CN113788780B - Synthesis method of N-acetyl-5-methoxy tryptamine - Google Patents
Synthesis method of N-acetyl-5-methoxy tryptamine Download PDFInfo
- Publication number
- CN113788780B CN113788780B CN202111202302.3A CN202111202302A CN113788780B CN 113788780 B CN113788780 B CN 113788780B CN 202111202302 A CN202111202302 A CN 202111202302A CN 113788780 B CN113788780 B CN 113788780B
- Authority
- CN
- China
- Prior art keywords
- controlling
- acetyl
- hydroxytryptamine
- temperature
- dropwise adding
- 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.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a synthesis method of N-acetyl-5-methoxy tryptamine, which comprises the following steps: under the nitrogen atmosphere, mixing 5-hydroxytryptamine hydrochloride solution with 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 dropwise adding dimethyl sulfate into the N-acetyl-5-hydroxytryptamine under the condition that the pH value is 11-11.5, and performing aftertreatment after the reaction is finished to obtain the N-acetyl-5-methoxy tryptamine. The invention takes 5-hydroxytryptamine hydrochloride as raw material, and prepares the finished melatonin through acetylation and methylation reaction, thereby avoiding waste caused by purifying and purifying products step by step, having the characteristics of short synthetic route, short synthetic period, few raw material types and the like, and the obtained product has high yield and purity which can meet market demands. The production method of melatonin provided by the invention saves 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-methoxy tryptamine.
Background
N-acetyl-5-methoxy tryptamine belongs to beta-indolylalanine derivatives, is an amine hormone generated by the pine cone of mammals after being stimulated by darkness, and is an important antioxidant in organisms. Can improve sleep quality of animal body. The secretion amount of N-acetyl-5-methoxy tryptamine gradually decreases with the age of the animal, thereby affecting the sleep quality of the animal. N-acetyl-5-methoxy tryptamine is firstly found in Niu Songguo body and is considered as an important neurohormone, after-research discovers that N-acetyl-5-methoxy tryptamine is distributed in various organs of human body and plays different important functions, and more researches show that N-acetyl-5-methoxy tryptamine not only can treat insomnia, but also has various physiological functions of resisting oxidation, resisting aging, regulating immunity, resisting cancer and the like.
Based on the various actions of melatonin, the use value and application of melatonin are of great interest. However, the preparation of melatonin has different processes, basically takes indole ring-containing compounds as substrates, and finally obtains the melatonin through multi-step chemical synthesis. The patent 200910033396.9 provides a synthesis method of melatonin, which mainly uses cheap 4-aminobutyric acid as a raw material, and comprises the steps of esterification of carboxyl, acylation of amino, reduction of ester, oxidation of hydroxyl, and fischer indole cyclization. In addition, the 5-methoxy indole is adopted as a starting material in the CN110229092A, and is subjected to carbonyl chloride acylation, dechlorination and amination, then lithium aluminum hydride is used for reduction to obtain 5-methoxy tryptamine, finally, 4 steps of reactions are performed in total in acetylation to prepare the melatonin, the synthesis of the 5-methoxy tryptamine involves complex procedures, the reaction conditions are harsh, the used raw materials and reagents have great harm to the environment, the synthesis process steps for synthesizing the melatonin are more, and the extremely toxic substances phosgene carbonyl chloride and flammable and explosive substances lithium aluminum hydride are used, so that the industrial production operation is not facilitated.
Disclosure of Invention
In view of the above, the invention aims to provide a synthesis method of N-acetyl-5-methoxy tryptamine, which is simple and has higher product yield and purity.
The invention provides a synthesis method of N-acetyl-5-methoxy tryptamine, which comprises the following steps:
under the nitrogen atmosphere, mixing 5-hydroxytryptamine hydrochloride solution with 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 dropwise adding dimethyl sulfate into the N-acetyl-5-hydroxytryptamine under the condition that the pH value is 11-11.5, and performing aftertreatment after the reaction is finished to obtain the N-acetyl-5-methoxy tryptamine.
