A process for the preparation of N-alkoxalylmethyl substituted-1,2,3-triazoles

Abstract

The present application relates to the field of synthetic chemistry, in particular to a preparation method of N-alkoxyacylmethyl substituted-1,2,3-triazole compound, the preparation method is that alkynes, alpha-diazoacetate and azidotrimethylsilane are used as reaction raw materials, copper salt catalyst and alkali are added, reaction is carried out in organic solvent under nitrogen condition, reaction temperature is 60-100 DEG C, time is 6h, after reaction is completed, reaction liquid is concentrated and treated and column chromatography is separated, and the target product N-alkoxyacylmethyl substituted-1,2,3-triazole compound is obtained; the N-alkoxyacylmethyl substituted-1,2,3-triazole compound can be prepared by simple raw materials and simple steps, and the preparation method has the advantages of simple operation, easy-to-obtain raw materials and good functional group compatibility.

Description

Technical Field

[0001] This invention relates to the field of synthetic chemistry, specifically to a method for preparing N-alkoxymethyl-substituted-1,2,3-triazole compounds. Background Technology

[0002] The information disclosed in the background section of this invention is intended only to enhance the understanding of the overall background of the invention and is not necessarily to be regarded as an admission or in any way implying that such information constitutes prior art known to those skilled in the art.

[0003] N-substituted-1,2,3-triazoles have significant applications in functional materials, pharmaceuticals, and synthetic chemistry. Compounds containing this structural framework can be used as metal coordination frameworks, dyes, chemical probes, and corrosion inhibitors. N-substituted-1,2,3-triazole compounds also possess a wide range of biological activities, such as anticancer, antibacterial, and anti-inflammatory effects. Tris(azido)methylsilanes, as a class of low-toxicity, stable, and readily available nitrogen sources, are frequently used to construct various nitrogen-containing compounds. In recent years, chemists have successively developed the following methods for synthesizing N-substituted-1,2,3-triazoles through multi-component reactions involving tris(azido)methylsilanes:

[0004] (1) A method for constructing N2-allyl-substituted-1,2,3-triazole by palladium / copper salt bimetallic co-catalyzed three-component cycloaddition reaction of alkyne, trimethylsilane azido and allyl ester (J.Am.Chem.Soc.2003,125,7786);

[0005] (2) Bimetallic Cu 0 / A method for constructing N1-methylthiomethyl-1,2,3-triazole by co-catalyzing a three-component reaction of alkynes, trimethyl azidosilane and dimethyl sulfoxide with Fe3O4 (Eur. J. Org. Chem. 2016, 27, 4629);

[0006] (3) A method for constructing N1-alkenyl-1,2,3-triazole by silver sulfate-catalyzed three-component reaction of alkynes, TMSN3 and 1,3-dione (Org. Biomol. Chem. 2019, 17, 4843);

[0007] (4) A method for selectively constructing N1- and N2-alkoxy-1,2,3-triazole by a three-component tandem reaction of a copper chloride-catalyzed alkyne, trimethylsilane azido, and ether (Org. Lett. 2019, 21, 7218.).

[0008] While the methods described above can construct partially N-substituted-1,2,3-triazoles, they suffer from drawbacks such as high cost, difficulty in obtaining raw materials, and significant limitations in substrate reactions. N-alkoxymethyl groups, as important functional groups, frequently appear in functional material and drug molecules, significantly altering their physicochemical properties. Therefore, developing a simple and efficient method for synthesizing N-alkoxymethyl-substituted-1,2,3-triazoles through multi-component reactions involving azidotrimethylsilane is of significant value. Summary of the Invention

[0009] To address the shortcomings and deficiencies of existing technologies, the present invention aims to provide a method for preparing N-alkoxymethyl-substituted-1,2,3-triazoles. This method uses trimethylsilane azide as a nitrogen source and combines it with alkynes and α-diazoacetic acid esters. N-alkoxymethyl-substituted-1,2,3-triazole compounds can be prepared through simple steps, which has the advantages of simple operation and readily available raw materials.

[0010] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0011] A method for preparing an N-alkoxymethyl-substituted-1,2,3-triazole compound, wherein the method comprises using an alkyne of general formula 1, an α-diazoacetate of general formula 2, and an azidetrimethylsilane of structural formula 3 as reactants, adding a catalyst and a base, and reacting in an organic solvent to obtain the N-alkoxymethyl-substituted-1,2,3-triazole compound of general formula 4; the reaction route is shown below:

[0012]

[0013] Among them, R 1 R is any substituted aryl, heteroaryl, or alkyl group; 2 It is an alkyl group.

[0014] Further, the alkyne is phenylacetylene, o-methylphenylacetylene, m-methylphenylacetylene, 4-methylphenylacetylene, 4-methoxyphenylacetylene, 4-ethylphenylacetylene, 4-n-butylphenylacetylene, o-fluorophenylacetylene, m-fluorophenylacetylene, o-chlorophenylacetylene, p-bromophenylacetylene, p-cyanophenylacetylene, p-nitrophenylacetylene, 3-ethynylthiophene, 1-hexyne, 5-methyl-1-hexyne, 1-heptyne, 1-octyne, or 3,3-dimethylbutyne; the α-diazoacetic acid ester is ethyl α-diazoacetate or tert-butyl α-diazoacetate.

[0015] Further, the molar volume ratio of the alkyne, α-diazoacetate, azidotrimethylsilane, base and organic solvent is 1 mmol:(1-3) mmol:(1-3) mmol:1 mmol:10 mL; preferably, the molar volume ratio of the alkyne, α-diazoacetate, azidotrimethylsilane, base and organic solvent is 1 mmol:2 mmol:2 mmol:1 mmol:10 mL.

[0016] Further, the catalyst is cuprous iodide, cuprous chloride, cuprous bromide, cuprous chloride, or copper acetate; preferably, the catalyst is cuprous iodide.

[0017] Further, the amount of catalyst added is 5-30 mol% of the alkyne; preferably, the amount of catalyst added is 20 mol% of the alkyne.

[0018] Further, the alkali is potassium carbonate, cesium carbonate, sodium carbonate, potassium hydroxide, or potassium phosphate; preferably, the alkali is potassium carbonate.

[0019] Further, the organic solvent is tetrahydrofuran, 1,2-dimethoxyethane, 1,2-dichloroethane, N,N-dimethylformamide, acetonitrile, or 1,4-dioxane; preferably, the organic solvent is acetonitrile.

[0020] Furthermore, the reaction temperature is 60-100℃ and the reaction time is 6 hours; preferably, the reaction temperature is 80℃.

[0021] Furthermore, the reaction is carried out under nitrogen conditions.

[0022] Furthermore, after the reaction is completed, the reaction solution needs to be concentrated and separated by column chromatography.

[0023] Further, the concentration step is as follows: vacuum concentration is performed under a pressure of 0.08 MPa to obtain a crude product free of organic solvents; the column chromatography separation step is as follows: washing with a mixed eluent of petroleum ether and ethyl acetate, and performing column chromatography separation through a silica gel column; the volume ratio of petroleum ether to ethyl acetate is (2-5):1.

