A selective deuterated 1,2,3-triazole synthesis method

Abstract

The present invention relates to a method for synthesizing selectively deuterated 1,2,3-triazole, comprising the following steps: #imgabs0# in an aqueous solvent, reacting an azide compound (Formula I) with deuterated acetylene in the presence of a catalyst to generate a compound of Formula II; wherein R is selected from a suitable substituent, preferably an optionally substituted aryl or alkyl group.

Description

Technical Field

[0001] The invention belongs to the fields of drug synthesis, organic chemical industry and the like, and particularly relates to a method for synthesizing selectively deuterated 1,2,3-triazole. Background Art

[0002] Deuterium-labeled compounds have been widely used in multiple fields. In organic synthetic chemistry, deuterium-labeled compounds are used in reaction mechanism studies. In the biomedicine field, drugs can be labeled with deuterium for proteomics research and studies on the absorption, distribution, metabolism, and excretion of drugs in the body. In addition to facilitating the localization and analysis of metabolites in organisms, deuterium-labeled drugs also help discover new metabolites for the study of metabolic mechanisms. Deuterium-labeled drugs may also slow down the rate of drug metabolism and even change metabolic pathways. Since the US FDA approved the first deuterium-labeled drug in 2017, the synthesis and preparation of related deuterium-labeled compounds have received widespread attention in the fields of medicinal chemistry and synthetic chemistry.

[0003] 1,2,3-Triazole is a unique five-membered heterocyclic ring. It is widely used in materials, pesticides, and pharmaceuticals. Clinical drugs such as tazobactam and rufinamide contain 1,2,3-triazole structures, and several other drugs containing 1,2,3-triazole fragments are currently in clinical trials. Developing synthetic methods for deuterium-labeled 1,2,3-triazole compounds is of great value.

[0004] Currently, the most common synthetic methods for preparing deuterium-labeled 1,2,3-triazoles include the cycloaddition of metal acetylenes with azides followed by heavy water quenching (e.g., Org. Lett. 2004, 6, 1237) and the base-assisted hydrogen-deuterium exchange of 1,2,3-triazoles in deuterated dimethyl sulfoxide (Tetrahedron 2016, 72, 6375). These reactions require large amounts of organometallic compounds, and the strong alkalinity of these organometallic compounds limits their applicability. Catalytic chemical reactions are the optimal solution for deuterium labeling of 1,2,3-triazoles. However, the ability to conveniently and selectively deuterate the C4 moiety in 1,2,3-triazole synthesis remains a technically unresolved challenge.

[0005] The present invention realizes a method for synthesizing deuterium-labeled 1,2,3-triazole. Specifically, the method realizes that only the C4 position of the 1,2,3-triazole ring is labeled with a deuterium atom while the C5 position is not deuterated (or only a very small proportion of the deuterium is substituted), thereby realizing 1,2,3-triazole labeled with deuterium at the C4 position. Summary of the Invention

[0006] The present invention provides a method for preparing a deuterium-labeled 1,2,3-triazole compound represented by Formula II, which is characterized by comprising the following steps:

[0007]

[0008] In an aqueous solvent, an azide compound (Formula I) reacts with deuterated acetylene in the presence of a catalyst to generate a compound of Formula II; wherein R is selected from a suitable substituent, preferably an optionally substituted aryl or alkyl group.

