CN104557696A - Method for synthesizing 4-polyfluoroaryl-substituted quinolinone compounds - Google Patents
Method for synthesizing 4-polyfluoroaryl-substituted quinolinone compounds Download PDFInfo
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- 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Abstract
The invention relates to a method for synthesizing 4-polyfluoroaryl-substituted quinolinone compounds. According to the method, convenient and easily-obtained 4-triflate-substituted quinolinone, simple polyfluoroarene and polyfluoroarene derivatives are taken as raw materials to produce various 4-polyfluoroaryl-substituted quinolinone compounds in moderate to good yields under the catalytic action of a catalytic amount of palladium. The structures of the compounds are represented by <1>H NMR, <13>C NMR, HRMS and other methods and are confirmed. The method provided by the invention takes simple polyfluoroarene, the polyfluoroarene derivatives and easily-obtained 4-triflate-substituted quinolinone are taken as raw materials, has the advantages of moderate reaction conditions, simplicity and convenience in operation, small catalyst dosage, wide application range of substrates and the like. Besides, the frameworks of the quinolinone compounds have broad-spectrum biological activity, and the obtained 4-polyfluoroaryl-substituted quinolinone compounds have very good application prospects in new drug research and development.
Description
Technical field
The invention belongs to technical field of organic chemistry, be specifically related to the new synthetic method of the quinolinone compounds that a kind of 4-polyfluoro aryl replaces.
Background technology
Due to the peculiar property of fluorine atom, itself or fluorine-containing functional group are incorporated into physical properties, chemical property and the biological activity that significantly can change compound in organic compound, therefore such group is widely used as structurally-modified instrument.Polyfluoro aryl also extensively comes across ((a) M ü ller.K. in drug molecule, pesticide molecule and organic photoelectrical material as fluorine structural unit; Faeh.C.; Diederich.F.Science, 2007,317,1881. (b) Murphy, A.R.; Frechet, J.M.Chem.Rev.2007,107,1066. (c) Purser, S.; Moore, P.R.; Swallow, S.; Gouverneur, V.Chem.Soc.Rev.2008,37,320. (d) Babudri, F.; Farinola, G.M.; Naso, F.; Ragni, R.Chem.Comm.2007,1003.).Such as Sitagliptin (sitagliptin) is as dipeptidyl peptidase-4 (DPP-4) inhibitor, controls glucose level, can be used for treating type ii diabetes by protection endogenous incretin and its effect of enhancing; NAK-1654 is a kind of pyrethroid insecticides, has strong action of contace poison, energy effectively preventing sanitary insect pest and store pest; P5FQ is as substructure unit (Stefopoulos, the A.A. of organic photovoltaic battery polymkeric substance; Kourkouli, S.N.; Economopoulos, S.; Ravani, F.; Andreopoulou, A.; Papagelis, K.; Siokou, A.; Kall itsis, J.K.Macromolecules, 2010,43,4827.).
The synthesis of current organic fluorocompound is divided into two kinds: one to be fluoro-building block method substantially, namely directly introduces using fluoro-containing intermediate as building block; The second is exactly direct fluorination, is namely fluoridized organic molecule by fluorination reagent.Current polyfluoro aromatic hydroxy compound mainly with the synthesis of building block method, generally passes through linked reaction (Facchetti, the A. of aryl borane reagent or tin aryl SnAr2 reagent and halogenated aryl hydrocarbon; Yoon, M.-H.; Stern, C.L.; Katz, H.E.; Marks, T.J.Angew.Chem.Int.Ed.2003,42,3900.), or with polyfluoro aromatic hydrocarbons and halogenated aryl hydrocarbon for raw material (Lafrance, M.; Shore, D.; Fagnou, K.Org.Lett.2006,8,5097.), or pass through dehydrogenation linked reaction (He, the C.-Y. of polyfluoro aromatic hydrocarbons and aromatic hydrocarbons; Fan, S.; Zhang, X.J.Am.Chem.Soc.2010,132,12850.).
