CN103554110A - Preparation method for synthesizing doxofylline - Google Patents
Preparation method for synthesizing doxofylline Download PDFInfo
- Publication number
- CN103554110A CN103554110A CN201310532936.4A CN201310532936A CN103554110A CN 103554110 A CN103554110 A CN 103554110A CN 201310532936 A CN201310532936 A CN 201310532936A CN 103554110 A CN103554110 A CN 103554110A
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- CN
- China
- Prior art keywords
- doxofylline
- bromoacetaldehyde
- preparation
- synthesizing
- dimethyl acetal
- Prior art date
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- C07D473/08—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1 and 3, e.g. theophylline
Abstract
The invention discloses a preparation method for synthesizing doxofylline. The preparation method comprises the following steps: firstly, carrying out bromination and alcoholization on vinyl acetate to obtain bromoacetaldehyde dimethyl acetal; mixing the bromoacetaldehyde dimethyl acetal with glycol to react to obtain bromoacetaldehyde ethylene acetal; adding potassium carbonate into bromoacetaldehyde ethylene acetal; and finally, separating out doxofylline under the catalytic effect of potassium carbonate. According to the preparation method for synthesizing the doxofylline, a plurality of paths of procedures are reduced; the whole reaction process is moderate in reaction conditions and the reaction process is easy to control; the cost is relatively low.
Description
Technical field
The present invention is specifically related to a kind of preparation method of synthetic doxofylline.
Background technology
Doxofylline is the derivative of methyl xanthine, can suppress the PDE in smooth muscle cell, and blocking-up Adenosine Receptors disturbs calcium ion in smooth muscle cell to move, lax bronchial smooth muscle; Also can suppress various inflammatory mediators and release of cytokines, thereby control airway inflammation, reduce airway hyperreactivity simultaneously.
Existing doxofylline preparation process is generally: by vinyl-acetic ester and bromine reaction, in retort, add vinyl-acetic ester, cooling, drip bromine under stirring, product bromoacetaldehyde methylal, uses dichloromethane extraction.Ethylene glycol drips bromoacetaldehyde methylal under heated and stirred, and decompression steams reaction product bromoacetaldehyde Glycol Acetal (being side chain); Theophylline is added in solvent dimethylformamide, drip bromoacetaldehyde Glycol Acetal, reflux, steams dimethyl formamide, obtains crude product doxofylline, then uses ethyl alcohol recrystallization, and activated carbon decolorizing, obtains product.
Summary of the invention
For addressing the above problem, the object of the invention is to provide a kind of reaction conditions gentle, convenient operation, the preparation method of synthetic doxofylline with low cost.
For achieving the above object, the technical solution adopted in the present invention is:
A preparation method for synthetic doxofylline, first obtains bromoacetaldehyde dimethyl acetal by vinyl acetate between to for plastic by upper bromine and alcoholization, then, and by bromoacetaldehyde dimethyl acetal and ethylene glycol hybrid reaction; Obtain bromoacetaldehyde condensed ethandiol, then salt of wormwood is added in bromoacetaldehyde condensed ethandiol; Under described salt of wormwood katalysis, finally separate out doxofylline.
Further, described bromoacetaldehyde condensed ethandiol reacts with theophylline in high polar solvent, separates out doxofylline.
Beneficial effect:
The preparation method of synthetic doxofylline of the present invention, compared with prior art, has reduced multiple working procedure, directly by repeatedly adding new reactant, carries out hybrid reaction, finally by adding potassium carbonate catalyst, directly separates out doxofylline; Whole reaction process reaction conditions is gentle, and reaction process is easily controlled, and operate easylier, and the while is owing to finally directly separating out product; Therefore cost is relatively cheap.
Embodiment
The preparation method of synthetic doxofylline of the present invention, first obtains bromoacetaldehyde dimethyl acetal by vinyl acetate between to for plastic by upper bromine and alcoholization, then, and by bromoacetaldehyde dimethyl acetal and ethylene glycol hybrid reaction; Obtain bromoacetaldehyde condensed ethandiol, then salt of wormwood is added in bromoacetaldehyde condensed ethandiol; Under described salt of wormwood katalysis, finally separate out doxofylline.
Described bromoacetaldehyde condensed ethandiol reacts with theophylline in high polar solvent, separates out doxofylline.
The preparation method of synthetic doxofylline of the present invention, has reduced multiple working procedure, directly by repeatedly adding new reactant, carries out hybrid reaction, finally by adding potassium carbonate catalyst, directly separates out doxofylline; Whole reaction process reaction conditions is gentle, and reaction process is easily controlled, and operate easylier, and the while is owing to finally directly separating out product; Therefore cost is relatively cheap.
