CN101941911A - Environment-friendly synthesis method for cinacalcet - Google Patents
Environment-friendly synthesis method for cinacalcet Download PDFInfo
- Publication number
- CN101941911A CN101941911A CN2010102890298A CN201010289029A CN101941911A CN 101941911 A CN101941911 A CN 101941911A CN 2010102890298 A CN2010102890298 A CN 2010102890298A CN 201010289029 A CN201010289029 A CN 201010289029A CN 101941911 A CN101941911 A CN 101941911A
- Authority
- CN
- China
- Prior art keywords
- structural formula
- jam
- west
- compound
- synthesis 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
Abstract
The invention discloses an environment-friendly synthesis method for cinacalcet. The cinacalcet is prepared by reacting R(+)-1-naphthyl ethamine and [3-(3'-trifluoromethyl)phenyl]-1-halopropane or [3-(3'-trifluoromethyl)phenyl]-1-propylsulfonate serving as raw materials with water serving as medium under the action of a phase-transfer catalyst. The process has the advantages of reducing the cost, along with high yield, no any organic solvent during the reaction, and low environmental pollution, and thus is a synthesis method suitable for industrialization.
Description
Technical field
The present invention relates to treat secondary hyperparathyroidism chiral drug west and receive the green synthesis method of jam.
Technical background
Jam (Cinacalcet) is received in the west, chemical name (R)-Alpha-Methyl-N-[3-[3 '-(trifluoromethyl) phenyl] propyl group]-1-menaphthyl amine, molecular formula is C
22H
22F
3N, CA number is 226256-56-0, its structure is as follows:
The jam hydrochloride is received in the west, and through the preparation of hydrochloric acid salify, molecular formula is C by cinacalcet
22H
22F
3N
.HCl, CA number is 364782-34-3, commodity are called Spensipar.Mimpara, are the plan calcium agent class medicines of first FDA approval, are used for the treatment of the secondary hyperparathyroidism of chronic nephropathy dialysis patient.When the extracellular Ca2 ion concentration of physiological concentration (5 mmol), but dose-dependently ground strengthens the susceptibility of the outer calcium ion of calcium-sensing receptor (CaR) pair cell, suppresses the PTH secretion, reduces calcium-phosphorus product.Can also increase the concentration of cytoplasm calcium ion of cultured human embryo tire nephrocyte etc.Its structural formula is as follows:
Patent US6211244 has reported and has passed through imines
3Or
6Also originally prepare the western method (route 1 and route 2) of receiving jam and analogue thereof.
Route 1
Route 2
Patent US6211244 report is that the method (route 3) of jam is received in the synthetic west of raw material with the m-trifluoromethyl benzenepropanenitrile.
Route 3
Need to use reagent such as diisobutyl aluminum and the different third oxygen titanium in the above synthesis technique, these reagent cost an arm and a leg, toxicity is big and not easy to operate, and raw material
2,
5,
7Long and the difficult preparation of synthetic route.
Patent WO2006125026 has reported and has passed through compound
10The method (route 4) of jam is received in (X represents a leavings group) and R (+)-1-naphthalene ethylamine prepared in reaction west.As reaction solvent, back flow reaction in alkaline environment obtain the target product west and receive jam, yet this reaction yield is lower, and solvent load is also bigger with acetonitrile etc.
Route 4
Comprehensive above several method can be found, passes through compound
10And R (+)-1-naphthalene ethylamine to be that raw material carries out the synthetic method comparatively easy, but existing technology still also has the improved place of needs.The present invention improves this technology, and a kind of green synthesis method of easy cinacalcet is provided, and does not add any organic solvent in the reaction.Not only easy and simple to handle, with low cost, yield is high, and environmental pollution is little.
Summary of the invention
The green synthesis method that provides a kind of west to receive jam for solving the above problems is provided.
Technical scheme of the present invention
The green synthesis method of jam is received in a kind of west, comprises the steps:
(1), the compound of structural formula II and R (+)-1-naphthalene ethylamine (structural formula II I) is under the effect of phase-transfer catalyst, with water is medium, in the presence of mineral alkali, react 4～24h under 0-100 ℃ the temperature and obtain containing the target product west and receive the reaction solution of jam (structural formula I);
Structural formula II structural formula II I
Be structural formula I
Wherein, the X in the structural formula II compound can be the sulfonate group of halogen atom or replacement.
