CN111793019A - Preparation method of polyfluoro-substituted phenylsulfonyl indolone compounds - Google Patents
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- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- BERDBZNNSLMMOF-UHFFFAOYSA-N C1(=CC=CC=C1)S(=O)(=O)C=1C(N=C2C=CC=CC=12)=O Chemical class C1(=CC=CC=C1)S(=O)(=O)C=1C(N=C2C=CC=CC=12)=O BERDBZNNSLMMOF-UHFFFAOYSA-N 0.000 title claims description 11
- 238000000034 method Methods 0.000 claims abstract description 23
- -1 phenylsulfonyl indolone compound Chemical class 0.000 claims abstract description 20
- 239000003960 organic solvent Substances 0.000 claims abstract description 8
- 230000035484 reaction time Effects 0.000 claims abstract description 5
- 239000007858 starting material Substances 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 22
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 17
- SVWAAPIAQYIKMT-UHFFFAOYSA-N FC(C(=O)OS(=O)(=O)C1=CC=CC=C1)F Chemical compound FC(C(=O)OS(=O)(=O)C1=CC=CC=C1)F SVWAAPIAQYIKMT-UHFFFAOYSA-N 0.000 claims description 11
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 239000000047 product Substances 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- 239000011261 inert gas Substances 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 5
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 4
- 238000004440 column chromatography Methods 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 2
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 claims description 2
- 229910052786 argon Inorganic materials 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 7
- 238000001308 synthesis method Methods 0.000 abstract description 3
- RDZSNJCMRDNQNB-UHFFFAOYSA-N 5-fluoro-1-methylindole Chemical compound FC1=CC=C2N(C)C=CC2=C1 RDZSNJCMRDNQNB-UHFFFAOYSA-N 0.000 abstract 1
- 229910052731 fluorine Inorganic materials 0.000 description 9
- 239000011737 fluorine Substances 0.000 description 9
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 8
- 230000008569 process Effects 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- JXDYKVIHCLTXOP-UHFFFAOYSA-N Pseudoisatin Natural products C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- UBQZRUJWPZZYQW-UHFFFAOYSA-N 5-fluoro-1-methyl-2,3-dihydroindole Chemical compound FC1=CC=C2N(C)CCC2=C1 UBQZRUJWPZZYQW-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000006114 decarboxylation reaction Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012847 fine chemical Substances 0.000 description 2
- 238000003682 fluorination reaction Methods 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 125000003709 fluoroalkyl group Chemical group 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 150000005623 oxindoles Chemical class 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- YOAPFRAMLPSSNR-UHFFFAOYSA-N 2-(benzenesulfonyl)-2,2-difluoroacetic acid Chemical compound OC(=O)C(F)(F)S(=O)(=O)C1=CC=CC=C1 YOAPFRAMLPSSNR-UHFFFAOYSA-N 0.000 description 1
- 229910014263 BrF3 Inorganic materials 0.000 description 1
- MEAOTVUIXQCKTR-UHFFFAOYSA-N CC(C(C=C1)NC(O)=O)(C=C1F)C(O)=O Chemical compound CC(C(C=C1)NC(O)=O)(C=C1F)C(O)=O MEAOTVUIXQCKTR-UHFFFAOYSA-N 0.000 description 1
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 240000000233 Melia azedarach Species 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003556 anti-epileptic effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- AZSZCFSOHXEJQE-UHFFFAOYSA-N dibromodifluoromethane Chemical compound FC(F)(Br)Br AZSZCFSOHXEJQE-UHFFFAOYSA-N 0.000 description 1
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Substances CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 229940011411 erythrosine Drugs 0.000 description 1
- 235000012732 erythrosine Nutrition 0.000 description 1
- 239000004174 erythrosine Substances 0.000 description 1
- 239000012025 fluorinating agent Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000005935 nucleophilic addition reaction Methods 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 150000004812 organic fluorine compounds Chemical class 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/38—Oxygen atoms in positions 2 and 3, e.g. isatin
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
Abstract
The invention relates to a preparation method of a polyfluoro-substituted phenylsulfonyl indolone compound, which comprises the step of reacting phenyl sulfonyl difluoroacetate serving as a starting material with 5-fluoro-1-methylindole under the condition of an organic solvent to obtain the polyfluoro-substituted phenylsulfonyl indolone compound. Compared with the prior art, the preparation process is direct, convenient and efficient, the required raw materials are cheap and easily available, the synthesis method is simple to operate, the reaction time is short, the yield of the product is high, and the method has a good application prospect.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and relates to a preparation method of a medicine, pesticide and fine chemical intermediate, in particular to a preparation method of a polyfluoro-substituted phenylsulfonyl indolone compound.
