CN110343104A - A kind of synthetic method of 2- methyl -7- azaindole - Google Patents
A kind of synthetic method of 2- methyl -7- azaindole Download PDFInfo
- Publication number
- CN110343104A CN110343104A CN201910796556.9A CN201910796556A CN110343104A CN 110343104 A CN110343104 A CN 110343104A CN 201910796556 A CN201910796556 A CN 201910796556A CN 110343104 A CN110343104 A CN 110343104A
- Authority
- CN
- China
- Prior art keywords
- methyl
- azaindole
- chloropyridine
- catalyst
- amino
- 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.)
- Pending
Links
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention discloses a kind of synthetic methods of 2- methyl -7- azaindole, comprising the following steps: 2- amino -3- chloropyridine is added in DMF, is heated to 150-220 DEG C, Cp is added2ZrCl2And catalyst, under stirring condition, propine is added, back flow reaction 4-6h is filtered after reaction, after filtrate decompression is distilled removal DMF, is extracted, is recrystallized with ethyl acetate, filtered, and 2- methyl -7- azaindole is made in drying.The synthetic method of the application uses one kettle way, easy to operate, is not necessarily to intermediate purification step, and feed stock conversion is high, has high economic benefit.
Description
Technical field
The present invention relates to medicine intermediate fields, more particularly to a kind of synthetic method of 2- methyl -7- azaindole.
Background technique
Benzazole compounds are one of heterocyclic compound important branch, are natures with multiple biological activities
The middle most commonly used heterocyclic compound of distribution.Benzazole compounds are important Organic Chemicals and product, can be used as doctor
Medicine, pesticide, dyestuff, fragrance and other fine chemical products intermediate, had a wide range of applications in multiple fields.
Azaindole can regard the bioisostere of indoles as, so azaindoles are in pharmaceutical activity
MOLECULE DESIGN and synthesis aspect play an important role.In terms of pharmacological action, azaindoles have anticancer, resist
The purposes such as bacterium, antiviral, treatment hypertension.Wherein, 7- azaindole is compound important in azaindole.7- azepine Yin
Diindyl is that the carbon atom in 7 number key of indole ring is replaced into nitrogen-atoms, so that 7- azaindole and indoles change in structure,
Its physicochemical properties is all different from indoles.The derivative of 7- azaindole can inhibit the activity of many protease, have latent
Bioactivity and medical value, can treat numerous diseases such as cardiovascular disease, tumour and diabetes.7- azaindole
That medically applies is very extensive, clinically to its pharmacological properties using more, patient can be helped to treat a variety of diseases
Disease, and be the puzzlement of patient's mitigation some diseases.Wherein, 2- methyl -7- azaindole is synthesis dopamine receptor inhibitor class
The intermediate of drug.Therefore, a kind of preparation method of 2- methyl -7- azaindole efficient, easy to operate is researched and developed with important
Meaning.
Chinese patent CN201110165165.0 discloses a kind of preparation method of 2- methyl -7- azaindole, including such as
Lower step: (1) 2- amino -3- picoline generates 2- acetylaminohydroxyphenylarsonic acid 3- picoline through aceticanhydride acylation reaction；(2) 2- acetyl
Cyclization reaction occurs under the action of Sodamide, methylphenylamine and generates 2- methyl -7- azaindole for amino -3- picoline.
There is the present invention raw material to be easy to get, reaction condition is relatively mild, easily controllable；High income (total recovery be greater than 60%) and at low cost
Advantage.Prepared product 2- methyl -7- azaindole is (>=99.5%) with high purity, is suitable for industrialized production.
Summary of the invention
The object of the present invention is to provide a kind of synthetic method of 2- methyl -7- azaindole, which uses one pot
Method, it is easy to operate, it is not necessarily to intermediate purification step, feed stock conversion is high, has high economic benefit.
