One-pot method for synthesizing 3-tetrasubstituted indolin-2-one compounds

Abstract

The present invention belongs to the field of organic chemical medicine, and relates to a method for synthesizing 3-tetrasubstituted indolin-2-one compounds by one-pot method. The present invention uses aniline derivatives, 3-diazoindolinone derivatives, and allyl carbonate derivatives as raw materials, rhodium salts, palladium salts, and phosphine ligands as catalysts, and then adds an appropriate amount of solvent, seals and fills with argon gas to react, stirs and reacts for a period of time near room temperature, and after the reaction is completed, the solvent is evaporated under reduced pressure, and the product is separated by silica gel column chromatography or recrystallization to obtain a target product; a three-component one-pot method is achieved to synthesize 3-tetrasubstituted indolin-2-one compounds. The advantages of this method are: easy to obtain raw materials, wide substrate adaptability, mild reaction conditions, simple operation, high efficiency, good atom economy, and more in line with the requirements of green chemistry.

Description

Technical Field

[0001] The invention belongs to the field of organic chemical medicine and relates to a method for synthesizing a 3-tetrasubstituted indolin-2-one compound through a three-component series reaction of an aniline derivative, a 3-diazoindolin-2-one derivative and an allyl carbonate catalyzed by a metal rhodium salt, a metal palladium salt and a phosphine ligand. Background Art

[0002] Indolinone compounds are common structures in natural products, drug molecules, and pesticide molecules. They have a wide range of biological activities, such as antibacterial, anticonvulsant, antitumor, antidepressant, and anti-HIV (Hu, W., et al. Org. Lett. 2019, 21, 9878; Banerjee, A., et al. Acc. Chem. Res. 2007, 40, 151).

[0003] In view of its special structure and application, its synthesis has attracted more and more attention. The traditional method for synthesizing indolinone mainly involves the oxidation of indole to synthesize indolinone (Schmid, W., et al. Monatsh. Chem. 2009, 140, 509). Due to the limitations of its substrate applicability, this method still has limitations. Another method is to synthesize indolinone compounds by reduction of indolequinone (Lin, W., et al. Tetrahedron Lett. 2014, 55, 2238). 3-Indolin-2-one introduces a quaternary carbon center of a spirocyclic structure (Hu, W., et al. Adv. Synth. Catal., 2017, 359, 58).

[0004] The present invention makes full use of the carbene precursor 3-diazoindolin-2-one derivative to form Rh carbene under the catalysis of Rh salt, inserts a CH bond into the para position of the aniline derivative, and then catalyzes the allylation with the third component raw material allyl carbonate through Pd and ligand synergistic relay. In this way, the three-component one-pot series reaction of the aniline derivative, the 3-diazoindolin-2-one derivative and the allyl carbonate is achieved through bimetallic relay catalysis to generate two types of active groups, p-aminophenyl and allyl, introduced at the 4 position of indolin-2-one at the same time, and a new quaternary carbon center is constructed. The raw materials are easy to obtain, the method is simple to operate, the atom economy is high, and it is environmentally friendly, which greatly enriches the synthesis methods and types of indolinone derivatives. Summary of the invention

[0005] The invention belongs to the field of organic chemical medicine and relates to a method for synthesizing 3-tetrasubstituted indolin-2-one compounds through a three-component series reaction of an aniline derivative, a 3-diazoindolin-2-one derivative and an allyl carbonate catalyzed by a metal rhodium salt, a metal palladium salt and a phosphine ligand.

[0006] The invention synthesizes 3-tetrasubstituted indolin-2-one compounds by a one-pot method. Firstly, a rhodium catalyst, a palladium catalyst and a phosphine ligand are added in the reaction. Then, an appropriate amount of solvent is added and, under the protection of argon, an aniline derivative, a 3-diazoindolin-2-one derivative and an allyl carbonate derivative are added. The reaction is stirred near room temperature for a certain time. After the reaction is completed, the solvent is evaporated under reduced pressure, and the target product is separated by column chromatography or mixed solvent recrystallization with silica gel adsorption. After the reaction, the product is purified by a column chromatography separation method, and a mixed solvent of petroleum ether and ethyl acetate is used as an eluent or an ethyl acetate / petroleum ether system is used as a recrystallization solvent to purify the product to obtain a pure 3-tetrasubstituted indolin-2-one compound.

[0007] The synthesis method of 3-tetrasubstituted indolin-2-one compound is:

[0008]

[0009] R 1 is benzyl, methyl, phenyl, p-toluenesulfonyl; R 2 is hydrogen, 4-bromo, 5-bromo, 5-methyl, 6-fluoro, 6-methoxy, 7-methyl; (R 3 )2 is dibenzyl, 1,4-butylidene, bis(2-methoxyethyl); R 4 is hydrogen, 3-methyl, 3-methoxy, 3-methoxycarbonyl, 2-methyl; R 5 It is hydrogen, phenyl, 4-methoxyphenyl, 4-chlorophenyl, 3-methylphenyl, 3-chlorophenyl, 2-methylphenyl, and piperon-4-yl.

[0010] Aniline derivatives have the following structure:

[0011]

[0012] 3-diazoindolin-2-one has the following structure:

[0013]

[0014] Allyl carbonate derivatives have the following structure:

[0015]

[0016] The rhodium catalysts used are Rh2(OAc)4, Rh2(PTTL)4, Rh2(Oct)4, Rh2(esp)2, Rh2(OPiv)4; the palladium catalysts are Pd(OAc)2, Pd(PhCN)2Cl2, Pd(TFA)2, Pd2(dba)3, Pd[(allyl)Cl]2; the phosphine ligands are Xantphos, XPhos, DavePhos, BINAP, SPhos, The equivalent ratio of [Rh]: [Pd]: [ligand]: aniline derivative is 1-2%: 1-5%: 3-12%.

[0017] The equivalent ratio of aniline derivative: 3-diazoindolin-2-one: allyl carbonate derivative is 1:1-2:1-2.

