CN104557696B - A kind of method for the quinolinone compounds for synthesizing the substitution of fluoro aryl more than 4 - Google Patents
A kind of method for the quinolinone compounds for synthesizing the substitution of fluoro aryl more than 4 Download PDFInfo
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- FEIFPOJYHMYZEL-UHFFFAOYSA-N CCN(c1ccccc1C(c(c(F)c(c(C(F)(F)F)c1F)F)c1F)=C1)C1=O Chemical compound CCN(c1ccccc1C(c(c(F)c(c(C(F)(F)F)c1F)F)c1F)=C1)C1=O FEIFPOJYHMYZEL-UHFFFAOYSA-N 0.000 description 1
- AXCOCGJDERQVDK-UHFFFAOYSA-N COc(c(F)c(cc1F)F)c1F Chemical compound COc(c(F)c(cc1F)F)c1F AXCOCGJDERQVDK-UHFFFAOYSA-N 0.000 description 1
- ZVPAJILXQHMKMT-UHFFFAOYSA-N FC(c(c(F)c(cc1F)F)c1F)(F)F Chemical compound FC(c(c(F)c(cc1F)F)c1F)(F)F ZVPAJILXQHMKMT-UHFFFAOYSA-N 0.000 description 1
- WACNXHCZHTVBJM-UHFFFAOYSA-N Fc(c(F)c1F)cc(F)c1F Chemical compound Fc(c(F)c1F)cc(F)c1F WACNXHCZHTVBJM-UHFFFAOYSA-N 0.000 description 1
- HWIPMBCMGVXOKN-UHFFFAOYSA-N Fc(c(F)n1)cc(F)c1F Chemical compound Fc(c(F)n1)cc(F)c1F HWIPMBCMGVXOKN-UHFFFAOYSA-N 0.000 description 1
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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
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- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The present invention relates to a kind of method for the quinolinone compounds for synthesizing the substitution of fluoro aryl more than 4, it is to facilitate the fragrant hydrocarbons and their derivates of the quinolinone that 4 triflates being easy to get replace and simple polyfluoro as raw material, under the palladium chtalyst of catalytic amount, when outstanding yield obtains the quinolinone compounds of the various substitutions of fluoro aryl more than 4 in.The structure warp of such compound1H NMR、13The methods such as C NMR, HRMS are characterized and confirmed.The quinolinone that the inventive method is replaced using the fragrant hydrocarbons and their derivates of simple polyfluoro and 4 triflates being conveniently easy to get is raw material, and, easy to operate, catalyst amount is small with reaction condition gently, the advantages of wide application range of substrates.In addition, quinolinones compound skeleton has the bioactivity of wide spectrum, the quinolinone compounds of the substitution of fluoro aryl more than 4 of gained have extraordinary application prospect in new drug development.
Description
Technical field
The invention belongs to technical field of organic chemistry, and in particular to a kind of quinolinone compounds of many fluoro aryl substitutions of 4-
New synthetic method.
Background technology
Due to the peculiar property of fluorine atom, itself or fluorine-containing functional group are incorporated into organic compound being capable of significantly changing
Physical property, chemical property and the bioactivity of compound, therefore such group is widely used as structurally-modified instrument.Polyfluoro virtue
Base also comes across in drug molecule, pesticide molecule and organic photoelectrical material ((a) M ü as fluorine construction unit extensively
ller.K.；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) suppresses as dipeptidyl peptidase-4 (DPP-4)
Agent, controls blood sugar level, available for treatment type ii diabetes by protecting endogenous duodenin and strengthening its effect；It is fragrant
Fluorine time woods is a kind of pyrethroid insecticides, with strong action of contace poison, can effectively preventing sanitary insect pest and storage evil
Worm；P5FQ as organic photovoltaic battery polymer substructure unit (Stefopoulos, A.A.；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 substantially：One is fluoro-building block method, i.e., be used as block using fluoro-containing intermediate
Block is introduced directly into；Second is exactly direct fluorination, i.e., organic molecule is fluorinated by fluorination reagent.Current polyfluoro aromatic hydrocarbons chemical combination
Thing is main to be synthesized with building block method, typically passes through the coupling reaction of aryl borane reagent or aryl tin reagent and halogenated aryl hydrocarbon
(Facchetti, A.；Yoon, M.-H.；Stern, C.L.；Katz, H.E.；Marks,
T.J.Angew.Chem.Int.Ed.2003,42,3900.), or using polyfluoro aromatic hydrocarbons and halogenated aryl hydrocarbon as raw material (Lafrance,
M.；Shore, D.；Fagnou, K.Org.Lett.2006,8,5097.), or be coupled instead by the dehydrogenation of polyfluoro aromatic hydrocarbons and aromatic hydrocarbons
Answer (He, C.-Y.；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 most common heterocycle structure, is widely present in many
Among natural products and drug molecule of the kind with notable biological activity, the quinolinones compound quilt that particularly 4- aryl replaces
It 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.).Contain fluoro quinolinone with potential source biomolecule activity to set up
The micromolecular compound storehouse of class skeleton, we have developed the quinolinone of the utilization triflate substitution that palladium promotes a kind of and many
Fluorine aromatic hydrocarbons is the new method of the quinolinones compound of many fluoro aryl substitutions of Material synthesis 4-.