To achieve the above object, the invention adopts the following technical scheme:
A kind of synthetic method of 2- methyl -7- azaindole, comprising the following steps:
2- amino -3- chloropyridine is added in DMF, is heated to 150-220 DEG C, Cp is added2ZrCl2And catalyst, stirring bar
Under part, propine is added, back flow reaction 4-6h is filtered after reaction, after filtrate decompression is distilled removal DMF, uses acetic acid
Ethyl ester is extracted, and is recrystallized, and is filtered, and 2- methyl -7- azaindole is made in drying；
The preparation method of the catalyst is, comprising the following steps:
Alchlor is soluble in water, zeolite is added under stirring condition, is heated to 40-60 DEG C, ultrasonic disperse 30-50min,
Heat preservation is stood for 24 hours, is dried, and the catalyst is made in washing, vacuum drying.
Preferably, the usage amount molal volume ratio of the 2- amino -3- chloropyridine and DMF are 1-1.4mol/L.
Preferably, the 2- amino -3- chloropyridine and Cp2ZrCl2Usage amount molar ratio be 1:0.7-0.9.
Preferably, the usage amount mass ratio of the 2- amino -3- chloropyridine and catalyst is 3:4.
Preferably, the usage amount molar ratio of the 2- amino -3- chloropyridine and propine is 1:1.2-1.5.
Preferably, mass ratio shared by alchlor is 13% in the catalyst.
The invention has the advantages that using 2- amino -3- chloropyridine and propine in catalyst and Cp2ZrCl2's
Under co-catalysis, cyclization reaction is carried out, 2- methyl -7- azaindole is made.In the preparation process of catalyst with zeolite be carry
Body, alchlor are carried on zeolite surface, and zeolite has good hole configurations, and biggish specific surface area can make trichlorine
Change aluminium to come into full contact with reactant, keeps good catalytic efficiency, while being conducive to the recycling and reusing of catalyst.The application uses
Using 2- amino -3- chloropyridine and propine as raw material, raw material is cheap and easy to get, and cost is relatively low, and preparation method is easy to operate, process flow
Shorter, by-product is less, and product postprocessing is relatively simple, is very suitable for large-scale industrial production.
Specific embodiment
In order to better understand the present invention, below by embodiment, the present invention is further described, and embodiment is served only for solving
The present invention is released, any restriction will not be constituted to the present invention.
Embodiment 1
A kind of synthetic method of 2- methyl -7- azaindole, comprising the following steps:
2- amino -3- chloropyridine is added in DMF, is heated to 150 DEG C, Cp is added2ZrCl2And catalyst, stirring condition
Under, propine is added, back flow reaction 4h is filtered after reaction, after filtrate decompression is distilled removal DMF, uses ethyl acetate
It is extracted, is recrystallized, filtered, 2- methyl -7- azaindole is made in drying；
The preparation method of the catalyst is, comprising the following steps:
Alchlor is soluble in water, zeolite is added under stirring condition, is heated to 40 DEG C, ultrasonic disperse 30min, keeps the temperature quiet
It sets for 24 hours, dries, the catalyst is made in washing, vacuum drying.
The usage amount molal volume ratio of 2- amino -3- chloropyridine and DMF are 1mol/L；2- amino -3- chloropyridine with
Cp2ZrCl2Usage amount molar ratio be 1:0.7；The usage amount mass ratio of 2- amino -3- chloropyridine and catalyst is 3:4；2- ammonia
The usage amount molar ratio of base -3- chloropyridine and propine is 1:1.2；Mass ratio shared by alchlor is 13% in catalyst.
The yield of 2- methyl -7- azaindole obtained is 92.2%, purity 99.2%.
