A method for synthesizing a 4,6-bis(trifluoromethyl)-1,3,5-triazabicyclo[3.1.0]hex-2-ene compound

Abstract

This invention discloses a method for synthesizing 4,6-bis(trifluoromethyl)-1,3,5-triazabicyclo[3.1.0]hex-2-ene compounds. Using nitrile compounds and diacaridine as raw materials, the method utilizes photo-induced decomposition of diacaridine to efficiently construct the target azabicyclo skeleton. This method features mild reaction conditions and a simple synthetic route. Furthermore, it exhibits broad functional tolerance, mild reaction conditions, high yield, and simple post-processing, making it a promising green chemical synthesis method. The novel skeleton can serve as a novel bioisostere, overcoming the bottlenecks of limited existing skeleton structures and high synthetic difficulty, providing technical support for drug molecule optimization and new drug development.

Description

Technical Field

[0001] This invention relates to a mild and efficient method for synthesizing 4,6-bis(trifluoromethyl)-1,3,5-triazabicyclo[3.1.0]hex-2-ene compounds. Background Technology

[0002] Nitriles are important chemical raw materials, abundant in nature and widely used in chemical, textile, pharmaceutical, and agricultural fields. Bisacrylidine is a nitrogen-containing heterocyclic organic compound with nitrogen atoms linked by double bonds, forming a structure similar to cyclopropene. It can serve as a carbene precursor; under light irradiation, bisacrylidine decomposes into nitrogen gas and the corresponding carbene, which then participate in various reactions.

[0003] In the fields of medicinal chemistry and new drug development, bioisosteric substitution strategies are one of the core technologies for optimizing the pharmacokinetic properties of drug molecules, improving pharmacodynamic activity, and reducing toxic side effects. The core principle is that groups or substituents with similar physicochemical properties can, while maintaining the basic interaction pattern between the drug molecule and the target biomolecule, achieve the preservation, enhancement, or reverse regulation of biological activity, thus providing ample space for the design and modification of new drug molecules.

[0004] However, the known bioisosteric skeletons are relatively limited, and some skeletons suffer from insufficient structural stability, high synthetic difficulty, and poor biocompatibility, making it difficult to meet the growing demand for new drug development. Against this backdrop, the 1,3,5-triazabicyclo[3.1.0]hex-2-ene skeleton, as a novel azabicyclostructure, possesses the core potential as a novel bioisosteric compound due to its unique ring system composition, rational arrangement of nitrogen atoms, and potential stereoelectronic properties. This skeleton retains the structural stability of heterocyclic compounds while introducing multiple nitrogen atoms to endow it with tunable electron distribution and hydrogen bonding interaction capabilities. It is expected to overcome the application limitations of existing bioisosteres and provide new technical tools and research directions for drug molecule structure optimization and new drug development. Summary of the Invention

[0005] Purpose of the invention: In order to overcome the limitations of existing technical methods, and to prepare a novel bioelectro-isosteric framework as a supplement to existing research on the synthesis of bioelectro-isosteric compounds, this invention provides a mild and efficient method for synthesizing 4,6-di(trifluoromethyl)-1,3,5-triazabicyclo[3.1.0]hex-2-ene compounds.

[0006] To address the aforementioned technical problems, the present invention provides the following technical solution.

[0007] One of the technical solutions of the present invention is a method for synthesizing a 4,6-bis(trifluoromethyl)-1,3,5-triazabicyclo[3.1.0]hex-2-ene compound, with the following structural formula:

[0008]

[0009] Wherein, R can be any of alkyl, aryl, heterocyclic, etc.

[0010] The second technical solution of the present invention provides a method for synthesizing the above-mentioned 4,6-bis(trifluoromethyl)-1,3,5-triazabicyclo[3.1.0]hex-2-ene compound, comprising the following steps:

[0011]

[0012] The nitrile compound shown in Formula 1 and the diacaridine shown in Formula 2 were dissolved in an organic solvent and reacted at room temperature for 6 hours under 440 nm blue light irradiation. After the reaction was completed, the reaction system was separated and purified to obtain the target product, that is, the target product Formula 3 was synthesized.

[0013] The visible light mentioned is blue light with a wavelength of 440nm.

[0014] The molar ratio of the compound shown in Formula 1 to the compound shown in Formula 2 can be 10:1.

[0015] The reaction is carried out in an inert atmosphere, which can be nitrogen.