[0024] Beneficial effects

[0025] This invention provides a method for preparing N-alkoxymethyl-substituted-1,2,3-triazole. The method utilizes inexpensive and readily available olefins, α-diazoacetate, and azidotrimethylsilane as reactants, adds a copper salt catalyst and a base, and obtains N-alkoxymethyl-substituted-1,2,3-triazole through simple steps. The preparation method has the advantages of simple operation, readily available raw materials, mild reaction conditions, and good functional group compatibility. Detailed Implementation

[0026] The following description further sets forth specific details of the invention to provide a thorough understanding of it. The terminology used in this specification is for illustrative purposes only and is not intended to limit the scope of the invention.

[0027] Unless otherwise defined, all technical and scientific terms used in this invention have the same meaning as understood by one of ordinary skill in the art. Unless otherwise specified, all pharmaceuticals or reagents used in this invention are used in accordance with the product instructions or conventional methods in the relevant field. The process of this invention will now be further described with reference to specific embodiments described in the specification.

[0028] Example 1

[0029] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 1, includes the following steps:

[0030]

[0031] At room temperature, cuprous iodide (20 mol%), phenylacetylene 1a (0.2 mmol), ethyl α-diazoacetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4a, a yellow oil, in 38.3 mg (83% yield).

[0032] The NMR results of product 4a in this embodiment are as follows: 1 H NMR (500MHz, CDCl3) δ7.92 (s, 1H), 7.85–7.83 (m, 2H), 7.43 (t, J = 7.6Hz, 2H), 7. 34(t,J=7.4Hz,1H),5.20(s,2H),4.28(q,J=7.1Hz,2H),1.30(t,J=7.1Hz,3H); 13 C NMR(126MHz, CDCl3)δ166.3,148.3,130.4,128.9,128.3,125.8,121.0,62.5,51.0,14.1; HRMS(ESI)m / z:[M+H] +Calcd forC 12 H 14 N3O2232.1086; found 232.1084.

[0033] The test results above show that the structure of the product 4a synthesized in this embodiment is as shown in route 1.

[0034] Example 2

[0035] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 2, includes the following steps:

[0036]

[0037] Route 2

[0038] At room temperature, cuprous bromide (10 mol%), phenylacetylene 1a (0.2 mmol), ethyl α-diazoacetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen atmosphere and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4a, a yellow oil, in 16.6 mg (36% yield).

[0039] The NMR results of product 4a in this embodiment are as follows: 1 H NMR (500MHz, CDCl3) δ7.92 (s, 1H), 7.85–7.83 (m, 2H), 7.43 (t, J = 7.6Hz, 2H), 7. 34(t,J=7.4Hz,1H),5.20(s,2H),4.28(q,J=7.1Hz,2H),1.30(t,J=7.1Hz,3H); 13 C NMR(126MHz, CDCl3)δ166.3,148.3,130.4,128.9,128.3,125.8,121.0,62.5,51.0,14.1; HRMS(ESI)m / z:[M+H] + Calcd forC 12 H 14 N3O2232.1086; found 232.1084.

[0040] The test results above show that the structure of the product 4a synthesized in this embodiment is as shown in route 2.

[0041] Example 3

[0042] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 3, includes the following steps:

[0043]

[0044] Route 3

[0045] At room temperature, copper chloride (10 mol%), phenylacetylene 1a (0.2 mmol), α-diazoethyl acetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen atmosphere and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4a, a yellow oil, in 17.1 mg (37% yield).

[0046] The NMR results of product 4a in this embodiment are as follows: 1 H NMR (500MHz, CDCl3) δ7.92 (s, 1H), 7.85–7.83 (m, 2H), 7.43 (t, J = 7.6Hz, 2H), 7. 34(t,J=7.4Hz,1H),5.20(s,2H),4.28(q,J=7.1Hz,2H),1.30(t,J=7.1Hz,3H); 13 C NMR(126MHz, CDCl3)δ166.3,148.3,130.4,128.9,128.3,125.8,121.0,62.5,51.0,14.1; HRMS(ESI)m / z:[M+H] + Calcd forC 12 H 14 N3O2232.1086; found 232.1084.

[0047] The test results above show that the structure of the product 4a synthesized in this embodiment is as shown in route 3.

[0048] Example 4

[0049] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 4, includes the following steps:

[0050]

[0051] Route 4

[0052] At room temperature, copper acetate (10 mol%), phenylacetylene 1a (0.2 mmol), α-diazoethyl ethyl acetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen atmosphere and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4a, a yellow oil, in 17.1 mg (37% yield).

[0053] The NMR results of product 4a in this embodiment are as follows: 1 H NMR (500MHz, CDCl3) δ7.92 (s, 1H), 7.85–7.83 (m, 2H), 7.43 (t, J = 7.6Hz, 2H), 7. 34(t,J=7.4Hz,1H),5.20(s,2H),4.28(q,J=7.1Hz,2H),1.30(t,J=7.1Hz,3H); 13 C NMR(126MHz, CDCl3)δ166.3,148.3,130.4,128.9,128.3,125.8,121.0,62.5,51.0,14.1; HRMS(ESI)m / z:[M+H] + Calcd forC 12 H 14 N3O2232.1086; found 232.1084.

[0054] The test results above show that the structure of the product 4a synthesized in this embodiment is as shown in route 4.

[0055] Example 5

[0056] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 5, includes the following steps:

[0057]

[0058] Route 5

[0059] At room temperature, cuprous chloride (10 mol%), phenylacetylene 1a (0.2 mmol), ethyl α-diazoacetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen atmosphere and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4a, a yellow oil, in 13.9 mg (30% yield).

[0060] The NMR results of product 4a in this embodiment are as follows: 1 H NMR (500MHz, CDCl3) δ7.92 (s, 1H), 7.85–7.83 (m, 2H), 7.43 (t, J = 7.6Hz, 2H), 7. 34(t,J=7.4Hz,1H),5.20(s,2H),4.28(q,J=7.1Hz,2H),1.30(t,J=7.1Hz,3H); 13 C NMR(126MHz, CDCl3)δ166.3,148.3,130.4,128.9,128.3,125.8,121.0,62.5,51.0,14.1; HRMS(ESI)m / z:[M+H] + Calcd forC 12 H 14 N3O2232.1086; found 232.1084.

[0061] The test results above show that the structure of the product 4a synthesized in this embodiment is as shown in route 5.

[0062] Example 6

[0063] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 6, includes the following steps:

[0064]

[0065] Route 6

[0066] At room temperature, cuprous iodide (20 mol%), phenylacetylene 1a (0.2 mmol), ethyl α-diazoacetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and 1,2-dichloroethane (DCE, 2 mL) was injected into the tube under nitrogen atmosphere and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4a, a yellow oil, in 24.0 mg (52% yield).

