Synthesis method of 1,4-dicarbonyl quinoxalinone derivatives

Abstract

The present invention discloses a method for synthesizing 1,4-dicarbonyl quinoxalinone derivatives. Under photoredox catalysis, diazo compound B generates a radical precursor through a proton-coupled electron transfer (PCET) process to add to quinoxalin-2(1H)-one compound A. Subsequently, compound G is obtained through the isomerization of enamine and imine. The alkyl radical adds to the imine again, and finally, a 1,4-dicarbonyl quinoxalinone derivative is obtained through single electron transfer and deprotonation. This method uses visible light as a green energy source for driving, methanol and water as reaction solvents, and has mild reaction conditions and is easy to operate.

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis, and particularly relates to a method for synthesizing 1,4-dicarbonyl quinoxalinone derivatives. Background Art

[0002] Quinoxalin-2(1H)-one compounds, as important organic synthesis intermediates, exist in bioactive natural molecules and synthetic drug molecules, and are applied in the fields of organic synthesis, materials, and medicine. Therefore, the synthesis research of quinoxalin-2(1H)-one derivatives has attracted the attention of synthetic chemists. Currently, the methods reported for realizing the C3-H alkylation of quinoxalin-2(1H)-one are already very mature, but the methods for synthesizing 1,4-dicarbonyl quinoxalin-2(1H)-one derivatives through the C3-H alkylation of quinoxalin-2(1H)-one are relatively few. The C3-H alkylation of quinoxalin-2(1H)-one can be classified into the following three types.

[0003] The first is the bromide ion-mediated electrochemical trifluoromethylation reaction of quinoxalin-2(1H)-one, in which Baran reagent (Zn(CF3SO2)2) is used as the trifluoromethylation reagent in the system. The bromide ion in tetraethylammonium bromide undergoes an oxidation reaction on the anode surface to generate elemental bromine, which then reacts with Baran reagent to obtain trifluoromethylsulfinyl bromide. This intermediate generates trifluoromethyl radicals through a cathodic single-electron reduction or a homolytic cleavage process and releases sulfur dioxide. Then, the trifluoromethyl radicals react with quinoxalin-2(1H)-one to obtain the final product. The results of the mechanism verification experiment prove that trifluoromethylsulfinyl bromide is the key reaction intermediate. Unfortunately, the reaction yield is relatively low, and the yield is only 27 - 47% (path A).

[0004] The second is the iron-catalyzed cyanoalkylation of quinoxalin-2(1H)-one with cyclobutanone oxime as the alkyl radical precursor. However, high temperature (100 °C) and a relatively large amount of catalyst (15 mol %) are required, which may pose problems for sensitive substrates (path B).

[0005] The third is the photoinduced deamination alkylation through Katritzky salts, that is, an EDA complex is formed between Katritzky salts and DBU, and alkyl radicals are formed through electron transfer under blue light irradiation, and then are captured by quinoxalin-2(1H)-one to obtain partial monocarbonyl compounds (path C).

[0006] Summary of the Invention

[0007] Through research, our research group found that under the irradiation of blue LED light, the ground-state photocatalyst Eosin Y Na reaches the excited state. Meanwhile, ethyl diazoacetate and the excited-state photocatalyst generate alkyl radicals through single-electron transfer, then add to the imine of quinoxalin-2(1H)-one, and then through the isomerization of enamine and imine, add to the alkyl radical again, and finally achieve the C3-H alkylation of quinoxalin-2(1H)-one through single-electron transfer and deprotonation, thereby obtaining 1,4-dicarbonyl quinoxalinone derivative I.

[0008] The reaction process is specifically described as follows:

[0009] First, under blue light irradiation, the ground-state photosensitizer Eosin Y Na reaches the excited state Eosin Y Na*. Ethyl diazoacetate B oxidatively quenches the excited-state photosensitizer Eosin Y Na* through the process of proton-coupled electron transfer (PCET) to obtain alkyl radicals and the oxidized photosensitizer Eosin Y Na; then, a radical addition reaction occurs to quinoxalin-2(1H)-one A to generate a new radical species D, followed by a single-electron transfer with the oxidized photosensitizer Eosin Y Na to obtain the cationic intermediate E, and then deprotonation occurs under the action of a base to obtain compound F; F isomerizes to G, then adds to the radical and is oxidized by the oxidized photosensitizer Eosin Y Na. At this time, the photosensitizer is regenerated and the intermediate H is obtained. After deprotonation of H under the action of a base, the final target product is formed.

[0010]

[0011] Based on the above research background, the present invention provides a synthesis method for obtaining 1,4-dicarbonyl quinoxalinone derivatives by realizing the C3-H alkylation of quinoxalin-2(1H)-one. The present invention uses redox photocatalysis to generate radical precursors through the process of proton-coupled electron transfer (PCET) of diazo compound B to add to quinoxalin-2(1H)-one compound A, and then through the isomerization of enamine and imine, add to the alkyl radical again, and achieve the C3-H alkylation of quinoxalin-2(1H)-one through single-electron transfer and deprotonation, thereby obtaining 1,4-dicarbonyl quinoxalinone derivative I. This method uses visible light as a green energy source for driving, methanol and water as reaction solvents, and the reaction conditions are mild and easy to operate.

[0012] Synthesis method of the 1,4-dicarbonyl quinoxalinone derivative of the present invention: Dissolve quinoxalin-2(1H)-one compound 1, diazo compound 2, Eosin Y Na, and N,N-diisopropylethylamine in solvents methanol and water. After gently shaking evenly by hand, perform degass operation three times continuously using liquid nitrogen and nitrogen (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) to remove trace oxygen in the system. Then place it in a 24 W blue LED lamp box, turn on the light and the fan, and react with stirring for 8 hours. After separation and purification, the target product 3 is obtained.

