CN102010388B - Preparation method of ranitidine - Google Patents
Preparation method of ranitidine Download PDFInfo
- Publication number
- CN102010388B CN102010388B CN200910144825A CN200910144825A CN102010388B CN 102010388 B CN102010388 B CN 102010388B CN 200910144825 A CN200910144825 A CN 200910144825A CN 200910144825 A CN200910144825 A CN 200910144825A CN 102010388 B CN102010388 B CN 102010388B
- Authority
- CN
- China
- Prior art keywords
- methyl
- ranitidine
- preparation
- hours
- reaction 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.)
- Expired - Fee Related
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
Abstract
The invention discloses a preparation method of ranitidine, comprising the following processing steps of: (1) mixing ethanol and 2-[[[5-(dimethylamino)methyl-2-furan]methyl]sulfhydryl] ethylamine; (2) adding N-methyl-1-methylmercapto-2-nitroethylene amine into a reaction solution, slowly heating to 40-45 DEG C and maintaining for 8-10 hours; (3) cooling a reaction solution to 4-8 DEG C and maintaining for 32-38 hours, and crystallizing for full precipitation; and (4) filtering the reaction solution, washing crystals, pumping and drying to obtain the white ranitidine. The preparation method of the ranitidine in the invention has the advantages of simple steps, higher yield and lower processing cost and is suitable for mass production.
Description
Technical field
The present invention relates to prepare the method for Ranitidine HCL, belong to medical technical field.
Background technology
Ranitidine HCL is the main raw material of preparation ranitidine hydrochloride; Ranitidine hydrochloride; English name: Ranitidine Leinitiding Piam, its pharmacology has the effect of competitive retardance histamine and H2 receptors bind, gastric acid inhibitory effect; Count 5 times～12 times of Cimitidine Type A/AB with mole, so be strong H2 receptor-blocking agent of imitating.Be mainly used in treatment duodenal ulcer, stomach ulcer, reflux esophagitis, Zhuo-Ai (Zollinger-Ellison) syndrome and other high gastric acid secretion diseases.
At present, prior art is for the preparation Ranitidine HCL, and its complex steps, yield is lower and tooling cost is higher, and is not suitable for production in enormous quantities.
Summary of the invention
To the problems referred to above, the present invention provides that a kind of step is simple, yield is higher and tooling cost is lower, is fit to produce in enormous quantities the preparation method of Ranitidine HCL.
For realizing above goal of the invention, the invention provides a kind of preparation method of Ranitidine HCL, process step is following:
(1) ethanol and 2-[[[5-(dimethylamino) methyl-2-furans] methyl] sulfenyl] ethamine are mixed;
(2) in reaction solution, add N-methyl isophthalic acid-methylthio group-2-nitroethylene amine, slowly heat up 40～45 ℃ and kept 8～10 hours again;
(3) reaction solution is cooled to 4～8 ℃ and kept 32～38 hours, crystallization is fully separated out;
(4) with reacting liquid filtering, and with crystal wash, drain, drying, the Ranitidine HCL of off-white color;
Wherein, the mol ratio of said 2-[[[5-(dimethylamino) methyl-2-furans] methyl] sulfenyl] ethamine and N-methyl isophthalic acid-methylthio group-2-nitroethylene amine is 1: 1;
Preferentially, the said washing of step (4) is with twice of cold washing with alcohol with crystallization.
Preferentially, the said drying of step (4) is vacuum-drying, and temperature is controlled at 30 ℃, and the time is 4 hours.
The preparation method of Ranitidine HCL according to the invention has following advantage: step is simple, yield is higher and tooling cost is lower, is fit to produce in enormous quantities.
Embodiment
In order to make those skilled in the art person understand the present invention program better, and make above-mentioned purpose of the present invention, feature and advantage can be more obviously understandable, below in conjunction with embodiment the present invention done further detailed explanation.