[0067] The NMR results of product 4a in this embodiment are as follows: 1 H NMR (500MHz, CDCl3) δ7.92 (s, 1H), 7.85–7.83 (m, 2H), 7.43 (t, J = 7.6Hz, 2H), 7. 34(t,J=7.4Hz,1H),5.20(s,2H),4.28(q,J=7.1Hz,2H),1.30(t,J=7.1Hz,3H); 13 C NMR(126MHz, CDCl3)δ166.3,148.3,130.4,128.9,128.3,125.8,121.0,62.5,51.0,14.1; HRMS(ESI)m / z:[M+H] + Calcd forC 12 H 14 N3O2232.1086; found 232.1084.

[0068] The test results above show that the structure of the product 4a synthesized in this embodiment is as shown in route 6.

[0069] Example 7

[0070] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 7, includes the following steps:

[0071]

[0072] Route 7

[0073] At room temperature, cuprous iodide (20 mol%), phenylacetylene 1a (0.2 mmol), ethyl α-diazoacetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect the reaction mixture, and tetrahydrofuran (THF, 2 mL) was injected into the reaction tube under nitrogen atmosphere and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until completion, and then concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4a, a yellow oil, in 29.1 mg (63% yield).

[0074] The NMR results of product 4a in this embodiment are as follows: 1 H NMR (500MHz, CDCl3) δ7.92 (s, 1H), 7.85–7.83 (m, 2H), 7.43 (t, J = 7.6Hz, 2H), 7. 34(t,J=7.4Hz,1H),5.20(s,2H),4.28(q,J=7.1Hz,2H),1.30(t,J=7.1Hz,3H); 13 C NMR(126MHz, CDCl3)δ166.3,148.3,130.4,128.9,128.3,125.8,121.0,62.5,51.0,14.1; HRMS(ESI)m / z:[M+H] + Calcd forC 12 H 14 N3O2232.1086; found 232.1084.

[0075] The test results above show that the structure of the product 4a synthesized in this embodiment is as shown in route 7.

[0076] Example 8

[0077] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 8, includes the following steps:

[0078]

[0079] Route 8

[0080] At room temperature, cuprous iodide (20 mol%), phenylacetylene 1a (0.2 mmol), ethyl α-diazoacetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then 1,4-dioxane (2 mL) was injected into the tube under nitrogen atmosphere and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and then concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4a, a yellow oil, in 24.9 mg (54% yield).

[0081] The NMR results of product 4a in this embodiment are as follows: 1 H NMR (500MHz, CDCl3) δ7.92 (s, 1H), 7.85–7.83 (m, 2H), 7.43 (t, J = 7.6Hz, 2H), 7. 34(t,J=7.4Hz,1H),5.20(s,2H),4.28(q,J=7.1Hz,2H),1.30(t,J=7.1Hz,3H); 13 C NMR(126MHz, CDCl3)δ166.3,148.3,130.4,128.9,128.3,125.8,121.0,62.5,51.0,14.1; HRMS(ESI)m / z:[M+H] + Calcd forC 12 H 14 N3O2232.1086; found 232.1084.

[0082] The test results above show that the structure of the product 4a synthesized in this embodiment is as shown in route 8.

[0083] Example 9

[0084] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 9, includes the following steps:

[0085]

[0086] Route 9

[0087] At room temperature, cuprous iodide (20 mol%), phenylacetylene 1a (0.2 mmol), ethyl α-diazoacetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and N,N-dimethylformamide (DMF, 2 mL) was injected into the tube under nitrogen atmosphere and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4a, a yellow oil, in 24.9 mg (54% yield).

[0088] The NMR results of product 4a in this embodiment are as follows: 1 H NMR (500MHz, CDCl3) δ7.92 (s, 1H), 7.85–7.83 (m, 2H), 7.43 (t, J = 7.6Hz, 2H), 7. 34(t,J=7.4Hz,1H),5.20(s,2H),4.28(q,J=7.1Hz,2H),1.30(t,J=7.1Hz,3H); 13 C NMR(126MHz, CDCl3)δ166.3,148.3,130.4,128.9,128.3,125.8,121.0,62.5,51.0,14.1; HRMS(ESI)m / z:[M+H] + Calcd forC 12 H 14 N3O2232.1086; found 232.1084.

[0089] The test results above show that the structure of the product 4a synthesized in this embodiment is as shown in route 9.

[0090] Example 10

[0091] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 10, includes the following steps:

[0092]

[0093] Route 10

[0094] At room temperature, cuprous iodide (20 mol%), phenylacetylene 1a (0.2 mmol), ethyl α-diazoacetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and 1,2-dimethoxyethane (DME, 2 mL) was injected into the tube under nitrogen atmosphere and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4a, a yellow oil, in 19.9 mg (43% yield).

[0095] The NMR results of product 4a in this embodiment are as follows: 1 H NMR (500MHz, CDCl3) δ7.92 (s, 1H), 7.85–7.83 (m, 2H), 7.43 (t, J = 7.6Hz, 2H), 7. 34(t,J=7.4Hz,1H),5.20(s,2H),4.28(q,J=7.1Hz,2H),1.30(t,J=7.1Hz,3H); 13 C NMR(126MHz, CDCl3)δ166.3,148.3,130.4,128.9,128.3,125.8,121.0,62.5,51.0,14.1; HRMS(ESI)m / z:[M+H] + Calcd forC 12 H 14 N3O2232.1086; found 232.1084.

[0096] The test results above show that the structure of the product 4a synthesized in this embodiment is as shown in route 10.

[0097] Example 11

[0098] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 11, includes the following steps:

[0099]

[0100] Route 11

[0101] At room temperature, cuprous iodide (30 mol%), phenylacetylene 1a (0.2 mmol), ethyl α-diazoacetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and sodium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen atmosphere and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4a, a yellow oil, in 36.5 mg (79% yield).

[0102] The NMR results of product 4a in this embodiment are as follows: 1 H NMR (500MHz, CDCl3) δ7.92 (s, 1H), 7.85–7.83 (m, 2H), 7.43 (t, J = 7.6Hz, 2H), 7. 34(t,J=7.4Hz,1H),5.20(s,2H),4.28(q,J=7.1Hz,2H),1.30(t,J=7.1Hz,3H); 13 C NMR(126MHz, CDCl3)δ166.3,148.3,130.4,128.9,128.3,125.8,121.0,62.5,51.0,14.1; HRMS(ESI)m / z:[M+H] + Calcd forC 12 H 14 N3O2232.1086; found 232.1084.

[0103] The test results above show that the structure of the product 4a synthesized in this embodiment is as shown in route 11.

[0104] Example 12

[0105] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 12, includes the following steps:

[0106]

[0107] Route 12

[0108] At room temperature, cuprous iodide (5 mol%), phenylacetylene 1a (0.2 mmol), ethyl α-diazoacetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium phosphate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen atmosphere and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4a, a yellow oil, in 24.0 mg (52% yield).

