CN108623581B - Method for preparing paninula compound - Google Patents
Method for preparing paninula compound Download PDFInfo
- Publication number
- CN108623581B CN108623581B CN201710180896.XA CN201710180896A CN108623581B CN 108623581 B CN108623581 B CN 108623581B CN 201710180896 A CN201710180896 A CN 201710180896A CN 108623581 B CN108623581 B CN 108623581B
- Authority
- CN
- China
- Prior art keywords
- acid
- compound
- reaction
- palladium
- carbonate
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Abstract
The invention belongs to the field of organic synthesis, and particularly relates to a synthesis method of a panini (penicinotam) compound. The invention uses aniline and ethoxy methylene malonic diester as initial raw materials to carry out condensation reaction, Gould-Jacob reaction forms quinoline mother ring, and then carries out bromination and suzuki reaction to prepare 2- (1- (tert-butyloxycarbonyl) -1HThe intermediate of the-pyrrole-2-yl) -4-chloroquinoline-3-ethyl formate is finally subjected to a ring closure reaction to prepare the target product panini-nuan.
Description
Technical Field
The invention belongs to the field of chemical synthesis, and particularly relates to a novel synthesis method of a panini nuno compound shown in a formula I.
Background
The documents Shao, Chang-Lun, Wang, Chang-Yun, Gu, Yu-Cheng, Wei, Mei-Yan, Pan, Jia-Hui, Deng, Dong-Sheng, She, Zhi-Gang, Lin, Yong-Cheng.Bioorganic & Medicinal Chemistry Letters(2010) 20(11), 3284-3286, discloses the structure and pesticidal activity of the active natural product, penicinotam.
Chinese patent CN 2009100183213 discloses the following compounds as insecticides.
Abe, Masaki; Imai, Tetsuya; Ishii, Naoki; Usui, Makio. Synthesis of quinolactacide via an acyl migration reaction and dehydrogenation with manganese dioxide, and its insecticidal activities. Bioscience, Biotechnology, and Biochemistry (2006) 70(1), 303-306 discloses the following compound, a synthetic method of quinolactacide.
In view of the unique chemical structure and physiological activity of the active natural product penicinotam, the method has important significance in deeply developing structural optimization and pharmacodynamic research and has important significance in structural optimization and pharmacodynamic research. At present, although the synthesis method of the compounds is reported, the existing method has the disadvantages of complicated steps, complex process and high cost, and acetone cyanohydrin used in a reagent used for reaction is a highly toxic chemical product and has great harm to human bodies and environment.
In order to meet the industrial demand, the invention develops a new route completely different from the existing synthetic method, and the new route is used for preparing the compound with the structure shown in the formula I with high yield, high purity and low cost. The invention uses hexyl ester of aniline ethoxy methylene malonic acid as initial raw material, and makes it undergo the processes of condensation reaction, Gould-Jacobs reaction to form quinoline mother ring, bromination and suzuki reaction so as to obtain 2- (1- (tert-butyloxycarbonyl) -1HAnd (3) preparing a target product, namely pennisotam, from an intermediate of (E) -pyrrole-2-yl) -4-chloroquinoline-3-ethyl formate through ester exchange and simple substitution reaction.
Disclosure of Invention
The invention aims to provide a method for synthesizing a quinolinone compound shown in a formula I, which comprises the following steps:
the invention aims to provide a method for synthesizing a quinolinone compound panini (penicotam) shown as a formula I, which comprises the following steps:
aniline and ethylene ethoxymethylidene malonate are condensed at high temperature and reacted by Gould-Jacobs to produce compound 2:
the solvent used in the reaction i is selected from dioxane, tetrahydrofuran, benzene, toluene, methanol, ethanol, hexane, octane, cyclohexane, cyclohexanone, acetonitrile, pyridine, phenol, DMF and DMSO, the reaction temperature is the boiling temperature of the used solvent, and the reaction time is 0.5 h-24 h; the solvent used in the reaction ii is selected from one or more of ethylene glycol methyl ether, diphenyl ether, anisole, 2, 4-dibromoanisole, 2, 5-difluoroanisole, 2, 6-dichloroanisole, 2-fluoro-5-bromoanisole, 2-fluoroanisole, 2-aminodiphenylsulfide, 2-chloro-4-fluoroanisole, 2-chloro-5-fluoroanisole, 2-chloroethylethyl sulfide, 2-chloroethylmethyl ether, 2-chloroethylphenyl sulfide, 2-chloroanisole, 2-bromo-4-fluoroanisole, phenyl ether and paraffin oil, the reaction temperature is normal temperature to reflux, and the reaction time is 0.5 h-24 h.
