Furo-nitrogen heterocyclic compound and preparation method thereof

Abstract

The invention provides a furo-nitrogen heterocyclic compound and a preparation method thereof, and relates to the technical field of organic chemistry, key reaction aldehyde and amine are condensed into imine, the imine, acid and isocyanide are subjected to a four-component Ugi reaction to generate an amide compound, and then the furo-nitrogen heterocyclic compound is generated through an alkyne 3 + 2 cycloaddition reaction catalyzed by intramolecular gold. According to the invention, a series of furo-nitrogen heterocyclic compounds are synthesized through Post-Ugi. Compared with the prior art, the method has the advantages of atom economy and low cost, and has the potential of being converted into industrial production.

Description

Technical Field

[0001] The present invention mainly relates to the technical field of organic chemistry, and in particular to a furanazaheterocyclic compound and a preparation method thereof. Background Art

[0002] There are many kinds of furan nitrogen heterocyclic compounds, which are widely distributed in the metabolites of plants and some bacterial colonies, and play an important role in the growth process of organisms. Most of them have excellent biological activity and important medicinal value. Many literatures have publicly reported the biological activities of various furan nitrogen heterocyclic compounds. For example: the literature: Journal of Medicinal Chemistry, 1989, 32(6): 1147-1156.52 reported the antipsychotic activity of this class of compounds; the literature: Bioorganic & Medicinal Chemistry, 2019, 27(19): 11504854; Synthetie Communications, 2017, 47(20): 1864-1873 reported the bactericidal activity of this class of compounds; the literature: Bioorganic & Medicinal Chemistry Letters, 2019 reported that this class of compounds has the potential to become anti-tuberculosis drugs; the literature: Bioorganic & Medicinal Chemistry, 2019, 27(12): 2592-2597 reported the anticancer activity of this class of compounds; the literature: Bioorganic & Medicinal Chemistry, 2019, 27(12): 2592-2597 reported the anticancer activity of this class of compounds; Chemistry, 2019, 27(12): 2592-2597 reported the anti-inflammatory activity of this class of compounds; Journal of Fluorescence, 2018, 28(2): 655-662 reported the antioxidant activity of this class of compounds In recent years, the research on the synthesis of furano-azaheterocyclic compounds has always been the focus of research in the field of organic synthesis. There are currently two mainstream synthesis methods. One is the alkyne-mediated construction of furano-azaheterocyclic compounds. In 2009, Conreaux et al. obtained 2-substituted furan derivatives through in situ continuous Sonogashira reaction-acetylene compound coupling, demethylation and furan cyclization reaction, but the reaction has the disadvantage of limited substrate range; in 2010, Delaunay et al. used acetic acid or triethylamine as solvent, 3-alkynyl-4-methoxypyridin-2-one as raw material, heated and cyclized, and selectively obtained furan [2,3-b] pyridone and its regional isomers. Using condensation reaction to construct furano-azaheterocyclic compounds is another method. In 2007, Gajdos et al. used compounds containing active methylene or methyl as initiators to carry out Knoevenagel condensation reaction. Some of the condensation products generated by the reaction were converted to form a fused heterocyclic aromatic system of furan ring and pyrrole fused. In 2013, Gandini et al. conducted preliminary research on Diels-Alder polymerization of monomers containing two furan rings on average using bismaleimide as a complementary monomer, and synthesized a condensation polymer with a furanopyrrole structure. In addition, as another idea for constructing heterocyclic skeletons, a four-component Post-Ugi reaction was used to construct furan-nitrogen heterocyclic compounds. This method has higher atom economy and a wider substrate range, which is very beneficial for discovering drug lead compounds with important biological activities. Summary of the invention

[0003] 1. Technical problems to be solved by the invention: The present invention provides a furanazine heterocyclic compound and a preparation method thereof, which are used to solve the technical problems existing in the above-mentioned background technology.

[0004] 2. Technical solution: In order to achieve the above object, the technical solution provided by the present invention is: a furan-nitrogen heterocyclic compound, the general structural formula of which is as follows: , in: R 1 is hydrogen, C 1-6 A straight chain or branched alkyl group, C 6-14 An aryl or substituted aryl group; R 2 is hydrogen, C 1-6 A straight chain or branched alkyl group, C 6-10 An aryl or substituted aryl group; R 3 is hydrogen, C 1-6 A straight chain or branched alkyl group, C 3-6 of a cycloalkyl group.