[0109] The NMR results of product 4a in this embodiment are as follows: 1 H NMR (500MHz, CDCl3) δ7.92 (s, 1H), 7.85–7.83 (m, 2H), 7.43 (t, J = 7.6Hz, 2H), 7. 34(t,J=7.4Hz,1H),5.20(s,2H),4.28(q,J=7.1Hz,2H),1.30(t,J=7.1Hz,3H); 13 C NMR(126MHz, CDCl3)δ166.3,148.3,130.4,128.9,128.3,125.8,121.0,62.5,51.0,14.1; HRMS(ESI)m / z:[M+H] + Calcd forC 12 H 14 N3O2232.1086; found 232.1084.

[0110] The test results above show that the structure of the product 4a synthesized in this embodiment is as shown in route 12.

[0111] Example 13

[0112] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 13, includes the following steps:

[0113]

[0114] Route 13

[0115] At room temperature, cuprous iodide (20 mol%), phenylacetylene 1a (0.2 mmol), ethyl α-diazoacetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and cesium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen atmosphere and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4a, a yellow oil, in 21.3 mg (46% yield).

[0116] The NMR results of product 4a in this embodiment are as follows: 1 H NMR (500MHz, CDCl3) δ7.92 (s, 1H), 7.85–7.83 (m, 2H), 7.43 (t, J = 7.6Hz, 2H), 7. 34(t,J=7.4Hz,1H),5.20(s,2H),4.28(q,J=7.1Hz,2H),1.30(t,J=7.1Hz,3H); 13 C NMR(126MHz, CDCl3)δ166.3,148.3,130.4,128.9,128.3,125.8,121.0,62.5,51.0,14.1; HRMS(ESI)m / z:[M+H] + Calcd forC 12 H 14 N3O2232.1086; found 232.1084.

[0117] The test results above show that the structure of the product 4a synthesized in this embodiment is as shown in route 13.

[0118] Example 14

[0119] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 14, includes the following steps:

[0120]

[0121] Route 14

[0122] At room temperature, cuprous iodide (30 mol%), phenylacetylene 1a (0.2 mmol), ethyl α-diazoacetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium hydroxide (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen atmosphere and mixed thoroughly. The reaction tube was then heated to 100 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4a, a yellow oil, in 37.9 mg (82% yield).

[0123] The NMR results of product 4a in this embodiment are as follows: 1 H NMR (500MHz, CDCl3) δ7.92 (s, 1H), 7.85–7.83 (m, 2H), 7.43 (t, J = 7.6Hz, 2H), 7. 34(t,J=7.4Hz,1H),5.20(s,2H),4.28(q,J=7.1Hz,2H),1.30(t,J=7.1Hz,3H); 13 C NMR(126MHz, CDCl3)δ166.3,148.3,130.4,128.9,128.3,125.8,121.0,62.5,51.0,14.1; HRMS(ESI)m / z:[M+H] + Calcd forC 12 H 14 N3O2232.1086; found 232.1084.

[0124] The test results above show that the structure of the product 4a synthesized in this embodiment is as shown in route 14.

[0125] Example 15

[0126] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 15, includes the following steps:

[0127]

[0128] Route 15

[0129] At room temperature, cuprous iodide (20 mol%), phenylacetylene 1a (0.2 mmol), ethyl α-diazoacetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen atmosphere and mixed thoroughly. The reaction tube was then heated to 60 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4a, a yellow oil, 10.2 mg in yield (22%).

[0130] The NMR results of product 4a in this embodiment are as follows: 1 H NMR (500MHz, CDCl3) δ7.92 (s, 1H), 7.85–7.83 (m, 2H), 7.43 (t, J = 7.6Hz, 2H), 7. 34(t,J=7.4Hz,1H),5.20(s,2H),4.28(q,J=7.1Hz,2H),1.30(t,J=7.1Hz,3H); 13 C NMR(126MHz, CDCl3)δ166.3,148.3,130.4,128.9,128.3,125.8,121.0,62.5,51.0,14.1; HRMS(ESI)m / z:[M+H] + Calcd forC 12 H 14 N3O2232.1086; found 232.1084.

[0131] The test results above show that the structure of the product 4a synthesized in this embodiment is as shown in route 15.

[0132] Example 15

[0133] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 15, includes the following steps:

[0134]

[0135] Route 15

[0136] At room temperature, cuprous iodide (20 mol%), phenylacetylene 1a (0.2 mmol), ethyl α-diazoacetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen atmosphere and mixed thoroughly. The reaction tube was then heated to 60 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4a, a yellow oil, 10.2 mg in yield (22%).

[0137] The NMR results of product 4a in this embodiment are as follows: 1 H NMR (500MHz, CDCl3) δ7.92 (s, 1H), 7.85–7.83 (m, 2H), 7.43 (t, J = 7.6Hz, 2H), 7. 34(t,J=7.4Hz,1H),5.20(s,2H),4.28(q,J=7.1Hz,2H),1.30(t,J=7.1Hz,3H); 13 C NMR(126MHz, CDCl3)δ166.3,148.3,130.4,128.9,128.3,125.8,121.0,62.5,51.0,14.1; HRMS(ESI)m / z:[M+H] + Calcd forC 12 H 14 N3O2232.1086; found 232.1084.

[0138] The test results above show that the structure of the product 4a synthesized in this embodiment is as shown in route 15.

[0139] Example 16

[0140] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 16, includes the following steps:

[0141]

[0142] Route 16

[0143] At room temperature, cuprous iodide (20 mol%), o-methylphenylacetylene 1b (0.2 mmol), α-diazoethyl acetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (3:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4b, a yellow oil, in 37.9 mg (77% yield).

[0144] The NMR results of product 4b in this embodiment are as follows: 1 H NMR (CDCl3, 500MHz, ppm): δ7.81 (s, 1H), 7.79–7.77 (m, 1H), 7.27 (d, J = 2.7Hz ,3H),5.22(s,2H),4.28(q,J=7.1Hz,2H),2.47(s,3H),1.31(t,J=7.1Hz,3H); 13 C{ 1 H}NMR(CDCl3,125MHz,ppm): δ166.4,147.5,135.6,130.9,129.7,129.0,128.3,126.1,123.2,62.4,50.9,21.3,14.1; HRMS(ESI)m / z:[M+H] + Calcdfor C 13 H 16 N3O2 246.1243; found 246.1241.

[0145] The test results above show that the structure of product 4b synthesized in this embodiment is as shown in route 16.

[0146] Example 17

[0147] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 17, includes the following steps:

[0148]

[0149] Route 17

[0150] At room temperature, cuprous iodide (20 mol%), m-methylphenylacetylene 1c (0.2 mmol), α-diazoethyl acetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and then concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4c, a yellow oil, 34.3 mg in yield (70%).

