CN110981795A - Method for preparing 2-amido isonicotinic acid by using methyl 2-cyanoisonicotinate - Google Patents
Method for preparing 2-amido isonicotinic acid by using methyl 2-cyanoisonicotinate Download PDFInfo
- Publication number
- CN110981795A CN110981795A CN201911313721.7A CN201911313721A CN110981795A CN 110981795 A CN110981795 A CN 110981795A CN 201911313721 A CN201911313721 A CN 201911313721A CN 110981795 A CN110981795 A CN 110981795A
- Authority
- CN
- China
- Prior art keywords
- acid
- methyl
- cyanoisonicotinate
- preparing
- reaction
- 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.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
Abstract
The invention discloses a method for preparing 2-amido isonicotinic acid by utilizing 2-cyano isonicotinic acid methyl ester, wherein dioxane is added to react in sodium hydroxide aqueous solution, so that the yield of the 2-amido isonicotinic acid is obviously improved; the whole preparation method is simple and easy to operate, and is very suitable for industrial scale production.
Description
Technical Field
The invention belongs to the field of pharmacy, and particularly relates to a method for preparing 2-amido isonicotinic acid by using methyl 2-cyanoisonicotinate.
Background
AMG333 is a potent, highly selective TRPM8 receptor antagonist, IC5013nM, which can be prepared by a variety of methods, and has the chemical formula:
2-amido isonicotinic acid is an important raw material of one method for preparing AMG333, and the chemical structural formula is as follows:
the chemical reaction equation for preparing AMG333 by using 2-amido isonicotinic acid is as follows:
in the prior art, a plurality of technical methods for obtaining different target products by hydrolyzing methyl 2-cyanoisonicotinate under different conditions exist, but no corresponding intensive research report is found for how to prepare 2-amido isonicotinate by using methyl 2-cyanoisonicotinate.
The existing technologies for obtaining different products by hydrolyzing methyl 2-cyanoisonicotinate are various, and different products can be obtained by hydrolyzing under the conditions of different temperatures and mixed solvents of alkali and other components. The prior patent CN107573330A provides a preparation method of topiroxostat, which uses 2-cyano methyl isonicotinate as a raw material to obtain an intermediate through hydrazinolysis, and then the intermediate reacts with 4-cyanopyridine under the action of sodium ethoxide to obtain the topiroxostat. Patent CN104910068B discloses a synthesis method of 2-cyanoisonicotinic acid hydrazide 1.5 p-toluenesulfonate, which comprises using methyl 2-cyanoisonicotinic acid as a starting material, obtaining 2-cyanoisonicotinic acid through alkaline hydrolysis, condensing with tert-butoxycarbonylhydrazine under the action of a condensing agent, and hydrolyzing the condensation product with p-toluenesulfonic acid-hydrate to obtain the target compound.
Because the methyl 2-cyanoisonicotinate contains both cyano and ester groups, amino and carboxyl are easily generated after substitution and hydrolysis, the yield of the target product has great difference due to different reaction conditions, which also causes difficulty in how to prepare the 2-acylamino isonicotinate. The prior art does not find a technology for preparing 2-amido isonicotinic acid by utilizing 2-cyano isonicotinic acid methyl ester, and the 2-amido isonicotinic acid is used as an important raw material required by a method for preparing AMG333, and has very important practical significance for the chemical synthesis of AMG 333.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a method for preparing 2-acylamino isonicotinic acid by using 2-cyanoisonicotinic acid methyl ester, which can prepare the 2-acylamino isonicotinic acid by using the 2-cyanoisonicotinic acid methyl ester through selecting special solvents and other special conditions, and has very high yield. Specifically, the following technique is used.
A method for preparing 2-amido isonicotinic acid by utilizing methyl 2-cyanoisonicotinate comprises the following steps:
s1, mixing the 2-cyano methyl isonicotinate and dioxane uniformly;
s2, adding 4M sodium hydroxide aqueous solution, reacting for 3-8h at 20-50 ℃, and tracking the reaction by TLC until the raw materials are completely reacted;
s3, adjusting the pH value to 6-7 by using 4M hydrochloric acid, extracting twice by using a DCM extracting agent, combining DCM layers, drying by using magnesium sulfate, and concentrating to remove the solvent to obtain the 2-acylamino isonicotinic acid.