Embodiment 2
A kind of synthetic method of 2- methyl -7- azaindole, comprising the following steps:
2- amino -3- chloropyridine is added in DMF, is heated to 220 DEG C, Cp is added2ZrCl2And catalyst, stirring condition
Under, propine is added, back flow reaction 6h is filtered after reaction, after filtrate decompression is distilled removal DMF, uses ethyl acetate
It is extracted, is recrystallized, filtered, 2- methyl -7- azaindole is made in drying；
The preparation method of the catalyst is, comprising the following steps:
Alchlor is soluble in water, zeolite is added under stirring condition, is heated to 60 DEG C, ultrasonic disperse 50min, keeps the temperature quiet
It sets for 24 hours, dries, the catalyst is made in washing, vacuum drying.
The usage amount molal volume ratio of 2- amino -3- chloropyridine and DMF are 1.4mol/L；2- amino -3- chloropyridine with
Cp2ZrCl2Usage amount molar ratio be 1:0.9；The usage amount mass ratio of 2- amino -3- chloropyridine and catalyst is 3:4；2- ammonia
The usage amount molar ratio of base -3- chloropyridine and propine is 1:1.5；Mass ratio shared by alchlor is 13% in catalyst.
The yield of 2- methyl -7- azaindole obtained is 93.1%, purity 99.3%.
Embodiment 3
A kind of synthetic method of 2- methyl -7- azaindole, comprising the following steps:
2- amino -3- chloropyridine is added in DMF, is heated to 150 DEG C, Cp is added2ZrCl2And catalyst, stirring condition
Under, propine is added, back flow reaction 6h is filtered after reaction, after filtrate decompression is distilled removal DMF, uses ethyl acetate
It is extracted, is recrystallized, filtered, 2- methyl -7- azaindole is made in drying；
The preparation method of the catalyst is, comprising the following steps:
Alchlor is soluble in water, zeolite is added under stirring condition, is heated to 40 DEG C, ultrasonic disperse 50min, keeps the temperature quiet
It sets for 24 hours, dries, the catalyst is made in washing, vacuum drying.
The usage amount molal volume ratio of 2- amino -3- chloropyridine and DMF are 1mol/L；2- amino -3- chloropyridine with
Cp2ZrCl2Usage amount molar ratio be 1:0.9；The usage amount mass ratio of 2- amino -3- chloropyridine and catalyst is 3:4；2- ammonia
The usage amount molar ratio of base -3- chloropyridine and propine is 1:1.2；Mass ratio shared by alchlor is 13% in catalyst.
The yield of 2- methyl -7- azaindole obtained is 93.4%, purity 99.2%.
Embodiment 4
A kind of synthetic method of 2- methyl -7- azaindole, comprising the following steps:
2- amino -3- chloropyridine is added in DMF, is heated to 220 DEG C, Cp is added2ZrCl2And catalyst, stirring condition
Under, propine is added, back flow reaction 4h is filtered after reaction, after filtrate decompression is distilled removal DMF, uses ethyl acetate
It is extracted, is recrystallized, filtered, 2- methyl -7- azaindole is made in drying；
The preparation method of the catalyst is, comprising the following steps:
Alchlor is soluble in water, zeolite is added under stirring condition, is heated to 60 DEG C, ultrasonic disperse 30min, keeps the temperature quiet
It sets for 24 hours, dries, the catalyst is made in washing, vacuum drying.
The usage amount molal volume ratio of 2- amino -3- chloropyridine and DMF are 1.4mol/L；2- amino -3- chloropyridine with
Cp2ZrCl2Usage amount molar ratio be 1:0.7；The usage amount mass ratio of 2- amino -3- chloropyridine and catalyst is 3:4；2- ammonia
The usage amount molar ratio of base -3- chloropyridine and propine is 1:1.5；Mass ratio shared by alchlor is 13% in catalyst.
The yield of 2- methyl -7- azaindole obtained is 92.5%, purity 99.4%.