In addition, as a kind of structural framework of wide spectrum, quinolinone is one of modal heterocycle structure, extensively be present in multiple there is notable biological activity natural product and drug molecule among, the quinolinones compound that particularly 4-aryl replaces is widely used in pharmaceutical chemistry ((a) Hewawasam, P.; Fan, W.; Knipe, J.; Moon, S.L.; Boissard, C.G.; Gribkoff, V.K.; Starret, J.E.Bioorg.Med.Chem.Lett.2002,12,1779. (b) Hewawasam, P.; Fan, W.; Ding, M.; Fl int, K.; Cook, D.; Goggings, G.D.; Myers, R.A.; Gribkoff, V.K.; Boissard, C.G.; Dworetzky, S.I.; Starret, J.E.; Lodge, N.J.J.Med.Chem.2003,46,2819. (c) Boy, K.M.; Guernon, J.M.; Sit, S.-Y.; Xie, K.; Hewawasam, P.; Boissard, C.G.; Dworetzky, S.I.; Natale, J.; Gribkoff, V.K.; Lodge, N.; Starret, J.E.Bioorg.Med.Chem.Lett.2004,14,5089. (d) Hewawasam, P.; Fan, W.; Cook, D.A.; Newberry, K.S.; Boissard, C.B.; Gribkoff, V.K., Starret, J.; Lodge, N.J.Bioorg.Med.Chem.Lett.2004,14,4479.).In order to set up the micromolecular compound storehouse of the fluorine-containing quinolinones skeleton with potential source biomolecule activity, we have developed the novel method of the quinolinone utilizing triflate to replace that a kind of palladium promotes and the quinolinones compound that polyfluoro aromatic hydrocarbons replaces for Material synthesis 4-polyfluoro aryl.
Summary of the invention
The method of the quinolinones compound that the object of the present invention is to provide a kind of easy, efficient acquisition 4-polyfluoro aryl to replace.
Method of the present invention further describes as in organic solvent, when there is additive, make the quinolinone that polyfluoro virtue hydrocarbons and their derivates and 4-triflate replace, under palladium catalyst and part promote, temperature of reaction is 80-90 DEG C, reaction 9-24 hour, aftertreatment obtains the quinolinones compound that described 4-polyfluoro aryl replaces;
The structure of described polyfluoro virtue hydrocarbons and their derivates is such as formula shown in (II):
The structure of the quinolinone that described 4-triflate replaces is such as formula shown in (III):
The structure of the quinolinone compounds that described 4-polyfluoro aryl replaces is such as formula shown in (I):
In formula (I)-Shi (III), R
1for C
1-4perfluoroalkyl, halogen or C
1-4alkoxyl group;
R
2for C
1-4alkyl or phenyl;
R
3for hydrogen, C
1-4alkyl or halogen.
Polyfluoro virtue hydrocarbons and their derivates described in further recommendation has following structural formula (II):
The structure of the quinolinone that the 4-triflate described in further recommendation replaces has following structural formula (III):
The mol ratio of quinolinone, palladium catalyst, phosphorous organic ligand and additive that polyfluoro virtue hydrocarbons and their derivates of the present invention, 4-triflate replace is preferably 2-3: 1: 0.05-0.15: 0.1-0.3: 2-3.
The palladium catalyst of use involved in the present invention is preferably palladium.
The phosphorous organic ligand of use involved in the present invention is preferably S-Phos.
The additive of use involved in the present invention is preferably salt of wormwood.
The organic solvent of use involved in the present invention is isopropyl acetate or ethyl acetate, is preferably isopropyl acetate.Reaction density scope is 0.1mmol/mL-1mmol/mL, and preferred concentration is 0.2mmol/mL-0.4mmol/mL.
As preferably, described range of reaction temperature is 80-90 DEG C.
As preferably, the described reaction times is 9-12 hour, reaction times long increase reaction cost, is then difficult on the contrary reaction raw materials is transformed completely.
In the present invention, described last handling process comprises: filter, silica gel mixed sample, eventually passes the quinolinones compound that column chromatography purification obtains the replacement of corresponding 4-polyfluoro aryl: or also can obtain product by the means of recrystallization.
The quinolinones compound (I) that the 4-polyfluoro aryl adopting method of the present invention can obtain following structural formula replaces:
The invention provides a kind of with the fragrant hydrocarbons and their derivates of the quinolinone facilitating the 4-triflate that is easy to get to replace and simple polyfluoro for raw material, under the palladium catalyst and organophosphorus ligand effect of catalytic amount, using salt of wormwood as additive, with in by the time outstanding yield obtain the method for the quinolinone compounds that various 4-polyfluoro aryl replaces.Such as formula the structure warp that the compound shown in (I) is all new compound, this compounds
1h NMR,
13the methods such as CNMR, HRMS characterize and are confirmed.The inventive method responds mild condition, easy and simple to handle, catalyst levels is little, the advantages such as wide application range of substrates, can the quinolinone compounds that replaces of design and synthesis difference replaces according to actual needs 4-polyfluoro aryl, and practicality is stronger.And this type of compound scaffold has the biological activity of wide spectrum, there is in new drug development extraordinary application prospect.
