Synthesis method of a 1,2,3-triazoloquinoxaline compound

Abstract

The present invention relates to a method for synthesizing 1,2,3-triazoloquinoxaline compounds. The synthesis method uses heterocyclic enaminones as substrates, and reacts with tosyl azide at room temperature in a solvent for 2 hours under the promotion of a base to generate 1,2,3-triazolo-[1,5-a]quinoxaline compounds. This method does not require the participation of transition metals, reacts at room temperature, has mild conditions, and conforms to the characteristics of green and sustainable chemical development.

Description

Technical Field

[0001] The present invention relates to the technical field of compound synthesis, and specifically to a method for synthesizing 1,2,3-triazoloquinoxaline compounds. Background Art

[0002] In recent years, 1,2,3-triazole polycyclic compounds have been widely used in medicinal chemistry research due to their various pharmacological activities such as anti-cancer, anti-tuberculosis, anti-viral, anti-inflammatory and antibacterial. For example, triazole quinoxalinones ( Figure 1 , A) have good affinity for benzodiazepine receptors and good affinity and selectivity for adenosine A1 receptor subtypes; triazole pyrimidinones ( Figure 1 , B) are designed as novel anti-tumor drugs; triazole benzodiazepinone ( Figure 1 , C) has achieved clinical success in the treatment of central nervous system diseases.

[0003] The 1,2,3-triazole-[1,5-a]quinoxaline skeleton exists in G protein-coupled nicotinic acid receptor 109A and inhibitors that bind to benzodiazepine and adenosine receptors, and has good clinical application prospects. Therefore, chemical engineers have begun to focus on the synthesis of such triazoles. The classical method requires multiple steps. First, a triazole intermediate is generated, and then ring amide formation or Pictet-Spengler cyclization is carried out starting from 2-nitrobenzyl azide or 1-fluoro-2-nitrobenzene respectively to obtain the target product ( Figure 2 , aand b).

[0004] In 2010, Gong, Chen, etc. utilized the cycloaddition reaction of N-(o-halophenyl) alkynyl imine with sodium azide, and then formed an aryl C-N bond through a copper-catalyzed Ullmann coupling reaction to obtain the 1,2,3-triazole-[1,5-a]quinoxaline skeleton. In 2014, He, etc. used o-heterocyclic substituted aromatic ring cyanide and PhI(OCOCy)2 as raw materials in DMF, with an iridium complex [fac-Ir(ppy)3] as a photocatalyst, and irradiated with a household 26W compact fluorescent lamp for 5 hours to obtain the 1,2,3-triazole-[1,5-a]quinoxaline product. In 2017, Li, etc. through the optimization of the CUAAC reaction, reacted 1-azido-2-isocyano-3,5-xylene and acetylene compounds under the catalysis of Cu(OAc)2 to obtain the product with a yield of 73%, and no triazole intermediate was detected during the reaction process. In 2021, Chen and Zhu, etc. successfully obtained a series of 1,2,3-triazole-[1,5-a]quinoxaline compounds through the reaction of N-propargyl-N-(2-iodoformyl)amide and sodium azide under the catalysis of copper.

[0005] Although the above reactions can all successfully synthesize 1,2,3-triazolo-[1,5-a]quinoxaline compounds, most of them use sodium azide as a raw material, which is somewhat dangerous; and using transition metals as catalysts is difficult to handle and prone to environmental pollution. Therefore, there is a particular need for a synthesis method of 1,2,3-triazoloquinoxaline compounds that is safe and environmentally friendly during the synthesis process. Summary of the Invention

[0006] The object of the present invention is to provide a synthesis method of 1,2,3-triazoloquinoxaline compounds to solve the above problems.

[0007] The solution of the present invention is as follows: A synthesis method of 1,2,3-triazoloquinoxaline compounds, wherein the synthesis method uses heterocyclic enaminones as substrates, and reacts with tosyl azide under the promotion of a base at room temperature in a solvent to generate 1,2,3-triazolo-[1,5-a]quinoxaline compounds.

[0008] Further, the base is one of potassium tert-butoxide, potassium hydroxide, cesium carbonate or 1,8-diazabicyclo[5.4.0]undec-7-ene.

[0009] Further, the solvent is acetonitrile or toluene.