[0151] The NMR results of product 4c in this embodiment are as follows: δ 7.90(s,1H), 7.70(s,1H), 7.61(d,J=7.7Hz,1H), 7.31(t,J=7.6Hz,1H), 7.16(d,J=7.6Hz,1H), 5.20(s,2H), 4.28(q,J=7.1Hz,2H), 2.40(s,3H), 1.31(t,J=7.1Hz,3H); 13 C{ 1 H}NMR(CDCl3,125MHz,ppm): δ166.3,148.4,138.6,130.2,129.1,128.8,126.5,122.9,120.9,62.5,51.0,21.4,14.1; HRMS(ESI)m / z:[M+H] + Calcd for C 13 H 16 N3O2 246.1243; found 246.1243.

[0152] The test results above show that the structure of the product 4c synthesized in this embodiment is as shown in route 17.

[0153] Example 18

[0154] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 18, includes the following steps:

[0155]

[0156] Route 18

[0157] At room temperature, cuprous iodide (20 mol%), 4-methylphenylacetylene 1d (0.2 mmol), α-diazoethyl ethyl 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (5:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4d, a yellow oil, in 31.8 mg (65% yield).

[0158] The NMR results of the product in this embodiment at 4 days are as follows: 1 H NMR (CDCl3, 500MHz, ppm): δ7.87 (s, 1H), 7.73 (d, J = 8.1Hz, 2H), 7.23 (d, J = 8.1H z,2H),5.18(s,2H),4.27(q,J=7.1Hz,2H),2.38(s,3H),1.30(t,J=7.1Hz,3H); 13 C{ 1 H}NMR(CDCl3,125MHz,ppm): δ166.4,148.3,138.1,129.5,127.6,125.7,120.8,62.4,50.9,21.3,14.1; HRMS(ESI)m / z:[M+H] + Calcd forC 13 H 16 N3O2 246.1243; found 246.1246.

[0159] The test results above show that the structure of the product 4d synthesized in this embodiment is as shown in route 18.

[0160] Example 19

[0161] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 19, includes the following steps:

[0162]

[0163] Route 19

[0164] At room temperature, cuprous iodide (20 mol%), 4-methoxyphenylacetylene 1e (0.2 mmol), α-diazoethyl ethyl 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4e, a yellow oil, in 39.4 mg (76% yield).

[0165] The NMR results of product 4e in this embodiment are as follows: 1 HNMR (500MHz, CDCl3): δ7.82(s,1H),7.76(d,J=8.8Hz,2H),6.96(d,J=8.8Hz ,2H),5.18(s,2H),4.27(q,J=7.1Hz,2H),3.84(s,3H),1.30(t,J=7.1Hz,3H); 13 C{ 1 H}NMR(125MHz, CDCl3): δ166.4,159.7,148.1,127.1,123.1,120.2,114.3,62.4,55.3,50.9,14.1; HRMS(ESI)m / z:[M+H] + Calcd for C 13 H 16 N3O3[M+Na] + 262.1192, found 262.1191.

[0166] The test results above show that the structure of the product 4e synthesized in this embodiment is as shown in route 19.

[0167] Example 20

[0168] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 20, includes the following steps:

[0169]

[0170] Route 20

[0171] At room temperature, cuprous iodide (20 mol%), 4-methoxyphenylacetylene 1f (0.2 mmol), α-diazoethyl ethyl acetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate in a 4:1 volume ratio, followed by rapid silica gel column chromatography to obtain product 4f, a yellow oil, in 37.3 mg (66% yield).

[0172] The NMR results of product 4f in this embodiment are as follows: 1 H NMR (CDCl3, 500MHz, ppm): δ7.88 (s, 1H), 7.77 (d, J = 8.2Hz, 2H), 7.45 (d, J = 8.2H z,2H),5.19(s,2H),4.27(q,J=7.1Hz,2H),1.35(s,9H),1.30(t,J=7.1Hz,3H); 13 C{ 1 H}NMR(CDCl3,125MHz,ppm): δ166.4,148.2,138.9,128.7,128.6,126.5,122.9,62.4,60.4,50.8,32.2,14.1; HRMS(ESI)m / z:[M+H] + Calcd forC 16 H 22 N3O2 288.1712; found 288.1730.

[0173] The test results above show that the structure of the product 4f synthesized in this embodiment is as shown in route 20.

[0174] Example 21

[0175] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 21, includes the following steps:

[0176]

[0177] Route 21

[0178] At room temperature, cuprous iodide (20 mol%), 1 g (0.2 mmol) of 4-ethylphenylacetylene, 2a (0.4 mmol) of α-diazoethyl acetylene, 3 (0.4 mmol) of azidotrimethylsilane, and 0.2 mmol of potassium carbonate were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect the reaction mixture, and then acetonitrile (CH3CN, 2 mL) was injected into the reaction tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until completion, and then concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate in a volume ratio of 3:1, followed by rapid silica gel column chromatography to obtain 4 g of the product of this example, which was 32.2 mg of a yellow oil, with a yield of 64%.

[0179] The NMR results for 4g of the product in this embodiment are as follows: 1 H NMR (CDCl3, 500MHz, ppm): δ7.87 (s, 1H), 7.76 (d, J=8.0Hz, 2H), 7.26 (d, J=7.9Hz, 2H), 5.19 (s, 2H), 4.28 (q, J=7.1Hz, 2H), 2.68 (q, J=7.6Hz, 2H), 1.30 (t, J=7.1Hz, 3H), 1.26 (t, J=7.6Hz, 3H); 13 C{ 1 H}NMR (CDCl3, 125MHz, ppm): δ166.3, 148.4, 144.5, 128.4, 127.8, 125.8, 120.6, 62.5, 51.0, 28.7, 15.5, 14.1; HRMS (ESI) m / z: [M+H] + Calcd for C 14 H 18 N3O2 260.1399; found 260.1405.

[0180] The test results above show that the structure of the product 4g synthesized in this embodiment is as shown in route 21.

[0181] Example 22

[0182] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 22, includes the following steps:

[0183]

[0184] Route 22

[0185] At room temperature, cuprous iodide (20 mol%), 4-n-butylphenylacetylene (0.2 mmol), α-diazoethyl ethyl 2a (0.4 mmol), azidotrimethylsilane (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain the product of this example, 4 h, as a yellow oil, 47.0 mg, with a yield of 82%.

[0186] The NMR results of the product in this embodiment after 4 hours are as follows: 1 H NMR (CDCl3, 500MHz, ppm): δ7.87 (s, 1H), 7.74 (d, J=8.1Hz, 2H), 7.24 (d, J=8.1Hz, 2H), 5.18 (s, 2H), 4.27 (q, J=7.1 Hz, 2H), 2.63 (t, J=7.7Hz, 2H), 1.65-1.59 (m, 2H), 1.41-1.35 (m, 2H) 1.30 (t, J=7.1Hz, 3H), 0.93 (t, J=7.4Hz, 3H); 13 C{ 1 H}NMR (CDCl3, 125MHz, ppm): δ166.3, 148.4, 143.2, 128.9, 127.8, 125.7, 120.7, 62.4, 51.0, 35.4, 33.5, 22.3, 14.1, 14.0; HRMS (ESI) m / z: [M+H] + Calcd forC 16 H 22 N3O2 288.1712; found 288.1735.