(2) The compound 2 is prepared under the action of a halogenating agent to obtain a compound 3:
wherein the halogenating agent is selected from one or more of thionyl chloride, oxalyl chloride, phosphorus trichloride or phosphorus pentachloride, the solvent is selected from one or more of dioxane, tetrahydrofuran, benzene, toluene, methanol, ethanol, hexane, octane, cyclohexane, cyclohexanone, acetonitrile, pyridine, phenol, DMF and DMSO, and the temperature is the boiling temperature of the solvent.
(3) Reacting the compound 3 under the action of an oxidant and a halogenating agent to prepare a compound 4:
wherein reactions i and ii are one-pot reactions; the oxidant used in the reaction i is selected from one or more of hydrogen peroxide, ammonium dichromate, potassium perchlorate, potassium periodate, perchloric acid, potassium persulfate, anhydrous sodium peroxide, sodium hypochlorite solution, performic acid, peracetic acid, perbenzoic acid, m-chloroperoxybenzoic acid, tert-butyl peroxide, ozone and dessimidine reagent, the solvent is one or more of dioxane, tetrahydrofuran, benzene, toluene, methanol, ethanol, hexane, octane, cyclohexane, cyclohexanone, acetonitrile, pyridine, phenol, DMF and DMSO, the temperature is normal temperature to reflux, the reaction time is 0.5h to 24h, the halogenating agent used in the reaction ii is selected from one or more of bromine water, phosphorus pentabromide, phosphorus tribromide, 3-bromobenzylsulfone, methyl 3-bromobenzoate, dibromosulfoxide, carbon tetrabromide, methyl p-bromobenzoate and phosphorus oxybromide, the solvent is dioxane, potassium perchlorate, anhydrous sodium peroxide, sodium hypochlorite solution, performic acid, peracetic acid, perbenzoate, sodium oxybromide and the like, One or more of tetrahydrofuran, benzene, toluene, methanol, ethanol, hexane, octane, cyclohexane, cyclohexanone, acetonitrile, pyridine, phenol, DMF and DMSO at the temperature of normal temperature to reflux, and the reaction time is 0.5-24 h.
(4) And (2) carrying out Suzuki coupling reaction on the compound 4 and (1- (tert-butyloxycarbonyl) -1H-pyrrol-2-yl) boric acid under alkaline conditions to prepare a compound 5:
wherein the alkaline reagent is selected from one or more of anhydrous sodium carbonate, potassium carbonate, cesium carbonate, lithium carbonate, ammonium carbonate, calcium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, magnesium hydroxide, barium hydroxide, ammonia water, basic zinc carbonate, basic magnesium carbonate, sodium methoxide, sodium ethoxide and potassium/sodium tert-butoxide; the catalyst is one or more of palladium powder, palladium carbon, palladium acetate, palladium oxide, palladium nitrate, palladium sulfate, palladium dibromide, palladium hydroxide, palladium chloride, palladium acetate, tetratriphenylphosphine palladium, triphenylphosphine palladium, bis (triphenylphosphine) palladium dichloride (II), dibromo bis (tri-tert-butylphosphine) dipalladium (I), bis (tri-o-tolylphosphine) palladium dichloride (II) and bis (methyldiphenylphosphine) palladium dichloride (II), the solvent is one or more of dioxane, tetrahydrofuran, benzene, toluene, methanol, ethanol, hexane, octane, cyclohexane, cyclohexanone, acetonitrile, pyridine, phenol, DMF, DMSO and water, the reaction temperature is from normal temperature to the boiling temperature of the selected solvent, and the reaction time is 0.5 h-24 h.
