CN106349242A - Preparation method of 7-azaindole with position 3 substituted by halogen - Google Patents
Preparation method of 7-azaindole with position 3 substituted by halogen Download PDFInfo
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- CN106349242A CN106349242A CN201610630073.8A CN201610630073A CN106349242A CN 106349242 A CN106349242 A CN 106349242A CN 201610630073 A CN201610630073 A CN 201610630073A CN 106349242 A CN106349242 A CN 106349242A
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- preparation
- halogen
- azaindole
- azaindoles
- halogen substiuted
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- IYMPPWVLCCLFGO-UHFFFAOYSA-N CC1=CNC2=C=NC=CC=C12 Chemical compound CC1=CNC2=C=NC=CC=C12 IYMPPWVLCCLFGO-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Abstract
The invention discloses a preparation method of 7-azaindole with the position 3 substituted by halogen. The preparation method includes the steps of dissolving 7-azaindole in an organic solvent, adding a halogen-source compound and a catalyst, reacting under catalysis of the catalyst, and purifying after reaction is finished so as to obtain the 7-azaindole with the position 3 substituted by the halogen. The preparation method has the advantages that the preparation method is capable of preparing the 7-azaindole with the position 3 substituted by the halogen through a one-step method, is high in reaction conversion rate and selectivity by the aid of a multiplex catalyst system and is mild in reaction condition, safe in raw materials and low in reaction cost, thereby being promising in industrialized production prospect.
Description
Technical field:
The present invention relates to medicine intermediate field, more particularly to a kind of preparation side of 3 halogen substiuted 7- azaindoles
Method.
Background technology:
Benzazole compounds are the important branches of one of heterocyclic compound, are widely distributed in nature, tool
There are multiple physiologically actives, be respectively provided with important effect in fields such as pesticide, medicine, dyestuff and luminescent materials.In terms of pesticide,
Benzazole compounds can be used as antibacterial or plant growth regulator etc..At medical aspect, there is antipyretic-antalgic, fall blood
The biological activitys such as pressure, expansion of blood vessels, antihistamine and anticancer.Additionally, indoles are also used as spice or the synthesis of dyestuff is former
Material.Benzazole compounds be applied to people daily biology closely bound up, therefore with regard to the study on the synthesis of Benzazole compounds
Significant.
7- azaindole is important a member in azaindole, is the isoelectronic specieses of indole and purine.With 7- azaindole it is
Parent nucleus can prepare multiple molecules with biological activity.The 7- azaindole of wherein 3 replacements has good anticancer effect,
There is important medical value.
Content of the invention:
It is an object of the invention to provide a kind of preparation method of three halogen substiuted 7- azaindoles, the method is using a step
Reaction method prepares three halogen substiuted 7- azaindoles, and using multiplex catalyst system, reaction conversion ratio is high, selectivity
By force.And, reaction condition needed for this preparation method is gentle, materials safety, and reaction cost is relatively low, has higher industrialized production
Prospect.
For achieving the above object, the present invention employs the following technical solutions:
A kind of preparation method of 3 halogen substiuted 7- azaindoles, comprises the following steps:
7- azaindole is dissolved in organic solvent, adds halogen source compound and catalyst, issue in catalyst
Raw reaction, after reaction terminates, purified prepared 3 halogen substiuted 7- azaindoles, reaction process is as follows:
Preferably, described catalyst is the mixture of nickel acetate and triethanolamine borate.
Preferably, described catalyst is nickel acetate and triethanolamine borate mol ratio is the mixture of 3:1.
Preferably, described organic solvent is one or more of isopropanol, ethyl acetate or ethanol mixture.
Preferably, described organic solvent is 1:1 for the mol ratio of isopropanol and ethyl acetate.
Preferably, the reaction temperature of described preparation method is 80-120 DEG C.
Preferably, described catalyst and the mol ratio of 7- azaindole are 1:2-3.
Preferably, described halogen source compound is one of fluorine, chlorine or bromine.
Preferably, described halogen source compound and the molar ratio of 7- azaindole are 2-3:1.
Preferably, the specific operation process of described preparation method is: 7- azaindole is dissolved in organic solvent, adds
In reactor, adding catalyst, maintain temperature at 80-120 DEG C, 60-90 turns/the rotating speed stirring of min, it is passed through/instills halogen source
Compound, after back flow reaction 2-3h, reaction completes, and purification is obtained 3 halogen substiuted 7- azaindoles.
