CN113788780A - Synthesis method of N-acetyl-5-methoxytryptamine - Google Patents
Synthesis method of N-acetyl-5-methoxytryptamine Download PDFInfo
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- CN113788780A CN113788780A CN202111202302.3A CN202111202302A CN113788780A CN 113788780 A CN113788780 A CN 113788780A CN 202111202302 A CN202111202302 A CN 202111202302A CN 113788780 A CN113788780 A CN 113788780A
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
- C07D209/16—Tryptamines
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- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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Abstract
The invention provides a synthesis method of N-acetyl-5-methoxytryptamine, which comprises the following steps: under the nitrogen atmosphere, mixing a 5-hydroxytryptamine hydrochloride solution and an additive, then dropwise adding acetyl chloride, neutralizing until the pH value is 8.5-9 after the reaction is finished, and washing with water until the pH value is neutral to obtain N-acetyl-5-hydroxytryptamine; and (2) dropwise adding dimethyl sulfate into the N-acetyl-5-hydroxytryptamine under the condition that the pH value is 11-11.5, and performing post-treatment after the reaction is finished to obtain the N-acetyl-5-methoxytryptamine. The method takes 5-hydroxytryptamine hydrochloride as a raw material, prepares the finished product melatonin through acetylation and methylation reactions, avoids waste caused by purifying products step by step, has the characteristics of short synthetic route, short synthetic period, few raw material types and the like, and can obtain the product with high yield and purity meeting market requirements. The production method of the melatonin provided by the invention saves the cost and is easy for industrial production.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical chemistry synthesis, and particularly relates to a synthesis method of N-acetyl-5-methoxytryptamine.
Background
N-acetyl-5-methoxytryptamine belongs to beta-indolylalanine derivatives, is an amine hormone generated by dark stimulation of mammalian pineal bodies, and is an important antioxidant in organisms. Can improve the sleep quality of animal body. As the animals age, the secretion of N-acetyl-5-methoxytryptamine gradually decreases, thereby affecting the quality of sleep of the animals. N-acetyl-5-methoxytryptamine is originally discovered in the bodies of the pine cones of the cows and is considered as an important neurohormone, later researches find that the N-acetyl-5-methoxytryptamine is distributed in each organ of the human body and plays different important functions, and more researches show that the N-acetyl-5-methoxytryptamine not only can treat insomnia, but also has various physiological functions of oxidation resistance, aging resistance, immunity regulation, cancer resistance and the like.
Based on various effects of melatonin, the use value and application of melatonin are widely concerned. However, the preparation of melatonin has different processes, and basically takes a compound containing an indole ring as a substrate to finally obtain the melatonin through multi-step chemical synthesis. Patent 200910033396.9 provides a method for synthesizing melatonin, which mainly uses cheap 4-aminobutyric acid as raw material, and prepares the melatonin through the steps of esterification of carboxyl, acylation of amino, reduction of ester, oxidation of hydroxyl, fischer indole cyclization and the like. In addition, in patent CN110229092A, 5-methoxyindole is used as an initiator, and is subjected to carbonyl chloride acylation, dechlorination amination, reduction by lithium aluminum hydride to 5-methoxytryptamine and final acetylation, the total of 4 steps of reaction are counted to prepare the melatonin, the synthesis of the 5-methoxytryptamine involves complex procedures and harsh reaction conditions, the used raw materials and reagents have great harm to the environment, the synthesis process for finally synthesizing the melatonin has many steps, and toxic phosgene and flammable and explosive substance lithium aluminum hydride are used, so that the industrial production operation is not facilitated.
Disclosure of Invention
In view of the above, the present invention aims to provide a method for synthesizing N-acetyl-5-methoxytryptamine, which is simple and has high product yield and purity.
The invention provides a synthesis method of N-acetyl-5-methoxytryptamine, which comprises the following steps:
under the nitrogen atmosphere, mixing a 5-hydroxytryptamine hydrochloride solution and an additive, then dropwise adding acetyl chloride, neutralizing until the pH value is 8.5-9 after the reaction is finished, and washing with water until the pH value is neutral to obtain N-acetyl-5-hydroxytryptamine;
and (2) dropwise adding dimethyl sulfate into the N-acetyl-5-hydroxytryptamine under the condition that the pH value is 11-11.5, and performing post-treatment after the reaction is finished to obtain the N-acetyl-5-methoxytryptamine.
In the invention, the mixing temperature of the 5-hydroxytryptamine hydrochloride solution and the additive is 0-25 ℃;
the molar ratio of the additive to the 5-hydroxytryptamine hydrochloride is 2.5-3.5: 1.
In the invention, the time for dripping acetyl chloride is 0.5-1 h, and the temperature for dripping acetyl chloride is 15-25 ℃;
and continuing to react for 1-2 h after the acetyl chloride is dripped.