Described halogen atom can be Cl, Br, I, is preferably the chlorine atom;
Described alkylsulfonyl can be tosic acid ester group, methylsulfonic acid ester group, Phenylsulfonic acid ester group.
The compound R (+) of the compound of structural formula II and structural formula II I-1-naphthalene ethylamine reaction mole proportioning is that compound R (+)-1-naphthalene ethylamine of the compound of structural formula II: structural formula II I is 1～2:1, is preferably 1-1.2:1;
The phase-transfer catalyst consumption is the 5%-30% of the weight of R (+)-1-naphthalene ethylamine, is preferably 5%-20%;
The consumption of mineral alkali is a mineral alkali by the mol ratio of mineral alkali and R (+)-1-naphthalene ethylamine (structural formula II I): R (+)-1-naphthalene ethylamine (structural formula II I) is 1-8:1, is preferably 1-3:1.
(2), the purifying of jam is received in the target product west
The reaction solution cooling of jam is received in the target product west that contains of step (1) gained, use dichloromethane extraction, extraction liquid is successively through dilute hydrochloric acid, saturated sodium bicarbonate and saturated common salt water washing, and anhydrous sodium sulfate drying filters, and the removal solvent obtains cinacalcet.
Mineral alkali described in the method for the present invention can be metal hydroxides or metal carbonate.Wherein said metal hydroxides can be sodium hydroxide, potassium hydroxide, lithium hydroxide etc., preferred sodium hydroxide, potassium hydroxide; Described metal carbonate can be yellow soda ash, salt of wormwood etc.
Phase-transfer catalyst described in the method for the present invention can be quarternary ammonium salt compound, crown ether or polyoxyethylene glycol.Wherein said quarternary ammonium salt compound can be Tetrabutyl amonium bromide, tetrabutyl iodate amine, 4-butyl ammonium hydrogen sulfate, tetraethylammonium bromide, tributyl-methyl phosphonium ammonium chloride, benzyltriethylammoinium chloride etc.; Described crown ether can be hexaoxacyclooctadecane-6-6,15-crown ether-5,12-crown ether-4 etc.; Described polyoxyethylene glycol can be PEG200, PEG400, PEG600, PEG800, PEG6000 etc., is preferably PEG6000 or PEG400.
This is reflected to be preferably under the 70-100 ℃ of temperature and carries out.
Beneficial effect of the present invention
Making water in the method for the present invention is reaction medium, does not add any organic solvent in the reaction.Not only easy and simple to handle, with low cost, yield is high, and can reduce the pollution to environment, is a kind of industrialized green synthesis method that is suitable for.
Embodiment
The present invention will further explain in following examples.Yet, should not think that the present invention is limited by it.Those of ordinary skills should understand and how to change cited synthetic method and obtain required result.
Embodiment 1
Add 0.6g R-(+)-1-naphthalene ethylamine, 0.86g [3-(3 '-trifluoromethyl) phenyl]-n-propyl chloride, the 8ml aqueous solution that is dissolved with 0.28g sodium hydroxide and 0.06g Tetrabutyl amonium bromide in the 50ml there-necked flask successively, stir, 70～75 ℃ of reaction 4h.Dichloromethane extraction is used in cooling, and extraction liquid is successively through dilute hydrochloric acid, saturated sodium bicarbonate and saturated common salt water washing, and anhydrous sodium sulfate drying filters, and removes solvent and obtains cinacalcet.Weak yellow liquid, yield are 82.1%, [α]
D=-8.6
o(C=1, methyl alcohol).
Embodiment 2
Add 0.6g R-(+)-1-naphthalene ethylamine, 0.86g [3-(3 '-trifluoromethyl) phenyl]-n-propyl chloride, the 8ml aqueous solution that is dissolved with 0.40g potassium hydroxide and 0.09g tetrabutylammonium iodide in the 50ml there-necked flask successively, stir, 70～75 ℃ of reaction 4h.Dichloromethane extraction is used in cooling, and extraction liquid is successively through dilute hydrochloric acid, saturated sodium bicarbonate and saturated common salt water washing, and anhydrous sodium sulfate drying filters, and removes solvent and obtains cinacalcet.Weak yellow liquid, yield are 83.0%, [α]
D=-9.2
o(C=1, methyl alcohol).
