CN110128500B - Ugi mixed solvent process for preparing alpha-amido amides - Google Patents
Ugi mixed solvent process for preparing alpha-amido amides Download PDFInfo
- Publication number
- CN110128500B CN110128500B CN201910355883.0A CN201910355883A CN110128500B CN 110128500 B CN110128500 B CN 110128500B CN 201910355883 A CN201910355883 A CN 201910355883A CN 110128500 B CN110128500 B CN 110128500B
- Authority
- CN
- China
- Prior art keywords
- mixed solvent
- ugi
- solvent
- ethyl
- mixed
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
- C07K5/06052—Val-amino acid
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a Ugi mixed solvent method for preparing alpha-acylamino amide substances, which comprises the following steps: under the protection of inert gas, isobutyraldehyde and m-trifluoromethylaniline are stirred in a mixed solvent at room temperature; then adding glacial acetic acid under an ice bath condition, uniformly stirring, dropwise adding ethyl isocyanoacetate, removing the ice bath after dropwise adding is finished, and stirring and reacting for 8-12 h at room temperature under the protection of inert gas; the obtained reaction solution is concentrated, and the obtained crude product is subjected to post-treatment to obtain N-acetyl-N- [3- (trifluoromethyl) phenyl ] valyl glycine ethyl ester. The method adopts mixed solvent, and can increase reaction conversion rate and yield.
Description
Technical Field
The invention relates to a synthetic method of an organic compound, in particular to an Ugi multi-component synthetic method (Ugi mixed solvent synthetic method) of an alpha-acylamino amide substance, namely N-acetyl-N- [3- (trifluoromethyl) phenyl ] valyl glycine ethyl ester.
Background
N-acetyl-N- [3- (trifluoromethyl) phenyl ] valyl glycine ethyl ester, of the formula:
the alpha-acylamino amide type compound belongs to an alpha-acylamino amide type substance, is applied to the research fields of medicines, cosmetics, biochemistry and the like according to records, and particularly has remarkable research efficacy in the aspect of resisting cell aging as a protease inhibitor.
Alpha-acylamino amide substances are important organic synthesis frameworks, the conventional multi-path synthesis method is complex, and a plurality of multi-component method reactions are frequently used for establishing a molecular library of the substances, which is commonly known as a Ugi reaction.
In the synthesis of N-acetyl-N- [3- (trifluoromethyl) phenyl ] valyl glycine ethyl ester, according to the mechanism, m-trifluoromethyl aniline and isobutyraldehyde are firstly reacted to generate imine, then the imine is protonated by carboxylic acid, finally isonitriles are combined to form aza alkyne positive ions, and then carboxylate radicals are combined for rearrangement to obtain target molecules.
While their efficacy is taught in the prior art, they are often prepared by an Ugi single solvent synthesis using a single solvent methanol, specifically (EP1275372a 1):
0.63ml of isobutyraldehyde and 1ml of m-trifluoromethylaniline (1.15 molar equivalents) were mixed in 15ml of methanol with stirring, and the mixture was reacted at 20 ℃ for 15 minutes, then 0.46ml of acetic acid (1.15 molar equivalents) was added and reacted at 20 ℃ for 10 minutes. Then 0.8ml of 95% isocyanoacetate (1 molar equivalent) was added and the reaction was allowed to proceed for 48 hours at 20 ℃. For work-up, the reaction medium is concentrated in a rotary evaporator and the residue is purified on a silica gel column, eluent heptane/ethyl acetate 3: 7 (v/v); rf is 0.5; the yield thereof was found to be 91%.
Disclosure of Invention
The technical problem solved by the invention is to provide an Ugi mixed solvent method for preparing alpha-acylamino amide substances, namely, an Ugi mixed solvent synthesis method of N-acetyl-N- [3- (trifluoromethyl) phenyl ] valyl glycine ethyl ester, which adopts mixed solvents, thereby improving the reaction conversion rate and yield.
