CN102675306A - Preparing method of moxifloxacin or slat thereof - Google Patents
Preparing method of moxifloxacin or slat thereof Download PDFInfo
- Publication number
- CN102675306A CN102675306A CN2011100643318A CN201110064331A CN102675306A CN 102675306 A CN102675306 A CN 102675306A CN 2011100643318 A CN2011100643318 A CN 2011100643318A CN 201110064331 A CN201110064331 A CN 201110064331A CN 102675306 A CN102675306 A CN 102675306A
- Authority
- CN
- China
- Prior art keywords
- moxifloxacin
- salt
- preparation
- ester
- cyclopropyl
- 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
- YBGOANBXNSVQAH-GFMNRZNCSA-N COc1c(C(C2CC2)C=C(C(O)=O)C2=O)c2cc(F)c1N1C[C@H]2NCCC[C@H]2C1 Chemical compound COc1c(C(C2CC2)C=C(C(O)=O)C2=O)c2cc(F)c1N1C[C@H]2NCCC[C@H]2C1 YBGOANBXNSVQAH-GFMNRZNCSA-N 0.000 description 1
Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
A preparing method of moxifloxacin or slat thereof includes that: 1-cyclopropyl-6,7-difluoro-8-methoxyl-4-oxo-1,4-dihydro-3-quinoline carboxylic acid ester and S,2-2,8-diazabicyclo(4.3.0) nonane are used as raw materials, catalysts are added into the raw materials for condensation reaction in mild condition, and before separation, condensation product moxifloxacin ester can be directly added with hydrolysis of ester group for separation to obtain moxifloxacin or slat thereof. By adopting the method, product purity is high, yield is high, the process is simple and can be controlled easily, and product manufacture cost is low. The preparing method is suitable for large-scale industrial production.
Description
Technical field
The invention belongs to the pharmaceutical chemistry field, be specifically related to a kind of method for preparing Moxifloxacin or its salt.
Background technology
Moxifloxacin hydrochloride (English moxifloxacin hydrochloride by name; Chemical name is 1-cyclopropyl-7-(S; S-2, two [4.3.0] nonanes of 8 diazas-8-yl)-6-fluoro-8-methoxyl group-4-oxo-1,4-dihydro-3-quinoline carboxylic acid hydrochloride) be the 4th generation the fluoroquinolone antibacterial agent thing.It has broad-spectrum antibacterial action, as human and animal's antibacterials, can treat the infection that various bacteria causes effectively.Its structural formula is following:
US5157117 and CN101514201 disclose 1-cyclopropyl-6; 7-two fluoro-8-methoxyl group-4-oxos-1; 4-dihydro-3-quinoline carboxylic acid ethyl ester prepares corresponding ethyl-borate inner complex with boric acid and acetic anhydride in the presence of zinc chloride; Again with S, S-2, the preparation technology of 8-diazabicyclo [4.3.0] nonane prepared in reaction Moxifloxacin.
WO2008059223A2 discloses 1-cyclopropyl-6; 7-two fluoro-8-methoxyl group-4-oxos-1; 4-dihydro-3-quinoline carboxylic acid ethyl ester and boric acid and the corresponding boric acid propyl ester of propionic anhydride prepared in reaction inner complex; Again with S, S-2, the preparation technology of 8-diazabicyclo [4.3.0] nonane prepared in reaction Moxifloxacin.
EP1992626 discloses 1-cyclopropyl-6,7-two fluoro-8-methoxyl group-4-oxos-1,4-dihydro-3-quinoline carboxylic acid and S, S-2, the preparation technology of 8-diazabicyclo [4.3.0] nonane prepared in reaction Moxifloxacin.Because temperature of reaction is higher, the racemization of side chain in the preparation process, occurs, need fractionation just can obtain the high finished product of optical purity.
CN101941969 discloses 1-cyclopropyl-6,7-two fluoro-8-methoxyl group-4-oxos-1,4-dihydro-3-quinoline carboxylic acid and S, S-2, the preparation technology of 8-diazabicyclo [4.3.0] nonane prepared in reaction Moxifloxacin.But reaction yield is on the low side, and bullion purity is also on the low side.