[0187] The test results above show that the structure of the product 4h synthesized in this embodiment is as shown in route 22.

[0188] Example 23

[0189] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 23, includes the following steps:

[0190]

[0191] Route 23.

[0192] At room temperature, cuprous iodide (20 mol%), o-fluorophenylacetylene 1i (0.2 mmol), α-diazoethyl ethyl 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and then concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4i, a yellow oil, 37.9 mg, in a yield of 69%.

[0193] The NMR results of product 4i in this embodiment are as follows: 1 H NMR(500 MHz, CDCl3): δ8.32-8.29 (m, 1H), 8.08 (d, J=3.6Hz, 1H), 7.33-7.30 (m, 1H), 7.27-7.24 (m, 1H), 7.16-7.12 (m, 1H), 5.23 (s, 2H), 4.28 (q, J=7.1Hz, 2H), 1.30 (t, J=7.1Hz, 3H); 13 C{ 1 H} NMR (125MHz, CDCl3): δ166.2, 159.3 (d, J=246.5Hz), 141.6, 129.4 (d, J=8.4Hz), 127.8 (d, J=3.5Hz), 124.6 (d, J =3.4Hz), 124.1 (d, J = 12.9Hz), 118.4 (d, J = 12.8Hz), 115.8 (d, J = 21.6Hz), 62.5, 51.0, 14.1; HRMS (ESI) m / z: [M+H] + Calcd for C 12 H 13 FN3O2[M+H] + 250.0992, found 250.0995.

[0194] The test results above show that the structure of the product 4i synthesized in this embodiment is as shown in route 23.

[0195] Example 24

[0196] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 24, includes the following steps:

[0197]

[0198] Route 24

[0199] At room temperature, cuprous iodide (20 mol%), m-fluorophenylacetylene 1j (0.2 mmol), α-diazoethyl acetylene 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and then concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4j, a yellow oil, in 33.3 mg (67% yield).

[0200] The NMR results of product 4j in this embodiment are as follows: 1 H NMR (500MHz, CDCl3): δ7.94 (s, 1H), 7.61-7.56 (m, 2H), 7.41-7.37 (m, 1H), 7 .05-7.02 (m, 1H), 5.21 (s, 2H), 4.29 (q, J=7.1Hz, 2H), 1.32 (t, J=7.1Hz, 3H); 13 C{ 1 H} NMR (125MHz, CDCl3): δ 166.2, 164.2 (d, J = 244.2Hz), 147.2, 132.5 (d, J = 8.5Hz), 130.4 (d, J = 8.4Hz), 121 .4 (d, J=3.0Hz), 121.3, 115.2 (d, J=21.1Hz), 112.7 (d, J=22.9Hz), 62.6, 51.0, 14.1; HRMS (ESI) m / z: [M+H] + Calcd forC 12 H 13 FN3O2[M+H] + 250.0992, found 250.0989.

[0201] The test results above show that the structure of the product 4j synthesized in this embodiment is as shown in route 24.

[0202] Example 25

[0203] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 25, includes the following steps:

[0204]

[0205] Route 25

[0206] At room temperature, cuprous iodide (20 mol%), o-chlorophenylacetylene 1k (0.2 mmol), α-diazoethyl ethyl 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and then concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (3:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4k, a yellow oil, in 42.1 mg (76% yield).

[0207] The 4k NMR results of the product in this embodiment are as follows: 1 HNMR (500MHz, CDCl3): δ8.34 (s, 1H), 8.25 (dd, J=7.9, 1.7Hz, 1H), 7.45 (dd, J=8.0, 1.1Hz, 1H), 7 .39-7.36 (m, 1H), 7.30-7.26 (m, 1H), 5.24 (s, 2H), 4.28 (q, J=7.1Hz, 2H), 1.31 (t, J=7.1Hz, 3H); 13 C{ 1 H}NMR(125MHz, CDCl3): δ166.2,144.4,131.3,130.2,129.9,129.2,129.0,127.2,124.6,62.5,51.0,14.1; HRMS(ESI)m / z:[M+H] + Calcd for C 12 H 13 ClN3O2[M+Na] + 266.0692, found 266.0693.

[0208] The test results above show that the structure of the product 4k synthesized in this embodiment is as shown in route 25.

[0209] Example 26

[0210] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 26, includes the following steps:

[0211]

[0212] Route 26

[0213] At room temperature, cuprous iodide (20 mol%), p-bromophenylacetylene 1L (0.2 mmol), α-diazoethyl ethyl 2A (0.4 mmol), azidetrimethylsilane 3L (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate in a 4:1 volume ratio, followed by rapid silica gel column chromatography to obtain 4L of the product of this example, which was 41.1 mg of a yellow oil, with a yield of 67%.

[0214] The NMR results of product 4l in this embodiment are as follows: 1 H NMR (CDCl3, 500MHz, ppm): δ7.92 (s, 1H), 7.71 (d, J = 8.5Hz, 2H), 7.55 (d, J = 8.5Hz, 2H), 5.20 (s, 2H), 4.29 (q, J = 7.1Hz, 2H), 1.31 (t, J = 7.1Hz, 3H); 13 C{ 1 H}NMR(CDCl3,125MHz,ppm): δ166.2,147.2,132.0,129.3,127.3,122.2,121.1,62.6,51.0,14.1; HRMS(ESI)m / z:[M+H] + Calcd for C 12 H 13 BrN3O2310.0192; found 310.0179.

[0215] The test results above show that the structure of the product 4l synthesized in this embodiment is as shown in route 26.

[0216] Example 27

[0217] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 27, includes the following steps:

[0218]

[0219] Route 27

[0220] At room temperature, cuprous iodide (20 mol%), p-cyanophenylacetylene 1m (0.2 mmol), α-diazoethyl acetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate in a 4:1 volume ratio, followed by rapid silica gel column chromatography to obtain product 4m, a yellow oil, in 36.4 mg, with a yield of 71%.

[0221] The NMR results of the product at 4m in this embodiment are as follows: 1 H NMR (CDCl3, 500MHz, ppm): δ8.04 (s, 1H), 7.97 (d, J = 8.5Hz, 2H), 7.72 (d, J = 8.5Hz, 2H), 5.24 (s, 2H), 4.31 (q, J = 7.1Hz, 2H), 1.33 (t, J = 7.1Hz, 3H); 13 C{ 1 H}NMR(125MHz, CDCl3): δ166.1,146.4,134.8,132.8,126.2,122.2,118.8,111.7,62.7,51.0,14.1; HRMS(ESI)m / z:[M+H] + Calcd for C 13 H 13 N4O2[M+H] + 257.0977, found 257.1035.

[0222] The test results above show that the structure of the product 4m synthesized in this embodiment is as shown in route 27.

