CN110590771A - [1,5-a ] -pyridylimidazole-1-nitrile and chemical synthesis method thereof - Google Patents
[1,5-a ] -pyridylimidazole-1-nitrile and chemical synthesis method thereof Download PDFInfo
- Publication number
- CN110590771A CN110590771A CN201910836615.0A CN201910836615A CN110590771A CN 110590771 A CN110590771 A CN 110590771A CN 201910836615 A CN201910836615 A CN 201910836615A CN 110590771 A CN110590771 A CN 110590771A
- Authority
- CN
- China
- Prior art keywords
- pyridylimidazole
- compound
- chemical synthesis
- hours
- pyridoimidazole
- 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
- 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 relates to a chemical synthesis method of [1,5-a ] -pyridylimidazole-1-nitrile. The method comprises the following steps: 2-fluoropyridine is used as a raw material, and is subjected to five-step reaction including ring closing, hydrolysis, acyl halogenation, amidation and dehydration to synthesize the [1,5-a ] -pyridylimidazole-1-nitrile, so that an efficient synthesis method is provided for the synthesis of the compound.
Description
Technical Field
The invention relates to [1,5-a ] -pyridylimidazole-1-nitrile and a chemical synthesis method thereof.
Background
The pyridimidazoles have antiviral, antibacterial, antimicrobial activity, antifatigue and anxiolytic effects, and can be widely used in drugs for treating tumors, hypertension, gastric ulcer, psychosis, etc. The imidazopyridine compound is used as an intermediate of fine chemical products, and has wide application in the fields of catalysts, medicines, pesticides and the like. Therefore, the synthesis of the imidazopyridine compound has very important significance.
The [1,5-a ] -pyridylimidazole-1-nitrile is an important medical intermediate, so that the [1,5-a ] -pyridylimidazole-1-nitrile has important practical significance for the synthesis and research of the compound.
Disclosure of Invention
The present invention aims to provide a compound useful as a pharmaceutical intermediate, which is: [1,5-a ] -pyridoimidazole-1-carbonitrile, and a chemical synthesis method thereof.
In order to achieve the purpose, the technical scheme of the invention is as follows:
a compound I, namely: [1,5-a ] -pyridylimidazole-1-carbonitrile, which is characterized in that the molecular structural formula is shown as formula 1.
The chemical synthesis method of the compound I is characterized in that 2-fluoropyridine is used as a raw material, and the compound I is synthesized through five-step reaction, wherein the reaction is shown as a formula 2.
The chemical synthesis method of the compound I is characterized by comprising the following synthesis steps:
s1, under the protection of nitrogen, adding sodium hydride into dimethyl sulfoxide, controlling the temperature at 0 ℃, adding ethyl cyanoacetate, and stirring for 0.5 h. Then adding 2-fluoropyridine, controlling the reaction temperature, and reacting for 12h to obtain [1,5-a ] -pyridylimidazole-1-ethyl formate;
s2, adding the [1,5-a ] -pyridoimidazole-1-ethyl formate obtained in the step S1 into methanol, then adding an aqueous solution of an inorganic base, controlling the reaction temperature to react for 3 hours, and then adding hydrochloric acid to obtain [1,5-a ] -pyridoimidazole-1-formic acid;
s3, adding the [1,5-a ] -pyridylimidazole-1-formic acid obtained in the step S2 into dichloromethane, then adding thionyl chloride, and refluxing for 3 hours to obtain [1,5-a ] -pyridylimidazole-1-formyl chloride;
s4, controlling ammonia water to a certain temperature, adding the [1,5-a ] -pyridylimidazole-1-formyl chloride obtained in the step S3, and reacting for 3 hours under stirring to obtain [1,5-a ] -pyridylimidazole-1-formamide;
s5, adding the [1,5-a ] -pyridylimidazole-1-formamide obtained in the step S4 into phosphorus oxychloride, reacting for 2 hours at a certain temperature, and reacting to obtain [1,5-a ] -pyridylimidazole-1-carbonitrile.
Further, the reaction temperature of the step S1 is 30 to 70 ℃.
Further, the reaction temperature of step S2 is 30-100 ℃, and the inorganic base is one of sodium hydroxide, potassium carbonate, and potassium hydroxide.
Further, the certain temperature of the step S4 is-10-20 ℃.
Further, the certain temperature of the step S5 is 50-110 ℃.