The content of the invention
It is an object of the invention to provide a kind of easy, quinolinones compound that is efficiently obtaining many fluoro aryl substitutions of 4-
Method.
The method of the present invention is further depicted as in organic solvent, when there is additive, makes polyfluoro aromatic hydrocarbons and its derivative
Thing and the quinolinone of 4- triflates substitution, in the case where palladium catalyst and part promote, reaction temperature is 80-90 DEG C, reaction
9-24 hours, post processing obtained the quinolinones compound of many fluoro aryl substitutions of described 4-；
Shown in the structure such as formula (II) of the fragrant hydrocarbons and their derivates of described polyfluoro：
Shown in the structure such as formula (III) of the quinolinone of described 4- triflates substitution：
Shown in the structure such as formula (I) of the quinolinone compounds of many fluoro aryl substitutions of described 4-：
In formula (I)-formula (III), R1For C1-4Perfluoroalkyl, halogen or C1-4Alkoxy；
R2For C1-4Alkyl or phenyl；
R3For hydrogen, C1-4Alkyl or halogen.
It is further recommended that the fragrant hydrocarbons and their derivates of described polyfluoro have following structural formula (II)：
It is further recommended that the structure of the quinolinone of described 4- triflates substitution has following structural formula
(III)：
The fragrant hydrocarbons and their derivates of polyfluoro of the present invention, the quinolinone of 4- triflates substitution, palladium catalyst, contain
The mol ratio of phosphorus organic ligand and additive is preferably 2-3: 1: 0.05-0.15: 0.1-0.3: 2-3.
The palladium catalyst involved in the present invention used preferably palladium.
The phosphorous organic ligand preferably S-Phos involved in the present invention used.
The additive involved in the present invention used preferably potassium carbonate.
The organic solvent involved in the present invention used is isopropyl acetate or ethyl acetate, preferably isopropyl acetate.Instead
It is 0.1mmol/mL-1mmol/mL to answer concentration range, and preferred concentration is 0.2mmol/mL-0.4mmol/mL.
Preferably, described range of reaction temperature is 80-90 DEG C.
Preferably, the described reaction time is 9-12 hours, reaction time long increase reaction cost is conversely then difficult to
Make reaction raw materials conversion complete.
In the present invention, described last handling process includes：Filtering, silica gel mixed sample eventually passes column chromatography purifying and obtains phase
The quinolinones compound for many fluoro aryl substitutions of 4- answered：Or can also obtain product by the means of recrystallization.
The quinolinones compound for many fluoro aryl substitutions of 4- that following structural formula can be obtained using the method for the present invention
(I)：
The invention provides a kind of quinolinone of 4- triflates substitution being easy to get with facilitating and simple polyfluoro virtue
Hydrocarbons and their derivates are raw material, under palladium catalyst and the organophosphorus ligand effect of catalytic amount, using potassium carbonate as additive, with
In obtain the quinolinone compounds of various 4- many fluoro aryls substitution when outstanding yield method.Chemical combination as shown in formula (I)
The all noval chemical compounds of thing, the structure warp of such compound1H NMR、13The methods such as CNMR, HRMS are characterized and confirmed.This hair
Bright method has reaction condition gentle, and easy to operate, catalyst amount is small, the advantages of wide application range of substrates, can be according to actual need
The quinolinone compounds for synthesizing the different many fluoro aryl substitutions of substituted 4- are designed, practicality is stronger.And such compound bone
Frame has the bioactivity of wide spectrum, has extraordinary application prospect in new drug development.
Embodiment
With reference to specific embodiment, the invention will be further described, but is not intended to limit present disclosure.
Embodiment 1
Phenyl-pentafluoride (2.0-3.0 equivalents) is added into 4- trifluoromethanesulfonic acid ester groups quinolinone (1.0 equivalent), K2CO3(2.0-3.0
Equivalent), Pd (OAc)2(5%) and S-Phos (10%) isopropyl acetate solution in, and stir at a temperature of 80-90 DEG C 9-
12 hours, TLC monitorings terminated；Reaction solution is washed with water, is extracted with ethyl acetate, dries, concentrates and column chromatography for separation obtains phase
The quinolinone compounds of many fluoro aryls substitutions of the 4- that answers, white solid, yield is up to 83%.