Embodiment 5
A kind of synthetic method of 2- methyl -7- azaindole, comprising the following steps:
2- amino -3- chloropyridine is added in DMF, is heated to 190 DEG C, Cp is added2ZrCl2And catalyst, stirring condition
Under, propine is added, back flow reaction 5h is filtered after reaction, after filtrate decompression is distilled removal DMF, uses ethyl acetate
It is extracted, is recrystallized, filtered, 2- methyl -7- azaindole is made in drying；
The preparation method of the catalyst is, comprising the following steps:
Alchlor is soluble in water, zeolite is added under stirring condition, is heated to 50 DEG C, ultrasonic disperse 40min, keeps the temperature quiet
It sets for 24 hours, dries, the catalyst is made in washing, vacuum drying.
The usage amount molal volume ratio of 2- amino -3- chloropyridine and DMF are 1.3mol/L；2- amino -3- chloropyridine with
Cp2ZrCl2Usage amount molar ratio be 1:0.8；The usage amount mass ratio of 2- amino -3- chloropyridine and catalyst is 3:4；2- ammonia
The usage amount molar ratio of base -3- chloropyridine and propine is 1:1.3；Mass ratio shared by alchlor is 13% in catalyst.
The yield of 2- methyl -7- azaindole obtained is 94.5%, purity 99.6%.
Claims (6)
1. a kind of synthetic method of 2- methyl -7- azaindole, which comprises the following steps:
2- amino -3- chloropyridine is added in DMF, is heated to 150-220 DEG C, Cp is added2ZrCl2And catalyst, stirring condition
Under, propine is added, back flow reaction 4-6h is filtered after reaction, after filtrate decompression is distilled removal DMF, with acetic acid second
Ester is extracted, and is recrystallized, and is filtered, and 2- methyl -7- azaindole is made in drying；
The preparation method of the catalyst is, comprising the following steps:
Alchlor is soluble in water, zeolite is added under stirring condition, is heated to 40-60 DEG C, ultrasonic disperse 30-50min, heat preservation
It stands for 24 hours, dries, the catalyst is made in washing, vacuum drying.
2. the synthetic method of 2- methyl -7- azaindole according to claim 1, it is characterised in that: the 2- amino -3-
The usage amount molal volume ratio of chloropyridine and DMF are 1-1.4mol/L.
3. the synthetic method of 2- methyl -7- azaindole according to claim 1, it is characterised in that: the 2- amino -3-
Chloropyridine and Cp2ZrCl2Usage amount molar ratio be 1:0.7-0.9.
4. the synthetic method of 2- methyl -7- azaindole according to claim 1, it is characterised in that: the 2- amino -3-
The usage amount mass ratio of chloropyridine and catalyst is 3:4.
5. the synthetic method of 2- methyl -7- azaindole according to claim 1, it is characterised in that: the 2- amino -3-
The usage amount molar ratio of chloropyridine and propine is 1:1.2-1.5.
