Synthetic method of indole [3, 2-c] coumarin compound

Abstract

The invention belongs to the technical field of organic synthesis, and discloses a synthesis method of an indole [3, 2-c] coumarin compound. The synthetic method of the indole [3, 2-c] coumarin compound comprises the following steps: taking a compound I as shown in a formula (I), a palladium catalyst, an oxidizing agent and a co-oxidizing agent, and adding carbon monoxide for reaction to obtain the indole [3, 2-c] coumarin compound as shown in a formula (II). According to the synthetic method disclosed by the invention, the indole [3, 2-c] coumarin compound is synthesized in one step by taking the 2-aryl substituted indole derivative as a substrate, so that the reaction steps are reduced, and the process duration and the production period of the indole [3, 2-c] coumarin compound are greatly shortened; the used raw materials are easy to obtain, the reaction conditions are mild, and dangerous reagents such as NaN3 are not needed; meanwhile, few three wastes are generated in the technological process, and the method is environmentally friendly, suitable for green large-scale production, efficient, environmentally friendly and easy to control.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and in particular to a method for synthesizing indole[3,2-c]coumarin compounds. Background Art

[0002] Coumarin compounds and their derivatives, a class of organic compounds widely found in nature, play an important role in drug development, natural product research, and biological research. Among them, indole[3,2-c]coumarin, as a key member of the polycyclic coumarin derivatives, is an important pharmacophore skeleton in medicinal chemistry, exhibiting a variety of excellent biological activities, such as anti-tumor, angiogenesis inhibition, estrogen-like activity, antifungal, anticoagulant, and anti-HIV activities. Therefore, indole[3,2-c]coumarin plays a vital role in various fields, including medicine, fragrances, food, and agriculture. With in-depth research on its biological activity and mechanism of action, its outstanding performance and advantages have made it a major force in the pharmaceutical market, promising to bring greater benefits and higher quality to related industries.

[0003] The synthesis of indole[3,2-c]coumarin is a complex process. The existing synthesis methods include the following: (1) using 4-azido-3-arylcoumarin as the starting material, thermodynamic cyclization is carried out at 150 ° C to synthesize indole[3,2-c]coumarin; however, the preparation process of the starting material 4-azido-3-arylcoumarin in this route is tedious and complicated, and the thermodynamic cyclization at high temperature will lead to the formation of by-products, which will affect the purity and yield of the product; (2) using iodine indole derivatives as raw materials, and using palladium Catalytic glycosylation / lactonization reaction is used to efficiently synthesize natural coumestrol, coumestrol and related analogues; however, the glycosylation / lactonization reaction needs to be carried out under specific temperature and pressure conditions to ensure the smooth progress of the reaction and the stability of the product; at the same time, this route will produce a variety of by-products, making it difficult to obtain the product efficiently; (3) Coumarin compounds are constructed using metal copper-mediated / microwave-assisted CO lactonization reaction; however, the precursors of coumarin compounds have poor adaptability in this synthesis method, which limits the scope of application of this method.

[0004] In summary, the various synthetic methods for indolo[3,2-c]coumarins mentioned above all suffer from common problems such as difficult starting materials, expensive reagents, demanding reaction conditions, poor substrate versatility, and inconvenience in industrial production. Furthermore, the synthesis of indolo[3,2-c]coumarins using transition metal catalysis is often limited by drawbacks such as difficult screening conditions, low reaction yields, and environmental concerns, resulting in significantly reduced yields and insufficient purity of the final products. Therefore, the development of a more efficient, stable, environmentally friendly, and easily controllable synthetic method for indolo[3,2-c]coumarins is urgently needed. Summary of the Invention

[0005] The purpose of the present invention is to overcome the shortcomings of the prior art and provide a method for synthesizing indole[3,2-c]coumarin compounds.

[0006] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0007] In a first aspect, the present invention provides a method for synthesizing an indole[3,2-c]coumarin compound, comprising the following steps: taking a compound I represented by formula (I), a palladium catalyst, an oxidant, and a co-oxidant, adding carbon monoxide to react to obtain an indole[3,2-c]coumarin compound represented by formula (II);

[0008]

[0009] Wherein, R is any one of hydrogen, alkyl, alkoxy, heteroalkyl, aryl, aralkyloxy, and halogen; 1 is any one of hydrogen, alkyl, alkoxy, heteroalkyl, aryl, aralkyloxy, and halogen; 2 It is any one of hydrogen, alkyl, alkoxy, heteroalkyl, aryl, aralkyloxy and halogen.

[0010] In the synthesis method of indole[3,2-c]coumarin compounds of the present invention, 2-aryl substituted indole derivatives are used as substrates. Under the action of carbon monoxide gas and palladium catalyst, they are oxidized by an oxidant and a co-oxidant to cause intramolecular carbon-hydrogen activation / oxidative carbonylation reaction, thereby directly constructing an indole[3,2-c]coumarin ring with good biological activity in one step. During the entire reaction process (reaction mechanism see Figure 2 ), first, the C3 carbon-hydrogen bond of the indole ring and the palladium catalyst undergo electrophilic palladium reaction to obtain palladium intermediate A; then, intermediate A reacts with carbon monoxide gas to obtain intermediate B, and intermediate B then undergoes intramolecular alcoholysis reaction to obtain the target product indole [3,2-c] coumarin compound; at the same time, the divalent palladium catalyst is reduced to zero-valent palladium through a reduction elimination process, and under the action of a co-oxidant, the oxidant oxidizes the zero-valent palladium to divalent palladium, thereby entering the next catalytic cycle. Compared with the traditional synthesis method using coumarin derivatives as substrates, the synthesis method of the present invention does not use hazardous reagents such as NaN3, and in the process of synthesizing the indole [3,2-c] coumarin ring, the present invention uses 2-aryl substituted indole derivatives as substrates, and the indole ring directly participates in the lactonization reaction to synthesize the indole [3,2-c] coumarin compound in one step, which simplifies the synthesis path, reduces the generation and treatment of intermediates, improves the overall efficiency of the reaction, has high atom economy, reduces resource waste, and conforms to the concept of green chemistry.