[0223] Example 28

[0224] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 28, includes the following steps:

[0225]

[0226] Route 28

[0227] At room temperature, cuprous iodide (20 mol%), p-nitrophenylacetylene 1n (0.2 mmol), α-diazoethyl acetate 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and then concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (2:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4n, a yellow oil, in 40.5 mg (73% yield).

[0228] The NMR results of product 4n in this embodiment are as follows: 1 H NMR (CDCl3, 500MHz, ppm): δ8.30 (d, J = 8.2Hz, 2H), 8.10 (s, 1H), 8.03 (d, J = 8.2Hz, 2H), 5.26 (s, 2H), 4.32 (q, J = 7.1Hz, 2H), 1.34 (t, J = 7.1Hz, 3H); 13 C NMR (CDCl3, 125MHz, ppm): δ166.1, 147.4, 146.1, 136.6, 126.3, 124.3, 122.5, 62.7, 51.0, 14.1; HRMS (ESI) m / z: [M+H] + Calcd for C 12 H 13 N4O4[M+H] + 277.0925; found 277.0932.

[0229] The test results above show that the structure of the product 4n synthesized in this embodiment is as shown in route 28.

[0230] Example 29

[0231] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 29, includes the following steps:

[0232]

[0233] Route 29

[0234] At room temperature, cuprous iodide (20 mol%), 3-ethynylthiophene 1o (0.2 mmol), α-diazoethyl ethyl 2a (0.4 mmol), azidotrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4o, a yellow oil, in 41.6 mg (72% yield).

[0235] The NMR results of product 4o in this embodiment are as follows: 1 H NMR (500MHz, CDCl3): δ7.82(s,1H),7.70(d,J=2.7Hz,1H),7.46(d,J=5.0Hz,1H ),7.39-7.38(m,1H),5.18(s,2H),4.28(q,J=7.1Hz,2H),1.31(t,J=7.1Hz,3H); 13 C{ 1 H}NMR(125MHz, CDCl3): δ166.30,144.4,131.6,126.4,125.9,121.4,120.8,62.5,50.9,14.0; HRMS(ESI)m / z:[M+H] + Calcd for C 10 H 12 N3O2S[M+H] + 238.0650, found 238.0647.

[0236] The test results above show that the structure of the product 4o synthesized in this embodiment is as shown in route 29.

[0237] Example 30

[0238] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 30, includes the following steps:

[0239] Route 30

[0240] At room temperature, cuprous iodide (20 mol%), 1-hexyne 1p (0.2 mmol), α-diazoethyl ethyl 2a (0.4 mmol), azidotrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate in a volume ratio of 4:1, followed by rapid silica gel column chromatography to obtain product 4p, a yellow oil, in 31.5 mg (75% yield).

[0241] The NMR results of the 4p product in this embodiment are as follows: 1 H NMR(500 MHz, CDCl3): δ7.41 (s, 1H), 5.12 (s, 2H), 4.26 (q, J=5.7Hz, 2H), 2.75 (t, J=7.7Hz, 2H) , 1.70-1.64 (m, 2H), 1.42-1.37 (m, 2H), 1.30 (t, J=7.1Hz, 3H), 0.94 (t, J=7.4Hz, 3H); 13 C{ 1 H}NMR (125MHz, CDCl3): δ166.5, 148.9, 122.0, 62.3, 50.8, 31.4, 25.3, 22.3, 14.1, 13.8; HRMS (ESI) m / z: [M+H] + Calcd forC 10 H 18 N3O2 212.1399; found 212.1404.

[0242] The test results above show that the structure of the product 4p synthesized in this embodiment is as shown in route 30.

[0243] Example 31

[0244] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 31, includes the following steps:

[0245]

[0246] Route 31

[0247] At room temperature, cuprous iodide (20 mol%), 5-methyl-1-hexyne 1q (0.2 mmol), α-diazoethyl acetate 2a (0.4 mmol), azide-trimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (3:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4q, a yellow oil, in 33.3 mg (74% yield).

[0248] The NMR results of the product 4q in this embodiment are as follows: 1 H NMR (CDCl3, 500MHz, ppm): δ7.41 (s, 1H), 5.12 (s, 2H), 4.26 (q, J=7.1Hz, 2H), 2.75 (q, J=7 .9Hz, 2H), 1.80 (s, 1H), 1.61-1.57 (m, 2H), 1.30 (t, J=7.1Hz, 3H), 0.94 (d, J=6.3Hz, 6H); 13 C{ 1 H}NMR (CDCl3, 125MHz, ppm): δ166.5, 149.1, 121.9, 100.0, 62.3, 50.8, 38.4, 27.6, 23.6, 22.4, 14.1; HRMS (ESI) m / z: [M+H] + Calcd for C 11 H 20 N3O2 226.1556; found 226.1558.

[0249] The test results above show that the structure of the product 4q synthesized in this embodiment is as shown in route 31.

[0250] Example 32

[0251] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 32, includes the following steps:

[0252] Route 32

[0253] At room temperature, cuprous iodide (20 mol%), 1-heptaynyl 1r (0.2 mmol), α-diazoethyl ethyl 2a (0.4 mmol), azidotrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and then concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain product 4r, a yellow oil, in 33.3 mg (74% yield).

[0254] The NMR results of the product 4r in this embodiment are as follows: 1 H NMR (500MHz, CDCl3): δ7.41 (s, 1H), 5.12 (s, 2H), 4.26 (q, J=7.1Hz, 2H), 2.74 (t, J=6.1Hz , 2H), 1.72-1.66 (m, 2H), 1.37-1.34 (m, 4H), 1.30 (t, J=7.1Hz, 3H), 0.90 (t, J=7.0Hz, 3H); 13 C{ 1 H}NMR (125MHz, CDCl3): δ166.5, 149.0, 121.9, 62.3, 50.8, 31.4, 29.0, 25.6, 22.41, 14.0 (d, J=8.3Hz); HRMS (ESI) m / z: [M+H] + Calcd for C 11 H 20 N3O2[M+H] + 226.1556, found 226.1547.

[0255] The test results above show that the structure of the product 4r synthesized in this embodiment is as shown in route 32.

[0256] Example 33

[0257] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 33, includes the following steps:

[0258]

[0259] Route 33

[0260] At room temperature, cuprous iodide (20 mol%), 1-octyne 1s (0.2 mmol), α-diazoethyl ethyl 2a (0.4 mmol), azidotrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and the mixture was concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (v / v) and subjected to rapid silica gel column chromatography to obtain the product 4s, a yellow oil, in 38.1 mg (80% yield).

[0261] The NMR results of the product 4s in this embodiment are as follows: 1 H NMR (CDCl3, 500MHz, ppm): δ7.42 (s, 1H), 5.12 (s, 2H), 4.26 (q, J=7.1Hz, 2H), 2.74 (t, J=6.2 Hz, 2H), 1.71-1.65 (m, 2H), 1.37-1.34 (m, 2H), 1.30 (t, J=7.1Hz, 7H), 0.88 (t, J=7.0Hz, 3H); 13 C{ 1 H}NMR (CDCl3, 125MHz, ppm): δ166.6, 158.2, 120.0, 62.3, 50.8, 30.8, 30.3, 14.1; HRMS (ESI) m / z: [M+H] + Calcd forC 12 H 22 N3O2 240.1712; found 240.1732.