[0013] The synthesis route is as follows:

[0014]

[0015] The substituent R in compound 1 1 is H, methyl, ethyl, n-propyl, phenyl, benzyl, ester group, cyclopropylmethyl, 1-bromopropyl or 1-hydroxyethyl, and the substituent R 2 is H, methyl or halogen.

[0016] The substituent R in compound 2 3 is ester group or amide.

[0017] The said separation and purification is by the way of separation and purification through silica gel column chromatography, and the eluent is petroleum ether and ethyl acetate, with a volume ratio of 10:1 - 3:1.

[0018] Compared with the prior art, the beneficial effects of the present invention are reflected in:

[0019] 1. The raw materials used are easy to prepare, and ethyl diazoacetate can be commercially purchased.

[0020] 2. Irradiate with an ordinary blue LED lamp.

[0021] 3. The reaction conditions are mild and easy to operate.

[0022] 4. Nitrogen is used as the only by-product, which conforms to the concept of green chemistry.

[0023] 5. The target product can be used as an intermediate to further synthesize other compounds, such as carboxylic acid. Specific embodiments

[0024] The technical solution of the present invention will be further described in detail below in combination with specific embodiments.

[0025] Example 1:

[0026]

[0027] In a 10 mL reaction flask, add compound 1a (0.2 mmol, 32.0 mg), ethyl diazoacetate 2a (1.2 mmol, 136.9 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (1 mL), and water (0.1 mL). After gently shaking evenly by hand, perform three consecutive degass operations (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) using liquid nitrogen and nitrogen to remove trace oxygen in the system. Place it in a 24 W blue LED light box, turn on the light and the fan, and stir the reaction for 8 hours. Separate and purify by silica gel column chromatography [V (petroleum ether):V (ethyl acetate) = 10:1 - 3:1, in this example, V (petroleum ether):V (ethyl acetate) = 5:1 is preferred], and a pure product, yellow oil, is obtained with a yield of 90%.

[0028] Compound 3aa was tested as follows:

[0029] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.81 (d, J = 8.0 Hz, 1H), 7.55 (t, J = 7.8 Hz, 1H), 7.35 - 7.29 (m, 2H), 4.72 (t, J = 7.3 Hz, 1H), 4.20 (q, J = 7.1 Hz, 2H), 4.13 (q, J = 7.1 Hz, 2H), 3.69 (s, 3H), 3.17 - 3.04 (m, 2H), 1.25 - 1.20 (m, 6H).

[0030] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 171.4, 171.0, 156.2, 154.2, 133.3, 132.4, 130.4, 130.2, 123.7, 113.6, 61.4, 60.7, 45.6, 33.9, 29.1, 14.2, 14.1.

[0031] Example 2:

[0032]

[0033] In a 10 mL reaction flask, add compound 1b (0.2 mmol, 34.8 mg), ethyl diazoacetate 2a (1.2 mmol, 136.9 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (1 mL), and water (0.1 mL). After gently shaking by hand, perform three consecutive degass operations (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) using liquid nitrogen and nitrogen to remove trace oxygen in the system. Place it in a 24 W blue LED light box, turn on the light and the fan, and stir the reaction for 8 hours. Purify by silica gel column chromatography [V (petroleum ether):V (ethyl acetate) = 10:1 - 3:1, in this example, V (petroleum ether):V (ethyl acetate) = 5:1 is preferred], and a pure product, yellow oil, is obtained with a yield of 86%.

[0034] Compound 3ba was tested as follows:

[0035] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.82 (d, J = 7.5 Hz, 1H), 7.55 (t, J = 7.8 Hz, 1H), 7.32 (t, J = 7.8 Hz, 2H), 4.71 (t, J = 7.3 Hz, 1H), 4.36 - 4.26 (m, 2H), 4.22 - 4.11 (m, 4H), 3.17 - 3.03 (m, 2H), 1.36 (t, J = 7.2 Hz, 3H), 1.22 (t, J = 7.2 Hz, 6H).

[0036] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 171.4, 171.0, 156.2, 153.7, 132.7, 132.3, 130.5, 130.4, 123.4, 113.4, 61.3, 60.6, 45.6, 37.4, 33.9, 14.1, 14.0, 12.4.

[0037] Example 3:

[0038]

[0039] In a 10 mL reaction flask, add compound 1c (0.2 mmol, 37.7 mg), ethyl diazoacetate 2a (1.2 mmol, 136.9 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (1 mL), and water (0.1 mL). After gently shaking by hand, perform three consecutive degass operations using liquid nitrogen and nitrogen (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) to remove trace oxygen in the system. Place it in a 24 W blue LED light box, turn on the light and the fan, and stir the reaction for 8 hours. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 10:1 - 3:1, in this example, V (petroleum ether): V (ethyl acetate) = 5:1 is preferred], and a pure product, yellow oil, is obtained with a yield of 79%.

[0040] Compound 3ca was tested as follows:

[0041] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = δ 7.82 (d, J = 8.0 Hz, 1H), 7.53 (t, J = 7.8 Hz, 1H), 7.31 (t, J = 7.6 Hz, 2H), 4.70 (t, J = 7.3 Hz, 1H), 4.23 - 4.10 (m, 6H), 3.17 - 3.02 (m, 2H), 1.78 (q, J = 7.6 Hz, 2H), 1.24 - 1.19 (m, 6H), 1.03 (t, J = 7.5 Hz, 3H).

[0042] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 171.4, 171.0, 156.2, 154.0, 132.6, 132.5, 130.5, 130.3, 123.4, 113.6, 61.3, 60.6, 45.7, 43.8, 33.8, 20.6, 14.1, 14.0, 11.2.