[0011] As a preferred embodiment of the synthesis method of the indole [3,2-c] coumarin compounds of the present invention, the structural formula of the compound I is as follows:

[0012]

[0013] Wherein, R is any one of hydrogen, alkyl, alkoxy, heteroalkyl, aryl, aralkyloxy, and halogen; 1 is any one of hydrogen, alkyl, alkoxy, heteroalkyl, aryl, aralkyloxy, and halogen; 2 It is any one of hydrogen, alkyl, alkoxy, heteroalkyl, aryl, aralkyloxy and halogen.

[0014] As a preferred embodiment of the method for synthesizing the indole[3,2-c]coumarin compounds of the present invention, the structural formula of the indole[3,2-c]coumarin compounds is as follows:

[0015]

[0016] Wherein, R is any one of hydrogen, alkyl, alkoxy, heteroalkyl, aryl, aralkyloxy, and halogen; 1 is any one of hydrogen, alkyl, alkoxy, heteroalkyl, aryl, aralkyloxy, and halogen; 2 It is any one of hydrogen, alkyl, alkoxy, heteroalkyl, aryl, aralkyloxy and halogen.

[0017] Preferably, the R is methyl; the R 1 is hydrogen; said R 2 For hydrogen.

[0018] Preferably, the R is a methoxy group; the R 1 is hydrogen; said R 2 For hydrogen.

[0019] Preferably, the R is (trimethylsilyl)ethoxymethyl; the R 1 is a methoxy group; the R 2 It is a methoxy group.

[0020] As a preferred embodiment of the synthesis method of indole[3,2-c]coumarin compounds described in the present invention, the alkyl group is a straight-chain or branched alkyl group having 1-10 carbon atoms; the alkoxy group is a straight-chain or branched alkoxy group having 1-10 carbon atoms; the heteroalkyl group is a straight-chain or branched heteroalkyl group having 1-10 carbon atoms; the aryl group is a straight-chain or branched aryl group having 6-10 carbon atoms; the aryloxy group is a straight-chain or branched aryloxy group having 6-10 carbon atoms; and the halogen is any one of fluorine, chlorine, bromine, and iodine.

[0021] Preferably, the alkyl group is methyl; the alkoxy group is methoxy; and the heteroalkyl group is (trimethylsilyl)ethoxymethyl.

[0022] As a preferred embodiment of the method for synthesizing indole[3,2-c]coumarin compounds of the present invention, the palladium catalyst is tetrakis(triphenylphosphine)palladium.

[0023] As a preferred embodiment of the method for synthesizing indole[3,2-c]coumarin compounds of the present invention, the molar amount of the palladium catalyst is 5%-30% of the molar amount of the compound I.

[0024] Preferably, the molar amount of the palladium catalyst is 10%-30% of the molar amount of the compound I.

[0025] More preferably, the molar amount of the palladium catalyst is any one of 10%, 20%, and 30% of the molar amount of the compound I, or a range value between the two.

[0026] As a preferred embodiment of the method for synthesizing indole[3,2-c]coumarin compounds of the present invention, the oxidant is 1,4-benzoquinone; and the co-oxidant includes at least one of copper bromide, copper acetate, copper trifluoromethanesulfonate, copper acetylacetonate, and copper diethylhexanoate.

[0027] Preferably, the co-oxidant is copper bromide.

[0028] As a preferred embodiment of the method for synthesizing indole[3,2-c]coumarin compounds of the present invention, a solvent is further added to the reaction; the solvent is at least one of toluene, N,N-dimethylformamide, N,N-dimethylacetamide, and dimethylamine.

[0029] Preferably, the solvent is toluene and / or N,N-dimethylformamide.

[0030] As a preferred embodiment of the method for synthesizing indole[3,2-c]coumarin compounds of the present invention, the reaction temperature is 90°C-120°C.

[0031] Preferably, the reaction temperature is 110°C-120°C.

[0032] Compared with the prior art, the present invention has the following beneficial effects: first, in the synthesis method of indole[3,2-c]coumarin compounds of the present invention, 2-aryl substituted indole derivatives are used as substrates, the indole ring directly participates in the lactonization reaction, and the indole[3,2-c]coumarin compounds are synthesized in one step, which reduces the reaction steps and greatly shortens the process time and production cycle of indole[3,2-c]coumarin compounds; secondly, the raw materials used in the synthesis method of the present invention are easy to obtain, the reaction conditions are mild, and no hazardous reagents such as NaN3 are required, which not only improves the process of indole[3,2-c]coumarin compounds production, but also reduces the production cost. The invention is safe and does not contain toxic and harmful substances such as azide in the generated waste, thereby reducing the difficulty and cost of post-processing; at the same time, the amount of three wastes (waste gas, wastewater and solid waste) generated in the entire process is small, which is environmentally friendly and suitable for green large-scale production; in addition, the synthesis method of the present invention can quickly and efficiently prepare a series of indole [3,2-c] coumarin compounds substituted with different functional groups, and can fully utilize the raw materials in the synthesis process, reduce the generation of by-products, improve the utilization rate of the raw materials and the purity of the products, and thus has broad application prospects and practical value in the fields of drug development, materials science and so on. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 Schematic diagram of the structure of the indole [3,2-c] coumarin compound of the present invention;

[0034] Figure 2 Schematic diagram of the reaction mechanism of the method for synthesizing indole[3,2-c]coumarin compounds of the present invention. DETAILED DESCRIPTION

[0035] To better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments. Those skilled in the art should understand that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0036] The following is an elaboration with reference to specific embodiments to illustrate the practical effects of the present invention.

[0037] Unless otherwise specified, the experimental methods used in the examples are conventional methods; the materials, reagents, equipment, etc. used are all available from commercial sources unless otherwise specified.

[0038] Example 1:

[0039] (1) Under nitrogen, phenylhydrazine (Compound 1) (1.081 g, 10 mmol), o-hydroxyacetophenone (Compound 2) (1.361 g, 10 mmol), and ethanol (10 ml) were added sequentially to a 100 ml dry three-necked round-bottom flask and stirred thoroughly. Acetic acid (50 μL) was added and the system was heated to 80°C and refluxed for 1 h. The reaction was monitored by TLC and concentrated by vacuum distillation to obtain 2.037 g of a yellow solid, Compound 3, with a yield of 90%.

