CN108101842B - Preparation method of 2-hydroxy-4-carboxyquinoline - Google Patents
Preparation method of 2-hydroxy-4-carboxyquinoline Download PDFInfo
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- CN108101842B CN108101842B CN201711469792.7A CN201711469792A CN108101842B CN 108101842 B CN108101842 B CN 108101842B CN 201711469792 A CN201711469792 A CN 201711469792A CN 108101842 B CN108101842 B CN 108101842B
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- Prior art keywords
- acetic acid
- glacial acetic
- hydroxy
- carboxyquinoline
- isatin
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- MFSHNFBQNVGXJX-UHFFFAOYSA-N 2-oxo-1,2-dihydroquinoline-4-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CC(=O)NC2=C1 MFSHNFBQNVGXJX-UHFFFAOYSA-N 0.000 title claims abstract description 43
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 88
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 claims abstract description 56
- 229960000583 acetic acid Drugs 0.000 claims abstract description 44
- 239000012362 glacial acetic acid Substances 0.000 claims abstract description 44
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 39
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims abstract description 30
- 238000006243 chemical reaction Methods 0.000 claims abstract description 27
- 238000000034 method Methods 0.000 claims abstract description 22
- 238000010992 reflux Methods 0.000 claims abstract description 22
- 238000002386 leaching Methods 0.000 claims abstract description 18
- 238000003756 stirring Methods 0.000 claims abstract description 18
- 239000000463 material Substances 0.000 claims abstract description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 16
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims abstract description 15
- 239000001632 sodium acetate Substances 0.000 claims abstract description 15
- 235000017281 sodium acetate Nutrition 0.000 claims abstract description 15
- 239000008367 deionised water Substances 0.000 claims abstract description 13
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 13
- 238000001704 evaporation Methods 0.000 claims abstract description 13
- 230000008020 evaporation Effects 0.000 claims abstract description 10
- 238000001914 filtration Methods 0.000 claims abstract description 10
- 238000001816 cooling Methods 0.000 claims abstract description 9
- 238000001035 drying Methods 0.000 claims abstract description 9
- 238000010438 heat treatment Methods 0.000 claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 claims abstract description 9
- 238000002425 crystallisation Methods 0.000 claims abstract description 6
- 230000008025 crystallization Effects 0.000 claims abstract description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 8
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 239000011259 mixed solution Substances 0.000 claims description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 4
- 239000000243 solution Substances 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 2
- 235000017550 sodium carbonate Nutrition 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- IVHBBMHQKZBJEU-UHFFFAOYSA-N cinchocaine hydrochloride Chemical compound [Cl-].C1=CC=CC2=NC(OCCCC)=CC(C(=O)NCC[NH+](CC)CC)=C21 IVHBBMHQKZBJEU-UHFFFAOYSA-N 0.000 abstract description 3
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 3
- 238000005580 one pot reaction Methods 0.000 abstract description 2
- 238000001308 synthesis method Methods 0.000 abstract description 2
- 238000010025 steaming Methods 0.000 abstract 1
- 239000000047 product Substances 0.000 description 14
- 239000007791 liquid phase Substances 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- LPGDEHBASRKTDG-UHFFFAOYSA-N N-acetylisatin Chemical compound C1=CC=C2N(C(=O)C)C(=O)C(=O)C2=C1 LPGDEHBASRKTDG-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- VYFOAVADNIHPTR-UHFFFAOYSA-N isatoic anhydride Chemical compound NC1=CC=CC=C1CO VYFOAVADNIHPTR-UHFFFAOYSA-N 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000002351 wastewater Substances 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/50—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention belongs to the technical field of chemical synthesis, and particularly relates to a production and preparation method of a cinchocaine hydrochloride intermediate 2-hydroxy-4-carboxyquinoline. The method comprises (1) placing glacial acetic acid into a reaction kettle, adding isatin, malonic acid and sodium acetate under stirring; (2) heating the solution in the step (1) to reflux, and cooling to room temperature after the reflux is finished; (3) the materials in the step (2) are subjected to reduced pressure steaming to remove glacial acetic acid (recovered and reused); (4) and (3) adding deionized water into the material subjected to glacial acetic acid evaporation in the step (3), stirring for crystallization, performing filtration by throwing after crystallization is finished, leaching with glacial acetic acid, leaching with methanol, and drying a wet product to obtain the 2-hydroxy-4-carboxyquinoline. The synthesis method adopts a process of one-pot to obtain a target product, simplifies the operation, shortens the production period and reduces the production cost; the obtained product has high purity and high yield, and is suitable for large-scale production.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a production and preparation method of a cinchocaine hydrochloride intermediate 2-hydroxy-4-carboxyquinoline.
