CN106699730A - Preparation method of 2-methyl-5-(5-bromopyridine-2-group) tetrazole - Google Patents
Preparation method of 2-methyl-5-(5-bromopyridine-2-group) tetrazole Download PDFInfo
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- CN106699730A CN106699730A CN201611201469.7A CN201611201469A CN106699730A CN 106699730 A CN106699730 A CN 106699730A CN 201611201469 A CN201611201469 A CN 201611201469A CN 106699730 A CN106699730 A CN 106699730A
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- bromopyridine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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Abstract
The invention relates to a preparation method of 2-methyl-5-(5-bromopyridine-2-group) tetrazole. The method is simple in reaction steps and high in yield, and can realize mass production.
Description
1st, technical field
The invention belongs to pharmaceutical technology field, it is related to one kind to prepare 2- methyl -5- (5- bromopyridine -2- bases) tetrazole ester
Method.
2nd, background technology
Monophosphate monophosphate specially azoles amine is bis- oxazolidinone antimicrobial of FDA approvals, for treating by gram sun
Acute skin and skin structure infections (ABSSSI) that property bacterium (MRSA etc.) causes.Additionally, monophosphate monophosphate specially azoles amine is now
The indication of EMA examination ＆ approval is complicated Skin and soft tissue infection (cSSTI).
At present in the prior art, specially azoles amine and wherein is described if in CN102177156A and CN104892592A
The preparation method of mesosome 2- methyl -5- (5- bromopyridine -2- bases) tetrazole, with the bromo- 2- cyanopyridines of 5-, ammonium chloride and Sodium azide
It is obtained for initiation material carries out reaction, but preparation method is cumbersome, yield is low, and only 33%.
3rd, the content of the invention
It is an object of the invention to provide it is a kind of synthesize it is simple, safely, be easy to amplify the 2- carbonyl indolone -6- carboxylic acids of production
The preparation method of methyl esters, concrete technical scheme is as follows：
The bromo- 2- cyanopyridines of (a) 5- and sodium azide, ammonium chloride carry out Dipolar Cycloaddition obtain 5- (5- bromopyridines-
2- yls) tetrazole；
B () 5- (5- bromopyridine -2- bases) tetrazoles with dimethyl suflfate methylate and obtain 2- methyl -5- (5- bromine pyrroles
Pyridine -2- bases) tetrazole；
C 2- methyl -5- (5- bromopyridine -2- bases) tetrazole crude product is added watery hydrochloric acid, stirring, filtering, water mutually to use hydrogen by ()
Sodium oxide molybdena adjusts PH, i.e. analysis obtains out 2- methyl -5- (5- bromopyridine -2- bases) tetrazole.
Reaction dissolvent in the step a is dimethyl sulfoxide (DMSO)；The bromo- 2- cyanopyridines of 5- and sodium azide, ammonium chloride
Mol ratio is 1:1:1~1:5:5, preferably 1:2:2~1:2:2, optimal is 1:1.5:1.5；Reaction temperature is 80-100 DEG C, excellent
Elect 95 DEG C as；Reaction time is 3-8 hours, preferably 4 hours.
5- (5- bromopyridine -2- bases) tetrazoles and the mol ratio of dimethyl suflfate are 1 in the step b:1~1:5, preferably
It is 1:1~1:3, optimal is 1:1~1:1.2；Reaction temperature is 35-70 DEG C, preferably 50 DEG C；Reaction time is 16-34 hours,
Preferably 24 hours.
Naoh concentration is 10-60%, preferably 30-50% in the step c, and optimal is 40%；Regulation pH to 9~
10。
The present invention has advantages below：
1) two steps merge a step, simplify operation, so as to reduce solvent usage amount, environmental protection, reduces cost；
2) high income of reactions steps of the invention, up to 75%；
3) production technology of the present invention can realize industrialization, can carry out hundred feather weight productions.
4th, specific embodiment
The specific embodiment of form, makees further specifically to the above of the invention by the following examples
It is bright.But this scope for being interpreted as above-mentioned theme of the invention should not be only limitted to following examples.
The preparation of the 2- methyl -5- of embodiment 1 (5- bromopyridine -2- bases) tetrazole
The bromo- 2- cyanopyridines (800g, 4.4mol) of 5-, dimethyl sulfoxide (DMSO) (4L) are added in 20L bottles, nitrine is dividedly in some parts
Change sodium (425.7g, 6.55mol), ammonium chloride (350.3g, 6.55mol), stirring is warming up to 95 degree, stirs 4 hours, is cooled to
Room temperature.
NaOH (470g, 11.8mol) is added, dimethyl suflfate (665g, 5.3mol) is added dropwise, be warming up to 50 degree, stirred
Mix 24 hours, reaction is finished, add water (11L), centrifugal drying obtains crude product.
Crude product is added into watery hydrochloric acid, is stirred 3 hours, filtering, water mutually adjusts PH=9-10 with 40% NaOH, separates out
2- methyl -5- (5- bromopyridine -2- bases) tetrazole, (792g, 3.3mol), yield：75%.