[0009] The catalyst is selected from a monovalent copper complex or a combination of a monovalent copper salt and a ligand; the amount of the catalyst used, calculated as copper salt, is such that the molar ratio of the copper salt to the azide compound of formula I is 10 mol% to 100 mol%, preferably 10 mol% to 20 mol%; the monovalent copper salt is preferably cuprous chloride, cuprous bromide, cuprous iodide, cuprous acetate, cuprous nitrate, or the like; the ligand is a nitrogen-containing ligand, preferably triethylamine, pyridine, diisopropylethylamine, triphenylphosphine and its substituents, 1,10-phenanthroline and its substituents, 2,2'-bipyridine, or the like. The above-mentioned monovalent copper complex can be prepared in advance and then added to the reaction, or it can be prepared in situ by adding the copper salt and ligand to the reactor. The pre-prepared catalyst may include but is not limited to tris(triphenylphosphine)copper(I) complex, dichloro(1,10-phenanthroline)copper, (1,10-phenanthroline)bis(triphenylphosphine)cuprous nitrate, bromo(1,10-phenanthroline)(triphenylphosphine)copper(I), and other corresponding complexes. 1,10-phenanthroline substituted compounds include but are not limited to 4,7-diphenyl-1,10-phenanthroline, 3,4,7,8-tetramethyl-1,10-phenanthroline, and 2,9-dimethyl-4,7-biphenyl-1,10-phenanthroline.

[0010] Another embodiment of the present invention provides a method for preparing the deuterium-labeled 1,2,3-triazole compound represented by the above formula II, characterized in that the reaction occurs in an aqueous environment, and the amount of water used in the reaction is 25 to 120 times the molar amount of the azide compound of formula I.

[0011] Another embodiment of the present invention provides a method for preparing the deuterium-labeled 1,2,3-triazole compound represented by Formula II, characterized in that a solvent other than water may or may not be added to the reaction environment. Such solvents used with water include dimethyl sulfoxide, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, tetrahydrofuran, hexamethylphosphoramide, dioxane, methyl tert-butyl ether, and 2-methylfuran.

[0012] Another embodiment of the present invention provides a method for preparing the deuterium-labeled 1,2,3-triazole compound represented by the above formula II, characterized in that the deuterium label in formula II is at the C4 position, and the C5 position is not deuterated or is only deuterated in a very small proportion (the deuteration rate does not exceed 10%).

[0013] Another embodiment of the present invention provides a method for preparing a deuterium-labeled 1,2,3-triazole compound represented by Formula II above, characterized in that an azide compound, a catalyst, and HO / solvent are added to a reaction vessel. After the air in the reaction vessel is replaced, deuterated acetylene gas is introduced into the reaction system. The reaction mixture is stirred at 0-50 degrees Celsius for 10-24 hours. After the reaction is completed, the reaction mixture is separated by extraction, column chromatography, or other separation methods to obtain the corresponding deuterium-labeled 1,2,3-triazole compound. The reaction can be carried out under pressure or at atmospheric pressure.

[0014] Another embodiment of the present invention provides a method for preparing the deuterium-labeled 1,2,3-triazole compound represented by the above formula II, characterized in that the deuterated acetylene gas can be the collected gas from the reaction of calcium carbide and heavy water, or can be prepared in situ in a reactor through a multi-branch reactor or a built-in reactor.

[0015] The aryl group of the present invention is further preferably a C5-C10 aryl group optionally substituted with one or more C1-C6 alkyl groups, C1-C6 alkoxy groups, cyano groups, halogen groups, azido groups, nitro groups, hydroxyl groups and the like; the alkyl group is further preferably a C1-C12 alkyl group optionally substituted with one or more C1-C6 alkyl groups, C1-C6 alkoxy groups, cyano groups, halogen groups, azido groups, nitro groups, hydroxyl groups and the like; the aryl group of the present invention is preferably a C6-C10 aryl group or a C5-C6 heteroaryl group, and is further preferably a phenyl group, a naphthyl group, a pyridyl group, a thienyl group, a furyl group and the like.

[0016] Compared with the prior art, the advantages of the present invention are: (1) the present invention can selectively introduce a high-deuteration-rate deuterium atom label at the C4 position on the mono-N-substituted 1,2,3-triazole ring; (2) the present invention uses deuterated acetylene or deuterated acetylene prepared in situ from calcium carbide as a raw material to achieve the synthesis of deuterated-labeled 1,2,3-triazole; (3) the reaction temperature and time of the present invention are greatly reduced compared with the prior art, thereby greatly improving the synthesis efficiency of deuterium-labeled 1,2,3-triazole compounds.