[0005] Preferably, when C 6-14 When it is a substituted aryl group, the substituted aryl group is C 1-6 Alkyl substituted aryl, C 1-3 The invention further comprises an aryl group substituted with an alkoxy group, an aryl group substituted with a nitro group or a halogenated aryl group.

[0006] Preferably, when C 6-10 When it is a substituted aryl group, the substituted aryl group is an aryl group substituted with a methoxy group or a halogenated aryl group.

[0007] Preferably, the alkyl group is selected from at least one of n-butyl and tert-butyl.

[0008] Preferably, the cycloalkyl group is selected from at least one of a cyclopentyl group and a cyclohexyl group.

[0009] Preferably, the substituted aryl group is: 4-bromophenyl, 4-chlorophenyl, 4-fluorophenyl, 4-cyanophenyl, 4-nitrophenyl, 4-methylphenyl, 4-methoxyphenyl, 4-xanthoylphenyl, phenyl, 2-bromophenyl, 2-chlorophenyl, 2-fluorophenyl, 2-trifluoromethylphenyl, 3-chlorophenyl, 3-trifluoromethylphenyl, 4-bromo-2-fluorophenyl.

[0010] A method for preparing a furanoazaheterocyclic compound comprises the following steps: , Aldehydes and amines condense to form imines, which then react with acids (or carboxylic acids) and isocyanates in a four-component Ugi reaction to form amide compounds, which are then subjected to an intramolecular gold-catalyzed 3+2 cycloaddition reaction of alkynes to form furano-azaheterocyclic compounds.

[0011] Preferably, S1, at room temperature, measure 0.12 mmol of aldehyde, 0.1 mmol of amine and 2.0 mL of methanol, and then put them into a 10 mL dry vial; S2, stirring the above solution containing aldehyde, amine and methanol at room temperature for 10-15 minutes to allow the aldehyde and amine to be fully mixed and initially reacted and condensed to form an imine intermediate; S3, then add 0.1mmol of acid to the mixture and continue stirring; S4, adding 0.1 mmol of isocyanide to the mixture to form a four-component system, and then stirring continuously at room temperature for 8 hours to allow the reaction to proceed fully, complete the Ugi reaction, and generate an amide compound; S5. After the reaction is completed, the mixture is directly purified by flash column chromatography to obtain pure amide; S6, take 0.1 mmol of the amide obtained in step S5, 0.005 mmol of triphenylphosphine trifluoromethanesulfonate gold and 2.0 mL of chloroform, and put them into a 10 mL dry vial; S7, stirring the obtained solution at 80° C. to initiate the intramolecular gold-catalyzed alkyne 3+2 cycloaddition reaction, and then maintaining stirring at 80° C. for 8 hours to complete the reaction; S8. After the reaction is completed, the mixture is purified by rapid column chromatography to finally obtain a furanazaheterocyclic compound.

[0012] Preferably, the aldehyde is furanaldehyde, the amine is n-propylamine, n-pentylamine, methoxybenzylamine or cyclobutylamine, the acid is but-2-ynoic acid, pent-2-ynoic acid, phenylpropiolic acid or propiolic acid, and the isocyanide is tert-butyl isocyanide, cyclohexyl isocyanide, cyclopentyl isocyanide or 2-isocyanpropane.

[0013] 3. Beneficial effects: Compared with the prior art, the technical solution provided by the present invention has the following beneficial effects: The invention synthesizes a series of furano-azaheterocyclic compounds by Post-Ugi. Compared with the existing technology, the method is more atom-economical and low-cost, and has the potential to be converted into industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 The synthetic flow chart of the present invention is shown in FIG. DETAILED DESCRIPTION

[0015] To facilitate understanding of the present invention, the present invention will be described more comprehensively below with reference to the relevant drawings. Several embodiments of the present invention are shown in the drawings. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of the present invention more thorough and comprehensive.

[0016] In the description of the present invention, it should be understood that the terms "center", "longitudinal", "lateral", "length", "width", "thickness", "up", "down", "front", "back", "left", "right", "vertical", "horizontal", "page", "bottom", "inside", "outside", "clockwise", "counterclockwise" and the like indicating orientations or positional relationships are based on the orientations or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, and do not indicate or imply that the referred device or element must have a specific orientation, be constructed and operated in a specific orientation, and therefore should not be understood as limiting the present invention.

