A method for synthesizing 2,5-diaminopyrrole compounds

Abstract

The application discloses a synthesis method of 2,5-diaminopyrrole compounds. The synthesis method is as follows: in a reactor, N-trifluoroacetanilide compounds, alkyne halides, isonitriles, palladium salt catalysts, alkalis, additives, solvents are stirred and reacted at 60 DEG C, and the reaction solution is separated and purified to obtain 2,5-diaminopyrrole compounds. The method develops a three-component four-molecule tandem cyclization reaction of N-trifluoroacetanilide, alkyne halides and isonitriles to construct a series of highly functionalized 2,5-diaminopyrrole compounds. The main features of the reaction are mild reaction conditions, easy-to-obtain raw materials, simple operation, good regioselectivity and wide substrate universality.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for synthesizing 2,5-diaminopyrrole compounds. Background Technology

[0002] Pyrroles and their derivatives, as an important class of five-membered aromatic heterocyclic compounds, are key components of many natural products or bioactive substances. Due to their unique chemical properties and biological activity, they are widely used in numerous fields such as medicine, materials, and dyes. Therefore, developing new strategies for the synthesis of these compounds has been a research hotspot for scientists in recent years. Traditional methods for synthesizing pyrrole compounds, such as the Knorr reaction, Hantzsch reaction, and Paal-Knorr reaction, mainly utilize the condensation of carbonyl compounds and amines (Knorr, L. Ann. 1886, 236, 290; Hantzsch, A. Ber. Dtsch. Chem. Ges. 1890, 23, 1474; Knorr, L. Dtsch. Chem. Ges. 1884, 17, 1635; Paal, C. Ber. Dtsch. Chem. Ges. 1885, 18, 367). However, these reactions typically involve harsh and dangerous conditions such as high temperatures and strong acids, thus limiting their applicability.

[0003] The synthesis of pyrrole and its derivatives via transition metal-catalyzed cyclization has been one of the most favored synthetic strategies by scientists in recent decades, such as [4+1], [3+2], [3+1+1], and [2+1+1+1] cycloaddition reactions. Among the reported methods for the synthesis of pyrrole and its derivatives via transition metal catalysis (D. Srimani, YB David, D. Milstein, Angew. Chem. Int. Ed. 2013, 125, 4104; J. Liu, ZX Fang, Q. Zhang, Q...),... Liu, .Gao,W.Hu,Y.Gao,M.Hu,W.Wu,Y.Ren,H.Jiang,Org.Lett.2016,18,5924;G.Qiu,Q.Wang,J.Zhu,Org.Lett.2017,1 9,270; Y. Zhou, L. Zhou, LT Jesikiewicz, P. Liu, SLB, J. Am. Chem. Soc. 2020, 142, 9908; K. Huang, JB Liu, ZFChen, YC Wang, S. Yadav, G. Qiu, Org. Lett. 2020, 22, 5931). Besides simple pyrroles, the synthesis of polysubstituted pyrrole compounds usually requires the use of relatively complex starting materials, resulting in cumbersome operations and poor atom economy. Therefore, developing new synthetic methods that use simple starting materials to construct polysubstituted pyrrole compounds in one step remains of significant value.

[0004] Isonitriles are a class of highly reactive small molecules containing (-NC) structures. Their unique valence bond structure endows them with a wide range of chemical properties. In recent decades, through transition metal-catalyzed coupling cyclization reactions of isonitriles with various reagents such as amines, alkenes, alkynes, diazo compounds, and carbonyl compounds, many nitrogen-containing heterocyclic compounds have been constructed (Peng, J.; Gao, Yang.; Zhu, C.; Liu, B.; Gao, Y.; Hu, M.; Wu, W.; Jiang, HJO, JOrg. Chem. 2017, 82, 3581; Wang, J.; Gao, D.-W.; Huang, J.; Tang, S.; Xiong, Z.; Hu, H.; You, S.-L.; Zhu, Q. ACS Catalysis.2017,7,3832;Wu,W.;Li,M.;Zheng,J.;Hu,W.;Li,C.;Jiang,H.Chem.Commun.201 8,54,6855;Yuan,WK;Liu,YF;Lan,Z.;Wen,LR;Li,M.Org.Lett.2018,20,7158;Collet,JW;Van Der Nol, EA; Roose, TR; Maes, BUW; Ruijter, E.; Orru, RVA, J.O.R. G. Chem. 2020, 85, 7378; Zhu, Y.-M.; Fang, Y.; Li, H.; Xu, XP; Ji, S.-J. Org. Lett. 2021, 23, 7342; Li, M.; Zhang, R.; Gao, Q.; Jiang, H.; Lei, M.; Wu, W. Angew. Chem. Int. Ed. 2022, 61, e202208203). However, most current methods involve a single isonitrile in the reaction. Although reactions involving bimolecular or multimolecular isonitriles in the synthesis of heterocyclic compounds have been reported in recent years, in most cases the isonitriles have a single reaction site and lack selectivity. This has limited the diversity of isonitrile chemistry to some extent; furthermore, the synthesis of functionalized 2,5-diaminopyrrole compounds using two simple isonitrile molecules simultaneously has not been reported. In summary, the synthesis of 2,5-diaminopyrrole compounds using simple N-trifluoroacetanilides, acetylic halides, and two isonitrile molecules, achieving efficient one-step construction of new carbon-carbon and carbon-nitrogen bonds through a tandem cyclization process, is not only novel in methodology but also holds promising application prospects. Summary of the Invention

