CN114605304A - Method for synthesizing (+/-) -ethyl 2- (4- (1-oxoisoindol-2-yl) phenyl) butyrate - Google Patents
Method for synthesizing (+/-) -ethyl 2- (4- (1-oxoisoindol-2-yl) phenyl) butyrate Download PDFInfo
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- 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
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/46—Iso-indoles; Hydrogenated iso-indoles with an oxygen atom in position 1
Abstract
The invention discloses a method for synthesizing (+/-) -2- (4- (1-oxoisoindole-2-yl) phenyl) ethyl butyrate, which takes a compound shown in a formula I and a compound shown in a formula II as raw materials, takes a metal complex as a catalyst, and performs a coupling reaction in an organic solvent under the action of an alkaline substance to obtain the 2- (4- (1-oxoisoindole-2-yl) phenyl) ethyl butyrate shown in the formula III. The substrate of the invention has wide and stable source, simple synthetic route, mild reaction condition and simple and convenient operation steps, and the adopted monovalent copper complex catalyst is cheap, stable and easy to obtain.
Description
Technical Field
The invention discloses a method for synthesizing (+/-) -2- (4- (1-oxoisoindole-2-yl) phenyl) ethyl butyrate.
Background
Indobufen (indobufen), chemical name (. + -.) -2- [4- (1-oxo-2-indolinyl) phenyl ] butanoic acid (II), was first marketed in Italy in 1984 as an anti-platelet aggregation drug.
(±) -2- [4- (1-oxo-2 isoindolinyl) phenyl ] ethyl butyrate (I) is an ethylation product of indobufen (II) and is also an important intermediate in the synthesis of non-steroidal anti-inflammatory and anti-hemagglutination drugs.
Most of the synthetic methods reported in the literature use ethyl 2- (4-aminophenyl) butyrate, phthalic anhydride, benzaldehyde or alpha-cyanobenzyl bromide as starting materials, and the methods have high cost, long steps and complex operation.
Therefore, it is necessary to develop a new method for synthesizing (±) -2- (4- (1-oxoisoindol-2-yl) phenyl) butyric acid ethyl ester.
Disclosure of Invention
In order to solve the problems in the prior art, the invention provides a novel method for synthesizing (+/-) -2- (4- (1-oxoisoindol-2-yl) phenyl) ethyl butyrate.
In order to achieve the purpose, the invention adopts the following technical scheme:
a novel process for the synthesis of ethyl (±) -2- (4- (1-oxoisoindol-2-yl) phenyl) butanoate, said process comprising:
in the formula I, X is Br or I;
taking a compound shown in a formula I and a compound shown in a formula II as raw materials, taking a metal complex as a catalyst, and completely performing coupling reaction in an organic solvent under the action of an alkaline substance to obtain 2- (4- (1-oxo-isoindole-2-yl) phenyl) ethyl butyrate shown in a formula III; the metal complex is formed by cuprous salt and ligand.
Further, the cuprous salt is cuprous chloride, cuprous bromide, cuprous iodide or their respective hydrates, preferably cuprous iodide.
Further, the ligand is selected from
Further, preferably, the ligand is selected from
Still further, it is preferable that
Further, the alkaline substance is lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, sodium methoxide, sodium ethoxide, cesium carbonate, potassium carbonate or potassium phosphate, preferably potassium carbonate or cesium carbonate.
Further, the mol ratio of the compound shown in the formula I to the compound shown in the formula II, the alkaline substance and the catalyst is 1: 1-3: 1-3: 0.05-0.5, preferably 1: 1.1-1.5: 1.5-2.5: 0.06 to 0.2.
Further, the reaction temperature is 60-150 ℃, preferably 90-130 ℃.
Further, the organic solvent is dimethylformamide, and the organic solvent is selected from DMSO, DMF, DMA, NMP or PEG, preferably DMF.
Furthermore, the adding amount of the organic solvent is 5-20 ml/mmol based on the substance amount of the compound shown in the formula I.