[0018] Firstly, a rhodium catalyst, a palladium catalyst and a phosphine ligand are added, and then an appropriate amount of solvent is added and protected by argon. Under the condition of argon, an aniline derivative, a 3-diazoindolone derivative and an allyl carbonate derivative are added, and the reaction is stirred at room temperature for 3-36 hours. After the reaction is completed, the solvent is evaporated under reduced pressure, and the product is purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether)=1 / 10] to obtain the product, or it can be purified by recrystallization using an ethyl acetate / petroleum ether system.

[0019] The reaction solvent is an organic solvent, and the specific organic solvent is one of toluene, xylene, acetonitrile, tetrahydrofuran, chloroform and dichloromethane.

[0020] Preferably, the rhodium catalyst is Rh2(PTTL)4; the palladium catalyst is Pd2(dba)3; the ligand is XPhos; the solvent is DCM; and the preferred molar ratio of Rh2(PTTL)4:Pd2(dba)3 and XPhos ligand is 1:2.5:6.

[0021] The concentration of the aniline derivative in the solvent is 0.05-0.2 mol / L.

[0022] The invention synthesizes 3-tetrasubstituted indolin-2-one compounds.

[0023] The present invention uses aniline derivatives, 3-diazoindolin-2-one derivatives, and allyl carbonate derivatives as raw materials, and introduces substituted p-aminophenyl and substituted allyl groups at three positions of indolin-2-one derivatives in a simple one-pot feeding method through bimetallic relay catalysis and screening of conditions, thereby constructing a new quaternary carbon center, thereby synthesizing a novel indolin-2-one derivative. The structures of all products are 1 H NMR, 13 The reaction was confirmed by C NMR, HRMS and melting point. The reaction was simple to feed and had a wide range of substrate adaptability.

[0024] Beneficial effects:

[0025] 1). The reaction raw materials are readily available, commercially available or easy to prepare.

[0026] 2). The reaction operation is relatively simple, and the intermediate product can be used for the next reaction without separation, and a three-component series reaction can be achieved.

[0027] 3). The reaction conditions are relatively mild and can be achieved at room temperature. The reaction time of most substrates is short and the efficiency is high.

[0028] 4). The atom economy is high, and the by-products are only nitrogen and substituted carbonates. It is environmentally friendly and more in line with the requirements of green chemistry.

[0029] 5) The substrate has wide adaptability and excellent yield. A new quaternary carbon center is constructed at the 3-position of the indolin-2-one derivative. Especially when a commercially available chiral phosphine ligand is used, it has moderate enantioselectivity and greatly enriches the structure of the indolin-2-one derivative. In addition, the p-aminophenyl and allyl groups introduced at the 3-position can be easily derivatized to obtain more abundant indolin-2-one derivatives, which is beneficial to provide a molecular library for subsequent efficient drug screening. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 The 4aaa obtained in Example 1 1 H-NMR (nuclear magnetic resonance spectroscopy);

[0031] Figure 2 The 4aaa obtained in Example 1 13 C-NMR (Nuclear Magnetic Carbon Spectroscopy);

[0032] Figure 3 This is the HRMS (high resolution mass spectrometry) of 4aaa obtained in Example 1. DETAILED DESCRIPTION

[0033] The present invention will be further described below in conjunction with embodiments, but is not limited thereto.

[0034] Example 1

[0035]

[0036] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd(OAc)2 2.2mg (0.01mmol), XantPhos 7mg (0.012mmol) and 2mL toluene to the reaction tube in sequence, then add aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL toluene. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain white solid 4aaa 86.5mg, yield 81%. mp121-123°C;1 H NMR (400MHz, CDCl3) δ7.32-7.29(m,4H),7.2-7.21(m,12H),7.16-7.12(m,3H),7.04-7.00(m,1H),6.70-6.65(m,3H),5.46-5.35(m,1H),5.0 7-5.03(m,1H),4.98(d,J=15.6Hz,1H),4.92-4.89(m,1H),4.75(d,J=15.6Hz,1H),4.66-4.57(m,4H),3.12-3.07(m,1H),3.01-2.96(m,1H). 13 C NMR (75MHz, CDCl3) δ178.8,148.4,143.0,138.6,136.0,133.0,132.2,128.7,128.7,127.9,127.9,127.5,1 27.5,127.4,127.0,126.7,125.1,122.4,119.1,112.4,109.2,55.8,54.3,43.9,41.9.HRMS(ESI)m / z:[M+H] + Calcdfor C 38 H 35 N2O 535.2744; Found 535.2742.

[0037] Example 2

[0038] Add catalyst Rh2(Oct)4 2.3mg (0.002mmol), Pd(OAc)2 2.2mg (0.01mmol), XantPhos 7mg (0.012mmol) and 2mL toluene to the reaction tube in sequence, then add aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL toluene. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 80.1mg of white solid 4aaa, with a yield of 75%.

[0039] Example 3

[0040] Add catalyst Rh2(Opiv)4 2.3mg (0.002mmol), Pd(OAc)2 2.2mg (0.01mmol), XantPhos 7mg (0.012mmol) and 2mL toluene to the reaction tube in sequence, then add aniline derivative 1a54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL toluene. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 4aaa 76.9mg of white solid, with a yield of 72%.

[0041] Example 4

[0042] Add catalyst Rh2(esp)2 1.5mg (0.002mmol), Pd(OAc)2 2.2mg (0.01mmol), XantPhos 7mg (0.012mmol) and 2mL toluene to the reaction tube in sequence, then add aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL toluene. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 4aaa 66.2mg of white solid, with a yield of 62%.

[0043] Example 5

[0044] Add catalyst Rh2(OAc)4 0.88mg (0.002mmol), Pd(OAc)2 2.2mg (0.01mmol), XantPhos 7mg (0.012mmol) and 2mL toluene to the reaction tube in sequence, then add aniline derivative 1a54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL toluene. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 4aaa 60.8mg of white solid, with a yield of 57%.