[0005] The purpose of this invention is to address the shortcomings and deficiencies of existing technologies by providing a method for synthesizing 2,5-diaminopyrrole compounds. This method uses readily available N-trifluoroacetanilide and alkyne halides as raw materials, common palladium salts as catalysts, cesium salts as bases, lithium bromide as additives, and water and toluene as mixed solvents. Employing a base-promoted, palladium-catalyzed cyclization strategy, it selectively constructs pyrrole derivatives with amino substitutions at the 2- and 5-positions. This method offers advantages such as high atom economy, single selectivity, simple and safe operation, and wide substrate applicability, demonstrating promising application prospects in practical production and research.

[0006] The objective of this invention is achieved through the following technical solution.

[0007] A method for synthesizing a 2,5-diaminopyrrole compound, comprising the following steps:

[0008] In a reactor, substrate N-trifluoroacetanilide compounds, acetylide halides, palladium salt catalysts, bases, additives, water, and solvents are added, and the reaction is stirred at 40–100 °C. After the reaction is completed, the mixture is cooled to room temperature, and the product is separated and purified to obtain the 2,5-diaminopyrrole compounds.

[0009] Furthermore, the chemical reaction equations for the synthesis process are shown below:

[0010]

[0011] In the formula, R 1 The substituents on N-trifluoroacetanilide are selected from one or more of hydrogen, 3-fluoro, 3-chloro, 3-methyl, 3-cyano, 4-methoxy, and 4-alkenyl.

[0012] R 2 The substituents on the alkynyl halide are hydrogen, 4-bromo, 4-methyl, 4-carboxylic acid methyl ester, and 3-chloro;

[0013] R 3 The substituents on the isonitrile are tert-butyl and 1,1,3,3-tetramethylbutyl.

[0014] Furthermore, the N-trifluoroacetanilide compound is N-trifluoroacetanilide; the acetylene halide is (bromoacetylenyl)benzene.

[0015] Furthermore, the palladium salt catalyst is one or more of tetra(triphenylphosphine)palladium, palladium chloride, and palladium acetate.

[0016] Furthermore, the molar ratio of the palladium salt catalyst to the N-trifluoroacetanilide compound is 0.05 to 0.1:1.

[0017] Furthermore, the molar ratio of the added acetylene halide to the N-trifluoroacetanilide compound is 1.5 to 3.0:1.

[0018] Further, the base is one or more of cesium carbonate, potassium carbonate, and 1,8-diazabicyclo[5.4.0]undec-7-ene.

[0019] Furthermore, the molar ratio of the added alkali to the N-trifluoroacetanilide compound is 1.0 to 3.0:1.

[0020] Furthermore, the additive is one or more of sodium chloride, potassium bromide, and lithium bromide.

[0021] Furthermore, the molar ratio of the additive to the N-trifluoroacetanilide compound is 0.5 to 2.0:1.

[0022] Further, the solvent is one of dichloroethane, dimethyl sulfoxide, 1,4-hexacyclohexane, toluene, or a mixture of water and toluene in a volume ratio of 1:100.

[0023] Furthermore, the stirring reaction time is 4 to 16 hours, preferably 8 to 12 hours.

[0024] Further, the separation and purification operation is as follows: the reaction solution is extracted with ethyl acetate, the organic phases are combined, dried with anhydrous magnesium sulfate, filtered, and the organic solvent is removed by vacuum distillation to obtain the crude product, which is then purified by column chromatography to obtain the 2,5-diaminopyrrole compound.

[0025] Furthermore, the eluent for the column chromatography is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 20 to 150:1, preferably a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of 50 to 100:1.

[0026] The reaction principle of the synthesis method of this invention is that, under the promotion of a base, N-trifluoroacetanilide, an alkyne halide and a molecule of isonitrile undergo an addition reaction to generate an alkenyl halide intermediate. Subsequently, a palladium salt catalyst reacts with this intermediate to undergo oxidative addition. After the isonitrile migrates and inserts, intramolecular cyclization, reductive elimination and isomerization are performed to obtain 2,5-diaminopyrrole compounds.

[0027] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0028] (1) This invention develops a method for synthesizing 2,5-diaminopyrrole compounds by the tandem cyclization reaction of N-trifluoroacetanilide, alkyne halide and isonitrile under palladium catalysis. The basic raw material N-trifluoroacetanilide can be synthesized from inexpensive aniline and trifluoroacetic anhydride, and the alkyne halide can be obtained in one step from phenylacetylene and N-halosuccinimide. It has the characteristics of simple and readily available raw materials, safe and simple operation, mild conditions, high atom economy and wide substrate applicability.