(5) Compound 5 compound 6 was prepared under bronsted acidic high temperature conditions:
wherein the Bronsted acid is one or more of hydrogen bromide, sulfurous acid, hypophosphorous acid, fluoboric acid, hydrofluoric acid, hydrobromic acid, hydroiodic acid, silicotungstic acid, boric acid, iodic acid, phosphoric acid, periodic acid, hydrofluoric acid, hydrochloric acid, sulfuric acid, nitric acid, formic acid, acetic acid, phosphorous acid, polyphosphoric acid, fluoboric acid, fluorophosphoric acid, hydrofluoric acid, hydroiodic acid, sulfamic acid, pyrophosphoric acid, phosphoric acid, phosphomolybdic acid solution and p-toluenesulfonic acid, one or more of solvents of dioxane, tetrahydrofuran, benzene, toluene, methanol, ethanol, hexane, octane, cyclohexane, cyclohexanone, acetonitrile, pyridine, phenol, DMF, DMSO and water, the reaction temperature is 50-200 ℃, and the reaction time is 0.5-48 h.
(6) Performing a ring closing reaction on the compound 6 under an alkaline condition at a high temperature to obtain a target product, namely panini (penicotam):
wherein the alkaline reagent is selected from one or more of anhydrous sodium carbonate, potassium carbonate, cesium carbonate, lithium carbonate, ammonium carbonate, calcium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, magnesium hydroxide, barium hydroxide, ammonia water, basic zinc carbonate, basic magnesium carbonate, sodium methoxide, sodium ethoxide and potassium/sodium tert-butoxide, the solvent is one or more of dioxane, tetrahydrofuran, benzene, toluene, methanol, ethanol, hexane, octane, cyclohexane, cyclohexanone, acetonitrile, pyridine, phenol, DMF, DMSO and water, the reaction temperature is from normal temperature to the boiling temperature of the selected solvent, and the reaction time is 0.5 to 24 hours.
Detailed Description
In order to further clarify the invention, the following examples are given by way of illustration only and are not to be construed as limiting the invention in any way.
Examples
4-Hydroxyquinoline-3-carboxylic acid ethyl ester
Weighing aniline (1.02 mL, 0.011 mol) and diethyl ethoxymethylene malonate (0.5-2 eq) and adding the aniline and the diethyl ethoxymethylene malonate into ethanol, heating the mixture at the temperature of 100-;
ESI-MS m/z 218.32 [M+H]+
1 H NMR (500 MHz， DMSO-d 6 ): 10.62 (brs, 1H), 8.80 (s, 1H), 8.46-7.78 (m, 4H), 4.10 (q, J =7.1 Hz, 2H), 1.30 (t, J =7.1 Hz， 3H)。
4-chloroquinoline-3-carboxylic acid ethyl ester
Weighing 4-hydroxyquinoline-3-carboxylic acid ethyl ester (1.6 g, 7.3 mmol), dissolving in tetrahydrofuran, adding phosphorus oxychloride (0.5-10 eq), mixing, heating at 100 ℃ for one hour, pouring the reaction liquid into ice water after the reaction is finished, adjusting the pH to be neutral by using a saturated potassium bicarbonate solution, extracting by using ethyl acetate (100mL multiplied by 2), combining organic phases, washing the organic phases by using saturated saline solution, drying by using anhydrous sodium sulfate, filtering, concentrating the organic phases, and performing silica gel column chromatography on the residue to obtain 1.1g (64% yield) of a white solid;
ESI-MS m/z 237.42 [M+H]+