[0045] Example 6

[0046] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd(PhCN)2Cl2 2.2mg (0.01mmol), XantPhos 7mg (0.012mmol) and 2mL toluene to the reaction tube in sequence, then add aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL toluene. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 42.7mg of white solid 4aaa, with a yield of 40%.

[0047] Example 7

[0048] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd(TFA)2 2.2mg (0.01mmol), XantPhos 7mg (0.012mmol) and 2mL toluene to the reaction tube in sequence, then add aniline derivative 1a54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL toluene. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 46.0mg of white solid 4aaa, with a yield of 43%.

[0049] Example 8

[0050] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XantPhos 7mg (0.012mmol) and 2mL toluene to the reaction tube in sequence, then add aniline derivative 1a54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL toluene. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 89.7mg of white solid 4aaa, with a yield of 84%.

[0051] Example 9

[0052] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), [Pd(allyl)Cl] 22.3mg (0.01mmol), XantPhos 7mg (0.012mmol) and 2mL toluene to the reaction tube in sequence, then add aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL toluene. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 4aaa 71.6mg of white solid, with a yield of 67%.

[0053] Example 10

[0054] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) and 2mL toluene to the reaction tube in sequence, then add aniline derivative 1a54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL toluene. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 89.7mg of white solid 4aaa, with a yield of 84%.

[0055] Embodiment 11

[0056] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), DavePhos 5.6mg (0.012mmol) and 2mL toluene to the reaction tube in sequence, then add aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL toluene. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 4aaa 78.0mg of white solid, with a yield of 73%.

[0057] Example 12

[0058] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), BINAP 5.6mg (0.012mmol) and 2mL toluene to the reaction tube in sequence, then add aniline derivative 1a54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL toluene. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 4aaa 64.1mg of white solid, with a yield of 60%.

[0059] Embodiment 13

[0060] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), SPhos 5.6mg (0.012mmol) and 2mL toluene to the reaction tube in sequence, then add aniline derivative 1a54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL toluene. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 83.3mg of white solid 4aaa, with a yield of 78%.

[0061] Embodiment 14

[0062] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 4aaa 102.6mg of white solid, with a yield of 96%.

[0063] Example 14-1

[0064] Amplification reaction: Add catalyst Rh2(PTTL)4 2.5mg (0.02mmol), Pd2(dba)3 46mg (0.05mmol), XPhos 56mg (0.12mmol) 20mL DCM to a 100mL reaction tube, then add aniline derivative 1a 0.55g (2mmol), 3-diazoindolinone derivative 2a 0.80g (3.2mmol), allyl carbonate derivative 3a 0.63g (4mmol) and 20mL DCM. Seal and fill with argon to react. The reaction was reacted at 30°C for 3h, filtered with diatomaceous earth, washed with ethyl acetate, and the mother liquor was collected and the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 4aaa 1.01g of white solid, with a yield of 96%. Alternatively, the product was first filtered through diatomaceous earth, washed with ethyl acetate, the mother liquor was collected and the solvent was evaporated under reduced pressure, and recrystallized using petroleum ether / ethyl acetate (4 / 1) to obtain 0.908 g of the product with a yield of 85%.

[0065] Embodiment 15

[0066] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) and 2mL xylene to the reaction tube in sequence, then add aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL xylene. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 97.2mg of white solid 4aaa, with a yield of 91%.

[0067] Example 16

[0068] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) and 2mL tetrahydrofuran to the reaction tube in sequence, then add aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL tetrahydrofuran. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 4aaa32.0mg of white solid, with a yield of 30%.

[0069] Embodiment 17

[0070] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) and 2mL acetonitrile to the reaction tube in sequence, then add aniline derivative 1a54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL acetonitrile. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 4aaa 56.6mg of white solid, with a yield of 53%.

[0071] Embodiment 18

[0072] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) and 2mL chloroform in the reaction tube, then add aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL chloroform. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 4aaa37.4mg of white solid, with a yield of 35%.

[0073] Embodiment 19

[0074] Catalyst Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) and 2mL DCM were added to the reaction tube in sequence, and then aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM were added. The reaction was sealed and filled with argon. The reaction was carried out at 30°C for 3h, and no product was obtained.

[0075] Embodiment 20

[0076] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), XPhos 5.6mg (0.012mmol) and 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h, and no product was obtained.

[0077] Embodiment 21

[0078] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h, and no product was obtained.

[0079] Embodiment 22

[0080] Add catalyst Rh2(PTTL)4 1.2mg (0.001mmol), Pd2(dba)3 4.6mg (0.0025mmol), XPhos 5.6mg (0.006mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 6h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 4aaa 96.1mg of white solid, with a yield of 90%.

[0081] Embodiment 23

[0082] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a54.6mg (0.2mmol), 3-diazoindolinone derivative 2a 59.8mg (0.24mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 4aaa 96.1mg of white solid, with a yield of 90%.

[0083] Embodiment 24

[0084] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 1mL DCM to the reaction tube in sequence, then add aniline derivative 1a54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 1mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 4aaa 98.3mg of white solid, with a yield of 92%.

[0085] Embodiment 25

[0086] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a54.6mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 25°C for 5h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 4aaa 97.2mg of white solid, with a yield of 91%.

[0087] Embodiment 26

[0088]

[0089] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2b 55.4mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 80.7mg of light yellow oil 4aba, with a yield of 88%; 1 H NMR (400MHz, CDCl3) δ7.30-7.19(m,12H),7.15-7.12(m,2H),7.07-7.03(m,1H),6.83-6.81(m,1H),6.64-6.62(m, 1H),5.43-5.32(m,1H),5.00-4.97(m,1H),4.89-4.86(m,1H),4.63-4.54(m,4H),3.14(s,3H),2.99-2.92(m,2H). 13C NMR (100MHz, CDCl3) δ178.6,148.3,143.9,138.6,132.9,132.1,128.7,128.0,127.9,127.3,1 27.0,126.7,125.2,122.3,118.9,112.4,108.1,55.7,54.3,42.0,26.3.HRMS(ESI)m / z:[M+H] + Calcd for C 32 H 31 N2O 459.2431; Found 459.2432.