Aforesaid method more or less exists some shortcomings: patent EP1992626 and exists product yield on the low side, needs the problem of chiral separation; Patent US5157117 and WO2008059223A2 process the boric acid ester inner complex earlier with parent nucleus and carry out condensation reaction with side chain again, and preparation section is on the high side, and product yield is not high; Preparation technology's product purity of patent CN101941969 is on the low side, and yield is not high yet.The deficiency of above-mentioned several method has strengthened the manufacturing cost of Moxifloxacin, has restricted the suitability for industrialized production of Moxifloxacin.
Summary of the invention
The objective of the invention is for the preparation method of a kind of Moxifloxacin or its salt is provided; This method has overcome the deficiency that exists in the above-mentioned patent, provides a kind of cost low, and yield is high; One step prepared the method for Moxifloxacin hydrochloride or its salt, can be fit to the requirement of industrialized production preferably.
The object of the invention can reach through following method:
A kind of Moxifloxacin or its salt the preparation method, the preparation process of this method is following:
1-cyclopropyl-6,7-two fluoro-8-methoxyl group-4-oxos-1,4-dihydro-3-quinoline carboxylic ester and S; S-2,8-diazabicyclo [4.3.0] nonane in organic solvent, with organic bases or mineral alkali as acid-capture agent; In the presence of catalyzer, react, obtain the reaction solution of Moxifloxacin ester, need not separate the Moxifloxacin ester; Directly add concentrated hydrochloric acid acidification hydrolization ester group, obtain Moxifloxacin hydrochloride with concentrated hydrochloric acid acidification hydrolization ester group.
The reaction scheme of present method is following:
Above-mentioned reaction formula
Middle R represents the alkane of 1～4 carbon atom.
Organic solvent described in the aforesaid method is one or more in acetonitrile, methyl alcohol, ethanol, THF, the N, particular methanol or ethanol.
Catalyzer described in the aforesaid method is aluminum chloride, zinc chloride, iron(ic)chloride or their mixture, preferred aluminum chloride or aluminum chloride/zinc chloride.
Selected mineral alkali is yellow soda ash or salt of wormwood in the aforesaid method, and organic bases is a triethylamine.
Organic solvent ethanol and 1-cyclopropyl-6 in the aforesaid method, 7-two fluoro-g-methoxyl group-4-oxos-1, the envelope-bulk to weight ratio of 4-dihydro-3-quinoline carboxylic ester is 15～25: 1.
Organic bases triethylamine and 1-cyclopropyl-6 in the aforesaid method, 7-two fluoro-8-methoxyl group-4-oxos-1, the mol ratio of 4-dihydro-3-quinoline carboxylic ester is 0.2～1: 1, is preferably 0.2～0.5: 1.
Catalyzer aluminum chloride and 1-cyclopropyl-6 in the aforesaid method, 7-two fluoro-8-methoxyl group-4-oxos-1, the weight ratio of 4-dihydro-3-quinoline carboxylic ester is 1～5: 100, is preferably 1～3: 100.
1-cyclopropyl-6 in the aforesaid method, 7-two fluoro-g-methoxyl group-4-oxos-1,4-dihydro-3-quinoline carboxylic ester and S, S-2, the mol ratio of 8-diazabicyclo [4.3.0] nonane is 1: 1～1.2, be preferably 1: 1.05～1.1.
1-cyclopropyl-6 in the aforesaid method, 7-two fluoro-8-methoxyl group-4-oxos-1,4-dihydro-3-quinoline carboxylic ester and S, S-2,8-diazabicyclo [4.3.0] nonane setting-up point is 20～100 ℃, preferred 20～60 ℃.
After obtaining the reaction solution of Moxifloxacin ester in the aforesaid method, need not separate the Moxifloxacin ester, directly add concentrated hydrochloric acid acidification hydrolization ester group, obtain Moxifloxacin hydrochloride.
Concentrated hydrochloric acid described in the aforesaid method is 35%～37% concentrated hydrochloric acid.
The gained Moxifloxacin hydrochloride can be further purified and obtains the higher Moxifloxacin hydrochloride of purity in the aforesaid method.
In embodiments, the operation for preparing Moxifloxacin hydrochloride with present method is following: with 1-cyclopropyl-6, and 7-two fluoro-8-methoxyl group-4-oxos-1,4-dihydro-3-quinoline carboxylic ester is dissolved in the ethanol; Add S, S-2,8-diazabicyclo [4.3.0] nonane and triethylamine stir; Add catalyzer, the temperature control stirring reaction adds concentrated hydrochloric acid and regulates pH value to 2-3; Temperature control stirred 2 hours, was cooled to crystallization below 10 ℃, crossed to filter Moxifloxacin hydrochloride.