[0029] (2) The synthesis method of the present invention is convenient to operate and has high conversion efficiency. It also has good tolerance to functional groups, and therefore is expected to be applied to actual industrial production and further derivatization. Attached Figure Description

[0030] Figure 1 and Figure 2 These are the proton and carbon spectra of the target product obtained in Example 1, respectively.

[0031] Figure 3 and Figure 4 These are the proton and carbon spectra of the target product obtained in Example 2, respectively.

[0032] Figure 5 and Figure 6 These are the proton and carbon spectra of the target product obtained in Example 3, respectively.

[0033] Figure 7 and Figure 8 These are the proton and carbon spectra of the target product obtained in Example 4, respectively.

[0034] Figure 9 and Figure 10 These are the proton and carbon spectra of the target product obtained in Example 5, respectively.

[0035] Figure 11 and Figure 12 These are the proton and carbon spectra of the target product obtained in Example 6, respectively.

[0036] Figure 13 and Figure 14 These are the proton and carbon spectra of the target product obtained in Example 7, respectively.

[0037] Figure 15 and Figure 16 These are the proton and carbon spectra of the target product obtained in Example 8, respectively.

[0038] Figure 17 and Figure 18 These are the proton and carbon spectra of the target product obtained in Example 9, respectively.

[0039] Figure 19 and Figure 20 These are the proton and carbon spectra of the target product obtained in Example 10, respectively.

[0040] Figure 21 and Figure 22 These are the proton and carbon spectra of the target product obtained in Example 11, respectively.

[0041] Figure 23 and Figure 24 These are the hydrogen spectrum and carbon spectrum of the target product obtained in Example 12, respectively. Detailed Implementation

[0042] The technical solution of the present invention will be further described in detail below with reference to specific embodiments and accompanying drawings, but the scope of protection and implementation of the present invention are not limited thereto.

[0043] Example 1

[0044] In a reaction tube, 0.1 mmol N-trifluoroacetanilide, 0.01 mmol tetra(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, 0.1 mmol lithium bromide, 0.2 mmol (bromoacetylene)benzene, 0.3 mmol tert-butylisocyanate, 1.0 mL toluene, and 0.7 mmol water were added as solvents. The mixture was stirred at 60 °C and 500 rpm for 12 hours. After stirring was stopped, 5 mL of water was added, and the mixture was extracted three times with ethyl acetate. The organic phases were combined and dried over 0.5 g anhydrous magnesium sulfate. The mixture was filtered, concentrated under reduced pressure, and then purified by column chromatography using a 50:1 (v / v) mixture of petroleum ether and ethyl acetate as the eluent. The target product was obtained in 92% yield.

[0045] The proton and carbon spectra of the obtained target product are as follows: Figure 1 and Figure 2 As shown, the structural characterization data is as follows:

[0046] 1 H NMR(400MHz, CDCl3) δ7.66(d,J=6.8Hz,2H),7.51(t,J=7.6Hz,2H),7.44-7.36( m,3H),7.31-7.21(m,3H),6.32(s,1H),2.93(s,1H),1.05(s,9H),0.67(s,9H);

[0047] 13 C NMR (100MHz, CDCl3) δ158.2 (q, J = 32.7Hz), 137.2, 136.7, 130.9, 129.1, 128.5, 128.3, 1 28.0,127.5,125.6,122.6,118.0,116.5(q,J=288.4Hz),109.1,63.2,55.5,29.9,26.9.

[0048] IR(KBr)ν max 3388,2972,1703,1598,1527,1497,1371,1195,1154,755,701cm -1 ;

[0049] HRMS(ESI)Calcd for C 25 H 33 N₂Si[M+H] + :458.2414,Found458.2407.

[0050] Based on the above data, the structure of the target product is inferred as follows:

[0051]

[0052] Example 2

[0053] In a reaction tube, 0.1 mmol N-(3-fluorophenyl)-2,2,2-trifluoroacetamide, 0.01 mmol tetra(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, 0.1 mmol lithium bromide, 0.2 mmol (bromoacetylene)benzene, 0.3 mmol tert-butylisocyanate, 1.0 mL toluene, and 0.7 mmol water were added as solvents. The mixture was stirred at 60 °C and 500 rpm for 12 hours. After stirring was stopped, 5 mL of water was added, and the mixture was extracted three times with ethyl acetate. The organic phases were combined and dried over 0.5 g anhydrous magnesium sulfate. The mixture was filtered, concentrated under reduced pressure, and then purified by column chromatography using a 50:1 (v / v) mixture of petroleum ether and ethyl acetate as the eluent. The target product was obtained in 90% yield.