[0010] Further, after the reaction is completed, the acetonitrile is rotary evaporated, water and ethyl acetate are added for extraction, the organic layer is dried with anhydrous Na2SO4, and then separated by silica gel column chromatography. The eluent: petroleum ether / ethyl acetate = 10 / 1, 8 / 1, v / v, and the white solid obtained is the target compound.

[0011] Further, the molar ratio of the heterocyclic enaminone to tosyl azide is 2:3.

[0012] Further, the amount of the solvent used is 2 mL.

[0013] Further, the amount of water used is 20 - 30 mL, and the amount of ethyl acetate used is 3×10 - 15 mL.

[0014] Advantages of the Present Invention:

[0015] The present invention uses heterocyclic enaminones as substrates and reacts with TsN3 under the promotion of a base to successfully obtain 1,2,3-triazolo-[1,5-a]quinoxaline compounds. Moreover, this method does not require the participation of transition metals, reacts at room temperature, and has mild conditions, meeting the characteristics of green and sustainable chemical development. Description of the Drawings

[0016] Figure 1 Shown are examples of bioactive 1,2,3-triazole polycyclic compounds;

[0017] Figure 2Shown is the classical synthesis method of 1,2,3-triazole-[1,5-a]quinoxaline;

[0018] Figure 3 Shown is the synthesis of 1,2,3-triazole-[1,5-a]quinoxaline by copper-catalyzed Ullmann coupling reaction;

[0019] Figure 4 Shown is the photocatalytic synthesis method of 1,2,3-triazole-[1,5-a]quinoxaline;

[0020] Figure 5 Shown is the optimized CUAA reaction for the synthesis of 1,2,3-triazole-[1,5-a]quinoxaline;

[0021] Figure 6 Shown is the synthesis of 1,2,3-triazole-[1,5-a]quinoxaline using N-propargyl-N-(2-iodoformyl)amide as the raw material;

[0022] Figure 7 Shown is the synthesis of 1,2,3-triazole-fused quinoxaline compounds;

[0023] Figure 8 Shown is the synthesis method of enaminone substrates;

[0024] Figure 9 Shown are 1,2,3-triazole-fused quinoxaline compounds obtained from different substrates. Detailed implementation mode

[0025] The present invention will be described in detail below with reference to the accompanying drawings and specific embodiments:

[0026] Reagents used in the present invention:

[0027] Acetophenone, Adamas-beta; Iodine, Aladdin Chemistry; Cuprous iodide, Aladdin Chemistry; o-Phenylenediamine, Aladdin Chemistry; p-Toluenesulfonyl azide, Aladdin Chemistry; Potassium tert-butoxide, Aladdin Chemistry; N,N-Dimethylformamide, Macklin; Dichloromethane, Xilong Chemical; Toluene, Tianjin Fuchen Chemical Reagent Factory; Acetone, Guangzhou Chemical Reagent Factory; Chloroform, Guangzhou Chemical Reagent Factory; Acetonitrile, Aladdin; 1,4-Dioxane, Aladdin; Dimethyl sulfoxide, Aladdin; Sodium thiosulfate, Xilong Chemical; Isopropanol, Aladdin Chemistry; Ethyl acetate, GALAXY-REAGENT; Petroleum ether, GALAXY-REAGENT; Anhydrous magnesium sulfate, Xilong Chemical; Cesium carbonate, Aladdin Chemistry; Potassium carbonate, Aladdin Chemistry; Sodium carbonate, Aladdin Chemistry; Lithium tert-butoxide, Aladdin Chemistry; Sodium tert-butoxide, Aladdin Chemistry; Lithium hydroxide, Aladdin Chemistry; Sodium hydroxide, GALAXY-REAGENT; Potassium hydroxide, Xilong Chemical; Triethylamine, Xilong Chemical; DBU, Adamas-beta; DABCO, Methanol, Xilong Chemical; Tetrahydrofuran, Xilong Chemical; Water, Ethanol, GALAXY-REAGENT; N-Methylpyrrolidone, Tianjin Damao Chemical Reagent Factory.