The invention has the beneficial effects that: the chemical synthesis method takes 2-fluoropyridine as a raw material to synthesize the [1,5-a ] -pyridylimidazole-1-nitrile through five-step reaction. The method is simple and low in cost, and provides a solid foundation for mass production and subsequent research of the compound materials.
Drawings
FIG. 1 is a 1H-NMR spectrum of compound I prepared in example 1.
Detailed description of the invention
The following detailed description will provide specific embodiments of the present invention. These embodiments are merely illustrative and not intended to limit the scope or the principles of the invention, which is defined by the claims and includes obvious modifications and variations based thereon.
Example 1
Synthesis of S1, [1,5-a ] -pyridoimidazole-1-carboxylic acid ethyl ester:
96g of sodium hydrogen is added into a 5L four-neck flask, 2L of DMSO is added dropwise at the temperature of 0 ℃ under the mechanical stirring, 271g of ethyl cyanoacetate is slowly added dropwise after the addition, the stirring is carried out for 30min, and 194g of 2-fluoropyridine is also slowly added dropwise into the system. After dropping, the reaction was stirred at 50 ℃ for 12 hours. Performing thin-layer chromatography analysis on raw materials to completely react, cooling to 0 ℃, dropwise adding 100mL of water to quench the reaction, adding 6L of water, extracting with ethyl acetate for 3 times (3X 2L), drying an organic phase with anhydrous sodium sulfate, and concentrating to dryness to obtain 131g of [1,5-a ] -pyridylimidazole-1-ethyl formate, wherein the yield is 35%.
Synthesis of S2, [1,5-a ] -pyridoimidazole-1-carboxylic acid:
in a 1L four-necked flask 40g of [1,5-a ] -pyridoimidazole-1-carboxylic acid ethyl ester were dissolved in 200mL of 12.6g sodium hydroxide solution and stirred at 70 ℃ for 3 hours. The raw materials are completely reacted by thin-layer chromatography analysis, the reaction product is cooled to room temperature, the pH value is adjusted to 3-4 by 12M hydrochloric acid, a large amount of solid is separated out, the solid is filtered, a filter cake is leached by water and dried, 32.8g of [1,5-a ] -pyridylimidazole-1-formic acid is obtained, and the yield is 96.2%.
Synthesis of S3, [1,5-a ] -pyridoimidazole-1-carbonyl chloride:
120.5g of thionyl chloride was added to a 0.25L reaction flask and dissolved in 0.1L of acetonitrile, and 32.8g of [1,5-a ] -pyridoimidazole-1-carboxylic acid was added in portions under magnetic stirring, and the mixture was heated under reflux for 3 hours. The raw materials are analyzed by thin layer chromatography to react completely, and the raw materials are concentrated to be dry to obtain [1,5-a ] -pyridine imidazole-1-formyl chloride which is directly carried out to the next step.
Synthesis of S4, [1,5-a ] -pyridoimidazole-1-carboxamide:
the [1,5-a ] -pyridylimidazole-1-carbonyl chloride of the previous step was added to a 1L four-necked flask and dissolved in 0.2L of methyl tert-butyl ether, and the above acid chloride solution was slowly added to 400mL of ammonia water at a temperature of 15 ℃ under magnetic stirring, and stirring was continued for 3 hours after the addition was completed. TLC analysis of the starting material reaction was complete, filtration, cake washing with water, oven drying, filtrate extraction with dichloromethane 8 times (8X 200mL), anhydrous sodium sulfate drying, concentration to dryness, oven drying, total 27g of [1,5-a ] -pyridoimidazole-1-carboxamide was obtained in 83.1% yield.
Synthesis of S5, [1,5-a ] -pyridoimidazole-1-carbonitrile:
in a 100mL three-necked flask, 24g of [1,5-a ] -pyridoimidazole-1-carboxamide and 25mL of phosphorus oxychloride were added and reacted at 110 ℃ for 2 hours. Thin layer chromatography analysis shows that the raw materials completely react, phosphorus oxychloride is completely concentrated, the residue is added into ice water, ethyl acetate 500mL is added, stirring is carried out for 0.5H, silica gel is filled for filtration, a filter cake is leached by ethyl acetate, liquid separation is carried out, an organic phase is dried, concentration and methyl tert-butyl ether pulping are carried out, 18g of [1,5-a ] -pyridine imidazole-1-nitrile is obtained, and a 1H-NMR spectrum is shown in figure 1. The yield was 84.5%.