Embodiment
Below in conjunction with specific embodiment, the invention will be further described, but do not limit content of the present invention.
Embodiment 1
Penta fluoro benzene (2.0-3.0 equivalent) is added 4-trifluoromethanesulfonic acid ester group quinolinone (1.0 equivalent), K
2cO
3(2.0-3.0 equivalent), Pd (OAc)
2(5%) and in the solution of the isopropyl acetate of S-Phos (10%), and stir 9-12 hour at 80-90 DEG C of temperature, TLC monitors end; Wash reaction solution with water, be extracted with ethyl acetate, dry, concentrated and column chromatography for separation obtains the quinolinone compounds of corresponding 4-polyfluoro aryl replacement, and white solid, yield reaches 83%.
1H NMR(500 MHz，CDCl3)δ7.67(ddd，J＝8.5，7.0，1.5Hz，1H)，7.50(d，J＝8.5Hz，1H)，7.25(ddd，J＝8.0，7.0，1.0Hz，1H)，7.21(dd，J＝8.0，1.5Hz，1H)，6.77(s，1H)，3.83(s，3H)；
13C NMR(100MHz，CDCl3)δ160.9，144.0(dm，J＝248.8Hz)，141.7(dm，J＝262.8Hz)，140.2，137.8(dm，J＝253.6Hz)，135.9，131.5，126.1，124.9，122.6，119.1，114.8，110.9(m)，29.7；
19FNMR(376MHz，CDCl3)δ-138.9(dd，J＝21.1，6.8Hz，2F)，-152.1(t，J＝20.8Hz，1F)，-160.4(td，J＝21.1，6.8Hz，2F)；HRMS(ESI)calcd for C
16H
9F
5NO[M+H]
+326.0599，found 326.0587.
Embodiment 2
Polyfluoro benzene (2.0-3.0 equivalent) is added 4-trifluoromethanesulfonic acid ester group quinolinone (1.0 equivalent), K
2cO
3(2.0-3.0 equivalent), Pd (OAc)
2(5%) and in the solution of the isopropyl acetate of S-Phos (10%), and stir 9-12 hour at 80-90 DEG C of temperature, TLC monitors end; Wash reaction solution with water, be extracted with ethyl acetate, dry, concentrated and column chromatography for separation obtains the quinolinone compounds of corresponding 4-polyfluoro aryl replacement, and white solid, yield reaches 66%.
1H NMR(400MHz，CDCl3)δ7.63(ddd，J＝8.4，6.0，2.0Hz，1H)，7.47(d，J＝8.4Hz，1H)，7.21(m，2H)，6.77(s，1H)，4.18(s，3H)，3.83(s，3H)；
13C NMR(100MHz，CDCl3)δ161.1，144.2(dm，J＝246.6Hz)，141.0(dm，J＝246.3Hz)，140.1，139.1(m)，136.9，131.3，126.4，124.7，122.5，119.5，114.7，108.9(t，J＝19.1Hz)，62.2(t，J＝3.7Hz)，29.6；
19F NMR(376MHz，CDCl3)δ-140.9(dd，J＝20.5，7.1Hz，2F)，-156.8(dd，J＝20.9，7.7Hz，2F)；HRMS(ESI)calcd for C
17H
12F
4NO
2[M+H]
+338.0799，found 338.0797.
Embodiment 3
Polyfluoro benzene (2.0-3.0 equivalent) is added 4-trifluoromethanesulfonic acid ester group quinolinone (1.0 equivalent), K
2cO
3(2.0-3.0 equivalent), Pd (OAc)
2(5%) and in the solution of the isopropyl acetate of S-Phos (10%), and stir 9-12 hour at 80-90 DEG C of temperature, TLC monitors end; Wash reaction solution with water, be extracted with ethyl acetate, dry, concentrated and column chromatography for separation obtains the quinolinone compounds of corresponding 4-polyfluoro aryl replacement, and white solid, yield reaches 67%.