In the preparation method, the chemical reaction equation of the methyl 2-cyanoisonicotinate under the conditions of Dioxane (Dioxane), sodium hydroxide and water is as follows:
by adopting the method, the ester group can be effectively hydrolyzed to form carboxyl, the cyano group can also react to form amide group, the yield of the finally prepared 2-acylamino isonicotinic acid reaches more than 80 percent, and the highest yield is close to 90 percent. If other solvent combinations are adopted, such as dioxane and sodium carbonate aqueous solution, the yield of the 2-amido isonicotinic acid is less than 20 percent, the rest is mostly unreacted raw materials, and the small part is impurities of non-target products; tetrahydrofuran and a potassium carbonate/sodium carbonate aqueous solution or isopropanol and a sodium carbonate/sodium bicarbonate aqueous solution can only obtain other impurities, and the target product 2-acylamino isonicotinic acid cannot be obtained.
Preferably, the volume-mass ratio of the dioxane to the 2-cyanoisonicotinic acid is 5-10 mL/g.
More preferably, the volume-to-mass ratio of the dioxane to the 2-cyanoisonicotinic acid is 8 mL/g.
Preferably, the volume-to-mass ratio of the 4M aqueous sodium hydroxide solution to the 2-cyanoisonicotinic acid is 6-8 mL/g.
More preferably, the volume-to-mass ratio of the 4M aqueous sodium hydroxide solution to the 2-cyanoisonicotinic acid is 6.5 mL/g.
Preferably, in step S2, the reaction temperature is 35 ℃ and the reaction time is 5 h.
Preferably, in step S3, the pH adjusted with 4M hydrochloric acid is 6.2.
Compared with the prior art, the invention has the advantages that: by adopting the preparation method, 2-amido isonicotinic acid can be prepared by fully utilizing 2-cyano isonicotinic acid methyl ester, and very high yield can be obtained; the reaction condition is mild, the operation is simple, and the method is very suitable for industrial large-scale production.
Detailed Description
The technical solutions of the present invention will be described clearly and completely below, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
A method for preparing 2-amido isonicotinic acid by utilizing methyl 2-cyanoisonicotinate comprises the following steps:
s1, adding 1g (6.17mmol) of methyl 2-cyanoisonicotinate and 8mL of dioxane into a reaction bottle, and uniformly stirring;
s2, adding 6.5mL of 4M sodium hydroxide aqueous solution, reacting for 5h at 35 ℃, and tracking the reaction by TLC until the raw materials react completely;
s3, adjusting pH to 6.2 with 4M hydrochloric acid, extracting twice with DCM extractant, combining DCM layers, drying with magnesium sulfate, concentrating and removing solvent to obtain 2-amido isonicotinic acid.
By calculation, 0.92g of white solid was finally prepared with a yield of 89.5%. And (3) product verification:1H-NMR(400MHz,DMSO-d6):δ7.52(br s,1H),7.81(dd,J=4.8,1.5Hz,1H),8.03(br s,1H),8.34(dd,J=1.5,0.8Hz,1H),8.52ppm(dd,J=4.8,0.8Hz,1H)。
example 2
The preparation method of this example is substantially the same as that of example 1 except that: step S1 is: methyl 2-cyanoisonicotinate (1 g, 6.17mmol) and dioxane (10 mL) were added to the reaction flask and stirred uniformly.
By calculation, 0.87g of white solid was finally prepared with a yield of 84.7%. And (3) product verification:1H-NMR(400MHz,DMSO-d6):δ7.52(br s,1H),7.81(dd,J=4.8,1.5Hz,1H),8.03(br s,1H),8.34(dd,J=1.5,0.8Hz,1H),8.52ppm(dd,J=4.8,0.8Hz,1H)。
example 3
The preparation method of this example is substantially the same as that of example 1 except that: step S1 is: methyl 2-cyanoisonicotinate (1 g, 6.17mmol) and dioxane (5 mL) were added to the reaction flask and stirred uniformly.