[0017] It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features described in detail below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be listed here one by one. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 The product of Example 1, 4-deuterium 1-phenyl-1,2,3-triazole 1 H NMR spectrum;

[0019] Figure 2 The product of Example 1, 4-deuterium 1-phenyl-1,2,3-triazole 13 C NMR spectrum;

[0020] Figure 3 The product of Example 2, 4-deuterium 1-(3-methylphenyl)-1,2,3-triazole 1 H NMR spectra;

[0021] Figure 4 The product of Example 2, 4-deuterium 1-(3-methylphenyl)-1,2,3-triazole 13 C NMR spectrum;

[0022] Figure 5 The product of Example 3, 4-deuterium 1-(4-methylphenyl)-1,2,3-triazole 1 H NMR spectrum;

[0023] Figure 6 The product of Example 3, 4-deuterium 1-(4-methylphenyl)-1,2,3-triazole 13 C NMR spectrum;

[0024] Figure 7 The product of Example 4 1 H NMR spectra;

[0025] Figure 8 The product of Example 4 13 C NMR spectrum;

[0026] Figure 9 The product of Example 5 1 H NMR spectra;

[0027] Figure 10 The product of Example 5 13 C NMR spectrum;

[0028] Figure 11 The product of Example 6 1 H NMR spectra;

[0029] Figure 12 The product of Example 6 13 C NMR spectrum;

[0030] Figure 13 The product of Example 7 1 H NMR spectrum;

[0031] Figure 14 The product of Example 7 13 C NMR spectrum;

[0032] Figure 15 The product of Example 8 1 H NMR spectrum;

[0033] Figure 16 The product of Example 8 13 C NMR spectrum;

[0034] Figure 17 The product of Example 9 1 H NMR spectrum;

[0035] Figure 18 The product of Example 9 13 C NMR spectrum;

[0036] Figure 19 The product of Example 10 1 H NMR spectrum;

[0037] Figure 20 The product of Example 10 13 C NMR spectrum;

[0038] Figure 21 The product of Example 11 1 H NMR spectrum;

[0039] Figure 22 The product of Example 11 13 C NMR spectrum. DETAILED DESCRIPTION

[0040] In order to facilitate further understanding of the present invention, the following examples are provided to illustrate it in more detail. However, these examples are only for better understanding of the invention and are not intended to limit the scope or implementation principles of the present invention. The embodiments of the present invention are not limited to the following.

[0041] Example 1 Preparation of 4-deuterated 1-phenyl-1,2,3-triazole

[0042] To a dry 10 mL round-bottom flask, phenylazide (1.0 mmol, 1.0 equiv.), [Cu(phen)(PPh3)2]NO3 (0.1 mmol, 10 mol%), N,N-dimethylformamide (1.5 mL), and H2O (0.5 mL) were added sequentially. The reaction system was then replaced with deuterated acetylene gas and stirred at room temperature for 24 hours. After completion of the reaction, the reaction solution was extracted, washed, dried, and the solvent removed. Column chromatography was performed to obtain the corresponding product, 4-deuterium-1-phenyl-1,2,3-triazole, in a 65% yield. The deuteration rate of C4 was 97%, and the deuteration rate of C5 was 10%.

[0043] 1 H NMR (400MHz, Chloroform-d) δ7.99 (s, 0.89H), 7.77 (d, J = 1.1Hz, 0.03H), 7.70–7.62 (m, 2H), 7.49–7.41 (m, 2H), 7.40–7.32 (m, 1H). 13 C NMR (100MHz, Chloroform-d) δ136.90,132.57,132.47,129.68,128.70,120.53.