1H NMR(400MHz，CDCl3)δ7.66(ddd，J＝8.4，7.2，1.2Hz，1H)，7.49(d，J＝8.5Hz，1H)，7.23(t，J＝7.5Hz，1H)，7.16(dd，J＝7.9，1.0Hz，1H)，6.76(s，1H)，3.81(s，3H)；
13C NMR(150MHz，CDCl3)δ160.7，144.3(dm，J＝260.4Hz)，144.1(dm，J＝251.0Hz)，140.2，135.5，131.7，125.9，124.5，122.7，120.6(q，J＝273.6Hz)，120.1(m)，118.5，114.9，29.7；
19F NMR(376MHz，CDCl3)δ-56.4(t，J＝21.8Hz，3F)，-136.9(m，2F)，-138.8(m，2F)；HRMS(ESI)calcd forC
17H
9F
7NO[M+H]
+376.0567，found 376.0552.
Embodiment 4
Ptfe pyridine (2.0-3.0 equivalent) is added 4-trifluoromethanesulfonic acid ester group quinolinone (1.0 equivalent), K
2cO
3(2.0-3.0 equivalent), Pd (OAc)
2(5%) and in the solution of the isopropyl acetate of S-Phos (10%), and stir 9-12 hour at 80-90 DEG C of temperature, TLC monitors end; Wash reaction solution with water, be extracted with ethyl acetate, dry, concentrated and column chromatography for separation obtains the quinolinone compounds of corresponding 4-polyfluoro aryl replacement, and white solid, yield reaches 74%.
1H NMR(400MHz，CDCl3)δ7.67(ddd，J＝8.4，7.3，1.2Hz，1H)，7.50(d，J＝8.6Hz，1H)，7.25(t，J＝7.5Hz，1H)，7.16(dd，J＝8.0，1.0Hz，1H)，6.77(s，1H)，3.81(s，3H)；
13C NMR(150MHz，CDCl3)δ160.5，143.7(dm，J＝246.3Hz)，140.2，139.3(dm，J＝261.3Hz)，135.3，131.9，129.1(m)，125.8，124.2，122.8，117.9，115.0，29.8；
19F NMR(376MHz，CDCl3)δ-88.5(m，2F)，-140.2(m，2F)；HRMS(ESI)calcd for C
15H
9F
4N
2O[M+H]
+309.0646，found 309.0639.
Embodiment 5
Polyfluoro benzene (2.0-3.0 equivalent) is added 4-trifluoromethanesulfonic acid ester group quinolinone (1.0 equivalent), K
2cO
3(2.0-3.0 equivalent), Pd (OAc)
2(5%) and in the solution of the isopropyl acetate of S-Phos (10%), and stir 9-12 hour at 80-90 DEG C of temperature, TLC monitors end; Wash reaction solution with water, be extracted with ethyl acetate, dry, concentrated and column chromatography for separation obtains the quinolinone compounds of corresponding 4-polyfluoro aryl replacement, and white solid, yield reaches 79%.
1H NMR(400MHz，CDCl3)δ7.65(td，J＝7.8，1.6Hz，1H)，7.52(d，J＝8.4Hz，1H)，7.23(t，J＝7.2Hz，1H)，7.17(d，J＝7.6Hz，1H)，6.76(s，1H)，4.44(q，J＝7.2Hz，2H)，1.44(t，J＝7.2Hz，3H)；
13C NMR(100MHz，CDCl3)δ160.3，145.4(m)，142.8(m)，139.2，135.6，131.7，126.1，124.5，122.5，120.1(m)，118.7，114.8；
19F NMR(376MHz，CDCl3)δ-56.4(t，J＝21.5Hz，3F)，-136.9(m，2F)，-138.9(m，2F)；HRMS(ESI)calcd for C
18H
10F
7NNaO[M+Na]
+412.0543，found412.0553.
Embodiment 6
Penta fluoro benzene (2.0-3.0 equivalent) is added 4-trifluoromethanesulfonic acid ester group quinolinone (1.0 equivalent), K
2cO
3(2.0-3.0 equivalent), Pd (OAc)
2(5%) and in the solution of the isopropyl acetate of S-Phos (10%), and stir 9-12 hour at 80-90 DEG C of temperature, TLC monitors end; Wash reaction solution with water, be extracted with ethyl acetate, dry, concentrated and column chromatography for separation obtains the quinolinone compounds of corresponding 4-polyfluoro aryl replacement, and white solid, yield reaches 45%.
1H NMR(400MHz，CDCl3)δ7.65(m，2H)，7.57(m，1H)，7.39(m，3H)，7.19(m，2H)，6.83(s，1H)，6.78(d，J＝8.4Hz，1H)；
13C NMR(100MHz，CDCl3)δ160.9，144.2(dm，J＝249.1Hz)，141.8(dm，J＝261.1Hz)，141.3，137.9(dm，J＝253.8Hz)，137.2，136.8，131.0，130.4，129.2，128.7，125.7，125.4，122.8，118.8，116.9，110.9(m)；
19F NMR(376MHz，CDCl3)δ-138.7(dd，J＝21.9，6.8Hz，2F)，-151.8(t，J＝21.1Hz，1F)，-160.2(m，2F)；HRMS(ESI)calcd for C
21H
10F
5NNaO[M+Na]
+410.0575，found 410.0578.