In the invention, the molar ratio of acetyl chloride to 5-hydroxytryptamine hydrochloride is 2.2-2.5: 1.
In the invention, the molar ratio of the dimethyl sulfate to the 5-hydroxytryptamine hydrochloride is 1.6-2.0: 1;
the temperature of the dimethyl sulfate is 20-30 ℃, and the time of the dimethyl sulfate is 0.5-1 h.
In the invention, the dimethyl sulfate is dripped and then the reaction is continued for 1-2 h.
In the present invention, the post-treatment after the completion of the reaction comprises:
and after the reaction is finished, neutralizing the reaction product until the pH value is 7-7.5, washing with a mixture of water and dichloromethane, standing for layering to obtain a dichloromethane phase, and heating to remove dichloromethane to obtain the N-acetyl-5-methoxytryptamine.
In the invention, the 5-hydroxytryptamine hydrochloride solution is prepared according to the following method:
adding 5-hydroxytryptamine hydrochloride into dry anhydrous dichloromethane under nitrogen, and stirring to obtain 5-hydroxytryptamine hydrochloride solution;
the mass ratio of the 5-hydroxytryptamine hydrochloride to the dichloromethane is 5-9: 1.
The invention provides a synthesis method of N-acetyl-5-methoxytryptamine, which comprises the following steps: under the nitrogen atmosphere, mixing a 5-hydroxytryptamine hydrochloride solution and an additive, then dropwise adding acetyl chloride, neutralizing until the pH value is 8.5-9 after the reaction is finished, and washing with water until the pH value is neutral to obtain N-acetyl-5-hydroxytryptamine; and (2) dropwise adding dimethyl sulfate into the N-acetyl-5-hydroxytryptamine under the condition that the pH value is 11-11.5, and performing post-treatment after the reaction is finished to obtain the N-acetyl-5-methoxytryptamine. The method takes 5-hydroxytryptamine hydrochloride as a raw material, prepares the finished product melatonin through acetylation and methylation reactions, avoids waste caused by purifying products step by step, has the characteristics of short synthetic route, short synthetic period, few raw material types and the like, and can obtain the product with high yield and purity meeting market requirements. The production method of the melatonin provided by the invention saves the cost and is easy for industrial production.
Drawings
FIG. 1 is a chromatogram of N-acetyl-5-hydroxy tryptophan prepared in example 1 of the present invention;
fig. 2 is a nuclear magnetic resonance hydrogen spectrum of melatonin prepared in example 1 of the present invention;
fig. 3 is a chromatogram of melatonin produced in example 1 of the present invention.
Detailed Description
In order to further illustrate the present invention, the synthesis method of N-acetyl-5-methoxytryptamine provided by the present invention is described in detail below with reference to the following examples, which should not be construed as limiting the scope of the present invention.
Example 1
Adding 120ml of anhydrous dichloromethane into a 2L three-neck flask under the protection of nitrogen flow, adding 21.25g of 5-hydroxytryptamine hydrochloride under stirring, placing the mixture in a circulating cold water bath, controlling the temperature to be 0-10 ℃, starting to add 30.3g of triethylamine, dropwise adding 17.2g of acetyl chloride, dropwise adding for 0.5 hour, controlling the temperature to be 15-20 ℃, stirring for 1.5 hours after the dropwise adding is finished, sampling, controlling the temperature to be less than 0.2% of 5-hydroxytryptamine hydrochloride, adding 20% of sodium hydroxide solution to neutralize until the pH value of the system is 8.5-9, and washing the solution with water to be neutral to obtain the N-acetyl-5-hydroxytryptamine solution.
TABLE 1 chromatographic data analysis of N-acetyl-5-hydroxytryptamine
Adding a sodium hydroxide solution with the mass fraction of 20%, controlling the temperature to be 20-25 ℃, controlling the pH to be 11-11.5, beginning to drip 20.2g of dimethyl sulfate, dripping for 0.5h, controlling the temperature to be 20-25 ℃, stirring for 1.5h after finishing dripping, sampling, controlling the concentration, adding 50% of sulfuric acid to neutralize until the pH is 7.5, adding 120ml of water to wash a dichloromethane phase for three times, then heating to remove a dichloromethane solvent, controlling the water bath temperature to be 40-50 ℃, vacuum-0.09-0.095, desolventizing an organic layer to obtain 22.6g of melatonin, wherein the molar yield is 96.98%, and the HPLC purity is 99.58%.