[0262] The test results above show that the structure of the product 4s synthesized in this embodiment is as shown in route 33.

[0263] Example 34

[0264] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 34, includes the following steps:

[0265]

[0266] Route 34

[0267] At room temperature, cuprous iodide (20 mol%), 3,3-dimethylbutyne 1 t (0.2 mmol), α-diazoethyl ethyl 2a (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and then concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate in a volume ratio of 4:1, followed by rapid silica gel column chromatography to obtain 4 t of the product of this example, which was 33.3 mg of a yellow oil, with a yield of 74%.

[0268] The NMR results of product 4t in this embodiment are as follows: 1 H NMR (500MHz, CDCl3): δ7.40 (s, 1H), 5.12 (s, 2H), 4.26 (q, J=7.1Hz, 2H), 1.37 (s, 9H), 1.30 (t, J=7.1Hz, 3H); 13 C{ 1 ¹H NMR (100MHz, CDCl₃): δ 13 C NMR (125MHz, CDCl3) δ166.6, 158.2, 120.0, 62.3, 50.8, 30.8, 30.3, 14.1.; HRMS (ESI) m / z: [M+H] + Calcd for C 10 H 18 N3O2[M+H] + 212.1399, found 212.1399.

[0269] The test results above show that the structure of the product 4t synthesized in this embodiment is as shown in route 34.

[0270] Example 35

[0271] A method for preparing N-alkoxymethyl-substituted-1,2,3-triazole, referring to route 35, includes the following steps:

[0272]

[0273] Route 35

[0274] At room temperature, cuprous iodide (20 mol%), phenylacetylene 1a (0.2 mmol), tert-butyl α-diazoacetate 2b (0.4 mmol), azidetrimethylsilane 3 (0.4 mmol), and potassium carbonate (0.2 mmol) were added sequentially to a 15 mL reaction tube. The reaction mixture was purged with nitrogen to protect it, and then acetonitrile (CH3CN, 2 mL) was injected into the tube under nitrogen and mixed thoroughly. The reaction tube was then heated to 80 °C and reacted for 6 h. The reaction was monitored by TLC until complete, and then concentrated under vacuum (0.08 MPa) until solvent-free to obtain a crude product. The crude product was then washed with a mixture of petroleum ether and ethyl acetate (4:1 v / v) as eluent, followed by rapid silica gel column chromatography to obtain 4 u of the product of this example, which was 44.5 mg of a yellow oil, with a yield of 86%.

[0275] The NMR results of the product 4u in this embodiment are as follows: 1 H NMR (CDCl3, 500MHz, ppm): 7.91 (s, 1H), 7.84 (d, J=7.2Hz, 2H), 7.42 (t, J=7.5Hz, 2H), 7.34 (t, J=7.4Hz, 1H), 5.10 (s, 2H), 1.50 (s, 9H); 13 C{ 1 H}NMR (CDCl3, 125MHz, ppm): δ165.3, 148.2, 130.5, 128.8, 128.2, 125.8, 120.9, 83.9, 51.6, 28.0; HRMS (ESI) m / z: [M+H] + Calcd for C 14 H 18 N3O2 260.1399; found260.1343.

[0276] The test results above show that the structure of the product 4u synthesized in this embodiment is as shown in route 35.

[0277] The N-alkoxymethyl-substituted-1,2,3-triazole compounds prepared in this invention can be used to prepare metal coordination frameworks, dyes, chemical probes and corrosion inhibitors; the N-alkoxymethyl-substituted-1,2,3-triazole compounds prepared in this invention have a wide range of biological activities and can be used for anticancer, antibacterial and anti-inflammatory purposes.

[0278] The above description merely illustrates several embodiments of the present invention and should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make modifications, substitutions, and improvements without departing from the concept and scope of the present invention, and these all fall within the protection scope of the present invention. Therefore, the patent protection scope of the present invention should be determined by the described claims.

Claims

1. A process for the preparation of N-alkoxalylmethyl substituted-1,2,3-triazole compounds, characterized in that, The preparation method is to use the acetylene represented by general formula 1, the alpha-diazoacetic ester represented by general formula 2 and the azidotrimethylsilane represented by structural formula 3 as the reaction raw materials, add the catalyst and the alkali, and react in the organic solvent to obtain the N-alkoxyacylmethyl-substituted-1,2,3-triazole compound represented by general formula 4; the reaction route is shown in the following: The acetylene is phenylacetylene, o-methylphenylacetylene, m-methylphenylacetylene, 4-methylphenylacetylene, 4-methoxyphenylacetylene, 4-ethylphenylacetylene, 4-n-butylphenylacetylene, o-fluorophenylacetylene, m-fluorophenylacetylene, o-chlorophenylacetylene, p-bromophenylacetylene, p-cyanophenylacetylene, p-nitrophenylacetylene, 3-ethynylthiophene, 1-hexyne, 5-methyl-1-hexyne, 1-heptyne, 1-octyne or 3,3-dimethylbutyne; the alpha-diazoacetic ester is alpha-diazoacetic ethyl ester or alpha-diazoacetic tert-butyl ester; The catalyst is cuprous iodide, cuprous chloride, cuprous bromide, copper chloride or copper acetate; The alkali is potassium carbonate, cesium carbonate, sodium carbonate, potassium hydroxide or potassium phosphate.

2. The production method according to claim 1, characterized by, The molar volume ratio of the acetylene, the alpha-diazoacetic ester, the azidotrimethylsilane, the alkali and the organic solvent is 1 mmol:(1-3) mmol:(1-3) mmol:1 mmol:10 mL.

3. The preparation method according to claim 1, characterized in that, The addition amount of the catalyst is 5-30 mol% of the acetylene.

4. The production method according to claim 1, characterized by, The organic solvent is tetrahydrofuran, 1,2-dimethoxyethane, 1,2-dichloroethane, N,N-dimethylformamide, acetonitrile or 1,4-dioxane.

5. The production method according to claim 1, characterized by, The reaction is carried out under the condition of nitrogen; the temperature of the reaction is 60-100 ℃, and the time is 6 h.

6. The method of claim 1, wherein, After the reaction is completed, the reaction liquid still needs to be concentrated and separated by column chromatography.

7. The production method according to claim 6, wherein The step of concentration is vacuum reduction concentration treatment under the pressure state of 0.08 MPa to obtain the crude product without organic solvent; the step of column chromatography separation is to use the mixed eluent of petroleum ether and ethyl acetate to flush and separate by column chromatography through the silica gel column; the volume ratio of the petroleum ether and the ethyl acetate is (2-5):1.

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