CN111303020A - Synthetic method of 5-chloro-2- (pyridine-3-yl) pyridine-3-amine - Google Patents
Synthetic method of 5-chloro-2- (pyridine-3-yl) pyridine-3-amine Download PDFInfo
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
Abstract
The invention belongs to the technical field of synthesis of drug intermediates, and particularly relates to a synthesis method of 5-chloro-2- (pyridine-3-yl) pyridine-3-amine. The invention provides a synthetic method of 5-chloro-2- (pyridine-3-yl) pyridine-3-amine for the first time, and provides a synthetic route for the synthetic method of 5-chloro-2- (pyridine-3-yl) pyridine-3-amine; the synthesis method of the 5-chloro-2- (pyridine-3-yl) pyridine-3-amine is a one-step reaction, and has the advantages of short route, reasonable design, simple operation and easy control.
Description
Technical Field
The invention belongs to the technical field of synthesis of drug intermediates, and particularly relates to a synthesis method of 5-chloro-2- (pyridine-3-yl) pyridine-3-amine.
Background
The synthesis method of the compound 5-chloro-2- (pyridine-3-yl) pyridine-3-amine and related derivatives have wide application in pharmaceutical chemistry and organic synthesis. At present, the synthesis method of 5-chloro-2- (pyridine-3-yl) pyridine-3-amine is only reported in documents. Therefore, it is necessary to develop a synthesis method which has easily available raw materials, convenient operation, easy control of reaction, proper overall yield and suitability for industrial production.
Disclosure of Invention
The technical problems to be solved by the invention are as follows: aiming at the existing problems, a synthesis method of 5-chloro-2- (pyridine-3-yl) pyridine-3-amine is provided.
In order to solve the technical problems, the invention adopts the following technical scheme:
a method for synthesizing 5-chloro-2- (pyridin-3-yl) pyridin-3-amine, comprising the steps of:
(1) adding a compound A and a compound B into a reaction container, uniformly stirring, adding a solvent for dissolving, adding a solution formed by mixing carbonate and water, protecting with nitrogen, adding a catalyst, heating, and stirring for reaction;
(2) after the reaction is finished, adding water with the mass 5-10 times of that of the compound A, extracting with ethyl acetate, drying, and carrying out column chromatography to obtain a compound C, namely 5-chloro-2- (pyridine-3-yl) pyridine-3-amine;
the reaction formula of the synthesis method is as follows:
wherein, R in the compound A represents any one of bromine, iodine and chlorine.
More preferably, R in compound a represents any one of bromine and iodine.
Most preferably, R in compound a represents bromo.
Preferably, the carbonate is any one of cesium carbonate, potassium carbonate and sodium carbonate.
Preferably, the carbonate is cesium carbonate.
Preferably, the catalyst is palladium chloride.
Preferably, the solvent is dioxane.
Preferably, the mass ratio of the compound A to the compound B is 5: 2-4, the solid-liquid ratio (g/mL) of the compound A to the solvent is 1: 9-12, the solid-liquid ratio (g/mL) of the carbonate and water is 14-16: 25, and the volume ratio of the solvent to the water is 2:1, and the mass ratio of the compound A to the catalyst is 5-7: 1.
Preferably, the heating temperature in the step (1) is 80-100 ℃, and the reaction time is 2-4 h.
Compared with other methods, the method has the beneficial technical effects that:
(1) the invention provides a synthetic method of 5-chloro-2- (pyridine-3-yl) pyridine-3-amine for the first time, and provides a synthetic route for the synthetic method of 5-chloro-2- (pyridine-3-yl) pyridine-3-amine;
(2) the synthesis method of the 5-chloro-2- (pyridine-3-yl) pyridine-3-amine is a one-step reaction, has a short route, is reasonable in design, simple to operate and easy to control;
(3) the product obtained by the method has high yield.