[0040] The reaction formula is as follows:

[0041]

[0042] The hydrogen and carbon nuclear magnetic resonance spectrum data of the obtained product are shown below:

[0043] 1 H NMR (500MHz, (CD3)2SO) δ12.82(s,1H),9.53(s,1H),7.56(dd,J=8.3,1.6Hz,1H),7.30(dd,J=8.6,7.2Hz,2 H),7.22(ddd,J=8.4,7.3,1.6Hz,1H),7.12-7.05(m,2H),6.87(dtt,J=21.1,7.3,1.2Hz,3H),2.40(s,3H).

[0044] 13 C NMR (126MHz, (CD3)2SO) δ157.76,148.15,145.39,129.96,129.80,127.76,120.90,120.24,119.25,117.04,112.94,13.61.

[0045] (2) Under nitrogen atmosphere, compound 3 (2.037 g, 9 mmol) and polyphosphoric acid (9 mL) were added to a 100 mL round-bottom flask in sequence, and the temperature was slowly raised to 120°C and stirred vigorously for 1.5 hours. After the reaction was complete as monitored by TLC, the reaction system was poured into 100 mL of ice water to quench the reaction. The mixed system was extracted with ethyl acetate, and the organic phase was washed twice with water and once with saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The mixture was concentrated by distillation under reduced pressure and purified by column chromatography to obtain 0.979 g of compound 4 with a yield of 52%.

[0046] The reaction formula is as follows:

[0047]

[0048] The hydrogen and carbon nuclear magnetic resonance spectrum data of the obtained product are shown below:

[0049] 1 H NMR(500MHz, (CD3)2SO) δ11.17-11.10(m,1H),10.15(s,1H),7.76(dd,J=7.8,1.6Hz,1H),7.53(d,J=7.8Hz,1H),7.50-7.45( m,1H),7.15(ddd,J=8.6,7.3,1.7Hz,1H),7.07(ddd,J=8.2,6.9,1.2Hz,1H),7.04-6.95(m,3H),6.91(td,J=7.5,1.3Hz,1H).

[0050] 13 C NMR (126MHz, (CD3)2SO) δ154.30,136.27,135.34,128.29,128.25,127.48,121.00,119.71,119.47,118.99,118.88,116.47,111.37,100.79.

[0051] (3) Under nitrogen atmosphere, compound 4 (0.628 g, 3 mmol), potassium carbonate (0.83 g, 6 mmol) and DMF (30 mL) were added sequentially to a 100 mL round-bottom flask and stirred thoroughly. Benzyl bromide (0.56 g, 0.39 mL, 3.3 mmol) was slowly added dropwise at 0°C and the reaction was stirred overnight. TLC monitored the reaction completion. Water was added dropwise at 0°C to quench the reaction. The mixture was extracted with ethyl acetate, and the organic phase was washed twice with water and once with saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The mixture was concentrated by distillation under reduced pressure and purified by column chromatography to obtain 0.871 g of compound 5 with a yield of 97%.

[0052] The reaction formula is as follows:

[0053]

[0054] The hydrogen and carbon nuclear magnetic resonance spectrum data of the obtained product are shown below:

[0055] 1H NMR(400MHz, (CD3)2SO) δ11.28-11.21(m,1H),7.82(dd,J=7.8,1.7Hz,1H),7.50(dd,J=14.3,7.5Hz,3H),7.41(t d,J=7.8,5.4Hz,3H),7.36-7.24(m2H),7.20(d,J=8.2Hz,1H),7.13-7.03(m,2H),7.01-6.94(m,2H),5.33(s,2H).

[0056] 13 C NMR(101MHz,(CD3)2SO)δ155.04,137.13,136.31,134.35,128.49,128.44,128.32,127.82 ,127.77,127.46,121.36,121.13,120.98,119.91,119.06,113.49,111.18,102.16,69.61.

[0057] (4) Under nitrogen atmosphere, compound 5 (0.515 g, 1.72 mmol) was added to a 100 mL round-bottom flask, and 17 mL of DMF was added and stirred thoroughly. Sodium hydride (0.14 g, 3.44 mmol) was added at 0°C, and the mixture was vigorously stirred at room temperature for 1 hour. Then, iodomethane (0.488 g, 0.214 mL, 3.44 mmol) was slowly added dropwise at 0°C. The reaction was monitored by TLC to be complete. The reaction system was quenched by adding saturated ammonium chloride solution dropwise at 0°C. The mixture was extracted with ethyl acetate, and the organic phase was washed twice with water and once with saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The mixture was concentrated by distillation under reduced pressure and purified by column chromatography to obtain 0.528 g of compound 6 with a yield of 98%.

[0058] The reaction formula is as follows:

[0059]

[0060] The hydrogen and carbon nuclear magnetic resonance spectrum data of the obtained product are shown below:

[0061] 1H NMR(500MHz,(CD3)2SO)δ7.52(dt,J=7.9,1.0Hz,1H),7.43-7.36(m,2H),7.33(dd,J=7.4,1.8Hz,1H),7.28-7.1 9(m,6H),7.12(ddd,J=8.2,7.0,1.2Hz,1H),7.07-7.00(m,2H),6.42(d,J=0.8Hz,1H),5.11(s,2H),3.50(s,3H).

[0062] 13 C NMR(126MHz,(CD3)2SO)δ156.16,138.28,137.26,136.88,132.24,130.24,128.37,127.73,12 7.45,127.25,121.54,121.01,120.89,119.91,119.17,112.97,109.69,101.42,69.53,30.75.

[0063] (5) Under nitrogen atmosphere, compound 6 (0.523 g, 1.7 mmol) was added to a 100 mL round-bottom flask, and 17 mL of dichloromethane was added and stirred thoroughly. Boron tribromide (1 mol / L in dichloromethane) (8.5 mL, 8.5 mmol) was added at 0°C, and the mixture was stirred at room temperature for 15 minutes. TLC monitored the reaction completion, and water was added dropwise to the reaction system at 0°C to quench the reaction. The mixture was extracted with ethyl acetate, and the organic phase was washed twice with water and once with saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The mixture was concentrated by distillation under reduced pressure and purified by column chromatography to obtain 0.298 g of compound 7 with a yield of 80%.