Background
Introduction of fluorine atoms into organic molecules can effectively change their physical, chemical and biological properties due to their large electronegativity and small atomic radius (Fier, p.s.; Hartwing, j.f.j.j.am. chem.soc.2012,134, 6548.). This has led to the widespread use of fluorine-containing compounds in the fields of biology, medicine, materials and the like ([1]]Chowdhury,M.A.；Abdellatif,K.R.A.；Dong,Y.；Suresh,M.R.；Knaus,E.E.J.Med.Chem.2009,52,1525.[2]Kaneko,K.；Yamazaki,T.；Kitazume,T.J.Org.Chem.1993,58,2302.[3]Ritter,S.K.C&E News 2012,90, 10.). Meanwhile, fluorine atoms are introduced into aryl or alkyl groups, so that the properties of organic molecules are affected differently, particularly, the electron cloud arrangement, dipole moment and acid-base property of the molecules are possibly greatly changed, and the monofluorine substitution and the polyfluorine substitution have different effects on the properties of the molecules. Based on the above facts, we explored the synthesis of polyfluoro-substituted compounds, the basic idea of which is to introduce fluoroalkyl ([1] into aryl-fluorine-containing organic molecules]Iseki,K.Tetrahedron 1998,54,13877-13886.[2]Shi,M.；Chen,L.H.；Li,C.Q.J.Am.Chem.Soc.2005,127,3790-3800.[3]Ni,C.；Hu,M.；Hu,J.Chem.Rev.2015,115,765.[4]Shibata,N.；Matsnev,A.；Cahard,D.Beilstein J.Org.Chem.2010,6,65.[5]ang,X.；Wu,T.；Phipps,R.J.；Toste,F.D.Chem.Rev.2015,115,826.[6]Hu, j.j.fluorinenechem.2009, 130, 1130). Current methods of introducing fluoroalkyl groups can be broadly divided into two categories: direct fluorination and fluorine-containing block processes. The direct fluorination process is by using a fluorinating agent, such as SF4，DAST，TBAF，BrF3Introducing fluorine-containing groups into organic molecules, but the method has harsh reaction conditions and high reagent toxicity; the fluorine-containing block is obtained by introducing a fluorine-containing group ([1] by converting a functional group or breaking a carbon-carbon bond into a raw material containing fluorine, which is inexpensive and easily available]Rozen,S.Acc.Chem.Res.1988,21,307-312.[2]Davis,F.；Han,W.；Murphy,C.J.Org.Chem.1995,60,4730-4737.[3]Umemoto,T.；Tomizawa,G.；Kawada,K.J.Am.Chem.Soc.1990,112,8563-8575.[4]Guo, c.; wang, w.r.; qing, f.l.j.fluorine chem.2012,143, 135-142). In the field of fluoroalkylation, chlorodifluoromethane and dibromodifluoromethane (both of which are ozone-depleting substances) are commonly used to construct CF2And (4) a H part. However, in the course of developing the difluoromethylation process with the development of organofluorine chemistry in recent years, we found that PhSO2CF2H，PhSO2CF2SiMe3And PhSO2CF2Br Compounds are powerful nucleophilic difluoromethylating agents ([1]]Prakash,G.K.S.；Hu,J.Acc.Chem.Res.2007,40,921-930.)。
Oxidized indole building blocks are widely present in many natural products, and these have a variety of biological activities, such as antibacterial, antiepileptic, anticancer, antiviral, anti-aging, etc. (1 Candido-Bacani, P.M.; Dos Reis, M.B.; Serpeloni, J.M.; et al.J.Mutation Research,2011,19,47-51.[2] Kandasam, R.; Park, S.J.; Boyapalle, S.; et al. International Immunophalogy, 2010,10,218- -225.[3] Jiang, T.; Kuhen, K.L.; Wolff, K.; et al. bioorganic & chemical Chem.letters,2006,16, 2109.. I.). In addition, oxindole derivatives are also important intermediates for a variety of drugs and dyes.