[0016] In the eluent, the volume ratio of petroleum ether to ethyl acetate is 1000:1 to 5:1.

[0017] The progress of the reaction can be monitored using conventional monitoring methods in the art (e.g., TLC).

[0018] The separation and purification steps of the reaction system are as follows: the reaction system is directly concentrated under reduced pressure, and the resulting concentrate is separated and purified by column chromatography with silica gel. The eluent is petroleum ether or a mixture of petroleum ether and ethyl acetate. The eluent is collected and the solvent is evaporated to obtain the target product.

[0019] In one aspect of the present invention, the 1,3,5-triazabicyclo[3.1.0]hex-2-ene skeleton as shown in Formula 3 includes, but is not limited to, any of the following structures:

[0020]

[0021] The beneficial effects of this invention are as follows: This invention relates to a mild and efficient method for synthesizing 4,6-bis(trifluoromethyl)-1,3,5-triazabicyclo[3.1.0]hex-2-ene compounds. The reaction conditions are mild, the experimental operation is simple, the production capacity is high, the functional group tolerance is wide, and the chemical selectivity is good. It is a green chemical synthesis method with good application prospects. Attached Figure Description

[0022] To more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings used in the description of the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort. Wherein:

[0023] Figure 1 The reaction formula is for nitrile compounds with diacylpropionyl;

[0024] Figure 2-1 The proton NMR spectrum of compound 3a prepared for example;

[0025] Figure 2-2 The carbon NMR spectrum of compound 3a prepared for the example;

[0026] Figure 3-1 The proton NMR spectrum of compound 3b prepared for the example;

[0027] Figure 3-2 The carbon NMR spectrum of compound 3b prepared for the example;

[0028] Figure 4-1 The proton NMR spectrum of compound 3c prepared for the example;

[0029] Figure 4-2 The carbon NMR spectrum of compound 3c prepared for the example;

[0030] Figure 5-1 The 1H NMR spectrum of the compound prepared for the example;

[0031] Figure 5-2 The carbon NMR spectrum of the compound prepared for the example;

[0032] Figure 6-1 The proton NMR spectrum of compound 3e prepared for the example;

[0033] Figure 6-2 The carbon NMR spectrum of compound 3e prepared for the example:

[0034] Figure 7-1The proton NMR spectrum of 3g of the compound prepared for the example;

[0035] Figure 7-2 The carbon NMR spectrum of 3g of the compound prepared for the example;

[0036] Figure 8-1 The proton NMR spectrum of the compound prepared for the example at 3h;

[0037] Figure 8-2 The carbon NMR spectrum of the compound prepared for the example at 3h;

[0038] Figure 9-1 The proton NMR spectrum of compound 3i prepared for the example;

[0039] Figure 9-2 The carbon NMR spectrum of compound 3i prepared for the example;

[0040] Figure 10-1 The proton NMR spectrum of compound 3o prepared for the example;

[0041] Figure 10-2 The carbon NMR spectrum of compound 3o prepared for the example;

[0042] Figure 11-1 The proton NMR spectrum of compound 3r prepared for the example;

[0043] Figure 11-2 The carbon NMR spectrum of compound 3r prepared for the example; Detailed Implementation

[0044] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the examples in the specification.

[0045] Many specific details are set forth in the following description in order to provide a full understanding of the invention. However, the invention may also be practiced in other ways different from those described herein, and those skilled in the art can make similar extensions without departing from the spirit of the invention. Therefore, the invention is not limited to the specific embodiments disclosed below.

[0046] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in different places in this specification does not necessarily refer to the same embodiment, nor is it a single or selective embodiment that is mutually exclusive with other embodiments.

[0047] Example 1: Preparation of 3a, the reaction equation is as follows:

[0048]

[0049] In a nitrogen-filled glove box, piperonitrile (0.6 mmol, 3.0 equiv.), diazinonide (0.2 mmol, 1.0 equiv.), and 0.5 mL of solvent (DCM) were added to a 10 mL reaction tube. The reaction mixture was sealed and removed from the glove box, irradiated with a 40 W blue LED lamp at 440 nm, and stirred at room temperature for 6 hours. After the reaction was complete, the system was concentrated under reduced pressure to remove the solvent, yielding the crude product. This crude product was then purified by column chromatography using petroleum ether to ethyl acetate at a volume ratio of 1000:1–5:1 to obtain 39.8 mg of product, with a yield of 77%.