[0054] The proton and carbon spectra of the obtained target product are as follows: Figure 3 and Figure 4 As shown, the structural characterization data is as follows:

[0055] 1 H NMR(400MHz, CDCl3) δ7.54(d,J=6.8Hz,2H),7.47-7.40(m,1H),7.37(t,J=7.6Hz,2H),7.2 3(t,J=7.6Hz,1H),7.12-7.02(m,3H),6.28(s,1H),2.74(s,1H),1.05(s,9H),0.64(s,9H);

[0056] 13C NMR (100MHz, CDCl3) δ162.7 (d, J = 246.2Hz), 158.2 (q, J = 32.9Hz), 138.8 (d, J = 9.7Hz), 136.4, 131.0, 130.1 (d, J = 9.0Hz), 128.4 ,128.1,125.9,124.2,122.6,118.6,117.9(q,J=288.2Hz),116.3(d,J=23.4Hz),114.4,114.6,109.7,63.4,55.6,29.9,27.0.

[0057] IR(KBr)ν max 3739,2969,1701,1631,1599,1524,1491,1393,1161,861,760,694cm -1 ;

[0058] HRMS(ESI)Calcd for C 26 H 35 N₂Si[M+H] + :466.3040,Found466.3034.

[0059] Based on the above data, the structure of the target product is inferred as follows:

[0060]

[0061] Example 3

[0062] In a reaction tube, 0.1 mmol N-(3-chlorophenyl)-2,2,2-trifluoroacetamide, 0.01 mmol tetra(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, 0.1 mmol lithium bromide, 0.2 mmol (bromoacetylene)benzene, 0.3 mmol tert-butylisocyanate, 1.0 mL toluene, and 0.7 mmol water were added as solvents. The mixture was stirred at 60 °C and 500 rpm for 12 hours. After stirring was stopped, 5 mL of water was added, and the mixture was extracted three times with ethyl acetate. The organic phases were combined and dried over 0.5 g anhydrous magnesium sulfate. The mixture was filtered, concentrated under reduced pressure, and then purified by column chromatography using a 50:1 (v / v) mixture of petroleum ether and ethyl acetate as the eluent. The target product was obtained in 78% yield.

[0063] The proton and carbon spectra of the obtained target product are as follows: Figure 5 and Figure 6 As shown, the structural characterization data is as follows:

[0064] 1H NMR(400MHz, CDCl3)δ7.52(d,J=6.8Hz,2H),7.43-7.32(m,5H),7.25-7.20(m,1H) ,7.15(dt,J=7.8,2.0Hz,1H),6.28(s,1H),2.81(s,1H),1.05(s,9H),0.64(s,9H);

[0065] 13 C NMR (100MHz, CDCl3) δ158.23 (q, J = 32.8Hz), 138.6, 136.3, 134.4, 131.1, 129.9, 129.0, 1208.4, 128.1,127.5,126.5,126.0,122.6,118.7,117.9(q,J=288.2Hz),109.8,63.4,55.6,29.9,27.0.

[0066] IR(KBr)ν max 2972,1703,1592,1526,1481,1367,1267,1197,1158,760,699cm -1 ;

[0067] HRMS(ESI)Calcd for C 26 H 35 N₂Si[M+H] + :492.2024,Found492.2016.

[0068] Based on the above data, the structure of the target product is inferred as follows:

[0069]

[0070] Example 4

[0071] In a reaction tube, 0.1 mmol of N-(3-methylphenyl)-2,2,2-trifluoroacetamide, 0.01 mmol of tetra(triphenylphosphine)palladium, 0.2 mmol of cesium carbonate, 0.1 mmol of lithium bromide, 0.2 mmol of (bromoacetylene)benzene, 0.3 mmol of tert-butylisocyanate, 1.0 mL of toluene, and 0.7 mmol of water were added as solvents. The mixture was stirred at 60 °C and 500 rpm for 12 hours. After stirring was stopped, 5 mL of water was added, and the mixture was extracted three times with ethyl acetate. The organic phases were combined and dried over 0.5 g of anhydrous magnesium sulfate. The mixture was filtered, concentrated under reduced pressure, and then purified by column chromatography using a 50:1 (v / v) mixture of petroleum ether and ethyl acetate as the eluent. The target product was obtained in 94% yield.

[0072] The proton and carbon spectra of the obtained target product are as follows: Figure 7 and Figure 8 As shown, the structural characterization data is as follows:

[0073] 1 H NMR (400MHz, CDCl3) δ7.63 (d, J=6.8Hz, 2H), 7.35 (td, J=7.6, 2.0Hz, 3H), 7.22-7.16 (m, 2H ),7.03(d,J=8.4Hz,2H),6.27(s,1H),2.75(s,1H),2.41(s,3H),1.01(s,9H),0.65(s,9H);

[0074] 13 C NMR (100MHz, CDCl3) δ158.3 (q, J = 32.9Hz), 139.2, 137.1, 136.8, 130.8, 129.0, 128.3, 12 8.0,125.6,125.5,122.7,117.9(q,J=288.1Hz),117.8,109.0,63.2,29.9,26.9,21.4.;

[0075] IR(KBr)ν max 2969,1702,1599,1526,1490,1368,1192,1154,760,699cm -1 ;

[0076] HRMS(ESI)Calcd for C 25 H 32 FN2Si[M+H] + :472.2570,Found472.2564.