In order to solve the above technical problems, the present invention provides an Ugi mixed solvent process for preparing α -acylamidoamide compounds, comprising the steps of:
1) under the protection of inert gas (such as nitrogen), firstly, stirring isobutyraldehyde and m-trifluoromethylaniline in a mixed solvent at room temperature for 1 +/-0.2 h, then, adding glacial acetic acid under the condition of ice bath (0-5 ℃) and uniformly stirring (the stirring time is about 5min), then, dropwise adding (slowly dropwise adding) ethyl isocyanoacetate (or a mixed solution of the ethyl isocyanoacetate), controlling the temperature of a system to be less than or equal to 5 ℃ in the dropwise adding process, removing the ice bath after the dropwise adding is finished, and stirring and reacting for 8-12 h under the conditions of room temperature and the protection of the inert gas;
isobutyraldehyde: m-trifluoromethylbenzene: glacial acetic acid: (ii) the molar ratio of ethyl isocyanoacetate to 1 (1 + -0.02) to (1 + -0.02);
note: removing the ice bath, and naturally heating to room temperature; reaction monitoring by HPLC; the whole reaction process needs to be protected by inert gas (such as nitrogen);
2) concentrating the reaction liquid obtained in the step 1) (rotary evaporation concentration to remove the mixed solvent), and carrying out post-treatment (mainly column chromatography) on the obtained crude product (dark brown oily product) to obtain the N-acetyl-N- [3- (trifluoromethyl) phenyl ] valyl glycine ethyl ester.
As an improvement of the Ugi mixed solvent method for preparing the alpha-acylamino amide substances of the invention:
the mixed solvent is prepared from a polar protic solvent: the polar aprotic solvent is mixed at a volume ratio (v/v) of 5:1 to 3: 1.
As a further improvement of the Ugi mixed solvent process of the present invention for preparing α -acylamidoamide species:
the polar protic solvent is lower alcohol, and the lower alcohol comprises methanol and ethanol;
the polar aprotic solvent is anhydrous acetonitrile.
As a further improvement of the Ugi mixed solvent process of the present invention for preparing α -acylamidoamide species:
in the step 1), the liquid-to-material ratio of the mixed solvent to the ethyl isocyanoacetate is (10 +/-2) ml/1 g.
As a further improvement of the Ugi mixed solvent process of the present invention for preparing α -acylamidoamide species:
the mixed solvent is prepared from methanol: acetonitrile is mixed according to a volume ratio (v/v) of 3-4: 1; the liquid-to-feed ratio of the mixed solvent to ethyl isocyanoacetate was 10ml/1 g.
As a further improvement of the Ugi mixed solvent process of the present invention for preparing α -acylamidoamide species:
in the step 1), the isocyanoacetic acid ethyl ester is mixed with the mixed solvent to form mixed solution of the isocyanoacetic acid ethyl ester; in the mixed solution, the volume content of the ethyl isocyanoacetate is 40-60%;
then dropwise adding (slowly dropwise adding) mixed solution of ethyl isocyanoacetate; the temperature of the system is controlled to be less than or equal to 5 ℃ in the dropping process.
As a further improvement of the Ugi mixed solvent process of the present invention for preparing α -acylamidoamide species: the post-treatment of the step 2) comprises the following steps:
dissolving the crude product with ethyl acetate, washing with water, drying (drying with sodium sulfate), adding silica gel, stirring, and purifying with column to obtain N-acetyl-N- [3- (trifluoromethyl) phenyl ] valyl glycine ethyl ester (yellow white solid, purity greater than or equal to 98%).
As a further improvement of the Ugi mixed solvent process of the present invention for preparing α -acylamidoamide species: in the post-treatment of the step 2):
the feed-liquid ratio of the crude product to the ethyl acetate is 1g/(10 +/-2) ml;
and the water washing is carried out by adopting water or a NaCL water solution, the washing frequency is 2-3 times, and the using amount of the water or the NaCL water solution is 0.2 +/-0.1 times of the volume of the ethyl acetate in each washing.
Note: and separating liquid after each washing, and then carrying out subsequent water washing.
As a further improvement of the Ugi mixed solvent process of the present invention for preparing α -acylamidoamide species: in the post-treatment of the step 2):
the silica gel is 200-mesh 300-mesh silica gel, and the silica gel: the crude product is (1.2 +/-0.1): 1, and the eluent in column purification is petroleum ether: ethyl acetate at a volume ratio of 5:1 (v/v).
Note: after the solvent (ethyl acetate dissolved in the crude product) in silica gel was drained, column purification was performed.
The synthesis method comprises the steps of dividing the reaction product into two stages (glacial acetic acid and ethyl isocyanoacetate are added between the 2 stages under the ice bath condition) at the normal temperature of 25 ℃ to carry out one-pot reaction, wherein the total reaction time is about 9-13 h, and finally, carrying out column purification to obtain high-yield N-acetyl-N- [3- (trifluoromethyl) phenyl ] valyl glycine ethyl ester; the yield of the method can reach 98-99%.
