CN110669045A - 1-methyl- [1,5-a ] -pyridylimidazole-3-nitrile and chemical synthesis method thereof - Google Patents
1-methyl- [1,5-a ] -pyridylimidazole-3-nitrile and chemical synthesis method thereof Download PDFInfo
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Abstract
The invention relates to a chemical synthesis method of 1-methyl- [1,5-a ] -pyridine imidazole-3-nitrile. The method comprises the following steps: the 1-methyl- [1,5-a ] -pyridylimidazole-3-nitrile is synthesized by starting from 2-pyridinylethanone as a raw material through seven steps of reactions including oximation, reduction, substitution, ring closing, hydrolysis, amidation and dehydration, and an efficient synthesis method is provided for the synthesis of the compound.
Description
Technical Field
The invention relates to 1-methyl- [1,5-a ] -pyridine imidazole-3-nitrile and a chemical synthesis method thereof.
Background
The imidazopyridine compounds have antiviral, antibacterial, antimicrobial, antifatigue and anxiolytic effects, and can be widely used in medicines for treating tumor, 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.
1-methyl- [1,5-a ] -pyridine imidazole-3-nitrile is an important medical intermediate, so that the compound has important practical significance for the synthesis research of the compound.
Disclosure of Invention
The invention aims to provide a compound which can be used as a medical intermediate, namely 1-methyl- [1,5-a ] -pyridine imidazole-3-nitrile, and also provides a high-efficiency chemical synthesis method.
In order to achieve the purpose, the technical scheme of the invention is as follows:
a compound I, namely: 1-methyl- [1,5-a ] -pyridine imidazole-3-nitrile, which is characterized in that the molecular structure is shown as formula 1.
The synthesis method of the compound I is characterized in that 2-pyridine ethanone is used as a raw material, and the compound I is synthesized through six steps of reaction, wherein the synthetic route is shown as a formula 2:
the synthesis method of the compound I is characterized by comprising the following synthesis steps:
s1, adding 2-pyridine ethyl ketone into ethanol and water, adding inorganic base, controlling the reaction system to be 0 ℃, adding hydroxylamine hydrochloride, and reacting for 3 hours to prepare 2-pyridine ethyl ketone oxime;
s2, adding the 2-pyridine ethanone oxime obtained in the step S1 into methanol, then adding ammonium chloride, then adding zinc powder in batches, controlling the reaction temperature, reacting for 12 hours, and synthesizing 2' -pyridine-1-ethylamine;
s3, adding the 2 ' -pyridine-1-ethylamine obtained in the step S2 into dichloromethane, then adding organic base, controlling the reaction temperature, adding oxalyl chloride monoethyl ester, and reacting for 1h to obtain 2- (2 ' -pyridyl-1 ' -ethylamino) -2-carbonyl-ethyl acetate;
s4, adding the 2- (2 '-pyridyl-1' -ethylamino) -2-carbonyl-ethyl acetate obtained in the step S3 into dichloromethane, adding organic base, controlling the temperature to be 0 ℃, then adding trifluoroacetic anhydride, and reacting for 1h to obtain 1-methyl- [1,5-a ] -pyridoimidazole-3-ethyl formate;
s5, adding the ethyl 1-methyl- [1,5-a ] -pyridoimidazole-3-carboxylate obtained in the step S4 into ammonia water, and controlling the reaction temperature to obtain 1-methyl- [1,5-a ] -pyridoimidazole-3-formamide;
s6, adding the 1-methyl- [1,5-a ] -pyridylimidazole-3-formamide obtained in the step S5 into tetrahydrofuran, then adding an organic base, controlling the reaction temperature, then adding trifluoroacetic anhydride, stirring for 1h after the addition is finished, and reacting to obtain 1-methyl- [1,5-a ] -pyridylimidazole-3-carbonitrile.
Further, the inorganic base in step S1 is one of sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate.
Further, the reaction temperature of the step S2 is 10-50 ℃.
Further, the reaction temperature of the step S3 is-20-10 ℃, and the organic base is one of triethylamine, pyridine and triethanolamine.
Further, the organic base in step S4 is one of triethylamine, pyridine, and triethanolamine.
Further, the reaction temperature of the step S5 is 30-100 ℃.
Further, in the step S6, the reaction temperature is-10 to 10 ℃, and the organic base is one of triethylamine, pyridine, and triethanolamine.