[0043] Example 4:

[0044]

[0045] In a 10 mL reaction flask, add compound 1d (0.2 mmol, 29.3 mg), ethyl diazoacetate 2a (1.2 mmol, 136.9 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (1 mL) and water (0.1 mL). After gently shaking evenly by hand, perform degass operation three times continuously using liquid nitrogen and nitrogen (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) to remove trace oxygen in the system. Place it in a 24 W blue LED lamp box, turn on the light and the fan, and stir the reaction for 8 hours. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 10:1 - 3:1, in this example, V (petroleum ether): V (ethyl acetate) = 3:1 is preferred], and a pure product, yellow oil, is obtained with a yield of 78%.

[0046] Compound 3da was tested as follows:

[0047] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.81 (d, J = 8.2 Hz, 1H), 7.52 (t, J = 7.8 Hz, 1H), 7.39 - 7.30 (m, 2H), 4.79 (t, J = 7.3 Hz, 1H), 4.24 - 4.12 (m, 4H), 3.25 - 3.08 (m, 2H), 1.26 - 1.20 (m, 6H).

[0048] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 171.4, 170.9, 156.6, 156.1, 132.5, 131.2, 130.5, 129.2, 124.3, 115.9, 61.4, 60.8, 44.8, 33.9, 14.1, 14.0.

[0049] Example 5:

[0050]

[0051] In a 10 mL reaction flask, add compound 1e (0.2 mmol, 44.4 mg), ethyl diazoacetate 2a (1.2 mmol, 136.9 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (1 mL) and water (0.1 mL). After gently shaking evenly by hand, perform three consecutive degass operations (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) using liquid nitrogen and nitrogen to remove trace oxygen in the system. Place it in a 24 W blue LED light box, turn on the light and the fan, and stir the reaction for 8 hours. Purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 10:1 - 3:1, in this example, V (petroleum ether): V (ethyl acetate) = 3:1 is preferred], and a pure product, yellow oil, is obtained with a yield of 53%.

[0052] Compound 3ea was tested as follows:

[0053] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.86 (d, J = 7.1 Hz, 1H), 7.60 (t, J = 7.5 Hz, 2H), 7.54 (t, J = 7.3 Hz, 1H), 7.37 - 7.27 (m, 4H), 6.69 (d, J = 8.0 Hz, 1H), 4.73 (t, J = 7.2 Hz, 1H), 4.23 - 4.14 (m, 4H), 3.25 - 3.03 (m, 2H), 1.24 (d, J = 7.1 Hz, 6H).

[0054] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 171.4, 170.9, 156.9, 153.9, 135.5, 134.2, 132.2, 130.2, 130.2, 130.0, 129.8, 129.5, 128.2, 128.2, 123.8, 115.4, 61.3, 60.7, 45.7, 33.9, 14.2, 14.0.

[0055] Example 6:

[0056]

[0057] In a 10 mL reaction flask, add compound 1f (0.2 mmol, 47.3 mg), ethyl diazoacetate 2a (1.2 mmol, 136.9 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (1 mL), and water (0.1 mL). After gently shaking evenly by hand, perform three consecutive degass operations (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) using liquid nitrogen and nitrogen to remove trace oxygen in the system. Place it in a 24 W blue LED lamp box, turn on the light and the fan, and stir the reaction for 8 hours. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 10:1 - 3:1, in this example, V (petroleum ether): V (ethyl acetate) = 5:1 is preferred], and a pure product, yellow oil, is obtained with a yield of 85%.

[0058] Compound 3fa was tested:

[0059] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.82 (d, J = 8.1 Hz, 1H), 7.42 (t, J = 7.9 Hz, 1H), 7.31 - 7.21 (m, 7H), 5.48 (t, J = 13.3 Hz, 2H), 4.79 (t, J = 7.2 Hz, 1H), 4.24 - 4.12 (m, 4H), 3.26 - 3.06 (m, 2H), 1.26 - 1.20 (m, 6H).

[0060] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 171.3, 170.9, 156.3, 154.3, 135.0, 132.6, 132.6, 130.3, 130.3, 128.9, 127.7, 126.8, 123.7, 114.4, 61.4, 60.7, 45.8, 45.7, 33.9, 14.1, 14.0.

[0061] Example 7:

[0062]

[0063] In a 10 mL reaction flask, add 1 g (0.2 mmol, 50.1 mg) of compound 1, ethyl diazoacetate 2a (1.2 mmol, 136.9 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (1 mL), and water (0.1 mL). After gently shaking evenly by hand, perform three consecutive degass operations using liquid nitrogen and nitrogen (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) to remove trace oxygen in the system. Place it in a 24 W blue LED light box, turn on the light and the fan, and react with stirring for 8 hours. Purify by silica gel column chromatography [V (petroleum ether):V (ethyl acetate) = 10:1 - 3:1, in this example, V (petroleum ether):V (ethyl acetate) = 5:1 is preferred], and a pure product, yellow oil, is obtained with a yield of 69%.

[0064] Compound 3ga was tested as follows:

[0065] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.80 (d, J = 7.7 Hz, 1H),7.41 (t, J = 7.7 Hz, 1H), 7.29 - 7.24 (m, 2H), 7.14 - 7.06 (m, 4H), 5.50 - 5.38 (m,2H), 4.77 (t, J = 7.2 Hz, 1H), 4.24 - 4.10 (m, 4H), 3.23 - 3.05 (m, 2H), 2.28 (s,3H), 1.25 - 1.19 (m, 6H).

[0066] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 171.4, 170.9, 156.4, 154.4,137.4, 132.6, 132.1, 130.3, 130.3, 129.6, 126.8, 123.6, 114.4, 61.4, 60.7,45.7, 33.9, 21.0, 14.2, 14.0.