By calculation, 0.89g of white solid was finally prepared with a yield of 86.8%. And (3) product verification:1H-NMR(400MHz,DMSO-d6):δ7.52(br s,1H),7.81(dd,J=4.8,1.5Hz,1H),8.03(br s,1H),8.34(dd,J=1.5,0.8Hz,1H),8.52ppm(dd,J=4.8,0.8Hz,1H)。
example 4
The preparation method of this example is substantially the same as that of example 1 except that: step S2 is: then 8mL of 4M aqueous sodium hydroxide solution was added, the reaction was carried out at 35 ℃ for 5 hours, and the reaction was followed by TLC until the starting material reaction was complete.
By calculation, 0.88g of white solid was finally prepared with a yield of 86.4%. And (3) product verification:1H-NMR(400MHz,DMSO-d6):δ7.52(br s,1H),7.81(dd,J=4.8,1.5Hz,1H),8.03(br s,1H),8.34(dd,J=1.5,0.8Hz,1H),8.52ppm(dd,J=4.8,0.8Hz,1H)。
example 5
The preparation method of this example is substantially the same as that of example 1 except that: step S2 is: then 6mL of 4M aqueous sodium hydroxide solution was added, the reaction was carried out at 35 ℃ for 5 hours, and the reaction was followed by TLC until the starting material was reacted completely.
By calculation, 0.84g of white solid was finally prepared with a yield of 82.1%. And (3) product verification:1H-NMR(400MHz,DMSO-d6):δ7.52(br s,1H),7.81(dd,J=4.8,1.5Hz,1H),8.03(br s,1H),8.34(dd,J=1.5,0.8Hz,1H),8.52ppm(dd,J=4.8,0.8Hz,1H)。
example 6
The preparation method of this example is substantially the same as that of example 1 except that: step S2 is: then 6.5mL of 4M aqueous sodium hydroxide solution was added and the reaction was followed by TLC for 3h at 50 ℃ until the starting material was reacted completely.
By calculation, 0.86g of a white solid was finally prepared in a yield of 83.9%. And (3) product verification:1H-NMR(400MHz,DMSO-d6):δ7.52(br s,1H),7.81(dd,J=4.8,1.5Hz,1H),8.03(br s,1H),8.34(dd,J=1.5,0.8Hz,1H),8.52ppm(dd,J=4.8,0.8Hz,1H)。
example 7
The preparation method of this example is substantially the same as that of example 1 except that: step S2 is: then 6.5mL of 4M aqueous sodium hydroxide solution was added, the reaction was carried out at 20 ℃ for 8 hours, and the reaction was followed by TLC until the starting material reaction was complete.
By calculation, 0.82g of white solid was finally prepared with a yield of 80.6%. And (3) product verification:1H-NMR(400MHz,DMSO-d6):δ7.52(br s,1H),7.81(dd,J=4.8,1.5Hz,1H),8.03(br s,1H),8.34(dd,J=1.5,0.8Hz,1H),8.52ppm(dd,J=4.8,0.8Hz,1H)。
example 8
The preparation method of this example is substantially the same as that of example 1 except that: in step S3, the pH was adjusted to 7 with 4M hydrochloric acid.
By calculation, 0.83g of white solid was finally prepared with a yield of 81.2%. And (3) product verification:1H-NMR(400MHz,DMSO-d6):δ7.52(br s,1H),7.81(dd,J=4.8,1.5Hz,1H),8.03(br s,1H),8.34(dd,J=1.5,0.8Hz,1H),8.52ppm(dd,J=4.8,0.8Hz,1H)。
example 9
The preparation method of this example is substantially the same as that of example 1 except that: in step S3, the pH is adjusted to 6 with 4M hydrochloric acid.
By calculation, 0.84g of white solid was finally prepared with a yield of 82.2%. And (3) product verification:1H-NMR(400MHz,DMSO-d6):δ7.52(br s,1H),7.81(dd,J=4.8,1.5Hz,1H),8.03(br s,1H),8.34(dd,J=1.5,0.8Hz,1H),8.52ppm(dd,J=4.8,0.8Hz,1H)。
comparative example 1
The comparative example was prepared substantially the same as example 1 except that step S1 was: methyl 2-cyanoisonicotinate (1 g, 6.17mmol) and dioxane (12 mL) were added to the reaction flask and stirred uniformly.