[0017] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" and "second" may explicitly or implicitly include one or more of the features. In the description of the present invention, the meaning of "plurality" is two or more, unless otherwise clearly and specifically defined.

[0018] In the present invention, unless otherwise clearly specified and limited, the terms "installed", "connected", "connected", "fixed", "provided with", etc. should be understood in a broad sense, for example, it can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection, or it can be indirectly connected through an intermediate medium, or it can be internal communication between two components. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0019] It should be noted that the structures not introduced in the present invention are the same as the prior art or can be implemented by using the prior art, and are not described in detail here because they do not involve the design points and improvement directions of the present invention.

[0020] See attached Figure 1 , a furanoazaheterocyclic compound, the general structural formula of which is as follows: , in: R 1 is hydrogen, C 1-6 A straight chain or branched alkyl group, C 6-14 An aryl or substituted aryl group; R 2 is hydrogen, C 1-6 A straight chain or branched alkyl group, C 6-10 An aryl or substituted aryl group; R 3 is hydrogen, C 1-6 A straight chain or branched alkyl group, C 3-6 of a cycloalkyl group.

[0021] When C 6-14 When it is a substituted aryl group, the substituted aryl group is C 1-6 Alkyl substituted aryl, C 1-3 The invention further comprises an aryl group substituted with an alkoxy group, an aryl group substituted with a nitro group or a halogenated aryl group.

[0022] When C 6-10 In the case of a substituted aryl group, the substituted aryl group is an aryl group substituted with a methoxy group or a halogenated aryl group.

[0023] The alkyl group is selected from at least one of an n-butyl group and a tert-butyl group.

[0024] The cycloalkyl group is selected from at least one of a cyclopentyl group and a cyclohexyl group.

[0025] Substituted aryl groups are: 4-bromophenyl, 4-chlorophenyl, 4-fluorophenyl, 4-cyanophenyl, 4-nitrophenyl, 4-methylphenyl, 4-methoxyphenyl, 4-xanthoylphenyl, phenyl, 2-bromophenyl, 2-chlorophenyl, 2-fluorophenyl, 2-trifluoromethylphenyl, 3-chlorophenyl, 3-trifluoromethylphenyl, 4-bromo-2-fluorophenyl.

[0026] A method for preparing a furanoazaheterocyclic compound comprises the following steps: , Aldehydes and amines condense to form imines, which then react with acids (or carboxylic acids) and isocyanates in a four-component Ugi reaction to form amide compounds, which are then subjected to an intramolecular gold-catalyzed 3+2 cycloaddition reaction of alkynes to form furano-azaheterocyclic compounds.

[0027] S1. At room temperature, measure 0.12 mmol of aldehyde, 0.1 mmol of amine and 2.0 mL of methanol, and then put them into a 10 mL dry vial; S2, stirring the above solution containing aldehyde, amine and methanol at room temperature for 10-15 minutes to allow the aldehyde and amine to be fully mixed and initially reacted and condensed to form an imine intermediate; S3, then add 0.1mmol of acid to the mixture and continue stirring; S4, adding 0.1 mmol of isocyanide to the mixture to form a four-component system, and then stirring continuously at room temperature for 8 hours to allow the reaction to proceed fully, complete the Ugi reaction, and generate an amide compound; S5. After the reaction is completed, the mixture is directly purified by flash column chromatography to obtain pure amide; S6, take 0.1 mmol of the amide obtained in step S5, 0.005 mmol of triphenylphosphine trifluoromethanesulfonate gold and 2.0 mL of chloroform, and put them into a 10 mL dry vial; S7, stirring the obtained solution at 80° C. to initiate the intramolecular gold-catalyzed alkyne 3+2 cycloaddition reaction, and then maintaining stirring at 80° C. for 8 hours to complete the reaction; S8. After the reaction is completed, the mixture is purified by rapid column chromatography to finally obtain a furanazaheterocyclic compound.

[0028] The aldehyde is furanaldehyde, the amine is n-propylamine, n-pentylamine, methoxybenzylamine or cyclobutylamine, the acid is but-2-ynoic acid, pent-2-ynoic acid, phenylpropiolic acid or propiolic acid, and the isocyanide is tert-butyl isocyanide, cyclohexyl isocyanide, cyclopentyl isocyanide or 2-isocyanpropane.