Detailed Description
The invention is further illustrated by the following examples, without restricting its scope to these examples. Numerous other changes and modifications can be made by those skilled in the art without departing from the spirit and scope of the invention. In particular, certain agents which are both chemically and structurally related may be substituted for the agents described herein to achieve the same or similar results, and reactions may be carried out under conditions outside the preferred ranges, albeit less than optimally. Accordingly, such obvious substitutions and modifications are intended to be included within the scope of the appended claims.
The catalyst is palladium chloride.
The solvent is dioxane.
A method for synthesizing 5-chloro-2- (pyridin-3-yl) pyridin-3-amine, comprising the steps of:
(1) adding a compound A and a compound B into the mixture according to a mass ratio of 5: 2-4, uniformly stirring, adding dioxane into the mixture according to a solid-liquid ratio (g/mL) of the compound A to a solvent of 1: 9-12 for dissolving, adding a catalyst into the mixture according to a solid-liquid ratio (g/mL) of carbonate to water of 14-16: 25 and a volume ratio of the solvent to water of 2:1, heating the mixture to 80-100 ℃, and stirring for reacting for 2-4 hours, wherein the carbonate and the water are mixed to form a solution, and then adding nitrogen for protection, and the compound A and the catalyst are added into the solution according to a mass ratio of 5-7: 1;
(2) and after the reaction is finished, adding water with the mass 5-10 times of that of the compound A, extracting with ethyl acetate, drying, and passing through a column to obtain a compound C, namely 5-chloro-2- (pyridine-3-yl) pyridine-3-amine.
Example 1
When R in the compound A is represented by bromine, the compound A is named as 2-bromo-5-chloropyridin-3-amine, and the compound B is named as pyridin-3-ylboronic acid.
The carbonate is any one of potassium carbonate and sodium carbonate.
The catalyst is palladium chloride.
The solvent is dioxane.
A method for synthesizing 5-chloro-2- (pyridin-3-yl) pyridin-3-amine, comprising the steps of:
(1) placing 500g of the compound A and 300g of the compound B into a reactor, uniformly stirring, adding 5000mL of dioxane for dissolving, firstly mixing 1580g of carbonate and 2500mL of water to form a solution, adding the solution into the reactor, adding 90g of catalyst under the protection of nitrogen, heating to 80 ℃, and stirring for reacting for 3 hours;
(2) after the reaction is finished, water with the mass 8 times of that of the compound A is added, and the mixture is extracted by ethyl acetate, dried and subjected to column chromatography to obtain 451.7g of a compound C, so that 451.7g of 5-chloro-2- (pyridine-3-yl) pyridine-3-amine is obtained, wherein the yield is 89.99%.
1H NMR（d6-DMSO）：8.81 (dd,J= 2.3 Hz, 0.8 Hz, 1H), 8.57 (d,J= 1.8Hz, 1H), 8.00 (m, 1H), 7.91 (d,J= 2.1 Hz, 1H), 7.46 (m, 1H), 7.23 (d,J=2.1 Hz, 1H), 5.60 (brs, 2H)。
Example 2
When R in the compound A is represented by bromine, the compound A is named as 2-bromo-5-chloropyridin-3-amine, and the compound B is named as pyridin-3-ylboronic acid.
The carbonate is any one of cesium carbonate.
The catalyst is palladium chloride.
The solvent is dioxane.
A method for synthesizing 5-chloro-2- (pyridin-3-yl) pyridin-3-amine, comprising the steps of:
(1) placing 500g of the compound A and 300g of the compound B into a reactor, uniformly stirring, adding 5000mL of dioxane for dissolving, firstly mixing 1580g of carbonate and 2500mL of water to form a solution, adding the solution into the reactor, adding 90g of catalyst under the protection of nitrogen, heating to 80 ℃, and stirring for reacting for 3 hours;
(2) after the reaction is finished, water with the mass 8 times of that of the compound A is added, ethyl acetate is used for extraction, drying and column chromatography are carried out, so as to obtain 476.7g of a compound C, and 476.7g of 5-chloro-2- (pyridine-3-yl) pyridine-3-amine is obtained, wherein the yield is 94.98%.