In the invention, the temperature for mixing the 5-hydroxytryptamine hydrochloride solution and the additive is 0-25 ℃;
the mol 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 after the acetyl chloride is added dropwise, continuing to react for 1-2 h.
In the invention, the mol 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, dimethyl sulfate is added dropwise and then the reaction is continued for 1 to 2 hours.
In the present invention, the post-treatment after the completion of the reaction includes:
and after the reaction is finished, neutralizing the reaction product to a pH value of 7-7.5, washing by adopting a mixture of water and dichloromethane, standing for layering to obtain a dichloromethane phase, and heating to remove the dichloromethane to obtain the N-acetyl-5-methoxy tryptamine.
In the present invention, the 5-hydroxytryptamine hydrochloride solution is prepared according to the following method:
under nitrogen, adding 5-hydroxytryptamine hydrochloride into dry anhydrous dichloromethane, 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-methoxy tryptamine, which comprises the following steps: under the nitrogen atmosphere, mixing 5-hydroxytryptamine hydrochloride solution with 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 dropwise adding dimethyl sulfate into the N-acetyl-5-hydroxytryptamine under the condition that the pH value is 11-11.5, and performing aftertreatment after the reaction is finished to obtain the N-acetyl-5-methoxy tryptamine. The invention takes 5-hydroxytryptamine hydrochloride as raw material, and prepares the finished melatonin through acetylation and methylation reaction, thereby avoiding waste caused by purifying and purifying products step by step, having the characteristics of short synthetic route, short synthetic period, few raw material types and the like, and the obtained product has high yield and purity which can meet market demands. The production method of melatonin provided by the invention saves cost and is easy for industrial production.
Drawings
FIG. 1 is a chromatogram of N-acetyl-5-hydroxytryptamine 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 prepared in example 1 of the present invention.
Detailed Description
In order to further illustrate the present invention, a method for synthesizing N-acetyl-5-methoxy tryptamine according to the present invention is described in detail below with reference to examples, but they should not be construed as limiting the scope of the present invention.
Example 1
120ml of anhydrous dichloromethane is added into a 2L three-neck flask under the protection of nitrogen flow, 21.25g of 5-hydroxytryptamine hydrochloride is added under stirring, the mixture is placed into a circulating cold water bath, the temperature is controlled to be 0-10 ℃, 30.3g of triethylamine is added, 17.2g of acetyl chloride is added dropwise, the temperature is controlled to be 15-20 ℃ for 0.5 hour, stirring is carried out for 1.5 hours after the dropwise addition, sampling is carried out, the control is carried out, the residual content of 5-hydroxytryptamine hydrochloride is less than 0.2%, 20% sodium hydroxide solution is added for neutralization until the pH value of the system is 8.5-9, and then the mixture is washed with water until the mixture is neutral, thus obtaining the N-acetyl-5-hydroxytryptamine solution.
TABLE 1 chromatographic data analysis of N-acetyl-5-hydroxytryptamine
Adding 20% sodium hydroxide solution by mass percent into the mixture, controlling the temperature to be 20-25 ℃, controlling the pH to be 11-11.5, beginning to drop 20.2g of dimethyl sulfate, dropwise adding 0.5h, controlling the temperature to be 20-25 ℃, stirring for 1.5h after the dropwise adding is finished, sampling, centering, controlling the N-acetyl-5-hydroxytryptamine to be less than 0.2%, adding 50% sulfuric acid to neutralize to pH=7.5, adding 120ml of water each time to wash dichloromethane phase three times, then heating to remove dichloromethane solvent, heating in a water bath at 40-50 ℃, vacuum-0.09-0.095 Mpa, obtaining 22.6g of melatonin by organic layer desolventizing, and obtaining 96.98% of melatonin by mole yield and 99.58% of HPLC purity.
