CN108864048A - A kind of preparation method of dabigatran etexilate methanesulfonate - Google Patents
A kind of preparation method of dabigatran etexilate methanesulfonate Download PDFInfo
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
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Abstract
The invention belongs to technical field of medicine preparation, and in particular to a kind of preparation method of new oral anticoagulation medicine dabigatran etexilate methanesulfonate.This method includes：（1）By 3-, [[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -2- base) amino]-ethyl propionate tosilate, potassium carbonate are added in lytic agent and are uniformly mixed；（2）The just own ester reaction of chloro-carbonic acid is added；（3）Refining solvent is added to dissolve to obtain dabigatran etcxilate；（4）Reaction dissolvent is added to dissolve, dropwise addition methanesulfonic acid reaction and etc..Generally, dabigatran etexilate methanesulfonate preparation method provided herein, reaction condition is more mild in its preparation process, reaction time is shorter, and it is also generated without poisonous and harmful substance in finished product purification process, in addition final finished dabigatran etexilate methanesulfonate yield is higher, therefore, there is preferable practical value and promote and apply meaning.
Description
Technical field
The invention belongs to technical field of medicine preparation, and in particular to a kind of new oral anticoagulation medicine methanesulfonic acid Da Bijia
The preparation method of group's ester.
Background technique
Dabigatran etcxilate (dabigatran etexilate) trade name Pradaxa, is by German Bo Linge Yin lattice
The new oral anticoagulation medicine of writing brush (Boehringer Ingelheim) company exploitation belongs to the direct fibrin ferment suppression of non-peptides
Preparation was taken the lead in ratifying listing by European Union EMA in March, 2008, and on September 20th, 2010, FDA ratified it in the U.S.
The stroke prevention that city, the thrombus prevention postoperative for hip joint and knee prosthesis and atrium vibration (AF) cause.It uses
When, dabigatran etcxilate is converted into active dabigatran, the latter is by directly inhibiting fibrin ferment hair as prodrug in vivo
Wave anticoagulation effect.The medicine is oral, potent, few without Medication monitor, drug interaction due to having the characteristics that, clinical
Application prospect is optimistic.
For the preparation of the medicine, existing preparation method is usually by 3- [[[2- [[(4- carbamimido-phenyl) amino] methyl] -1-
Methyl-1 H- benzimidazole -5- carbonyl] (pyridine -2- base) amino]-ethyl propionate and the just own ester of chloro-carbonic acid directly carry out being condensed it is anti-
Dabigatran etexilate methanesulfonate should be prepared into.But analysis and research show in existing preparation process, that there are reaction temperatures is low, reaction when
Between it is long, complicated for operation, purification needs silica gel column chromatography, and the defects of yield is low, purity is low, the period is long, limits mass production,
Further limit the popularization and application of the medicine.
Summary of the invention
The application is designed to provide a kind of new preparation method of dabigatran etexilate methanesulfonate, which reacted
Reaction condition is more mild in journey, and no poisonous and harmful substance generates, and preparation gained dabigatran etexilate methanesulfonate yield is higher, from
It and is that certain basis is established in the mass production of the medicine.
Details are as follows for the technical solution that the application is taken.