[0028] Instruments used in this invention:

[0029] Rotary evaporator (Model N-1300), Shanghai Ailang Instrument Co., Ltd.; Circulating water vacuum pump (Model SHZ-DⅢ), Gongyi Yuhua Instrument Co., Ltd.; Diaphragm vacuum pump (Model MVP-1000), Shanghai Ailang Instrument Co., Ltd.; Low-temperature coolant circulating pump (Model DLSB-5), Gongyi Yuhua Instrument Co., Ltd.; Ultrasonic cleaner (Model KQ-100V), Kunshan Ultrasonic Instrument Co., Ltd.; Magnetic heating stirrer (Model 78-1), Changzhou Aohua Instrument Co., Ltd.; Analytical balance (Model XS105DR), Mettler Toledo International Co., Ltd.; Electronic balance (Model FA1104), Shanghai Liangping Instrument Co., Ltd.; Dark box type ultraviolet analyzer (Model ZF-20D), Gongyi Ruide Instrument Equipment Co., Ltd.; LCD digital control heating type magnetic stirrer (Model MS-H-Pro), BlueSpin; Forced air drying oven (Model DHG-9240A), Shanghai Jingqi Instrument Co., Ltd.; Thin layer chromatography silica gel plate (HSGF254), Yantai Jiangyou Silica Gel Development Co., Ltd.; Melting point apparatus (Model WRR), Shanghai Yidian Physical Optics Instrument Co., Ltd.; Nuclear magnetic resonance spectrometer (Model AVANCE600), Bruker.

[0030] Synthesis of heterocyclic enaminones

[0031] Acetophenone (5.67 g, 30 mmol) was added to a 250 mL eggplant-shaped flask containing 150 mL of dimethyl sulfoxide. Then, copper oxide (7.2 g, 90 mmol) and iodine (15.24 g, 60 mmol) were added successively. After stirring at 70 °C for 18 h, it was cooled to room temperature. After filtration, saturated sodium thiosulfate solution was added until the purple color disappeared. It was extracted with ethyl acetate (3 × 50 mL). After drying the organic layer, it was concentrated under reduced pressure and separated by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 6 / 1, 3 / 1, 2 / 1, v / v) to obtain a yellow oily liquid (Compound 1, 3 g, yield 35%). Compound 1 (1.354 g, 4.8 mmol) and o-phenylenediamine (0.5184 g, 4.8 mmol) were added to a 50 mL eggplant-shaped flask, and then 10 mL of isopropanol was added to dissolve. After refluxing at 85 °C for 12 h, it was filtered and washed to obtain a yellow solid (Compound 2aa, 0.98 g, yield 62.5%).

[0032] Example 1

[0033] Synthesis of 1,2,3-triazoloquinoxaline compounds

[0034] The synthesis reaction process of the 1,2,3-triazoloquinoxaline compounds of the present invention and the structural formula of the obtained product are as Figure 7 shown. Compound heterocyclic enaminone (2aa) (0.162 g, 0.5 mmol) and potassium tert-butoxide (0.112 g, 1 mmol) were dissolved in 2 mL of acetonitrile, and then p-toluenesulfonyl azide (TsN3, 0.147 g, 0.75 mmol) was added dropwise. After reacting at room temperature for 2 h, the acetonitrile was evaporated to dryness, water (20 mL) was added, and it was extracted with ethyl acetate (3 × 10 mL). After drying the organic layer with anhydrous Na2SO4, it was separated by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 10 / 1, 8 / 1, v / v) to obtain a white solid (Compound 1,2,3-triazolo-[1,5-a]quinoxaline compound (3aa), 0.154 g, yield 88%).

[0035] Examples 2 - 11

[0036] As Figure 9 shown, we dissolved heterocyclic enaminone compound 2 with different substituents and TsN3 in acetonitrile and reacted at room temperature for 2 hours to successfully obtain Compound 3. By expanding the substrate, 10 compounds were obtained, namely 3ab, 3ac, 3ad, 3ae, 3af, 3ag, 3ah, 3ai, 3ba, 3ca in Figure 9 , and other conditions were the same as in Example 1.

[0037] Example 12

[0038] The compound heterocyclic enaminone (2aa) (0.162 g, 0.5 mmol) and potassium hydroxide (0.112 g, 1 mmol) were dissolved in 2 mL of toluene, and then p-toluenesulfonyl azide (TsN3, 0.147 g, 0.75 mmol) was added dropwise. After reacting at room temperature for 2 h, the toluene was evaporated to dryness. Water (20 mL) was added, and the mixture was extracted with ethyl acetate (3 × 15 mL). The organic layer was dried over anhydrous Na2SO4 and then separated by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 10 / 1, 8 / 1, v / v) to obtain a white solid (the yield of compound 1,2,3-triazole-[1,5-a]quinoxaline compound (3aa) was 83%).