Fig. 3 is a chromatogram of melatonin prepared in example 1 of the present invention;
table 2 chromatogram of melatonin prepared in example 1
Example 2
Adding 180ml of anhydrous dichloromethane into a 2L three-neck flask under the protection of nitrogen flow, adding 21.25g of 5-hydroxytryptamine hydrochloride under stirring, placing the mixture in a circulating cold water bath, controlling the temperature to be 0-10 ℃, starting to add 30.3g of triethylamine, dropwise adding 19.6g of acetyl chloride, dropwise adding for 1h, controlling the temperature to be 15-20 ℃, stirring for 2h after the dropwise adding is finished, sampling, controlling the pH value to be 8.5-9, adding 20% of sodium hydroxide solution to neutralize the pH value of the system, and washing the solution with water to be neutral to obtain the N-acetyl-5-hydroxytryptamine solution.
Adding a sodium hydroxide solution with the mass fraction of 20%, controlling the temperature to be 25-30 ℃, controlling the pH to be 11-11.5, beginning to drip 25.2g of dimethyl sulfate, dripping for 1h, controlling the temperature to be 25-30 ℃, stirring for 2h after finishing dripping, controlling in sampling, adding 50% sulfuric acid to neutralize until the pH is 7.5, adding 180ml of water to wash a dichloromethane phase for three times each time, then heating to remove a dichloromethane solvent, controlling the temperature of a water bath to be 40-50 ℃, and carrying out vacuum-0.09-0.095 Mpa, desolventizing an organic layer to obtain 22.8g of melatonin, wherein the molar yield is 98.2%, and the HPLC purity is 99.54%.
Example 3
Adding 150ml of anhydrous dichloromethane into a 2L three-neck flask under the protection of nitrogen flow, adding 21.25g of 5-hydroxytryptamine hydrochloride under stirring, placing the mixture in a circulating cold water bath, controlling the temperature to be 0-10 ℃, starting to add 30.3g of triethylamine, dropwise adding 18.1g of acetyl chloride, dropwise adding for 1h, controlling the temperature to be 20-25 ℃, stirring for 2h after the dropwise adding is finished, sampling, controlling the temperature to be middle, adding less than 0.2% of 5-hydroxytryptamine hydrochloride, adding 20% of sodium hydroxide solution to neutralize until the pH value of the system is 8.5-9, and washing with water to be neutral to obtain the N-acetyl-5-hydroxytryptamine solution.
Adding 20% sodium hydroxide solution by mass, controlling the temperature to be 25-30 ℃, controlling the pH to be 11-11.5, beginning to drip 23.2g of dimethyl sulfate, dripping for 1h, controlling the temperature to be 25-30 ℃, stirring for 1.5h after finishing dripping, controlling in sampling, adding 50% sulfuric acid to neutralize until the pH is 7.5, adding 150ml of water to wash dichloromethane for three times, then heating to remove dichloromethane solvent, controlling the water bath temperature to be 40-50 ℃, and vacuum-0.09-0.095 Mpa, desolventizing an organic layer to obtain 22.6g of melatonin, wherein the molar yield is 97.4%, and the HPLC purity is 99.51%.
From the above examples, the present invention provides a method for synthesizing N-acetyl-5-methoxytryptamine, comprising the following steps: under the nitrogen atmosphere, mixing a 5-hydroxytryptamine hydrochloride solution and an additive, then dropwise adding acetyl chloride, neutralizing until the pH value is 8.5-9 after the reaction is finished, and washing with water until the pH value is neutral to obtain N-acetyl-5-hydroxytryptamine; and (2) dropwise adding dimethyl sulfate into the N-acetyl-5-hydroxytryptamine under the condition that the pH value is 11-11.5, and performing post-treatment after the reaction is finished to obtain the N-acetyl-5-methoxytryptamine. The method takes 5-hydroxytryptamine hydrochloride as a raw material, prepares the finished product melatonin through acetylation and methylation reactions, avoids waste caused by purifying products step by step, has the characteristics of short synthetic route, short synthetic period, few raw material types and the like, and can obtain the product with high yield and purity meeting market requirements. The production method of the melatonin provided by the invention saves the cost and is easy for industrial production. The experimental results show that: the HPLC purity of the melatonin prepared by the method is more than 99.5%, and the molar yield is 97-98%.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (8)
1. A method for synthesizing N-acetyl-5-methoxytryptamine comprises the following steps:
under the nitrogen atmosphere, mixing a 5-hydroxytryptamine hydrochloride solution and an additive, then dropwise adding acetyl chloride, neutralizing until the pH value is 8.5-9 after the reaction is finished, and washing with water until the pH value is neutral to obtain N-acetyl-5-hydroxytryptamine;
and (2) dropwise adding dimethyl sulfate into the N-acetyl-5-hydroxytryptamine under the condition that the pH value is 11-11.5, and performing post-treatment after the reaction is finished to obtain the N-acetyl-5-methoxytryptamine.
2. The synthesis method of claim 1, wherein the temperature for mixing the 5-hydroxytryptamine hydrochloride solution and the additive is 0-25 ℃;
the molar ratio of the additive to the 5-hydroxytryptamine hydrochloride is 2.5-3.5: 1.