[0029] Example 1: At room temperature, furan carboxaldehyde (0.12 mmol), n-propylamine (0.1 mmol) and methanol (2.0 mL) were placed in a 10 mL dry vial. The resulting solution was stirred at room temperature for 10-15 minutes, then but-2-ynoic acid (0.1 mmol) was added to the mixture, and finally tert-butyl isocyanide (0.1 mmol) was added to the mixture. The mixture was then stirred at room temperature for 8 hours, and the mixture was directly purified by flash column chromatography to obtain a pure product. After that, amide (0.1 mmol), triphenylphosphine trifluoromethanesulfonate gold (0.005 mmol) and chloroform (2.0 mL) were placed in a 10 mL dry vial. The resulting solution was stirred at 80 ° C, and then the mixture was stirred at 80 ° C for 8 hours. The mixture was directly purified by flash column chromatography to obtain 17 g of furan and nitrogen heterocyclic compounds, with a yield of 56%.

[0030] 1 H NMR (300 MHz, CDCl3): δ = 6.61 (d, J = 2.87 Hz, 1 H), 6.19 (d,J =2.87 Hz, 1 H), 5.87 (s, 1 H), 5.63 (s, 1 H), 4.81 (s, 1 H), 2.11 (s, 3 H),1.29–1.24 (m, 13 H), 0.85 (t, J = 7.08 Hz, 3 H).

[0031] Example 2: At room temperature, furan carboxaldehyde (0.12 mmol), n-propylamine (0.1 mmol) and methanol (2.0 mL) were placed in a 10 mL dry vial. The resulting solution was stirred at room temperature for 10-15 minutes, then pent-2-ynoic acid (0.1 mmol) was added to the mixture, and finally tert-butyl isocyanide (0.1 mmol) was added to the mixture. The mixture was then stirred at room temperature for 8 hours, and the mixture was directly purified by flash column chromatography to obtain a pure product. After that, amide (0.1 mmol), triphenylphosphine trifluoromethanesulfonate gold (0.005 mmol), and chloroform (2.0 mL) were placed in a 10 mL dry vial. The resulting solution was stirred at 80 ° C, and then the mixture was stirred at 80 ° C for 8 hours. The mixture was directly purified by flash column chromatography to obtain 16 g of furan and nitrogen heterocyclic compounds, with a yield of 51%.

[0032] 1H NMR (300 MHz, CDCl3): δ = 6.71 (d, J = 2.87 Hz, 1 H), 6.07 (d,J =2.87 Hz, 1 H), 5.71 (s, 1 H), 5.53 (s, 1 H), 4.61 (s, 1 H), 2.21 (s, 3 H),1.30–1.24 (m, 15 H), 0.86 (t, J = 7.08 Hz, 3 H).

[0033] Example 3: At room temperature, furan carboxaldehyde (0.12 mmol), n-propylamine (0.1 mmol) and methanol (2.0 mL) were placed in a 10 mL dry vial. The resulting solution was stirred at room temperature for 10-15 minutes, and then phenylpropiolic acid (0.1 mmol) was added to the mixture, and finally tert-butyl isocyanide (0.1 mmol) was added to the mixture. The mixture was then stirred at room temperature for 8 hours, and the mixture was directly purified by flash column chromatography to obtain a pure product. After that, amide (0.1 mmol), triphenylphosphine trifluoromethanesulfonate gold (0.005 mmol), and chloroform (2.0 mL) were placed in a 10 mL dry vial. The resulting solution was stirred at 80 ° C, and then the mixture was stirred at 80 ° C for 8 hours. The mixture was directly purified by flash column chromatography to obtain 20 g of furan and nitrogen heterocyclic compounds, with a yield of 54%.