[0067] Example 8:

[0068]

[0069] In a 10 mL reaction flask, add compound 1h (0.2 mmol, 54.2 mg), ethyl diazoacetate 2a (1.2 mmol, 136.9 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (1 mL), and water (0.1 mL). After gently shaking evenly by hand, perform three consecutive degass operations using liquid nitrogen and nitrogen (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) to remove trace oxygen in the system. Place it in a 24 W blue LED light box, turn on the light and the fan, and stir the reaction for 8 hours. Separate and purify by silica gel column chromatography [V (petroleum ether):V (ethyl acetate) = 10:1 - 3:1, in this example, V (petroleum ether):V (ethyl acetate) = 5:1 is preferred], and a pure product, yellow oil, is obtained with a yield of 62%.

[0070] Compound 3ha was tested as follows:

[0071] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.82 (d, J = 8.0 Hz, 1H), 7.42 (t, J = 7.8 Hz, 1H), 7.31 - 7.25 (m, 2H), 7.17 (t, J = 7.5 Hz, 3H), 5.51 - 5.38 (m, 2H), 4.81 - 4.72 (m, 1H), 4.22 - 4.10 (m, 4H), 3.23 - 3.07 (m, 2H), 1.25 - 1.19 (m, 6H).

[0072] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 171.3, 170.9, 156.3, 154.3, 133.6, 132.6, 132.4, 130.5, 129.1, 128.3, 123.9, 114.1, 61.4, 60.7, 45.6, 45.3, 33.9, 14.2, 14.0.

[0073] Example 9:

[0074]

[0075] In a 10 mL reaction flask, add compound 1i (0.2 mmol, 43.6 mg), ethyl diazoacetate 2a (1.2 mmol, 136.9 mg), N,N-diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (1 mL), and water (0.1 mL). After gently shaking evenly by hand, perform three consecutive degass operations using liquid nitrogen and nitrogen (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) to remove trace oxygen in the system. Place it in a 24 W blue LED light box, turn on the light and the fan, and stir the reaction for 8 hours. Purify by silica gel column chromatography [V(petroleum ether):V(ethyl acetate) = 10:1 - 3:1, in this example, V(petroleum ether):V(ethyl acetate) = 2:1 is preferred], and a pure product, yellow oil, is obtained with a yield of 72%.

[0076] Compound 3ia was tested as follows:

[0077] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.84 (d, J = 8.0 Hz, 1H), 7.52 (t, J = 7.8 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 7.07 (d, J = 8.4 Hz, 1H), 5.10 - 4.97 (m, 2H), 4.72 (t, J = 7.2 Hz, 1H), 4.22 - 4.11 (m, 4H), 3.77 (s, 3H), 3.18 - 3.05 (m, 2H), 1.24 - 1.19 (m, 2H).

[0078] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 171.3, 170.8, 167.4, 156.1, 153.8, 132.4, 130.7, 130.6, 124.0, 113.0, 61.4, 60.7, 52.8, 45.5, 43.4, 33.9, 14.1, 14.0.

[0079] Example 10:

[0080]

[0081] In a 10 mL reaction flask, add compound 1j (0.2 mmol, 46.5 mg), ethyl diazoacetate 2a (1.2 mmol, 136.9 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (1 mL), and water (0.1 mL). After gently shaking evenly by hand, perform degassing operation three times continuously using liquid nitrogen and nitrogen (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) to remove trace oxygen in the system. Place it in a 24 W blue LED light box, turn on the light and the fan, and stir the reaction for 8 hours. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 10:1 - 3:1, in this example, preferably V (petroleum ether): V (ethyl acetate) = 3:1], and then obtain the pure product, which is a yellow oil, with a yield of 43%.

[0082] Compound 3ja was tested as follows:

[0083] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.84 (d, J = 8.0 Hz, 1H), 7.52 (t, J = 7.9 Hz, 1H), 7.34 (t, J = 7.7 Hz, 1H), 7.07 (d, J = 8.4 Hz, 1H), 5.07 - 4.95 (m, 2H), 4.72 (t, J = 7.3 Hz, 1H), 4.25 - 4.12 (m, 6H), 3.17 - 3.04 (m, 2H), 1.26 - 1.19 (m, 9H).

[0084] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 171.3, 170.7, 166.8, 156.1, 153.8, 132.5, 132.4, 130.6, 130.5, 123.9, 113.1, 62.0, 61.4, 60.7, 45.5, 43.5, 33.9, 14.1, 14.0, 14.0.

[0085] Example 11:

[0086]

[0087] In a 10 mL reaction flask, add compound 1j (0.2 mmol, 53.4 mg), ethyl diazoacetate 2a (1.2 mmol, 136.9 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (1 mL) and water (0.1 mL). After gently shaking evenly by hand, perform three consecutive degass operations (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) using liquid nitrogen and nitrogen to remove trace oxygen in the system. Place it in a 24 W blue LED light box, turn on the light and the fan, and react with stirring for 8 hours. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 10:1 - 3:1, in this example, V (petroleum ether): V (ethyl acetate) = 3:1 is preferred], and a pure product, yellow oil, is obtained with a yield of 77%.

[0088] Compound 3ka was tested as follows:

[0089] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.83 (d, J = 8.0 Hz, 1H), 7.57 (t, J = 7.8 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H), 4.70 (t, J = 7.3 Hz, 1H), 4.41 (t, J = 7.5 Hz, 2H), 4.22 - 4.11 (m, 4H), 3.52 (t, J = 6.2 Hz, 2H), 3.19 - 3.02 (m, 2H), 2.38 - 2.27 (m, 2H), 1.23 (t, J = 7.1 Hz, 6H).

[0090] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 171.3, 170.9, 156.0, 154.1, 132.6, 132.3, 130.6, 130.6, 123.7, 113.3, 61.4, 60.7, 45.5, 41.2, 33.8, 30.3, 30.0, 14.2, 14.1.

