07-22 | Incyte Corporation | Processes for preparing jak inhibitors and related intermediate compounds |
Non-Patent Citations (1)
| Title |
|---|
| ALEXANDRE V. IVACHTCHENKO ET AL.: ""Synthesis of Pinacol Esters of 1-Alkyl-1H-pyrazol-5-yl- and 1-Alkyl-1H-pyrazol-4-ylboronic Acids"", 《J. HETEROCYCLIC CHEM.》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103145746A (en) * | 2012-12-20 | 2013-06-12 | 大连联化化学有限公司 | Process method for synthesizing cyclopentene/ hexene-1-boronic acid pinacol cyclic ester |
| CN105440067B (en) * | 2016-01-10 | 2017-03-29 | 沧州普瑞东方科技有限公司 | A kind of technique of 4 borate of synthesis N substituted pyrazolecarboxylics |
| CN109053788A (en) * | 2018-09-20 | 2018-12-21 | 山东谛爱生物技术有限公司 | A kind of preparation method of pyrazole compound |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105384188B (en) | Cesium lead bromide powder preparation method | |
| CN109232628A (en) | A kind of method of one pot process difluorine oxalic acid boracic acid lithium | |
| CN104876995A (en) | A preparing method of a chenodeoxycholic acid derivative | |
| CN102690281A (en) | Synthetic method of 1-methyl 4-pyrazole pinacol ester | |
| CN105669733A (en) | Synthetic method of 1-methyl-1H-pyrazole-3-boronic acid pinacol ester | |
| CN103342372B (en) | Method for preparing lithium tetrafluoroborate | |
| CN101863912A (en) | Preparation method of cyclopropylboronic acid | |
| CN103159790A (en) | Luminescent microporous polymer as material and method for preparing same | |
| CN105693737B (en) | Bipyridine ligand with axial chirality and synthetic method thereof | |
| CN109232301B (en) | Preparation method of tetraisopropyl hydrazine | |
| CN104130292A (en) | Three dimensional coordination polymer with double core structure and preparation method thereof | |
| CN104310420A (en) | Method for preparing boron-10 acid from boron trifluoride-10 | |
| CN101391988B (en) | Method for preparing 2-(4-hydroxyl phenyl)-4-methyl-1,3-thiazole-5-carboxylic acid ethyl ester by one pot method | |
| CN103030599B (en) | Gefitinib intermediate and preparation method thereof | |
| CN102212026A (en) | Preparation method for 1-tertbutyloxycarbonyl-3-iodoazetidine | |
| CN113956493A (en) | Non-alkyl tin oxide cluster compound and synthesis method and application thereof | |
| CN105197969A (en) | Preparation method of millimeter-grade radial nesquehonite crystal | |
| CN108084217A (en) | A kind of preparation method of 2,6- dichloros phenyl boric acid | |
| CN103641733A (en) | Preparation method of 18O-dimethylformamide | |
| CN102924369A (en) | Method for synthesizing 3,5-dibromo-4-iodopyridine by one step | |
| CN114605477B (en) | Preparation method of cinnamyl palladium chloride dimer | |
| CN103910668B (en) | A kind of preparation method of 3 alkyl-indol | |
| CN102603693A (en) | Preparation process of ethyl chromane-4-formate | |
| CN101560202B (en) | Preparation method of 2-(2-thienyl) ethyl-4-methylbenzenesulfonate | |
| CN105669710A (en) | Preparation method and synthetic method for copper complex crystal |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C53 | Correction of patent of invention or patent application | ||
| CB02 | Change of applicant information |
Address after: 200131 Shanghai City, Pudong New Area Waigaoqiao Free Trade Zone Foote Road No. 288 Applicant after: Shanghai Yaoming Kangde New Medicine Development Co., Ltd. Applicant after: Shanghai SynTheAll Pharmaceutical Co., Ltd. Address before: 200131 Shanghai City, Pudong New Area Waigaoqiao Free Trade Zone Foote Road No. 288 Applicant before: Shanghai Yaoming Kangde New Medicine Development Co., Ltd. Applicant before: Hequan Pharmaceutical Co., Ltd., Shanghai |
|
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| ASS | Succession or assignment of patent right |
Owner name: CHANGZHOU HEQUAN PHARMACEUTICAL CO., LTD. SHANGHAI Free format text: FORMER OWNER: SHANGHAI SYNTHEALL PHARMACEUTICAL CO., LTD. Effective date: 20141215 Owner name: SHANGHAI SYNTHEALL PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: SHANGHAI YAOMING KANGDE NEW MEDICINE DEVELOPMENT CO., LTD. Effective date: 20141215 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 200131 PUDONG NEW AREA, SHANGHAI TO: 201507 JINSHAN, SHANGHAI |
|
| TA01 | Transfer of patent application right |
Effective date of registration: 20141215 Address after: Jinshan District of Shanghai chemical industrial zone of Shanghai city Jinshan District 201507 (West) Yuegong Road No. 9 Applicant after: Shanghai SynTheAll Pharmaceutical Co., Ltd. Applicant after: CHANGZHOU HEQUAN PHARMACEUTICAL CO., LTD. Applicant after: Shanghai STA Pharmaceutical R & D Co., Ltd. Address before: 200131 Shanghai City, Pudong New Area Waigaoqiao Free Trade Zone Foote Road No. 288 Applicant before: Shanghai Yaoming Kangde New Medicine Development Co., Ltd. Applicant before: Shanghai SynTheAll Pharmaceutical Co., Ltd. |
|
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20120926 |