More specifically, the compound of formula i can be prepared as follows:
and (3) carrying out esterification reaction on the compound shown in the formula IV and ethanol to obtain the compound shown in the formula I.
Compared with the prior art, the invention has the beneficial effects that:
the substrate of the invention has wide and stable source, simple synthetic route, mild reaction condition and simple and convenient operation steps, and the adopted monovalent copper complex catalyst is cheap, stable and easy to obtain.
Detailed Description
To further illustrate the technical means and effects of the present invention adopted to achieve the predetermined objects, the detailed description of the embodiments, features and effects of the technical solutions according to the present invention is provided below.
When X is Br, the compound represented by formula 1 according to the present invention is prepared using the scheme of example 1.
Example 1
Dissolving 2- (4-bromophenyl) butyric acid (2.00g, 8.277mmol, 1.00equiv) in 30ml of absolute ethanol, cooling to 0 ℃ in an ice bath, dropwise adding thionyl chloride (4.89g, 41.106mmol, 5.00equiv), stirring and reacting at 60 ℃ for 4 hours, and after the reaction is completed, concentrating the reaction solution to obtain a crude product, and allowing the crude product to pass through a normal phase (petroleum ether: ethyl acetate: 3: 1) to obtain a target product, namely ethyl 2- (4-bromophenyl) butyrate (2.27g, light yellow oil).
Example 2
Taking a 2ml small bottle, adding anhydrous K2CO3(13.81mg, 0.1mmol, 2.00equiv), dissolving ethyl 2- (4-bromophenyl) butyrate 338.75mg and isoindolin-1-one 199.5mg in 10ml DMF, placing 0.4ml in 2ml vials, placing ethyl 2- (4-bromophenyl) butyrate (13.55mg, 0.05mmol, 1.00equiv) and isoindolin-1-one (7.98mg, 0.06mmol, 1.2equiv) in each vial, and placing CuI (0.95mg, 0.005mmol, 0.1equiv) and ligand
(0.005mmol, 0.1equiv) were added to each 0.1ml DMF bottle, and after stirring and complexing for 10min, the mixture was added to the bottle, and stirred at 120 ℃ overnight, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC), and 38.3% of product was formed.
Example 3
Replacement of the ligand in example 2 by
The remaining steps and parameter conditions were identical to those of example 2, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to yield 62.5% of the product.
Example 4
Replacement of the ligand in example 2 by
The remaining steps and parameter conditions were kept the same as in example 2, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to yield 36.9% of the product, followed by workup.
Example 5
Replacement of the ligand in example 2 by
The remaining steps and parameter conditions were kept the same as in example 2, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC), 49% of the product was produced, and post-treated.
Example 6
Replacement of the ligand in example 2 by
The remaining steps and parameter conditions were identical to those of example 2, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to yield 61% of the product, followed by workup.
Example 7
Replacement of the ligand in example 2 by
The remaining steps and parameter conditions were identical to those in example 2, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to yield 34% of the product, and worked up.
Example 8
Replacement of the ligand in example 2 by
The remaining steps and parameter conditions were kept the same as in example 2, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to yield 70.7% of the product, followed by workup.
Example 9
Replacement of the ligand in example 2 with
The remaining steps and parameter conditions were identical to those of example 2, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to yield 75.8% of the product.
Example 10
Replacement of the ligand in example 2 by
The remaining steps and parameter conditions were kept the same as in example 2, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to produce 33.6% of the product, followed by workup.
Example 11
Replacement of the ligand in example 2 by
The remaining steps and parameter conditions were identical to those of example 2, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to yield 28.6% of the product.
Example 12
Replacement of the ligand in example 2 by
The remaining steps and parameter conditions were identical to those of example 2, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to yield 21.8% of the product.
Example 13
Replacement of the ligand in example 2 with
The remaining steps and parameter conditions were kept the same as in example 2, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC), 61.1% of product formation.
Example 14
Replacement of the ligand in example 2 by
The rest steps and parameter conditions were kept the same as in example 2, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) without generation of a target product.