[0091] Example 12:

[0092]

[0093] In a 10 mL reaction flask, add compound 1j (0.2 mmol, 38.1 mg), ethyl diazoacetate 2a (1.2 mmol, 136.9 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (1 mL) and water (0.1 mL). After gently shaking evenly by hand, perform degass operation three times continuously using liquid nitrogen and nitrogen (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) to remove trace oxygen in the system. Place it in a 24 W blue LED light box, turn on the light and the fan, and react with stirring for 8 hours. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 10:1 - 3:1, in this example, V (petroleum ether): V (ethyl acetate) = 5:1 is preferred], and a pure product, yellow oil, is obtained, with a yield of 75%.

[0094] Compound 3la was tested as follows:

[0095] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.83 (d, J = 8.0 Hz, 1H), 7.55 (t, J = 7.8 Hz, 1H), 7.44 (d, J = 8.3 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H), 4.71 (t, J = 7.3 Hz, 1H), 4.48 (t, J = 4.1 Hz, 2H), 4.23 - 4.11 (m, 4H), 4.02 (t, J = 5.6 Hz, 2H), 3.21 - 2.99 (m, 2H), 2.05 (s, 1H), 1.26 - 1.21 (m, 6H).

[0096] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 171.4, 171.0, 155.9, 155.0, 132.9, 132.7, 130.5, 123.8, 113.9, 61.4, 60.8, 60.4, 45.5, 44.9, 33.9, 14.2, 14.0.

[0097] Example 13:

[0098]

[0099] In a 10 mL reaction flask, add compound 1m (0.2 mmol, 40.1 mg), ethyl diazoacetate 2a (1.2 mmol, 136.9 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (1 mL) and water (0.1 mL). After gently shaking evenly by hand, perform degass operation three times continuously using liquid nitrogen and nitrogen (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) to remove trace oxygen in the system. Place it in a 24 W blue LED light box, turn on the light and the fan, and stir the reaction for 8 hours. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 10:1 - 3:1, in this example, preferably V (petroleum ether): V (ethyl acetate) = 5:1], then obtain the pure product, yellow oil, yield: 81%.

[0100] Compound 3ma was tested as follows:

[0101] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.85 - 7.79 (m, 1H), 7.58 - 7.52(m, 1H), 7.43 (d, J = 8.4 Hz, 1H), 7.32 (t, J = 7.6 Hz, 1H), 4.69 (t, J = 7.3Hz, 1H), 4.22 - 4.11 (m, 6H), 3.17 - 3.02 (m, 2H), 1.26 - 1.19 (m, 7H), 0.57 - 0.49(m, 4H).

[0102] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) =171.5, 171.1, 156.5, 154.3,132.9, 132.7, 130.6, 130.4, 123.5, 114.0, 61.4, 60.8, 46.2, 45.9, 34.0, 14.2,14.1, 9.7, 4.3, 4.1.

[0103] Example 14:

[0104]

[0105] In a 10 mL reaction flask, add compound 1n (0.2 mmol, 34.8 mg), ethyl diazoacetate 2a (1.2 mmol, 136.9 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (1 mL), and water (0.1 mL). After gently shaking by hand, perform degass operation three times continuously using liquid nitrogen and nitrogen (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) to remove trace oxygen in the system. Place it in a 24 W blue LED light box, turn on the light and the fan, and stir the reaction for 8 hours. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 10:1 - 3:1, in this example, V (petroleum ether): V (ethyl acetate) = 5:1 is preferred], and a pure product, yellow oil, is obtained with a yield of 79%.

[0106] Compound 3na was tested as follows:

[0107] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = δ 7.62 (s, 1H), 7.37 (d, J = 8.5 Hz, 1H), 7.20 (d, J = 8.5 Hz, 1H), 4.72 (t, J = 7.3 Hz, 1H), 4.20 (q, J = 7.1 Hz, 2H), 4.13 (q, J = 7.1 Hz, 2H), 3.68 (s, 3H), 3.16 - 3.03 (m, 2H), 2.44 (s, 3H), 1.25 - 1.20 (m, 6H).

[0108] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 171.4, 171.1, 156.1, 154.2, 133.5, 132.3, 131.6, 131.1, 130.1, 113.4, 61.3, 60.7, 45.6, 33.9, 29.1, 20.6, 14.2, 14.1.

[0109] Example 15:

[0110]

[0111] In a 10 mL reaction flask, add compound 1o (0.2 mmol, 38.9 mg), ethyl diazoacetate 2a (1.2 mmol, 136.9 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (1 mL), and water (0.1 mL). After gently shaking by hand, perform three consecutive degass operations (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) using liquid nitrogen and nitrogen to remove trace oxygen in the system. Place it in a 24 W blue LED light box, turn on the light and the fan, and stir the reaction for 8 hours. Separate and purify by silica gel column chromatography [V (petroleum ether) : V (ethyl acetate) = 10:1 - 3:1, in this example, preferably V (petroleum ether) : V (ethyl acetate) = 5:1], and a pure product, yellow oil, is obtained with a yield of 67%.

[0112] Compound 3oa was tested as follows:

[0113] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.86 - 7.81 (m, 1H), 7.57 - 7.50 (m, 1H), 7.30 - 7.27 (m, 1H), 4.75 (t, J = 7.2 Hz, 1H), 4.26 - 4.13 (m, 4H), 3.71 (s, 3H), 3.23 - 3.03 (m, 2H), 1.26 (t, J = 7.2 Hz, 6H).

[0114] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 171.2, 170.7, 157.7, 153.9, 132.8, 132.1, 130.4, 129.5, 129.0, 114.8, 61.5, 60.8, 45.5, 33.8, 29.3, 14.2, 14.1.