A kind of preparation method of dabigatran etexilate methanesulfonate, operating procedure are：
（1）By 3- [[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -2-
Base) amino]-ethyl propionate tosilate, potassium carbonate be added lytic agent in be uniformly mixed；
In terms of specific dosage, 3- [[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl]
(pyridine -2- base) amino]-ethyl propionate tosilate dosage be 40g, carbonic acid potassium application rate be 50 ~ 60g；
When hybrid manipulation, the lytic agent is preferably acetone-water system；The acetone-water system, specifically by 1000ml acetone and
500 ~ 600ml water is uniformly mixed and is formulated solution；
The 3- [[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -2- base)
Amino]-ethyl propionate tosilate, acquisition can be made by the steps：
A, by 3- [[[2- [[(4- cyano-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- base] carbonyl] pyridine -2-
Base amino] ethyl propionate, methanol be added reaction kettle in；
By quality ratio, methanol additional amount is 3- [[[2- [[(4- cyano-phenyl) amino] methyl] -1- methyl-1 H- benzo miaow
Azoles -5- base] carbonyl] pyridine -2- base amino] 5 ~ 7 times of ethyl propionate quality；
B, hydrogen chloride gas is passed through to being saturated, and is reacted at room temperature 24 hours；
C, methanol dissolution is added after evaporated under reduced pressure, is passed through ammonia to being saturated, room temperature reaction is for 24 hours；
D, p-methyl benzenesulfonic acid is then added, stirring and crystallizing is filtered, washed（It is washed for example, by using acetone）, it is dry to get 3-
[[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -2- base) amino]-propionic acid
Ethyl ester tosilate；
By quality ratio, p-methyl benzenesulfonic acid additional amount is 3- [[[2- [[(4- cyano-phenyl) amino] methyl] -1- methyl-1 H- benzene
And imidazoles -5- base] carbonyl] pyridine -2- base amino] 0.6 ~ 0.7 times of ethyl propionate quality；
（2）To step（1）In the just own ester of chloro-carbonic acid is added in the reaction system that is uniformly mixed, under room temperature（15~30℃）Reaction 2 ~
4h；Then crystallization is carried out under the conditions of 0-5 DEG C, filter to obtain crude product；
Corresponding step（1）In dosage, the just own ester dosage of chloro-carbonic acid be 10-15g；
（3）By step（2）Gained crude product adds 60 ~ 65 DEG C of refining solvent dissolutions that reaction solution is cooled to 0 ~ 5 DEG C after dissolution completely
Crystallization is carried out, filtering obtains dabigatran etcxilate；
The refining solvent is preferably ethyl alcohol；
（4）By step（3）Gained dabigatran etcxilate adds 40 ~ 45 DEG C of reaction dissolvent dissolutions, methanesulfonic acid is added dropwise after dissolving completely, sufficiently
Reaction solution is cooled to 0 ~ 5 DEG C of crystallization after reaction, is filtered, by 7~8h of filtration cakes torrefaction, gained is dabigatran etexilate methanesulfonate；
The reaction dissolvent is acetone；
In terms of specific dosage, 0.15 ~ 0.2 times that quality is dabigatran etcxilate quality is added in methanesulfonic acid.
Compared with prior art, the major technique advantage of the application is embodied in following aspects：
（1）Reaction dissolvent is done by using acetone-water system, reaction temperature is increased to by 0 DEG C and is reacted at room temperature, is reduced anti-
Difficulty is answered, while the reaction time is shortened into 2 ~ 4h by 8 ~ 10h, process flow is substantially reduced, reduces energy consumption；
（2）In purification process, crude product is purified using ethyl alcohol, avoids the complexity of subsequent silica gel column chromatography purification, simultaneously
Testing result also indicates that finished product prepared by purification mode is with high purity in the application, simultaneously because purification reagent alcohol can recycling
Recycling, therefore can preferably reduce cost for purification.
Generally, dabigatran etexilate methanesulfonate preparation method provided herein, reaction condition is more in preparation process
Mildly, reaction time is shorter, and also generates without poisonous and harmful substance in finished product purification process, in addition final finished methanesulfonic acid reaches
Than adding group ester yield higher, therefore, there is preferable practical value and promote and apply meaning.
Specific embodiment
Explanation is further explained to the application below with reference to embodiment.
Embodiment 1
The preparation method of dabigatran etexilate methanesulfonate provided herein, operating process are specifically described as follows.
（1）By 3- [[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -
2- yl) amino]-ethyl propionate tosilate, potassium carbonate be added lytic agent in be uniformly mixed；
In terms of specific dosage, 3- [[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl]
(pyridine -2- base) amino]-ethyl propionate tosilate dosage be 40g, carbonic acid potassium application rate be 56g；
When hybrid manipulation, the lytic agent is acetone-water system；The acetone-water system, specifically by 1000ml acetone and
550ml water is uniformly mixed and is formulated solution.
