CN102250112A - Preparation method of 7-bromine-4-amino-thienopyrimidine - Google Patents
Preparation method of 7-bromine-4-amino-thienopyrimidine Download PDFInfo
- Publication number
- CN102250112A CN102250112A CN2010101785097A CN201010178509A CN102250112A CN 102250112 A CN102250112 A CN 102250112A CN 2010101785097 A CN2010101785097 A CN 2010101785097A CN 201010178509 A CN201010178509 A CN 201010178509A CN 102250112 A CN102250112 A CN 102250112A
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- China
- Prior art keywords
- medicament
- thienopyrimidine
- aminothiophene
- pyrimidine
- preparation
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Abstract
The invention relates to a thienopyrimidine medicament which is a novel antineoplastic medicament (inhibiting SRC family protein kinases), and multiple foreign companies all devote to researching the novel antineoplastic medicament and already obtain certain achievements. An important intermediate, i.e. 7-bromine-4-amino-thienopyrimidine, is used for the novel antineoplastic medicament, thus a synthetic method and the process improvement of the intermediate both have rather important significance. In the invention, a needed product is finally synthesized through classical methods, i.e. cyclization, bromization, chlorination, ammonolysis, and the like, by taking 3-aminothiophene-2-methyl formate as a raw material; and the product belongs to a medicament intermediate innovated through an important process and has the capability of greatly reducing the production cost of the traditional medicaments, is obviously improved on the aspects of energy saving and consumption reduction and is the medicament and the medicament intermediate which is in urgent need on the market and has higher export earning potential.
Description
[technical field]
The present invention relates to the preparation and the process innovation of 7-bromo-4-aminothiophene and this product of pyrimidine, belong to the pharmaceutical intermediate technical field of great process innovation.
[background technology]
The thienopyrimidines medicine is a kind of novel antitumor class medicine (by suppressing SRC family protein kinases), and external a lot of companies all are devoted to research and develop this kind new medicine, and have obtained certain achievement.This kind new medicine all will be used important an intermediate 7-bromo-4-aminothiophene and a pyrimidine, and the synthetic method of intermediate and process modification have considerable meaning hereto.
[summary of the invention]
3-aminothiophene-2-methyl-formiate is a raw material, by closing ring, and last bromine, chlorination, ammonia classical way such as is separated and has finally been synthesized desired product.
Description of drawings
Accompanying drawing is the preparation route map of 7-bromo-4-aminothiophene and pyrimidine.
Concrete technical scheme of the present invention is as follows:
1. compound 3-amino-2-methyl-formiate thiophene and compound 2 join reflux in the ethylene glycol monomethyl ether, after total overall reaction is finished by the time, add saturated aqueous common salt when being screwed into a small amount of solvent, filter and obtain solid 4-hydroxyl Thienopyrimidine.Yield: 93%
2. compound 4-hydroxy base Thienopyrimidine adds NBS, after reacting completely, adds water and stirs, and filters, and obtains compound 4-hydroxy base-7-bromothiophene and pyrimidine yield: 76%
3. compound 4-hydroxy base-7-bromothiophene and pyrimidine add POCl3, reflux, and the TLC detection reaction is complete, pours in a large amount of trash ices, stirs, and has solid to generate, and filters, and dries to obtain compound 7-bromo-4-chlorothiophene and pyrimidine.Yield: 88%
4. compound 7-bromo-4-chlorothiophene and pyrimidine are joined in the autoclave, add ammoniacal liquor, 60 degree reactions are spent the night, cooling, and solid filtering washes with water, obtains compound 7-bromo-4-aminothiophene and pyrimidine.Yield: 88.2%.
Claims (6)
1.7-the preparation method of bromo-4-chlorothiophene and pyrimidine is characterized in that, comprises step:
With molecular formula be
Compound and ammoniacal liquor reaction, obtain 7-bromo-4-aminothiophene and pyrimidine.
2. the preparation method of 7-bromo-4-aminothiophene according to claim 1 and pyrimidine is characterized in that, described compound is done reaction solvent with ammoniacal liquor and reacted with ammoniacal liquor.
