CN107501107A - The intermediate synthetic method of quinolone medicine - Google Patents
The intermediate synthetic method of quinolone medicine Download PDFInfo
- Publication number
- CN107501107A CN107501107A CN201710883203.3A CN201710883203A CN107501107A CN 107501107 A CN107501107 A CN 107501107A CN 201710883203 A CN201710883203 A CN 201710883203A CN 107501107 A CN107501107 A CN 107501107A
- Authority
- CN
- China
- Prior art keywords
- solid
- hours
- stirring
- white
- solution
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/16—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions not involving the amino or carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
- C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
Abstract
The invention discloses a kind of intermediate synthetic method of quinolone medicine, comprise the following steps：（1）, by the mixture of 3 dimethylamino ETHYL CYANOACRYLATEs and triethylamine, be stirred at room temperature, pass through charging hopper, the solution of the fluorobenzoyl chloride of 2.4 dichloro 5 is added, after stirring, 80 90 DEG C are reacted 3 hours, filtering forms mixture, and solid is washed with toluene, the solid washed, dissolved with water, ethyl acetate is gradually added dropwise, be completely dissolved solution, cooling, it is static to white solid is separated out, centrifuge, dry 2 hours, obtain the solid of white.The present invention is reasonable in design, selects a kind of new ethylamino- 2 of synthesis 3（The fluoro benzoyl of 2,4 dichloro 5）The method of ethyl acrylate has good market application value.
Description
Technical field
The present invention relates to technical field of pharmaceutical chemistry, the intermediate synthetic method of specially a kind of quinolone medicine.
Background technology
3- ethylamino-s -2-（The chloro- 5- fluoro benzoyls of 2,4- bis-）Ethyl acrylate is a kind of centre for producing quinolones
Body, quinolones anti-infectives have the advantages of has a broad antifungal spectrum, antibacterial activity is strong compared with other antibiotic.
The content of the invention
It is an object of the present invention to provide one kind first to take separation intermediate product, takes recrystallization afterwards, then takes low-temp reaction,
To synthesize 3- ethylamino-s -2-（The chloro- 5- fluoro benzoyls of 2,4- bis-）The method of ethyl acrylate, reduce the by-product of substitution and addition
Thing.
The present invention adopts the following technical scheme that realization：
A kind of intermediate synthetic method of quinolone medicine, comprises the following steps：
（1）, by the mixture of 3- dimethylamino ETHYL CYANOACRYLATE and triethylamine, be stirred at room temperature, pass through charging hopper, add
The solution of the chloro- 5- fluorobenzoyl chlorides of 2.4- bis-, after stirring, 80-90 DEG C is reacted 3 hours, and filtering forms mixture, solid toluene
Washing, the solid washed, is dissolved with water, ethyl acetate is gradually added dropwise, be completely dissolved solution, is cooled, static white to separating out
Color solid, centrifugation, dry 2 hours, obtain the solid of white；
（2）, in reactor put into above-mentioned solid, add ethanol, after stirring, temperature control at 0-5 DEG C starts that 30% ethamine is added dropwise
Solution, after dripping, react 3 hours, stirring, separate out solid, centrifugation, dry 2 hours, obtain white solid, i.e., 3- ethylamino-s-
2-（The chloro- 5- fluoro benzoyls of 2,4- bis-）Ethyl acrylate.
Above-mentioned course of reaction is as follows：
Compared with prior art, the inventive method has the following advantages that：
1st, this method synthesizes the parent of quinolone using the chloro- 5- fluorobenzoyl chlorides of 2,4- bis- and 3- dimethylamino ETHYL CYANOACRYLATE,
Reaction condition is gentle, and raw material is easy to get, and yield is higher, and traditional handicraft uses the chloro- 4- fluoroanilines of 3- as initiation material, expensive starting materials,
Reaction temperature higher yields are relatively low.
2nd, conventional method synthesis carbostyril compound uses that bromoethane class compound is expensive, and environmental pollution is tight
Weight, this method use ethylamine solution, and waste is easily processed, and meet increasingly strict environmental requirement.
3rd, this method reduces the accessory substance of substitution and addition, reduces production cost.
In a word, the present invention is reasonable in design, selects a kind of new synthesis 3- ethylamino-s -2-（The chloro- 5- fluorobenzoyls of 2,4- bis-
Base）The method of ethyl acrylate has good market application value.
Embodiment
The specific embodiment of the present invention is described in detail below.