The invention has the beneficial effects that: the chemical synthesis method of the invention takes 2-pyridine ethanone as raw material and synthesizes 1-methyl- [1,5-a ] -pyridine imidazole-3-nitrile through six steps of reactions. 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 provided only for describing and not for limiting the scope or the principle of the present invention, and the scope of the present invention is defined by the claims, and includes obvious variations or modifications based on the basic idea.
Example 1
S1, synthesis of 2-pyridine ethyl ketoxime:
dissolving 500g of 2-pyridinylethanone in 2L of ethanol and 1L of water in a 5L four-neck flask, adding 306g of sodium carbonate under mechanical stirring, cooling to below 0 ℃ by using a low-temperature circulating cooling pump, slowly adding 373g of hydroxylamine hydrochloride in batches, and naturally heating to room temperature for 3 hours after dropwise addition. Thin-layer chromatography analysis shows that the raw materials completely react, the raw materials are filtered, a filter cake is washed with water, the filtrate is concentrated to obtain ethanol, 1L of water is added, ethyl acetate is extracted for 2 times (2X 1L), anhydrous sodium sulfate is dried, the concentration and the drying are carried out, 556g of 2-pyridine ketoxime solid is obtained in total, and the yield is 91%.
Synthesis of S2, 2' -pyridin-1-ethylamine:
406g of 2-pyridinylethanone oxime was dissolved in 3L of methanol in a 5L four-necked flask, 471g of ammonium chloride was added with mechanical stirring, and 573.5g of zinc powder was slowly added in portions at room temperature. After the addition, the reaction was carried out at 20 ℃ for 12 hours. Thin layer chromatography analysis of the raw materials reaction completely, filtering, leaching the filter cake with methanol, concentrating the filtrate to dryness, adding 2L of water, adjusting the pH value to 13-14 with sodium hydroxide, adding 2L of dichloromethane, filtering with silica gel pad, leaching the filter cake with dichloromethane, separating, extracting the aqueous phase with dichloromethane for 10 times (10X 1L), drying with anhydrous sodium sulfate, and concentrating to dryness. Vacuum distilling (external temperature 70 deg.C, 30Pa), collecting 40-45 deg.C fraction to obtain 200g 2' -pyridine-1-ethylamine with yield of 55.8%.
Synthesis of S3, 2- (2 "-pyridyl-1' -ethylamino) -2-carbonyl-ethyl acetate:
100g of 2' -pyridine-1-ethylamine is added into a reaction flask of 3L and dissolved in 1L of dichloromethane, 108 g of triethylamine is added under mechanical stirring, the temperature is reduced to-5 ℃, 123g of oxalyl chloride monoethyl ester is slowly dripped, and the temperature is kept for 1h at 0 ℃ after the dripping. Thin layer chromatography analysis of the reaction of raw materials completely, adding water 1.5L, separating, dichloromethane phase washing once with water, saturated saline water washing once, anhydrous sodium sulfate drying, concentrating to dryness, to obtain 2- (2 '-pyridyl-1' -ethylamino) -2-carbonyl-ethyl acetate, directly carrying out the next step.
Synthesis of S4, ethyl 1-methyl- [1,5-a ] -pyridoimidazole-3-carboxylate:
350g of 2- (2 '-pyridyl-1' -ethylamino) -2-carbonyl-ethyl acetate are added into a 3L four-necked bottle and dissolved in 2L of dichloromethane, 299g of pyridine is added under mechanical stirring, and after the temperature is reduced to below 0 ℃ by using a low-temperature circulating cooling pump, 397g of trifluoroacetic anhydride is slowly dropped. After the dripping is finished, the temperature is kept for 1h at 0 ℃. Thin layer chromatography analysis of the raw materials reaction completely, water 2L, liquid separation, dichloromethane phase water washing 2 times, saturated saline water washing once, anhydrous sodium sulfate drying, concentrated to dryness. Dissolving with 1.5L, adding active carbon, refluxing and decolorizing for 0.5h, filtering with silica gel pad, concentrating the filtrate to dryness, pulping with 500mL petroleum ether and 50mL ethyl acetate to obtain 163g of 1-methyl- [1,5-a ] -pyridoimidazole-3-ethyl formate with a yield of 50.8%.