[0050] NMR analysis: 1 H NMR (400MHz, CDCl3) δ7.92-7.81 (m, 2H), 7.60 (d, J=1.6Hz, 1H), 7.38-7.31 (m, 1H), 6.97 (d, J=8.2Hz, 1H), 6.95-6 .87 (m, 2H), 6.55 (d, J=8.0Hz, 2H), 6.37 (d, J=7.8Hz, 2H), 6.12 (dd, J=7.6, 1.3Hz, 2H), 2.41 (s, 3H), 2.15 (s, 3H).

[0051] 13 C NMR(101MHz,CDCl3)δ 169.3, 152.1, 148.5, 139.9 (d, J=4.2Hz), 130.4, 129.3, 129.0, 128.8 (d, J=2.4Hz), 128.4 (d, J=2.2Hz), 128.0, 125.6, 123.6 ( d, J=286.8Hz), 123.6, 121.6 (d, J=279.7Hz), 120.0, 108.9, 108.9, 102.2, 97.7 (d, J=28.3Hz), 68.4 (q, J=35.8Hz), 21.4, 21.3.

[0052] Example 2: Preparation of 3b was carried out in the same manner as in Example 1, except that the piperonitrile in Example 1 was replaced with acetonitrile (2.0 mmol, 10.0 equiv.), yielding 34.4 mg of the target compound in 83% yield. Acetonitrile is liquid at room temperature. Without adding a solvent, the same method as in Example 1 was used to obtain 31.4 mg of the target compound in 76% yield, except that the piperonitrile in Example 1 was replaced with acetonitrile (2.0 mmol, 10.0 equiv.).

[0053] NMR analysis: 1H NMR (400MHz, CDCl3) δ7.83 (d, J=8.1Hz, 1H), 7.35 (d, J=8.1Hz, 1H), 6.97-6.83 (m, 2H) , 6.76 (d, J = 8.0Hz, 2H), 6.52 (d, J = 7.9Hz, 2H), 2.47 (s, 3H), 2.41 (s, 3H), 2.23 (s, 3H).

[0054] 13 C NMR (101MHz, CDCl3) δ172.0, 140.3 (d, J = 25.2Hz), 130.4, 129.5, 129.1, 128.8, 128.4, 128.4, 123.4 (q , J=286.7Hz), 121.4 (q, J=279.8Hz), 120.4, 97.4 (q, J=28.3Hz), 69.2 (q, J=35.8Hz), 21.3, 21.2, 17.5.

[0055] Example 3: Preparation of 3c was carried out in the same manner as in Example 1, except that the piperonitrile in Example 1 was replaced with butyronitrile (2.0 mmol, 10.0 equiv.), yielding 34.7 mg of the target compound in a 79% yield. Butyronitrile is liquid at room temperature. Without adding a solvent, the preparation was carried out in the same manner as in Example 1, except that the piperonitrile in Example 1 was replaced with butyronitrile (2.0 mmol, 10.0 equiv.), yielding 30.5 mg of the target compound in a 69% yield.

[0056] NMR analysis: 1 H NMR(400MHz, CDCl3)δ 7.87-7.77(m, 1H), 7.38-7.28(m, 1H), 6.93-6.84(m, 2H), 6.74(d, J=8.0Hz, 2H), 6.51(d, J=7.8Hz, 2H), 2 .82-2.63(m, 2H), 2.41(s, 3H), 2.23(s, 3H), 1.99-1.85(m, 1H), 1.84-1.68(m, 1H), 1.08(t, J=7.4Hz, 3H).

[0057] 13C NMR (101MHz, CDCl3) δ175.5, 140.1 (d, J=19.5Hz), 130.5, 129.2 (d, J=37.2Hz), 128.8, 128.6, 128.4 (d, J=2.0Hz), 128.3, 1 23.4 (q, J=286.7Hz), 121.5 (q, J=279.8Hz), 120.6, 97.4 (q, J=28.2Hz), 69.0 (q, J=35.8Hz), 33.5, 21.4, 21.3, 20.7, 13.8.

[0058] Example 4: Preparation on day 3, except that piperonitrile in Example 1 was replaced with valerate (2.0 mmol, 10.0 equiv.), proceeded in the same manner as in Example 1, yielding 36.7 mg of the target compound, with a yield of 81%. Valerate is liquid at room temperature. Except that piperonitrile in Example 1 was replaced with valerate (2.0 mmol, 10.0 equiv.), no solvent was added, and proceeded in the same manner as in Example 1, yielding 35.1 mg of the target compound, with a yield of 77%.