Example 2
Synthesis of S1, [1,5-a ] -pyridoimidazole-1-carboxylic acid ethyl ester:
96g of sodium hydrogen is added into a 5L four-neck flask, 2L of DMSO is added dropwise while controlling the temperature of the system at 0 ℃ under mechanical stirring, 271g of ethyl cyanoacetate is slowly added dropwise while stirring for 30min, and 194g of 2-fluoropyridine is also slowly added dropwise into the system. After dropping, the mixture is stirred and reacted for 12 hours at the temperature of 30 ℃. Performing thin-layer chromatography analysis on raw materials to completely react, cooling to 0 ℃, dropwise adding 100mL of water to quench the reaction, adding 6L of water, extracting with ethyl acetate for 3 times (3X 2L), drying an organic phase with anhydrous sodium sulfate, and concentrating to dryness to obtain 123g of [1,5-a ] -pyridylimidazole-1-ethyl formate, wherein the yield is 32.9%.
Synthesis of S2, [1,5-a ] -pyridoimidazole-1-carboxylic acid:
in a 1L four-necked flask 40g of [1,5-a ] -pyridoimidazole-1-carboxylic acid ethyl ester were dissolved in 200mL of 12.6g sodium hydroxide solution and stirred at 50 ℃ for 3 hours. The raw materials are completely reacted by thin-layer chromatography analysis, the reaction product is cooled to room temperature, the pH value is adjusted to 3-4 by 12M hydrochloric acid, a large amount of solid is separated out, the solid is filtered, a filter cake is leached by water and dried, 32.0g of [1,5-a ] -pyridylimidazole-1-formic acid is obtained, and the yield is 93.9%.
Synthesis of S3, [1,5-a ] -pyridoimidazole-1-carbonyl chloride:
120.5g of thionyl chloride was added to a 0.25L reaction flask and dissolved in 0.1L of acetonitrile, and 32.8g of [1,5-a ] -pyridoimidazole-1-carboxylic acid was added in portions under magnetic stirring, and the mixture was heated under reflux for 3 hours. The raw materials are analyzed by thin layer chromatography to react completely, and the raw materials are concentrated to be dry to obtain [1,5-a ] -pyridine imidazole-1-formyl chloride which is directly carried out to the next step.
Synthesis of S4, [1,5-a ] -pyridoimidazole-1-carboxamide:
adding the [1,5-a ] -pyridylimidazole-1-formyl chloride obtained in the previous step into a 1L four-neck bottle, dissolving in 0.2L methyl tert-butyl ether, slowly adding the acyl chloride solution into 400mL ammonia water with the temperature of below 10 ℃ under magnetic stirring, and continuing to stir for 3 hours after the addition is finished. TLC analysis of the reaction of the starting materials was complete, filtration, washing of the filter cake with water, drying, extraction of the filtrate with dichloromethane 8 times (8X 200mL), drying over anhydrous sodium sulfate, concentration to dryness, drying to give a total of 21g of [1,5-a ] -pyridoimidazole-1-carboxamide in 64.6% yield.
Synthesis of S5, [1,5-a ] -pyridoimidazole-1-carbonitrile:
in a 100mL three-necked flask, 24g of [1,5-a ] -pyridoimidazole-1-carboxamide and 25mL of phosphorus oxychloride were added and reacted at 80 ℃ for 2 hours. And (3) analyzing by thin layer chromatography that the raw materials completely react, the phosphorus oxychloride is completely concentrated, the remainder is added into ice water, 500mL of ethyl acetate is added, the stirring is carried out for 0.5h, silica gel is filled for filtration, a filter cake is leached by ethyl acetate, liquid separation is carried out, an organic phase is dried, the concentration is carried out, and methyl tert-butyl ether is beaten to obtain 16g of [1,5-a ] -pyridylimidazole-1-carbonitrile, wherein the yield is 75.1%.