[0090] Embodiment 27

[0091]

[0092] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2c 75.2mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain light yellow oil 4aca 89.5mg, yield 86%; 1 H NMR (400MHz, CDCl3) δ7.48-7.44(m,2H),7.36-7.27(m,8H),7.25-7.17(m,9H),7.10-7.07(m,1H),6.82-6.80(m,1H),6.68-6. 66(m,2H),5.52-5.42(m,1H),5.10-5.06(m,1H),4.98-4.95(m,1H),δ4.66-4.57(m,4H),3.16-3.10(m,1H),3.02-2.97(m,1H). 13C NMR (100MHz, CDCl3) δ178.1,148.4,143.9,138.6,134.8,132.8,132.0,129.,128.7,128.0,127.9,127.9 ,127.4,127.0,126.8,126.7,125.4,122.8,119.2,112.4,109.4,55.8,54.3,42.4.HRMS(ESI)m / z:[M+H] + Calcd for C 37 H 33 N2O 521.2587; Found 521.2587.

[0093] Embodiment 28

[0094]

[0095] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2d 100.0mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain light yellow oil 4ada 83.5mg, yield 70%; 1 H NMR (400MHz, CDCl3) δ7.97-7.95(m,1H),7.91-7.89(m,2H),7.32-7.15(m,15H),6.92-6.90(m,2H),6.57-6.55(m,2H),4.98 -4.88(m,1H),4.73-4.69(m,1H),4.64-4.55(m,4H),4.50-4.47(m,1H),3.00-2.95(m,1H),2.77-2.72(m,1H),2.35(s,3H). 13C NMR (100MHz, CDCl3) δ177.0,148.7,145.5,139.3,138.4,135.4,131.6,131.2,129.6,128.8,128.7,128.1,1 27.8,127.1,126.6,126.3,125.4,124.9,119.5,113.8,112.4,56.2,54.3,42.2,21.8.HRMS(ESI)m / z:[M+H] + Calcd for C 38 H 35 N2O3S 599.2363; Found 599.2358.

[0096] Embodiment 29

[0097]

[0098] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2e 105.0mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain a light yellow oil 4aea 100.4mg, with a yield of 82%; 1 H NMR (400MHz, CDCl3) δ7.30-7.27(m,4H),7.23-7.18(m,11H),7.12-7.10(m,1H),7.01-6.96(m,3H),6.67-6.61(m,3H),5.39-5.29(m,1H),5. 18-5.13(m,1H),4.95(d,J=15.6Hz,1H),4.89-4.86(m,1H),4.71(d,J= 15.6Hz,1H),4.64-4.55(m,4H),3.50-3.45(m,1H),3.30-3.25(m,1H). 13C NMR (100MHz, CDCl3) δ178.2,148.6,145.3,138.6,135.6,132.6,130.7,129.6,128.7,128.7,127.7,127.7,1 27.4,127.0,126.8,126.8,125.5,120.4,119.1,112.5,108.1,58.1,54.2,44.1,37.5.HRMS(ESI)m / z:[M+H] + Calcd for C 38 H 34 BrN2O613.1849; Found 613.1847.

[0099] Embodiment 30

[0100]

[0101] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2f 105.0mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain light yellow oil 4afa 110.2mg, yield 90%; 1 H NMR (400MHz, CDCl3) δ7.33-7.29(m,5H),7.26-7.21(m,12H),7.12-7.10(m,2H),6.78-6.66(m,2H),6.56-6.53(m,1H),5.45-5 .34(m,1H),5.09-5.05(m,1H),4.97-4.93(m,2H),4.75-4.70(m,1H),4.67-4.58(m,4H),3.10-3.05(m,1H),2.98-2.93(m,1H). 13C NMR (100MHz, CDCl3) δ178.2,148.6,142.1,138.5,135.6,134.6,132.4,130.8,128.8,128.8,128.1,127.8,1 27.7,127.4,127.0,126.8,126.7,119.7,115.3,112.5,110.7,56.0,54.3,44.0,41.7.HRMS(ESI)m / z:[M+H] + Calcd for C 38 H 34 BrN2O613.1849; Found 613.1846.

[0102] Embodiment 31

[0103]

[0104] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2g 84.2mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain white solid 4aga 93.2mg, yield 85%, mp: 148-150°C; 1 H NMR (300MHz, CDCl3) δ7.32-7.14(m,17H),7.03(s,1H),6.94-6.91(m,1H),6.67-6.64(m,2H),6.58-6.55(m,1H),5.47-5.34(m,1H) ),5.10-5.04(m,1H),4.98-4.89(m,2H),4.75-4.70(m,1H),4.66-4.55(m,4H),3.13-3.06(m,1H),3.00-2.93(m,1H),2.27(s,3H). 13C NMR (75MHz, CDCl3) δ178.7,148.4,140.6,138.6,136.2,133.1,132.4,131.9,128.7,128.7,128.2,127.9,127. 8,127.5,127.4,127.0,126.7,125.8,119.1,112.4,109.0,55.9,54.3,43.9,41.8,21.3.HRMS(ESI)m / z:[M+H] + Calcd for C 39 H 37 N2O549.2900; Found 549.2898.