S5, synthesis of 1-methyl- [1,5-a ] -pyridoimidazole-3-carboxamide:
50g of 1-methyl- [1,5-a ] -pyridoimidazole-3-carboxylic acid ethyl ester was added to a 1L four-necked flask in 0.5L of aqueous ammonia, and reacted at 70 ℃ overnight. And (3) analyzing the reaction of the raw materials by thin layer chromatography, cooling to room temperature, filtering, washing a filter cake with water, and drying. The filtrate was concentrated to dryness, purified with 1:1 methyl tert-butyl ether: 100mL of isopropyl alcohol was slurried, filtered, and dried to obtain 19.5g of 1-methyl- [1,5-a ] -pyridoimidazole-3-carboxamide in a total yield of 44.9%.
S6, Synthesis of 1-methyl- [1,5-a ] -pyridoimidazole-3-carbonitrile:
19.5g of 1-methyl- [1,5-a ] -pyridylimidazol-3-carboxamide is added to a 0.25L three-necked flask and dissolved in 50mL of tetrahydrofuran, 33.8g of triethylamine is added with magnetic stirring, the temperature is reduced to 0 ℃, 35g of trifluoroacetic anhydride is added dropwise, and the temperature is kept for 1h below 0 ℃ after the dropwise addition. Thin layer chromatography analysis of the raw materials reaction completely, adding 0.2L water, ethyl acetate extraction 2 times (2X 300mL), organic phase with potassium carbonate solution washing 2 times, saturated saline water washing once, anhydrous sodium sulfate drying, concentrating to dryness, with 100mL petroleum ether slurry 0.5 h. Filtration, cake leaching with petroleum ether and drying to obtain 17g of 1-methyl- [1,5-a ] -pyridoimidazole-3-nitrile, the 1H-NMR spectrum of which is shown in figure 1. The yield was 97%.
Example 2
S1, synthesis of 2-pyridine ethyl ketoxime:
dissolving 500g of 2-pyridinylethanone in 2L of ethanol and 1L of water in a 5L four-neck flask, adding 306g of potassium bicarbonate under mechanical stirring, cooling to below 0 ℃ by using a low-temperature circulating cooling pump, slowly adding 373g of hydroxylamine hydrochloride in batches, and naturally heating to room temperature for 3 hours after dropwise addition. The raw materials are completely reacted by thin-layer chromatography analysis, the raw materials are filtered, filter cakes are washed by water, filtrate is concentrated by ethanol, 1L of water is added, ethyl acetate is extracted for 2 times (2 multiplied by 1L), anhydrous sodium sulfate is dried, the concentration and the drying are carried out, 558g of 2-pyridine ethyl ketoxime solid is obtained in total, and the yield is 99%.
Synthesis of S2, 2' -pyridin-1-ethylamine:
406g of 2-pyridinylethanone oxime was dissolved in 3L of methanol in a 5L four-necked flask, 471g of ammonium chloride was added with mechanical stirring, and 573.5g of zinc powder was slowly added in portions at room temperature. After the addition of 50 ℃ the reaction was carried out for 12 h. Thin layer chromatography analysis of the raw materials reaction completely, filtering, leaching the filter cake with methanol, concentrating the filtrate to dryness, adding 2L of water, adjusting the pH value to 13-14 with sodium hydroxide, adding 2L of dichloromethane, filtering with silica gel pad, leaching the filter cake with dichloromethane, separating, extracting the aqueous phase with dichloromethane for 10 times (10X 1L), drying with anhydrous sodium sulfate, and concentrating to dryness. Vacuum distilling (external temperature 70 deg.C, 30Pa), collecting 40-45 deg.C fraction to obtain 190g of 2' -pyridine-1-ethylamine with yield of 52.9%.
Synthesis of S3, 2- (2 "-pyridyl-1' -ethylamino) -2-carbonyl-ethyl acetate:
100g of 2' -pyridine-1-ethylamine is added into a reaction flask with 3L and dissolved in 1L of dichloromethane, 85 g of pyridine is added under mechanical stirring, the temperature is reduced to-5 ℃, 123g of oxalyl chloride monoethyl ester is slowly dripped, and the temperature is kept for 1h at 0 ℃ after the dripping. Thin layer chromatography analysis of raw materials reaction completely, water 1.5L, liquid separation, dichloromethane phase washing once, saturated saline water washing once, anhydrous sodium sulfate drying, concentration to dry, 2- (2 '-pyridyl-1' -ethylamino) -2-carbonyl-ethyl acetate, directly on the next step.