Embodiment 1
Get ethanol 200kg, 2-[[[5-(dimethylamino) methyl-2-furans] methyl] sulfenyl] ethamine 17.0kg in a retort, to wherein adding N-methyl isophthalic acid-methylthio group-2-nitroethylene amine 12.3kg.Finish, slowly heat up 40 ℃ and make it solubilizing reaction, and kept 8～10 hours.
Reaction finishes, and reaction solution is cooled to 4 ℃ kept 36 hours, and crystallization is fully separated out; Filter then, crystallization is drained with cold washing with alcohol twice (20ml/ time); Crystal vacuum-drying (30 ℃ of temperature, 4 hours time), the Ranitidine HCL crystallization 21.09kg of off-white color.
Embodiment 2
Get ethanol 200kg, 2-[[[5-(dimethylamino) methyl-2-furans] methyl] sulfenyl] ethamine 17.0kg in a retort, to wherein adding N-methyl isophthalic acid-methylthio group-2-nitroethylene amine 12.3kg.Finish, slowly heat up 42 ℃ and make it solubilizing reaction, and kept 8～10 hours.
Reaction finishes, and reaction solution is cooled to 6 ℃ kept 36 hours, and crystallization is fully separated out; Filter then, crystallization is drained with cold washing with alcohol twice (20ml/ time); Crystal vacuum-drying (30 ℃ of temperature, 4 hours time), the Ranitidine HCL crystallization 21.04kg of off-white color.
Embodiment 3
Get ethanol 200kg, 2-[[[5-(dimethylamino) methyl-2-furans] methyl] sulfenyl] ethamine 17.0kg in a retort, to wherein adding N-methyl isophthalic acid-methylthio group-2-nitroethylene amine 12.3kg.Finish, slowly heat up 45 ℃ and make it solubilizing reaction, and kept 8～10 hours.
Reaction finishes, and reaction solution is cooled to 8 ℃ kept 36 hours, and crystallization is fully separated out; Filter then, crystallization is drained with cold washing with alcohol twice (20ml/ time); Crystal vacuum-drying (30 ℃ of temperature, 4 hours time), the Ranitidine HCL crystallization 21.09kg of off-white color.
The solid ranitidine hydrochloride that the method for the invention makes, yield about 84.9%, fusing point: 69.2～70.4 ℃.
The above; Be merely embodiment of the present invention; Should be noted that protection scope of the present invention is not limited thereto; Any technician who is familiar with the present technique field is in the technical scope that the present invention discloses, and the variation that can expect easily or replacement all should be encompassed within protection scope of the present invention.Therefore, protection scope of the present invention should be as the criterion with the protection domain that claim was defined.
Claims (3)
1. the preparation method of a Ranitidine HCL is characterized in that, process step is following:
(1) ethanol and 2-[[[5-(dimethylamino) methyl-2-furans] methyl] sulfenyl] ethamine are mixed;
(2) in reaction solution, add N-methyl isophthalic acid-methylthio group-2-nitroethylene amine, slowly heat up 40～45 ℃ and kept 8～10 hours again;
(3) reaction solution is cooled to 4～8 ℃ and kept 32～38 hours, crystallization is fully separated out;
(4) with reacting liquid filtering, and with crystal wash, drain, drying, the Ranitidine HCL of off-white color;
Wherein, the mol ratio of said 2-[[[5-(dimethylamino) methyl-2-furans] methyl] sulfenyl] ethamine and N-methyl isophthalic acid-methylthio group-2-nitroethylene amine is 1: 1.
2. the preparation method of Ranitidine HCL according to claim 1 is characterized in that, the said washing of step (4) is with twice of cold washing with alcohol with crystallization.