Wherein, the method for purification of 3 halogen substiuted 7- azaindoles is that those skilled in the art can according to circumstances be carried out
Select, here is no longer described in detail.
The invention has the advantages that, using new composite catalyst so that reaction has stronger selectivity,
Product purity is high, and yield is high.Secondly, needed for reaction, condition is more gentle, simple to operate, and one-step method reaction can effectively improve
That reacts enters line efficiency, wastes less.The method running cost is low, and production efficiency is high, has good industrial applications prospect.
Specific embodiment:
In order to be better understood from the present invention, below by embodiment, the present invention is further described, and embodiment is served only for solving
Release the present invention, any restriction will not be constituted to the present invention.
Embodiment 1
100mmol 7- azaindole is dissolved in organic solvent, adds in reactor, add 35mmol catalyst, dimension
Hold temperature at 90 DEG C, the rotating speed stirring of 90 turns/min, it is passed through/instills 200mmol chlorine, after back flow reaction 3h, reaction completes, and carries
The chloro- 7- azaindole of pure prepared 3-.Wherein catalyst is nickel acetate and triethanolamine borate mol ratio is the mixture of 3:1.
The yield of product is 98.4%
Embodiment 2
100mmol7- azaindole is dissolved in organic solvent, adds in reactor, add 45mmol catalyst, dimension
Hold temperature at 90 DEG C, the rotating speed stirring of 60 turns/min, it is passed through 300mmol chlorine, after back flow reaction 3h, reaction completes, purification system
Obtain 3- chloro- 7- azaindole.Wherein catalyst is nickel acetate and triethanolamine borate mol ratio is the mixture of 3:1.Product
Yield be 97.5%
Embodiment 3
100mmol7- azaindole is dissolved in organic solvent, adds in reactor, add 50mmol catalyst, dimension
Hold temperature at 90 DEG C, the rotating speed stirring of 80 turns/min, it is passed through 300mmol chlorine, after back flow reaction 3h, reaction completes, purification system
Obtain 3- chloro- 7- azaindole.Wherein catalyst is nickel acetate and triethanolamine borate mol ratio is the mixture of 3:1.Product
Yield be 99.3%
Embodiment 4
100mmol7- azaindole is dissolved in organic solvent, adds in reactor, add 50mmol catalyst, dimension
Hold temperature at 100 DEG C, the rotating speed stirring of 80 turns/min, instill 300mmol bromine, after back flow reaction 3h, reaction completes, purification system
Obtain 3- bromo-7-azaindole.Wherein catalyst is nickel acetate and triethanolamine borate mol ratio is the mixture of 3:1.Product
Yield be 97.9%.
Embodiment 5
100mmol7- azaindole is dissolved in organic solvent, adds in reactor, add 45mmol catalyst, dimension
Hold temperature at 110 DEG C, the rotating speed stirring of 90 turns/min, instill 250mmol bromine, after back flow reaction 3h, reaction completes, purification system
Obtain 3- bromo-7-azaindole.Wherein catalyst is nickel acetate and triethanolamine borate mol ratio is the mixture of 3:1.Product
Yield be 96.7%
Embodiment 6
100mmol7- azaindole is dissolved in organic solvent, adds in reactor, add 40mmol catalyst, dimension
Hold temperature at 100 DEG C, the rotating speed stirring of 90 turns/min, instill 300mmol bromine, after back flow reaction 3h, reaction completes, purification system
Obtain 3- bromo-7-azaindole.Wherein catalyst is nickel acetate and triethanolamine borate mol ratio is the mixture of 3:1.Product
Yield be 99.0%
Claims (10)
1. a kind of preparation method of 3 halogen substiuted 7- azaindoles is it is characterised in that comprise the following steps:
7- azaindole is dissolved in organic solvent, adds halogen source compound and catalyst, occur anti-under catalyst
Should, after reaction terminates, purified prepared 3 halogen substiuted 7- azaindoles.
2. 3 halogen substiuted 7- azaindoles according to claim 1 preparation method it is characterised in that: described catalysis
Agent is the mixture of nickel acetate and triethanolamine borate.
3. 3 halogen substiuted 7- azaindoles according to claim 1 preparation method it is characterised in that: described catalysis
Agent is nickel acetate and triethanolamine borate mol ratio is the mixture of 3:1.