Example 15
Replacement of the ligand in example 2 by
The remaining steps and parameter conditions were identical to those of example 2, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to yield 66.9% of the product.
Example 16
Replacement of the ligand in example 2 by
The rest steps and parameter conditions were kept the same as in example 2, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC), 27.2% of the product was produced, and the reaction system was relatively complicated.
Example 17
Replacement of the ligand in example 2 by
The rest steps and parameter conditions were kept the same as in example 2, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) without generation of a target product.
Example 18
Replacement of the ligand in example 2 by
The remaining steps and parameter conditions were identical to those of example 2, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to yield 31.3% of the product.
Example 19
Will be as in example 2Replacement of the ligand by
The rest steps and parameter conditions were kept consistent with those of example 2, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC), and only 9.5% of the product was produced, and the reaction system was relatively complicated.
Example 20
Replacement of the ligand in example 2 by
The remaining steps and parameter conditions were identical to those of example 2, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to yield 21.6% of the product.
Example 21
Replacement of the ligand in example 2 by
The remaining steps and parameter conditions were identical to those of example 2, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to yield 22% of the product.
Example 22
Taking a 5000ml reaction bottle, and adding anhydrous K2CO3(1.381g, 0.01mol, 2.00equiv), ethyl 2- (4-bromophenyl) butanoate (33.875g, 0.125mol, 1.00equiv) and isoindolin-1-one (19.95g, 0.15mol, 1.2equiv), dissolved in 1000ml DMF, CuI (23.75g, 0.125mol, 0.1equiv) and ligand
(0.125mmol, 0.1equiv), stirring at 120 deg.C for reaction overnight, analyzing the reaction solution with High Performance Liquid Chromatography (HPLC) to obtain 85% product, cooling to room temperature, adding 2000ml of pure water dropwise, precipitating solid, vacuum filtering, and oven drying to obtain solid 30.29g with yield of 75%.
Example 23
The base in example 9 was replaced with cesium carbonate, the remaining steps and parametric conditions were identical to those in example 9, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to yield 75% of the product.
Example 24
When X is I, the compound of formula I is prepared according to example 24.
(1)
Dissolving diisopropylamine (1.12ml, 8.014mmol, 2.1equiv) in 5ml of redistilled THF, adding DMPU (1.2ml, 9.361mmol, 2.6equiv), cooling liquid nitrogen to-78 deg.C, adding n-hexane solution of n-butyllithium (3.21ml, 8.018mmol, 2.1equiv) dropwise, after dropwise addition, stirring at-78 deg.C for 30 minutes, dissolving 4-iodophenylacetic acid (1.00g, 3.816mmol, 1.00equiv) in 5ml of redistilled THF, adding DMPU (1.2ml, 9.361mmol, 2.6equiv) dropwise, adding to the above reaction solution, stirring at-78 deg.C for 45 minutes, dissolving iodoethane (0.9g, 5.724mmol, 1.5equiv) in 2ml of redistilled THF, adding dropwise at-78 deg.C, after dropwise addition, stirring at room temperature for 30 hours, removing tetrahydrofuran, adding 10% ethyl acetate solution, extracting saturated aqueous solution of acetic acid (20 ml), backwashing at 20ml), drying with anhydrous sodium sulfate, filtering, concentrating the filtrate to obtain crude product, and passing through reverse phase (0.05% formic acid acetonitrile system) to obtain target product 2- (4-iodophenyl) butyric acid (660mg, pale yellow solid);
(2)
dissolving 2- (4-iodophenyl) butyric acid (660mg, 2.275mmol, 1.00equiv) in 12ml of absolute ethanol, cooling to 0 ℃ in an ice bath, dropwise adding thionyl chloride (1353.22mg, 11.375mmol, 5.00equiv), stirring and reacting for 4 hours at 60 ℃, concentrating the reaction solution to obtain a crude product, and passing the crude product through a normal phase (petroleum ether: ethyl acetate: 5:1) to obtain a target product, namely ethyl 2- (4-iodophenyl) butyrate (650mg, light yellow oil).