Background
The 2-hydroxy-4-carboxyl quinoline is an important intermediate of the cinchocaine hydrochloride, and has wide application prospect in the fields of catalysis, molecular conductors, luminescent materials, molecular magnets, nonlinear optics and the like.
The current synthesis process route mainly comprises the steps of obtaining acetyl isatin through the reflux reaction of isatin and acetic anhydride, hydrolyzing and rearranging N-acetyl isatin in a sodium hydroxide aqueous solution to obtain a product, and refining the product if the product with high liquid phase purity is obtained. The smell of the material throwing process is extremely large during the preparation of the N-acetylisatin, and the method is not suitable for the current safe and environment-friendly situation. And a large amount of water is used in the hydrolysis and rearrangement processes, so that a large amount of waste liquid is generated. The method has the defects of high cost, complex operation, large labor capacity, long period, low yield, high safety and environmental protection pressure and the like. The literature mentions that isatin and malonic acid can be irradiated by microwave to obtain 2-hydroxy-4-carboxyquinoline, but the scheme is not suitable for large-scale production.
Patent CN106966975A discloses an improved process for the synthesis of 4-chloro-1-hydro-quinolin-2-one-3-carboxylic acid methyl ester from isatoic anhydride. In the method, the isatoic anhydride reacts with dimethyl malonate in DMF, and then the reaction product is purified in a mode of filtering and then acidifying, so that the use amounts of water and hydrochloric acid are obviously reduced, and the generation of waste water is reduced. In the method, a dangerous chemical substance sodium hydride is adopted during preparation, and the sodium hydride is combustible and explosive when meeting water and releasing hydrogen from wet air. Therefore, the potential safety hazard in production is high.
Disclosure of Invention
The invention aims to provide a preparation method of 2-hydroxy-4-carboxyl quinoline aiming at the defects. The method adopts isatin, malonic acid, sodium acetate and glacial acetic acid for reaction, and directly carries out reflux reaction, and the method only needs to recover the solvent after the reaction is finished, has less organic solvent discharge amount and is environment-friendly; simple reaction and safe operation. The 2-hydroxy-4-carboxyl quinoline prepared by the technical scheme not only can greatly shorten the production period and reduce the cost and the labor intensity, but also can improve the yield of the product.
The invention is realized by the following technical scheme:
a preparation method of 2-hydroxy-4-carboxyquinoline is characterized by comprising the following steps:
(1) putting glacial acetic acid into a reaction kettle, and adding isatin, malonic acid and sodium acetate under stirring;
(2) heating the solution in the step (1) to reflux, and cooling to room temperature after the reflux is finished;
(3) evaporating the material in the step (2) under reduced pressure to remove glacial acetic acid;
(4) and (3) adding deionized water into the material subjected to glacial acetic acid evaporation in the step (3), stirring for crystallization, performing filtration after crystallization is finished, leaching with cold glacial acetic acid, leaching with cold methanol, and drying the wet product to obtain the 2-hydroxy-4-carboxyquinoline.
The reaction formula is as follows:
in the above preparation method of 2-hydroxy-4-carboxyquinoline, sodium acetate in step (1) may be replaced by sodium carbonate or sodium bicarbonate.
In the above preparation method of 2-hydroxy-4-carboxyquinoline, in the step (1), the weight ratio of isatin to malonic acid to sodium acetate to glacial acetic acid is 1:1.3-2:0.1-0.3: 3-8.
Preferably, in the above method for preparing 2-hydroxy-4-carboxyquinoline, in the step (1), the weight ratio of isatin to malonic acid to sodium acetate to glacial acetic acid is 1:1.6:0.15: 4.
In the above method for preparing 2-hydroxy-4-carboxyquinoline, the reflux reaction time in the step (2) is 3 to 9 hours.
In the above preparation method of 2-hydroxy-4-carboxyquinoline, the weight ratio of the deionized water in the step (4) to the isatin in the step (1) is 2-7: 1.
Preferably, in the above preparation method of 2-hydroxy-4-carboxyquinoline, the weight ratio of the deionized water in the step (4) to the isatin in the step (1) is 3: 1.
In the above method for preparing 2-hydroxy-4-carboxyquinoline, in the step (4), the weight ratio of glacial acetic acid to isatin is 0.25-0.5:1, and the weight ratio of methanol to isatin is 0.25-0.5: 1.
Preferably, in the above preparation method of 2-hydroxy-4-carboxyquinoline, in the step (4), the weight ratio of glacial acetic acid to isatin is 0.4:1, and the weight ratio of methanol to isatin is 0.4: 1.