Synthesis of S4, ethyl 1-methyl- [1,5-a ] -pyridoimidazole-3-carboxylate:
350g of 2- (2 '-pyridyl-1' -ethylamino) -2-carbonyl-ethyl acetate are dissolved in 2L of dichloromethane in a 3L four-necked flask, 382g of triethylamine are added under mechanical stirring, and after the temperature is reduced to below 0 ℃ by using a low-temperature circulating cooling pump, 397g of trifluoroacetic anhydride are slowly added dropwise. After the dripping is finished, the temperature is kept for 1h at 0 ℃. Thin layer chromatography analysis of the raw materials reaction completely, water 2L, liquid separation, dichloromethane phase water washing 2 times, saturated saline water washing once, anhydrous sodium sulfate drying, concentrated to dryness. Dissolving with 1.5L, adding active carbon, refluxing and decolorizing for 0.5h, filtering with silica gel pad, concentrating the filtrate to dryness, pulping with 500mL petroleum ether and 50mL ethyl acetate to obtain 158g 1-methyl- [1,5-a ] -pyridoimidazole-3-ethyl formate with a yield of 49.8%.
S5, synthesis of 1-methyl- [1,5-a ] -pyridoimidazole-3-carboxamide:
50g of 1-methyl- [1,5-a ] -pyridoimidazole-3-carboxylic acid ethyl ester was added to a 1L four-necked flask in 0.5L of aqueous ammonia, and reacted at 30 ℃ overnight. And (3) analyzing the reaction of the raw materials by thin layer chromatography, cooling to room temperature, filtering, washing a filter cake with water, and drying. The filtrate was concentrated to dryness, purified with 1:1 methyl tert-butyl ether: 100mL of isopropyl alcohol was slurried, filtered, and dried to obtain 13.2g in total of 1-methyl- [1,5-a ] -pyridoimidazole-3-carboxamide at a yield of 30.4%.
S6, Synthesis of 1-methyl- [1,5-a ] -pyridoimidazole-3-carbonitrile:
19.5g of 1-methyl- [1,5-a ] -pyridylimidazol-3-carboxamide is added to a 0.25L three-necked flask and dissolved in 50mL of tetrahydrofuran, 33.8g of triethylamine is added with magnetic stirring, the temperature is reduced to 10 ℃, 35g of trifluoroacetic anhydride is added dropwise, and the temperature is kept for 1h below 10 ℃. Thin layer chromatography analysis of the raw materials reaction completely, adding 0.2L water, ethyl acetate extraction 2 times (2X 300mL), organic phase with potassium carbonate solution washing 2 times, saturated saline water washing once, anhydrous sodium sulfate drying, concentrating to dryness, 100mL petroleum ether pulping for 0.5 h. Filtering, eluting the filter cake with petroleum ether, and drying to obtain 15g of 1-methyl- [1,5-a ] -pyridylimidazole-3-carbonitrile with the yield of 85.6%.
Example 3
S1, synthesis of 2-pyridine ethyl ketoxime:
500g of 2-pyridinylethanone is dissolved in 2L of ethanol and 1L of water in a 5L four-neck flask, 306g of sodium bicarbonate is added under mechanical stirring, after the temperature is reduced to below 0 ℃ by using a low-temperature circulating cooling pump, 373g of hydroxylamine hydrochloride is slowly added in batches, and the mixture is naturally heated to room temperature for 3 hours after the dropwise addition. Thin-layer chromatography analysis shows that the raw materials completely react, the raw materials are filtered, filter cakes are washed with water, filtrate is concentrated to complete ethanol, 1L of water is added, ethyl acetate is extracted for 2 times (2X 1L), anhydrous sodium sulfate is dried, the concentration and the drying are carried out, 543g of 2-pyridine ethyl ketoxime solid is obtained in total, and the yield is 96.7%.