The reaction formula of the invention is as follows:
the invention completes the reaction of the Ugi four components in the presence of a mixed solvent (consisting of a polar protic solvent and a polar aprotic solvent), achieves the aim of improving the conversion rate and the yield, and has the advantages of simple reaction operation and low solvent cost.
In summary, the preparation method of N-acetyl-N- [3- (trifluoromethyl) phenyl ] valyl glycine ethyl ester Ugi mixed solvent has the following technical advantages:
1. compared with the conventional single-solvent method reaction and conventional feeding, the method has the advantages of short reaction completion time, high conversion rate and high yield; the synthesis cost is saved.
2. The adopted mixed solvent is a common cheap and low-toxicity organic solvent, and has low cost and small acquisition difficulty.
Detailed Description
In the following cases: room temperature, generally 20-25 ℃; the stirring speed is about 600-800 rpm.
The nitrogen environment may be provided by a tee and nitrogen ball displacement, which is conventional.
Example 1, a Ugi mixed solvent process for the preparation of α -acylamidoamide species, sequentially following steps:
firstly, reaction:
1) a magnetic rotor was added to a 250ml three-necked flask at room temperature, equipped with a thermometer, and a mixed solvent (methanol: acetonitrile 3:1, v/v)95 ml;
under the protection of nitrogen, 6.06g (83.98mmol, 1.0eq) of isobutyraldehyde and 13.53g (83.98mmol, 1.0eq) of m-aminobenzotrifluoride are added and stirred at room temperature for 1 h;
2) continuously placing the obtained substance in the step 1) in an ice bath under the protection of nitrogen, stirring until the thermometer reading is reduced to 0-5 ℃, adding 5.04g (83.98mmol, 1.0eq) of glacial acetic acid, stirring for 5min, then slowly dropwise adding 9.50g (83.98mmol, 1.0eq) of ethyl isocyanoacetate by using a dropping funnel, and controlling the speed in the dropwise adding process so as to control the temperature of the system to be less than or equal to 5 ℃ and the dropwise adding time to be about 15 min; after the dropwise addition is finished, removing the ice bath, naturally heating the system to room temperature, and stirring for reaction for 12 hours; at this point, the reaction was monitored by HPLC for completion.
Secondly, the reaction liquid obtained in the first step is concentrated by rotary evaporation (the pressure of 0.02mpa and the temperature of 40 ℃) so as to remove the mixed solvent, and 35.0g of crude product of dark brown oil is obtained;
dissolving the crude product in 388ml of ethyl acetate, and washing with saturated NaCl aqueous solution for 3 times, wherein the amount of the saturated NaCl aqueous solution is 78ml in each washing (separating liquid after each washing and then carrying out subsequent washing); then drying by using sodium sulfate, adding 42.0g (1.2 times of the crude product by mass) of 200-mesh silica gel with 300 meshes into the filtrate obtained after filtration, mixing and pumping out the sample (namely, removing the contained ethyl acetate by using rotary evaporation concentration (the pressure of 0.02mpa and the temperature of 40 ℃)), and purifying by using a column;
adopting petroleum ether: taking a mixed solution of ethyl acetate-5: 1(v/v) as an eluent, and stopping elution until TLC developed eluent does not show the fluorescence of the product under the ultraviolet wavelength of 254nm, wherein the dosage of the eluent is about 1200 ml;
all the eluates were collected and concentrated (0.02mpa pressure, 40 ℃ C.) to give 31.9g of a white yellow solid, ethyl- - - -N-acetyl-N- [3- (trifluoromethyl) phenyl ] valylglycinate (purity. gtoreq.98%), yield 98.0%.
Example 2, a Ugi mixed solvent process for the preparation of α -acylamidoamide species, sequentially following steps:
firstly, reaction:
1) a magnetic rotor was added to a 250ml three-necked flask at room temperature, equipped with a thermometer, and a mixed solvent (ethanol: acetonitrile 5:1)40 ml;
under the protection of nitrogen, 3.19g (44.2mmol, 1.0eq) of isobutyraldehyde and 7.12g (44.2mmol, 1.0eq) of m-aminobenzotrifluoride are added and stirred for 1h at room temperature;
2) continuously placing the obtained substance in the step 1) in an ice bath under the protection of nitrogen, stirring, adding 2.65g (44.2mmol, 1.0eq) of glacial acetic acid when the thermometer reading value is reduced to 0-5 ℃, stirring for 5min, then slowly dropwise adding 10ml of a solution containing 5.00g (44.2mmol, 1.0eq) of ethyl isocyanoacetate by using a dropping funnel, wherein the 10ml of the solution consists of 44.2mmol (4.83ml) of ethyl isocyanoacetate and the rest of a mixed solvent, and controlling the speed in the dropwise adding process so as to control the temperature of the system to be less than or equal to 5 ℃, and the dropwise adding time is about 15 min; after the dropwise addition is finished, removing the ice bath, naturally heating the system to room temperature, and stirring for reacting for 8 hours; at this point, the reaction was monitored by HPLC for completion.