[0064] The reaction formula is as follows:

[0065]

[0066] The hydrogen and carbon nuclear magnetic resonance spectrum data of the obtained product are shown below:

[0067] 1 H NMR(500MHz, (CD3)2SO) δ9.81(d,J=1.6Hz,1H),7.55(d,J=7.8Hz,1H),7.44(d,J=8.3Hz,1H),7.36-7.2 6(m,2H),7.21-7.13(m,1H),7.10-7.00(m,2H),6.98-6.90(m,1H),6.40(s,1H),3.59(d,J=1.4Hz,3H).

[0068] 13 C NMR(126MHz,(CD3)2SO)δ155.94,139.44,137.67,132.52,130.44,127.98 ,121.26,120.23,120.02,119.62,119.53,116.21,110.15,101.44,31.10.

[0069] (6) Under nitrogen atmosphere, compound 7 (0.045 g, 0.2 mmol), tetrakis(triphenylphosphine)palladium (0.023 g, 0.02 mmol), copper bromide (0.005 g, 0.02 mmol), and 1,4-benzoquinone (0.043 g, 0.4 mmol) were added to a 15 mL pressure tube in sequence. 2 mL of toluene was added and stirred thoroughly. The gas in the pressure tube was completely replaced with carbon monoxide gas (1 atm). The temperature was gradually raised to 110 ° C and stirred vigorously for 48 hours. TLC monitored the reaction completion. The reaction system was quenched by adding water dropwise at 0 ° C. The mixed system was extracted with ethyl acetate, and the organic phase was washed twice with water and once with saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The mixture was concentrated by distillation under reduced pressure and purified by column chromatography to obtain 0.038 g of compound 8 with a yield of 76%.

[0070] The reaction formula is as follows:

[0071]

[0072] The hydrogen and carbon nuclear magnetic resonance spectrum data of the obtained product are shown below:

[0073] 1 H NMR(400MHz, (CD3)2SO) δ8.46(dd,J=8.1,1.5Hz,1H),8.10(dd,J=7.8,1.1Hz,1H),7.85(d,J=8.3Hz,1H),7.66(ddd,J=8 .5,7.1,1.5Hz,1H),7.57(dd,J=8.4,1.4Hz,1H),7.47(tt,J=7.2,1.2Hz,2H),7.37(td,J=7.6,1.0Hz,1H),4.31(s,3H).

[0074] 13 C NMR(101MHz,(CD3)2SO)δ157.58,152.83,140.90,139.45,130.58,124.76,124 .31,123.79,123.43,122.71,120.22,117.67,113.69,111.03,100.27,33.24.

[0075] Example 2:

[0076] (1) Under nitrogen atmosphere, compound 5 (0.418 g, 2 mmol) was added to a 100 mL round-bottom flask, and 20 mL of DMF was added and stirred thoroughly. Sodium hydride (0.16 g, 4 mmol) was added at 0°C, and the mixture was gradually heated to room temperature and stirred vigorously for 1 hour. Chloromethyl methyl ether (0.322 g, 0.3 mL, 4 mmol) was then slowly added dropwise at 0°C, and the temperature was slowly raised. The reaction was stirred overnight. TLC monitored the reaction to be complete. The reaction system was quenched by adding saturated ammonium chloride solution dropwise at 0°C. The mixture was extracted with ethyl acetate, and the organic phase was washed twice with water and once with saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The mixture was concentrated by distillation under reduced pressure and purified by column chromatography to obtain 1.25 g of compound 9 with a yield of 91%.

[0077] The reaction formula is as follows:

[0078]

[0079] The hydrogen and carbon nuclear magnetic resonance spectrum data of the obtained product are shown below:

[0080] 1 H NMR (500MHz, CDCl3) δ7.66(d,J=7.8Hz,1H),7.53(d,J=8.2Hz,1H),7.47(dt,J=7.5,1.2Hz,1H),7.40(td,J=7.9,1.8Hz ,1H),7.30-7.21(m,5H),7.18(t,J=7.4Hz,1H),7.11-7.04(m,2H),6.56(s,1H),5.37(s,2H),5.07(s,2H),2.99(s,3H).

[0081] 13 C NMR (126MHz, CDCl3) δ156.66,138.54,137.60,137.13,133.10,130.52,129.05,128.89,128.16,127 .22,122.68,122.28,121.69,120.85,120.66,113.63,110.88,104.15,77.62,75.75,70.84,55.88.

[0082] (2) Under nitrogen atmosphere, compound 9 (0.293 g, 0.853 mmol) and 10% palladium carbon (55% water) (0.272 g, 0.256 mmol) were added to a 100 mL round-bottom flask, and 10 mL of ethyl acetate was added and stirred thoroughly. The mixture was then degassed three times, and a hydrogen balloon was inserted. The mixture was stirred vigorously at room temperature for 6 hours. TLC monitored the reaction to be complete, and the reaction system was filtered and rinsed with ethyl acetate as an organic solvent. The filtrate was washed with water twice for the organic phase, and with saturated brine once for the organic phase. The organic phases were combined and dried over anhydrous sodium sulfate. The mixture was concentrated by distillation under reduced pressure and purified by column chromatography to obtain 0.162 g of compound 10 with a yield of 75%.

[0083] The reaction formula is as follows:

[0084]

[0085] The hydrogen and carbon nuclear magnetic resonance spectrum data of the obtained product are shown below:

[0086] 1 H NMR(400MHz, (CD3)2SO) δ9.78(s,1H),7.59-7.53(m,2H),7.31(ddd,J=15.8,7.7,1.7Hz,2H),7.17(ddd,J=8.0,5.7,1.3Hz ,1H),7.14-7.05(m,1H),6.99(dd,J=8.2,1.1Hz,1H),6.93(td,J=7.4,1.2Hz,1H),6.44(s,1H),5.39(s,2H),2.92(s,3H).

[0087] 13 C NMR(101MHz,(CD3)2SO)δ155.02,138.60,136.96,132.09,130.03,128.12 ,121.39,119.93,119.24,119.18,115.78,110.59,102.86,74.55,55.13.