[0034] 1 H NMR (600 MHz, CDCl3) δ 7.27 (d, J = 7.5 Hz, 2H), 7.20-7.19 (m, 3H), 6.72 (d, J = 2.87 Hz, 1 H), 6.31 (d,J =2.87 Hz, 1 H), 5.71 (s, 1 H), 5.54 (s, 1 H), 4.80 (s, 1 H), 1.29–1.24 (m, 13 H), 0.85 (t, J = 7.08 Hz, 3 H);

[0035] Example 4: At room temperature, furan carboxaldehyde (0.12 mmol), n-pentylamine (0.1 mmol) and methanol (2.0 mL) were placed in a 10 mL dry vial. The resulting solution was stirred at room temperature for 10-15 minutes, then but-2-ynoic acid (0.1 mmol) was added to the mixture, and finally tert-butyl isocyanide (0.1 mmol) was added to the mixture. The mixture was then stirred at room temperature for 8 hours, and the mixture was directly purified by flash column chromatography to obtain a pure product. After that, amide (0.1 mmol), triphenylphosphine trifluoromethanesulfonate gold (0.005 mmol), and chloroform (2.0 mL) were placed in a 10 mL dry vial. The resulting solution was stirred at 80°C, and then the mixture was stirred at 80°C for 8 hours to react. The mixture was directly purified by flash column chromatography to obtain 18 g of furan and nitrogen heterocyclic compounds, with a yield of 48%.

[0036] 1 H NMR (300 MHz, CDCl3): δ = 6.65 (d, J = 2.87 Hz, 1 H), 6.17 (d,J =2.87 Hz, 1 H), 5.77 (s, 1 H), 5.63 ( s, 1 H), 4.91 (s, 1 H), 2.21 (s, 3 H),1.32–1.21 (m, 17 H), 0.88 (t, J = 7.08 Hz, 3 H).

[0037] Example 5: At room temperature, furan carboxaldehyde (0.12 mmol), cyclobutylamine (0.1 mmol) and methanol (2.0 mL) were placed in a 10 mL dry vial. The resulting solution was stirred at room temperature for 10-15 minutes, then but-2-ynoic acid (0.1 mmol) was added to the mixture, and finally tert-butyl isocyanide (0.1 mmol) was added to the mixture. The mixture was then stirred at room temperature for 8 hours, and the mixture was directly purified by flash column chromatography to obtain a pure product. After that, amide (0.1 mmol), triphenylphosphine trifluoromethanesulfonate gold (0.005 mmol) and chloroform (2.0 mL) were placed in a 10 mL dry vial. The resulting solution was stirred at 80 ° C, and then the mixture was stirred at 80 ° C for 8 hours. The mixture was directly purified by flash column chromatography to obtain 14 g of furan and nitrogen heterocyclic compounds with a yield of 44%.

[0038] 1H NMR (300 MHz, CDCl3): δ = 6.87 (d, J = 2.87 Hz, 1 H), 6.31 (d,J =2.87 Hz, 1 H), 5.98 (s, 1 H), 5.54 ( s, 1 H), 4.91 (s, 1 H), 2.41 (s, 3 H),1.28–1.23 (m, 16 H), 0.87 (t, J = 7.08 Hz, 3 H).

[0039] Example 6: At room temperature, furan carboxaldehyde (0.12 mmol), p-methoxybenzylamine (0.1 mmol) and methanol (2.0 mL) were placed in a 10 mL dry vial. The resulting solution was stirred at room temperature for 10-15 minutes, then but-2-ynoic acid (0.1 mmol) was added to the mixture, and finally tert-butyl isocyanide (0.1 mmol) was added to the mixture. The mixture was then stirred at room temperature for 8 hours, and the mixture was directly purified by flash column chromatography to obtain a pure product. After that, amide (0.1 mmol), triphenylphosphine trifluoromethanesulfonate gold (0.005 mmol), and chloroform (2.0 mL) were placed in a 10 mL dry vial. The resulting solution was stirred at 80 ° C, and then the mixture was stirred at 80 ° C for 8 hours. The mixture was directly purified by flash column chromatography to obtain 22 g of furan and nitrogen heterocyclic compounds, with a yield of 58%.