Embodiment 3
Add 0.6g R-(+)-1-naphthalene ethylamine, 0.93g [3-(3 '-trifluoromethyl) phenyl]-n-propyl chloride, the 10ml aqueous solution that is dissolved with 1.1g yellow soda ash and 0.09g PEG6000 in the 50ml there-necked flask successively, stir, 95～100 ℃ of reaction 24h.Dichloromethane extraction is used in cooling, and extraction liquid is successively through dilute hydrochloric acid, saturated sodium bicarbonate and saturated common salt water washing, and anhydrous sodium sulfate drying filters, and removes solvent and obtains cinacalcet.Weak yellow liquid, yield are 78.5%, [α]
D=-8.8
o(C=1, methyl alcohol).
Embodiment 4
Add 0.6g R-(+)-1-naphthalene ethylamine, 0.86g [3-(3 '-trifluoromethyl) phenyl]-n-propyl chloride, the 8ml aqueous solution that is dissolved with 0.28g sodium hydroxide and 0.06g 4-butyl ammonium hydrogen sulfate in the 50ml there-necked flask successively, stir, 80 ℃-90 ℃ reaction 4h.Dichloromethane extraction is used in cooling, and extraction liquid is successively through dilute hydrochloric acid, saturated sodium bicarbonate and saturated common salt water washing, and anhydrous sodium sulfate drying filters, and removes solvent and obtains cinacalcet.Weak yellow liquid, yield are 84.6%, [α]
D=-8.5
o(C=1, methyl alcohol).
Embodiment 5
Add 0.6g R-(+)-1-naphthalene ethylamine, 1.33g [3-(3 '-trifluoromethyl) phenyl]-1-Phenylsulfonic acid ester group propane, the 12ml aqueous solution that is dissolved with 1.5g salt of wormwood and 0.1g tributyl-methyl phosphonium ammonium chloride in the 50ml there-necked flask successively, stir 95～100 ℃ of reaction 20h.Dichloromethane extraction is used in cooling, and extraction liquid is successively through dilute hydrochloric acid, saturated sodium bicarbonate and saturated common salt water washing, and anhydrous sodium sulfate drying filters, and removes solvent and obtains cinacalcet.Weak yellow liquid, yield are 82.6%, [α]
D=-9.3
o(C=1, methyl alcohol).
Embodiment 6
Add 0.6g R-(+)-1-naphthalene ethylamine, 1.38g [3-(3 '-trifluoromethyl) phenyl]-1-tosic acid ester group propane, the 8ml aqueous solution that is dissolved with 0.32g sodium hydroxide and 0.1g PEG400 in the 50ml there-necked flask successively, stir 70 ℃-80 ℃ reaction 10h.Dichloromethane extraction is used in cooling, and extraction liquid is successively through dilute hydrochloric acid, saturated sodium bicarbonate and saturated common salt water washing, and anhydrous sodium sulfate drying filters, and removes solvent and obtains cinacalcet.Weak yellow liquid, yield are 79.6%, [α]
D=-9.1
o(C=1, methyl alcohol).
Embodiment 7
Add 0.6g R-(+)-1-naphthalene ethylamine, 1.03g [3-(3 '-trifluoromethyl) phenyl]-1-N-PROPYLE BROMIDE, the 8ml aqueous solution that is dissolved with 0.40g potassium hydroxide and 0.08g Tetrabutyl amonium bromide in the 50ml there-necked flask successively, stir, 70～75 ℃ of reaction 5h.Dichloromethane extraction is used in cooling, and extraction liquid is successively through dilute hydrochloric acid, saturated sodium bicarbonate and saturated common salt water washing, and anhydrous sodium sulfate drying filters, and removes solvent and obtains cinacalcet.Weak yellow liquid, yield are 75.1%, [α]
D=-9.6
o(C=1, methyl alcohol).