Embodiment 7
Penta fluoro benzene (2.0-3.0 equivalent) is added 4-trifluoromethanesulfonic acid ester group quinolinone (1.0 equivalent), K
2cO
3(2.0-3.0 equivalent), Pd (OAc)
2(5%) and in the solution of the isopropyl acetate of S-Phos (10%), and stir 9-12 hour at 80-90 DEG C of temperature, TLC monitors end; Wash reaction solution with water, be extracted with ethyl acetate, dry, concentrated and column chromatography for separation obtains the quinolinone compounds of corresponding 4-polyfluoro aryl replacement, and white solid, yield reaches 90%.
1H NMR(400MHz，CDCl3)δ7.70(d，J＝8.8Hz，1H)，7.60(d，J＝8.8Hz，1H)，7.23(s，1H)，6.81(s，1H)，3.84(s，3H)；
13C NMR(100MHz，CDCl3)δ160.8，145.4(m)，142.9(m)，140.5，139.2(m)，136.7(m)，135.7，132.9，127.8，125.9，120.7，119.3，115.3，29.8；
19F NMR(376MHz，CDCl3)δ-138.8(dd，J＝21.1，6.4Hz，2F)，-143.4(dd，J＝22.6，7.9Hz，2F)，-151.1(t，J＝21.1Hz，1F)，-154.4(t，J＝21.1Hz，1F)，-159.8(td，J＝21.1，6.4Hz，2F)，-161.4(td，J＝22.2，7.9Hz，2F)；HRMS(ESI)calcd for C
17H
10F
5NNaO[M+Na]
+362.0575，found 362.0579.
Embodiment 8
Polyfluoro benzene (2.0-3.0 equivalent) is added 4-trifluoromethanesulfonic acid ester group quinolinone (1.0 equivalent), K
2cO
3(2.0-3.0 equivalent), Pd (OAc)
2(5%) and in the solution of the isopropyl acetate of S-Phos (10%), and stir 9-12 hour at 80-90 DEG C of temperature, TLC monitors end; Wash reaction solution with water, be extracted with ethyl acetate, dry, concentrated and column chromatography for separation obtains the quinolinone compounds of corresponding 4-polyfluoro aryl replacement, and white solid, yield reaches 26%.
1H NMR(400MHz，CDCl3)δ7.61(dd，J＝9.2，2.4Hz，1H)，7.43(d，J＝9.2Hz，1H)，7.10(s，1H)，6.79(s，1H)，3.79(s，3H)；
13C NMR(150MHz，CDCl3)δ160.3，144.4(dm，J＝261.2Hz)，144.0(dm，J＝248.6Hz)，138.8，134.6，131.8，128.5，125.8，125.0，119.6，119.3(m)，116.4，29.9；
19F NMR(376MHz，CDCl3)δ-56.4(t，J＝21.8Hz，3F)，-136.8(m，2F)，-138.2(m，2F)；HRMS(ESI)calcd for C
17H
8ClF
7NO[M+H]
+410.0177，found 410.0168.
Claims (12)
1. the synthetic method of the quinolinone compounds of a 4-polyfluoro aryl replacement, it is characterized in that: in organic solvent, when there is additive, make the quinolinone that polyfluoro virtue hydrocarbons and their derivates and 4-triflate replace, under palladium catalyst and part promote, temperature of reaction is 80-90 DEG C, reaction 9-24 hour, and aftertreatment obtains the quinolinones compound that 4-polyfluoro aryl replaces;
The structure of described polyfluoro virtue hydrocarbons and their derivates is such as formula shown in (II):
The structure of the quinolinone that described 4-triflate replaces is such as formula shown in (III):
The structure of the quinolinone compounds that described 4-polyfluoro aryl replaces is such as formula shown in (I):
In formula (I)-Shi (III), R
1for C
1-4perfluoroalkyl, halogen or C
1-4alkoxyl group;
R
2for C
1-4alkyl or phenyl;
R
3for hydrogen, C
1-4alkyl or halogen.