1H NMR (500 MHz, DMSO-d 6) δ12.56（s, 1H）, 8.57(s, 1H), 8.19 (d, J=8.0Hz, 1), 7.74(dd, J=8.0, 7.0Hz 1H), 7.68(d, J=8Hz，1H), 7.45(t, J=7Hz，1H), 4.25(q，J=7Hz, 2H), 1.31(t, J=7Hz，3H) 。
2-bromo-4-chloroquinoline-3-carboxylic acid ethyl ester
Weighing 4-chloroquinoline-3-ethyl formate (1.1g, 4.7 mmol), dissolving in chloroform (20 mL), adding 85% peroxybenzoic acid (0.5-2 eq) at room temperature, stirring at room temperature for 4 hours, adding tribromooxyphosphorus acid (0.5-2 eq) to the reaction solution, stirring for 1 hour, pouring the reaction solution into ice water after the reaction is finished, adjusting the pH value to 8 by using saturated potassium carbonate solution, extracting by using ethyl acetate (100mL multiplied by 2), combining organic phases, washing the organic phase by using saturated common salt water, drying by using anhydrous sodium sulfate, filtering, concentrating the organic phase, and carrying out column chromatography on the residue to obtain a white solid (1.1g, 74% yield);
ESI-MS m/z: 316.0 [M+H]+
1H NMR (500 MHz， CDCl3) δ 8.32-8.19 (m, 1H), 8.15-8.04 (m， 1H), 7.91-7.81 (m， 1H), 7.78-7.68 (m, 1H), 4.56 (q, J = 7.1 Hz, 2H), 1.49 (t, J = 7.1 Hz, 3H) 。
2- (1- (tert-Butoxycarbonyl) -1H-pyrrol-2-yl) -4-chloroquinoline-3-carboxylic acid ethyl ester
Ethyl 2-bromo-4-chloroquinoline-3-carboxylate (1.1g, 3.2 mmol) and (1- (tert-butoxycarbonyl) -1 were weighedH-pyrrol-2-yl) boronic acid (0.69 g, 3.3 mmol) was dissolved in 1, 4-dioxane (15 mL), cesium carbonate (4.0 g, 6.5 mmol) and palladium acetate (360 mg, 0.3 mmol) were added thereto, and the reaction solution was heated at 75 deg.CoAfter the reaction was completed, the reaction mixture was poured into ice water and extracted with ethyl acetate (100 mL. times.2). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and the residue was chromatographed to give the product as a colorless oil (734 mg, 53% yield);
ESI-MS m/z: 345.2 [M+H]+
1H NMR (500 MHz， CDCl3 )，δ 11.65 (s, 1H), 11.59 (s, 1H), 8.07 (d, J = 7.6 Hz， 1H)， 7.77-7.61 (m, 2H), 7.36 (t, J = 7.3 Hz, 1H), 7.13 (s, 1H), 6.49 (d, J = 2.5 Hz， 1H), 6.33-6.18 (m， 1H), 4.14 (q, J = 7.1 Hz, 2H), 1.14 (t, J = 7.1 Hz, 3H) 。
4-oxo-2- (1)H-pyrrol-2-yl) -1, 4-dihydroquinoline-3-carboxylic acid ethyl ester
Reacting 2- (1- (tert-butyloxycarbonyl) -1H-pyrrol-2-yl) -4-chloroquinoline-3-carboxylic acid ethyl ester (643 mg, 1.7 mmol) dissolved in acetic acid (10 mL), ethanol (6 mL), water (5 mL) and warmed to 80%oC for 18 hours, distilling under reduced pressure to remove acetic acid and ethanol, diluting the obtained residue with water, adjusting to neutrality by using a saturated potassium carbonate solution, extracting by using ethyl acetate (100mL multiplied by 2), combining organic phases, washing the organic phases by using saturated saline solution, drying by using anhydrous sodium sulfate, filtering, and concentrating the organic phases. The residue was chromatographed to give the product as a pale yellow solid (258mg, 54% yield);
ESI-MS m/z 283.82 [M+H]+;
1H NMR (500 MHz， DMSO-d6) δ 16.12 (s, 1H)， 12.40 (s, 1H), 11.81 (s, 1H)， 8.25 (d， J = 8.0 Hz, 1H), 7.95-7.78 (m, 2H), 7.60-7.48 (m, 1H), 7.15 (d, J = 1.4 Hz, 1H), 6.82 (s， 1H)， 6.33-6.24 (m, 1H) 。