[0088] (3) Under nitrogen atmosphere, compound 10 (0.045 g, 0.2 mmol), tetrakis(triphenylphosphine)palladium (0.023 g, 0.02 mmol), copper bromide (0.005 g, 0.02 mmol), and 1,4-benzoquinone (0.043 g, 0.4 mmol) were added to a 15 mL pressure tube in sequence. 2 mL of toluene was added and stirred thoroughly. The gas in the pressure tube was completely replaced with carbon monoxide gas (1 atm). The temperature was gradually raised to 110 ° C and stirred vigorously for 48 hours. TLC monitored the reaction completion. Water was added dropwise to the reaction system at 0 ° C to quench the reaction. The mixed system was extracted with ethyl acetate, and the organic phase was washed twice with water and once with saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The mixture was concentrated by distillation under reduced pressure and purified by column chromatography to obtain 0.025 g of a white solid, namely compound 11, with a yield of 45%.

[0089] The reaction formula is as follows:

[0090]

[0091] The hydrogen and carbon nuclear magnetic resonance spectrum data of the obtained product are shown below:

[0092] 1 H NMR (500MHz, CDCl3) δ8.34(dd,J=7.8,1.2Hz,1H),8.24(dd,J=8.1,1.4Hz,1H),7.60(d,J=8.3Hz,1H),7.57-7.49 (m,2H),7.46(ddd,J=8.4,7.1,1.3Hz,1H),7.38(ddd,J=8.5,7.0,1.5Hz,2H),5.87(s,2H),3.47(d,J=0.9Hz,3H).

[0093] 13 C NMR (126MHz, CDCl3) δ158.83,153.60,141.85,139.89,130.60,125.59,124.49, 124.31,123.88,123.50,122.06,118.23,113.56,109.47,103.64,75.26,56.71.

[0094] Example 3:

[0095] (1) Under nitrogen atmosphere, compound 14 (0.189 g, 0.756 mmol, 1 equiv.) and K2CO3 (0.21 g, 1.512 mmol, 2 equiv.) were added to a 100 mL round-bottom flask. 7 mL of DMF solvent was added via syringe and stirred thoroughly. Benzyl bromide (0.155 g, 0.11 mL, 0.907 mmol, 1.2 equiv.) was slowly added dropwise at 0°C and vigorously stirred at room temperature overnight. TLC monitored the reaction completion. The reaction system was quenched by adding saturated ammonium chloride solution dropwise at 0°C. The mixture was extracted with ethyl acetate, and the organic phase was washed twice with water and once with saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The mixture was concentrated by distillation under reduced pressure and purified by column chromatography to obtain 0.257 g of a colorless oily liquid, i.e., compound 15, with a yield of 99%.

[0096] The reaction formula is as follows:

[0097]

[0098] The hydrogen and carbon nuclear magnetic resonance spectrum data of the obtained product are shown below:

[0099] 1 H NMR (400MHz, CDCl3) δ7.65 (d, J=8.6Hz, 1H), 7.51 (ddd, J=7.6, 1.4, 0.7Hz, 2H), 7.44-7.37 (m, 2H) ,7.36-7.30(m,1H),6.48(d,J=2.6Hz,1H),6.34(dd,J=8.6,2.7Hz,1H),5.13(s,2H),3.77(s,3H).

[0100] 13 C NMR (101MHz, CDCl3) δ161.23,157.96,139.22,136.42,128.59,127.91,127.02,107.51,100.86,75.59,70.81,55.53.

[0101] (2) Under nitrogen atmosphere, indole 16 (0.029 g, 0.2 mmol, 1 equiv.), PdCl2(MeCN)2 (0.005 g, 0.02 mmol, 10% mol), K2CO3 (0.055 g, 0.4 mmol, 2 equiv.), and norbornene (0.038 g, 0.4 mmol, 2 equiv.) were added sequentially to a 15 mL Shrek tube. 1 mL of a 0.5 M solution of water (H2O) dissolved in N,N-dimethylacetamide (DMA) was added via syringe. The argon atmosphere in the above system was replaced three times, and compound 15 (0.136 g, 0.4 mmol, 2 equiv.) was added. The mixture was vigorously stirred at 70°C under argon balloon pressure for 17 h. The reaction was monitored by TLC to determine completion. The above mixture was filtered through celite and rinsed with ethyl acetate. The filtrate was washed with water and saturated brine in sequence, and the organic phase was dried over anhydrous sodium sulfate. The residue was concentrated by distillation under reduced pressure and purified by column chromatography to obtain 0.029 g of compound 17 with a yield of 40%.

[0102] The reaction formula is as follows:

[0103]

[0104] The hydrogen and carbon nuclear magnetic resonance spectrum data of the obtained product are shown below:

[0105] 1H NMR(400MHz, (CD3)2SO) δ10.95-10.91(m,1H),7.66(d,J=8.6Hz,1H),7.57-7.49(m,2H),7.45-7.37(m,2H),7.37-7.28(m,2H) ,6.90(d,J=2.3Hz,1H),6.75(dd,J=10.1,2.2Hz,2H),6.63(ddd,J=10.8,8.6,2.4Hz,2H),5.31(s,2H),3.77(d,J=0.8Hz,6H).

[0106] 13C NMR(101MHz,(CD3)2SO)δ159.32,155.79,155.38,137.10,136.88,133.39,128.50,127.98,127.8 1,127.47,122.78,120.15,114.43,108.98,105.71,100.60,100.55,94.21,69.60,55.28,55.12.

[0107] (3) Under nitrogen atmosphere, compound 17 (0.082 g, 0.557 mmol) was added to a 25 mL round-bottom flask. 5 mL of DMF was added and stirred thoroughly. Sodium hydride (0.045 g, 1.114 mmol) was added at 0°C, and the mixture was gradually warmed to room temperature and stirred vigorously for 1 hour. Then, SEMCl (0.102 g, 0.11 mL, 0.613 mmol) was slowly added dropwise at 0°C. The mixture was then slowly warmed to room temperature and stirred overnight. TLC monitored the reaction completion. The reaction system was quenched by adding saturated ammonium chloride solution dropwise at 0°C. The mixture was extracted with ethyl acetate, and the organic phase was washed twice with water and once with saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The mixture was concentrated by distillation under reduced pressure and purified by column chromatography to obtain 0.196 g of compound 18 with a yield of 72%.