[0044] Example 2 Preparation of 4-deuterated 1-(3-methylphenyl)-1,2,3-triazole

[0045] To a dry 10 mL round-bottom flask, 3-azidotoluene (1.0 mmol, 1.0 equiv.), [Cu(phen)(PPh3)2]NO3 (0.1 mmol, 10 mol%), triethylamine (0.4 mmol, 40 mol%), N,N-dimethylformamide (1.5 mL), and H2O (0.5 mL) were added sequentially. The reaction system was then replaced with deuterated acetylene gas, and the reaction was stirred at room temperature for 10 h. After completion of the reaction, the reaction solution was extracted, washed, dried, and the solvent removed. Column chromatography was performed to obtain the corresponding product, 4-deuterated 1-(3-methylphenyl)-1,2,3-triazole, in a 73% yield. The deuteration rate of C4 was 96%, and C5 was undeuterated.

[0046] 1 H NMR(400MHz,Chloroform-d)δ7.97(s,1H),7.77(d,J=1.1Hz,0.04H),7.52(s,1H) ,7.46(d,J=8.0Hz,1H),7.33(t,J=7.8Hz,1H),7.18(d,J=7.6Hz,1H),2.38(s,3H). 13CNMR(100MHz,Chloroform-d)δ139.95,136.91,129.49,129.47,121.75,121.24,117.64,21.33.

[0047] Example 3 Preparation of 4-deuterated 1-(4-methylphenyl)-1,2,3-triazole

[0048] In a dry, double-branched reactor, 4-azidotoluene (1.0 mmol, 1.0 equiv.), CuI (0.1 mmol, 10 mol%), 1,10-phenanthroline (0.1 mmol, 10 mol%), triethylamine (0.2 mmol, 40 mol%), N,N-dimethylformamide (1.5 mL), and H2O (0.5 mL) were added sequentially to one branch. Deuterated water (0.5 mL) was added to the other branch, followed by calcium carbide (2.0 g). The reaction was capped and stirred. The reaction was stirred at room temperature for 24 hours. After completion of the reaction, the reaction solution was extracted, washed, dried, and the solvent removed. Column chromatography was performed to obtain the corresponding product, 4-deuterated-1-(4-methylphenyl)-1,2,3-triazole, in a 62% yield. The deuteration rate of C4 was 93%, and C5 was undeuterated.

[0049] 1 H NMR (400MHz, Chloroform-d) δ7.98 (s, 1H), 7.81 (d, J = 1.1Hz, 0.07H), 7.60 (d, J = 8.5Hz, 2H), 7.30 (d, J = 8.3Hz, 2H). 13 C NMR (100MHz, Chloroform-d) δ 138.86, 134.73, 134.34 (d, J = 9.1Hz), 134.08, 133.79, 130.23, 121.70, 120.53.

[0050] Example 4 Preparation of 4-deuterated 1-(4-chlorophenyl)-1,2,3-triazole

[0051] To a dry 10 mL round-bottom flask were added 4-azidochlorobenzene (1.0 mmol, 1.0 equiv.), CuI (0.1 mmol, 10 mol%), 1,10-phenanthroline (0.1 mmol, 10 mol%), triethylamine (0.2 mmol, 40 mol%), N,N-dimethylformamide (1.5 mL), and H2O (0.5 mL). The reaction system was then replaced with deuterated acetylene gas and stirred at room temperature for 24 h. After completion of the reaction, the reaction solution was extracted, washed, dried, and the solvent removed. Column chromatography was performed to obtain the corresponding product, 4-deuterated-1-(4-chlorophenyl)-1,2,3-triazole, with a yield of 75%, a C4 deuteration rate of 92%, and no C5 deuteration.

[0052] 1 H NMR (400MHz, Chloroform-d) δ7.99 (s, 1H), 7.81 (d, J = 1.1Hz, 0.08H), 7.71–7.61 (m, 2H), 7.52–7.39 (m, 2H). 13 C NMR (101MHz, Chloroform-d) δ135.55,134.57,129.98,121.85,121.70.