[0105] Embodiment 32

[0106]

[0107] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2h 85.5mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain light yellow oil 4aha 103.8mg, yield 94%; 1 H NMR (400MHz, CDCl3) δ7.31-7.20(m,15H),7.15-7.12(m,3H),6.71-6.65(m,3H),6.44-6.41(m,1H),5.45-5.34(m,1H ),5.02-5.02(m,1H),4.96-4.90(m,2H),4.72-4.68(m,1H),4.65-4.56(m,4H),3.09-3.04(m,1H),2.98-2.93(m,1H). 13C NMR (100MHz, CDCl3) δ179.0,162.7(d,J=243.1Hz),148.5,144.5(d,J=11.3Hz),138.5,135.5,132.7,128.8,128.7,127.8,127.7,127.5(d, J=2.9Hz),127.4,127.2,127.0,126.7,126.1(d,J=9.5Hz),119.4,112.5,108.6(d,J=22.0Hz),98.0(d,J=27.2Hz),55.4,54.3,44.1,42.0. 19 F NMR(282MHz,CDCl3)δ-112.3.HRMS(ESI)m / z:[M+H] + Calcd for C 38 H 34 FN2O553.2650;Found 553.2648.

[0108] Embodiment 33

[0109]

[0110] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2i 89.4mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain light yellow oil 4aia 103.8mg, yield 92%; 1H NMR (400MHz, CDCl3) δ7.31-7.27(m,4H),7.24-7.18(m,11H),7.17-7.15(m, 2H),7.12-7.10(m,1H),6.66-6.64(m,2H),6.53-6.51(m,1H),6.29-6.29(m, 1H),5.47-5.37(m,1H),5.07-5.03(m,1H),4.96-4.89(m,2H),4.72-4.68(m ,1H),4.64-4.56(m,4H),3.68(s,3H),3.08-3.03(m,1H),2.98-2.98(m,1H). 13 C NMR (100MHz, CDCl3) δ179.3,159.8,148.4,144.3,138.6,136.1,133.2,128.7,127.9,127.6,127.5,127 .0,126.7,125.7,124.1,119.1,112.4,106.2,97.3,55.4,55.3,54.3,44.0,42.2.HRMS(ESI)m / z:[M+H] + Calcd for C 39 H 37 N2O2 565.2850; Found 565.2849.

[0111] Embodiment 34

[0112]

[0113] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a 54.6mg (0.2mmol), 3-diazoindolone derivative 2j 84.2mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain light yellow oil 4aja 102.0mg, yield 93%; 1H NMR (400MHz, CDCl3) δ7.30-7.26(m,4H),7.23-7.14(m,11H),7.11-7.08(m,3H),6.96-6.89(m,2H),6.66-6.64(m,2H),5.53-5.42(m, 1H),5.19-5.15(m,1H),5.09-5.05(m,2H),4.97-4.94(m,1H),4.64-4.55(m,4H),3.17-3.11(m,1H),3.00-2.94(m,1H),2.23(s,3H). 13 C NMR (100MHz, CDCl3) δ179.7,148.3,141.2,138.6,138.0,133.3,132.9,131.9,128.7,128.7,128.1,127.9,127 .0,127.0,126.7,125.9,123.2,122.5,119.7,119.1,112.4,55.1,54.3,45.1,42.1,19.0.HRMS(ESI)m / z:[M+H] + Calcd for C 39 H 37 N2O 549.2900; Found 549.2898.

[0114] Embodiment 35

[0115]

[0116] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1b 29.4mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 4baa 62.1mg of light yellow oil, with a yield of 76%; 1H NMR (400MHz, CDCl3) δ7.27-7.21(m,8H),7.18-7.14(m,1H),7.06-7.02(m,1H),6.73-6.71(m,1H),6.52-6.50(m,2H),5.49-5.39(m,1H) ),5.19-5.05(m,1H),4.97-4.91(m,2H),4.83-4.79(m,1H),3.26-3.22(m,4H),3.13-3.07(m,1H),3.04-3.0(m,1H),1.97-1.94(m,4H). 13 C NMR (100MHz, CDCl3) δ178.8,147.2,143.1,136.2,133.1,132.5,128.7,127.9,127.5,127 .4,125.2,122.4,119.1,111.8,109.2,55.8,47.7,43.9,42.0,25.6.HRMS(ESI)m / z:[M+H] + Calcd for C 28 H 29 N2O 409.2274; Found 409.2273.

[0117] Embodiment 36

[0118]

[0119] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1c 36.2mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain light yellow oil 4caa 89.4mg, yield 95%; 1H NMR (400MHz, CDCl3) δ7.29-7.14(m,9H),7.06-7.02(m,1H),6.73-6.73(m,1H),6.65-6.63(m,2H),5.48-5.38(m,1H),5.09-5.05(m,1H), 4.97(d,J=15.6Hz,1H),4.94-4.91(m,1H),4.79(d,J=15.6Hz,1H),3.53-3.51(m,8H),3.33(s,6H),3.13-3.08(m,1H),3.03-2.98(m,1H). 13 C NMR (100MHz, CDCl3) δ178.7,147.0,143.1,136.1,133.0,132.3,128.7,128.0,127.9,127.5,127.4, 126.8,125.2,122.4,119.2,111.7,109.2,70.1,59.1,55.7,50.9,43.9,42.0.HRMS(ESI)m / z:[M+H] + Calcd for C 30 H 35 N2O3471.2642;Found471.2643.

[0120] Embodiment 37

[0121]

[0122] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1d 57.4mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 4daa 98.7mg of light yellow oil, with a yield of 90%; 1H NMR (400MHz, CDCl3) δ7.43-7.40(m,3H),7.31-7.29(m,6H),7.25-7.21(m,7H),7.15-7. 1(m,1H),6.96-6.91(m,2H),6.78-6.76(m,1H),6.62-6.59(m,1H),6.44-6.43(m,1H),5 .38-5.28(m,1H),5.08(d,J=15.2Hz,1H),5.02-4.98(m,1H),4.88-4.86(m,1H),4.74(d ,J=15.2Hz,1H),4.63-4.54(m,4H),3.08-3.03(m,1H),3.00-2.96(m,1H),1.49(s,3H). 13 C NMR (100MHz, CDCl3) δ179.1,148.6,143.2,138.7,138.0,136.2,133.5,132.3,128.7,128.7,128.5,128.2,127.7,127 .6,127.0,126.8,126.0,123.6,122.8,119.4,115.8,109.6,108.7,55.6,53.9,44.4,42.9,20.4.HRMS(ESI)m / z:[M+H] + Calcd for C 39 H 37 N2O549.2900; Found 549.2899.