[0108] The reaction formula is as follows:

[0109]

[0110] The hydrogen and carbon nuclear magnetic resonance spectrum data of the obtained product are shown below:

[0111] 1 H NMR(400MHz, (CD3)2SO) δ7.40(d,J=8.6Hz,1H),7.35-7.23(m,6H),7.06(d,J=2.3Hz,1H),6.79(d,J=2.4Hz,1H),6.72(dd,J=8.6,2.2Hz,1H),6.65( dd,J=8.4,2.4Hz,1H),6.32(s,1H),5.33(s,2H),5.13(s,2H),3.79(d,J= 4.0Hz, 6H), 3.19-3.06 (m, 2H), 0.59 (dd, J = 8.8, 7.4Hz, 2H), -0.19 (s, 9H).

[0112] 13 C NMR(101MHz,(CD3)2SO)δ160.91,156.85,155.61,137.72,136.86,136.75,132.96,128.42,127.77,127.32,122 .21,120.43,113.99,109.63,105.51,102.60,100.18,94.40,72.50,69.51,64.68,55.38,55.34,17.04,-1.48.

[0113] (4) Under nitrogen atmosphere, compound 18 (0.117 g, 0.239 mmol, 1 equiv.) and 10% palladium carbon (55% water) (0.076 g, 0.072 mmol, 0.3 equiv.) were added to a 10 mL round-bottom flask, and 3 mL of ethyl acetate was added and stirred thoroughly. The mixture was then rapidly degassed by three freeze-pump-thaw cycles under liquid nitrogen cooling and high vacuum conditions. A hydrogen balloon was inserted and the mixture was vigorously stirred at room temperature for 6 hours. The reaction was monitored for completion by TLC. The reaction system was filtered through celite and rinsed with ethyl acetate. The organic phase was washed twice with water and once with saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The mixture was concentrated by distillation under reduced pressure and purified by column chromatography to obtain 0.073 g of compound 12 with a yield of 76%.

[0114] The reaction formula is as follows:

[0115]

[0116] The hydrogen and carbon nuclear magnetic resonance spectrum data of the obtained product are shown below:

[0117] 1 H NMR(400MHz, (CD3)2SO) δ9.78(s,1H),7.39(d,J=8.6Hz,1H),7.17(d,J=8.4Hz,1H),7.06(d,J=2.3Hz,1H),6.71(dd,J=8.5,2.2Hz ,1H),6.58-6.45(m,2H),6.26(s,1H),5.37(s,2H),3.79(s,3H),3.75(s,3H),3.21-3.02(m,2H),0.68-0.52(m,2H),-0.18(s,9H).

[0118] 13 C NMR(101MHz,(CD3)2SO)δ160.64,156.06,155.50,137.66,137.44,132.84,122.34,120.30, 112.30,109.53,104.94,102.12,101.41,94.40,72.42,64.62,55.34,55.07,17.06,-1.47.

[0119] (5) Under nitrogen atmosphere, compound 12 (0.080 g, 0.2 mmol), tetrakis(triphenylphosphine)palladium (0.023 g, 0.02 mmol), copper bromide (0.005 g, 0.02 mmol), and 1,4-benzoquinone (0.043 g, 0.4 mmol) were added to a 15 mL pressure tube in sequence. 2 mL of toluene was added and stirred thoroughly. The gas in the pressure tube was completely replaced with carbon monoxide gas (1 atm). The temperature was gradually raised to 110 ° C and stirred vigorously for 48 hours. TLC monitored the reaction completion. The reaction system was quenched by adding water dropwise at 0 ° C. The mixture was extracted with ethyl acetate, and the organic phase was washed twice with water and once with saturated brine. The organic phases were combined and dried over anhydrous sodium sulfate. The mixture was concentrated by distillation under reduced pressure and purified by column chromatography to obtain 0.076 g of a white solid, namely compound 13, with a yield of 89%.

[0120] The reaction formula is as follows:

[0121]

[0122] The hydrogen and carbon nuclear magnetic resonance spectrum data of the obtained product are shown below:

[0123] 1 H NMR(400MHz, (CD3)2SO)) δ8.17(d,J=9.0Hz,1H),7.92(d,J=8.6Hz,1H),7.52(s,1H),7.12(s,1H),7.0 9-6.95(m,2H),6.01(s,2H),3.88(s,6H),3.69(t,J=7.9Hz,2H),0.87(t,J=7.9Hz,2H),-0.13(s,9H).

[0124] 13 C NMR(101MHz,(CD3)2SO))δ161.35,158.49,158.22,154.80,141.70,141.11,125.62,121.16,11 7.48,112.67,112.56,106.77,102.17,100.47,95.41,73.57,66.24,56.28,56.19,17.75,1.0.

[0125] Example 4:

[0126] The only difference between the synthesis method described in this example and that in Example 1 is that in step (6), copper bromide (CuBr2) is replaced by copper acetate (Cu(OAc)2), and the yield of the obtained product is 45%.

[0127] Example 5:

[0128] The only difference between the synthesis method described in this example and that in Example 1 is that in step (6), copper bromide (CuBr2) is replaced by copper trifluoromethanesulfonate (Cu(OTf)2), and the product yield obtained is 63%.

[0129] Example 6:

[0130] The only difference between the synthesis method described in this example and that in Example 1 is that in step (6), copper bromide (CuBr2) is replaced by copper acetylacetonate (Cu(acac)2), and the yield of the obtained product is 44%.

[0131] Example 7:

[0132] The only difference between the synthesis method described in this example and that in Example 1 is that in step (6), copper bromide (CuBr2) is replaced by copper diethylhexanoate (Cu(2-ethylhexanoate)2), and the product yield obtained is 53%.

[0133] Example 8:

[0134] The only difference between the synthesis method described in this example and that in Example 1 is that in step (6), toluene is replaced by N,N-dimethylformamide (DMF), and the yield of the obtained product is 74%.

[0135] Example 9:

[0136] The only difference between the synthesis method described in this example and that in Example 1 is that in step (6), toluene is replaced by N,N-dimethylacetamide (DMAc), and the yield of the obtained product is 60%.

[0137] Example 10:

[0138] The only difference between the synthesis method described in this example and that in Example 1 is that in step (6), toluene is replaced by dimethylamine (DMA), and the yield of the obtained product is 46%.

[0139] Example 11:

[0140] The only difference between the synthesis method described in this example and that in Example 1 is that in step (6), the reaction temperature is 120° C. and the yield of the product is 76%.

