Pyridyne-phenylyne bis-aryne precursors, methods of synthesis and use thereof

Abstract

The application discloses a pyridine-yne-benzene-yne diaromatic yne precursor, which is the first aromatic yne precursor capable of continuously generating pyridine-yne-benzene-yne. The diaromatic yne precursor can be compatible with multiple substituted alkyl, aryl, silicon, alkoxy, halogen and other functional groups. The diaromatic yne precursor can have a high-selectivity nucleophilic reaction with oxygen, nitrogen, sulfur and other nucleophilic reagents to quickly construct carbon-heteroatom bonds, and can have a [4+2] cycloaddition reaction with diene to quickly construct double carbon-carbon bonds, so that the diaromatic yne precursor can be used for efficiently and quickly preparing multiple substituted pyridine, benzene ring and other derivatives, and has a wide application prospect.

Description

Technical Field

[0001] This invention belongs to the field of organic compound process application technology, and relates to a novel method for in-situ release of pyridyne-benzyne active intermediates. Background Technology

[0002] Aromatic alkynes, as a class of highly reactive intermediates, have been extensively and deeply studied from a methodological perspective. The design, synthesis, and application of aromatic alkyne precursors have gradually been incorporated into synthesis over several decades. High-iodine salts, as a novel type of pyridyne precursor, offer excellent procedural economy in their preparation. However, the conditions required for the production of pyridyne from high-iodine salts are still quite demanding, making the development of a more moderate method essential.

[0003] Building upon the use of high-iodine salts as pyridyne precursors, further modifications and designs are needed to enhance the atom utilization of high-iodine salts and improve the efficiency and complexity of molecular library construction. While no prior reports have described high-iodine salts as pyridyne-benzyne biaromatic precursors, they can significantly improve the atom economy of aromatic rings, enabling the rapid construction of complex and practical polyaromatic compounds with potential value in organic optoelectronic materials. Furthermore, the novel reaction mechanisms resulting from this aromatic precursor design will contribute to fundamental research in organic chemistry, expanding the types of reactions involving pyridyne or benzyne, enriching their chemical research, and providing a feasible approach to addressing selectivity issues in pyridyne or benzyne reactions, thereby improving the selectivity of pyridyne and benzyne reactions. Summary of the Invention

[0004] To address the shortcomings of existing technologies, the present invention aims to provide a class of pyridyne-benzyne biaromatic propionates that can release pyridyne-benzyne active intermediates in situ twice consecutively.

[0005] This invention, through screening of the functional groups of diaryl cyclic high-iodine salts, can very mildly achieve the release of two consecutive active aromatic yne intermediates under the action of certain bases and solvents, rapidly realize the reaction involving diaryl yne, quickly construct carbon-carbon, carbon-oxygen, carbon-nitrogen and carbon-sulfur bonds, and efficiently obtain pyridine derivatives.

[0006] This invention provides a class of pyridine-benzyne diaromatic precursors, also known as diarylcyclic pyridine periodic salts, with the following structural formula:

[0007]

[0008] In Equation 1, a and b represent only selectivity and can be omitted, so Equation 1 can be:

[0009] Among them, R 1R 2 R 3 R 4 R 5 Each of the following is independently selected from one or more of hydrogen, alkyl, alkoxy, trifluoromethyl, trifluoromethoxy, aryl, silyl, and halogen.

[0010] Preferably,

[0011] R 1 It includes hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, methoxy, trifluoromethyl, trifluoromethoxy, phenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-aldehydephenyl, 4-formylphenyl, other phenyl compounds, as well as thiophene, thiazole, benzothiophene, benzothiazole, benzoisothiazole, dibenzothiophene, phenoxthiazide, thianthracene, alkoxy, dimethylamino, and halogens.

[0012] R 2 It includes hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, methoxy, trifluoromethyl, trifluoromethoxy, phenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-aldehydephenyl, 4-formylphenyl, other phenyl compounds, as well as thiophene, thiazole, benzothiophene, benzothiazole, benzoisothiazole, dibenzothiophene, phenoxthiazide, thianthracene, alkoxy, dimethylamino, and halogens.

[0013] R 3 It includes hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, methoxy, trifluoromethyl, trifluoromethoxy, phenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-aldehydephenyl, 4-formylphenyl, other phenyl compounds, as well as thiophene, thiazole, benzothiophene, benzothiazole, benzoisothiazole, dibenzothiophene, phenoxthiazide, thianthracene, alkoxy, dimethylamino, and halogens.

[0014] R 4 It includes hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, methoxy, trifluoromethyl, trifluoromethoxy, phenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-aldehydephenyl, 4-formylphenyl, other phenyl compounds, as well as thiophene, thiazole, benzothiophene, benzothiazole, benzoisothiazole, dibenzothiophene, phenoxthiazide, thianthracene, alkoxy, dimethylamino, and halogens.

[0015] R 5 It includes hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, methoxy, trifluoromethyl, trifluoromethoxy, phenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-aldehydephenyl, 4-formylphenyl, other phenyl compounds, as well as thiophene, thiazole, benzothiophene, benzothiazole, benzoisothiazole, dibenzothiophene, phenoxthiazide, thianthracene, alkoxy, dimethylamino, and halogens.