[0053] Example 5 Preparation of 4-deuterated 1-(4-bromophenyl)-1,2,3-triazole

[0054] In a round-bottom flask connected by a suitable connector, 4-azidobromobenzene (1.0 mmol, 1.0 equiv.), CuI (0.1 mmol, 10 mol%), 1,10-phenanthroline (0.1 mmol, 10 mol%), triethylamine (0.2 mmol, 40 mol%), and H2O (2.0 mL) were added sequentially. In a separate dry reactor, calcium carbide (4.0 mmol, 4.0 equiv.) was placed. The two flasks were connected through a glass tube or a double-ended needle, and deuterated water was slowly added. The reaction was stirred at room temperature for 24 hours. After completion of the reaction, the reaction solution was extracted, washed, dried, and the solvent was removed. Column chromatography was then performed to obtain the corresponding product, 4-deuterated-1-(4-bromophenyl)-1,2,3-triazole, with an 83% yield, a 94% deuteration rate at C4, and no deuteration at C5.

[0055] 1 H NMR(400MHz,Chloroform-d)δ7.99(s,1H),7.83–7.77(m,0.06H),7.66–7.54(m,4H). 13C NMR (100MHz, Chloroform-d) δ135.99,134.80,134.21,132.93,122.42,122.06,121.65.

[0056] Example 6 Preparation of 4-deuterated 1-(2-bromophenyl)-1,2,3-triazole

[0057] To a dry 10 mL round-bottom flask were added 2-azido-1-bromobenzene (1.0 mmol, 1.0 equiv.), CuBr (0.1 mmol, 10 mol%), 1,10-phenanthroline (0.1 mmol, 10 mol%), triphenylphosphine (0.2 mmol, 20 mol%), N,N-dimethylformamide (1.5 mL), and H2O (0.5 mL). The reaction system was then replaced with deuterated acetylene gas, and the reaction was stirred at room temperature for 18 hours. After completion of the reaction, the reaction solution was extracted, washed, dried, and the solvent removed. Column chromatography was performed to obtain the corresponding product, 4-deuterated-1-(2-bromophenyl)-1,2,3-triazole, in an 82% yield, with a C4 deuteration rate of 92% and a C5 deuteration rate of 3%.

[0058] 1 H NMR (400MHz, Chloroform-d) δ7.94(d,J=1.5Hz,0.97H),7.82(d,J=1.2Hz,0.08H),7.71(dt,J=8.1,1.4Hz,1H),7.54–7.41(m,2H),7.41–7.31(m,1H). 13 C NMR (100MHz, Chloroform-d) δ136.48,133.90,131.25,128.54,128.25,118.68.

[0059] Example 7 Preparation of 4-deuterated 1-(4-ethylphenyl)-1,2,3-triazole

[0060] To a dry 10 mL round-bottom flask, 4-ethyl-1-benzeneazide (1.0 mmol, 1.0 equiv.), CuBr (0.1 mmol, 10 mol%), 4,7-dimethoxy-1,10-phenanthroline (0.2 mmol, 20 mol%), dimethyl sulfoxide (1.5 mL), and H₂O (0.5 mL) were added sequentially. Deuterated acetylene gas was introduced under vacuum, and the reaction was stirred at room temperature for 24 h. After completion of the reaction, the reaction solution was extracted, washed, dried, and the solvent removed. Column chromatography was performed to obtain the corresponding product, 4-deuterated-1-(4-ethylphenyl)-1,2,3-triazole, with an 82% yield, a 92% C4 deuteration rate, and a 5% C5 deuteration rate.

[0061] 1 H NMR (400MHz, Chloroform-d) δ7.95 (s, 0.95H), 7.79 (d, J = 1.1Hz, 0.08H), 7.60 (d, J=8.6Hz,2H),7.30(d,J=8.7Hz,2H),2.67(q,J=7.6Hz,2H),1.23(t,J=7.6Hz,3H). 13 C NMR (100MHz, Chloroform-d) δ145.19,134.89,129.09,121.73,120.67,28.44,15.45.