3. The synthesis method according to claim 1, wherein the time for dripping acetyl chloride is 0.5-1 h, and the temperature for dripping acetyl chloride is 15-25 ℃;
and continuing to react for 1-2 h after the acetyl chloride is dripped.
4. The synthesis method according to claim 1, wherein the molar ratio of acetyl chloride to 5-hydroxytryptamine hydrochloride is 2.2-2.5: 1.
5. The synthesis method according to claim 1, wherein the molar ratio of the dimethyl sulfate to the 5-hydroxytryptamine hydrochloride is 1.6-2.0: 1;
the temperature of the dimethyl sulfate is 20-30 ℃, and the time of the dimethyl sulfate is 0.5-1 h.
6. The synthesis method of claim 1, wherein the reaction is continued for 1-2 hours after the dimethyl sulfate is added dropwise.
7. The synthesis method according to claim 1, wherein the post-treatment after the reaction comprises:
and after the reaction is finished, neutralizing the reaction product until the pH value is 7-7.5, washing with a mixture of water and dichloromethane, standing for layering to obtain a dichloromethane phase, and heating to remove dichloromethane to obtain the N-acetyl-5-methoxytryptamine.
8. The method of claim 1, wherein the 5-hydroxytryptamine hydrochloride solution is prepared by the following method:
adding 5-hydroxytryptamine hydrochloride into dry anhydrous dichloromethane under nitrogen, and stirring to obtain 5-hydroxytryptamine hydrochloride solution;
the mass ratio of the 5-hydroxytryptamine hydrochloride to the dichloromethane is 5-9: 1.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116375627A (en) * | 2023-03-30 | 2023-07-04 | 南京神奇科技开发有限公司 | Preparation method of melatonin |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4506080A (en) * | 1983-07-01 | 1985-03-19 | Nestec S. A. | Preparation of serotonine and derivatives |
| WO2011047156A1 (en) * | 2009-10-15 | 2011-04-21 | Hercules Technology Management Co V, Inc. | Sepiapterin reductase inhibitors for the treatment of pain |
| CN102329263A (en) * | 2011-10-17 | 2012-01-25 | 上海化学试剂研究所 | Preparation method of N-acetyl-5-methoxytryptamine |
| CN113214133A (en) * | 2021-05-08 | 2021-08-06 | 保定保利瑞合生物科技有限公司 | Synthesis method of melatonin |
| CN113387868A (en) * | 2021-07-13 | 2021-09-14 | 河北维达康生物科技有限公司 | Synthesis process of melatonin intermediate N-acetyl serotonin |
| CN113402437A (en) * | 2021-06-29 | 2021-09-17 | 河北维达康生物科技有限公司 | Novel method for synthesizing dietary supplement melatonin |
-
2021
- 2021-10-15 CN CN202111202302.3A patent/CN113788780B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4506080A (en) * | 1983-07-01 | 1985-03-19 | Nestec S. A. | Preparation of serotonine and derivatives |
| WO2011047156A1 (en) * | 2009-10-15 | 2011-04-21 | Hercules Technology Management Co V, Inc. | Sepiapterin reductase inhibitors for the treatment of pain |
| CN102329263A (en) * | 2011-10-17 | 2012-01-25 | 上海化学试剂研究所 | Preparation method of N-acetyl-5-methoxytryptamine |
| CN113214133A (en) * | 2021-05-08 | 2021-08-06 | 保定保利瑞合生物科技有限公司 | Synthesis method of melatonin |
| CN113402437A (en) * | 2021-06-29 | 2021-09-17 | 河北维达康生物科技有限公司 | Novel method for synthesizing dietary supplement melatonin |
| CN113387868A (en) * | 2021-07-13 | 2021-09-14 | 河北维达康生物科技有限公司 | Synthesis process of melatonin intermediate N-acetyl serotonin |
Non-Patent Citations (2)
| Title |
|---|
| DENISE WOLRAB ET AL: "Quantification of the neurotransmitters melatonin and N-acetyl-serotonin in human serum by supercritical fluid chromatography coupled with tandem mass spectrometry", 《ANALYTICA CHIMICA ACTA》 * |
| 杨建武等: "褪黑激素的合成与表征", 《化学研究》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116375627A (en) * | 2023-03-30 | 2023-07-04 | 南京神奇科技开发有限公司 | Preparation method of melatonin |
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Inventor after: Zhao Yunxian Inventor after: Yang Zhibin Inventor after: Cui Jinwang Inventor before: Zhao Yunxian Inventor before: Tian Junbo Inventor before: Li Qian Inventor before: Yang Zhibin Inventor before: Cui Jinwang Inventor before: Zhao Zejia Inventor before: Xing Ruijing |
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