1H NMR（d6-DMSO）：8.81 (dd,J= 2.3 Hz, 0.8 Hz, 1H), 8.57 (d,J= 1.8Hz, 1H), 8.00 (m, 1H), 7.91 (d,J= 2.1 Hz, 1H), 7.46 (m, 1H), 7.23 (d,J=2.1 Hz, 1H), 5.60 (brs, 2H)。
Example 3
The carbonate is cesium carbonate.
When R in the compound A is iodine or chlorine, the compound A is named as 5-chloro-2-iodopyridin-3-amine or 2, 5-dichloropyridin-3-amine, and the compound B is named as pyridin-3-ylboronic acid.
The catalyst is palladium chloride.
The solvent is dioxane.
A method for synthesizing 5-chloro-2- (pyridin-3-yl) pyridin-3-amine, comprising the steps of:
(1) placing 500g of the compound A and 300g of the compound B into a reactor, uniformly stirring, adding 5000mL of dioxane for dissolving, firstly mixing 1580g of carbonate and 2500mL of water to form a solution, adding the solution into the reactor, adding 90g of catalyst under the protection of nitrogen, heating to 80 ℃, and stirring for reacting for 3 hours;
(2) after the reaction is finished, water with the mass 8 times of that of the compound A is added, and the mixture is extracted by ethyl acetate, dried and subjected to column chromatography to obtain 436.6g of a compound C, namely 431.6g of 5-chloro-2- (pyridine-3-yl) pyridine-3-amine, wherein the yield is 86.99%.
1H NMR（d6-DMSO）：8.81 (dd,J= 2.3 Hz, 0.8 Hz, 1H), 8.57 (d,J= 1.8Hz, 1H), 8.00 (m, 1H), 7.91 (d,J= 2.1 Hz, 1H), 7.46 (m, 1H), 7.23 (d,J=2.1 Hz, 1H), 5.60 (brs, 2H)。
From the above examples, it is understood that example 2 is the most preferable example since the yield of 5-chloro-2- (pyridin-3-yl) pyridin-3-amine as a product is the highest when compound a is 2-bromo-5-chloropyridin-3-amine and the carbonate is cesium carbonate.
Example 4
When R in the compound A is represented by bromine, the compound A is named as 2-bromo-5-chloropyridin-3-amine, and the compound B is named as pyridin-3-ylboronic acid.
The carbonate is any one of cesium carbonate.
The catalyst is palladium chloride.
The solvent is dioxane.
A method for synthesizing 5-chloro-2- (pyridin-3-yl) pyridin-3-amine, comprising the steps of:
(1) putting 500g of the compound A and 200g of the compound B into a reactor, uniformly stirring, adding 4500mL of dioxane for dissolving, firstly mixing 1260g of carbonate and 2250mL of water to form a solution, adding into the reactor, adding 100g of catalyst under the protection of nitrogen, heating to 85 ℃, and stirring for reacting for 2 hours;
(2) after the reaction is finished, water with the mass 8 times of that of the compound A is added, ethyl acetate is used for extraction, drying and column chromatography are carried out, 307.8g of compound C is obtained, 307.8g of 5-chloro-2- (pyridine-3-yl) pyridine-3-amine is obtained, and the yield is 91.99%.
1H NMR（d6-DMSO）：8.81 (dd,J= 2.3 Hz, 0.8 Hz, 1H), 8.57 (d,J= 1.8Hz, 1H), 8.00 (m, 1H), 7.91 (d,J= 2.1 Hz, 1H), 7.46 (m, 1H), 7.23 (d,J=2.1 Hz, 1H), 5.60 (brs, 2H)。
Example 5
When R in the compound A is represented by bromine, the compound A is named as 2-bromo-5-chloropyridin-3-amine, and the compound B is named as pyridin-3-ylboronic acid.
The carbonate is any one of cesium carbonate.
The catalyst is palladium chloride.