[0115] Example 16:

[0116]

[0117] In a 10 mL reaction flask, add compound 1p (0.2 mmol, 47.8 mg), ethyl diazoacetate 2a (1.2 mmol, 136.9 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (1 mL), and water (0.1 mL). After gently shaking by hand, perform three consecutive degass operations using liquid nitrogen and nitrogen (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) to remove trace oxygen in the system. Place it in a 24 W blue LED lamp box, turn on the light and the fan, and stir the reaction for 8 hours. Separate and purify by silica gel column chromatography [V (petroleum ether):V (ethyl acetate) = 10:1 - 3:1, in this example, V (petroleum ether):V (ethyl acetate) = 5:1 is preferred], and a pure product, yellow oil, is obtained with a yield of 68%.

[0118] Compound 3pa was tested as follows:

[0119] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.96 (s, 1H), 7.63 (d, J = 8.9 Hz, 1H), 7.18 (d, J = 8.9 Hz, 1H), 4.72 (t, J = 7.2 Hz, 1H), 4.22 - 4.09 (m, 4H), 3.67 (s, 3H), 3.20 - 3.00 (m, 2H), 1.23 (t, J = 7.1 Hz, 6H).

[0120] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 171.2, 170.7, 157.6, 153.9, 133.1, 132.5, 132.5, 116.2, 115.1, 61.5, 60.8, 45.4, 33.8, 29.3, 14.1, 14.0.

[0121] Example 17:

[0122]

[0123] In a 10 mL reaction flask, add compound 1q (0.2 mmol, 37.7 mg), ethyl diazoacetate 2a (1.2 mmol, 136.9 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (1 mL), and water (0.1 mL). After gently shaking by hand, perform degassing three times continuously using liquid nitrogen and nitrogen (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) to remove trace oxygen in the system. Place it in a 24 W blue LED lamp box, turn on the light and the fan, and stir the reaction for 8 hours. Separate and purify by silica gel column chromatography [V (petroleum ether):V (ethyl acetate) = 10:1 - 3:1, in this example, V (petroleum ether):V (ethyl acetate) = 5:1 is preferred], and a pure product, yellow oil, is obtained with a yield of 82%.

[0124] Compound 3qa was tested as follows:

[0125] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.57 (s, 1H), 7.06 (s, 1H), 4.70 (t, J = 7.3 Hz, 1H), 4.22 - 4.09 (m, 4H), 3.66 (s, 3H), 3.14 - 3.02 (m, 2H), 2.40 (s, 3H), 2.33 (s, 3H), 1.22 (t, J = 7.1 Hz, 6H).

[0126] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 171.4, 171.2, 154.9, 154.3, 140.3, 132.6, 131.3, 130.8, 130.2, 114.2, 61.2, 60.6, 45.5, 34.0, 29.0, 20.5, 19.1, 14.1, 14.1.

[0127] Example 18:

[0128]

[0129] In a 10 mL reaction flask, add compound 1q (0.2 mmol, 45.8 mg), ethyl diazoacetate 2a (1.2 mmol, 136.9 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (1 mL) and water (0.1 mL). After gently shaking by hand, perform three consecutive degass operations using liquid nitrogen and nitrogen (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) to remove trace oxygen in the system. Place it in a 24 W blue LED light box, turn on the light and the fan, and stir the reaction for 8 hours. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 10:1 - 3:1, in this example, V (petroleum ether): V (ethyl acetate) = 5:1 is preferred], and a pure product, yellow oil, is obtained with a yield of 66%.

[0130] Compound 3ra was tested:

[0131] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.89 (s, 1H), 7.40 (s, 1H), 4.73 - 4.688 (m, 1H), 4.22 - 4.09 (m, 4H), 3.65 (s, 3H), 3.18 - 2.98 (m, 2H), 1.23 (t, J = 7.1 Hz, 6H).

[0132] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 171.2, 170.6, 157.8, 153.7, 134.6, 132.7, 131.3, 130.9, 130.9, 127.5, 61.5, 60.8, 45.4, 33.7, 29.5, 14.2, 14.1.

[0133] Example 19:

[0134]

[0135] In a 10 mL reaction flask, add compound 1a (0.2 mmol, 32.0 mg), ethyl diazoacetate 2b (1.2 mmol, 153.8 mg), N,N-diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (0.1 mL) and water (0.9 mL). After gently shaking evenly by hand, perform degass operation three times continuously using liquid nitrogen and nitrogen (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) to remove trace oxygen in the system. Place it in a 24W blue LED lamp box, turn on the light and the fan, and react and stir for 8 hours. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 10:1 - 3:1, in this example, V (petroleum ether): V (ethyl acetate) = 5:1 is preferred], and a pure product, yellow oil, is obtained, with a yield of 90%.

[0136] Compound 3ab was tested as follows:

[0137] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.77 (d, J = 7.9 Hz, 1H), 7.51 (t, J = 7.9 Hz, 1H), 7.32 - 7.24 (m, 2H), 5.09 - 5.01 (m, 1H), 5.00 - 4.93 (m, 1H), 4.63 (t, J = 7.3 Hz, 1H), 3.65 (s, 3H), 3.12 - 2.92 (m, 2H), 1.21 - 1.15 (m, 12H).

[0138] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 170.8, 170.5, 156.3, 154.1, 133.3, 132.3, 130.3, 130.0, 123.5, 113.6, 68.7, 67.9, 45.9, 34.1, 29.0, 21.7, 21.6, 21.5.

[0139] Example 20:

[0140]

[0141] In a 10 mL reaction flask, add compound 1a (0.2 mmol, 32.0 mg), ethyl diazoacetate 2c (1.2 mmol, 153.8 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (0.1 mL) and water (0.9 mL). After gently shaking evenly by hand, perform degass operation three times continuously using liquid nitrogen and nitrogen (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) to remove trace oxygen in the system. Place it in a 24W blue LED lamp box, turn on the light and the fan, and stir the reaction for 8 hours. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 10:1 - 3:1, in this example, V (petroleum ether): V (ethyl acetate) = 5:1 is preferred], and a pure product, yellow oil, is obtained with a yield of 91%.