[0039] Example 13

[0040] The compound heterocyclic enaminone (2aa) (0.162 g, 0.5 mmol) and cesium carbonate Cs2CO3 (0.112 g, 1 mmol) were dissolved in 2 mL of acetonitrile, and then p-toluenesulfonyl azide (TsN3, 0.147 g, 0.75 mmol) was added dropwise. After reacting at room temperature for 2 h, the acetonitrile was evaporated to dryness. Water (25 mL) was added, and the mixture was extracted with ethyl acetate (3 × 10 mL). The organic layer was dried over anhydrous Na2SO4 and then separated by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 10 / 1, 8 / 1, v / v) to obtain a white solid (the yield of compound 1,2,3-triazole-[1,5-a]quinoxaline compound (3aa) was 25%).

[0041] Example 14

[0042] The compound heterocyclic enaminone (2aa) (0.162 g, 0.5 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene DBU (0.112 g, 1 mmol) were dissolved in 2 mL of toluene, and then p-toluenesulfonyl azide (TsN3, 0.147 g, 0.75 mmol) was added dropwise. After reacting at room temperature for 2 h, the acetonitrile was evaporated to dryness. Water (30 mL) was added, and the mixture was extracted with ethyl acetate (3 × 15 mL). The organic layer was dried over anhydrous Na2SO4 and then separated by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 10 / 1, 8 / 1, v / v) to obtain a white solid (compound 1,2,3-triazole-[1,5-a]quinoxaline compound (3aa), yield 49%).

[0043] From the above examples, we found that the substituents R2 in the aromatic ring of enaminone with electron-donating groups (Me, OMe) ( Figure 9 3ab&3ac&3ad in Figure 9,3ae&3af) have relatively high yields. And by comparing the yields of 3ab and 3ac (92% vs. 90%), and 3ag and 3ah (57% vs. 54%), it was found that steric hindrance had no obvious effect on the reaction. Subsequently, we also studied the heterocyclic substituent (thiophene), and its yield was quite impressive, at 70%. In addition, we found that enaminones with different substituents R1 also had good tolerance during the synthesis process (3ba&3ca), and there was no obvious regularity in the change of yield.

[0044] Structural characterization of the obtained compounds

[0045] phenyl(4-phenyl-[1,2,3]triazolo[1,5-a]quinoxalin-3-yl)methanone(3aa)white solid,mp 201-205℃. 1 H NMR (400MHz, CDCl3) δ8.82(d,J=8.0Hz,1H),8.27(d,J=8.0Hz,1H),8.04(d,J=8.0Hz, 2H),7.86-7.79(m,2H),7.65-7.59(m,3H),7.49-7.44(m,3H),7.38(t,J=8.0Hz,2H); 13 C{ 1 H}NMR(100MHz,CDCl3)δ186.6,153.2,141.1,137.0,136.8,136.6,133.6(2C),130.5 6(2C),130.55(2C),130.4,130.2,129.5,128.4(2C),128.3(2C),125.5,124.4(2C).

[0046] o-tolyl(4-(o-tolyl)-[1,2,3]triazolo[1,5-a]quinoxalin-3-yl)methanone(3ab)yellow solid,mp 165-168℃. 1 H NMR(400MHz, CDCl3) δ8.85(d,J=8.0Hz,1H),8.27(d,J=8.0Hz,1H),7.91-7. 82(m,2H),7.40-7.28(m,3H),7.22-7.14(m,5H),2.33(s,3H),2.22(s,3H); 13 C{ 11H NMR (100 MHz, CDCl3) δ 186.6, 154.0, 142.2, 139.3, 136.7, 136.5, 135.7, 131.9, 131.7, 131.4, 130.75 (2C), 130.73 (2C), 130.2, 129.6, 129.5, 128.0, 125.8, 125.2, 124.5, 115.9, 21.2, 19.7.

[0047] p-tolyl(4-(p-tolyl)-[1,2,3]triazolo[1,5-a]quinoxalin-3-yl)methanone (3ac), yellow solid, mp 192 - 197 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.81 - 8.79 (m, 1H), 8.25 - 8.23 (m, 1H), 8.07 (d, J = 12.0 Hz, 2H), 7.83 - 7.78 (m, 2H), 7.63 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 8.0 Hz, 2H), 6.87 (d, J = 8.0 Hz, 2H), 3.90 (s, 3H), 3.83 (s, 3H); 13 C{ 1 13C{1H} NMR (100 MHz, CDCl3) δ 185.4, 164.1, 161.5, 152.7, 141.4, 137.0, 133.0 (2C), 130.1 (2C), 129.9 (2C), 129.8, 129.4 (2C), 129.3, 125.3, 124.3, 115.8 (2C), 113.8 (2C), 55.5, 55.3.