[0077] Based on the above data, the structure of the target product is inferred as follows:

[0078]

[0079] Example 5

[0080] In a reaction tube, 0.1 mmol N-(3-cyanophenyl)-2,2,2-trifluoroacetamide, 0.01 mmol tetra(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, 0.1 mmol lithium bromide, 0.2 mmol (bromoacetylene)benzene, 0.3 mmol tert-butylisocyanate, 1.0 mL toluene, and 0.7 mmol water were added as solvents. The mixture was stirred at 60 °C and 500 rpm for 12 hours. After stirring was stopped, 5 mL of water was added, and the mixture was extracted three times with ethyl acetate. The organic phases were combined and dried over 0.5 g anhydrous magnesium sulfate. The mixture was filtered, concentrated under reduced pressure, and then purified by column chromatography using a 50:1 (v / v) mixture of petroleum ether and ethyl acetate as the eluent. The target product was obtained in 86% yield.

[0081] The proton and carbon spectra of the obtained target product are as follows: Figure 9 and Figure 10 As shown, the structural characterization data is as follows:

[0082] 1 H NMR (400MHz, CDCl3) δ7.70-7.63(m,2H),7.59(t,J=8.0Hz,1H),7.50(d,J=8.0Hz,1H),7. 47-7.37(m,4H),7.29-7.24(m,1H),6.31(s,1H),2.95(s,1H),1.04(s,9H),0.60(s,9H);

[0083] 13 C NMR (100MHz, CDCl3) δ158.2 (q, J = 33.2Hz), 138.5, 135.9, 132.7 (d, J = 15.2Hz), 131.1, 130.6, 129.8, 12 8.6,128.1,126.3,122.4,119.4,117.9,116.3(q,J=288.5Hz),113.0,110.4,63.6,55.8,29.8,27.0.;

[0084] IR(KBr)ν max 3387,2972,2233,1704,1592,1526,1485,1370,1197,1166,762,699cm -1 ;

[0085] HRMS(ESI)Calcd for C 25 H 32 ClN2Si[M+H] + ,483.2366,found483.2361.

[0086] Based on the above data, the structure of the target product is inferred as follows:

[0087]

[0088] Example 6

[0089] In a reaction tube, 0.1 mmol N-(4-enylphenyl)-2,2,2-trifluoroacetamide, 0.01 mmol tetra(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, 0.1 mmol lithium bromide, 0.2 mmol (bromoacetylene)benzene, 0.3 mmol tert-butylisocyanate, 1.0 mL toluene, and 0.7 mmol water were added as solvents. The mixture was stirred at 60 °C and 500 rpm for 12 hours. After stirring was stopped, 5 mL of water was added, and the mixture was extracted three times with ethyl acetate. The organic phases were combined and dried over 0.5 g anhydrous magnesium sulfate. The mixture was filtered, concentrated under reduced pressure, and then purified by column chromatography using a 50:1 (v / v) mixture of petroleum ether and ethyl acetate as the eluent. The target product was obtained in 89% yield.

[0090] The proton and carbon spectra of the obtained target product are as follows: Figure 11 and Figure 12 As shown, the structural characterization data is as follows:

[0091] 1 H NMR(400MHz, CDCl3)δ7.61(d,J=7.2Hz,2H),7.35(t,J=7.6Hz,2H),7.22-7.12(m,3H),6 .99(d,J=8.8Hz,2H),6.26(s,1H),3.85(s,3H),2.65(s,1H),1.03(s,9H),0.65(s,9H);

[0092] 13 C NMR (100MHz, CDCl3) δ158.4 (q, J=32.8Hz), 136.8, 130.9, 129.9, 128.2, 128.0, 125. 6,122.7,117.6,116.5(q,J=288.1Hz),114.3,108.8,63.1,55.5,55.5,29.9,27.0;

[0093] IR(KBr)ν max 3739,3615,3365,2922,1700,1634,1516,1465,1393,1250,1188,1032,838,759,700cm -1 ;

[0094] HRMS(ESI)Calcd for C 25H 32 ClN2Si[M+H] + :488.2519,Found488.2512.

[0095] Based on the above data, the structure of the target product is inferred as follows:

[0096]

[0097] Example 7

[0098] In a reaction tube, 0.1 mmol N-(4-nitrophenyl)-2,2,2-trifluoroacetamide, 0.01 mmol tetra(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, 0.1 mmol lithium bromide, 0.2 mmol (bromoacetylene)benzene, 0.3 mmol tert-butylisocyanate, 1.0 mL toluene, and 0.7 mmol water were added as solvents. The mixture was stirred at 60 °C and 500 rpm for 12 hours. After stirring was stopped, 5 mL of water was added, and the mixture was extracted three times with ethyl acetate. The organic phases were combined and dried over 0.5 g anhydrous magnesium sulfate. The mixture was filtered, concentrated under reduced pressure, and then purified by column chromatography using a 50:1 (v / v) mixture of petroleum ether and ethyl acetate as the eluent. The target product was obtained in 90% yield.