Embodiment 8
Add 0.6g R-(+)-1-naphthalene ethylamine, 1.13g [3-(3 '-trifluoromethyl) phenyl]-1-methylsulfonic acid ester group propane in the 50ml there-necked flask successively, be dissolved with the 4ml aqueous solution and the 0.08gPEG6000 of 0.2g sodium hydroxide, stir, 70～75 ℃ of reaction 5h.Dichloromethane extraction is used in cooling, and extraction liquid is successively through dilute hydrochloric acid, saturated sodium bicarbonate and saturated common salt water washing, and anhydrous sodium sulfate drying filters, and removes solvent and obtains cinacalcet.Weak yellow liquid, yield are 75.1%, [α]
D=-9.6
o(C=1, methyl alcohol).
Embodiment 9
Add 0.6g R-(+)-1-naphthalene ethylamine, 1.03g [3-(3 '-trifluoromethyl) phenyl]-1-N-PROPYLE BROMIDE, the 8ml aqueous solution that is dissolved with 0.40g potassium hydroxide and 0.1g benzyltriethylammoinium chloride in the 50ml there-necked flask successively, magnetic agitation, 70～75 ℃ of reaction 5h.Dichloromethane extraction is used in cooling, and extraction liquid is successively through dilute hydrochloric acid, saturated sodium bicarbonate and saturated common salt water washing, and anhydrous sodium sulfate drying filters, and removes solvent and obtains cinacalcet.Weak yellow liquid, yield are 75.1%, [α]
D=-9.6
o(C=1, methyl alcohol).
Described content only is the basic explanation of the present invention under conceiving, and according to any equivalent transformation that technical scheme of the present invention is done, all should belong to protection scope of the present invention.
Claims (12)
1. the green synthesis method of jam is received in a west, it is characterized in that may further comprise the steps:
(1), the compound R (+) of the compound of structural formula II and structural formula II I-1-naphthalene ethylamine is under the effect of phase-transfer catalyst, with water is medium, in the presence of mineral alkali, 0-100 ℃ down reaction 4～24h target product west of obtaining containing structural formula I receive the reaction solution of jam;
Structural formula II
X is halogen atom or sulfonate group in the compound of structural formula II;
Structural formula II I
Structural formula I
Wherein said mineral alkali is metal hydroxides or metal carbonate;
Wherein said phase-transfer catalyst is quarternary ammonium salt compound, crown ether or polyoxyethylene glycol;
The compound R (+) of the compound of structural formula II and structural formula II I-1-naphthalene ethylamine reaction mole proportioning is that compound R (+)-1-naphthalene ethylamine of the compound of structural formula II: structural formula II I is 1～2:1;
The phase-transfer catalyst consumption is the 5%-30% of weight of compound R (+)-1-naphthalene ethylamine of structural formula II I;
The consumption of mineral alkali is a mineral alkali by the mol ratio of compound R (+)-1-naphthalene ethylamine of mineral alkali and structural formula II I: R (+)-1-naphthalene ethylamine (structural formula II I) is 1～8:1;
(2), the purifying of jam is received in the target product west
The target product of step (1) gained is contained the west receive the reaction solution cooling of jam, use dichloromethane extraction, extraction liquid is successively through dilute hydrochloric acid, saturated sodium bicarbonate and saturated common salt water washing, and anhydrous sodium sulfate drying filters, and the removal solvent obtains cinacalcet.
2. the green synthesis method of jam is received in a kind of west as claimed in claim 1, it is characterized in that:
Described halogen atom is Cl, Br or I;
Described alkylsulfonyl can be tosic acid ester group, methylsulfonic acid ester group, Phenylsulfonic acid ester group.
3. the green synthesis method of jam is received in a kind of west as claimed in claim 1, it is characterized in that:
Described halogen atom is preferably the chlorine atom.
4. the green synthesis method of jam is received in a kind of west as claimed in claim 1, it is characterized in that in the step (1):
The compound R (+) of the compound of structural formula II and structural formula II I-1-naphthalene ethylamine reaction mole proportioning is that compound R (+)-1-naphthalene ethylamine thing of the compound of structural formula II: structural formula II I is preferably 1-1.2:1;
The phase-transfer catalyst consumption is preferably the 8%-20% of the weight of R (+)-1-naphthalene ethylamine;
The consumption of mineral alkali is a mineral alkali by the mol ratio of mineral alkali and R (+)-1-naphthalene ethylamine (structural formula II I): R (+)-1-naphthalene ethylamine (structural formula II I) is preferably 1-3:1.