[0048] methoxyphenyl)(4-(4-methoxyphenyl)-[1,2,3]triazolo[1,5-a]quinoxalin-3-yl)methanone (3ad), yellow solid, mp 198 - 202 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.81 - 8.79 (m, 1H), 8.25 (d, J = 8.0 Hz, 1H), 7.96 (d, J = 8.0 Hz, 2H), 7.84 - 7.77 (m, 2H), 7.56 (d, J = 4.0 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 2.44 (s, 3H), 2.37 (s, 3H); 13 C{ 11H NMR (100 MHz, CDCl3) δ 168.4, 153.2, 144.7, 141.3, 140.8, 137.0, 134.2, 134.0, 130.7 (2C), 130.1, 130.0, 129.4, 129.2 (2C), 129.1 (2C), 128.3 (2C), 125.4, 124.3, 115.7, 21.76, 21.50.

[0049] (4-fluorophenyl)(4-(4-fluorophenyl)-[1,2,3]triazolo[1,5-a]quinoxalin-3-yl)methanone (3ae) white solid, mp 178 - 183 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.82 (d, J = 8.0 Hz, 1H), 8.27 (d, J = 8.0 Hz, 1H), 8.16 - 8.13 (m, 2H), 7.89 - 7.82 (m, 2H), 7.66 - 7.63 (m, 2H), 7.18 (t, J = 8.0 Hz, 2H), 7.10 (t, J = 8.0 Hz, 2H); 13 C{ 1 1H NMR (100 MHz, CDCl3) δ 184.8, 167.5, 165.3, 164.9, 162.8, 152.0, 140.7, 136.9, 133.4, 133.3, 133.0, 132.9, 130.7, 130.5, 130.4, 130.1, 129.8, 125.5, 124.2, 115.9, 115.8, 115.76, 115.70, 115.5.

[0050] (4-iodophenyl)(4-(4-iodophenyl)-[1,2,3]triazolo[1,5-a]quinoxalin-3-yl)methanone (3af) white solid, mp 238 - 242 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.82 (d, J = 8.0 Hz, 1H), 8.28 (d, J = 8.0 Hz, 1H), 7.89 - 7.74 (m, 8H), 7.34 (d, J = 8.0 Hz, 2H); 13 C{ 11H NMR (100 MHz, CDCl3) δ 185.6, 152.1, 140.5, 137.9 (2C), 137.6 (2C), 136.9, 136.2, 135.8, 131.9 (2C), 130.9, 130.2, 129.9 (2C), 129.8, 125.3, 124.3, 115.9, 102.4, 97.5.

[0051] naphthalen-1-yl(4-(naphthalen-1-yl)-[1,2,3]triazolo[1,5-a]quinoxalin-3-yl)methanone (3ag) yellow solid, mp 176 - 179 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.92 (d, J = 8.0 Hz, 1H), 8.30 (d, J = 8.0 Hz, 1H), 8.14 (d, J = 8.0 Hz, 1H), 7.95 - 7.84 (m, 2H), 7.68 - 7.54 (m, 4H), 7.49 - 7.30 (m, 7H), 7.08 (t, J = 8.0 Hz, 1H), 6.97 (t, J = 8.0 Hz, 1H); 13 13C{ 1 1H}NMR (100 MHz, CDCl3) δ 188.0, 153.2, 142.6, 136.8, 134.1, 133.8, 133.3, 132.7, 131.3, 130.9, 130.3, 130.2, 129.9, 129.7 (2C), 129.4 (2C), 128.6, 128.1, 127.7, 126.7, 126.5, 126.4, 126.2, 125.7, 124.9, 124.7, 124.2, 123.4, 116.0.