3. the preparation method of Ranitidine HCL according to claim 1 is characterized in that, the said drying of step (4) is vacuum-drying, and temperature is controlled at 30 ℃, and the time is 4 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910144825A CN102010388B (en) | 2009-09-04 | 2009-09-04 | Preparation method of ranitidine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910144825A CN102010388B (en) | 2009-09-04 | 2009-09-04 | Preparation method of ranitidine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102010388A CN102010388A (en) | 2011-04-13 |
| CN102010388B true CN102010388B (en) | 2012-09-05 |
Family
ID=43840742
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200910144825A Expired - Fee Related CN102010388B (en) | 2009-09-04 | 2009-09-04 | Preparation method of ranitidine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102010388B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0059082A1 (en) * | 1981-02-20 | 1982-09-01 | Glaxo Group Limited | Process for the preparation of a furan derivative |
| GB2169600A (en) * | 1985-01-11 | 1986-07-16 | Richter Gedeon Vegyeszet | Process for preparing a basic thioether and the salt thereof |
| CN1724526A (en) * | 2005-07-11 | 2006-01-25 | 石药集团中诺药业（石家庄）有限公司 | Synthesis method of ranitidine alkali and its hydrochloride |
-
2009
- 2009-09-04 CN CN200910144825A patent/CN102010388B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0059082A1 (en) * | 1981-02-20 | 1982-09-01 | Glaxo Group Limited | Process for the preparation of a furan derivative |
| GB2169600A (en) * | 1985-01-11 | 1986-07-16 | Richter Gedeon Vegyeszet | Process for preparing a basic thioether and the salt thereof |
| CN1724526A (en) * | 2005-07-11 | 2006-01-25 | 石药集团中诺药业（石家庄）有限公司 | Synthesis method of ranitidine alkali and its hydrochloride |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102010388A (en) | 2011-04-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101144600B1 (en) | Process for Preparing and Conversion of Ilaprazole Crystalline Form A, B | |
| CA2593044A1 (en) | Substituted oxindole derivatives, medicaments containing said derivatives and use thereof | |
| JP2012500819A5 (en) | ||
| CN103709143A (en) | Preparation method of esomeprazole and magnesium salt thereof | |
| CN102010389B (en) | Method for preparing ranitidine hydrochloride | |
| CN107298646A (en) | A kind of preparation method of noradrenalin | |
| CN104557720B (en) | A kind of preparation method of cimetidine | |
| CN104829590B (en) | Method for purifying trelagliptin | |
| CN104530033B (en) | A kind of preparation technology new method of Arotinolol Hydrochlorid | |
| CN102010388B (en) | Preparation method of ranitidine | |
| CN107298678B (en) | Preparation method of bulk drug suvorexant | |
| WO2019196802A1 (en) | Crystal form of 3-(4-methyl-1h-imidazol-1-yl)-5-trifluoromethylaniline monohydrochloride and use thereof | |
| CN105440019A (en) | Preparation method of drug for treating gastric acid related diseases | |
| CN105777750A (en) | Synthesis method for moxifloxacin side chain | |
| CN107814758B (en) | Preparation of pyrrole sulfonic acid compound salt | |
| CN106831759A (en) | The preparation method of Pabuk former times profit cloth and its intermediate | |
| JP5315337B2 (en) | Crystalline form of topotecan hydrochloride and method for producing the same | |
| JP2010502682A5 (en) | ||
| CN107400118B (en) | Preparation method of esomeprazole intermediate | |
| WO2013020461A1 (en) | Preparation method for gefitinib intermediate | |
| TW200844100A (en) | Regio-selective Ullmann synthesis of 4-bromo-3-methyl-5-propoxy-thiophene-2-carboxylic acid | |
| CN110845405A (en) | Synthesis method of 7-chloroquinaldine | |
| WO2008139484A3 (en) | New process for the synthesis of loferpramine maleate: a stable salt of loferpramine | |
| JP2004002230A (en) | Method for producing microaqueous benzimidazole compound | |
| CN104693177A (en) | Refining method of esomeprazole sodium |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20120905 Termination date: 20150904 |
|
| EXPY | Termination of patent right or utility model |