The present invention is with 1-cyclopropyl-6,7-two fluoro-8-methoxyl group-4-oxos-1,4-dihydro-3-quinoline carboxylic ester and S, S-2; 8-diazabicyclo [4.3.0] nonane is a raw material, through adding catalyzer, under mild conditions, carries out condensation reaction, and condensation product Moxifloxacin ester can be without separation; Separation obtains Moxifloxacin or its salt after directly adding concentrated hydrochloric acid acidification hydrolization ester group, and product purity is high, and yield is high; Technology is simple and easy to control, and cost of goods manifactured is low, is fit to big industrial production.
Embodiment
Below in conjunction with specific embodiment technical scheme of the present invention is done further detailed explanation, but protection scope of the present invention is not limited to following examples:
Embodiment 1
Get 700 milliliters of ethanol, add 32.3 gram 1-cyclopropyl-6,7-two fluoro-8-methoxyl group-4-oxos-1,4-dihydro-3-quinoline carboxylic acid ethyl ester and 13.2 gram S; S-2,8-diazabicyclo [4.3.0] nonane adds 0.4 gram anhydrous chlorides of rase Al catalysts, stirs; Add 2.5 gram triethylamines, 45 ℃ of stirring reactions of temperature control, TLC (thin-layer chromatography) judges reaction to terminal, and is cold slightly; Concentrated hydrochloric acid with 35%～37% is regulated pH value to 2～3, and 70 ℃ of stirring reactions of temperature control 2 to 3 hours are cooled to crystallization below 10 ℃, filters; Vacuum-drying gets product-Moxifloxacin hydrochloride 39.8 grams, yield 91%, purity 99.2%.
Embodiment 2
Get 1300 milliliters of methyl alcohol, add 61.8 gram 1-cyclopropyl-6,7-two fluoro-8-methoxyl group-4-oxos-1,4-dihydro-3-quinoline carboxylic acid methyl esters and 26.4 gram S; S-2,8-diazabicyclo [4.3.0] nonane adds 0.4 gram Aluminum chloride anhydrous/0.8 gram zinc chloride catalyzer, stirs; Add 5.0 gram triethylamines, 45 ℃ of stirring reactions of temperature control, TLC judges reaction to terminal, and is cold slightly; Concentrated hydrochloric acid with 35%～37% is regulated pH value to 2～3, and 70 ℃ of stirring reactions of temperature control 2 to 3 hours are cooled to crystallization below 10 ℃, filters; Vacuum-drying gets product-Moxifloxacin hydrochloride 78.0 grams, yield 89.0%, purity 99.1%.
Embodiment 3
Get 700 milliliters of ethanol, add 32.3 gram 1-cyclopropyl-6,7-two fluoro-8-methoxyl group-4-oxos-1,4-dihydro-3-quinoline carboxylic acid ethyl ester and 12.5 gram S; S-2,8-diazabicyclo [4.3.0] nonane adds 0.4 gram anhydrous chlorides of rase Al catalysts, stirs; Add 2.5 gram triethylamines, 45 ℃ of stirring reactions of temperature control, TLC judges reaction to terminal, and is cold slightly; Concentrated hydrochloric acid with 35%～37% is regulated pH value to 2～3, and 70 ℃ of stirring reactions of temperature control two to three hours are cooled to crystallization below 10 ℃, filters; Vacuum-drying gets product-Moxifloxacin hydrochloride 39.5 grams, yield 90.2%, purity 99.4%.
Embodiment 4
Get 1400 milliliters of ethanol, add 84.6 gram 1-cyclopropyl-6,7-two fluoro-8-methoxyl group-4-oxos-1,4-dihydro-3-quinoline carboxylic acid ethyl ester and 26.2 gram S; S-2,8-diazabicyclo [4.3.0] nonane adds 0.5 gram Aluminum chloride anhydrous/0.5 gram ferric chloride catalyst, stirs; Add 5.0 gram triethylamines, 45 ℃ of stirring reactions of temperature control, TLC judges reaction to terminal, and is cold slightly; Concentrated hydrochloric acid with 35%～37% is regulated pH value to 2～3, and 70 ℃ of stirring reactions of temperature control 2 to 3 hours are cooled to crystallization below 10 ℃, filters; Vacuum-drying gets product-Moxifloxacin hydrochloride 77.5 grams, yield 88.5%, purity 98.9%.