Example 3
Synthesis of S1, [1,5-a ] -pyridoimidazole-1-carboxylic acid ethyl ester:
96g of sodium hydrogen is added into a 5L four-neck flask, 2L of DMSO is added dropwise at the temperature of 0 ℃ under the mechanical stirring, 271g of ethyl cyanoacetate is slowly added dropwise after the addition, the stirring is carried out for 30min, and 194g of 2-fluoropyridine is also slowly added dropwise into the system. After dropping, the reaction was stirred at 70 ℃ for 12 hours. Thin layer chromatography analysis raw materials react completely, the temperature is reduced to 0 ℃, 100mL of water is added dropwise to quench the reaction, 6L of water is added, ethyl acetate is extracted for 3 times (3X 2L), anhydrous sodium sulfate is used for drying an organic phase, and the organic phase is concentrated to dryness to obtain 133g of [1,5-a ] -pyridylimidazole-1-ethyl formate, wherein the yield is 35.5%.
Synthesis of S2, [1,5-a ] -pyridoimidazole-1-carboxylic acid:
in a 1L four-necked flask 40g of [1,5-a ] -pyridoimidazole-1-carboxylic acid ethyl ester were dissolved in 200mL of 12.6g sodium hydroxide solution and stirred at 100 ℃ for 3 hours. The raw materials are completely reacted by thin-layer chromatography analysis, the reaction product is cooled to room temperature, the pH value is adjusted to 3-4 by 12M hydrochloric acid, a large amount of solid is separated out, the solid is filtered, a filter cake is leached by water and dried, 33.2g of [1,5-a ] -pyridylimidazole-1-formic acid is obtained, and the yield is 97.4%.
Synthesis of S3, [1,5-a ] -pyridoimidazole-1-carbonyl chloride:
120.5g of thionyl chloride was added to a 0.25L reaction flask and dissolved in 0.1L of acetonitrile, and 32.8g of [1,5-a ] -pyridoimidazole-1-carboxylic acid was added in portions under magnetic stirring, and the mixture was heated under reflux for 3 hours. The raw materials are analyzed by thin layer chromatography to react completely, and the raw materials are concentrated to be dry to obtain [1,5-a ] -pyridine imidazole-1-formyl chloride which is directly carried out to the next step.
Synthesis of S4, [1,5-a ] -pyridoimidazole-1-carboxamide:
the [1,5-a ] -pyridylimidazole-1-carbonyl chloride of the previous step was added to a 1L four-necked flask and dissolved in 0.2L of methyl tert-butyl ether, and the above acid chloride solution was slowly added to 400mL of ammonia water at a temperature of 5 ℃ under magnetic stirring, and stirring was continued for 3 hours after the addition was completed. TLC analysis raw material reaction is complete, filtration, filter cake washing, drying, filtrate extraction with dichloromethane 8 times (8X 200mL), anhydrous sodium sulfate drying, concentration to dryness, drying, 30g of [1,5-a ] -pyridine imidazole-1-formamide is obtained, yield is 92.1%.
Synthesis of S5, [1,5-a ] -pyridoimidazole-1-carbonitrile:
in a 100mL three-necked flask, 24g of [1,5-a ] -pyridoimidazole-1-carboxamide and 25mL of phosphorus oxychloride were added and reacted at 50 ℃ for 2 hours. And (3) analyzing by thin layer chromatography that the raw materials completely react, the phosphorus oxychloride is completely concentrated, the residue is added into ice water, 500mL of ethyl acetate is added, the stirring is carried out for 0.5h, silica gel is filled for filtration, a filter cake is leached by ethyl acetate, liquid separation is carried out, an organic phase is dried, the concentration is carried out, and methyl tert-butyl ether is beaten to obtain 13g of [1,5-a ] -pyridylimidazole-1-carbonitrile, wherein the yield is 61%.
Claims (7)
1. A compound I, namely: [1,5-a ] -pyridylimidazole-1-carbonitrile, which is characterized in that the molecular structural formula is shown as formula 1.
2. The chemical synthesis method of the compound I as claimed in claim 1, wherein 2-fluoropyridine is used as a raw material to synthesize the compound I through five-step reaction, as shown in formula 2.