Synthesis of S2, 2' -pyridin-1-ethylamine:
406g of 2-pyridinylethanone oxime was dissolved in 3L of methanol in a 5L four-necked flask, 471g of ammonium chloride was added with mechanical stirring, and 573.5g of zinc powder was slowly added in portions at room temperature. After the addition of 30 ℃ the reaction was carried out for 12 h. Thin layer chromatography analysis of the raw materials reaction completely, filtering, leaching the filter cake with methanol, concentrating the filtrate to dryness, adding 2L of water, adjusting the pH value to 13-14 with sodium hydroxide, adding 2L of dichloromethane, filtering with silica gel pad, leaching the filter cake with dichloromethane, separating, extracting the aqueous phase with dichloromethane for 10 times (10X 1L), drying with anhydrous sodium sulfate, and concentrating to dryness. Vacuum distilling (external temperature 70 deg.C, 30Pa), collecting 40-45 deg.C fraction to obtain 208g of 2' -pyridine-1-ethylamine with yield of 58%.
Synthesis of S3, 2- (2 "-pyridyl-1' -ethylamino) -2-carbonyl-ethyl acetate:
adding 100g of 2' -pyridine-1-ethylamine into a 3L reaction flask, dissolving in 1L of dichloromethane, adding 108 g of triethanolamine under mechanical stirring, cooling to-5 ℃, slowly dropwise adding 123g of oxalyl chloride monoethyl ester, and keeping the temperature for 1h at 0 ℃ after dropwise adding. Thin layer chromatography analysis of the raw material reaction completely, water 1.5L, liquid separation, dichloromethane phase washing once, saturated saline washing once, anhydrous sodium sulfate drying, concentration to dryness, 2- (2 '-pyridyl-1' -ethylamino) -2-carbonyl-ethyl acetate, direct implementation of the next step, yield according to 100%.
Synthesis of S4, ethyl 1-methyl- [1,5-a ] -pyridoimidazole-3-carboxylate:
350g of 2- (2 '-pyridyl-1' -ethylamino) -2-carbonyl-ethyl acetate are dissolved in 2L of dichloromethane in a 3L four-necked flask, 563g of triethanolamine are added with mechanical stirring, and after the temperature is reduced to below 0 ℃ by using a low-temperature circulating cooling pump, 397g of trifluoroacetic anhydride are slowly added dropwise. After the dripping is finished, the temperature is kept for 1h at 0 ℃. Thin layer chromatography analysis of the raw materials reaction completely, adding water 2L, separating, washing the dichloromethane phase with water for 2 times, washing with saturated saline once, drying with anhydrous sodium sulfate, and concentrating to dryness. Dissolving with 1.5L, adding active carbon, refluxing and decolorizing for 0.5h, filtering with silica gel pad, concentrating the filtrate to dryness, pulping with 500mL petroleum ether and 50mL ethyl acetate to obtain 149g 1-methyl- [1,5-a ] -pyridoimidazole-3-ethyl formate with a yield of 46.4%.
S5, synthesis of 1-methyl- [1,5-a ] -pyridoimidazole-3-carboxamide:
50g of 1-methyl- [1,5-a ] -pyridoimidazole-3-carboxylic acid ethyl ester was added to a 1L four-necked flask in 0.5L of aqueous ammonia, and reacted at 50 ℃ overnight. And (3) analyzing the reaction of the raw materials by thin layer chromatography, cooling to room temperature, filtering, washing a filter cake with water, and drying. The filtrate was concentrated to dryness, purified with 1:1 methyl tert-butyl ether: 100mL of isopropyl alcohol was slurried, filtered, and dried to obtain a total of 17g of 1-methyl- [1,5-a ] -pyridoimidazole-3-carboxamide with a yield of 38.5%.
S6, Synthesis of 1-methyl- [1,5-a ] -pyridoimidazole-3-carbonitrile:
19.5g of 1-methyl- [1,5-a ] -pyridylimidazole-3-carboxamide is added to a 0.25L three-necked flask and dissolved in 50mL of tetrahydrofuran, 33.8g of triethylamine is added with magnetic stirring, the temperature is reduced to-10 ℃, 35g of trifluoroacetic anhydride is added dropwise, and the temperature is kept for 1h below 10 ℃. Thin layer chromatography analysis of the raw materials reaction completely, adding 0.2L water, ethyl acetate extraction 2 times (2X 300mL), organic phase with potassium carbonate solution washing 2 times, saturated saline water washing once, anhydrous sodium sulfate drying, concentrating to dryness, 100mL petroleum ether pulping for 0.5 h. Filtering, eluting the filter cake with petroleum ether, and drying to obtain 17.5g of 1-methyl- [1,5-a ] -pyridylimidazole-3-carbonitrile with the yield of 99%.