Embodiment 5
Get 700 milliliters of ethanol, add 32.3 gram 1-cyclopropyl-6,7-two fluoro-8-methoxyl group-4-oxos-1,4-dihydro-3-quinoline carboxylic acid ethyl ester and 13.2 gram S; S-2,8-diazabicyclo [4.3.0] nonane adds 0.4 gram anhydrous chlorides of rase Al catalysts, stirs; Add 3.5 gram triethylamines, 45 ℃ of stirring reactions of temperature control, TLC judges reaction to terminal, and is cold slightly; Concentrated hydrochloric acid with 35%～37% is regulated pH value to 2～3, and 70 ℃ of stirring reactions of temperature control 2 to 3 hours are cooled to crystallization below 10 ℃, filters; Vacuum-drying gets product-Moxifloxacin hydrochloride 38.8 grams, yield 88.6%, purity 99.0%.
Embodiment 6
Get 700 milliliters of ethanol, add 34.7 gram 1-cyclopropyl-6,7-two fluoro-8-methoxyl group-4-oxos-1,4-dihydro-3-quinoline carboxylic acid butyl ester and 13.2 gram S; S-2,8-diazabicyclo [4.3.0] nonane adds 0.4 gram anhydrous chlorides of rase Al catalysts, stirs; Add 2.5 gram triethylamines, 55 ℃ of stirring reactions of temperature control, TLC judges reaction to terminal, and is cold slightly; Concentrated hydrochloric acid with 35%～37% is regulated pH value to 2～3, and 70 ℃ of stirring reactions of temperature control 2 to 3 hours are cooled to crystallization below 10 ℃, filters; Vacuum-drying gets product-Moxifloxacin hydrochloride 39.5 grams, yield 90.2%, purity 99.4%.
Embodiment 7
Get 700 milliliters of ethanol, add 33.7 gram 1-cyclopropyl-6,7-two fluoro-8-methoxyl group-4-oxos-1,4-dihydro-3-quinoline carboxylic acid propyl ester and 13.2 gram S; S-2,8-diazabicyclo [4.3.0] nonane adds 0.4 gram anhydrous chlorides of rase Al catalysts, stirs; Add 2.5 gram triethylamines, 45 ℃ of stirring reactions of temperature control, TLC judges reaction to terminal, and is cold slightly; Concentrated hydrochloric acid with 35%～37% is regulated pH value to 2～3, and 70 ℃ of stirring reactions of temperature control 2 to 3 hours are cooled to crystallization below 10 ℃, filters; Vacuum-drying gets product-Moxifloxacin hydrochloride 39.0 grams, yield 89%, purity 99.2%.
Claims (10)
1. the preparation method of a Moxifloxacin or its salt, its characteristic is following: in organic solvent, in the presence of organic bases or mineral alkali; Through adding catalyzer, when temperature is 20 ℃-100 ℃, with 1-cyclopropyl-6; 7-two fluoro-8-methoxyl group-4-oxos-1,4-dihydro-3-quinoline carboxylic ester and S, S-2; 8-diazabicyclo [4.3.0] nonane reacts, and obtains the reaction solution of Moxifloxacin ester, obtains Moxifloxacin or its salt through further hydrolysis ester group.
2. the preparation method of Moxifloxacin according to claim 1 or its salt is characterized in that the catalyzer described in this method is aluminum chloride, zinc chloride, iron(ic)chloride or their mixture, preferred aluminum chloride.
3. the preparation method of Moxifloxacin according to claim 1 or its salt; It is characterized in that catalyzer aluminum chloride described in the method and 1-cyclopropyl-6; 7-two fluoro-8-methoxyl group-4-oxos-1, the weight ratio of 4-dihydro-3-quinoline carboxylic ester is 1～5: 100, is preferably 1～3: 100.
4. the preparation method of Moxifloxacin according to claim 1 or its salt is characterized in that the organic solvent described in the method is one or more in acetonitrile, methyl alcohol, ethanol, THF, the N, particular methanol or ethanol.
5. the preparation method of Moxifloxacin according to claim 1 or its salt is characterized in that organic solvent ethanol and 1-cyclopropyl-6 in the method, 7-two fluoro-8-methoxyl group-4-oxos-1, and the envelope-bulk to weight ratio of 4-dihydro-3-quinoline carboxylic ester is 15～25: 1.