[0059] NMR analysis: 1 H NMR (400MHz, CDCl3) δ7.81 (d, J=8.0Hz, 1H), 7.33 (d, J=8.9Hz, 1H), 6.93-6.82 (m, 2H), 6.73 (d, J=8.0Hz, 2H), 6.50 (d, J=7.7Hz, 2 H), 2.84-2.64(m, 2H), 2.41(s, 3H), 2.23(s, 3H), 1.96-1.80(m, 1H), 1.76-1.61(m, 1H), 1.52-1.44(m, 2H), 0.99(t, J=7.4Hz, 3H).

[0060] 13 C NMR(101MHz, CDCl3)δ 175.7, 140.1 (d, J = 19.8Hz), 130.5, 129.2 (d, J = 37.9Hz), 128.8, 128.6, 128.4 (d, J = 2.1Hz), 128.3, 123.4 (d, J = 28 6.7Hz), 121.4 (d, J=279.8Hz), 120.6, 97.3 (d, J=28.3Hz), 69.0 (d, J=35.9Hz), 31.4, 29.1, 22.4, 21.4, 21.3, 13.9.

[0061] Example 5: Preparation of 3e, except that the piperonitrile in Example 1 was replaced with isovaleronitrile (2.0 mmol, 10.0 equiv.), proceeded in the same manner as in Example 1, yielding 36.6 mg of the target compound in 80% yield. Isovaleronitrile is liquid at room temperature. Except that the piperonitrile in Example 1 was replaced with isovaleronitrile (2.0 mmol, 10.0 equiv.), no solvent was added, and proceeded in the same manner as in Example 1, yielding 36.0 mg of the target compound in 79% yield.

[0062] NMR analysis: 1 H NMR(400MHz, CDCl3)δ 7.85-7.78 (m, 1H), 7.34 (dd, J=8.1, 1.9Hz, 1H), 6.93-6.84 (m, 2H), 6.73 (d, J=8.0Hz, 2H), 6.50 (d, J=7.8Hz, 2H), 2.70 (dd, J= 14.7, 6.5Hz, 1H), 2.52 (dd, J=14.7, 7.2Hz, 1H), 2.41 (s, 3H), 2.31-2.17 (m, 4H), 1.13 (d, J=6.6Hz, 3H), 1.05 (d, J=6.7Hz, 3H).

[0063] 13 C NMR (101MHz, CDCl3) δ 174.8, 140.1 (d, J = 18.2Hz), 130.6, 129.2 (d, J = 37.8Hz), 128.8, 128.7, 128.5 (d, J = 2.2Hz), 128.2, 123 .4 (d, J=286.7Hz), 121.4 (d, J=279.8Hz), 120.6, 97.4 (d, J=28.2Hz), 69.1 (d, J=35.8Hz), 40.4, 28.0, 22.9, 22.5, 21.4, 21.3.

[0064] Example 6: Preparation of 3g of the target compound was carried out in the same manner as in Example 1, except that the piperonitrile in Example 1 was replaced with decanoic acid (2.0 mmol, 10.0 equiv.), yielding 28.0 mg of the target compound in 53% yield. Decanoic acid is liquid at room temperature. Without adding a solvent, the preparation was carried out in the same manner as in Example 1, except that the piperonitrile in Example 1 was replaced with decanoic acid (2.0 mmol, 10.0 equiv.), yielding 28.7 mg of the target compound in 55% yield.

[0065] NMR analysis: 1H NMR(400MHz, CDCl3)δ 7.85-7.78 (m, 1H), 7.34 (dd, J=8.1, 1.9Hz, 1H), 6.94-6.81 (m, 2H), 6.73 (d, J=7.9Hz, 2H), 6.50 (d, J=7.7Hz, 2H), 2.83-2.63 (m, 2H), 2.41(s, 3H), 2.23(s, 3H), 1.97-1.81(m, 1H), 1.78-1.62(m, 1H), 1.51-1.41(m, 2H), 1.40-1.24(m, 10H), 0.94-0.84(m, 3H).