[0142] Compound 3ac was tested as follows:

[0143] 1 1H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.81 (d, J = 7.3 Hz, 1H), 7.55 (t, J = 7.8 Hz, 1H), 7.36 - 7.28 (m, 2H), 4.75 (t, J = 7.3 Hz, 1H), 4.10 (t, J = 6.0 Hz, 2H), 4.03 (t, J = 6.7 Hz, 2H), 3.70 (s, 3H), 3.22 - 3.03 (m, 2H), 1.65 - 1.58 (m, 4H), 0.91 - 0.85 (m, 6H).

[0144] 13 13C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 171.4, 171.1, 156.3, 154.2, 133.3, 132.4, 130.4, 130.2, 123.6, 113.6, 66.9, 66.3, 45.6, 33.8, 29.1, 21.9, 21.8, 10.3, 10.2.

[0145] Example 21:

[0146]

[0147] In a 10 mL reaction flask, add compound 1a (0.2 mmol, 32.0 mg), ethyl diazoacetate 2d (1.2 mmol, 168.2 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (0.1 mL) and water (0.9 mL). After gently shaking evenly by hand, perform three consecutive degass operations (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) using liquid nitrogen and nitrogen to remove trace oxygen in the system. Place it in a 24W blue LED light box, turn on the light and the fan, and stir the reaction for 8 hours. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 10:1 - 3:1, in this example, V (petroleum ether): V (ethyl acetate) = 5:1 is preferred], and a pure product, yellow oil, is obtained with a yield of 85%.

[0148] Compound 3ad was tested:

[0149] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.80 (d, J = 7.9 Hz, 1H), 7.53 (t, J = 7.8 Hz, 1H), 7.34 - 7.27 (m, 2H), 5.06 - 4.91 (m, 2H), 4.66 (t, J = 7.2 Hz, 1H), 3.67 (s, 3H), 3.14 - 2.95 (m, 2H), 2.36 - 2.24 (m, 4H), 2.10 - 1.98 (m, 4H), 1.79 - 1.69 (m, 2H), 1.63 - 1.52 (m, 2H).

[0150] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 170.6, 170.3, 156.1, 154.1, 133.3, 132.3, 130.4, 130.1, 123.6, 113.6, 69.8, 69.0, 45.5, 33.7, 30.1, 30.1, 30.0, 29.1, 13.5.

[0151] Example 22:

[0152]

[0153] In a 10 mL reaction flask, add compound 1a (0.2 mmol, 32.0 mg), ethyl diazoacetate 2e (1.2 mmol, 185.0 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (0.1 mL) and water (0.9 mL). After gently shaking evenly by hand, perform the degass operation three times continuously using liquid nitrogen and nitrogen (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) to remove trace oxygen in the system. Place it in a 24W blue LED lamp box, turn on the light and the fan, and stir the reaction for 8 hours. Purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 10:1 - 3:1, in this example, preferably V (petroleum ether): V (ethyl acetate) = 5:1], and then a pure product, yellow oil, is obtained with a yield of 82%.

[0154] Compound 3ae was tested:

[0155] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.80 (d, J = 7.9 Hz, 1H), 7.53 (t, J = 7.8 Hz, 1H), 7.34 - 7.27 (m, 2H), 5.06 - 4.91 (m, 2H), 4.66 (t, J = 7.2 Hz, 1H), 3.67 (s, 3H), 3.14 - 2.95 (m, 2H), 2.36 - 2.24 (m, 4H), 2.10 - 1.98 (m, 4H), 1.79 - 1.69 (m, 2H), 1.63 - 1.52 (m, 2H).

[0156] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 170.6, 170.3, 156.1, 154.1, 133.3, 132.3, 130.4, 130.1, 123.6, 113.6, 69.8, 69.0, 45.5, 33.7, 30.1, 30.1, 30.0, 29.1, 13.5.

[0157] Example 23:

[0158]

[0159] In a 10 mL reaction flask, add compound 1a (0.2 mmol, 32.0 mg), ethyl diazoacetate 2f (1.2 mmol, 218.6 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (0.1 mL) and water (0.9 mL). After gently shaking by hand, perform the degass operation three times continuously using liquid nitrogen and nitrogen (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) to remove trace oxygen in the system. Place it in a 24W blue LED lamp box, turn on the light and the fan, and react with stirring for 8 hours. Purify by silica gel column chromatography [V (petroleum ether):V (ethyl acetate) = 10:1 - 3:1, in this example, V (petroleum ether):V (ethyl acetate) = 5:1 is preferred], and a pure product, yellow oil, is obtained with a yield of 60%.

[0160] Compound 3af was tested as follows:

[0161] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.62 (d, J = 7.9 Hz, 1H), 7.48 (t, J = 7.8 Hz, 1H), 7.24 - 7.16 (m, 4H), 7.00 - 6.94 (m, 2H), 6.89 - 6.83 (m, 2H), 5.25 (s, 2H), 5.17 (d, J = 3.6 Hz, 2H), 4.71 (t, J = 7.3 Hz, 1H), 3.60 (s, 3H), 3.17 - 2.99 (m, 2H).

[0162] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 170.8, 170.5, 155.6, 154.1, 137.6, 137.5, 133.3, 132.3, 130.5, 130.4, 128.2, 128.2, 126.7, 126.7, 123.6, 113.5, 61.4, 60.7, 45.4, 33.6, 29.1.