[0099] The proton and carbon spectra of the obtained target product are as follows: Figure 13 and Figure 14 As shown, the structural characterization data is as follows:

[0100] 1 H NMR (400MHz, CDCl3) δ7.60(d,J=7.2Hz,2H),7.51(d,J=8.4Hz,2H),7.36(t,J=7.6Hz,2H),7.24-7.17(m,3H),6.75(dd,J =17.6,10.8Hz,1H),6.28(s,1H),5.82(d,J=17.6Hz,1H),5.34(d,J=10.8Hz,1H),2.81(s,1H),1.03(s,9H),0.64(s,9H);

[0101] 13 C NMR (100MHz, CDCl3) δ158.3 (q, J = 32.8Hz), 136.7, 136.6, 136.6, 135.7, 130.8, 128.6, 128.3, 1 28.0,126.8,125.7,122.7,118.2,116.5(q,J=288.2Hz),115.0,109.3,63.3,55.7,29.9,27.0;

[0102] IR(KBr)ν max 3411,2970,1702,1519,1370,1193,1154,912,848,759,701cm -1 ;

[0103] HRMS(ESI)Calcd for C 26 H 35 N₂Si[M+H] + :484.2570,Found484.2565.

[0104] Based on the above data, the structure of the target product is inferred as follows:

[0105]

[0106] Example 8

[0107] In a reaction tube, 0.1 mmol N-trifluoroacetanilide, 0.01 mmol tetra(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, 0.1 mmol lithium bromide, 0.2 mmol 1-(bromoynyl)-4-bromobenzene, 0.3 mmol tert-butylisocyanate, 1.0 mL toluene, and 0.7 mmol water were added as solvents. The mixture was stirred at 60 °C and 500 rpm for 12 hours. After stirring was stopped, 5 mL of water was added, and the mixture was extracted three times with ethyl acetate. The organic phases were combined and dried over 0.5 g anhydrous magnesium sulfate. The mixture was filtered, concentrated under reduced pressure, and then purified by column chromatography using a 50:1 (v / v) mixture of petroleum ether and ethyl acetate as the eluent. The target product was obtained in 92% yield.

[0108] The proton and carbon spectra of the obtained target product are as follows: Figure 15 and Figure 16 As shown, the structural characterization data is as follows:

[0109] 1 H NMR(400MHz, CDCl3)δ7.57(d,J=8.4Hz,2H),7.52-7.43(m,4H),7.38(t,J=7.6Hz ,1H),7.22(d,J=7.2Hz,2H),6.27(s,1H),3.00(s,1H),1.01(s,9H),0.65(s,9H);

[0110] 13C NMR (100MHz, CDCl3) δ158.1 (q, J = 32.8Hz), 136.9, 135.6, 131.2, 130.8, 129.5, 129.3, 1 28.4,127.8,123.0,119.2,116.8,116.4(q,J=288.2Hz),108.6,63.1,55.6,29.9,26.9;

[0111] IR(KBr)ν max 2970,1703,1595,1525,1491,1370,1195,1152,761,705cm -1 ;

[0112] HRMS(ESI)Calcd for C 26 H 32 N3Si[M+H] + :536.1519,Found 536.1511.

[0113] Based on the above data, the structure of the target product is inferred as follows:

[0114]

[0115] Example 9

[0116] In a reaction tube, 0.1 mmol N-trifluoroacetanilide, 0.01 mmol tetra(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, 0.1 mmol lithium bromide, 0.2 mmol 1-(bromoynyl)-4-bromobenzene, 0.3 mmol tert-butylisocyanate, 1.0 mL toluene, and 0.7 mmol water were added as solvents. The mixture was stirred at 60 °C and 500 rpm for 12 hours. After stirring was stopped, 5 mL of water was added, and the mixture was extracted three times with ethyl acetate. The organic phases were combined and dried over 0.5 g anhydrous magnesium sulfate. The mixture was filtered, concentrated under reduced pressure, and then purified by column chromatography using a 50:1 (v / v) mixture of petroleum ether and ethyl acetate as the eluent. The target product was obtained in 79% yield.

[0117] The proton and carbon spectra of the obtained target product are as follows: Figure 17 and Figure 18 As shown, the structural characterization data is as follows:

[0118] 1H NMR (400MHz, CDCl3) δ7.51-7.44(m,4H),7.36(t,J=7.6Hz,1H),7.23(d,J=7.2Hz,2H),7 .17(d,J=8.0Hz,2H),6.25(s,1H),2.60(s,1H),2.36(s,3H),1.00(s,9H),0.63(s,9H);

[0119] 13 C NMR (100MHz, CDCl3) δ158.3 (q, J=32.9Hz), 137.3, 135.2, 133.7, 130.7, 129.1, 129.0, 128. 6,127.8,127.4,122.5,117.9,116.5(q,J=288.1Hz),109.1,63.2,55.5,29.9,26.9,21.1;

[0120] IR(KBr)ν max 3465,2968,2923,1702,1530,1374,1191,1156,756,706cm -1 ;

[0121] HRMS(ESI)Calcd for C 25 H 32 FN2Si[M+H] + :536.1519,Found536.1511.