3. according to the preparation method of the described 7-bromo-of claim 4-aminothiophene and pyrimidine, it is characterized in that the temperature of reaction of step a is 120 ℃～130 ℃.
4. according to the preparation method of the described 7-bromo-of claim 4-aminothiophene and pyrimidine, it is characterized in that the temperature of reaction of step b is 5 ℃～25 ℃.
5. according to the preparation method of the described 7-bromo-of claim 4-aminothiophene and pyrimidine, it is characterized in that the temperature of reaction of step c is 120 ℃～130 ℃.
6. according to the preparation method of the described 7-bromo-of claim 4-aminothiophene and pyrimidine, it is characterized in that the temperature of reaction of steps d is 60 ℃～80 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101785097A CN102250112A (en) | 2010-05-18 | 2010-05-18 | Preparation method of 7-bromine-4-amino-thienopyrimidine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2010101785097A CN102250112A (en) | 2010-05-18 | 2010-05-18 | Preparation method of 7-bromine-4-amino-thienopyrimidine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102250112A true CN102250112A (en) | 2011-11-23 |
Family
ID=44977720
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010101785097A Pending CN102250112A (en) | 2010-05-18 | 2010-05-18 | Preparation method of 7-bromine-4-amino-thienopyrimidine |
Country Status (1)
| Country | Link |
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| CN (1) | CN102250112A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105218560A (en) * | 2015-11-04 | 2016-01-06 | 上海泰坦科技股份有限公司 | The synthesis technique of 7-bromo-4-diuril phenol also [3,2-D] pyrimidine |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1280580A (en) * | 1997-11-11 | 2001-01-17 | 辉瑞产品公司 | Thienopyrimidine and thienopyridine derivatives useful as anti-cancer agents |
| WO2002002534A1 (en) * | 2000-07-03 | 2002-01-10 | Astrazeneca Ab | Quinazolines with therapeutic use |
| CN1942475A (en) * | 2004-02-05 | 2007-04-04 | 阿斯利康(瑞典)有限公司 | Substituted thieno - and thiazolo - [2, 3-d] pyridines as inhibitors of Tie2 |
| US7285556B2 (en) * | 2000-10-23 | 2007-10-23 | Board Of Regents, The University Of Texas Systems | Thienopyrimidine-based inhibitors of the src family |
-
2010
- 2010-05-18 CN CN2010101785097A patent/CN102250112A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1280580A (en) * | 1997-11-11 | 2001-01-17 | 辉瑞产品公司 | Thienopyrimidine and thienopyridine derivatives useful as anti-cancer agents |
| WO2002002534A1 (en) * | 2000-07-03 | 2002-01-10 | Astrazeneca Ab | Quinazolines with therapeutic use |
| US7285556B2 (en) * | 2000-10-23 | 2007-10-23 | Board Of Regents, The University Of Texas Systems | Thienopyrimidine-based inhibitors of the src family |
| CN1942475A (en) * | 2004-02-05 | 2007-04-04 | 阿斯利康(瑞典)有限公司 | Substituted thieno - and thiazolo - [2, 3-d] pyridines as inhibitors of Tie2 |
Non-Patent Citations (1)
| Title |
|---|
| JINSONG PENG,等: "Preparation of a 7-Arylthieno[3,2-d]pyrimidin-4-Amine Library", 《JOURNAL OF COMBINATORIAL CHEMISTRY》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105218560A (en) * | 2015-11-04 | 2016-01-06 | 上海泰坦科技股份有限公司 | The synthesis technique of 7-bromo-4-diuril phenol also [3,2-D] pyrimidine |
| CN105218560B (en) * | 2015-11-04 | 2017-09-29 | 上海泰坦科技股份有限公司 | The synthesis technique of the chlorothiophene of 7 bromine 4 simultaneously [3,2 D] pyrimidine |
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| PB01 | Publication | ||
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Application publication date: 20111123 |