6. the preparation method of Moxifloxacin according to claim 1 or its salt is characterized in that selected mineral alkali is yellow soda ash or salt of wormwood in the method, and organic bases is a triethylamine.
7. the preparation method of Moxifloxacin according to claim 1 or its salt; It is characterized in that organic bases triethylamine and 1-cyclopropyl-6 in the method; 7-two fluoro-8-methoxyl group-4-oxos-1, the mol ratio of 4-dihydro-3-quinoline carboxylic ester is 0.2～1: 1, is preferably 0.2～0.5: 1.
8. the preparation method of Moxifloxacin according to claim 1 or its salt; It is characterized in that 1-cyclopropyl-6 in the method; 7-two fluoro-8-methoxyl group-4-oxos-1,4-dihydro-3-quinoline carboxylic ester and S, S-2; The mol ratio of 8-diazabicyclo [4.3.0] nonane is 1: 1～1.2, be preferably 1: 1.05～and 1.1.
9. the preparation method of Moxifloxacin according to claim 1 or its salt; It is characterized in that 1-cyclopropyl-6 in the method; 7-two fluoro-8-methoxyl group-4-oxos-1,4-dihydro-3-quinoline carboxylic ester and S, S-2; 8-diazabicyclo [4.3.0] nonane setting-up point is 20～100 ℃, preferred 20～60 ℃.
10. the preparation method of Moxifloxacin according to claim 1 or its salt, obtain the reaction solution of Moxifloxacin ester after, need not separate the Moxifloxacin ester, directly add concentrated hydrochloric acid acidification hydrolization ester group, obtain Moxifloxacin hydrochloride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011100643318A CN102675306A (en) | 2011-03-17 | 2011-03-17 | Preparing method of moxifloxacin or slat thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011100643318A CN102675306A (en) | 2011-03-17 | 2011-03-17 | Preparing method of moxifloxacin or slat thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102675306A true CN102675306A (en) | 2012-09-19 |
Family
ID=46807917
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011100643318A Pending CN102675306A (en) | 2011-03-17 | 2011-03-17 | Preparing method of moxifloxacin or slat thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102675306A (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105237535A (en) * | 2015-11-15 | 2016-01-13 | 青岛麦瑞特医药技术有限公司 | Method for preparing moxifloxacin hydrochloride |
| CN105524060A (en) * | 2016-03-10 | 2016-04-27 | 陈红 | Method for preparing moxifloxacin hydrochloride |
| CN105669671A (en) * | 2016-03-10 | 2016-06-15 | 陈红 | Preparation method of moxifloxacin hydrochloride |
| CN109096276A (en) * | 2018-08-01 | 2018-12-28 | 上海博志研新药物技术有限公司 | The preparation method of moxifloxacin hydrochloride and its intermediate |
| CN110194767A (en) * | 2019-06-06 | 2019-09-03 | 浙江国邦药业有限公司 | A kind of preparation method of moxifloxacin hydrochloride and its intermediate |
| CN110981874A (en) * | 2020-03-05 | 2020-04-10 | 北京四环生物制药有限公司 | Preparation method of moxifloxacin hydrochloride |
| CN111320622A (en) * | 2018-12-15 | 2020-06-23 | 上虞京新药业有限公司 | Method for synthesizing moxifloxacin hydrochloride |
| CN114249722A (en) * | 2020-09-23 | 2022-03-29 | 常州方圆制药有限公司 | Preparation method of moxifloxacin hydrochloride |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1109877A (en) * | 1993-12-10 | 1995-10-11 | 拜尔公司 | One-pot process for the preparation of 3-quinolone carboxylic acid derivatives |
| CN1491944A (en) * | 2003-09-19 | 2004-04-28 | 中国医学科学院医药生物技术研究所 | 5-amino-8-methoxy quinolone carboxylic acid derivatives and its preparation |
| EP1992626A1 (en) * | 2007-05-10 | 2008-11-19 | Sandoz AG | Process for the preparation of moxifloxacin hydrochloride |
| CN101941969A (en) * | 2010-09-30 | 2011-01-12 | 江苏正大丰海制药有限公司 | Preparation method of moxifloxacin hydrochloride |
-
2011