Embodiment 1
A kind of intermediate synthetic method of quinolone medicine, comprises the following steps：
1st, by 3- dimethylamino ETHYL CYANOACRYLATEs（3.1g, 21.6mmol）And triethylamine（4.4g, 43.6mmol）Mixture,
Stir at room temperature, by charging hopper, add the chloro- 5- fluorobenzoyl chlorides of 2,4- bis-（5.1g、26.5mmol）Solution, stirring 20
After minute, 80-90 DEG C is reacted 3 hours, and filtering forms mixture, and solid is washed with toluene, the solid washed, is dissolved with water,
A small amount of ethyl acetate is gradually added dropwise, is completely dissolved solution, cools, it is static to white solid is separated out, centrifugation, dry 2 hours, obtain
To the solid of white.
2nd, above-mentioned solid 32.6g is put into reactor, adds ethanol 100mL, stirred 10 minutes, temperature control is opened at 0-5 DEG C
Begin that 30% ethylamine solution 18mL is added dropwise, after dripping, react 3 hours, stirring, separate out solid, centrifugation, dry 2 hours, obtain white
Color solid, i.e. 3- ethylamino-s -2-（The chloro- 5- fluoro benzoyls of 2,4- bis-）Ethyl acrylate（27.5g, yield 84%）.
Embodiment 2
A kind of intermediate synthetic method of quinolone medicine, comprises the following steps：
1st, by 3- dimethylamino ETHYL CYANOACRYLATEs（3.4g, 23.8mmol）And triethylamine（5.9g, 58.4mmol）Mixture,
Stir at room temperature, by charging hopper, add the chloro- 5- fluorobenzoyl chlorides of 2.4- bis-（4.92g 25.6mmol）Solution, stirring
After 20 minutes, 80-90 DEG C is reacted 3 hours, and filtering forms mixture, and solid is washed with toluene, the solid washed, and use is water-soluble
Solution, is gradually added dropwise a small amount of ethyl acetate, is completely dissolved solution, cools, static to white solid is separated out, and centrifugation, it is small to dry 2
When, obtain the solid of white.
2nd, above-mentioned solid 32.6g is put into reactor, adds ethanol 100mL, stirred 10 minutes, temperature control is opened at 0-5 DEG C
Begin that 30% ethylamine solution 18mL is added dropwise, after dripping, react 3 hours, stirring, separate out solid, centrifugation, dry 2 hours, obtain white
Color solid, i.e. 3- ethylamino-s -2-（The chloro- 5- fluoro benzoyls of 2,4- bis-）Ethyl acrylate（26.5g, yield 81%）.
Embodiment 3
A kind of intermediate synthetic method of quinolone medicine, comprises the following steps：
1st, by 3- dimethylamino ETHYL CYANOACRYLATEs（2.9g, 20.3mmol）And triethylamine（4.1g, 40.6mmol）Mixture,
Stir at room temperature, by charging hopper, add the chloro- 5- fluorobenzoyl chlorides of 2.4- bis-（4.7g, 24.5mmol）Solution, stirring 20
After minute, 80-90 DEG C is reacted 3 hours, and filtering forms mixture, and solid is washed with toluene, the solid washed, is dissolved with water,
A small amount of ethyl acetate is gradually added dropwise, is completely dissolved solution, cools, it is static to white solid is separated out, centrifugation, dry 2 hours, obtain
To the solid of white.
2nd, above-mentioned solid 32.6g is put into reactor, adds ethanol 100mL, stirred 10 minutes, temperature control is opened at 0-5 DEG C
Begin that 30% ethylamine solution 18mL is added dropwise, after dripping, react 3 hours, stirring, separate out solid, centrifugation, dry 2 hours, obtain white
Color solid, i.e. 3- ethylamino-s -2-（The chloro- 5- fluoro benzoyls of 2,4- bis-）Ethyl acrylate（28g, yield 85%）.
It should be noted last that the above embodiments are merely illustrative of the technical solutions of the present invention and it is unrestricted, although ginseng
It is described in detail according to the embodiment of the present invention, it will be understood by those within the art that, to technical scheme
Modify or equivalent substitution, without departure from the spirit and scope of technical scheme, it all should cover claim
In protection domain.