[0062] Example 8 Preparation of 4-deuterated 1-(4-methoxyphenyl)-1,2,3-triazole

[0063] To a dry 10 mL round-bottom flask, 4-azidoanisole (1.0 mmol, 1.0 equiv.), CuBr (0.1 mmol, 10 mol%), 3,4,7,8-tetramethyl-1,10-phenanthroline (0.2 mmol, 20 mol%), tetrahydrofuran (1.5 mL), and H2O (0.5 mL) were added sequentially. The reaction system was then purged with deuterated acetylene gas, and the reaction was stirred at room temperature for 24 h. After completion of the reaction, the reaction solution was extracted, washed, dried, and the solvent removed. Column chromatography was performed to obtain the corresponding product, 4-deuterated-1-(4-methoxyphenyl)-1,2,3-triazole, with an 82% yield, a 91% deuteration rate at C4, and no deuteration at C5.

[0064] 1 H NMR (400MHz, Chloroform-d) δ7.95 (s, 1H), 7.80 (d, J = 1.1Hz, 0.09H), 7.68–7.52 (m, 2H), 7.06–6.90 (m, 2H), 3.85 (s, 3H). 13 C NMR (100MHz, Chloroform-d) δ159.75,130.41,122.20,121.85,114.72,55.57.

[0065] Example 9 Preparation of 4-deuterated 1-(4-cyanophenyl)-1,2,3-triazole

[0066] To a dry 10 mL round-bottom flask were added 4-azidobenzonitrile (1.0 mmol, 1.0 equiv.), CuBr (0.1 mmol, 10 mol%), 2,9-dimethyl-4,7-biphenyl-1,10-phenanthroline (0.2 mmol, 20 mol%), dioxane (1.5 mL), and H2O (0.5 mL). The reaction system was then purged with deuterated acetylene gas, and the reaction was stirred at room temperature for 24 h. After completion of the reaction, the reaction solution was extracted, washed, dried, and the solvent removed. Column chromatography was performed to obtain the corresponding product, 4-deuterated-1-(4-cyanophenyl)-1,2,3-triazole, in a 79% yield. The deuteration rate at C4 was 92%, and C5 was undeuterated.

[0067] 1 H NMR (400MHz, Chloroform-d) δ8.10 (s, 1H), 7.97–7.91 (m, 2H), 7.89 (d, J = 1.1Hz, 0.08H), 7.86–7.82 (m, 2H). 13 C NMR (100MHz, Chloroform-d) δ139.90,134.06,121.58,120.81,117.80,112.53.

[0068] Example 10 Preparation of 4-deuterated 1-(2-chlorophenyl)-1,2,3-triazole

[0069] To a dry 10 mL round-bottom flask were added 2-azido-1-chlorobenzene (1.0 mmol, 1.0 equiv.), [Cu(PPh3)2]NO3 (0.1 mmol, 10 mol%), 2,9-dimethyl-4,7-biphenyl-1,10-phenanthroline (0.2 mmol, 20 mol%), N-methylpyrrolidone (1.5 mL), and H2O (0.5 mL). The reaction system was then replaced with deuterated acetylene gas, and the reaction was stirred at room temperature for 24 hours. After completion of the reaction, the reaction solution was extracted, washed, dried, and the solvent removed. Column chromatography was performed to obtain the corresponding product, 4-deuterated-1-(2-methoxyphenyl)-1,2,3-triazole, in an 84% yield. The deuteration rate at C4 was 97%, and C5 was undeuterated.

[0070] 1 H NMR (400MHz, Chloroform-d) δ7.98 (s, 1H), 7.82 (d, J = 1.1Hz, 0.03H), 7.61–7.48 (m, 2H), 7.45–7.36 (m, 2H). 13C NMR(100MHz,Chloroform-d)δ134.85,133.92–132.48(m),130.83,130.77,128.69,127.96,127.84,125.65.