1H NMR (500 MHz, CDCl3) δ 7.67 (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) δ 160.9,144.0 (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 C16H9F5NO[M+H]+326.0599,
found 326.0587.
Embodiment 2
Many fluorobenzene (2.0-3.0 equivalents) are added into 4- trifluoromethanesulfonic acid ester groups quinolinone (1.0 equivalent), K2CO3(2.0-3.0
Equivalent), Pd (OAc)2(5%) and S-Phos (10%) isopropyl acetate solution in, and stir at a temperature of 80-90 DEG C 9-
12 hours, TLC monitorings terminated；Reaction solution is washed with water, is extracted with ethyl acetate, dries, concentrates and column chromatography for separation obtains phase
The quinolinone compounds of many fluoro aryls substitutions of the 4- that answers, white solid, yield is up to 66%.
1H NMR (400MHz, CDCl3) δ 7.63 (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) δ 161.1,
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 C17H12F4NO2[M+H]+338.0799, found 338.0797.
Embodiment 3
Many fluorobenzene (2.0-3.0 equivalents) are added into 4- trifluoromethanesulfonic acid ester groups quinolinone (1.0 equivalent), K2CO3(2.0-3.0
Equivalent), Pd (OAc)2(5%) and S-Phos (10%) isopropyl acetate solution in, and stir at a temperature of 80-90 DEG C 9-
12 hours, TLC monitorings terminated；Reaction solution is washed with water, is extracted with ethyl acetate, dries, concentrates and column chromatography for separation obtains phase
The quinolinone compounds of many fluoro aryls substitutions of the 4- that answers, white solid, yield is up to 67%.
1H NMR (400MHz, CDCl3) δ 7.66 (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) δ 160.7,144.3 (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
for C17H9F7NO[M+H]+376.0567, found 376.0552.
Embodiment 4
Ptfe pyridine (2.0-3.0 equivalents) is added into 4- trifluoromethanesulfonic acid ester groups quinolinone (1.0 equivalent), K2CO3(2.0-
3.0 equivalents), Pd (OAc)2(5%) and S-Phos (10%) isopropyl acetate solution in, and stirred at a temperature of 80-90 DEG C
Mix 9-12 hours, TLC monitorings terminate；Reaction solution is washed with water, is extracted with ethyl acetate, dries, concentrates and column chromatography for separation is obtained
To the quinolinone compounds of corresponding 4- many fluoro aryls substitution, white solid, yield is up to 74%.
1H NMR (400MHz, CDCl3) δ 7.67 (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) δ 160.5,143.7 (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 C15H9F4N2O[M+H]+309.0646, found 309.0639.
Embodiment 5
Many fluorobenzene (2.0-3.0 equivalents) are added into 4- trifluoromethanesulfonic acid ester groups quinolinone (1.0 equivalent), K2CO3(2.0-3.0
Equivalent), Pd (OAc)2(5%) and S-Phos (10%) isopropyl acetate solution in, and stir at a temperature of 80-90 DEG C 9-
12 hours, TLC monitorings terminated；Reaction solution is washed with water, is extracted with ethyl acetate, dries, concentrates and column chromatography for separation obtains phase
The quinolinone compounds of many fluoro aryls substitutions of the 4- that answers, white solid, yield is up to 79%.
1H NMR (400MHz, CDCl3) δ 7.65 (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) δ 160.3,145.4 (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 C18H10F7NNaO[M+Na]+
412.0543, found412.0553.
Embodiment 6
Phenyl-pentafluoride (2.0-3.0 equivalents) is added into 4- trifluoromethanesulfonic acid ester groups quinolinone (1.0 equivalent), K2CO3(2.0-3.0
Equivalent), Pd (OAc)2(5%) and S-Phos (10%) isopropyl acetate solution in, and stir at a temperature of 80-90 DEG C 9-
12 hours, TLC monitorings terminated；Reaction solution is washed with water, is extracted with ethyl acetate, dries, concentrates and column chromatography for separation obtains phase
The quinolinone compounds of many fluoro aryls substitutions of the 4- that answers, white solid, yield is up to 45%.
1H NMR (400MHz, CDCl3) δ 7.65 (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) δ 160.9,144.2 (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 C21H10F5NNaO[M+Na]+410.0575, found 410.0578.