[0066] 13 C NMR (101MHz, CDCl3) δ175.7, 140.1 (d, J=18.9Hz), 130.5, 129.2 (d, J=37.7Hz), 128.8, 128.6, 128.4, 128.3, 123.4 (d, J=286.7Hz), 12 1.5 (d, J=279.8Hz), 120.6, 97.3 (d, J=28.3Hz), 69.0 (d, J=35.9Hz), 32.0, 31.7, 29.6, 29.4, 29.4, 29.3, 27.1, 22.8, 21.4, 21.3, 14.3.

[0067] Example 7: Preparation over 3 hours, except that piperonitrile in Example 1 was replaced with dodecanoic acid (2.0 mmol, 10.0 equiv.), proceeded in the same manner as in Example 1, yielding 41.3 mg of the target compound, with a yield of 77%. Dodecanoic acid is liquid at room temperature. Except that piperonitrile in Example 1 was replaced with dodecanoic acid (2.0 mmol, 10.0 equiv.), no solvent was added, and proceeded in the same manner as in Example 1, yielding 45.8 mg of the target compound, with a yield of 83%.

[0068] NMR analysis: 1 H NMR (400MHz, CDCl3) δ7.81 (d, J=8.1Hz, 1H), 7.33 (d, J=8.0Hz, 1H), 6.92-6.82 (m, 2H), 6.73 (d, J=8.0Hz, 2H), 6.49 (d, J=7.8Hz, 2H), 2.82 -2.62(m,2H),2.41(s,3H),2.22(s,3H),1.96-1.80(m,1H),1.77-1.61(m,1H),1.49-1.39(m,2H),1.34-1.24(m,14H),0.92-0.86(m,3H).

[0069] 13 C NMR(101MHz, CDCl3)δ 175.7, 140.1 (d, J = 19.0Hz), 130.5, 129.2 (d, J = 38.5Hz), 128.8, 128.6, 128.4, 128.3, 123.4 (d, J = 286.9Hz), 121.4 (d, J = 279.7H z), 120.6, 97.3 (d, J=28.2Hz), 69.0 (d, J=35.9Hz), 32.1, 31.7, 29.8, 29.7, 29.6, 29.5, 29.4, 29.3, 27.1, 22.8, 21.4, 21.3, 14.3.

[0070] 19 F NMR (377MHz, CDCl3) δ-76.39, -81.32.

[0071] Example 8: Preparation of 3i was carried out in the same manner as in Example 1, except that the piperonitrile in Example 1 was replaced with cyclopropylnitrile (2.0 mmol, 10.0 equiv.), yielding 48.4 mg of the target compound in 70% yield. Dodecanoic acid is liquid at room temperature. The same method as in Example 1 was carried out without adding solvent, except that the piperonitrile in Example 1 was replaced with dodecanoic acid (2.0 mmol, 10.0 equiv.), yielding 214 mg of the target compound in 49% yield.

[0072] NMR analysis: 1 H NMR(400MHz, CDCl3)δ 7.78 (d, J=8.0Hz, 1H), 7.31 (d, J=7.9Hz, 1H), 6.85 (d, J=7.2Hz, 1H), 6.77-6.64 (m, 5H ), 2.39(s, 3H), 2.23(s, 3H), 2.20-2.09(m, 1H), 1.35-1.27(m, 2H), 1.26-1.17(m, 2H).

[0073] 13 C NMR (101MHz, CDCl3) δ 177.2, 139.9 (d, J = 14.4Hz), 130.7, 129.1 (d, J = 35.8Hz), 128.7, 128.6, 128.3, 128.1, 123.5 ( d, J=286.9Hz), 121.5 (d, J=279.7Hz), 120.4, 97.1 (d, J=28.1Hz), 68.8 (q, J=35.8Hz), 21.4, 21.3, 12.9, 12.5, 10.9.

[0074] Example 9:30 was prepared by replacing piperonitrile in Example 1 with an equimolar amount of p-chlorobenzonitrile, and proceeding in the same manner as in Example 1, yielding 32.5 mg of the target compound in a yield of 64%.

[0075] NMR analysis: 1 H NMR(400MHz, CDCl3)δ 8.21-8.12 (m, 2H), 7.86 (d, J=6.9Hz, 1H), 7.58-7.49 (m, 2H), 7.37 (d, J=8.7Hz, 1H), 6.9 8-6.88 (m, 2H), 6.55 (d, J=8.5Hz, 2H), 6.31 (d, J=7.8Hz, 21H), 2.42 (s, 3H), 2.15 (s, 3H).