[0123] Embodiment 38

[0124]

[0125] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1e 60.7mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon for reaction. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain light yellow oil 4eaa 82.4mg, yield 73%; 1H NMR (400MHz, CDCl3) δ7.44-7.42(m,2H),7.34-7.27(m,7H),7.24-7.20(m,7H),7.08-7.04(m,1H),6.91-6.85(m,2H),6.70-6.68(m,1H),6.39 -6.36(m,1H),6.12-6.11(m,1H),5.41-5.31(m,1H),5.03-4.94(m,2H) ,4.90-4.84(m,2H),4.64-4.55(m,4H),3.02(s,3H),2.97-2.96(m,2H). 13 C NMR (100MHz, CDCl3) δ179.8,158.1,150.0,143.5,138.7,136.8,134.2,132.4,128.7,128.5,128.1,128.1,127.4,127 .1,127.0,126.7,122.7,122.0,119.1,117.7,108.1,104.7,97.7,55.4,54.5,53.3,44.1,41.0.HRMS(ESI)m / z:[M+H] + Calcd for C 39 H 37 N2O2 565.2850; Found 565.2848.

[0126] Embodiment 39

[0127]

[0128] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1f 66.3mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain light yellow oil 4faa 82.9mg, yield 70%; 1H NMR (400MHz, CDCl3) δ7.61-7.59(m,1H),7.44-7.42(m,2H),7.34-7.20(m,14H),7.14-7.10(m,1H),6.98-6.92(m,2H),6.86-6.80(m,2H) ),6.73-6.71(m,1H),5.43-5.32(m,1H),5.26-5.23(m,1H),4.99-4.95(m,1H),4.90-4.87(m,1H),4.69-4.55(m,5H),3.00-2.90(m,5H). 13 C NMR (100MHz, CDCl3) δ179.6,169.8,148.1,144.1,137.9,136.6,134.2,133.0,132.3,130.5,128.9,128.6,128.0,127.9, 127.5,127.2,126.8,124.0,123.9,122.1,119.5,114.1,112.7,108.6,55.0,53.7,51.8,44.7,43.6.HRMS(ESI)m / z:[M+H] + Calcd for C 40 H 37 N2O3 593.2799; Found 593.2796.

[0129] Embodiment 40

[0130]

[0131] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1g 57.4mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 3h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain 4gaa 62.5mg of light yellow oil, with a yield of 57%; 1H NMR (400MHz, CDCl3) δ7.28-7.15(m,18H),7.06-6.01(m,2H),6.87-6.85(m,1H),6.74-6.72(m,1H),5.43-5.33(m,1H),5.08-5.04(m,1H), 4.96(d,J=15.8Hz,1H),4.93-4.90(m,1H),4.82(d,J=15.8Hz,1H),4.07-3.99(m,4H),3.13-3.08(m,1H),3.03-2.98(m,1H),2.42(s,3H). 13 C NMR (100MHz, CDCl3) δ178.5,149.4,143.0,138.6,136.1,134.4,133.6,132.8,132.1,129.8,128.8,128.7,128.3,128 .0,127.6,127.5,127.0,125.3,124.7,122.5,122.1,119.3,109.3,56.7,56.1,44.0,42.1,19.1.HRMS(ESI)m / z:[M+H] + Calcd for C 39 H 37 N2O 549.2900; Found 549.2898.

[0132] Embodiment 41

[0133]

[0134] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a 57.4mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3b 76.8mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 24h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain light red oil 4aab 100.4mg, yield 82%; 1H NMR (400MHz, CDCl3) δ7.32-7.01(m,23H),6.91-6.88(m,2H),6.68-6.60(m,3H),6.45-6.41(m,1H),5.80-5.72( m,1H),5.13(d,J=15.8Hz,1H),4.66-4.57(m,4H),4.52(d,J=15.8Hz,1H),3.32-3.27(m,1H),3.15-3.10(m,1H). 13 C NMR (100MHz, CDCl3) δ178.7,148.5,143.0,138.6,137.2,135.7,134.2,132.1,128.8,128.7,128.5,128.1,127.9,127. 7,127.3,127.1,127.0,126.7,126.4,125.1,124.5,122.5,112.5,109.5,56.3,54.3,44.0,41.4.HRMS(ESI)m / z:[M+H] + Calcd for C 44 H 39 N2O 611.3057; Found 611.3057.

[0135] Embodiment 42

[0136]

[0137] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a 57.4mg (0.2mmol), 3-diazoindolinone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3c 88.8mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 24h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain light red oil 4aac 112.7mg, yield 88%; 1H NMR(400MHz, CDCl3)δ7.33-7.19(m,13H),7.14-7.08(m,4H),7.05-7.01(m,3H ),6.96-6.92(m,2H),6.76-6.74(m,2H),6.69-6.66(m,2H),6.63-6.60(m,1H), 6.40-6.36(m,1H),5.66-5.57(m,1H),5.13(d,J=15.8Hz,1H),4.67-4.58(m,4 H), 4.54 (d, J = 15.8Hz, 1H), 3.76 (s, 3H), 3.30-3.24 (m, 1H), 3.14-3.08 (m, 1H). 13 C NMR (100MHz, CDCl3) δ178.7,159.0,148.5,143.1,138.6,135.8,133.6,132.2,130.1,128.8,128.7,128.0,128.0,127.7,127 .5,127.3,127.1,127.0,126.7,125.1,122.5,122.2,113.9,112.5,109.4,56.4,55.4,54.3,44.0,41.5.HRMS(ESI)m / z:[M+H] + Calcd for C 45 H 41 N2O2641.3163;Found641.3163.