Embodiment recited above is described the preferred embodiment of the present invention, not the spirit and scope of the present invention is limited.Do not departing under the prerequisite of design concept of the present invention; various modification and improvement that this area ordinary person makes technical scheme of the present invention; all should drop into protection scope of the present invention, the technology contents that the present invention asks for protection, is all documented in claims.
Claims (2)
1. the preparation method of a synthetic doxofylline, it is characterized in that: first vinyl acetate between to for plastic is obtained to bromoacetaldehyde dimethyl acetal by upper bromine and alcoholization, then, by bromoacetaldehyde dimethyl acetal and ethylene glycol hybrid reaction: obtain bromoacetaldehyde condensed ethandiol, then salt of wormwood is added in bromoacetaldehyde condensed ethandiol: under described salt of wormwood katalysis, finally separate out doxofylline.
2. the preparation method of synthetic doxofylline according to claim 1, is characterized in that: described bromoacetaldehyde condensed ethandiol reacts with theophylline in high polar solvent, separates out doxofylline.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310532936.4A CN103554110A (en) | 2013-10-29 | 2013-10-29 | Preparation method for synthesizing doxofylline |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310532936.4A CN103554110A (en) | 2013-10-29 | 2013-10-29 | Preparation method for synthesizing doxofylline |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103554110A true CN103554110A (en) | 2014-02-05 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310532936.4A Pending CN103554110A (en) | 2013-10-29 | 2013-10-29 | Preparation method for synthesizing doxofylline |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103554110A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105237538A (en) * | 2015-10-10 | 2016-01-13 | 斯卫东 | Preparation methods of doxofylline |
| CN106916156A (en) * | 2015-12-23 | 2017-07-04 | 北京颐方生物科技有限公司 | A kind of preparation method of doxofylline |
| CN111233864A (en) * | 2020-03-07 | 2020-06-05 | 安徽恒星制药有限公司 | Novel method for simply, conveniently and industrially producing doxofylline in green |
| CN111995625A (en) * | 2020-08-28 | 2020-11-27 | 开封康诺药业有限公司 | Preparation method of doxofylline |
| CN113234076A (en) * | 2021-05-26 | 2021-08-10 | 湖北午时药业股份有限公司 | Preparation method of doxofylline |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2146016A (en) * | 1983-09-06 | 1985-04-11 | Ciba Geigy Ag | Method for the preparation of haloacetals and halodioxolanes |
| CN102936248A (en) * | 2012-10-30 | 2013-02-20 | 开封明仁药业有限公司 | Method for preparing doxofylline |
-
2013
- 2013-10-29 CN CN201310532936.4A patent/CN103554110A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2146016A (en) * | 1983-09-06 | 1985-04-11 | Ciba Geigy Ag | Method for the preparation of haloacetals and halodioxolanes |
| CN102936248A (en) * | 2012-10-30 | 2013-02-20 | 开封明仁药业有限公司 | Method for preparing doxofylline |
Non-Patent Citations (1)
| Title |
|---|
| 金嵇煜: "2,2-二甲氧基乙胺的制备", 《精细化工中间体》 * |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105237538A (en) * | 2015-10-10 | 2016-01-13 | 斯卫东 | Preparation methods of doxofylline |
| CN105237538B (en) * | 2015-10-10 | 2017-08-08 | 斯卫东 | A kind of preparation method of doxofylline |
| CN106916156A (en) * | 2015-12-23 | 2017-07-04 | 北京颐方生物科技有限公司 | A kind of preparation method of doxofylline |
| CN106916156B (en) * | 2015-12-23 | 2019-03-26 | 北京颐方生物科技有限公司 | A kind of preparation method of doxofylline |
| CN111233864A (en) * | 2020-03-07 | 2020-06-05 | 安徽恒星制药有限公司 | Novel method for simply, conveniently and industrially producing doxofylline in green |
| CN111233864B (en) * | 2020-03-07 | 2020-12-22 | 安徽恒星制药有限公司 | Method for industrially producing doxofylline |
| CN111995625A (en) * | 2020-08-28 | 2020-11-27 | 开封康诺药业有限公司 | Preparation method of doxofylline |
| CN111995625B (en) * | 2020-08-28 | 2024-03-26 | 开封康诺药业有限公司 | Preparation method of doxofylline |
| CN113234076A (en) * | 2021-05-26 | 2021-08-10 | 湖北午时药业股份有限公司 | Preparation method of doxofylline |
| CN113234076B (en) * | 2021-05-26 | 2023-08-18 | 湖北午时药业股份有限公司 | Preparation method of doxofylline |
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Application publication date: 20140205 |