Described 3- [[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -
2- yl) amino]-ethyl propionate tosilate, acquisition is made by the steps：
A, by 3- [[[2- [[(4- cyano-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- base] carbonyl] pyridine -2-
Base amino] ethyl propionate, methanol be added reaction kettle in；
In terms of specific dosage, methanol additional amount is 300g, 3- [[[2- [[(4- cyano-phenyl) amino] methyl] -1- methyl-1 H-
Benzimidazole -5- base] carbonyl] pyridine -2- base amino] and ethyl propionate dosage be 50g, that is, methanol additional amount be 3- [[[2-
[[(4- cyano-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- base] carbonyl] pyridine -2- base amino] ethyl propionate
6 times of quality；
B, hydrogen chloride gas is passed through to being saturated, and is reacted at room temperature 24 hours；
C, methanol 300g dissolution is added after evaporated under reduced pressure, is passed through ammonia to being saturated, room temperature reaction is for 24 hours；
D, p-methyl benzenesulfonic acid is then added, stirring and crystallizing is filtered, washed（It is washed using acetone）, it is dry to get 3-
[[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -2- base) amino]-propionic acid
Ethyl ester tosilate；
In terms of specific dosage, p-methyl benzenesulfonic acid dosage is 31g；
Finally obtained 3- [[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -
2- yl) amino]-ethyl propionate tosilate 42.0g.
（2）To step（1）In the just own ester of chloro-carbonic acid is added in the reaction system that is uniformly mixed, under room temperature（20 DEG C or so）Instead
Answer 3h or so；Then 4 DEG C or so progress crystallizations, filter to obtain crude product；
Corresponding step（1）In dosage, the just own ester dosage of chloro-carbonic acid be 11g.
（3）By step（2）Gained crude product adds refining solvent ethyl alcohol 300ml to dissolve in 60 DEG C or so, will after dissolution completely
Reaction solution is cooled to 4 DEG C or so progress crystallizations, and filtering obtains dabigatran etcxilate 25.0g.
（4）By step（3）Gained dabigatran etcxilate 20.0g adds reaction dissolvent acetone 200ml to dissolve in 42 DEG C or so, molten
Solution completely after methanesulfonic acid 3.2g is added dropwise, reaction solution is sufficiently cooled to 4 DEG C or so crystallizations after reaction, is filtered, by filtration cakes torrefaction 7~
8h, gained are dabigatran etexilate methanesulfonate, obtain 21.4g altogether.
Further obtained finished product is detected, final calculating and testing result show：With 3- [[[2- [[(4- amidino groups
Phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -2- base) amino]-ethyl propionate p-methyl benzenesulfonic acid
Salt meter, weight yield 66.9%；And high performance liquid chromatography（HPLC）Measuring purity is：99.8%, largest single impurity 0.08%.
Embodiment 2
The preparation method of dabigatran etexilate methanesulfonate provided by the present embodiment, detailed process is substantially with embodiment 1, only adjustment section
Divide response parameter as follows：
Step（1）In：
When dissolving hybrid manipulation：In terms of specific dosage, 3- [[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzene
And imidazoles -5- carbonyl] (pyridine -2- base) amino]-ethyl propionate tosilate dosage be 40g, carbonic acid potassium application rate be 58g；
It prepares 3- [[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -2- base)
Amino]-ethyl propionate tosilate when：
In step A, methanol additional amount is 320g, 3- [[[2- [[(4- cyano-phenyl) amino] methyl] -1- methyl-1 H- benzo miaow
Azoles -5- base] carbonyl] pyridine -2- base amino] and ethyl propionate dosage be 50g；
Methanol 320g dissolution is added in step C, after evaporated under reduced pressure；
In step D, p-methyl benzenesulfonic acid dosage is 33g；
Finally obtained 3- [[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -
2- yl) amino]-ethyl propionate tosilate 43.0g；
Step（2）In：
The just own ester dosage of chloro-carbonic acid is 13g；
Step（3）In：
Obtain dabigatran etcxilate 25.3g.