FIG. 3 is a chromatogram of melatonin prepared in example 1 of the present invention;
table 2 chromatograms of melatonin prepared in example 1
Example 2
180ml of anhydrous dichloromethane is added into a 2L three-neck flask under the protection of nitrogen flow, 21.25g of 5-hydroxytryptamine hydrochloride is added under stirring, the mixture is placed into a circulating cold water bath tank for temperature control, the temperature is controlled to be 0-10 ℃, 30.3g of triethylamine is added, 19.6g of acetyl chloride is added dropwise, the temperature is controlled to be 15-20 ℃, stirring is carried out for 2 hours after the dropwise is finished, sampling is controlled, the 5-hydroxytryptamine hydrochloride is remained to be less than 0.2%, a 20% sodium hydroxide solution is added for neutralization until the pH value of the system is 8.5-9, and then the mixture is washed with water until the mixture is neutral, thus obtaining N-acetyl-5-hydroxytryptamine solution.
Adding 20% sodium hydroxide solution by mass percent into the mixture, controlling the temperature to be 25-30 ℃, controlling the pH to be 11-11.5, beginning to drop 25.2g of dimethyl sulfate, dropwise adding for 1h, controlling the temperature to be 25-30 ℃, stirring for 2h after the dropwise adding is finished, sampling and centrally controlling, wherein the residual content of N-acetyl-5-hydroxytryptamine is less than 0.2%, adding 50% sulfuric acid to neutralize to pH=7.5, adding 180ml of water for washing dichloromethane phase three times each time, then heating to remove dichloromethane solvent, heating to 40-50 ℃, vacuum-0.09-0.095 Mpa, desolventizing an organic layer to obtain 22.8g of melatonin, and obtaining the product with 98.2% molar yield and 99.54% of HPLC purity.
Example 3
150ml of anhydrous dichloromethane is added into a 2L three-neck flask under the protection of nitrogen flow, 21.25g of 5-hydroxytryptamine hydrochloride is added under stirring, the mixture is placed into a circulating cold water bath for temperature control, the temperature is controlled to be 0-10 ℃, 30.3g of triethylamine is added, 18.1g of acetyl chloride is added dropwise, the temperature is controlled to be 20-25 ℃, stirring is carried out for 2 hours after the dropwise is finished, sampling is controlled, the 5-hydroxytryptamine hydrochloride is remained to be less than 0.2%, a 20% sodium hydroxide solution is added for neutralization until the pH value of the system is 8.5-9, and then the mixture is washed with water until the mixture is neutral, thus obtaining the N-acetyl-5-hydroxytryptamine solution.
Adding 20% sodium hydroxide solution by mass percent into the mixture, controlling the temperature to be 25-30 ℃, controlling the pH to be 11-11.5, beginning to drop 23.2g of dimethyl sulfate, dropwise adding for 1h, controlling the temperature to be 25-30 ℃, stirring for 1.5h after the completion of dropwise adding, sampling, controlling the concentration, adding 50% sulfuric acid to neutralize to pH=7.5, adding 150ml of water for washing dichloromethane phase three times each time, then heating to remove dichloromethane solvent, heating to 40-50 ℃ in a water bath, vacuum-0.09-0.095 Mpa, obtaining 22.6g of melatonin by organic layer desolventizing, and obtaining 97.4% molar yield and 99.51% of HPLC purity.