Secondly, carrying out rotary evaporation and concentration on the reaction liquid obtained in the first step, thereby removing the mixed solvent and obtaining 18.1g of crude product of dark brown oil;
dissolving the crude product in 200ml of ethyl acetate, and washing with saturated NaCl aqueous solution for 3 times, wherein the amount of the saturated NaCl aqueous solution is 40ml in each washing (separating liquid after each washing and then carrying out subsequent washing); then drying by adopting sodium sulfate, adding 21.7g (1.2 times of the crude product mass) of 200-mesh silica gel with 300 meshes into the filtrate obtained after filtration, mixing the sample, pumping the sample, and purifying the sample on a column;
adopting petroleum ether: taking a mixed solution of ethyl acetate-5: 1(v/v) as an eluent, and stopping elution until TLC developed eluent does not show the fluorescence of the product at the ultraviolet wavelength of 254nm, wherein the dosage of the eluent is about 600 ml; (ii) a
All the eluates were collected and concentrated to give 17.0g of ethyl- - (N-acetyl) -N- [3- (trifluoromethyl) phenyl ] valyl glycinate as a yellow-white solid (purity. gtoreq.98%) in 99% yield.
Example 3 "dropwise addition of a solution containing 5.00g (44.2mmol, 1.0 eq)" of ethyl isocyanoacetate in "dropwise addition of 10ml of the solution in step one 2) of example 2" was changed to "dropwise addition of 5.00g (44.2mmol, 1.0 eq)"; the rest is equivalent to the embodiment 2;
the final yield was 97%.
Example 4, a Ugi mixed solvent process for the preparation of α -acylamidoamide species, sequentially following steps:
firstly, reaction:
1) a magnetic rotor was charged into a 100ml three-necked flask at room temperature, equipped with a thermometer, and a mixed solvent (methanol: acetonitrile 4:1)20 ml;
under the protection of nitrogen, 1.28g (17.68mmol, 1.0eq) of isobutyraldehyde and 2.85g (17.68mmol, 1.0eq) of m-aminobenzotrifluoride are added and stirred at room temperature for 1 h;
2) continuously placing the obtained substance in the step 1) in an ice bath under the protection of nitrogen, stirring until the thermometer reading is reduced to 0-5 ℃, adding 1.06g (17.68mmol, 1.0eq) of glacial acetic acid, stirring for 5min, then slowly dropwise adding 2.00g (17.68mmol, 1.0eq) of ethyl isocyanoacetate by using a dropping funnel, and controlling the speed in the dropwise adding process so as to control the temperature of the system to be less than or equal to 5 ℃ and the dropwise adding time to be about 10 min; after the dropwise addition is finished, removing the ice bath, naturally heating the system to room temperature, and stirring for reaction for 10 hours; at this point, the reaction was monitored by HPLC for completion.
Secondly, carrying out rotary evaporation and concentration on the reaction liquid obtained in the first step, thereby removing the mixed solvent and obtaining 7.3g of crude product of dark brown oil;
dissolving the crude product in 80ml of ethyl acetate, and washing with saturated NaCL aqueous solution for 3 times, wherein the consumption of the saturated NaCL aqueous solution is 16ml in each washing (separating liquid after each washing and then carrying out subsequent washing); then drying by adopting sodium sulfate, adding 8.8g (1.2 times of the crude product mass) of 200-mesh silica gel with 300 meshes into the filtrate obtained after filtration, mixing the sample, pumping the sample, and purifying the sample on a column;
adopting petroleum ether: taking a mixed solution of ethyl acetate-5: 1(v/v) as an eluent, and stopping elution until TLC development eluent does not show the fluorescence of the product at the ultraviolet wavelength of 254nm, wherein the dosage of the eluent is about 250 ml;
all the eluates were collected and concentrated to give 6.75g of a yellow-white solid, ethyl- - (N-acetyl-N- [3- (trifluoromethyl) phenyl ] valyl glycinate, - - (- -N-acetyl-N- [3- (trifluoromethyl) phenyl) valyl glycinate, -) (purity: 98%) in 98.4% yield.