Step（4）In：
By step（3）Gained dabigatran etcxilate 20.0g adds reaction dissolvent acetone 200ml to dissolve in 42 DEG C or so, after dissolution completely
Methanesulfonic acid 3.3g is added dropwise, reaction solution is sufficiently cooled to 4 DEG C or so crystallizations after reaction, is filtered, by 7~8h of filtration cakes torrefaction, gained
As dabigatran etexilate methanesulfonate obtains 21.6g altogether.
Further obtained finished product is detected, final calculating and testing result show：With 3- [[[2- [[(4- amidino groups
Phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -2- base) amino]-ethyl propionate p-methyl benzenesulfonic acid
Salt meter, weight yield 68.3%；And high performance liquid chromatography（HPLC）Measuring purity is：99.6%, largest single impurity 0.1%.
Embodiment 3
The preparation method of dabigatran etexilate methanesulfonate provided by the present embodiment, detailed process is substantially with embodiment 1, only adjustment section
Divide response parameter as follows：
Step（1）In：
When dissolving hybrid manipulation：In terms of specific dosage, 3- [[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzene
And imidazoles -5- carbonyl] (pyridine -2- base) amino]-ethyl propionate tosilate dosage be 40g, carbonic acid potassium application rate be 56g；
It prepares 3- [[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -2- base)
Amino]-ethyl propionate tosilate when：
In step A, methanol additional amount is 300g, 3- [[[2- [[(4- cyano-phenyl) amino] methyl] -1- methyl-1 H- benzo miaow
Azoles -5- base] carbonyl] pyridine -2- base amino] and ethyl propionate dosage be 50g；
Methanol 320g dissolution is added in step C, after evaporated under reduced pressure；
In step D, p-methyl benzenesulfonic acid dosage is 31g；
Finally obtained 3- [[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -
2- yl) amino]-ethyl propionate tosilate 41.5g.
Step（2）In：
The just own ester dosage of chloro-carbonic acid is 12g；
Step（3）In：
Obtain dabigatran etcxilate 25.6g.
Step（4）In：
By step（3）Gained dabigatran etcxilate 20.0g adds reaction dissolvent acetone 200ml to dissolve in 42 DEG C or so, after dissolution completely
Methanesulfonic acid 3.5g is added dropwise, reaction solution is sufficiently cooled to 4 DEG C or so crystallizations after reaction, is filtered, by 7~8h of filtration cakes torrefaction, gained
As dabigatran etexilate methanesulfonate obtains 21.5g altogether.
Further obtained finished product is detected, final calculating and testing result show：With 3- [[[2- [[(4- amidino groups
Phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -2- base) amino]-ethyl propionate p-methyl benzenesulfonic acid
Salt meter, weight yield 68.8%；And high performance liquid chromatography（HPLC）Measuring purity is：99.5%, largest single impurity 0.1%.
Embodiment 4
The preparation method of dabigatran etexilate methanesulfonate provided by the present embodiment, detailed process is substantially with embodiment 1, only adjustment section
Divide response parameter as follows：
Step（1）In：
When dissolving hybrid manipulation：In terms of specific dosage, 3- [[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzene
And imidazoles -5- carbonyl] (pyridine -2- base) amino]-ethyl propionate tosilate dosage be 40g, carbonic acid potassium application rate be 56g；
It prepares 3- [[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -2- base)
Amino]-ethyl propionate tosilate when：
In step A, methanol additional amount is 330g, 3- [[[2- [[(4- cyano-phenyl) amino] methyl] -1- methyl-1 H- benzo miaow
Azoles -5- base] carbonyl] pyridine -2- base amino] and ethyl propionate dosage be 50g；
Methanol 330g dissolution is added in step C, after evaporated under reduced pressure；
In step D, p-methyl benzenesulfonic acid dosage is 32g；
Finally obtained 3- [[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -
2- yl) amino]-ethyl propionate tosilate 42.4g.