Example 25
Taking a 2ml small bottle, adding anhydrous K2CO3(13.81mg, 0.1mmol, 2.00equiv), dissolving ethyl 2- (4-iodophenyl) butyrate 397.5mg and isoindolin-1-one 199.5mg in 10ml DMF, placing 0.4ml in a 2ml vial, placing ethyl 2- (4-iodophenyl) butyrate (13.55mg, 0.05mmol, 1.00equiv) and isoindolin-1-one (7.98mg, 0.06mmol, 1.2equiv) in the vial, and placing CuI (0.95mg, 0.005mmol, 0.1equiv) and ligand
(0.005mmol, 0.1equiv) are respectively added into a 0.1ml DMF bottle, stirred and complexed for 10min, then respectively added into the bottles, stirred and reacted at 120 ℃ overnight, and the reaction liquid is analyzed by a High Performance Liquid Chromatography (HPLC), so that the products with 11.3 percent of SM1, 6.4 percent of SM2 and 48.7 percent are generated.
Example 26
Replacement of the ligand in example 25 by
The remaining steps and parametric conditions were identical to those in example 25, and the reaction mixture was analyzed by High Performance Liquid Chromatography (HPLC) to yield a product having a SM1 content of 9.7%, a SM2 content of 4.5%, and a product having a content of 70.2%.
Example 27
Replacement of the ligand in example 25 by
The remaining steps and parametric conditions were in accordance with those in example 25, and the reaction mixture was analyzed by High Performance Liquid Chromatography (HPLC) to yield a product having a SM1 content of 9.2%, a SM2 content of 2.4%, and 63.7%.
Example 28
Replacement of the ligand in example 25 by
The remaining steps and parameter conditions were the same as in example 25, and the reaction solution was subjected to high performance liquid chromatography(HPLC) analysis showed 4.4% SM1, 3.5% SM2, 43.1% product formation.
Example 29
Replacement of the ligand in example 25 by
The remaining steps and parametric conditions were in accordance with those in example 25, and the reaction mixture was analyzed by High Performance Liquid Chromatography (HPLC) to yield a product having a SM1 content of 9.9%, a SM2 content of 4.7%, and a 62.3%.
Example 30
Replacement of the ligand in example 25 by
The remaining steps and parameter conditions were in accordance with those of example 25, and the reaction mixture was analyzed by High Performance Liquid Chromatography (HPLC) to yield 8.6% SM1, 65.4% SM 2.
Example 31
Replacement of the ligand in example 25 by
The remaining steps and parameter conditions were in accordance with those in example 25, and the reaction mixture was analyzed by High Performance Liquid Chromatography (HPLC) to produce a product containing 4.2% SM1 and 49.9%, followed by workup.
Example 32
Replacement of the ligand in example 25 by
The remaining steps and parametric conditions were in accordance with example 25 and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to yield a product having 7.6% SM1 and 74.4%.
Example 33
Replacement of the ligand in example 25 by
The rest steps and parameter conditions are kept consistent with those of example 25, and the reaction solution is used efficientlyLiquid Chromatography (HPLC) analysis showed 8.1% SM1 content, 81.1% product formation.
Example 34
Replacement of the ligand in example 25 by
The remaining steps and the parameter conditions were in accordance with example 25, and the reaction mixture was analyzed by High Performance Liquid Chromatography (HPLC) to yield 13.7% SM1, 7% SM2 and 67.8% SM 2.
Example 35
Replacement of the ligand in example 25 by
The remaining steps and parametric conditions were identical to those of example 25, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to yield a product having an SM1 content, an SM2 content of 1.4% and a 42.6% content.
Example 36
Replacement of the ligand in example 25 by
The remaining steps and parametric conditions were consistent with those in example 25, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to yield 1.3% SM2, 23.3% of product, and 8.8% of ligand.