2. the synthetic method of the quinolinone compounds of 4-polyfluoro aryl replacement as claimed in claim 1, is characterized in that described polyfluoro virtue hydrocarbons and their derivates has following structural formula:
3. the synthetic method of the quinolinone compounds of 4-polyfluoro aryl replacement as claimed in claim 1, is characterized in that the quinolinone that described 4-triflate replaces has following structural formula:
4. the synthetic method of the quinolinone compounds of 4-polyfluoro aryl replacement as claimed in claim 1, it is characterized in that, the mol ratio of quinolinone, palladium catalyst, part and additive that described polyfluoro virtue hydrocarbons and their derivates, 4-triflate replace is 1-3: 1: 0.01-0.2: 0.02-0.4: 2-5.
5. the synthetic method of the quinolinone compounds of 4-polyfluoro aryl replacement as claimed in claim 1, is characterized in that described palladium catalyst is Palladous chloride, palladium bromide, palladium or tetra-triphenylphosphine palladium.
6. the synthetic method of the quinolinone compounds of 4-polyfluoro aryl replacement as claimed in claim 1, is characterized in that described part is phosphorous organic ligand.
7. the synthetic method of the quinolinone compounds of 4-polyfluoro aryl replacement as claimed in claim 6, is characterized in that described phosphorous organic ligand is S-Phos or X-Phos.
8. the synthetic method of the quinolinone compounds of 4-polyfluoro aryl replacement as claimed in claim 1, is characterized in that described additive is salt of wormwood or potassiumphosphate.
9. the synthetic method of the quinolinone compounds of 4-polyfluoro aryl replacement as claimed in claim 1, is characterized in that described organic solvent is isopropyl acetate or ethyl acetate.
10. the synthetic method of the quinolinone compounds of 4-polyfluoro aryl replacement as claimed in claim 1, is characterized in that described temperature of reaction is 80-90 DEG C.
The synthetic method of the quinolinone compounds that 11. 4-polyfluoro aryl as claimed in claim 1 replace, is characterized in that the reaction times is 9-24 hour.
The synthetic method of the quinolinone compounds that 12. 4-polyfluoro aryl as claimed in claim 1 replace, is characterized in that the quinolinone compounds that described 4-polyfluoro aryl replaces has following structural formula:
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104961684A (en) * | 2015-07-21 | 2015-10-07 | 重庆大学 | Preparation method of 1,3,5-triaryl-4-trifluoromethyl-1-H pyrazol compounds |
| CN108003150A (en) * | 2016-10-31 | 2018-05-08 | 河南工业大学 | The preparation method and applications of 4- heteroaryl qualone derivatives |
| CN110606829A (en) * | 2019-09-26 | 2019-12-24 | 上海城建职业学院 | Method for synthesizing 4-substituted quinoline derivative under palladium catalysis |
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| JPS61129168A (en) * | 1984-11-27 | 1986-06-17 | Dainippon Pharmaceut Co Ltd | 2-(4-substituted piperazin-4-oxyd-1-yl)-4-phenyl-quinoline derivative |
| US6143766A (en) * | 1999-04-16 | 2000-11-07 | Warner-Lambert Company | Benzopyranone and quinolone inhibitors of ras farnesyl transferase |
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2015
- 2015-01-21 CN CN201510036570.0A patent/CN104557696B/en not_active Expired - Fee Related
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| JPS61129168A (en) * | 1984-11-27 | 1986-06-17 | Dainippon Pharmaceut Co Ltd | 2-(4-substituted piperazin-4-oxyd-1-yl)-4-phenyl-quinoline derivative |
| US6143766A (en) * | 1999-04-16 | 2000-11-07 | Warner-Lambert Company | Benzopyranone and quinolone inhibitors of ras farnesyl transferase |
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| DMITRY S. RYABUKHIN等: "Superelectrophilic activation of N-aryl amides of 3-arylpropynoic acids: synthesis of quinolin-2(1H)-one derivatives", 《TETRAHEDRON》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104961684A (en) * | 2015-07-21 | 2015-10-07 | 重庆大学 | Preparation method of 1,3,5-triaryl-4-trifluoromethyl-1-H pyrazol compounds |
| CN108003150A (en) * | 2016-10-31 | 2018-05-08 | 河南工业大学 | The preparation method and applications of 4- heteroaryl qualone derivatives |
| CN110606829A (en) * | 2019-09-26 | 2019-12-24 | 上海城建职业学院 | Method for synthesizing 4-substituted quinoline derivative under palladium catalysis |
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| CN104557696B (en) | 2017-08-11 |
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