3. The chemical synthesis process of compound i according to claim 2, comprising the following synthesis steps:
s1, under the protection of nitrogen, adding sodium hydride into dimethyl sulfoxide, controlling the temperature at 0 ℃, adding ethyl cyanoacetate, and stirring for 0.5 h. Then adding 2-fluoropyridine, controlling the reaction temperature, and reacting for 12h to obtain [1,5-a ] -pyridylimidazole-1-ethyl formate;
s2, adding the [1,5-a ] -pyridoimidazole-1-ethyl formate obtained in the step S1 into methanol, then adding an aqueous solution of an inorganic base, controlling the reaction temperature to react for 3 hours, and then adding hydrochloric acid to obtain [1,5-a ] -pyridoimidazole-1-formic acid;
s3, adding the [1,5-a ] -pyridylimidazole-1-formic acid obtained in the step S2 into dichloromethane, then adding thionyl chloride, and refluxing for 3 hours to obtain [1,5-a ] -pyridylimidazole-1-formyl chloride;
s4, controlling ammonia water to a certain temperature, adding the [1,5-a ] -pyridylimidazole-1-formyl chloride obtained in the step S3, and reacting for 3 hours under stirring to obtain [1,5-a ] -pyridylimidazole-1-formamide;
s5, adding the [1,5-a ] -pyridylimidazole-1-formamide obtained in the step S4 into phosphorus oxychloride, reacting for 2 hours at a certain temperature, and reacting to obtain [1,5-a ] -pyridylimidazole-1-carbonitrile.
4. A process for the chemical synthesis of compound i according to claim 3, characterized in that: the reaction temperature of the step S1 is 30-70 ℃.
5. A process for the chemical synthesis of compound i according to claim 3, characterized in that: the reaction temperature of the step S2 is 30-100 ℃, and the inorganic base is one of sodium hydroxide, potassium carbonate and potassium hydroxide.
6. A process for the chemical synthesis of compound i according to claim 3, characterized in that: the certain temperature of the step S4 is-10-20 ℃.
7. A process for the chemical synthesis of compound i according to claim 3, characterized in that: the certain temperature of the step S5 is 50-110 ℃.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910836615.0A CN110590771B (en) | 2019-09-05 | 2019-09-05 | [1,5-a ] -pyridylimidazole-1-nitrile and chemical synthesis method thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201910836615.0A CN110590771B (en) | 2019-09-05 | 2019-09-05 | [1,5-a ] -pyridylimidazole-1-nitrile and chemical synthesis method thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN110590771A true CN110590771A (en) | 2019-12-20 |
CN110590771B CN110590771B (en) | 2021-11-12 |
Family
ID=68857681
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201910836615.0A Active CN110590771B (en) | 2019-09-05 | 2019-09-05 | [1,5-a ] -pyridylimidazole-1-nitrile and chemical synthesis method thereof |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN110590771B (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111233770A (en) * | 2020-02-28 | 2020-06-05 | 南通大学 | Chiral pyrazole derivative and synthesis method thereof |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN87104648A (en) * | 1986-07-08 | 1988-04-13 | 合成实验室公司 | Nitrofuran derivatives and preparation method thereof and the application in treatment |
CN103864786A (en) * | 2014-03-13 | 2014-06-18 | 定陶县友帮化工有限公司 | Method for synthesizing 6-fluoroimidazo-[1,2-a]-pyridine-3-formic acid |
CN103965190A (en) * | 2014-05-20 | 2014-08-06 | 定陶县友帮化工有限公司 | Synthesis method of imidazo[1,2-alpha]pyridyl-3-formic acid |
CN106632320A (en) * | 2016-11-23 | 2017-05-10 | 山东友帮生化科技有限公司 | Preparation method of 6-chlorine-imidazo[1,2a]pyridine-3-formamide |
CN106632321A (en) * | 2016-11-23 | 2017-05-10 | 山东友帮生化科技有限公司 | Preparation method of 6-bromine-imidazo[1,2a]pyridine-3-formamide |
CN109081810A (en) * | 2018-09-20 | 2018-12-25 | 沈阳药科大学 | The synthetic method of 1- methyl-3-((methylamino) methyl)-1H- pyrazoles-5- nitrile |
CN110183442A (en) * | 2019-06-06 | 2019-08-30 | 无锡合全药业有限公司 | A kind of synthetic method of 1-(carbethoxyl group) imidazo [1,5] pyridine-6- carboxylic acid |