perninol' an
Reacting 4-oxo-2- (1)H-pyrrol-2-yl) -1, 4-dihydroquinoline-3-carboxylic acid ethyl ester (50 mg,0.18 mmol), potassium carbonate (10 mg, 0.054 mmol) dissolved in acetonitrile 20mL, stirred at 60 ℃ for 12h, and iodomethane (10. mu.L, 0.20 mmol) added. After the reaction, the reaction solution was poured into ice water, the pH was adjusted to neutral with dilute hydrochloric acid solution, ethyl acetate extraction (50 mL × 2) was performed, organic phases were combined, the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, concentrated, and the residue was subjected to silica gel column chromatography to obtain a product as a yellow solid (34 mg, 68% yield),
1H NMR (500 MHz, DMSO-d 6) δ 8.20(dd, J=8.0,1.6Hz，1H), 7.89 (d, J=8.0,1.6Hz, 1H), 7.78(ddd, J = 8.0,8.0,1.6Hz ,1H), 7.51 (ddd, J = 8.0,8.0,1.6Hz ,1H),7.47（dd, J = 3.0,1.0Hz,1H）, 7.0 (dd, J = 3.5,1.0Hz, 1H), 6.45 (dd,J=3.0,1.0Hz，1H), 3.9（s,1H）。
Claims (7)
1. a method for preparing quinolinone compound panini nuo' an with a structure of formula I,
the compound shown in the formula I is prepared according to the following synthetic route, and comprises the following steps:
step (1) aniline and ethoxy methylene malonic acid ethylene diester are condensed and reacted by Gould-Jacobs to form a compound 2;
preparing a compound 3 from the compound 2 under the action of a halogenating agent;
preparing a compound 4 from the compound 3 under the action of an oxidant and a halogenating agent;
step (4), preparing a compound 5 by Suzuki coupling reaction of the compound 4 under alkaline conditions;
reacting the compound 5 with Bronsted acid at high temperature to obtain a compound 6;
reacting the compound 6 under alkaline conditions to obtain a compound shown in the formula I;
2. the preparation method according to claim 1, wherein the solvent used in the reaction i in the step (1) is selected from dioxane, tetrahydrofuran, benzene, toluene, methanol, ethanol, hexane, octane, cyclohexane, cyclohexanone, acetonitrile, pyridine, phenol, DMF and DMSO, the reaction temperature is boiling temperature of the used solvent, and the reaction time is 0.5 h-24 h; the solvent used in the reaction ii is one or more selected from ethylene glycol methyl ether, diphenyl ether, anisole, 2, 4-dibromoanisole, 2, 5-difluoroanisole, 2, 6-dichloroanisole, 2-fluoro-5-bromoanisole, 2-fluoroanisole, 2-aminodiphenylsulfide, 2-chloro-4-fluoroanisole, 2-chloro-5-fluoroanisole, 2-chloroethylethyl sulfide, 2-chloroethylmethyl ether, 2-chloroethylphenylsulfide, 2-chloroanisole, 2-bromo-4-fluoroanisole, phenyl ether and paraffin oil, the reaction temperature is normal temperature to reflux, and the reaction time is 0.5-24 hours.
3. The process according to claim 1, wherein the halogenating agent used in step (2) is one or more selected from thionyl chloride, oxalyl chloride, phosphorus trichloride, and phosphorus pentachloride, and the solvent is one or more selected from dioxane, tetrahydrofuran, benzene, toluene, methanol, ethanol, hexane, octane, cyclohexane, cyclohexanone, acetonitrile, pyridine, phenol, DMF, and DMSO, and the temperature is the boiling temperature of the solvent.