Preferably, the preparation method of the 2-hydroxy-4-carboxyquinoline comprises the following steps:
(1) placing 800kg of glacial acetic acid with the addition of 300-charge into a 1000L reaction kettle, and adding 100kg of isatin, 200kg of malonic acid with the addition of 130-30 kg of sodium acetate or sodium carbonate or sodium bicarbonate with stirring to obtain a mixed solution;
(2) heating the solution in the step (1) to reflux, carrying out reflux reaction for 3-9 hours, and cooling to room temperature after the reaction is finished;
(3) the material in the step (2) is subjected to reduced pressure evaporation to remove glacial acetic acid (which can be used indiscriminately);
(4) and (4) adding 200-700kg of deionized water into the material subjected to glacial acetic acid evaporation in the step (3), stirring and crystallizing, leaching with cold 25-50kg of glacial acetic acid, leaching with cold 25-50kg of methanol to obtain a wet 2-hydroxy-4-carboxyquinoline product, filtering by spinning, and drying to obtain the 2-hydroxy-4-carboxyquinoline.
More preferably, the preparation method of the 2-hydroxy-4-carboxyquinoline comprises the following detailed steps:
(1) putting 400kg of glacial acetic acid into a 1000L reaction kettle, and adding 100kg of isatin, 160kg of malonic acid and 15kg of sodium acetate under stirring to obtain a mixed solution;
(2) heating the solution in the step (1) to reflux, carrying out reflux reaction for 6 hours, and cooling to room temperature after the reaction is finished;
(3) the material in the step (2) is subjected to reduced pressure evaporation to remove glacial acetic acid (which can be used indiscriminately);
(4) adding 300kg of deionized water into the material subjected to glacial acetic acid evaporation in the step (3), stirring and crystallizing, leaching the filtered solid with 40kg of cold glacial acetic acid, then leaching with 4kg of cold methanol to obtain a wet 2-hydroxy-4-carboxyquinoline product, and drying the material at 45-70 ℃ for 24 hours after filtration to obtain the 2-hydroxy-4-carboxyquinoline.
In the preparation method of the 2-hydroxy-4-carboxyquinoline, the glacial acetic acid evaporated in the step (3) can be used indiscriminately.
In the present invention, all amounts and parts are by weight, and all raw materials and equipment are commercially available, unless otherwise specified.
Compared with the prior art, the invention has the advantages that:
1. the synthesis method adopts a process of one-pot to obtain a target product, simplifies the operation, shortens the production period and reduces the production cost;
2. in the preparation method of the 2-hydroxy-4-carboxyquinoline, the glacial acetic acid evaporated in the step (3) can be reused, the solvent consumption is low, and the generation of a large amount of waste water is avoided;
3. the obtained product has high purity and high yield, is safe and environment-friendly and is suitable for large-scale production.
Detailed Description
The present invention will be further described with reference to specific examples so that those skilled in the art may better understand the present invention, but the present invention is not limited thereto.
Example 1
400kg of glacial acetic acid is placed in a 1000L reaction kettle, and 100kg of isatin, 160kg of malonic acid and 15kg of sodium acetate are added with stirring. Heating to reflux, and reflux reaction for 6 hr. And after the reaction is finished, cooling to room temperature, carrying out reduced pressure evaporation to remove glacial acetic acid, adding 300kg of deionized water, stirring and crystallizing, leaching the filtered solid with cold 40kg of glacial acetic acid, then leaching with cold 40kg of methanol to obtain a wet 2-hydroxy-4-carboxyquinoline product, drying the material at 45-70 ℃ for 24 hours after the filtration to obtain 124.7kg of 2-hydroxy-4-carboxyquinoline, wherein the yield is 97%, and the purity of the liquid phase is 99.6%.
Example 2
400kg of recovered glacial acetic acid is placed in a 1000L reaction kettle, and 100kg of isatin, 160kg of malonic acid and 15kg of sodium acetate are added under stirring. Heating to reflux, and reflux reaction for 6 hr. And after the reaction is finished, cooling to room temperature, carrying out reduced pressure evaporation to remove glacial acetic acid, adding 300kg of deionized water, stirring and crystallizing, leaching the filtered solid with 30kg of cold glacial acetic acid, then leaching with 30kg of cold methanol to obtain a wet 2-hydroxy-4-carboxyquinoline product, drying the wet product at 45-70 ℃ for 24 hours after the filtration to obtain 125kg of 2-hydroxy-4-carboxyquinoline, wherein the yield is 97.3%, and the purity of the liquid phase is 99.6%.