By calculation, 0.50g of white solid was finally prepared with a yield of 48.5%. And (3) product verification:1H-NMR(400MHz,DMSO-d6):δ7.52(br s,1H),7.81(dd,J=4.8,1.5Hz,1H),8.03(br s,1H),8.34(dd,J=1.5,0.8Hz,1H),8.52ppm(dd,J=4.8,0.8Hz,1H)。
comparative example 2
The comparative example was prepared substantially the same as example 1 except that step S1 was: methyl 2-cyanoisonicotinate (1 g, 6.17mmol) and dioxane (3 mL) were added to the reaction flask and stirred uniformly.
By calculation, 0.44g of white solid was finally prepared with a yield of 42.6%. And (3) product verification:1H-NMR(400MHz,DMSO-d6):δ7.52(br s,1H),7.81(dd,J=4.8,1.5Hz,1H),8.03(br s,1H),8.34(dd,J=1.5,0.8Hz,1H),8.52ppm(dd,J=4.8,0.8Hz,1H)。
comparative example 3
The comparative example was prepared essentially the same as example 1, except that: step S2 is: then 10mL of 4M aqueous sodium hydroxide solution was added, the reaction was carried out at 35 ℃ for 5 hours, and the reaction was followed by TLC until the starting material reaction was complete.
By calculation, 0.42g of white solid was finally prepared with a yield of 40.9%. And (3) product verification:1H-NMR(400MHz,DMSO-d6):δ7.52(br s,1H),7.81(dd,J=4.8,1.5Hz,1H),8.03(br s,1H),8.34(dd,J=1.5,0.8Hz,1H),8.52ppm(dd,J=4.8,0.8Hz,1H)。
comparative example 4
The comparative example was prepared essentially the same as example 1, except that: step S2 is: then 4mL of 4M aqueous sodium hydroxide solution was added, the reaction was carried out at 35 ℃ for 5 hours, and the reaction was followed by TLC until the starting material reaction was complete.
By calculation, 0.53g of white solid was finally prepared in 41.4% yield. And (3) product verification:1H-NMR(400MHz,DMSO-d6):δ7.52(br s,1H),7.81(dd,J=4.8,1.5Hz,1H),8.03(br s,1H),8.34(dd,J=1.5,0.8Hz,1H),8.52ppm(dd,J=4.8,0.8Hz,1H)。
comparative example 5
The comparative example was prepared essentially the same as example 1, except that: step S2 is: then 6.5mL of 4M aqueous sodium hydroxide was added and the reaction was followed by TLC for 2h at 55 ℃ until the starting material was completely reacted.
By calculation, 0.51g of a white solid was finally prepared in a yield of 52.1%. And (3) product verification:1H-NMR(400MHz,DMSO-d6):δ7.52(br s,1H),7.81(dd,J=4.8,1.5Hz,1H),8.03(br s,1H),8.34(dd,J=1.5,0.8Hz,1H),8.52ppm(dd,J=4.8,0.8Hz,1H)。
comparative example 6
The comparative example was prepared essentially the same as example 1, except that: step S2 is: then 6.5mL of 4M aqueous sodium hydroxide was added, the reaction was carried out at 15 ℃ for 9 hours, and the reaction was followed by TLC until the starting material reaction was complete.
By calculation, 0.50g of white solid was finally prepared with a yield of 49.2%. And (3) product verification:1H-NMR(400MHz,DMSO-d6):δ7.52(br s,1H),7.81(dd,J=4.8,1.5Hz,1H),8.03(br s,1H),8.34(dd,J=1.5,0.8Hz,1H),8.52ppm(dd,J=4.8,0.8Hz,1H)。
comparative example 7
The comparative example was prepared essentially the same as example 1, except that: in step S3, the pH was adjusted to 7.5 with 4M hydrochloric acid.
By calculation, 0.53g of white solid was finally prepared in 51.8% yield. And (3) product verification:1H-NMR(400MHz,DMSO-d6):δ7.52(br s,1H),7.81(dd,J=4.8,1.5Hz,1H),8.03(br s,1H),8.34(dd,J=1.5,0.8Hz,1H),8.52ppm(dd,J=4.8,0.8Hz,1H)。
comparative example 8
The comparative example was prepared essentially the same as example 1, except that: in step S3, the pH was adjusted to 5.5 with 4M hydrochloric acid.