Embodiment 7
Phenyl-pentafluoride (2.0-3.0 equivalents) is added into 4- trifluoromethanesulfonic acid ester groups quinolinone (1.0 equivalent), K2CO3(2.0-3.0
Equivalent), Pd (OAc)2(5%) and S-Phos (10%) isopropyl acetate solution in, and stir at a temperature of 80-90 DEG C 9-
12 hours, TLC monitorings terminated；Reaction solution is washed with water, is extracted with ethyl acetate, dries, concentrates and column chromatography for separation obtains phase
The quinolinone compounds of many fluoro aryls substitutions of the 4- that answers, white solid, yield is up to 90%.
1H NMR (400MHz, CDCl3) δ 7.70 (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) δ 160.8,145.4 (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 C17H10F5NNaO[M+Na]+362.0575, found
362.0579.
Embodiment 8
Many fluorobenzene (2.0-3.0 equivalents) are added into 4- trifluoromethanesulfonic acid ester groups quinolinone (1.0 equivalent), K2CO3(2.0-3.0
Equivalent), Pd (OAc)2(5%) and S-Phos (10%) isopropyl acetate solution in, and stir at a temperature of 80-90 DEG C 9-
12 hours, TLC monitorings terminated；Reaction solution is washed with water, is extracted with ethyl acetate, dries, concentrates and column chromatography for separation obtains phase
The quinolinone compounds of many fluoro aryls substitutions of the 4- that answers, white solid, yield is up to 26%.
1H NMR (400MHz, CDCl3) δ 7.61 (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) δ 160.3,144.4 (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 C17H8ClF7NO[M+H]+410.0177, found 410.0168.
Claims (10)
1. a kind of synthetic method of the quinolinone compounds of many fluoro aryl substitutions of 4-, it is characterised in that：In organic solvent, exist
During additive, make the fragrant hydrocarbons and their derivates of polyfluoro and the quinolinone of 4- triflates substitution, promote in palladium catalyst and part
Under entering, reaction temperature is 80-90 DEG C, is reacted 9-24 hours, and post processing obtains the quinolinones compound of many fluoro aryl substitutions of 4-；
Shown in the structure such as formula (II) of the fragrant hydrocarbons and their derivates of described polyfluoro：
Shown in the structure such as formula (III) of the quinolinone of described 4- triflates substitution：
Shown in the structure such as formula (I) of the quinolinone compounds of many fluoro aryl substitutions of described 4-：
In formula (I)-formula (III), R1For C1-4Perfluoroalkyl, halogen or C1-4Alkoxy；
R2For C1-4Alkyl or phenyl；
R3For hydrogen, C1-4Alkyl or halogen.
2. the synthetic method of the quinolinone compounds of many fluoro aryl substitutions of 4- as claimed in claim 1, it is characterised in that described
The fragrant hydrocarbons and their derivates of polyfluoro have following structural formula：
3. the synthetic method of the quinolinone compounds of many fluoro aryl substitutions of 4- as claimed in claim 1, it is characterised in that described
4- triflates substitution quinolinone have following structural formula：
4. the synthetic method of the quinolinone compounds of many fluoro aryl substitutions of 4- as claimed in claim 1, it is characterised in that described
The fragrant hydrocarbons and their derivates of polyfluoro, the quinolinone of 4- triflates substitution, palladium catalyst, the mol ratio of part and additive
For 1-3: 1: 0.01-0.2: 0.02-0.4: 2-5.
5. the synthetic method of the quinolinone compounds of many fluoro aryl substitutions of 4- as claimed in claim 1, it is characterised in that described
Palladium catalyst be palladium bichloride, palladium bromide, palladium or tetra-triphenylphosphine palladium.
6. the synthetic method of the quinolinone compounds of many fluoro aryl substitutions of 4- as claimed in claim 1, it is characterised in that described
Part be phosphorous organic ligand.
7. the synthetic method of the quinolinone compounds of many fluoro aryl substitutions of 4- as claimed in claim 6, it is characterised in that described
Phosphorous organic ligand be S-Phos or X-Phos.
8. the synthetic method of the quinolinone compounds of many fluoro aryl substitutions of 4- as claimed in claim 1, it is characterised in that described
Additive be potassium carbonate or potassium phosphate.
9. the synthetic method of the quinolinone compounds of many fluoro aryl substitutions of 4- as claimed in claim 1, it is characterised in that described
Organic solvent be isopropyl acetate or ethyl acetate.
10. the synthetic method of the quinolinone compounds of many fluoro aryl substitutions of 4- as claimed in claim 1, it is characterised in that described
The quinolinone compounds of 4- many fluoro aryls substitution there is following structural formula：
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