[0122] Based on the above data, the structure of the target product is inferred as follows:

[0123]

[0124] Example 10

[0125] In a reaction tube, 0.1 mmol N-trifluoroacetanilide, 0.01 mmol tetra(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, 0.1 mmol lithium bromide, 0.2 mmol methyl 4-(bromoynyl)benzoate, 0.3 mmol tert-butylisocyanate, 1.0 mL toluene, and 0.7 mmol water were added as solvents. The mixture was stirred at 60 °C and 500 rpm for 12 hours. After stirring was stopped, 5 mL of water was added, and the mixture was extracted three times with ethyl acetate. The organic phases were combined and dried over 0.5 g anhydrous magnesium sulfate. The mixture was filtered, concentrated under reduced pressure, and then purified by column chromatography using a 50:1 (v / v) mixture of petroleum ether and ethyl acetate as the eluent. The target product was obtained in 87% yield.

[0126] The proton and carbon spectra of the obtained target product are as follows: Figure 19 and Figure 20 As shown, the structural characterization data is as follows:

[0127] 1 H NMR (400MHz, CDCl3) δ8.03(d,J=8.0Hz,2H),7.77(d,J=8.4Hz,2H),7.51(t,J=7.6Hz,2H),7.44-7. 38(m,1H),7.23(d,J=7.2Hz,2H),6.34(s,1H),3.93(s,3H),2.66(s,1H),1.01(s,9H),0.65(s,9H);

[0128] 13 C NMR(100MHz, CDCl3)δ167.2,158.2(q,J=32.9Hz),141.6,136.8,131.5,129.6,129.4,128.4,1 28.0,127.5,127.0,123.4,117.0,116.4(q,J=288.2Hz),108.8,63.2,56.0,51.9,29.9,26.9;

[0129] IR(KBr)ν max 3467,3419,2919,1705,1635,1530,1273,1190,1109,756cm -1 ;

[0130] HRMS(ESI)Calcd for C 25 H 32 ClN2Si[M+H] + ,516.2469,Found 516.2462.

[0131] Based on the above data, the structure of the target product is inferred as follows:

[0132]

[0133] Example 11

[0134] In a reaction tube, 0.1 mmol N-trifluoroacetanilide, 0.01 mmol tetra(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, 0.1 mmol lithium bromide, 0.2 mmol 1-(bromoynyl)-4-bromobenzene, 0.3 mmol tert-butylisocyanate, 1.0 mL toluene, and 0.7 mmol water were added as solvents. The mixture was stirred at 60 °C and 500 rpm for 12 hours. After stirring was stopped, 5 mL of water was added, and the mixture was extracted three times with ethyl acetate. The organic phases were combined and dried over 0.5 g anhydrous magnesium sulfate. The mixture was filtered, concentrated under reduced pressure, and then purified by column chromatography using a 50:1 (v / v) mixture of petroleum ether and ethyl acetate as the eluent. The target product was obtained in 78% yield.

[0135] The proton and carbon spectra of the obtained target product are as follows: Figure 21 and Figure 22 As shown, the structural characterization data is as follows:

[0136] 1 H NMR (400MHz, CDCl3) δ7.76-7.70(m,1H),7.56-7.47(m,3H),7.40(t,J=7.6Hz,1H),7.31-7.26(m,1 H),7.22(d,J=7.2Hz,2H),7.19-7.14(m,1H),6.28(s,1H),2.62(s,1H),1.00(s,9H),0.66(s,9H);

[0137] 13 C NMR (100MHz, CDCl3) δ158.2 (q, J=32.8Hz), 138.5, 136.9, 134.1, 131.1, 129.5, 129.4, 128. 5,127.9,125.9,125.6,123.1,116.7,116.4(q,J=288.5Hz),108.7,63.2,55.7,30.0,27.0;

[0138] IR(KBr)ν max 3496,2968,1702,1594,1525,1370,1194,1152,760,702cm -1 ;

[0139] HRMS(ESI)Calcd for C 25 H 31 Cl2N2Si[M+H] + ,492.2024,Found492.2018.

[0140] Based on the above data, the structure of the target product is inferred as follows:

[0141]

[0142] Example 12

[0143] In a reaction tube, 0.1 mmol N-trifluoroacetanilide, 0.01 mmol tetra(triphenylphosphine)palladium, 0.2 mmol cesium carbonate, 0.1 mmol lithium bromide, 0.2 mmol (bromoacetylene)benzene, 0.3 mmol 1,1,3,3-tetramethylbutylisocyanate, 1.0 mL toluene, and 0.7 mmol water were added as solvents. The mixture was stirred at 60 °C and 500 rpm for 12 hours. After stirring was stopped, 5 mL of water was added, and the mixture was extracted three times with ethyl acetate. The organic phases were combined and dried over 0.5 g anhydrous magnesium sulfate. The mixture was filtered, concentrated under reduced pressure, and then purified by column chromatography using a 50:1 (v / v) mixture of petroleum ether and ethyl acetate as the eluent. The target product was obtained in 84% yield.