The solvent is dioxane.
A method for synthesizing 5-chloro-2- (pyridin-3-yl) pyridin-3-amine, comprising the steps of:
(1) putting 500g of the compound A and 400g of the compound B into a reactor, uniformly stirring, adding 6000mL of dioxane for dissolving, firstly mixing 1920g of carbonate and 3000mL of water to form a solution, adding the solution into the reactor, adding 72g of catalyst under the protection of nitrogen, heating to 100 ℃, and stirring for reacting for 3 hours;
(2) after the reaction is finished, water with the mass 8 times of that of the compound A is added, ethyl acetate is used for extraction, drying and column chromatography are carried out, 448.5g of compound C is obtained, 448.5g of 5-chloro-2- (pyridine-3-yl) pyridine-3-amine is obtained, and the yield is 90.49%.
1H NMR（d6-DMSO）：8.81 (dd,J= 2.3 Hz, 0.8 Hz, 1H), 8.57 (d,J= 1.8Hz, 1H), 8.00 (m, 1H), 7.91 (d,J= 2.1 Hz, 1H), 7.46 (m, 1H), 7.23 (d,J=2.1 Hz, 1H), 5.60 (brs, 2H)。
The present invention has been further described with reference to specific embodiments, but it should be understood that the detailed description should not be construed as limiting the spirit and scope of the present invention, and various modifications made to the above-described embodiments by those of ordinary skill in the art after reading this specification are within the scope of the present invention.
Claims (9)
1. A method for synthesizing 5-chloro-2- (pyridin-3-yl) pyridin-3-amine, the method comprising the steps of:
(1) adding a compound A and a compound B into a reaction container, uniformly stirring, adding a solvent for dissolving, adding a solution formed by mixing carbonate and water, protecting with nitrogen, adding a catalyst, heating, and stirring for reaction;
(2) after the reaction is finished, adding water, extracting by ethyl acetate, drying and passing through a column to obtain a compound C, namely 5-chloro-2- (pyridine-3-yl) pyridine-3-amine;
the reaction formula of the synthesis method is as follows:
wherein, R in the compound A represents any one of bromine, iodine and chlorine.
2. The method for synthesizing 5-chloro-2- (pyridin-3-yl) pyridin-3-amine according to claim 1 wherein R in compound a represents any one of bromine and iodine.
3. The method for synthesizing 5-chloro-2- (pyridin-3-yl) pyridin-3-amine according to claim 1 wherein R in compound a represents bromine.
4. The method for synthesizing 5-chloro-2- (pyridin-3-yl) pyridin-3-amine according to claim 1 wherein the carbonate is any one of cesium carbonate, potassium carbonate, and sodium carbonate.
5. The method of synthesizing 5-chloro-2- (pyridin-3-yl) pyridin-3-amine of claim 1 wherein the carbonate is cesium carbonate.
6. The method of synthesizing 5-chloro-2- (pyridin-3-yl) pyridin-3-amine of claim 1 wherein the catalyst is palladium chloride.
7. The method of synthesizing 5-chloro-2- (pyridin-3-yl) pyridin-3-amine as claimed in claim 1 wherein the solvent is dioxane.
8. The method for synthesizing 5-chloro-2- (pyridin-3-yl) pyridin-3-amine according to claim 1, wherein in step (1) the mass ratio of compound a to compound B is 5:2 to 4, the solid-to-liquid ratio (g/mL) of compound a to solvent is 1:9 to 12, the solid-to-liquid ratio (g/mL) of carbonate to water is 14 to 16:25, the volume ratio of solvent to water is 2:1, and the mass ratio of compound a to catalyst is 5 to 7: 1.