By calculation, 0.52g of white solid was finally prepared with a yield of 50.6%. And (3) product verification:1H-NMR(400MHz,DMSO-d6):δ7.52(br s,1H),7.81(dd,J=4.8,1.5Hz,1H),8.03(br s,1H),8.34(dd,J=1.5,0.8Hz,1H),8.52ppm(dd,J=4.8,0.8Hz,1H)。
comparative example 9
The preparation method of the comparative example comprises the following steps:
s1, adding 1g (6.17mmol) of methyl 2-cyanoisonicotinate and 8mL of dioxane into a reaction bottle, and uniformly stirring;
s2, adding 6.5mL of 4M sodium carbonate aqueous solution, and reacting at 35 ℃ for 5 h;
s3, adjusting pH to 6.2 with 4M hydrochloric acid, extracting twice with DCM extractant, combining DCM layers, drying with magnesium sulfate, concentrating and removing solvent to obtain 2-amido isonicotinic acid.
By calculation, 0.14g of a white solid was finally prepared in a yield of 13.5%. And (3) product verification:1H-NMR(400MHz,DMSO-d6):δ7.52(br s,1H),7.81(dd,J=4.8,1.5Hz,1H),8.03(br s,1H),8.34(dd,J=1.5,0.8Hz,1H),8.52ppm(dd,J=4.8,0.8Hz,1H)。
comparative example 10
The preparation method of the comparative example comprises the following steps:
s1, adding 1g (6.17mmol) of methyl 2-cyanoisonicotinate and 8mL of tetrahydrofuran into a reaction bottle, and uniformly stirring;
s2, adding 6.5mL of 4M potassium carbonate aqueous solution, reacting for 5h at 35 ℃, and tracking the reaction by TLC until the raw materials are completely reacted;
s3, adjusting the pH value to 6.2 by using 4M hydrochloric acid, and extracting twice by using a DCM extractant.
By calculation, 0.05g of a white solid was finally prepared in a yield of 4.7%. And (3) product verification:1H-NMR(400MHz,DMSO-d6):δ7.52(br s,1H),7.81(dd,J=4.8,1.5Hz,1H),8.03(br s,1H),8.34(dd,J=1.5,0.8Hz,1H),8.52ppm(dd,J=4.8,0.8Hz,1H)。
comparative example 11
The preparation method of the comparative example comprises the following steps:
s1, adding 1g (6.17mmol) of methyl 2-cyanoisonicotinate and 8mL of isopropanol into a reaction bottle, and uniformly stirring;
s2, adding 6.5mL of 4M sodium bicarbonate aqueous solution, and reacting at 35 ℃ for 5 h;
s3, adjusting pH to 6.2 with 4M hydrochloric acid, extracting twice with DCM extractant, combining DCM layers, drying with magnesium sulfate, concentrating and removing solvent to obtain 2-amido isonicotinic acid.
The final liquid phase yield was calculated to be 0.3%, mostly other impurities. And (3) product verification:1H-NMR(400MHz,DMSO-d6):δ7.52(br s,1H),7.81(dd,J=4.8,1.5Hz,1H),8.03(br s,1H),8.34(dd,J=1.5,0.8Hz,1H),8.52ppm(dd,J=4.8,0.8Hz,1H)。
by the preparation methods of the above examples 1 to 9 and comparative examples 1 to 11, the parameters such as the yield and the like obtained by the calculation and detection can be known as follows: by adopting the preparation method, the yield of the prepared 2-acylamino isonicotinic acid is higher and is not lower than 80%. This shows that the ratio of the amount of methyl 2-cyanoisonicotinate to the amount of dioxane and sodium hydroxide has a significant effect on the yield of the final target product. In addition, the temperature, time and final pH of the reaction can affect the yield of the final desired product. If the combination of dioxane and sodium hydroxide is not selected, dioxane is replaced by other materials such as tetrahydrofuran, isopropanol and the like, or a sodium hydroxide solution is replaced by a sodium carbonate, potassium carbonate and a sodium bicarbonate aqueous solution, a large amount of 2-acylamino isonicotinic acid cannot be obtained, and even the 2-acylamino isonicotinic acid is not basically produced. In step S3 of the above comparative examples 9-11, it was found by TLC tracing that the reaction was not completed after 5h, and the analysis may result in that the reaction itself could not proceed due to the change of the preparation method or condition parameters, or the reaction rate was very slow, which all indicate that the technical effects of the solutions of the comparative examples 9-11 are not as good as the solutions of the present application.