4. The preparation method according to claim 1, wherein in step (3), the oxidant used in reaction i is selected from one or more of hydrogen peroxide, ammonium dichromate, potassium perchlorate, potassium periodate, perchloric acid, potassium persulfate, anhydrous sodium peroxide, sodium hypochlorite solution, performic acid, peracetic acid, m-chloroperoxybenzoic acid, tert-butyl peroxide, ozone and dessimutane reagent, the solvent is one or more of dioxane, tetrahydrofuran, benzene, toluene, methanol, ethanol, hexane, octane, cyclohexane, cyclohexanone, acetonitrile, pyridine, phenol, DMF and DMSO, the temperature is from room temperature to reflux, the reaction time is from 0.5h to 24h, the halogenating agent used in reaction ii is selected from one or more of bromine water, penta-bromo-oxy-phosphorus, phosphorus tribromide, 3-bromo-phenylmethanesulfone, methyl 3-bromo-benzoate, dibromo sulfoxide, carbon tetrabromide, methyl p-bromo-benzoate and phosphorus oxybromide, the solvent is one or more of dioxane, tetrahydrofuran, benzene, toluene, methanol, ethanol, hexane, octane, cyclohexane, cyclohexanone, acetonitrile, pyridine, phenol, DMF and DMSO, the temperature is from normal temperature to reflux, and the reaction time is 0.5 h-24 h.
5. The process according to claim 1, wherein in the step (4), the basic agent is one or more selected from the group consisting of anhydrous sodium carbonate, potassium carbonate, cesium carbonate, lithium carbonate, ammonium carbonate, calcium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, magnesium hydroxide, barium hydroxide, aqueous ammonia, basic zinc carbonate, basic magnesium carbonate, sodium methoxide, sodium ethoxide, and potassium/sodium t-butoxide; the catalyst is one or more of palladium powder, palladium carbon, palladium acetate, palladium oxide, palladium nitrate, palladium sulfate, palladium dibromide, palladium hydroxide, palladium chloride, tetratriphenylphosphine palladium, triphenylphosphine palladium, bis (triphenylphosphine) palladium dichloride (II), dibromo bis (tri-tert-butylphosphine) dipalladium (I), bis (tri-o-tolylphosphine) palladium dichloride (II) and bis (methyl diphenyl phosphine) palladium dichloride (II), the solvent is one or more of dioxane, tetrahydrofuran, benzene, toluene, methanol, ethanol, hexane, octane, cyclohexane, cyclohexanone, acetonitrile, pyridine, phenol, DMF, DMSO and water, the reaction temperature is from normal temperature to the boiling temperature of the selected solvent, and the reaction time is 0.5-24 hours.
6. The method according to claim 1, wherein the Bronsted acid in step (5) is one or more selected from hydrogen bromide, sulfurous acid, hypophosphorous acid, hydrofluoric acid, hydrobromic acid, hydroiodic acid, silicotungstic acid, boric acid, iodic acid, periodic acid, hydrochloric acid, sulfuric acid, nitric acid, formic acid, acetic acid, phosphorous acid, polyphosphoric acid, fluoroboric acid, fluorophosphoric acid, sulfamic acid, pyrophosphoric acid, phosphoric acid, phosphomolybdic acid, and p-toluenesulfonic acid, the solvent is one or more selected from dioxane, tetrahydrofuran, benzene, toluene, methanol, ethanol, hexane, octane, cyclohexane, cyclohexanone, acetonitrile, pyridine, phenol, DMF, DMSO, and water, the reaction temperature is 50-200 ℃, and the reaction time is 0.5-48 h.