[0138] Embodiment 43

[0139]

[0140] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a 57.4mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3d 90.4mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 24h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain light red oil 4aad 92.8mg, yield 72%; 1H NMR (400MHz, CDCl3) δ7.32-6.92(m,24H),6.69-6.63(m,3H),6.38-6.34(m,1H),5.75-5 .67(m,1H),5.13-5.09(m,1H),4.66-4.51(m,5H),3.31-3.25(m,1H),3.12-3.07(m,1H). 13 C NMR (100MHz, CDCl3) δ178.6,148.5,143.0,138.5,135.7,135.7,132.9,132.8,132.0,128.7,128.7,128.6,128.1,127.9,1 27.5,127.5,127.4,127.2,127.0,126.7,125.2,125.1,122.5,112.5,109.4,56.2,54.3,44.0,41.3.HRMS(ESI)m / z:[M+H] + Calcdfor C 44 H 38 ClN2O 645.2667; Found 645.2665.

[0141] Embodiment 44

[0142]

[0143] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a 57.4mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3e 82.4mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 24h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain a white solid 4aae 108.8mg, yield 87%, mp: 113-114°C; 1H NMR (400MHz, CDCl3) δ7.32-7.18(m,13H),7.13-6.97(m,7H),6.94-6.89(m,4H),6.90-6.66(m,2H),6.63-6.60(m,1H),6.4 3-6.38(m,1H),5.81-5.72(m,1H),5.1-5.10(m,1H),4.66-4.52(m,5H),3.32-3.25(m,1H),3.16-3.09(m,1H),2.24(s,3H). 13 CNMR (100MHz, CDCl3) δ178.7,148.5,143.0,138.6,138.0,137.1,135.7,134.4,132.1,128.7,128.7,128.4,128.1,128.0,127.9,127 .7,127.3,127.2,127.1,127.0,126.7,125.1,124.2,123.4,122.5,112.5,109.4,56.3,54.3,43.9,41.4,21.4.HRMS(ESI)m / z:[M+H] + Calcd for C 45 H 41 N2O 625.3213; Found 625.3213.

[0144] Embodiment 45

[0145]

[0146] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a 57.4mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3f 90.4mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 24h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain white solid 4aaf 96.6mg, yield 75%, mp: 139-140°C; 1H NMR (400MHz, CDCl3) δ7.33-7.18(m,13H),7.16-7.02(m,8H),6.98-6.93(m,3H),6.69-6.64(m,3H),6.37-6.33(m,1H),5. 81-5.73(m,1H),5.12(d,J=15.8Hz,1H),4.67-4.58(m,4H),4.55(d,J=15.8Hz,1H),3.31-3.25(m,1H),3.14-3.09(m,1H). 13 CNMR (100MHz, CDCl3) δ178.5,148.5,143.0,139.0,138.6,135.7,134.4,133.0,131.9,129.7,128.8,128.7,128.2,127.9,127 .5,127.3,127.1,127.0,126.7,126.2,126.2,125.1,124.6,122.6,112.5,109.5,56.1,54.3,44.0,41.3.HRMS(ESI)m / z:[M+H] + Calcdfor C 44 H 38 ClN2O 645.2667; Found 645.2667.

[0147] Embodiment 46

[0148]

[0149] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a 57.4mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3g 82.4mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 24h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain a light red solid 4aag 88.7mg, yield 71%, mp: 145-146°C; 1H NMR (400MHz, CDCl3) δ7.34-7.20(m,13H),7.14-7.0(m,9H),6.92-6.8(m,2H),6.69-6.67(m,2H),6.63-6.61(m,1H),6.57 -6.53(m,1H),5.72-5.65(m,1H),5.12-5.08(m,1H),4.67-4.5(m,5H),3.32-3.27(m,1H),3.16-3.10(m,1H),2.07(s,3H). 13 CNMR (100MHz, CDCl3) δ178.7,148.5,143.1,138.6,136.5,135.7,135.5,132.6,132.2,130.2,128.8,128.7,128.1,128.0,127.6, 127.3,127.2,127.0,126.8,126.0,125.9,125.9,125.2,122.5,112.5,109.5,56.4,54.4,43.9,41.7,19.7.HRMS(ESI)m / z:[M+H] + Calcd for C 45 H 41 N2O 625.3213; Found 625.3213.

[0150] Embodiment 47

[0151]

[0152] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add aniline derivative 1a 57.4mg (0.2mmol), 3-diazoindolone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3h 94.4mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 24h. After the reaction was completed, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 10] to obtain light yellow oil 4aah 113.8mg, yield 87%; 1H NMR (400MHz, CDCl3) δ7.33-7.29(m,4H),7.27-7.18(m,9H),7.15-7.10(m,4H),7.05-6.98(m,3H),6.68-6.62(m,4H),6.60-6.55(m, 2H),6.34-6.30(m,1H),5.89(s,2H),5.61-5.54(m,1H),5.13-5.09(m,1H),4.67-4.54(m,5H),3.27-3.22(m,1H),3.12-3.07(m,1H). 13 C NMR (100MHz, CDCl3) δ178.7,148.5,147.9,147.0,143.0,138.6,135.8,133.7,132.1,131.8,128.8,128.7,128.1,127.9,127.6,127. 4,127.2,127.0,126.7,125.1,122.7,122.5,121.0,112.5,109.4,108.3,105.7,101.0,56.3,54.3,44.0,41.3.HRMS(ESI)m / z:[M+H] + Calcd for C 45 H 39 N2O3 655.2955; Found 655.2954.