Claims (7)
1. A method for preparing 2-amido isonicotinic acid by utilizing methyl 2-cyanoisonicotinate is characterized by comprising the following steps:
s1, mixing the 2-cyano methyl isonicotinate and dioxane uniformly;
s2, adding 4M sodium hydroxide aqueous solution, reacting for 3-8h at 20-50 ℃, and tracking the reaction by TLC until the raw materials are completely reacted;
s3, adjusting the pH value to 6-7 by using 4M hydrochloric acid, extracting twice by using a DCM extracting agent, combining DCM layers, drying by using magnesium sulfate, and concentrating to remove the solvent to obtain the 2-acylamino isonicotinic acid.
2. The method for preparing 2-acylaminoisonicotinic acid using methyl-2-cyanoisonicotinate according to claim 1, characterized in that the volume-to-mass ratio of dioxane to 2-cyanoisonicotinic acid is 5-10 mL/g.
3. The method for preparing 2-acylaminoisonicotinic acid using methyl-2-cyanoisonicotinate according to claim 2, characterized in that the volume-to-mass ratio of dioxane to 2-cyanoisonicotinic acid is 8 mL/g.
4. The method for preparing 2-acylaminoisonicotinic acid by using methyl 2-cyanoisonicotinate according to claim 1, characterized in that the volume-to-mass ratio of the 4M aqueous sodium hydroxide solution to 2-cyanoisonicotinic acid is 6-8 mL/g.
5. The method for preparing 2-acylaminoisonicotinic acid using methyl-2-cyanoisonicotinate according to claim 4, characterized in that the volume to mass ratio of the 4M aqueous sodium hydroxide solution to 2-cyanoisonicotinic acid is 6.5 mL/g.
6. The method of claim 1, wherein the reaction temperature is 35 ℃ and the reaction time is 5 hours in step S2.
7. The method of claim 1, wherein the pH of the solution is adjusted to 6.2 with 4M HCl in step S3.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911313721.7A CN110981795B (en) | 2019-12-18 | 2019-12-18 | Method for preparing 2-aminoacyl isonicotinic acid by using methyl 2-cyanoisonicotinate |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201911313721.7A CN110981795B (en) | 2019-12-18 | 2019-12-18 | Method for preparing 2-aminoacyl isonicotinic acid by using methyl 2-cyanoisonicotinate |
Publications (2)
Publication Number | Publication Date |
---|---|
CN110981795A true CN110981795A (en) | 2020-04-10 |
CN110981795B CN110981795B (en) | 2021-02-12 |
Family
ID=70095691
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201911313721.7A Active CN110981795B (en) | 2019-12-18 | 2019-12-18 | Method for preparing 2-aminoacyl isonicotinic acid by using methyl 2-cyanoisonicotinate |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN110981795B (en) |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5614636A (en) * | 1993-06-01 | 1997-03-25 | Lonza Ltd. | Process for the preparation of 2,4-pyridine dicarboxylic acid |
CN101203518A (en) * | 2005-05-19 | 2008-06-18 | 艾文蒂斯药品公司 | Novel fluorene derivatives, composition containing said derivatives and the use thereof |
CN103906733A (en) * | 2011-06-24 | 2014-07-02 | 安姆根有限公司 | TRMP8 antagonists and their use in treatments |
CN104910068A (en) * | 2015-04-24 | 2015-09-16 | 南京医科大学 | 2-cyano isonicotinic acid hydrazide 1.5 p-toluenesulfonate synthetic method |
CN105130958A (en) * | 2015-08-31 | 2015-12-09 | 济南康和医药科技有限公司 | Preparation technology for 5-(2-cyano4-pyridyl)-3-(4-pyridyl)-1,2,4-troazole |
CN107108597A (en) * | 2014-10-31 | 2017-08-29 | 英立维尔英国有限公司 | Dopamine D 3 receptor agonist compounds |
CN107573330A (en) * | 2017-09-30 | 2018-01-12 | 河北中医学院 | A kind of preparation method of Topiroxostat |
-
2019
- 2019-12-18 CN CN201911313721.7A patent/CN110981795B/en active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5614636A (en) * | 1993-06-01 | 1997-03-25 | Lonza Ltd. | Process for the preparation of 2,4-pyridine dicarboxylic acid |