[0071] Example 11 Preparation of 4-deuterium 1-octyl-1,2,3-triazole

[0072] To a dry 10 mL round-bottom flask were added 1-azidooctane (1.0 mmol, 1.0 equiv.), [Cu(phen)(PPh3)2]NO3 (0.1 mmol, 10 mol%), 2,9-dimethyl-4,7-biphenyl-1,10-phenanthroline (0.2 mmol, 20 mol%), N,N-dimethylformamide (1.5 mL), and H2O (0.5 mL). The reaction system was then replaced with deuterated acetylene gas, and the reaction was stirred at room temperature for 24 hours. After completion of the reaction, the reaction solution was extracted, washed, dried, and the solvent removed. Column chromatography was performed to obtain the corresponding product, 4-deuterated-1-octyl-1,2,3-triazole, in an 84% yield, with a C4 deuteration rate of 86% and a C5 deuteration rate of 5%.

[0073] 1 H NMR (400MHz, Chloroform-d) δ7.60 (s, 0.14H), 7.50 (s, 0.94H), 4.30 (t, J = 7.2Hz, 2H), 1.82 (t, J = 7.2Hz, 2H), 1.35–1.04 (m, 12H), 0.90–0.58 (m, 3H). 13 C NMR(100MHz,Chloroform-d)δ134.57–131.06(m),123.15(d,J=10.0Hz),50.11,48.75,3 1.59 (d, J = 4.3Hz), 30.17 (d, J = 17.6Hz), 28.88 (dd, J = 11.1, 5.6Hz), 26.37, 22.51, 13.98.

Claims

1. A method for preparing a deuterium-labeled 1,2,3-triazole compound represented by formula II, characterized in that The steps include: In an aqueous solvent, an azide compound of formula I reacts with deuterated acetylene in the presence of a catalyst to produce a compound of formula II; wherein R is selected from an optionally substituted aryl or alkyl group; The catalyst is selected from a monovalent copper complex or a combination of a monovalent copper salt and a ligand; the monovalent copper complex is selected from tris(triphenylphosphine)copper(I) complex, dichloro(1,10-phenanthroline)copper, (1,10-phenanthroline)bis(triphenylphosphine)cuprous nitrate, and brominated(1,10-phenanthroline)(triphenylphosphine)copper(I); the monovalent copper salt is selected from cuprous chloride, cuprous bromide, cuprous iodide, cuprous acetate, and cuprous nitrate; the ligand is selected from triethylamine, pyridine, diisopropylethylamine, triphenylphosphine, 1,10-phenanthroline, 4,7-diphenyl-1,10-phenanthroline, 3,4,7,8-tetramethyl-1,10-phenanthroline, 2,9-dimethyl-4,7-biphenyl-1,10-phenanthroline, and 2,2'-bipyridine; The solvent used together with water is selected from dimethyl sulfoxide, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, tetrahydrofuran, hexamethylphosphoramide, dioxane, methyl tert-butyl ether, and 2-methylfuran.

2. The preparation method according to claim 1, characterized in that The amount of the catalyst used, calculated as copper salt, is such that the molar ratio of the copper salt to the azide compound of formula I is 10 mol% to 100 mol%.

3. The preparation method according to claim 2, characterized in that The molar ratio of the copper salt to the azide compound of formula I is 10 mol% to 20 mol%.

4. The preparation method according to claim 1, characterized in that The reaction takes place in a water-containing environment, and the amount of water used in the reaction is 25 to 120 times the molar amount of the azide compound of formula I.

5. The preparation method according to claim 1, characterized in that In formula II, the deuterium label is at the C4 position, while the C5 position is not deuterated or is deuterated at a very small proportion.

6. The preparation method according to claim 1, characterized in that An azide compound of formula I, a catalyst, and H2O / solvent are added to a reaction vessel. After the air in the reaction vessel is replaced, deuterated acetylene gas is introduced into the reaction system. The reaction mixture is stirred at 0-50 degrees Celsius for 10-24 hours. After the reaction is completed, the reaction mixture is separated by extraction and column chromatography to obtain the corresponding deuterium-labeled 1,2,3-triazole compound.

7. The preparation method according to claim 1, characterized in that The deuterated acetylene gas is selected from the collected gas from the reaction of calcium carbide and heavy water, or is prepared in situ in the reactor through a multi-branch reactor or a built-in reactor.

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