Step（2）In：
The just own ester dosage of chloro-carbonic acid is 11g；
Step（3）In：
Obtain dabigatran etcxilate 25.4g.
Step（4）In：
By step（3）Gained dabigatran etcxilate 20.0g adds reaction dissolvent acetone 200ml to dissolve in 42 DEG C or so, after dissolution completely
Methanesulfonic acid 3.3g is added dropwise, reaction solution is sufficiently cooled to 4 DEG C or so crystallizations after reaction, is filtered, by 7~8h of filtration cakes torrefaction, gained
As dabigatran etexilate methanesulfonate obtains 21.4g altogether.
Further obtained finished product is detected, final calculating and testing result show：With 3- [[[2- [[(4- amidino groups
Phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -2- base) amino]-ethyl propionate p-methyl benzenesulfonic acid
Salt meter, weight yield 67.9%；And high performance liquid chromatography（HPLC）Measuring purity is：99.7%, largest single impurity 0.09%.
Claims (6)
1. a kind of preparation method of dabigatran etexilate methanesulfonate, which is characterized in that this method comprises the following steps：
（1）By 3- [[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -2-
Base) amino]-ethyl propionate tosilate, potassium carbonate be added lytic agent in be uniformly mixed；
When hybrid manipulation, the lytic agent is acetone-water system；
（2）To step（1）In be uniformly mixed reaction system in be added the just own ester of chloro-carbonic acid, react 2 ~ 4h；Then crystallization is carried out,
Filter to obtain crude product；
（3）By step（2）Gained crude product adds refining solvent to dissolve, and after dissolution completely, reaction solution is cooled down and carries out crystallization, filtering,
Obtain dabigatran etcxilate；
（4）By step（3）Gained dabigatran etcxilate adds reaction dissolvent to dissolve, and methanesulfonic acid is added dropwise after dissolving completely, sufficiently after reaction
Reaction solution is cooled down crystallization, filtering, by filtration cakes torrefaction, gained is dabigatran etexilate methanesulfonate.
2. the preparation method of dabigatran etexilate methanesulfonate as described in claim 1, which is characterized in that step（1）In, 3- [[[2-
[[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -2- base) amino]-ethyl propionate
Tosilate dosage is 40g, and carbonic acid potassium application rate is 50 ~ 60g, at this time step（2）The just own ester dosage of middle chloro-carbonic acid is 10-
15g。
3. the preparation method of dabigatran etexilate methanesulfonate as described in claim 1, which is characterized in that step（3）In, the purification
Solvent is ethyl alcohol.
4. the preparation method of dabigatran etexilate methanesulfonate as described in claim 1, which is characterized in that step（4）In, the reaction
Solvent is acetone；In terms of specific dosage, 0.15 ~ 0.2 times that quality is dabigatran etcxilate quality is added in methanesulfonic acid.
5. the preparation method of dabigatran etexilate methanesulfonate as described in claim 1, which is characterized in that step（1）In, described third
Ketone-aqueous systems is uniformly mixed by 1000ml acetone and 500 ~ 600ml water and is formulated.