[0040] 1 H NMR (300 MHz, CDCl3): δ = 7.77 (d, J = 7.93 Hz, 1 H), 7.13–7.10(m, 3 H), 6.76 (d, J = 8.32 Hz, 2 H), 6.11 (s, 1 H), 5.84 (s, 1 H), 5.41 (s,1 H),5.08 (d, J = 14.33 Hz, 1 H), 4.35 (d, J = 14.33 Hz, 1 H), 3.67 (s, 3H), 3.38 (s, 3 H), 1.12 (s, 9 )

[0041] Example 7: At room temperature, furan carboxaldehyde (0.12 mmol), n-propylamine (0.1 mmol) and methanol (2.0 mL) were placed in a 10 mL dry vial. The resulting solution was stirred at room temperature for 10-15 minutes, then but-2-ynoic acid (0.1 mmol) was added to the mixture, and finally cyclohexyl isocyanide (0.1 mmol) was added to the mixture. The mixture was then stirred at room temperature for 8 hours, and the mixture was directly purified by flash column chromatography to obtain a pure product. After that, amide (0.1 mmol), triphenylphosphine trifluoromethanesulfonate gold (0.005 mmol), and chloroform (2.0 mL) were placed in a 10 mL dry vial. The resulting solution was stirred at 80 ° C, and then the mixture was stirred at 80 ° C for 8 hours. The mixture was directly purified by flash column chromatography to obtain 18 g of furan and nitrogen heterocyclic compounds, with a yield of 55%.

[0042] 1 H NMR (400 MHz, DMSO-d6): δ = 7.18 (t, J =7.69 Hz, 1H), 7.07 (t, J =7.36 Hz, 1 H), 6.83 (d, J = 8.15 Hz, 1 H), 5.68 (s, 1H), 5.16 (s, 1 H), 2.94–2.87 (m, 2 H), 2.73–2.63 (m, 1 H), 1.60–1.47 (m, 4 H), 1.26–1.12 (m, 5 H), 1.03 (t, J =7.41 Hz, 3 H), 0.85–0.67 (m, 2 H).

[0043] Example 8: At room temperature, furan carboxaldehyde (0.12 mmol), n-propylamine (0.1 mmol) and methanol (2.0 mL) were placed in a 10 mL dry vial. The resulting solution was stirred at room temperature for 10-15 minutes, then but-2-ynoic acid (0.1 mmol) was added to the mixture, and finally cyclopentyl isocyanide (0.1 mmol) was added to the mixture. The mixture was then stirred at room temperature for 8 hours, and the mixture was directly purified by flash column chromatography to obtain a pure product. After that, amide (0.1 mmol), triphenylphosphine trifluoromethanesulfonate gold (0.005 mmol) and chloroform (2.0 mL) were placed in a 10 mL dry vial. The resulting solution was stirred at 80 ° C, and then the mixture was stirred at 80 ° C for 8 hours. The mixture was directly purified by flash column chromatography to obtain 19 g of furan and nitrogen heterocyclic compounds, with a yield of 60%.

[0044] 1H NMR (400 MHz, DMSO-d6): δ = 7.32 (t, J =7.69 Hz, 1H), 7.19 (t, J =7.36 Hz, 1 H), 6.77 (d, J = 8.15 Hz, 1 H), 5.82 (s, 1H), 5.13 (s, 1 H), 2.94–2.87 (m, 3 H), 1.60–1.27 (m, 9 H), 1.03 (t, J =7.41 Hz, 3 H).

[0045] Example 9: At room temperature, furan carboxaldehyde (0.12 mmol), n-propylamine (0.1 mmol) and methanol (2.0 mL) were placed in a 10 mL dry vial. The resulting solution was stirred at room temperature for 10-15 minutes, then but-2-ynoic acid (0.1 mmol) was added to the mixture, and finally 2-isocyanpropane (0.1 mmol) was added to the mixture. The mixture was then stirred at room temperature for 8 hours, and the mixture was directly purified by flash column chromatography to obtain a pure product. After that, amide (0.1 mmol), triphenylphosphine trifluoromethanesulfonate gold (0.005 mmol) and chloroform (2.0 mL) were placed in a 10 mL dry vial. The resulting solution was stirred at 80 ° C, and then the mixture was stirred at 80 ° C for 8 hours. The mixture was directly purified by flash column chromatography to obtain 19 g of furan and nitrogen heterocyclic compound, with a yield of 60%.

[0046] 1 H NMR (300 MHz, CDCl3): δ = 6.81 (d, J = 2.87 Hz, 1 H), 6.25 (d,J =2.87 Hz, 1 H), 5.56 (s, 1 H), 5.34 ( s, 1 H), 4.78 (s, 1 H), 2.23 (s, 3 H),1.33–1.29 (m, 11 H), 0.75 (t, J = 7.08 Hz, 3 H).