5. the green synthesis method of jam is received in a kind of west as claimed in claim 1, it is characterized in that described metal hydroxides is sodium hydroxide, potassium hydroxide, lithium hydroxide etc.
6. the green synthesis method of jam is received in a kind of west as claimed in claim 1, it is characterized in that described metal hydroxides is preferably sodium hydroxide, potassium hydroxide.
7. the green synthesis method of jam is received in a kind of west as claimed in claim 1, it is characterized in that described metal carbonate is yellow soda ash or salt of wormwood.
8. the green synthesis method of jam is received in a kind of west as claimed in claim 1, it is characterized in that in the described phase-transfer catalyst:
Quarternary ammonium salt compound is Tetrabutyl amonium bromide, tetrabutyl iodate amine, 4-butyl ammonium hydrogen sulfate, tetraethylammonium bromide, tributyl-methyl phosphonium ammonium chloride or benzyltriethylammoinium chloride.
9. the green synthesis method of jam is received in a kind of west as claimed in claim 1, it is characterized in that in the described phase-transfer catalyst:
Described crown ether is hexaoxacyclooctadecane-6-6,15-crown ether-5 or 12-crown ether-4.
10. the green synthesis method of jam is received in a kind of west as claimed in claim 1, it is characterized in that in the described phase-transfer catalyst:
Described polyoxyethylene glycol is PEG200, PEG400, PEG600, PEG800 or PEG6000.
11. the green synthesis method of jam is received in a kind of west as claimed in claim 1, it is characterized in that in the described phase-transfer catalyst:
Described polyoxyethylene glycol is preferably PEG6000 or PEG400.
12. the green synthesis method of jam is received in a kind of west as claimed in claim 1, it is characterized in that temperature of reaction is preferably 70-100 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102890298A CN101941911A (en) | 2010-09-21 | 2010-09-21 | Environment-friendly synthesis method for cinacalcet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010102890298A CN101941911A (en) | 2010-09-21 | 2010-09-21 | Environment-friendly synthesis method for cinacalcet |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101941911A true CN101941911A (en) | 2011-01-12 |
Family
ID=43434149
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010102890298A Pending CN101941911A (en) | 2010-09-21 | 2010-09-21 | Environment-friendly synthesis method for cinacalcet |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101941911A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103044267A (en) * | 2012-12-06 | 2013-04-17 | 华润赛科药业有限责任公司 | Preparation method of high-purity cinacalcet hydrochloride |
| WO2013177938A1 (en) * | 2012-05-29 | 2013-12-05 | 上海京新生物医药有限公司 | Method of preparing cinacalcet hydrochloride |
| CN103664577A (en) * | 2012-09-06 | 2014-03-26 | 北京万生药业有限责任公司 | Preparation method of cinacalcet intermediate |
| CN113121388A (en) * | 2021-03-29 | 2021-07-16 | 西华大学 | Cinacalcet intermediate and synthetic method of cinacalcet hydrochloride |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006125026A2 (en) * | 2005-05-16 | 2006-11-23 | Teva Pharmaceutical Industries, Ltd. | Process for preparing cinacalcet hydrochloride |
| WO2006127941A2 (en) * | 2005-05-23 | 2006-11-30 | Teva Pharmaceutical Industries Ltd. | Amorphous cinacalcet hydrochloride and preparation thereof |
| WO2008063645A1 (en) * | 2006-11-20 | 2008-05-29 | Teva Pharmaceutical Industries Ltd. | Process for preparing cinacalcet |
| WO2010100429A1 (en) * | 2009-03-05 | 2010-09-10 | Cipla Limited | Process for the preparation of cinacalcet and salts thereof, and intermediates for use in the process |
-
2010
- 2010-09-21 CN CN2010102890298A patent/CN101941911A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006125026A2 (en) * | 2005-05-16 | 2006-11-23 | Teva Pharmaceutical Industries, Ltd. | Process for preparing cinacalcet hydrochloride |