4. 3 halogen substiuted 7- azaindoles according to claim 1 preparation method it is characterised in that: described organic
Solvent is one or more of isopropanol, ethyl acetate or ethanol mixture.
5. 3 halogen substiuted 7- azaindoles according to claim 1 preparation method it is characterised in that: described organic
Solvent is isopropanol is 1:1 with the mol ratio of ethyl acetate.
6. 3 halogen substiuted 7- azaindoles according to claim 1 preparation method it is characterised in that: described preparation
The reaction temperature of method is 80-120 DEG C.
7. 3 halogen substiuted 7- azaindoles according to claim 1 preparation method it is characterised in that: described catalysis
Agent is 1:2-3 with the mol ratio of 7- azaindole.
8. 3 halogen substiuted 7- azaindoles according to claim 1 preparation method it is characterised in that: described halogen
Source compound is one of fluorine, chlorine or bromine.
9. 3 halogen substiuted 7- azaindoles according to claim 1 preparation method it is characterised in that: described halogen
Source compound is 2-3:1 with the molar ratio of 7- azaindole.
10. 3 halogen substiuted 7- azaindoles according to claim 1 preparation method it is characterised in that: described preparation
The specific operation process of method is: 7- azaindole is dissolved in organic solvent, adds in reactor, add catalyst, dimension
Holding temperature at 80-120 DEG C, 60-90 turns/the rotating speed stirring of min, it is passed through/instills halogen source compound, after back flow reaction 2-3h,
Reaction completes, and purification is obtained 3 halogen substiuted 7- azaindoles.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201610630073.8A CN106349242A (en) | 2016-08-02 | 2016-08-02 | Preparation method of 7-azaindole with position 3 substituted by halogen |
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| CN201610630073.8A CN106349242A (en) | 2016-08-02 | 2016-08-02 | Preparation method of 7-azaindole with position 3 substituted by halogen |
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| CN106349242A true CN106349242A (en) | 2017-01-25 |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107235976A (en) * | 2017-07-12 | 2017-10-10 | 海门华祥医药科技有限公司 | A kind of synthetic method of the azaindole of 3 chlorine 7 |
| CN108069994A (en) * | 2017-12-20 | 2018-05-25 | 江苏中旗科技股份有限公司 | A kind of boron-containing compound and its application in catalytic fluorination reaction |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103582641A (en) * | 2011-03-16 | 2014-02-12 | 新日铁住金化学株式会社 | Nitrogen-containing aromatic compounds and organic electroluminescent elements |
| CN104649854A (en) * | 2015-02-03 | 2015-05-27 | 北京大学 | Cheap and efficient preparation method of aryl halides |
-
2016
- 2016-08-02 CN CN201610630073.8A patent/CN106349242A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103582641A (en) * | 2011-03-16 | 2014-02-12 | 新日铁住金化学株式会社 | Nitrogen-containing aromatic compounds and organic electroluminescent elements |
| CN104649854A (en) * | 2015-02-03 | 2015-05-27 | 北京大学 | Cheap and efficient preparation method of aryl halides |
Non-Patent Citations (4)
| Title |
|---|
| FABRICE GALLOU ET AL.: ""Practical Regioselective Bromination of Azaindoles and Diazaindoles"", 《SYNLETT》 * |
| ROMAN A. VALIULIN ET AL.: ""Taming Chlorine Azide: Access to 1,2-Azidochlorides from Alkenes"", 《JOURNAL OF ORGANIC CHEMISTRY》 * |
| SALHA HAMRI ET AL.: ""A convenient iodination of indoles and derivatives"", 《TETRAHEDRON》 * |
| SATOSHI MINAKATA ET AL.: ""Synthesis and biological activity of 1H-pyrrolo[2,3-b]pyridine derivatives: Correlation between inhibitory activity against the fungus causing rice blast and ionization potential"", 《JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107235976A (en) * | 2017-07-12 | 2017-10-10 | 海门华祥医药科技有限公司 | A kind of synthetic method of the azaindole of 3 chlorine 7 |
| CN108069994A (en) * | 2017-12-20 | 2018-05-25 | 江苏中旗科技股份有限公司 | A kind of boron-containing compound and its application in catalytic fluorination reaction |
| CN108069994B (en) * | 2017-12-20 | 2019-05-14 | 江苏中旗科技股份有限公司 | A kind of boron-containing compound and its application in catalytic fluorination reaction |
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