- 2011-03-17 CN CN2011100643318A patent/CN102675306A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1109877A (en) * | 1993-12-10 | 1995-10-11 | 拜尔公司 | One-pot process for the preparation of 3-quinolone carboxylic acid derivatives |
| CN1491944A (en) * | 2003-09-19 | 2004-04-28 | 中国医学科学院医药生物技术研究所 | 5-amino-8-methoxy quinolone carboxylic acid derivatives and its preparation |
| EP1992626A1 (en) * | 2007-05-10 | 2008-11-19 | Sandoz AG | Process for the preparation of moxifloxacin hydrochloride |
| CN101941969A (en) * | 2010-09-30 | 2011-01-12 | 江苏正大丰海制药有限公司 | Preparation method of moxifloxacin hydrochloride |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105237535A (en) * | 2015-11-15 | 2016-01-13 | 青岛麦瑞特医药技术有限公司 | Method for preparing moxifloxacin hydrochloride |
| CN105524060A (en) * | 2016-03-10 | 2016-04-27 | 陈红 | Method for preparing moxifloxacin hydrochloride |
| CN105669671A (en) * | 2016-03-10 | 2016-06-15 | 陈红 | Preparation method of moxifloxacin hydrochloride |
| CN105524060B (en) * | 2016-03-10 | 2017-03-22 | 青岛云天生物技术有限公司 | Method for preparing moxifloxacin hydrochloride |
| CN109096276A (en) * | 2018-08-01 | 2018-12-28 | 上海博志研新药物技术有限公司 | The preparation method of moxifloxacin hydrochloride and its intermediate |
| CN111320622A (en) * | 2018-12-15 | 2020-06-23 | 上虞京新药业有限公司 | Method for synthesizing moxifloxacin hydrochloride |
| CN110194767A (en) * | 2019-06-06 | 2019-09-03 | 浙江国邦药业有限公司 | A kind of preparation method of moxifloxacin hydrochloride and its intermediate |
| CN110981874A (en) * | 2020-03-05 | 2020-04-10 | 北京四环生物制药有限公司 | Preparation method of moxifloxacin hydrochloride |
| CN114249722A (en) * | 2020-09-23 | 2022-03-29 | 常州方圆制药有限公司 | Preparation method of moxifloxacin hydrochloride |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102675306A (en) | Preparing method of moxifloxacin or slat thereof | |
| CN100497349C (en) | Improved Biapenem preparation method | |
| CN100503601C (en) | Process of preparing troipisetron | |
| CN101941969B (en) | Preparation method of moxifloxacin hydrochloride | |
| CN104974060A (en) | Method for preparing sodium, 8-(2-hydroxybenzamido)octanoate | |
| CN102731496B (en) | The improvement of a kind of Moxifloxacin hydrochloride preparation method | |
| CN105541844B (en) | Simple preparation method of high-purity linagliptin | |
| CN1176094C (en) | Synthesis of trichlorosucrose | |
| CN103450225A (en) | Preparation method of cefoxitin sodium | |
| CN109293513B (en) | Preparation method of sitafloxacin intermediate | |
| CN108069998A (en) | A kind of synthetic method of penem-like pharmaceutical intermediate | |
| CN102911135A (en) | Synthetic method of 2-mercaptobenzothiazole derivative | |
| CN104610359A (en) | Key intermediate for preparing tedizolid phosphate, and preparation method of key intermediate | |
| CN104402909A (en) | Synthetic method of cefoxitin acid | |
| CN103992337B (en) | A kind of method preparing Aspoxicillin sodium easily | |
| CN102675313A (en) | Preparation method of moxifloxacin hydrochloride | |
| CN102146079A (en) | Preparation method of scopolamine butylbromide | |
| CN101565428B (en) | Preparation method of prulifloxacin | |
| CN105524060B (en) | Method for preparing moxifloxacin hydrochloride | |
| CN103121976A (en) | Preparation method of N-monosubstituted homopiperazines | |
| CN103788010A (en) | Febuxostat intermediate and preparation method thereof | |
| CN105669671A (en) | Preparation method of moxifloxacin hydrochloride | |
| CN103059046B (en) | Preparation method of faropenem | |
| CN102267934A (en) | Method for preparing 6-carbomethoxy indolone | |
| CN101575348A (en) | Method for synthesizing beta-sodium glycero-phosphate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20120919 |