From the above examples, the present invention provides a method for synthesizing N-acetyl-5-methoxy tryptamine, comprising the following steps: under the nitrogen atmosphere, mixing 5-hydroxytryptamine hydrochloride solution with 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 dropwise adding dimethyl sulfate into the N-acetyl-5-hydroxytryptamine under the condition that the pH value is 11-11.5, and performing aftertreatment after the reaction is finished to obtain the N-acetyl-5-methoxy tryptamine. The invention takes 5-hydroxytryptamine hydrochloride as raw material, and prepares the finished melatonin through acetylation and methylation reaction, thereby avoiding waste caused by purifying and purifying products step by step, having the characteristics of short synthetic route, short synthetic period, few raw material types and the like, and the obtained product has high yield and purity which can meet market demands. The production method of melatonin provided by the invention saves 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 merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (3)
1. A synthesis method of N-acetyl-5-methoxy tryptamine comprises the following steps:
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 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 dropwise adding, sampling, controlling the center, adding 20% sodium hydroxide solution for neutralizing until the pH value of the system is 8.5-9, and washing with water to be neutral to obtain N-acetyl-5-hydroxytryptamine solution;
adding 20% sodium hydroxide solution by mass percent into the mixture, controlling the temperature to be 20-25 ℃, controlling the pH to be 11-11.5, beginning to drop 20.2g of dimethyl sulfate, dropwise adding 0.5h, controlling the temperature to be 20-25 ℃, stirring for 1.5h after the dropwise adding is finished, sampling, centering, controlling the residual content of N-acetyl-5-hydroxytryptamine to be less than 0.2%, adding 50% sulfuric acid to neutralize to pH=7.5, adding water to wash dichloromethane phase three times, adding 120ml of water each time, then heating to remove dichloromethane solvent, heating to 40-50 ℃ in water bath, vacuumizing to 0.09Mpa, and desolventizing an organic layer to obtain 22.6g melatonin.
2. A synthesis method of N-acetyl-5-methoxy tryptamine comprises the following steps:
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 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 dropwise adding, sampling, controlling the center, adding 20% 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 N-acetyl-5-hydroxytryptamine solution;
adding 20% sodium hydroxide solution by mass percent into the mixture, controlling the temperature to be 25-30 ℃, controlling the pH to be 11-11.5, beginning to drop 25.2g of dimethyl sulfate, dropwise adding for 1h, controlling the temperature to be 25-30 ℃, stirring for 2h after the dropwise adding is finished, sampling and centering, controlling the residual content of N-acetyl-5-hydroxytryptamine to be less than 0.2%, adding 50% sulfuric acid to neutralize until the pH is 7.5, adding water to wash dichloromethane three times, adding 180ml of water each time, then heating to remove dichloromethane solvent, heating to 40-50 ℃ in a water bath, and carrying out vacuum-0.09 Mpa, thereby obtaining 22.8g of melatonin through desolventizing an organic layer.
3. A synthesis method of N-acetyl-5-methoxy tryptamine comprises the following steps:
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 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 dropwise adding, sampling, controlling the center, adding 20% 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 N-acetyl-5-hydroxytryptamine solution;
adding 20% sodium hydroxide solution by mass percent into the mixture, controlling the temperature to be 25-30 ℃, controlling the pH to be 11-11.5, beginning to drop 23.2g of dimethyl sulfate, dropwise adding for 1h, controlling the temperature to be 25-30 ℃, stirring for 1.5h after the completion of dropwise adding, sampling, centering, controlling the residual content of N-acetyl-5-hydroxytryptamine to be less than 0.2%, adding 50% sulfuric acid to neutralize to pH=7.5, adding water to wash a dichloromethane phase for three times, adding 150ml of water each time, then heating to remove dichloromethane solvent, heating to 40-50 ℃ in a water bath, vacuumizing to 0.09Mpa, and desolventizing an organic layer to obtain 22.6g melatonin.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111202302.3A CN113788780B (en) | 2021-10-15 | 2021-10-15 | Synthesis method of N-acetyl-5-methoxy tryptamine |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111202302.3A CN113788780B (en) | 2021-10-15 | 2021-10-15 | Synthesis method of N-acetyl-5-methoxy tryptamine |