-
2019
- 2019-09-05 CN CN201910836615.0A patent/CN110590771B/en active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN87104648A (en) * | 1986-07-08 | 1988-04-13 | 合成实验室公司 | Nitrofuran derivatives and preparation method thereof and the application in treatment |
CN103864786A (en) * | 2014-03-13 | 2014-06-18 | 定陶县友帮化工有限公司 | Method for synthesizing 6-fluoroimidazo-[1,2-a]-pyridine-3-formic acid |
CN103965190A (en) * | 2014-05-20 | 2014-08-06 | 定陶县友帮化工有限公司 | Synthesis method of imidazo[1,2-alpha]pyridyl-3-formic acid |
CN106632320A (en) * | 2016-11-23 | 2017-05-10 | 山东友帮生化科技有限公司 | Preparation method of 6-chlorine-imidazo[1,2a]pyridine-3-formamide |
CN106632321A (en) * | 2016-11-23 | 2017-05-10 | 山东友帮生化科技有限公司 | Preparation method of 6-bromine-imidazo[1,2a]pyridine-3-formamide |
CN109081810A (en) * | 2018-09-20 | 2018-12-25 | 沈阳药科大学 | The synthetic method of 1- methyl-3-((methylamino) methyl)-1H- pyrazoles-5- nitrile |
CN110183442A (en) * | 2019-06-06 | 2019-08-30 | 无锡合全药业有限公司 | A kind of synthetic method of 1-(carbethoxyl group) imidazo [1,5] pyridine-6- carboxylic acid |
Non-Patent Citations (1)
Title |
---|
冯承涛 等: "1-硫氰基咪唑并[1,5-a]吡啶合成工艺研究", 《安徽科技学院学报》 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN111233770A (en) * | 2020-02-28 | 2020-06-05 | 南通大学 | Chiral pyrazole derivative and synthesis method thereof |
CN111233770B (en) * | 2020-02-28 | 2022-12-27 | 南通大学 | Chiral pyrazole derivative and synthesis method thereof |
Also Published As
Publication number | Publication date |
---|---|
CN110590771B (en) | 2021-11-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN108017583A (en) | A kind of preparation method for winning U.S. | |
CN112679420A (en) | Preparation method of 2,5-dibromopyridine | |
CN111499586B (en) | Synthesis method of 5,5' -triazene bridged bis (2-methyl-4-nitro-1, 2, 3-triazole) compound | |
CN110669045A (en) | 1-methyl- [1,5-a ] -pyridylimidazole-3-nitrile and chemical synthesis method thereof | |
CN110590771B (en) | [1,5-a ] -pyridylimidazole-1-nitrile and chemical synthesis method thereof | |
CN114315823B (en) | Intermediate of berberine hydrochloride and analogues thereof and preparation method thereof | |
CN111100128B (en) | Synthetic method of Ribocini intermediate product and intermediate compound thereof | |
CN107118215B (en) | A kind of preparation method for treating breast cancer medicines Rui Boxini intermediate | |
CN111848546B (en) | 2- (aminomethyl) thiazole-5-nitrile and synthesis method thereof | |
CN108570085B (en) | Maleimide derivatives of the triazole structure containing xylose and the preparation method and application thereof | |
CN103773360B (en) | Schiff base fluorescent polymer and preparation method thereof | |
CN108299291B (en) | It is acylated the synthetic method of quinoline or isoquinilone derivatives | |
CN112079775A (en) | Synthesis method of 5-trifluoromethyl isoquinoline-8-formic acid | |
CN108640807B (en) | Preparation method of formylated heterocyclic derivative | |
CN106748725B (en) | preparation method of 4-chloro-2-fluoro-phenylpropionic acid | |
CN110563721A (en) | Preparation method of azasetron hydrochloride | |
EP3026047A1 (en) | Method for producing heterocyclic compound | |
CN110194760B (en) | Process for preparing 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindol-1-ones | |
CN108727360A (en) | A kind of preparation method of 2- pyrrole radicals -1,3- morpholine class compounds | |
CN105017219B (en) | Synthetic method for p53-MDM2-binding inhibitor dyhydroxyl quinoline derivative | |
CN112574106B (en) | Synthesis method of 7-amino-5-bromoquinoline | |
CN110590813B (en) | Thiazolo [4,5-b ] pyridine-6-carboxylic acid and chemical synthesis method thereof | |
CN110156649B (en) | Method for preparing 3-phenyl-2-phenyl disulfane methyl methacrylate compound by silver catalysis | |
CN114044762B (en) | Preparation method of chlormezanone intermediate | |
CN109384708B (en) | Akt inhibitor intermediate SM1 and preparation method thereof |
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 |