6. the synthetic method of 2- methyl -7- azaindole according to claim 1, it is characterised in that: in the catalyst
Mass ratio shared by alchlor is 13%.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910796556.9A CN110343104A (en) | 2019-08-27 | 2019-08-27 | A kind of synthetic method of 2- methyl -7- azaindole |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910796556.9A CN110343104A (en) | 2019-08-27 | 2019-08-27 | A kind of synthetic method of 2- methyl -7- azaindole |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110343104A true CN110343104A (en) | 2019-10-18 |
Family
ID=68181240
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910796556.9A Pending CN110343104A (en) | 2019-08-27 | 2019-08-27 | A kind of synthetic method of 2- methyl -7- azaindole |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110343104A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102827162A (en) * | 2011-06-17 | 2012-12-19 | 上海雅本化学有限公司 | Preparation method of 2-methyl-7-azaindole |
| WO2015073528A1 (en) * | 2013-11-12 | 2015-05-21 | Proteostasis Therapeutics, Inc. | Proteasome activity enhancing compounds |
| CN107759595A (en) * | 2017-12-01 | 2018-03-06 | 苏州艾缇克药物化学有限公司 | A kind of synthetic method of the azaindole of intermediate 7 |
| CN107903262A (en) * | 2017-12-26 | 2018-04-13 | 东莞市联洲知识产权运营管理有限公司 | A kind of synthetic method of 5 azaindole |
| CN109456320A (en) * | 2018-11-10 | 2019-03-12 | 嘉兴市秀洲区洪合镇中学 | A kind of synthetic method of medicine intermediate 7- azaindole |
-
2019
- 2019-08-27 CN CN201910796556.9A patent/CN110343104A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102827162A (en) * | 2011-06-17 | 2012-12-19 | 上海雅本化学有限公司 | Preparation method of 2-methyl-7-azaindole |
| WO2015073528A1 (en) * | 2013-11-12 | 2015-05-21 | Proteostasis Therapeutics, Inc. | Proteasome activity enhancing compounds |
| CN107759595A (en) * | 2017-12-01 | 2018-03-06 | 苏州艾缇克药物化学有限公司 | A kind of synthetic method of the azaindole of intermediate 7 |
| CN107903262A (en) * | 2017-12-26 | 2018-04-13 | 东莞市联洲知识产权运营管理有限公司 | A kind of synthetic method of 5 azaindole |
| CN109456320A (en) * | 2018-11-10 | 2019-03-12 | 嘉兴市秀洲区洪合镇中学 | A kind of synthetic method of medicine intermediate 7- azaindole |
Non-Patent Citations (1)
| Title |
|---|
| 谢荣华等: "《世界材料塑料大全（上册）》", 31 January 2002, 中国轻工业出版社 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101607955A (en) | A kind of preparation method of low-residue lipoic acid | |
| CN106977516B (en) | A kind of preparation method of Tadalafei | |
| CN102101847B (en) | Method for preparing N-methyl-N'-(2-chloroethyl)piperazine | |
| CN103275043B (en) | The synthetic method of 2-arylbenzofuran and derivative thereof | |
| CN104725335B (en) | High-purity hydrogen bromic acid irrigates the preparation method for Xi Ting | |
| CN109293574A (en) | A kind of dehydroabietic acid aryl amine benzimidizole derivatives with anti-tumor activity and its preparation method and application | |
| CN102863361B (en) | Chiral catalytic synthesis method of thiamphenicol | |
| CN108084076A (en) | A kind of synthetic method of 5- bromo-7-azaindoles | |
| CN110343104A (en) | A kind of synthetic method of 2- methyl -7- azaindole | |
| CN109456320A (en) | A kind of synthetic method of medicine intermediate 7- azaindole | |
| CN102351790A (en) | Method for synthesizing 7-bromo-6-chloro-4-quinazolinone | |
| CN106810554A (en) | A kind of preparation method of Tadalafei compound | |
| CN104693039A (en) | Adamantane amine derivative as well as preparation method and application of derivative | |
| CN102850296B (en) | Preparation method of trimetazidine | |
| CN102464699A (en) | Method for preparing carbenoxolone sodium | |
| CN104961642A (en) | Novel propranolol synthesis method | |
| CN109223741A (en) | A kind of purposes of Rimantadine schiff bases | |
| CN102093323B (en) | Quercetin preparation method | |
| CN111087401B (en) | Novel method for establishing spiro ring on 2-aryl quinazoline-4 (3H) -ketone compound | |
| CN110963937B (en) | Asymmetric synthesis method of colchicine and allocolchicine | |
| CN105085267A (en) | Synthetic method for salvianolic acid A | |
| CN109369772B (en) | Synthetic method and anti-tumor application of phenanthridine nitidine derivatives | |
| CN109456321A (en) | A kind of synthetic method of 7- azaindole -3- formaldehyde | |
| CN104341359A (en) | Preparation method of tetramethyl-pyrazine | |
| CN107903262A (en) | A kind of synthetic method of 5 azaindole |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20191018 |