[0144] The proton and carbon spectra of the obtained target product are as follows: Figure 23 and Figure 24 As shown, the structural characterization data is as follows:

[0145] 1 H NMR (400MHz, CDCl3) δ7.60-7.56(m,2H),7.48(t,J=7.6Hz,2H),7.40-7.34(m,3H),7.26-7.19(m,3H),6.31(s,1H),3.01(s,1H),2.0 7(d,J=14.8Hz,1H),1.15(s,3H),1.10(s,1H),1.08-0.96(m,2H),0.85(s,3H),0.83(s,9H),0.80(s,9H),0.64(s,3H),0.55(s,3H);

[0146] 13 C NMR (100MHz, CDCl3) δ158.1 (q, J=32.5Hz), 137.5, 137.0, 130.8, 129.2, 128.3, 127.7, 125.7, 122.5, 118. 3,116.5(q,J=288.9Hz),109.7,68.2,59.8,56.5,49.4,31.6,31.4,31.3,29.4,28.5,26.8(d,J=28.5Hz);

[0147] IR(KBr)ν max 2955,1703,1598,1492,1372,1194,1152,756,700cm -1;

[0148] HRMS(ESI)Calcd for C 26 H 35 N₂Si[M+H] + ,570.3666,found 570.3657.

[0149] Based on the above data, the structure of the target product is inferred as follows:

[0150]

[0151] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A method for synthesizing a 2,5-diaminopyrrole compound, characterized in that, It includes the following steps: Add the substrate to the reactor. N - Trifluoroacetanilide compounds, acetylide halides, isonitriles, palladium salt catalysts, bases, additives, water, and solvents were reacted with stirring at 50-90 °C. After the reaction was completed, the mixture was cooled to room temperature, and the product was separated and purified to obtain the 2,5-diaminopyrrole compounds. The chemical reaction equations for the synthesis process are shown below: In the formula, R 1 It is selected from one of hydrogen, 3-fluorine, 3-chloro, 3-methyl, 3-cyano, 4-methoxy, and 4-alkenyl; R 2 It can be hydrogen, 4-bromo, 4-methyl, 4-carboxylic acid methyl ester, or 3-chloro; R 3 It is tert-butyl or 1,1,3,3-tetramethylbutyl; The palladium salt catalyst is tetrakis(triphenylphosphine)palladium; the base is cesium carbonate; and the additive is lithium bromide.

2. The method for synthesizing a 2,5-diaminopyrrole compound according to claim 1, characterized in that, The N - Trifluoroacetanilide compounds are N - Trifluoroacetanilide; the acetylene halide is (bromoacetylene)benzene.

3. The method for synthesizing a 2,5-diaminopyrrole compound according to claim 1 or 2, characterized in that, The amount of palladium salt catalyst added is related to N - The molar ratio of trifluoroacetanilide compounds is 0.05~0.1:

1.

4. The method for synthesizing a 2,5-diaminopyrrole compound according to claim 1 or 2, characterized in that, The amount of the acetylene halide added is related to N - The molar ratio of trifluoroacetanilide compounds is 1.5~3.0:

1.

5. The method for synthesizing a 2,5-diaminopyrrole compound according to claim 1 or 2, characterized in that, The amount of isonitrile added is related to N - The molar ratio of trifluoroacetanilide compounds is 2.0~3.5:

1.

6. The method for synthesizing a 2,5-diaminopyrrole compound according to claim 1 or 2, characterized in that, The amount of alkali added is related to N - The molar ratio of trifluoroacetanilide compounds is 1.0~3.0:

1.

7. The method for synthesizing a 2,5-diaminopyrrole compound according to claim 1 or 2, characterized in that, The amount of the additive added is related to N - The molar ratio of trifluoroacetanilide compounds is 0.5~2.0:1; The solvent is dichloroethane, dimethyl sulfoxide, 1,4-hexacyclohexane, toluene, or a mixture of water and toluene in a volume ratio of 1:

100.

8. The method for synthesizing a 2,5-diaminopyrrole compound according to claim 1 or 2, characterized in that, The stirring reaction takes 4 to 16 hours.

9. The method for synthesizing a 2,5-diaminopyrrole compound according to claim 1 or 2, characterized in that, The separation and purification process is as follows: the reaction solution is extracted with ethyl acetate, the organic phases are combined, dried with anhydrous magnesium sulfate, filtered, and the organic solvent is removed by vacuum distillation to obtain the crude product, which is then purified by column chromatography to obtain the 2,5-diaminopyrrole compounds.

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