9. The method for synthesizing 5-chloro-2- (pyridin-3-yl) pyridin-3-amine according to claim 1, wherein the temperature of heating in step (1) is 80 to 100 ℃ and the reaction time is 2 to 4 hours.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111606845A (en) * | 2020-07-20 | 2020-09-01 | 阿里生物新材料（常州）有限公司 | Synthesis method of 4-chloro-6-fluoropyridine-2-alcohol |
| CN112174832A (en) * | 2020-10-29 | 2021-01-05 | 阿里生物新材料（常州）有限公司 | Method for synthesizing 5-chloro-2-methyl-4- (trifluoromethyl) aniline in one step |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107011273A (en) * | 2017-05-04 | 2017-08-04 | 无锡捷化医药科技有限公司 | The method of one kind synthesis amine of 6 iodine 3 (2,3 dichlorophenyl) pyrazine 2 |
| CN110724091A (en) * | 2019-12-04 | 2020-01-24 | 阿里生物新材料（常州）有限公司 | Synthetic method of 6- (difluoromethyl) -2-hydroxypyridine-3-sulfonyl chloride |
| CN110734397A (en) * | 2019-12-02 | 2020-01-31 | 阿里生物新材料（常州）有限公司 | Synthesis method of 4- (difluoromethyl) -2-hydroxypyridine-5-sulfonyl chloride |
| CN110981792A (en) * | 2019-12-26 | 2020-04-10 | 阿里生物新材料（常州）有限公司 | Synthetic method of [ (3-bromo-6-difluoromethyl) pyridin-2-yl ] methanol |
| CN110981793A (en) * | 2019-12-23 | 2020-04-10 | 阿里生物新材料（常州）有限公司 | Synthetic method of 2- (difluoromethyl) pyridine-3-alcohol |
-
2020
- 2020-04-26 CN CN202010338674.8A patent/CN111303020B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107011273A (en) * | 2017-05-04 | 2017-08-04 | 无锡捷化医药科技有限公司 | The method of one kind synthesis amine of 6 iodine 3 (2,3 dichlorophenyl) pyrazine 2 |
| CN110734397A (en) * | 2019-12-02 | 2020-01-31 | 阿里生物新材料（常州）有限公司 | Synthesis method of 4- (difluoromethyl) -2-hydroxypyridine-5-sulfonyl chloride |
| CN110724091A (en) * | 2019-12-04 | 2020-01-24 | 阿里生物新材料（常州）有限公司 | Synthetic method of 6- (difluoromethyl) -2-hydroxypyridine-3-sulfonyl chloride |
| CN110981793A (en) * | 2019-12-23 | 2020-04-10 | 阿里生物新材料（常州）有限公司 | Synthetic method of 2- (difluoromethyl) pyridine-3-alcohol |
| CN110981792A (en) * | 2019-12-26 | 2020-04-10 | 阿里生物新材料（常州）有限公司 | Synthetic method of [ (3-bromo-6-difluoromethyl) pyridin-2-yl ] methanol |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111606845A (en) * | 2020-07-20 | 2020-09-01 | 阿里生物新材料（常州）有限公司 | Synthesis method of 4-chloro-6-fluoropyridine-2-alcohol |
| CN111606845B (en) * | 2020-07-20 | 2022-03-11 | 阿里生物新材料（常州）有限公司 | Synthesis method of 4-chloro-6-fluoropyridine-2-alcohol |
| CN112174832A (en) * | 2020-10-29 | 2021-01-05 | 阿里生物新材料（常州）有限公司 | Method for synthesizing 5-chloro-2-methyl-4- (trifluoromethyl) aniline in one step |
| CN112174832B (en) * | 2020-10-29 | 2022-05-13 | 阿里生物新材料（常州）有限公司 | Method for synthesizing 5-chloro-2-methyl-4- (trifluoromethyl) aniline in one step |
| CN112979565A (en) * | 2021-03-24 | 2021-06-18 | 阿里生物新材料（常州）有限公司 | Synthetic method of 2-chloro-5- (difluoromethoxy) pyrazine |
| CN112979565B (en) * | 2021-03-24 | 2022-05-13 | 阿里生物新材料（常州）有限公司 | Synthetic method of 2-chloro-5- (difluoromethoxy) pyrazine |
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