[0163] Example 24:

[0164]

[0165] In a 10 mL reaction flask, add compound 1a (0.2 mmol, 32.0 mg), ethyl diazoacetate 2g (1.2 mmol, 211.4 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (0.1 mL) and water (0.9 mL). After gently shaking evenly by hand, perform three consecutive degass operations (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) using liquid nitrogen and nitrogen to remove trace oxygen in the system. Place it in a 24W blue LED light box, turn on the light and the fan, and react with stirring for 8 hours. Separate and purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 10:1 - 3:1, in this example, V (petroleum ether): V (ethyl acetate) = 5:1 is preferred], and a pure product, yellow oil, is obtained with a yield of 63%.

[0166] Compound 3ag was tested as follows:

[0167] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.71 (d, J = 8.0 Hz, 1H), 7.54 (t, J = 7.8 Hz, 1H), 7.34 - 7.25 (m, 12H), 5.17 (s, 2H), 5.09 (s, 2H), 4.84 (t, J = 7.3 Hz, 1H), 3.64 (s, 3H), 3.32 - 3.05 (m, 2H).

[0168] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 171.1, 170.8, 155.8, 154.2, 135.7, 135.6, 133.3, 132.3, 130.5, 130.2, 128.4, 128.4, 128.1, 128.1, 128.0, 123.6, 113.6, 67.0, 66.5, 45.5, 33.8, 29.1.

[0169] Example 25:

[0170]

[0171] In a 10 mL reaction flask, add compound 1a (0.2 mmol, 32.0 mg), ethyl diazoacetate 2h (1.2 mmol, 169.4 mg), N,N - diisopropylethylamine (0.2 mmol, 25.8 mg), Eosin Y Na (1 mol%, 1.4 mg), methanol (0.1 mL) and water (0.9 mL). After gently shaking evenly by hand, perform three consecutive degass operations (liquid nitrogen freezing system - oil pump evacuation - warm water thawing) using liquid nitrogen and nitrogen to remove trace oxygen in the system. Place it in a 24W blue LED light box, turn on the light and the fan, and stir the reaction for 8 hours. Purify by silica gel column chromatography [V (petroleum ether): V (ethyl acetate) = 10:1 - 3:1, in this example, V (petroleum ether): V (ethyl acetate) = 5:1 is preferred], and a pure product, yellow oil, is obtained with a yield of 82%.

[0172] Compound 3ah was tested as follows:

[0173] 1 H NMR (400 MHz, CDCl3, 300 K): δ (ppm) = 7.73 (d, J = 7.9 Hz, 1H), 7.46 (t, J = 7.8 Hz, 1H), 7.25 - 7.19 (m, 2H), 5.13 - 5.01 (m, 1H), 3.61 (s, 3H), 3.56 - 3.24 (m, 8H), 2.68 - 2.46 (m, 1H), 1.87 (s, 1H), 1.39 - 1.29 (m, 6H), 1.11 (t, J = 7.1 Hz, 3H), 1.03 (t, J = 7.1 Hz, 3H).

[0174] 13 C NMR (100 MHz, CDCl3, 300 K): δ (ppm) = 171.3, 169.9, 157.3, 154.4, 133.3, 132.5, 129.9, 129.8, 123.2, 113.4, 43.1, 42.7, 42.2, 40.5, 40.5, 32.8, 29.0, 14.4, 14.2, 13.0, 12.8.

[0175] Example 26:

[0176]

[0177] In a 10 mL reaction flask, compound 3aa (0.2 mmol, 66.5 mg) and potassium hydroxide (1.0 mmol, 56.0 mg) were added to methanol (2 mL) and water (1 mL), and the mixture was stirred at 60 °C for 4 hours. After the reaction was completed, water (10 mL) was added for dilution, and the pH of the mixed solution was adjusted to 1.0 using hydrochloric acid (2 M). Then, it was extracted with ethyl acetate (10 mL × 3). It was separated and purified by silica gel column chromatography [V(methylene chloride):V(methanol) = 20:1] to obtain the pure product, a white solid, with a yield of 72%.

[0178] Compound 4 was tested as follows:

[0179] 1 H NMR (400 MHz, DMSO-d6): δ (ppm) = 12.11 (s, 1H), 7.73 (d, J = 7.5 Hz, 1H), 7.64 - 7.50 (m, 2H), 7.36 (t, J = 7.2 Hz, 1H), 3.62 (s, 3H), 3.04 (t, J = 7.0 Hz, 2H), 2.72 (t, J = 7.0 Hz, 2H).

[0180] 13 C NMR (100 MHz, DMSO-d6): δ (ppm) = 173.87, 158.71, 154.04, 132.86, 131.69, 129.73, 128.81, 123.32, 114.63, 29.54, 28.88, 28.27.

Claims

1. A synthesis method of 1,4-dicarbonyl quinoxalinone derivatives, characterized in that: Dissolve quinoxalin-2(1H)-one compound 1, diazo compound 2, eosin Y sodium, and N,N-diisopropylethylamine in a mixed solvent. After mixing evenly, perform degassing operations three times continuously with liquid nitrogen and nitrogen to remove trace oxygen in the system. Stir and react under the irradiation of a blue LED lamp, and obtain the target product 3 after separation and purification; The synthesis route is as follows: ； The substituent R in the quinoxalin-2(1H)-one compound 1 1 is H, methyl, ethyl, n-propyl, phenyl, benzyl, ester group, cyclopropylmethyl, 1-bromopropyl or 1-hydroxyethyl, and the substituent R 2 is H, methyl or halogen; The diazo compound 2 is selected from compounds with the following structures: 、 、 、 、 、 、 、 。 2. The synthesis method according to claim 1, characterized in that: The mixed solvent is composed of a mixture of methanol and water.

3. The synthesis method according to claim 2, characterized in that: The volume ratio of methanol to water in the mixed solvent is 10:

1.

4. The synthesis method according to claim 1, characterized in that: The separation and purification is carried out by silica gel column chromatography, and the eluent is petroleum ether and ethyl acetate with a volume ratio of 10:1 - 3:1.

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