[0153] Embodiment 48

[0154]

[0155] The catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), (R,R)-L 8.2mg (0.012mmol) were added to the reaction tube in sequence. MS (100 mg), Cs2CO3 (130 mg, 0.4 mmol) 2 mL DCE, then add aniline derivative 1a 57.4 mg (0.2 mmol), 3-diazoindolone derivative 2b 55.4 mg (0.32 mmol), allyl carbonate derivative 3b 76.8 mg (0.4 mmol) and 2 mL DCM. Seal and fill with argon to react. The reaction was carried out at 30 ° C for 3 h. After the reaction, the solvent was evaporated under reduced pressure. The product was purified by silica gel column chromatography [eluent: V (ethyl acetate) / V (petroleum ether) = 1 / 7] to obtain a white solid 4abb 61.2 mg, with a yield of 57% and an enantioselectivity of 68% ee; 1H NMR (400MHz, CDCl3) δ7.31-7.03(m,20H),6.81-6.79(m,1H),6.67-6.64(m,2H ),6.34-6.30(m,1H),5.81-5.74(m,1H),4.65-4.56(m,4H),3.15-3.03(m,5H). 13 C NMR (100 MHz, CDCl3) δ 178.6, 148.4, 143.9, 138.6, 137.4, 133.8, 128.7, 128.5, 128.1, 128.0, 127.2, 127.2, 127.0, 126.7, 126.2, 125.4, 124.6, 122.4, 112.4, 108.2, 56.1, 54.3, 41.3, 26.4. HPLC (IA, i-PrOH / n-hexane=30 / 70, flow rate=1.0 mL / min, I=215 nm) t R =8.69min(major),12.02min(minor),68%ee.[α] D 25 :59.4°(c:0.1,CHCl3).

[0156] Comparative Example 1

[0157] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add N,N-dibenzyl-2-chloroaniline 61.4mg (0.2mmol), 3-diazoindolinone derivative 2a 79.7mg (0.32mmol), allyl carbonate derivative 3a 63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 24h, and one equivalent of N,N-dibenzyl-2-chloroaniline was converted by 30%, and the yield of the target product was less than 5%.

[0158] Comparative Example 2

[0159] Add catalyst Rh2(PTTL)4 2.5mg (0.002mmol), Pd2(dba)3 4.6mg (0.005mmol), XPhos 5.6mg (0.012mmol) 2mL DCM to the reaction tube in sequence, then add N,N-dibenzylaniline 54.6mg (0.2mmol), 1-benzyl-3-diazo-7-nitroindol-2-one 94.2mg (0.32mmol), allyl carbonate derivative 3a63.2mg (0.4mmol) and 2mL DCM. Seal and fill with argon to react. The reaction was carried out at 30°C for 24h, and one equivalent of N,N-dibenzyl-2-chloroaniline was converted by 40%, and the yield of the target product was less than 20%.

Claims

1. A one-pot method for synthesizing 3-tetrasubstituted indolin-2-one compounds, characterized in that: A method for the difunctionalization of 3-diazoindolin-2-one derivatives by Rh / Pd dual catalysis with aniline derivatives and allyl carbonates; The specific reactions are: The reaction firstly adds a rhodium catalyst, a palladium catalyst and a phosphine ligand, then adds a solvent and under the protection of argon, adds an aniline derivative, a 3-diazoindolin-2-one derivative and an allyl carbonate derivative, and reacts at a reaction temperature of 20-35° C. to obtain a target product; ； Among them, R 1 is benzyl, methyl, phenyl, p-toluenesulfonyl; R 2 is hydrogen, 4-bromo, 5-bromo, 5-methyl, 6-fluoro, 6-methoxy, 7-methyl; (R 3 ) 2 is dibenzyl, 1,4-butylidene, bis(2-methoxyethyl); R 4 is hydrogen, 3-methyl, 3-methoxy, 3-methoxycarbonyl, 2-methyl; R 5 is hydrogen, phenyl, 4-methoxyphenyl, 4-chlorophenyl, 3-methylphenyl, 3-chlorophenyl, 2-methylphenyl, or piperonyl; R 6 Is -OBoc group or -OCO2Me group; The rhodium catalyst is Rh2(OAc)4, Rh2(PTTL)4, Rh2(Oct)4, Rh2(esp)2 or Rh2(OPiv)4; the palladium catalyst is Pd(OAc)2, Pd(PhCN)2Cl2, Pd(TFA)2, Pd2(dba)3 or Pd[(allyl)Cl]2; the phosphine ligand is Xantphos, XPhos, DavePhos, BINAP, SPhos or .

2. The method for synthesizing 3-tetrasubstituted indolin-2-one compounds in one pot according to claim 1, characterized in that: The aniline derivative is one of the following structural formulas: 。 3. The one-pot method for synthesizing 3-tetrasubstituted indolin-2-one compounds according to claim 1, characterized in that: The 3-diazoindolin-2-one derivative is one of the following structural formulas: 。 4. The one-pot method for synthesizing 3-tetrasubstituted indolin-2-one compounds according to claim 1, characterized in that: The allyl carbonate derivative is one of the following structural formulas: 。 5. The one-pot method for synthesizing 3-tetrasubstituted indolin-2-one compounds according to claim 1, characterized in that: The amount of the diazo compound used is 1 to 2 equivalents of the amount of the aniline derivative used, and the amount of the allyl carbonate derivative used is 1 to 2 equivalents of the amount of the aniline derivative used.

6. The one-pot method for synthesizing 3-tetrasubstituted indolin-2-one compounds according to claim 1, characterized in that: The amount of the rhodium catalyst used is 1-2% of the mole number of the aniline derivative; the amount of the palladium catalyst used is 1-5% of the mole number of the aniline derivative.

7. The one-pot method for synthesizing 3-tetrasubstituted indolin-2-one compounds according to claim 1, characterized in that: The amount of the phosphine ligand used is 3-12% of the molar number of the aniline derivative.

8. The one-pot method for synthesizing 3-tetrasubstituted indolin-2-one compounds according to claim 1, characterized in that: The solvent is one of toluene, xylene, tetrahydrofuran, chloroform, acetonitrile and dichloromethane; the concentration of the aniline derivative in the solvent is 0.05-0.2 mol / L.

9. The one-pot method for synthesizing 3-tetrasubstituted indolin-2-one compounds according to claim 1, characterized in that: The specific reaction time is 3 to 36 hours.

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