[0047] The above-described embodiments only express a certain implementation mode of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the patent scope of the present invention. It should be pointed out that, for ordinary technicians in this field, several modifications and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be based on the attached claims.

Claims

1. A furanoazaheterocyclic compound, characterized in that: Its general structure is as follows: ， in: R 1 is hydrogen, C 1-6 A straight chain or branched alkyl group, C 6-14 An aryl or substituted aryl group; R 2 is hydrogen, C 1-6 A straight chain or branched alkyl group, C 6-10 An aryl or substituted aryl group; R 3 is hydrogen, C 1-6 A straight chain or branched alkyl group, C 3-6 of a cycloalkyl group.

2. A furanoazaheterocyclic compound according to claim 1, characterized in that: When C 6-14 When it is a substituted aryl group, the substituted aryl group is C 1-6 Alkyl substituted aryl, C 1-3 The invention further comprises an aryl group substituted with an alkoxy group, an aryl group substituted with a nitro group or a halogenated aryl group.

3. A furanoazaheterocyclic compound according to claim 2, characterized in that: When C 6-10 When it is a substituted aryl group, the substituted aryl group is an aryl group substituted with a methoxy group or a halogenated aryl group.

4. A furanoazaheterocyclic compound according to claim 3, characterized in that: The alkyl group is selected from at least one of an n-butyl group and a tert-butyl group.

5. A furanoazaheterocyclic compound and a preparation method thereof according to claim 4, characterized in that: The cycloalkyl group is selected from at least one of a cyclopentyl group and a cyclohexyl group.

6. A furanoazaheterocyclic compound and a preparation method thereof according to claim 1, characterized in that: The substituted aryl groups are: 4-bromophenyl, 4-chlorophenyl, 4-fluorophenyl, 4-cyanophenyl, 4-nitrophenyl, 4-methylphenyl, 4-methoxyphenyl, 4-xanthoylphenyl, phenyl, 2-bromophenyl, 2-chlorophenyl, 2-fluorophenyl, 2-trifluoromethylphenyl, 3-chlorophenyl, 3-trifluoromethylphenyl, 4-bromo-2-fluorophenyl.

7. A method for preparing a furanoazaheterocyclic compound according to any one of claims 1 to 6, characterized in that: The following steps are involved: ， Aldehydes and amines condense to form imines, which then react with acids (or carboxylic acids) and isocyanate to form amide compounds, which are then subjected to intramolecular gold-catalyzed 3+2 cycloaddition reactions of alkynes to form furano-azaheterocyclic compounds.

8. The method for preparing a furanoazaheterocyclic compound according to claim 7, characterized in that: S1. At room temperature, measure 0.12 mmol of aldehyde, 0.1 mmol of amine and 2.0 mL of methanol, and then put them into a 10 mL dry vial; S2, stirring the above solution containing aldehyde, amine and methanol at room temperature for 10-15 minutes to allow the aldehyde and amine to be fully mixed and initially reacted and condensed to form an imine intermediate; S3, then add 0.1mmol of acid to the mixture and continue stirring; S4, adding 0.1 mmol of isocyanide to the mixture to form a four-component system, and then stirring continuously at room temperature for 8 hours to allow the reaction to proceed fully, complete the Ugi reaction, and generate an amide compound; S5. After the reaction is completed, the mixture is directly purified by flash column chromatography to obtain pure amide; S6, take 0.1 mmol of the amide obtained in step S5, 0.005 mmol of triphenylphosphine trifluoromethanesulfonate gold and 2.0 mL of chloroform, and put them into a 10 mL dry vial; S7, stirring the obtained solution at 80° C. to initiate the intramolecular gold-catalyzed alkyne 3+2 cycloaddition reaction, and then maintaining stirring at 80° C. for 8 hours to complete the reaction; S8. After the reaction is completed, the mixture is purified by rapid column chromatography to finally obtain a furanazaheterocyclic compound.

9. The method for preparing a furanoazaheterocyclic compound according to claim 1, characterized in that: The aldehyde is furanaldehyde, the amine is n-propylamine, n-pentylamine, methoxybenzylamine or cyclobutylamine, the acid is but-2-ynoic acid, pent-2-ynoic acid, phenylpropiolic acid or propiolic acid, and the isocyanide is tert-butyl isocyanide, cyclohexyl isocyanide, cyclopentyl isocyanide or 2-isocyanuric acid propane.

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