[0141] Example 12:

[0142] The only difference between the synthesis method described in this example and that in Example 1 is that in step (6), the molar amount of tetrakis(triphenylphosphine)palladium is 5% of the molar amount of compound 7, and the yield of the product is 50%.

[0143] Example 13:

[0144] The only difference between the synthesis method described in this example and that in Example 1 is that in step (6), the molar amount of tetrakis(triphenylphosphine)palladium is 20% of the molar amount of compound 7, and the yield of the product is 76%.

[0145] Example 14:

[0146] The only difference between the synthesis method described in this example and that in Example 1 is that in step (6), the molar amount of tetrakis(triphenylphosphine)palladium is 30% of the molar amount of compound 7, and the yield of the product is 76%.

[0147] Comparative Example 1:

[0148] The only difference between the synthesis method described in this comparative example and that of Example 1 is that in step (6), tetrakis(triphenylphosphine)palladium is replaced by palladium acetate (Pd(OAc)2), and copper bromide is replaced by copper acetate (Cu(OAc)2), and the yield of the product is 38%.

[0149] Comparative Example 2:

[0150] The only difference between the synthesis method described in this comparative example and that of Example 1 is that in step (6), tetrakis(triphenylphosphine)palladium is replaced by dichlorotriphenylphosphinepalladium (Pd(PPh3)Cl2), and copper bromide is replaced by copper acetate (Cu(OAc)2), and the yield of the product is 15%.

[0151] Comparative Example 3:

[0152] The only difference between the synthesis method described in this comparative example and that of Example 1 is that in step (6), tetrakis(triphenylphosphine)palladium is replaced by palladium dichloride (PdCl2), and copper bromide is replaced by copper acetate (Cu(OAc)2), and the yield of the product is 17%.

[0153] Comparative Example 4:

[0154] The only difference between the synthesis method described in this comparative example and that of Example 1 is that in step (6), tetrakis(triphenylphosphine)palladium is replaced by palladium trifluoroacetate (Pd(CF3COO)2), and copper bromide is replaced by copper acetate (Cu(OAc)2), and the yield of the product is 28%.

[0155] Comparative Example 5:

[0156] The only difference between the synthesis method described in this comparative example and that in Example 1 is that in step (6), copper bromide is replaced by copper acetate (Cu(OAc)2), and the yield of the product is 45%.

[0157] Comparative Example 6:

[0158] The only difference between the synthesis method described in this comparative example and that in Example 1 is that in step (6), tetrakis(triphenylphosphine)palladium is replaced by tris(dibenzylideneacetone)dipalladium (Pd2(dba)3), and copper bromide is replaced by copper acetate (Cu(OAc)2), and the amount of product is too small.

[0159] Comparative Example 7:

[0160] The only difference between the synthesis method described in this comparative example and that in Example 1 is that in step (6), tetrakis(triphenylphosphine)palladium is replaced by palladium tetraacetate ([Pd2(O2CCH3)4]), and copper bromide is replaced by copper acetate (Cu(OAc)2), and the amount of product is too small.

[0161] Comparative Example 8:

[0162] The only difference between the synthesis method described in this comparative example and that in Example 1 is that in step (6), tetrakis(triphenylphosphine)palladium is replaced by tetrakis(2-ethylhexanoate)palladium ([Pd2(O2CC7H 15 )4]), copper bromide was replaced by copper acetate (Cu(OAc)2), and the amount of product was too small.

[0163] Comparative Example 9:

[0164] The only difference between the synthesis method described in this comparative example and that of Example 1 is that in step (6), tetrakis(triphenylphosphine)palladium is replaced by dichloro(pentamethylcyclopentadienyl)rhodium dimer ([RhCp*Cl2]2), and copper bromide is replaced by copper acetate (Cu(OAc)2), and the yield of the product is 25%.

[0165] Comparative Example 10:

[0166] The only difference between the synthesis method described in this comparative example and that of Example 1 is that in step (6), tetrakis(triphenylphosphine)palladium is replaced by tris(triphenylphosphine)rhodium chloride (RhCl(PPh3)3), and copper bromide is replaced by copper acetate (Cu(OAc)2), and the yield of the product is less than 5%.

[0167] Comparative Example 11:

[0168] The only difference between the synthesis method described in this comparative example and that of Example 1 is that in step (6), tetrakis(triphenylphosphine)palladium is replaced by bis(1,5-cyclooctadiene)rhodium trifluoromethanesulfonate (Rh(COD)2OTf), and copper bromide is replaced by copper acetate (Cu(OAc)2), and the yield of the product is less than 5%.

[0169] Comparative Example 12:

[0170] The only difference between the synthesis method described in this comparative example and that in Example 1 is that in step (6), copper bromide is replaced by copper acetate (Cu(OAc)2) and 1,4-benzoquinone is replaced by oxygen (O2), and the yield of the product is 38%.

[0171] Comparative Example 13:

[0172] The only difference between the synthesis method described in this comparative example and that in Example 1 is that in step (6), copper bromide is replaced by copper acetate (Cu(OAc)2), and 1,4-benzoquinone is replaced by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The obtained product is a mixture and cannot be separated.

[0173] By comparing the results of the examples with comparative examples 1-13, it can be found that although common divalent palladium can also obtain the target product, it is not conducive to the occurrence of the oxidative carbonylation reaction, and its catalytic efficiency is low, resulting in an unsatisfactory yield of the target product. At the same time, the type of oxidant also has a great influence on the reaction itself. Oxygen (O2) has a low oxidation efficiency as an oxidant, while the strong oxidant DDQ will cause the substrate to be over-oxidized. However, the 1,4-benzoquinone used in the examples of the present invention is relatively conducive to obtaining the target product without the occurrence of over-oxidation.

[0174] Comparative Example 14:

[0175] The only difference between the synthesis method described in this comparative example and that in Example 1 is that in step (6), copper bromide (CuBr2) is replaced by cuprous acetate (CuOAc), and the yield of the obtained product is 21%.

[0176] Comparative Example 15:

[0177] The only difference between the synthesis method described in this comparative example and that in Example 1 is that in step (6), copper bromide (CuBr2) is replaced by cuprous bromide (CuBr), and the yield of the obtained product is 30%.

[0178] Comparative Example 16:

[0179] The only difference between the synthesis method described in this comparative example and that in Example 1 is that in step (6), copper bromide (CuBr2) is replaced by cuprous iodide (CuI), and the yield of the obtained product is 17%.