We imagine that difluorobenzenesulfonyl group is introduced into aryl fluorine substituted oxindole derivative to synthesize 3-difluorobenzenesulfonyl-3-hydroxy-5-fluoroindolone compound, but the present preparation method is few and the conditions are harsh, such as nucleophilic addition reaction between enol silyl ether compound of difluoroalkene and isatin compound, the enol silyl ether used in the method is complex in preparation and expensive. ([1] Y. -L.Liu, J.Zhou, chem.Commun.2012,48,1919-1921.[2] J. -S.Yu, Y. -L.Liu, J.Tang, X.Wang, J.Zhou, Angew.chem.2014,36,9666-9670.[3] Y. -L.Liu, F. -M.Liao, Y. -F.Niu, X. -L.ZHao, J.Zhou, org.chem.Front.2014,1, 742-747.).
Therefore, there is a need to develop a new method for preparing polyfluoro-substituted phenylsulfonyl indolones in higher yield and under mild conditions.
Disclosure of Invention
The invention aims to provide a preparation method of a polyfluoro-substituted phenylsulfonyl indolone compound, which does not need any catalyst, needs cheap and easily-obtained raw materials, and has the advantages of simple synthesis method operation, short reaction time, higher product yield and good application prospect.
The purpose of the invention can be realized by the following technical scheme:
a preparation method of a polyfluoro-substituted phenylsulfonyl indolone compound is characterized in that under the condition of an organic solvent, phenylsulfonyl difluoroacetate is used as a starting material and reacts with 5-fluoro-1-methylindolyl red to prepare the polyfluoro-substituted phenylsulfonyl indolone compound.
Further, the chemical structural formula of the phenylsulfonyl difluoroacetate is as follows:
furthermore, the molar ratio of the phenylsulfonyl difluoroacetate to the 5-fluoro-1-methylindoline is 1.5: 1-3: 1.
Further, the molar ratio of the phenylsulfonyl difluoroacetate to the 5-fluoro-1-methylindoline is 3: 1.
Further, the reaction temperature is 20-60 ℃.
Further, the reaction time is 6-15 h.
Further, the reaction is carried out under the protection of inert gas. Further, the inert gas is nitrogen or argon.
Further, the organic solvent is any one or more of DMSO, DMF, NMP, toluene or THF.
Further, after the reaction is finished, the reaction product is separated and purified by column chromatography to obtain the target product.
The reaction formula of the invention is as follows:
the invention also limits the process conditions in the reaction process, such as the reaction temperature, the organic solvent, the inert gas protection environment, the addition amount of each raw material and the like. Specifically, if the reaction temperature is too low, the decarboxylation process is difficult to proceed, and if the reaction temperature is too high, other by-products are likely to be produced. The kind of organic solvent affects the solubility of the reaction substrate, and thus the reaction effect. The inert gas atmosphere and the amount of the raw materials added are not within the defined ranges, and the reaction yield is affected.
Compared with the prior art, the method does not need to add any inorganic base and catalyst, and prepares the polyfluoro-substituted phenyl sulfone indolone compounds with high yield through the decarboxylation addition reaction of the commercial isatin reagent and phenyl sulfone difluoroacetate prepared by the literature. The preparation process is direct, convenient and efficient, the required raw materials are cheap and easy to obtain, the synthesis method is simple to operate, the reaction time is short, the yield of the product is high, and the method has good application prospects in the fields of medicines, pesticides, fine chemical intermediates and the like.
Detailed Description
The present invention will be described in detail with reference to specific examples. The present embodiment is implemented on the premise of the technical solution of the present invention, and a detailed implementation manner and a specific operation process are given, but the scope of the present invention is not limited to the following embodiments.
In the following examples, 5-fluoro-1-methylisatoic acid was used in accordance with the methods described in the literature ([1] Du, Y.; Yu, A.; Jia, J.; Zhang, Y.; Meng, X.Chem.Commun.2017,53,1684.). For the preparation of the phenylsulfonyldifluoroacetate (potassium salt), the methods described in the literature ([2] Zhu, y. -j.; Lei, z. -l.; Huang, d. -k.; Lian, b.; Liu, z. -j.; Hu, x. -j.; Liu, j. -t. tetrahedron lett.2018,59,3184.) can be used.