Example 37
Replacement of the ligand in example 25 by
The remaining steps and parameter conditions were in accordance with those of example 25, and the reaction mixture was analyzed by High Performance Liquid Chromatography (HPLC) to yield a product having 6.4% SM1, 30.4% SM2, and 57.2%.
Example 38
Replacement of the ligand in example 25 by
The remaining steps and parameter conditions were in accordance with example 25 andthe reaction solution was analyzed by High Performance Liquid Chromatography (HPLC), and 17.4% SM1, 10.4% SM2, and 24.4% of the product was formed, and 22.8% of the ligand was formed.
Example 39
Replacement of the ligand in example 25 by
The remaining steps and parametric conditions were in accordance with example 25, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to yield a product having 13.1% SM1 and 58.2%.
Example 40
Replacement of the ligand in example 25 by
The remaining steps and parametric conditions were in accordance with those in example 25, and the reaction mixture was analyzed by High Performance Liquid Chromatography (HPLC) to yield a product having a SM1 content of 7.6%, a SM2 content of 3.5%, and a content of 45.5%.
EXAMPLE 41
Replacement of the ligand in example 25 by
The remaining steps and parametric conditions were in accordance with example 25, and the reaction mixture was analyzed by High Performance Liquid Chromatography (HPLC) to yield a product having 16.5% SM1 content and 14.3% SM2 content, and 36% SM2 content.
Example 42
Replacement of the ligand in example 25 by
The remaining steps and parametric conditions were in accordance with example 25, and the reaction mixture was analyzed by High Performance Liquid Chromatography (HPLC) to yield a product having an SM1 content of 20.7%, an SM2 content of 15.8%, and a product having a content of 27.7%.
Example 43
Replacement of the ligand in example 25 by
The remaining steps and parametric conditions were in accordance with those in example 25, and the reaction mixture was analyzed by High Performance Liquid Chromatography (HPLC) to yield 13.9% SM1, 12.7% SM2, and 50.3% of the product.
Example 44
Replacement of the ligand in example 25 by
The remaining steps and parametric conditions were in accordance with example 25, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to yield a product having 13.8% SM1 content, 14.9% SM2 content, and 44.5% SM.
Example 45
Replacement of the ligand in example 25 by
The remaining steps and parametric conditions were in accordance with those of example 25, and the reaction mixture was analyzed by High Performance Liquid Chromatography (HPLC) to produce 14.8% SM1, 12.2% SM2, and 23.8% products.
Example 46
Replacement of the ligand in example 25 by
The remaining steps and parametric conditions were in accordance with those of example 25, and the reaction mixture was analyzed by High Performance Liquid Chromatography (HPLC) to produce 12.1% SM1, 7.7% SM2, and 36.6% products.
Example 47
Replacement of the ligand in example 25 by
The remaining steps and parametric conditions were in accordance with those in example 25, and the reaction mixture was analyzed by High Performance Liquid Chromatography (HPLC) to yield a product having a SM1 content of 5.9%, a SM2 content of 9.6%, and a 19.2%.
Example 48
Replacement of the ligand in example 25 by
The remaining steps and parametric conditions were in accordance with example 25, and the reaction mixture was analyzed by High Performance Liquid Chromatography (HPLC) to yield 11.6% SM1, 9% SM2 and 34.5% SM product.
Example 49
Replacement of the ligand in example 25 by
The remaining steps and the parameter conditions were in accordance with those of example 25, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to yield no product, 12% SM1, 9.7% SM2 and 30.3%.
Example 50
Taking a 5000ml reaction bottle, and adding anhydrous K2CO3(1.381g, 0.01mol, 2.00equiv), ethyl 2- (4-bromophenyl) butyrate (39.75g, 0.125mol, 1.00equiv) and isoindolin-1-one (19.95g, 0.15mol, 1.2equiv) were dissolved in 1000ml DMF, CuI (23.75g, 0.125mol, 0.1equiv) and ligand
(0.125mmol, 0.1equiv), stirring at 120 deg.C for reaction overnight, analyzing the reaction solution with High Performance Liquid Chromatography (HPLC) to obtain 90% product, cooling to room temperature, adding 2000ml of pure water dropwise, precipitating solid, vacuum filtering, and oven drying to obtain 32.7g solid with yield of 81.0%.