[0180] By comparing the results of the embodiment with comparative examples 14-15, it can be found that the co-oxidant metallic copper has a very important influence on the reaction, and monovalent copper is not conducive to the reaction, and the yield is low.

[0181] Comparative Example 17:

[0182] The only difference between the synthesis method described in this comparative example and that in Example 1 is that in step (6), toluene is replaced by N-methylpyrrolidone (NMP), and the yield of the obtained product is less than 5%.

[0183] Comparative Example 18:

[0184] The only difference between the synthesis method described in this comparative example and that in Example 1 is that in step (6), toluene is replaced by 1,4-dioxane, and the yield of the obtained product is 37%.

[0185] Comparative Example 19:

[0186] The only difference between the synthesis method described in this comparative example and that in Example 1 is that in step (6), toluene is replaced by dimethyl sulfoxide (DMSO), and the yield of the obtained product is 18%.

[0187] Comparative Example 20:

[0188] The only difference between the synthesis method described in this comparative example and that in Example 1 is that in step (6), toluene is replaced by dimethylacetamide (DMA), and the yield of the obtained product is 46%.

[0189] Comparative Example 21:

[0190] The only difference between the synthesis method described in this comparative example and that in Example 1 is that in step (6), toluene is replaced by tetrahydrofuran (THF), and the yield of the obtained product is 10%.

[0191] Comparative Example 22:

[0192] The only difference between the synthesis method described in this comparative example and that in Example 1 is that in step (6), toluene is replaced by diethylformamide (DEF), and the yield of the obtained product is 9%.

[0193] The above comparative examples 17-22 respectively screened a series of common high-boiling point solvents, and found that the toluene of the present invention was the most conducive to the occurrence of the reaction as the solvent.

[0194] Comparative Example 23:

[0195] The only difference between the synthesis method described in this comparative example and that in Example 1 is that in step (6), tetrakis(triphenylphosphine)palladium is not used, and the yield of the obtained product is 0%.

[0196] Comparative Example 24:

[0197] The only difference between the synthesis method described in this comparative example and that of Example 1 is that in step (6), the molar amount of tetrakis(triphenylphosphine)palladium is 5% of the molar amount of compound 7, and the yield of the product is 50%.

[0198] The results of the above Examples and Comparative Examples 17-22 demonstrate that the amount of transition metal palladium catalyst plays a significant role in the reaction. The optimal reaction activity was achieved when the amount of tetrakis(triphenylphosphine)palladium was 10% of the molar weight of compound 7. Without the addition of the transition metal palladium catalyst, the reaction did not occur. Furthermore, even with increasing amounts of the transition metal palladium catalyst, the reaction yield did not increase.

[0199] Comparative Example 25:

[0200] The only difference between the synthesis method described in this comparative example and that in Example 1 is that in step (6), the reaction temperature is 30° C. and the yield of the obtained product is 0%.

[0201] Comparative Example 26:

[0202] The only difference between the synthesis method described in this comparative example and that in Example 1 is that in step (6), the reaction temperature is 60° C. and the yield of the product is 0%.

[0203] Comparative Example 27:

[0204] The only difference between the synthesis method described in this comparative example and that in Example 1 is that in step (6), the reaction temperature is 90° C. and the yield of the product is 30%.

[0205] The results of the above examples and comparative examples 25-27 show that temperature plays a decisive role in the reaction. When the temperature is lower than 60°C, no target compound can be detected.

[0206] It can be seen from the above examples that the synthesis method of the present invention reduces the reaction steps and greatly shortens the process time and production cycle of indole [3,2-c] coumarin compounds; the raw materials used are easily available, the reaction conditions are mild, and there is no need to use hazardous reagents such as NaN3; at the same time, the three wastes generated in the process are small, the process is environmentally friendly, and suitable for green large-scale production. It is an efficient, environmentally friendly and easy-to-control green synthesis method.

[0207] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. A method for synthesizing indole[3,2-c]coumarin compounds, characterized in that: The following steps are involved: Compound I represented by formula (I), a palladium catalyst, an oxidant and a co-oxidant are added with carbon monoxide to react to obtain an indole [3,2-c] coumarin compound represented by formula (II); Wherein, R is any one of hydrogen, alkyl, alkoxy, heteroalkyl, aryl, aralkyloxy, and halogen; 1 is any one of hydrogen, alkyl, alkoxy, heteroalkyl, aryl, aralkyloxy, and halogen; 2 It is any one of hydrogen, alkyl, alkoxy, heteroalkyl, aryl, aralkyloxy and halogen.

2. The method for synthesizing indole[3,2-c]coumarin compounds according to claim 1, wherein The palladium catalyst is tetrakis(triphenylphosphine)palladium.

3. The method for synthesizing indole[3,2-c]coumarin compounds according to claim 1, wherein: The molar amount of the palladium catalyst is 5%-30% of the molar amount of the compound I.

4. The method for synthesizing indole[3,2-c]coumarin compounds according to claim 3, characterized in that: The molar amount of the palladium catalyst is 10%-30% of the molar amount of the compound I.

5. The method for synthesizing indole[3,2-c]coumarin compounds according to claim 1, wherein: The oxidant is 1,4-benzoquinone; the co-oxidant includes at least one of copper bromide, copper acetate, copper trifluoromethanesulfonate, copper acetylacetonate, and copper diethylhexanoate.

6. The method for synthesizing indole[3,2-c]coumarin compounds according to claim 5, characterized in that: The co-oxidant is copper bromide.

7. The method for synthesizing indole[3,2-c]coumarin compounds according to claim 1, characterized in that: A solvent is further added to the reaction; the solvent is at least one of toluene, N,N-dimethylformamide, N,N-dimethylacetamide, and dimethylamine.

8. The method for synthesizing indole[3,2-c]coumarin compounds according to claim 7, characterized in that: The solvent is toluene and / or N,N-dimethylformamide.

9. The method for synthesizing indole[3,2-c]coumarin compounds according to claim 1, characterized in that: The reaction temperature is 90°C-120°C.

10. The method for synthesizing indole[3,2-c]coumarin compounds according to claim 9, characterized in that: The reaction temperature is 110°C-120°C.

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