Comparative example 1, the meta-aminobenzotrifluoride and the glacial acetic acid in step one of example 4 were changed from 1.0eq to 1.15eq (i.e., from 17.68mmol to 20.332 mmol); the rest is equivalent to example 4;
the final product, ethyl N-acetyl-N- [3- (trifluoromethyl) phenyl ] valyl glycinate, was obtained in 91.4% yield.
Comparative example 2, the mixed solvent (methanol: acetonitrile 4:1) was changed to the solvent described in table 1 below, the amount used was unchanged, still 20 ml; the rest is equivalent to example 4; the final product yields are given in table 1 below.
TABLE 1
Comparative example 3, the setting of the "ice bath" in step one 2) of example 4 was cancelled; namely, the step one 2) is changed into the following steps:
2) adding 1.06g (17.68mmol, 1.0eq) of glacial acetic acid into the product obtained in the step 1) under the protection of nitrogen, stirring for 5min, then slowly dropwise adding 2.00g (17.68mmol, 1.0eq) of ethyl isocyanoacetate by using a dropping funnel, the dropwise adding time is the same as that of the example 4, and stirring the reaction after the dropwise adding is finished until the HPLC monitoring reaction is finished; the reaction time was about 11 h.
The final product yield was 94.6%.
Finally, it should also be noted that the above-mentioned lists merely illustrate individual embodiments of the invention. It is obvious that the invention is not limited to the above embodiments, but that many variations are possible. All modifications which can be derived or suggested by a person skilled in the art from the disclosure of the present invention are to be considered within the scope of the invention.
Claims (5)
1. The Ugi mixed solvent method for preparing the alpha-acylamino amide substance is characterized by comprising the following steps:
1) under the protection of inert gas, firstly, stirring isobutyraldehyde and m-trifluoromethylaniline in a mixed solvent at room temperature for 1 +/-0.2 h, then adding glacial acetic acid under an ice bath condition, uniformly stirring, dropwise adding ethyl isocyanoacetate, controlling the temperature of a system to be less than or equal to 5 ℃ in the dropwise adding process, removing the ice bath after dropwise adding is finished, and stirring and reacting for 8-12 h under the protection of inert gas at room temperature;
isobutyraldehyde: m-trifluoromethylbenzene: glacial acetic acid: (ii) ethyl isocyanoacetate in a molar ratio of 1:1:1: 1;
the mixed solvent is prepared from a polar protic solvent: the polar aprotic solvent is formed by mixing a polar aprotic solvent and a polar aprotic solvent in a volume ratio of 5: 1-3: 1, wherein the polar protic solvent is methanol or ethanol, and the polar aprotic solvent is anhydrous acetonitrile;
the liquid-material ratio of the mixed solvent to the ethyl isocyanoacetate is (10 +/-2) ml/1 g;
2) concentrating the reaction liquid obtained in the step 1), and carrying out post-treatment on the obtained crude product to obtain N-acetyl-N- [3- (trifluoromethyl) phenyl ] valyl glycine ethyl ester.
2. The Ugi mixed solvent process for the preparation of α -acylamidoamide based substances according to claim 1 characterized by:
in the step 1), the isocyanoacetic acid ethyl ester is mixed with the mixed solvent to form mixed solution of the isocyanoacetic acid ethyl ester; in the mixed solution, the volume content of the ethyl isocyanoacetate is 40-60%;
then dropwise adding mixed solution of ethyl isocyanoacetate; the temperature of the system is controlled to be less than or equal to 5 ℃ in the dropping process.
3. The Ugi mixed solvent process for the preparation of α -acylamidoamide based substances according to claim 1, characterized in that the post-treatment of step 2) is:
dissolving the crude product with ethyl acetate, washing with water, drying, adding silica gel, stirring, and purifying with column to obtain N-acetyl-N- [3- (trifluoromethyl) phenyl ] valyl glycine ethyl ester.
4. The Ugi mixed solvent process for producing α -acylamidoamide based substance according to claim 3, characterized in that in the post-treatment of the step 2):
the feed-liquid ratio of the crude product to the ethyl acetate is 1g/(10 +/-2) ml;
and the water washing is carried out by adopting water or a NaCl aqueous solution, the washing frequency is 2-3 times, and the using amount of the water or the NaCl aqueous solution is 0.2 +/-0.1 times of the volume of the ethyl acetate in each washing.