Example 51
The potassium carbonate in example 33 was replaced with cesium carbonate, the remaining steps and parametric conditions were identical to those in example 33, and the reaction solution was analyzed by High Performance Liquid Chromatography (HPLC) to yield 81% of the product.
Claims (10)
1. A method for synthesizing (+/-) -ethyl 2- (4- (1-oxoisoindol-2-yl) phenyl) butyrate is characterized by comprising the following steps: the method comprises the following steps:
x is Br or I;
taking a compound shown in a formula I and a compound shown in a formula II as raw materials, taking a metal complex as a catalyst, and completely performing coupling reaction in an organic solvent under the action of an alkaline substance to obtain 2- (4- (1-oxoisoindole-2-yl) phenyl) ethyl butyrate shown in a formula III; the metal complex is formed by cuprous salt and ligand.
2. The method of claim 1, wherein: the cuprous salt is cuprous chloride, cuprous bromide, cuprous iodide or their respective hydrates, preferably cuprous iodide.
3. The method of claim 1, wherein: the ligand is selected from
4. The method of claim 3, wherein: the ligand is selected from
Further preferred is
5. The method of claim 1, wherein: the alkaline substance is lithium hydroxide, sodium hydroxide, potassium hydroxide, lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, sodium methoxide, sodium ethoxide, cesium carbonate, potassium carbonate or potassium phosphate, preferably potassium carbonate or cesium carbonate.
6. The method of claim 1, wherein: the mol ratio of the compound shown in the formula I to the compound shown in the formula II, the alkaline substance and the catalyst is 1: 1-3: 1-3: 0.05 to 0.5, preferably 1: 1.1-1.5: 1.5-2.5: 0.06 to 0.2.
7. The method of claim 1, wherein: the reaction temperature is 60-150 ℃, preferably 90-130 ℃.
8. The method of claim 1, wherein: the organic solvent is selected from DMSO, DMF, DMA, NMP or PEG, and is preferably DMF.
9. The method of claim 1, wherein: the adding amount of the organic solvent is 5-20 ml/mmol based on the amount of the compound shown in the formula I.
10. The method of claim 1, wherein: the compound of formula i is prepared as follows:
and carrying out esterification reaction on the compound shown in the formula IV and ethanol to obtain the compound shown in the formula I.
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Citations (3)
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|---|---|---|---|---|
| CN103189369A (en) * | 2010-09-01 | 2013-07-03 | 吉利德康涅狄格有限公司 | Pyridinones/pyrazinones, method of making, and method of use thereof |
| KR20140090822A (en) * | 2013-01-10 | 2014-07-18 | 연세대학교 산학협력단 | method for preparing indobufen using micro flow reactor |
| CN107531660A (en) * | 2015-03-13 | 2018-01-02 | 福马治疗股份有限公司 | α cinnamide compounds and composition as HDAC8 inhibitor |
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2020
- 2020-12-04 CN CN202011397645.5A patent/CN114605304A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103189369A (en) * | 2010-09-01 | 2013-07-03 | 吉利德康涅狄格有限公司 | Pyridinones/pyrazinones, method of making, and method of use thereof |
| KR20140090822A (en) * | 2013-01-10 | 2014-07-18 | 연세대학교 산학협력단 | method for preparing indobufen using micro flow reactor |
| CN107531660A (en) * | 2015-03-13 | 2018-01-02 | 福马治疗股份有限公司 | α cinnamide compounds and composition as HDAC8 inhibitor |
Non-Patent Citations (1)
| Title |
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| 王松青，等: "（±）-2-［4-（1-氧代-2异吲哚啉基）苯基］丁酸乙酯的合成", 《沈阳药科大学学报》 * |
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