Claims (9)
1. A compound I, namely: 1-methyl- [1,5-a ] -pyridine imidazole-3-nitrile, which is characterized in that the molecular structure is shown as formula 1.
2. The method for synthesizing the compound I as claimed in claim 1, wherein the compound I is synthesized by taking 2-pyridine ethanone as a raw material through a six-step reaction, and the synthetic route is shown as formula 2:
3. the method of synthesizing compound i according to claim 2, comprising the following synthetic steps:
s1, adding 2-pyridine ethyl ketone into ethanol and water, adding inorganic base, controlling the reaction system to be 0 ℃, adding hydroxylamine hydrochloride, and reacting for 3 hours to prepare 2-pyridine ethyl ketone oxime;
s2, adding the 2-pyridine ethanone oxime obtained in the step S1 into methanol, then adding ammonium chloride, then adding zinc powder in batches, controlling the reaction temperature, reacting for 12 hours, and synthesizing 2' -pyridine-1-ethylamine;
s3, adding the 2 ' -pyridine-1-ethylamine obtained in the step S2 into dichloromethane, then adding organic base, controlling the reaction temperature, adding oxalyl chloride monoethyl ester, and reacting for 1h to obtain 2- (2 ' -pyridyl-1 ' -ethylamino) -2-carbonyl-ethyl acetate;
s4, adding the 2- (2 '-pyridyl-1' -ethylamino) -2-carbonyl-ethyl acetate obtained in the step S3 into dichloromethane, adding organic base, controlling the temperature to be 0 ℃, then adding trifluoroacetic anhydride, and reacting for 1h to obtain 1-methyl- [1,5-a ] -pyridoimidazole-3-ethyl formate;
s5, adding the 1-methyl- [1,5-a ] -pyridoimidazole-3-ethyl formate obtained in the step S4 into ammonia water, and controlling the reaction temperature to obtain 1-methyl- [1,5-a ] -pyridoimidazole-3-formamide;
s6, adding the 1-methyl- [1,5-a ] -pyridylimidazole-3-formamide obtained in the step S5 into tetrahydrofuran, then adding an organic base, controlling the reaction temperature, then adding trifluoroacetic anhydride, stirring for 1h after the addition is finished, and reacting to obtain 1-methyl- [1,5-a ] -pyridylimidazole-3-carbonitrile.
4. The process according to claim 3 for the synthesis of compound i, characterized in that: the inorganic base in the step S1 is one of sodium carbonate, potassium carbonate, sodium bicarbonate and potassium bicarbonate.
5. The process according to claim 3 for the synthesis of compound i, characterized in that: the reaction temperature of the step S2 is 10-50 ℃.
6. The process according to claim 3 for the synthesis of compound i, characterized in that: the reaction temperature of the step S3 is-20-10 ℃, and the organic base is one of triethylamine, pyridine and triethanolamine.
7. The process according to claim 3 for the synthesis of compound i, characterized in that: the organic base in the step S4 is one of triethylamine, pyridine and triethanolamine.
8. The process according to claim 3 for the synthesis of compound i, characterized in that: the reaction temperature of the step S5 is 30-100 ℃.
9. The process according to claim 3 for the synthesis of compound i, characterized in that: in the step S6, the reaction temperature is-10-10 ℃, and the organic base is one of triethylamine, pyridine and triethanolamine.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| 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 |
| CN111848545A (en) * | 2020-08-03 | 2020-10-30 | 南通大学 | 1- (2- (4-methoxyphenyl) thiazole-4-yl) ethylamine and synthetic method thereof |
| CN111848546A (en) * | 2020-08-03 | 2020-10-30 | 南通大学 | 2- (aminomethyl) thiazole-5-nitrile and synthesis method thereof |
| CN111848546B (en) * | 2020-08-03 | 2022-08-12 | 南通大学 | 2- (aminomethyl) thiazole-5-nitrile and synthesis method thereof |
| CN111848545B (en) * | 2020-08-03 | 2022-08-12 | 南通大学 | 1- (2- (4-methoxyphenyl) thiazole-4-yl) ethylamine and synthetic method thereof |
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