[0052] naphthalen-2-yl(4-(naphthalen-2-yl)-[1,2,3]triazolo[1,5-a]quinoxalin-3-yl)methanone (3ah) yellow solid, mp 223 - 226 °C. 11H NMR (400 MHz, CDCl3) δ 8.88 (d, J = 8.0 Hz, 1H), 8.54 (s, 1H), 8.33 (d, J = 8.0 Hz, 1H), 8.09 (s, 1H), 7.93 - 7.83 (m, 5H), 7.79 - 7.74 (m, 4H), 7.61 (t, J = 8.0 Hz, 1H), 7.55 - 7.46 (m, 3H), 7.38 (t, J = 8.0 Hz, 1H); 13 13C{ 1 1H} NMR (100 MHz, CDCl3) δ 186.9, 153.1, 141.4, 137.1, 135.8, 134.1, 134.0, 133.5, 132.5, 132.2, 130.5, 130.2, 129.8, 129.6, 128.9 (2C), 128.8, 128.5, 128.4, 128.3, 127.7 (2C), 127.3, 126.7, 126.6, 125.6, 124.9, 124.7, 124.5, 115.9.

[0053] thiophen-2-yl(4-(thiophen-2-yl)-[1,2,3]triazolo[1,5-a]quinoxalin-3-yl)methanone (3ai) yellow solid, mp 170 - 174 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.79 - 8.76 (m, 1H), 8.23 - 8.20 (s, 1H), 8.09 (d, J = 4.0 Hz, 1H), 7.83 - 7.79 (m, 3H), 7.56 (d, J = 4.0 Hz, 1H), 7.34 (d, J = 4.0 Hz, 1H), 7.22 (t, J = 4.0 Hz, 1H), 7.07 (t, J = 4.0 Hz, 2H); 13 13C{ 1 1H} NMR (100 MHz, CDCl3) δ 178.6, 146.6, 143.5, 140.6,, 139.2, 136.7 (2C), 136.1 (2C), 130.7, 130.3, 130.2, 129.8, 129.7, 128.5, 127.6, 124.2, 115.8.

[0054] Comparative example:

[0055] Using dichloromethane as the solvent and different bases to catalyze the reaction, it can be seen from the table that most bases cannot catalyze the reaction to occur; only Cs2CO3, KO tThe formation of product 3aa could be observed with these four bases Bu, KOH, DBU. Among them, the yields of the weak bases (Cs2CO3, DBU) were relatively low (Table 1, Entry 1 and Entry 11), while KO t Bu had a yield only 5% higher than that of KOH (Table 1, compare Entry 6 and Entry 9).

[0056] Using KO t Bu as the catalyst and reacting in different solvents, first using inexpensive and green water as the solvent, the formation of compound 3aa was not observed (Table 1, Entry 17); while when 1 used DMSO, DMF, NMP, THF, 1,4 - dioxane, EtOH as solvents, the yields were all less than 50%. When toluene and acetonitrile were used as solvents, the yields were higher than that of dichloromethane (Table 1, compare Entry 6, Entry 13, Entry 16), and the yields of these two solvents were not very different (85% and 88%). However, in actual operation, when toluene was used as the solvent, the product was a viscous liquid with poor fluidity, which increased the difficulty and time of post - treatment compared with the liquid state when acetonitrile was used as the solvent.

[0057] Table 1 Results of the cycloaddition reaction of quinoxalinyl enaminone with p - toluenesulfonyl azide under different solvent and catalyst conditions

[0058]

[0059] Reaction conditions: 2AA (0.5 mmol), TSN3 (0.75 mmol) and base (1.0 mmol), reacting in 2 mL of solvent at room temperature. n.d. means not detected.

Claims

1. A method for synthesizing 1,2,3-triazoloquinoxaline compounds, characterized in that, The synthesis method is that heterocyclic enaminones are used as substrates, and react with tosyl azide at room temperature in a solvent under the promotion of a base to generate 1,2,3-triazole-[1,5-a]quinoxaline compounds; The structural formula of the heterocyclic enaminone is as shown in Formula 2aa below: The structural formula of the 1,2,3-triazole-[1,5-a]quinoxaline compound is as shown in Formula 3aa below: The base is potassium tert-butoxide; The solvent is acetonitrile or toluene; The molar ratio of the heterocyclic enaminone to tosyl azide is 2:3; After the reaction is completed, acetonitrile or toluene is rotary evaporated, water and ethyl acetate are added for extraction. After the organic layer is dried with anhydrous Na2SO4, it is separated by silica gel column chromatography. Eluent: petroleum ether / ethyl acetate = 10 / 1, 8 / 1, v / v, and the white solid obtained is the target compound.

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