| WO2006127941A2 (en) * | 2005-05-23 | 2006-11-30 | Teva Pharmaceutical Industries Ltd. | Amorphous cinacalcet hydrochloride and preparation thereof |
| WO2008063645A1 (en) * | 2006-11-20 | 2008-05-29 | Teva Pharmaceutical Industries Ltd. | Process for preparing cinacalcet |
| WO2010100429A1 (en) * | 2009-03-05 | 2010-09-10 | Cipla Limited | Process for the preparation of cinacalcet and salts thereof, and intermediates for use in the process |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013177938A1 (en) * | 2012-05-29 | 2013-12-05 | 上海京新生物医药有限公司 | Method of preparing cinacalcet hydrochloride |
| US9469593B2 (en) | 2012-05-29 | 2016-10-18 | Shanghai Jingxin Biomedical Co., Ltd. | Process for preparing cinacalcet hydrochloride |
| CN103664577A (en) * | 2012-09-06 | 2014-03-26 | 北京万生药业有限责任公司 | Preparation method of cinacalcet intermediate |
| CN103664577B (en) * | 2012-09-06 | 2015-04-08 | 北京万生药业有限责任公司 | Preparation method of cinacalcet intermediate |
| CN103044267A (en) * | 2012-12-06 | 2013-04-17 | 华润赛科药业有限责任公司 | Preparation method of high-purity cinacalcet hydrochloride |
| CN113121388A (en) * | 2021-03-29 | 2021-07-16 | 西华大学 | Cinacalcet intermediate and synthetic method of cinacalcet hydrochloride |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1972886B (en) | Method for producing polyhalogenated diamantane and derivative thereof | |
| CN108745197B (en) | Easily degradable gemini quaternary ammonium salt and preparation method thereof | |
| CN101941911A (en) | Environment-friendly synthesis method for cinacalcet | |
| CN102500087B (en) | Method for preparing perfluorohexane surfactant serving as main agent of aqueous film-forming extinguishing agent directly | |
| CN102389745A (en) | Preparation method of fluorine-containing double-type cationic surfactant and use thereof | |
| CN104230852A (en) | Synthetic method of vortioxetine | |
| CN102070530A (en) | N-alkylamino-2-perfluoroalkylimidazoline quaternary ammonium salt and preparation method thereof | |
| CN104628545A (en) | Method for preparing anisic aldehyde | |
| CN103274959A (en) | Synthetic method of cooling agent N-, 2, 3-trimethyl-2-isopropyl butyrylamide | |
| CN102199102A (en) | Sitagliptin intermediate and preparation method and application thereof | |
| CN104607094A (en) | Dissymmetric cationic Gemini surfactant and preparation method thereof | |
| CN104292183B (en) | A kind of antidepressant drug irrigates the preparation method for Xi Ting | |
| CN106823987B (en) | A kind of hydrofluorocarbons carboxylic acid type surfactant and preparation method thereof | |
| CN110354755A (en) | A kind of novel fluorine betaine type amphoteric surfactant and its preparation method and application | |
| CN100434500C (en) | Guerbet anion surfactant, and its preparing method and use | |
| CN107129435B (en) | A method of preparing 2-amino-2-methyl-1-propanol | |
| CN106540630A (en) | A kind of carboxylic acid type anionic Gemini surfactant and preparation method thereof | |
| CN103288687A (en) | Preparation method of fatty alcohol polyethenoxy ether sulfonate | |
| CN102351755B (en) | Fluorine-containing imine cationic surfactant preparation method and application thereof | |
| CN113501796B (en) | Aminoethylated piperazine and preparation method thereof | |
| CN104884424A (en) | Halogenated aniline and method for producing same | |
| CN102351753A (en) | Fluorine-containing Gemini-like anionic surface active agent, its preparation method and its application | |
| CN105017232A (en) | Synthesis method of triazole bactericide | |
| CN103524313B (en) | 3,5-dimethylbenzaldehyde preparation method | |
| CN102827161A (en) | Method for purifying moxifloxacin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20110112 |