1HNMR(CDCl3)8.80(t,1H),8.13(dd,1H),7.98(dd,1H),4.42(s,3H)。
Claims (10)
1. a kind of preparation method of 2- methyl -5- (5- bromopyridine -2- bases) tetrazole, it is characterised in that comprise the following steps：
A the bromo- 2- cyanopyridines of () 5- carry out Dipolar Cycloaddition and obtain 5- (5- bromopyridines -2- with sodium azide, ammonium chloride
Base) tetrazole；
B () 5- (5- bromopyridine -2- bases) tetrazoles with dimethyl suflfate methylate and obtain 2- methyl -5- (5- bromopyridines -2-
Base) tetrazole；
C 2- methyl -5- (5- bromopyridine -2- bases) tetrazole crude product is added watery hydrochloric acid, stirring, filtering, water mutually to use hydroxide by ()
Sodium adjusts PH, i.e. analysis obtains out 2- methyl -5- (5- bromopyridine -2- bases) tetrazole.
2. preparation method according to claim 1, it is characterised in that：
Reaction dissolvent in the step a is dimethyl sulfoxide (DMSO)；
The bromo- 2- cyanopyridines of 5- are 1 with the mol ratio of sodium azide, ammonium chloride:1:1~1:5:5；
Reaction temperature is 80-100 DEG C；
Reaction time is 3-8 hours.
3. preparation method according to claim 2, it is characterised in that：
Reaction dissolvent in the step a is dimethyl sulfoxide (DMSO)；
The bromo- 2- cyanopyridines of 5- are 1 with the mol ratio of sodium azide, ammonium chloride:2:2；
Reaction temperature is 95 DEG C；
Reaction time is 4 hours.
4. preparation method according to claim 3, it is characterised in that：
Reaction dissolvent in the step a is dimethyl sulfoxide (DMSO)；
The bromo- 2- cyanopyridines of 5- are 1 with the mol ratio of sodium azide, ammonium chloride:1.5:1.5；
Reaction temperature is 95 DEG C；
Reaction time is 4 hours.
5. preparation method according to claim 1, it is characterised in that：
5- (5- bromopyridine -2- bases) tetrazoles and the mol ratio of dimethyl suflfate are 1 in the step b:1~1:5；
Reaction temperature is 35-70 DEG C；
Reaction time is 16-34 hours.
6. preparation method according to claim 5, it is characterised in that：
5- (5- bromopyridine -2- bases) tetrazoles and the mol ratio of dimethyl suflfate are 1 in the step b:1~1:3；
Reaction temperature is 50 DEG C；
Reaction time is 24 hours.
7. preparation method according to claim 6, it is characterised in that：
5- (5- bromopyridine -2- bases) tetrazoles and the mol ratio of dimethyl suflfate are 1 in the step b:1~1:1.2；
Reaction temperature is 50 DEG C；
Reaction time is 24 hours.
8. preparation method according to claim 1, it is characterised in that：
Naoh concentration is 10-60% in the step c；Regulation pH to 9~10.
9. preparation method according to claim 8, it is characterised in that：
Naoh concentration is 30-50% in the step c；Regulation pH to 9~10.
10. preparation method according to claim 9, it is characterised in that：
Naoh concentration is 40% in the step c；Regulation pH to 9~10.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611201469.7A CN106699730A (en) | 2016-12-23 | 2016-12-23 | Preparation method of 2-methyl-5-(5-bromopyridine-2-group) tetrazole |
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| CN201611201469.7A CN106699730A (en) | 2016-12-23 | 2016-12-23 | Preparation method of 2-methyl-5-(5-bromopyridine-2-group) tetrazole |
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| CN201611201469.7A Pending CN106699730A (en) | 2016-12-23 | 2016-12-23 | Preparation method of 2-methyl-5-(5-bromopyridine-2-group) tetrazole |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107235955A (en) * | 2017-07-20 | 2017-10-10 | 中山万远新药研发有限公司 | A kind of preparation technology of 2 methyl 5 (base of 5 bromopyridine 2) tetrazoles |
| CN107652439A (en) * | 2017-09-22 | 2018-02-02 | 宁波大学 | A kind of cadmium metal organic framework materials and its preparation method and application |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102177156A (en) * | 2008-10-10 | 2011-09-07 | 特留斯治疗学公司 | Methods for preparing oxazolidinones and compositions containing them |
| CN104892592A (en) * | 2015-03-30 | 2015-09-09 | 成都惟新医药科技有限公司 | Preparation method for tedizolid |
| CN105111237A (en) * | 2015-09-14 | 2015-12-02 | 成都维恒医药科技有限公司 | Method for compounding tedizolid phosphate |
-
2016
- 2016-12-23 CN CN201611201469.7A patent/CN106699730A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102177156A (en) * | 2008-10-10 | 2011-09-07 | 特留斯治疗学公司 | Methods for preparing oxazolidinones and compositions containing them |
| CN104892592A (en) * | 2015-03-30 | 2015-09-09 | 成都惟新医药科技有限公司 | Preparation method for tedizolid |
| CN105111237A (en) * | 2015-09-14 | 2015-12-02 | 成都维恒医药科技有限公司 | Method for compounding tedizolid phosphate |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107235955A (en) * | 2017-07-20 | 2017-10-10 | 中山万远新药研发有限公司 | A kind of preparation technology of 2 methyl 5 (base of 5 bromopyridine 2) tetrazoles |
| CN107652439A (en) * | 2017-09-22 | 2018-02-02 | 宁波大学 | A kind of cadmium metal organic framework materials and its preparation method and application |
| CN107652439B (en) * | 2017-09-22 | 2020-07-03 | 宁波大学 | Cadmium metal organic framework material and preparation method and application thereof |
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