Publications (2)
Publication Number | Publication Date |
---|---|
CN113788780A CN113788780A (en) | 2021-12-14 |
CN113788780B true CN113788780B (en) | 2023-06-16 |
Family
ID=79184900
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111202302.3A Active CN113788780B (en) | 2021-10-15 | 2021-10-15 | Synthesis method of N-acetyl-5-methoxy tryptamine |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113788780B (en) |
Families Citing this family (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 (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102329263A (en) * | 2011-10-17 | 2012-01-25 | 上海化学试剂研究所 | Preparation method of N-acetyl-5-methoxytryptamine |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4506080A (en) * | 1983-07-01 | 1985-03-19 | Nestec S. A. | Preparation of serotonine and derivatives |
EP2488025A4 (en) * | 2009-10-15 | 2013-04-03 | Childrens Medical Center | Sepiapterin reductase inhibitors for the treatment of pain |
CN113214133B (en) * | 2021-05-08 | 2023-03-07 | 河北维达康生物科技有限公司 | Synthesis method of melatonin |
CN113402437B (en) * | 2021-06-29 | 2023-07-14 | 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 |
-
2021
- 2021-10-15 CN CN202111202302.3A patent/CN113788780B/en active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102329263A (en) * | 2011-10-17 | 2012-01-25 | 上海化学试剂研究所 | Preparation method of N-acetyl-5-methoxytryptamine |
Also Published As
Publication number | Publication date |
---|---|
CN113788780A (en) | 2021-12-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN113788780B (en) | Synthesis method of N-acetyl-5-methoxy tryptamine | |
AU2005320525B2 (en) | Method for producing L-biopterin | |
CN110330500B (en) | Stereoselective synthesis method of 6 beta-hydroxy-7, 8-dihydro-morphine derivative | |
CN110615744A (en) | Buvalracetam intermediate and preparation method thereof | |
EP2397141A1 (en) | Process for the synthesis of beta-amino acids and derivatives thereof | |
KR101077609B1 (en) | Process for preparing tricyclic derivatives | |
CN1019972C (en) | Process of preparing 5,6-dihydroxyindoles and 3-alkyl derivatives and intermediate compounds | |
DE60031917D1 (en) | A process for producing light-insensitive silver fatty acid salt grains and an apparatus therefor | |
CN115260043B (en) | Synthesis method of meta-hydroxylamine bitartrate | |
CN102153500A (en) | Method for synthesizing diindolylmethane derivative | |
CN110627670A (en) | Preparation method of L-norvaline | |
CN106518865B (en) | Preparation method of 1-alkenyl indolizine derivative | |
CN114835652A (en) | Method for synthesizing imido benzotriazole compound under photocatalysis condition | |
CN105111134B (en) | The method that one kind prepares (R) or (S) 3 amino piperidine dihydrochloride | |
CN111454231B (en) | Method for synthesizing 2-amino-5-nitrothiazole | |
CN107954872B (en) | Method for synthesizing malonate type compound | |
CN107849003A (en) | Prepare the new method of chromanol derivative | |
CN115353477B (en) | Preparation method of diseleno maleimide compound | |
CN101255161B (en) | Method for synthesizing 3,9-diaza-2,4-dioxo-spiro[5.5] undecane template compounds | |
CN114181088B (en) | Ionic liquid [ TEA ] [ TfOH ]2Method for preparing alpha-halogenated acetophenone compound by catalysis | |
CN108440344A (en) | A kind of fatty amine preparation method that efficient mechanical force promotes | |
CN108101906B (en) | Preparation method of cyclopentyl [ f ] pyrrolo [2,1,5-cd ] indolizine derivative | |
JP5645494B2 (en) | Method for producing amine body | |
CN114133320B (en) | Oxygen-containing 1, 7-diacetylene and synthesis method thereof | |
CN107445879B (en) | Preparation method of Latricinib intermediate |
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 | ||
CB03 | Change of inventor or designer information |
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 |
|
CB03 | Change of inventor or designer information | ||
GR01 | Patent grant | ||
GR01 | Patent grant |