Example 3
300kg of glacial acetic acid is placed in a 1000L reaction vessel, and 50kg of isatin, 100kg of malonic acid and 15kg of sodium carbonate are added with stirring. Heating to reflux, and reflux reaction for 4 hr. And after the reaction is finished, cooling to room temperature, carrying out reduced pressure evaporation to remove glacial acetic acid, adding 300kg of deionized water, stirring and crystallizing, leaching the filtered solid with cold 20kg of glacial acetic acid, then leaching with cold 10kg of methanol to obtain a wet 2-hydroxy-4-carboxyquinoline product, drying the wet product at 45-70 ℃ for 24 hours after the filtration to obtain 61.7kg of 2-hydroxy-4-carboxyquinoline, wherein the yield is 96% and the liquid phase purity is 99.5%.
Claims (8)
1. The production and preparation method of the 2-hydroxy-4-carboxyquinoline is characterized by comprising the following steps:
(1) putting glacial acetic acid into a reaction kettle, and adding isatin, malonic acid and sodium acetate under stirring;
(2) heating the solution obtained in the step (1) to reflux, and cooling to room temperature after the reflux is finished;
(3) evaporating the material in the step (2) under reduced pressure to remove glacial acetic acid;
(4) adding deionized water into the material distilled off glacial acetic acid in the step (3), stirring for crystallization, performing filtration after crystallization is finished, leaching with glacial acetic acid, leaching with methanol, and drying the wet product to obtain 2-hydroxy-4-carboxyquinoline;
in the step (1), the weight ratio of isatin to malonic acid to sodium acetate to glacial acetic acid is 1:1.3-2:0.1-0.3: 3-8;
the reflux reaction time in the step (2) is 3-9 hours.
2. The method for preparing 2-hydroxy-4-carboxyquinoline according to claim 1, wherein sodium acetate is replaced by sodium carbonate or sodium bicarbonate in the step (1).
3. The method for preparing 2-hydroxy-4-carboxyquinoline according to claim 1, wherein in the step (1), the weight ratio of isatin to malonic acid to sodium acetate to glacial acetic acid is 1:1.6:0.15: 4.
4. The method for preparing 2-hydroxy-4-carboxyquinoline according to claim 1, wherein the weight ratio of the deionized water in the step (4) to the isatin in the step (1) is 2-7: 1.
5. The method for preparing 2-hydroxy-4-carboxyquinoline according to claim 4, wherein the weight ratio of the deionized water in the step (4) to the isatin in the step (1) is 3: 1.
6. The method for preparing 2-hydroxy-4-carboxyquinoline according to claim 1, wherein the weight ratio of glacial acetic acid to isatin in step (1) in step (4) is 0.25-0.5:1, and the weight ratio of methanol to isatin in step (1) is 0.25-0.5: 1.
7. The method according to claim 6, wherein the weight ratio of glacial acetic acid to isatin in step (1) in step (4) is 0.4:1, and the weight ratio of methanol to isatin in step (1) is 0.4: 1.
8. A preparation method of 2-hydroxy-4-carboxyquinoline is characterized by comprising the following steps:
(1) placing 800kg of glacial acetic acid with the addition of 300-charge into a 1000L reaction kettle, and adding 100kg of isatin, 200kg of malonic acid with the addition of 130-30 kg of sodium acetate or sodium carbonate or sodium bicarbonate with stirring to obtain a mixed solution;
(2) heating the mixed solution in the step (1) to reflux, carrying out reflux reaction for 3-9 hours, and cooling to room temperature after the reaction is finished;
(3) evaporating the material in the step (2) under reduced pressure to remove glacial acetic acid;
(4) and (3) adding 200-700kg of deionized water into the material subjected to glacial acetic acid evaporation in the step (3), stirring and crystallizing, leaching the filtered solid with cold 25-50kg of glacial acetic acid, leaching with cold 25-50kg of methanol to obtain a wet 2-hydroxy-4-carboxyquinoline, filtering, and drying to obtain the 2-hydroxy-4-carboxyquinoline.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20140075082A (en) * | 2012-12-10 | 2014-06-19 | 주식회사 이큐스앤자루 | Dihydroquinoline derivatives, preparation method thereof and pharmaceutically composition containing the same as an active ingredient for preventing or treatment of disease by influenza A virus |
| CN104302624A (en) * | 2012-04-10 | 2015-01-21 | 邓迪大学 | antimalarials |
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- 2017-12-29 CN CN201711469792.7A patent/CN108101842B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104302624A (en) * | 2012-04-10 | 2015-01-21 | 邓迪大学 | antimalarials |
| KR20140075082A (en) * | 2012-12-10 | 2014-06-19 | 주식회사 이큐스앤자루 | Dihydroquinoline derivatives, preparation method thereof and pharmaceutically composition containing the same as an active ingredient for preventing or treatment of disease by influenza A virus |
Non-Patent Citations (1)
| Title |
|---|
| Synthesis of the pentacyclic core of lihouidine;Ken S. Feldman et al.;《Tetrahedron Letters》;20080201;第49卷;第2137页Scheme 2 * |
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