5. The Ugi mixed solvent process for producing α -acylamidoamide based substance according to claim 4, characterized in that in the post-treatment of the step 2):
the silica gel is 200-mesh 300-mesh silica gel, and the silica gel: the crude product is (1.2 +/-0.1): 1, and the eluent in column purification is petroleum ether: ethyl acetate in a volume ratio of 5: 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910355883.0A CN110128500B (en) | 2019-04-29 | 2019-04-29 | Ugi mixed solvent process for preparing alpha-amido amides |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910355883.0A CN110128500B (en) | 2019-04-29 | 2019-04-29 | Ugi mixed solvent process for preparing alpha-amido amides |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110128500A CN110128500A (en) | 2019-08-16 |
| CN110128500B true CN110128500B (en) | 2020-12-22 |
Family
ID=67575782
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910355883.0A Active CN110128500B (en) | 2019-04-29 | 2019-04-29 | Ugi mixed solvent process for preparing alpha-amido amides |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110128500B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113999154B (en) * | 2021-06-23 | 2023-03-21 | 国药东风总医院 | Compound and preparation method and application thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2810033B1 (en) * | 2000-06-08 | 2004-04-30 | Oreal | NOVEL COMPOUNDS OF THE N-ACYLAMINO-AMIDE FAMILY, COMPOSITIONS COMPRISING SAME, AND USES |
| FR3030523B1 (en) * | 2014-12-18 | 2017-01-20 | Oreal | NOVEL COMPOUNDS OF THE N-ACYLAMINO-AMIDE FAMILY, COMPOSITIONS COMPRISING THE SAME, AND USES THEREOF |
-
2019
- 2019-04-29 CN CN201910355883.0A patent/CN110128500B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN110128500A (en) | 2019-08-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8680329B2 (en) | Process for preparation of α-ketoglutaric acid | |
| CN110128500B (en) | Ugi mixed solvent process for preparing alpha-amido amides | |
| CN110981806A (en) | Method for synthesizing aryl pyrazole nitrile and byproduct carbonic acid diester | |
| AU2021314375A1 (en) | Method for large-scale synthesis of tetrodotoxin | |
| AT406959B (en) | ENANTIOSELECTIVE METHOD FOR PRODUCING (S) -CYANHYDRINES | |
| CN107903226A (en) | A kind of preparation method of cis furan ammonium salt | |
| CN111138353A (en) | Nicotinate hydrate and preparation method thereof | |
| CN113501771B (en) | Preparation method of N- (2-aminoethyl) glycine derivative | |
| CN106518865B (en) | Preparation method of 1-alkenyl indolizine derivative | |
| CN110038632B (en) | Preparation of sulfonic acid functionalized lignin heterogeneous catalyst and method for synthesizing amide compound by adopting catalyst | |
| CN108929251B (en) | Method for direct trifluoromethylation of C (sp3) -H | |
| CN102093258B (en) | Aromatic diamidine compound and synthesis method thereof | |
| CN113845488A (en) | Preparation and refining method of parecoxib and intermediate thereof | |
| CN112724117A (en) | Refining method of doxepin hydrochloride | |
| CN113620977B (en) | Synthesis method of thiazolopyrimidinone acetic acid | |
| CN117185972B (en) | Preparation method of florfenicol intermediate | |
| CN116621835B (en) | Synthesis method for synthesizing polycyclic quinoline derivative based on isonitrile | |
| CN113861202B (en) | Large-scale preparation process of pterosin | |
| CN110441447B (en) | Deuterated sulfamethoxazole-d4Method of synthesis of | |
| CN118530185B (en) | Method for preparing 4-hydroxy-6-methylpyrimidine | |
| CN110194760B (en) | Process for preparing 3-benzylidene-2- (7' -quinoline) -2, 3-dihydro-isoindol-1-ones | |
| CN102899306A (en) | S-MeHNL extraction method and application of S-MeHNL in chiral synthesized acetic cyanhydrin ester | |
| Benrzeil et al. | Efficient direct asymmetric aldol reactions in water using chiral diamide as organocatalysts | |
| CN118388362A (en) | One-pot synthesis method and application of amino acid derivative | |
| CN101314574B (en) | Method for synthesizing acylated enamine |
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 |