Claims (1)
- A kind of 1. intermediate synthetic method of quinolone medicine, it is characterised in that：Comprise the following steps：（1）, by the mixture of 3- dimethylamino ETHYL CYANOACRYLATE and triethylamine, be stirred at room temperature, pass through charging hopper, add The solution of the chloro- 5- fluorobenzoyl chlorides of 2.4- bis-, after stirring, 80-90 DEG C is reacted 3 hours, and filtering forms mixture, solid toluene Washing, the solid washed, is dissolved with water, ethyl acetate is gradually added dropwise, be completely dissolved solution, is cooled, static white to separating out Color solid, centrifugation, dry 2 hours, obtain the solid of white；（2）, in reactor put into above-mentioned solid, add ethanol, after stirring, temperature control starts 30% ethamine is added dropwise molten at 0-5 DEG C Liquid, after dripping, react 3 hours, stirring, separate out solid, centrifugation, dry 2 hours, obtain white solid, i.e. 3- ethylamino-s -2- （The chloro- 5- fluoro benzoyls of 2,4- bis-）Ethyl acrylate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710883203.3A CN107501107A (en) | 2017-09-26 | 2017-09-26 | The intermediate synthetic method of quinolone medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710883203.3A CN107501107A (en) | 2017-09-26 | 2017-09-26 | The intermediate synthetic method of quinolone medicine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107501107A true CN107501107A (en) | 2017-12-22 |
Family
ID=60699381
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710883203.3A Pending CN107501107A (en) | 2017-09-26 | 2017-09-26 | The intermediate synthetic method of quinolone medicine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107501107A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111269131A (en) * | 2020-03-12 | 2020-06-12 | 常州飞宇化工有限公司 | Process for preparing cyclopropyl ethyl amide by taking tri-n-propylamine as acid acceptor |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1652784A (en) * | 2002-05-14 | 2005-08-10 | 加利福尼亚大学董事会 | Substituted quinolone carboxylic acids, their derivatives, site of action, and uses thereof |
| CN104292159A (en) * | 2014-10-10 | 2015-01-21 | 浙江同丰医药化工有限公司 | Preparation method of norfloxacin, ciprofloxacin and enrofloxacin |
-
2017
- 2017-09-26 CN CN201710883203.3A patent/CN107501107A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1652784A (en) * | 2002-05-14 | 2005-08-10 | 加利福尼亚大学董事会 | Substituted quinolone carboxylic acids, their derivatives, site of action, and uses thereof |
| CN104292159A (en) * | 2014-10-10 | 2015-01-21 | 浙江同丰医药化工有限公司 | Preparation method of norfloxacin, ciprofloxacin and enrofloxacin |
Non-Patent Citations (1)
| Title |
|---|
| 谢建刚等: "1-乙基-6-氟-7-(1-哌嗪基)-1,4-二氢-4-氧代喹啉-3-羧酸类似物的合成", 《郑州大学学报(理学版)》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111269131A (en) * | 2020-03-12 | 2020-06-12 | 常州飞宇化工有限公司 | Process for preparing cyclopropyl ethyl amide by taking tri-n-propylamine as acid acceptor |
| CN111269131B (en) * | 2020-03-12 | 2021-12-28 | 江苏飞宇医药科技股份有限公司 | Process for preparing cyclopropyl ethyl amide by taking tri-n-propylamine as acid acceptor |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103524440B (en) | The preparation method of gout therapertics Lesinurad and Lesinurad intermediate | |
| CN102786516B (en) | Method for synthesizing rivaroxaban | |
| CA2352436C (en) | Polymorphs of telmisartan, processes for preparing them and their use in the preparation of a pharmaceutical composition | |
| CN106748950A (en) | A kind of preparation method of Bu Waxitan and its intermediate | |
| EP2114889A1 (en) | Method of preparing montelukast and intermediates used therein | |
| CN107501107A (en) | The intermediate synthetic method of quinolone medicine | |
| CN107963993A (en) | A kind of preparation method of high-purity ethiprole | |
| CN108409768B (en) | A kind of preparation method of boron trifluoride benzylamine complex compound | |
| CN103588765A (en) | Synthesis method for azilsartan medoxomil or salt thereof, intermediate of azilsartan medoxomil or salt thereof and synthesis method for intermediate | |
| JP7454498B2 (en) | Method for producing salicylamide acetate | |
| CN104703967B (en) | The process for purification of fluvoxamine free alkali and the preparation method of the high-purity fluvoxamine maleate using which | |
| CN103288708B (en) | The preparation method of 1- aryl -2- indolinone derivative | |
| CN107445892A (en) | Norfloxacin chemical industry synthesis method | |
| CN110041206B (en) | Preparation method of cinacalcet impurity | |
| CN112679407B (en) | Preparation method of chiral 5-substituted proline compound | |
| CN109516935A (en) | A kind of naphthylthio carbonyl complex and its preparation method and application | |
| CN106032380A (en) | Industrial production method of midazolam | |
| CN109721587B (en) | Method for preparing phthaloyl amlodipine and application thereof | |
| CN104910068B (en) | A kind of synthetic method of the tosilate of 2 cyano group isonicotinic acid hydrazide 1.5 | |
| CN106748816A (en) | A kind of synthetic method of the amino butanol of Du Lutewei key intermediates (R) 3 | |
| CN103739502B (en) | A kind of separation and purification technique of ambroxol alkali | |
| CN101225069A (en) | Method for synthesizing meropenem intermediate | |
| CN101823986A (en) | Preparation method for tert-butyl carbazate | |
| CN105085263B (en) | Preparation method and intermediate of 2-alkylacylmethyl-1,4-succinic acid derivative | |
| CN108997237B (en) | Synthesis method of flutriafol |
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 | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20171222 |