[0076] 13 C NMR(101MHz, CDCl3)δ 169.2, 140.1 (d, J=7.1Hz), 139.8, 130.8, 130.5, 129.7, 129.3 (d, J=40.2Hz), 128.8, 128.54, 128.4 (d, J=2.2Hz), 12 8.0, 127.9, 123.4 (d, J=287.0Hz), 121.5 (d, J=279.7Hz), 119.8, 98.0 (d, J=28.6Hz), 68.9 (d, J=35.9Hz), 21.4, 21.3.

[0077] Example 10: Preparation of 3r, except that the piperonitrile in Example 1 was replaced with an equimolar amount of p-fluorobenzonitrile, was carried out in the same manner as in Example 1, yielding 26.1 mg of the target compound, with a yield of 53%.

[0078] NMR analysis: 1 H NMR(400MHz, CDCl3)δ 8.30-8.23 (m, 2H), 7.88 (d, J=8.1Hz, 1H), 7.38 (d, J=8.0Hz, 1H), 7.30-7.23 (m, 2H), 6.9 8-6.91 (m, 2H), 6.55 (d, J=8.0Hz, 2H), 6.33 (d, J=7.8Hz, 2H), 2.44 (s, 3H), 2.16 (s, 3H).

[0079] 13C NMR (101MHz, CDCl3) δ169.0, 165.9 (d, J=255.5Hz), 140.1 (d, J=6.9Hz), 132. 0 (d, J=9.1Hz), 130.5, 129.3 (d, J=39.2Hz), 128.8, 128.6, 128.4 (d, J=2.2Hz) , 128.0, 125.8 (d, J = 3.3Hz), 123.5 (d, J = 287.0Hz), 121.6 (d, J = 279.7Hz), 119 .9, 116.6 (d, J = 22.1Hz), 98.0 (d, J = 28.4Hz), 68.8 (d, J = 35.9Hz), 21.4, 21.2.

[0080] The above description of the embodiments is only for the purpose of helping to understand the method and core ideas of the present invention. It should be noted that any modifications, equivalent substitutions, and improvements made by those skilled in the art without departing from the principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for synthesizing a 4,6-bis(trifluoromethyl)-1,3,5-triazabicyclo[3.1.0]hex-2-ene compound, characterized in that... The nitrile compound shown in Formula 1 and the diacaridine shown in Formula 2 were dissolved in a solvent and reacted at room temperature for 6 hours under visible light irradiation. After the reaction was completed, the reaction system was separated and purified to obtain the target product, that is, the 1,3,5-triazabicyclo[3.1.0]hex-2-ene skeleton and its derivatives shown in Formula 3 were synthesized. The reaction formula is as follows:

2. The method for synthesizing a 4,6-bis(trifluoromethyl)-1,3,5-triazabicyclo[3.1.0]hex-2-ene compound according to claim 1, characterized in that... The visible light mentioned is blue light.

3. The method for synthesizing a 4,6-bis(trifluoromethyl)-1,3,5-triazabicyclo[3.1.0]hex-2-ene compound according to claim 1, characterized in that... The solvent is dichloromethane, 1,2-dichloroethane, etc.

4. The method for synthesizing a 4,6-bis(trifluoromethyl)-1,3,5-triazabicyclo[3.1.0]hex-2-ene compound according to claim 1, characterized in that... The molar ratio of the nitrile compound shown in Formula 1 and the diacylpropidine shown in Formula 2 is 10:1 to 3:

1.

5. The method for synthesizing a 4,6-bis(trifluoromethyl)-1,3,5-triazabicyclo[3.1.0]hex-2-ene compound according to claim 1, characterized in that... The reaction is preferably carried out under an inert atmosphere, which may be nitrogen.

6. The method for synthesizing a 4,6-bis(trifluoromethyl)-1,3,5-triazabicyclo[3.1.0]hex-2-ene compound according to claim 1, characterized in that... The reaction can be carried out directly without the addition of a solvent when the nitrile compound shown in Formula 1 is in a liquid state at room temperature.

7. The method for synthesizing a 4,6-bis(trifluoromethyl)-1,3,5-triazabicyclo[3.1.0]hex-2-ene compound according to claim 1, characterized in that... The steps for separating and purifying the reaction system are as follows: the reaction system is directly concentrated under reduced pressure, and the resulting concentrate is separated and purified by column chromatography with silica gel. The eluent is petroleum ether or a mixture of petroleum ether and ethyl acetate. The eluent is collected and the solvent is evaporated to obtain the target product.

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