The rest of the raw material reagents or processing techniques are conventional commercial products or conventional processing techniques in the field unless otherwise specified.
Example 1:
5-fluoro-1-methylindolyl erythrosine (35.8mg,0.2mmol), phenylsulfonyl difluoroacetate (164.4mg,0.6mmol), and DMSO (1 ml) were added to a reaction tube in one portion under nitrogen protection, and the mixture was stirred at room temperature and reacted for 8 hours. After the reaction is finished, the product is transferred into an egg-shaped bottle, rotary evaporation is carried out, and column chromatography is carried out to obtain 62.7mg of a product, wherein the yield is 84.5%.
Detecting the obtained product as
The hydrogen spectrum is as follows:
1H NMR(500MHz,DMSO)7.93-7.90(m,J＝15Hz,1H),7.79(s,1H),7.73-7.69(q,J＝20Hz,4H),7.42-7.39(t,J＝20Hz,1H),7.20-7.17(t,J＝15Hz,2H),3.24(s,3H).19F NMR(376MHz,DMSO)-108.56(d,J＝275.2Hz,1F),-109.48(d,J＝275.6Hz,1F).
comparative example 1:
compared with example 1, the reaction yield was 74.1% except that the amount of phenylsulfonyl difluoroacetate added was changed to 0.4 mmol.
Comparative example 2:
compared with example 1, the method is almost the same, except that the addition amount of the phenylsulfonyl difluoroacetate is changed to 0.2mmol, the reaction yield is 69.3 percent
Comparative example 3:
most of them were the same as in example 1, except that the reaction temperature was adjusted to 0 ℃ and no target product was produced.
Comparative example 4:
compared with example 1, most of them are the same except that the reaction temperature is adjusted to 80 ℃, and the reaction yield is reduced to 65.7%.
In the above examples, the organic solvent DMSO used was replaced by an equal volume of DMF, NMP, toluene or THF.
The embodiments described above are described to facilitate an understanding and use of the invention by those skilled in the art. It will be readily apparent to those skilled in the art that various modifications to these embodiments may be made, and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above embodiments, and those skilled in the art should make improvements and modifications within the scope of the present invention based on the disclosure of the present invention.
Claims (10)
1. A preparation method of a polyfluoro-substituted phenylsulfonyl indolone compound is characterized in that under the condition of an organic solvent, phenylsulfonyl difluoroacetate is used as a starting material and reacts with 5-fluoro-1-methylindolyl red to prepare the polyfluoro-substituted phenylsulfonyl indolone compound.
2. The method for preparing polyfluoro-substituted phenylsulfonyl indolones according to claim 1, wherein the chemical structural formula of the phenylsulfonyl difluoroacetates is as follows:
3. the preparation method of the polyfluoro-substituted phenylsulfonyl indolone compounds according to claim 1, wherein the molar ratio of phenylsulfonyl difluoroacetate to 5-fluoro-1-methylindolyl red is 1.5:1 to 3: 1.
4. The method for preparing a polyfluoro-substituted phenylsulfonyl indolone compound according to claim 1 or 3, wherein the molar ratio of phenylsulfonyl difluoroacetate to 5-fluoro-1-methylindolyl red is 3: 1.
5. The method for preparing polyfluoro-substituted phenylsulfonyl indolone compounds according to claim 1, wherein the reaction temperature is 20-60 ℃.
6. The preparation method of the polyfluoro-substituted phenylsulfonyl indolone compounds according to claim 1, wherein the reaction time is 6-15 hours.
7. The preparation method of the polyfluoro-substituted phenylsulfonyl indolone compounds according to claim 1, wherein the reaction is carried out under the protection of inert gas.
8. The method for preparing polyfluoro-substituted phenylsulfonyl indolones according to claim 7, wherein the inert gas is nitrogen or argon.
9. The method for preparing polyfluoro-substituted phenylsulfonyl indolone compounds according to claim 1, wherein the organic solvent is one or more of DMSO, DMF, NMP, toluene or THF.
10. The preparation method of the polyfluoro-substituted phenylsulfonyl indolone compounds according to claim 1, wherein the target product is obtained by separating and purifying the reaction product by column chromatography after the reaction is finished.
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