6. the preparation method of dabigatran etexilate methanesulfonate as described in claim 1, which is characterized in that step（1）In, the 3-
[[[2- [[(4- carbamimido-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -2- base) amino]-propionic acid
Ethyl ester tosilate, preparation method are：
A, by 3- [[[2- [[(4- cyano-phenyl) amino] methyl] -1- methyl-1 H- benzimidazole -5- base] carbonyl] pyridine -2-
Base amino] ethyl propionate, methanol be added reaction kettle in；
By quality ratio, methanol additional amount is 3- [[[2- [[(4- cyano-phenyl) amino] methyl] -1- methyl-1 H- benzo miaow
Azoles -5- base] carbonyl] pyridine -2- base amino] 5 ~ 7 times of ethyl propionate quality；
B, hydrogen chloride gas is passed through to being saturated, and is reacted at room temperature；
C, methanol dissolution is added after evaporated under reduced pressure, is passed through ammonia to being saturated, reacts at room temperature；
D, p-methyl benzenesulfonic acid is then added, stirring and crystallizing is filtered, washed, dries to get 3- [[[2- [[(4- carbamimido-phenyl) ammonia
Base] methyl] -1- methyl-1 H- benzimidazole -5- carbonyl] (pyridine -2- base) amino]-ethyl propionate tosilate；
By quality ratio, p-methyl benzenesulfonic acid additional amount is 3- [[[2- [[(4- cyano-phenyl) amino] methyl] -1- methyl-1 H- benzene
And imidazoles -5- base] carbonyl] pyridine -2- base amino] 0.6 ~ 0.7 times of ethyl propionate quality.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114716411A (en) * | 2022-04-29 | 2022-07-08 | 天方药业有限公司 | Method for recovering and preparing dabigatran etexilate mesylate from production mother liquor |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140148601A1 (en) * | 2010-12-06 | 2014-05-29 | Msn Laboratories Limited | Process for the preparation of benzimidazole derivatives and its salts |
| WO2014192030A2 (en) * | 2013-05-29 | 2014-12-04 | Laurus Labs Private Limited | An improved process for preparation of dabigatran etexilate and pharmaceutically acceptable acid addition salts thereof |
| CN104418839A (en) * | 2013-08-26 | 2015-03-18 | 深圳翰宇药业股份有限公司 | Synthetic method of dabigatran etexilate |
| CN104650037A (en) * | 2014-12-30 | 2015-05-27 | 青岛黄海制药有限责任公司 | Synthesis method of dabigatran etexilate |
| CN106397403A (en) * | 2016-08-30 | 2017-02-15 | 苏州天马精细化学品股份有限公司 | Method for purifying dabigatran etexilate mesylate intermediate |
| CN107686476A (en) * | 2017-09-04 | 2018-02-13 | 扬子江药业集团广州海瑞药业有限公司 | A kind of preparation technology of dabigatran etexilate methanesulfonate |
-
2018
- 2018-07-05 CN CN201810729075.1A patent/CN108864048A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140148601A1 (en) * | 2010-12-06 | 2014-05-29 | Msn Laboratories Limited | Process for the preparation of benzimidazole derivatives and its salts |
| WO2014192030A2 (en) * | 2013-05-29 | 2014-12-04 | Laurus Labs Private Limited | An improved process for preparation of dabigatran etexilate and pharmaceutically acceptable acid addition salts thereof |
| CN104418839A (en) * | 2013-08-26 | 2015-03-18 | 深圳翰宇药业股份有限公司 | Synthetic method of dabigatran etexilate |
| CN104650037A (en) * | 2014-12-30 | 2015-05-27 | 青岛黄海制药有限责任公司 | Synthesis method of dabigatran etexilate |
| CN106397403A (en) * | 2016-08-30 | 2017-02-15 | 苏州天马精细化学品股份有限公司 | Method for purifying dabigatran etexilate mesylate intermediate |
| CN107686476A (en) * | 2017-09-04 | 2018-02-13 | 扬子江药业集团广州海瑞药业有限公司 | A kind of preparation technology of dabigatran etexilate methanesulfonate |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114716411A (en) * | 2022-04-29 | 2022-07-08 | 天方药业有限公司 | Method for recovering and preparing dabigatran etexilate mesylate from production mother liquor |
| CN114716411B (en) * | 2022-04-29 | 2024-03-15 | 天方药业有限公司 | Method for recovering and preparing dabigatran etexilate mesylate from production mother liquor |
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Application publication date: 20181123 |