7. The process according to claim 1, wherein in step (6), the reactant is selected from methyl iodide, the alkaline agent is selected from one or more of anhydrous sodium carbonate, potassium carbonate, cesium carbonate, lithium carbonate, ammonium carbonate, calcium hydroxide, sodium hydroxide, potassium hydroxide, cesium hydroxide, magnesium hydroxide, barium hydroxide, ammonia water, basic zinc carbonate, basic magnesium carbonate, sodium methoxide, sodium ethoxide, and potassium/sodium tert-butoxide, and the solvent is one or more of dioxane, tetrahydrofuran, benzene, toluene, methanol, ethanol, hexane, octane, cyclohexane, cyclohexanone, acetonitrile, pyridine, phenol, DMF, DMSO, and water; the reaction temperature is from normal temperature to the boiling temperature of the selected solvent, and the reaction time is 0.5 h-24 h.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710180896.XA CN108623581B (en) | 2017-03-24 | 2017-03-24 | Method for preparing paninula compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710180896.XA CN108623581B (en) | 2017-03-24 | 2017-03-24 | Method for preparing paninula compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108623581A CN108623581A (en) | 2018-10-09 |
| CN108623581B true CN108623581B (en) | 2021-10-22 |
Family
ID=63706840
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710180896.XA Active CN108623581B (en) | 2017-03-24 | 2017-03-24 | Method for preparing paninula compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108623581B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101691368A (en) * | 2009-08-25 | 2010-04-07 | 中国海洋大学 | Dehydration methylate of quinolinone alkaloid derivative and preparation method and application |
-
2017
- 2017-03-24 CN CN201710180896.XA patent/CN108623581B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101691368A (en) * | 2009-08-25 | 2010-04-07 | 中国海洋大学 | Dehydration methylate of quinolinone alkaloid derivative and preparation method and application |
Non-Patent Citations (2)
| Title |
|---|
| Penicinoline, a new pyrrolyl 4-quinolinone alkaloid with an unprecedented ring system from an endophytic fungus Penicillium sp.;Chang-Lun Shao 等;《Bioorganic & Medicinal Chemistry Letters》;20100414;第20卷(第11期);全文 * |
| Synthesis of Quinolactacide via an Acyl Migration Rection and Dehydrogenation with Manganese Dioxide,and Its Insecticidal Activities;Masaki ABE等;《Bioscience,Biotechnology,Biochemistry》;20140522;第70卷(第1期);全文 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108623581A (en) | 2018-10-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6963557B2 (en) | 4-((6- (2- (2,4-difluorophenyl) -1,1-difluoro-2-hydroxy-3- (1H-1,2,4-triazole-1-yl) propyl) pyridine-3) -Il) Oxy) Benzonitrile and preparation method | |
| CA2954276C (en) | Process for the preparation of 4-alkoxy-3-hydroxypicolinic acids | |
| KR20180101343A (en) | 2-oxoethyl) pyridin-3-yl) oxy) benzonitrile and a method for preparing the same | |
| JP6896897B2 (en) | Method for preparing m-diamide compound | |
| CN104447686B (en) | Polysubstituted 2-pyrroles's pyridine derivate and preparation method thereof | |
| WO2010055042A1 (en) | 2-[(1-cyanopropyl)carbamoyl]-5-methoxymethyl nicotinic acids and the use thereof in manufacturing herbicidal imidazolinones | |
| US9981917B2 (en) | Preparation method for revaprazan hydrochloride | |
| CN105330598A (en) | Preparing method for pirfenidone | |
| CN108623581B (en) | Method for preparing paninula compound | |
| CN105153013B (en) | The synthetic method of the ketone of 6 bromine isoindoline 1 | |
| KR20180116371A (en) | Process for producing 4-alkoxy-3-hydroxypicolic acid | |
| CN114213424B (en) | Synthesis method of furan [3,2-b ] pyridine derivative | |
| EP2982673B1 (en) | Process for manufacturing 5-chloromethyl-2,3-dicarboxylic anhydride | |
| KR101459301B1 (en) | Synthetic method of montelukast sodium intermediate | |
| CN104418793A (en) | Method for preparing medicine Lu-AE-58054 for resisting alzheimer's disease | |
| EP1873145B1 (en) | Method for producing nicotinic acid derivative or salt thereof | |
| CN109952294A (en) | 4- ((6- (2- (2,4 difluorobenzene base) -1,1- two fluoro- 2- hydroxyl -3- (5- sulfydryl -1H-1,2,4- triazol-1-yl) propyl) pyridin-3-yl) oxygroup) benzonitrile and preparation method | |
| CN102382053B (en) | A kind of method preparing tolvaptan intermediate | |
| CN103755657A (en) | Preparation method of rivaroxaban intermediate | |
| CN106883185B (en) | Preparation method of 4-chloro-2-trifluoromethylpyrimidine | |
| CN111635368B (en) | Preparation method of amine compound | |
| CN113620867B (en) | Synthesis method of fluopyram | |
| CN113087669B (en) | Preparation method of 4-cyano-5-bromopyrimidine | |
| CN107400106A (en) | A kind of preparation method of 5- fluorine pyran derivate | |
| CN110218177B (en) | Preparation method of 2, 6-dichloro-3-nitropyridine |
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 |