CN101203518A (en) * | 2005-05-19 | 2008-06-18 | 艾文蒂斯药品公司 | Novel fluorene derivatives, composition containing said derivatives and the use thereof |
CN103906733A (en) * | 2011-06-24 | 2014-07-02 | 安姆根有限公司 | TRMP8 antagonists and their use in treatments |
CN107108597A (en) * | 2014-10-31 | 2017-08-29 | 英立维尔英国有限公司 | Dopamine D 3 receptor agonist compounds |
CN104910068A (en) * | 2015-04-24 | 2015-09-16 | 南京医科大学 | 2-cyano isonicotinic acid hydrazide 1.5 p-toluenesulfonate synthetic method |
CN105130958A (en) * | 2015-08-31 | 2015-12-09 | 济南康和医药科技有限公司 | Preparation technology for 5-(2-cyano4-pyridyl)-3-(4-pyridyl)-1,2,4-troazole |
CN107573330A (en) * | 2017-09-30 | 2018-01-12 | 河北中医学院 | A kind of preparation method of Topiroxostat |
Non-Patent Citations (3)
Title |
---|
HOLGER SIEBENEICHER等: "Identification and Optimization of the First Highly Selective GLUT1 Inhibitor BAY-876", 《CHEMMEDCHEM》 * |
刘耀华著: "《有机化学中的选择性氧化作用》", 30 June 2008 * |
杨锦宗编著: "《工业有机合成基础》", 31 December 1998, 北京:中国石化出版社 * |
Also Published As
Publication number | Publication date |
---|---|
CN110981795B (en) | 2021-02-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105175348A (en) | Preparation method for lesinurad | |
CN101654419A (en) | Preparation method of fluvoxamine maleate | |
CN105061405A (en) | Preparation method of fimasartan potassium salt hydrate | |
CN110981795B (en) | Method for preparing 2-aminoacyl isonicotinic acid by using methyl 2-cyanoisonicotinate | |
EP4140992A1 (en) | Method for preparing s-nicotine | |
CN105646285B (en) | One kind dimension Lactel sieve intermediate and its preparation method and application | |
CN111333543B (en) | Synthesis method of rilpivirine intermediate | |
CN105440012A (en) | Lenalidomide and lenalidomide intermediate preparation method | |
CN103880756B (en) | The preparation method of a kind of Azilsartan intermediate | |
CN115820762A (en) | Process for the synthesis of (S) -nicotine and intermediates thereof | |
CN113773229B (en) | Alpha, beta-unsaturated amino acid derivative and DL-selenium-methyl seleno amino acid derivative, synthetic method and application thereof | |
CN103304550A (en) | Preparation method of Olmesartan Medoxomil | |
CN104710413B (en) | The preparation method of two maleic acid Afatinibs | |
CN106946724B (en) | The synthetic method of monoamine base inhibitor class intermediate 2- acetylaminohydroxyphenylarsonic acid 2- benzyl malonic acid mono ethyl ester | |
CN102245591B (en) | Process for manufacturing 5-formyl-pyridine-2,3-dicarboxylic acid esters | |
CN107892699B (en) | A kind of synthesis technology of pyridine -4- boric acid | |
CN111349045A (en) | Synthetic method of lenvatinib and novel intermediate | |
CN107001250B (en) | A method of Ao Dangka is prepared for intermediate | |
CN104910068B (en) | A kind of synthetic method of the tosilate of 2 cyano group isonicotinic acid hydrazide 1.5 | |
CN104592333B (en) | The method of one kind synthesis deoxycytidine of 5 carboxyl 2 ' | |
CN113563180A (en) | (E) Preparation method of (E) -4-ene-1, 8-octanedioic acid | |
CN105085595B (en) | A kind of method of deacylation base protection 2,6 halosubstituted purine nucleosides of synthesis | |
CN109293507B (en) | Synthesis method and application of 4-methoxy methyl alkenyl-2-alkene dimethyl glutarate | |
CN109503482B (en) | Preparation method of varenicline key intermediate | |
CN102464663B (en) | Synthesis method of 1'-tert-butyloxycarbonyl-spiro[chroman-4,4'-piperidine]-2-formic acid |
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 | ||
GR01 | Patent grant | ||
GR01 | Patent grant |