[0016] The diaryl cyclic pyridine high-iodine salt includes, but is not limited to, the following components:

[0017]

[0018] This invention also provides a method for preparing a pyridyne-benzyne diaromaticyne precursor, the method comprising the following steps:

[0019] Step (1): Using substituted 2-halo-3-aminopyridine as a raw material, under the conditions of Pd catalyst, solvent, base and ligand, it undergoes Suzuki coupling reaction with polysubstituted arylboronic acid to obtain intermediate 1;

[0020] Step (2): The intermediate 1 obtained in step (1) is subjected to diazotization in the presence of acid, additives and solvent to replace the amino group with iodine to obtain intermediate 2;

[0021] Step (3): The intermediate 2 obtained in step (2) is oxidized in the presence of acid, oxidant, and solvent to obtain diarylpyridine periodic salt; the reaction equation is shown in equation A below:

[0022]

[0023] In equation A, R includes R 4 R 5 R' contains R 1 R 2 R 3 X is a halogen;

[0024] In step (1), the Pd catalyst is one or more of Pd(OAc)2, Pd(dba)2, Pd2(dba)3, Pd(Ph3P)4, PdCl2, Pd(MeCN)2Cl2, etc.; preferably, it is Pd(dba)2.

[0025] In step (1), the ligand is one or more of Dave-Phos, X-Phos, S-Phos, Ph3P, (Ph2P)2(CH2)2, (Ph2P)2(CH2)3, (Ph2P)2(CH2)4, tBu-Phos, etc.; preferably, it is X-Phos.

[0026] In step (1), the solvent is one or more of PhMe, MeOH, EtOH, H2O, THF, dioxane, EtOAc, MeCN, DCM, DMF, etc.; preferably, it is a mixed solvent of PhMe, EtOH and H2O, with an optimal volume ratio of 5 / 1 / 5.

[0027] In step (1), the alkali is one or more of Na2CO3, K2CO3, NaOH, KOH, tBuOLi, tBuONa, tBuOK, LiHMDS, LDA, etc.; preferably, it is Na2CO3.

[0028] In step (1), the molar ratio of the substituted 2-halo-3-aminopyridine, base, Pd catalyst, and ligand is 1:1-10:0.01-1:0.01-1; preferably, it is 1:5:0.02:0.04.

[0029] In step (1), the reaction temperature is room temperature - 120°C; preferably, it is 80-90°C.

[0030] In step (1), the reaction time is 1-24 hours; preferably, it is 12 hours.

[0031] In step (2), the acid is one or more of H2SO4, HCl, TFA, TfOH, TsOH, HBF4, etc.; preferably, it is TfOH.

[0032] In step (2), the additive is one or more of NaNO2, KNO2, tBuONO, etc.; preferably, it is tBuONO.

[0033] In step (2), the solvent is one or more of PhMe, MeOH, EtOH, H2O, THF, dioxane, EtOAc, MeCN, DCM, DMF, etc.; preferably, it is MeCN;

[0034] In step (2), the iodine source used is one or more of NaI, I2, KI, TBAI, etc.; preferably, it is TBAI.

[0035] In step (2), the molar ratio of intermediate 1, acid, additive, and iodine source is 1:1-10:0.5-2:0.5-2; preferably, it is 1:4:1.3:1.3.

[0036] In step (2), the reaction temperature is -80–100℃; preferably, it is -40℃.

[0037] In step (2), the reaction time is 1-24 hours; preferably, it is 12 hours.

[0038] In step (3), the oxidant is one or more of H2O2, m-CPBA, NaIO4, etc.; preferably, it is m-CPBA.

[0039] In step (3), the acid is one or more of H2SO4, HCl, TFA, TfOH, TsOH, HBF4, etc.; preferably, it is TfOH.

[0040] In step (3), the solvent is one or more of PhMe, MeOH, EtOH, H2O, THF, dioxane, EtOAc, MeCN, DCM, DMF, etc.; preferably, it is DCM.

[0041] In step (3), the molar ratio of intermediate 2, acid, and oxidant is 1:1-10:1-5; preferably, it is 1:4:1.75.

[0042] In step (3), the reaction temperature is -80–100℃; preferably, it is 0℃.

[0043] In step (3), the reaction time is 1-24 hours; preferably, it is 8 hours.

[0044] In one specific embodiment, the reaction steps are as follows: using substituted 2-halo-3-aminopyridine as a starting material, Pd(dba)2 as a catalyst, X-Phos as a ligand, and Na2CO3 as a base, a Suzuki coupling reaction is carried out with a polysubstituted arylboronic acid at 90°C. Subsequently, under the action of a strong acid TfOH, diazotization is carried out at -40°C using tBuONO as an activating agent, and TBAI is used as an iodine source for nucleophilic substitution to obtain an iodine compound. Finally, under the action of TfOH, at 0°C, mCPBA is used for oxidation to obtain a diarylcyclic pyridine periodide. The reaction equation is shown below:

[0045]

[0046] R contains R 4 R 5 R' contains R 1 R 2 R 3 X is a halogen;

[0047] This invention also provides the application of the pyridyne-benzyne biaromaticyne precursor in the preparation of multisubstituted pyridine derivatives, benzene ring derivatives, and pyridine heteroatom nucleophilic products.

[0048] The pyridyne-benzyne diaromaticyne precursor can release a pyridine ring-benzyne intermediate in situ twice consecutively. The intermediate can be captured by an active diene or a nucleophile. The reaction equation is shown below:

[0049]

[0050] The specific steps are as follows:

[0051] Using pyridyne-benzyne diaromaticyne precursors as raw materials, rapid and highly selective nucleophilic reactions can occur with oxygen, nitrogen, and sulfur nucleophiles under the action of base and solvent to generate pyridine heteroatom nucleophilic products. Additionally, the pyridyne-benzyne diaromaticyne precursors can undergo rapid [4+2] cycloaddition reactions with dienes (such as furan) to generate monobridged ring compounds, and secondary aromaticyne cycloaddition reactions can occur to obtain dibridged ring compounds.

[0052] To clarify the reaction process of continuous diaryryne precursors and the sufficiency of capturing aryryne intermediates, this invention uses furan and substituted furan in a [4+2] cycloaddition reaction, and benzyl azide and tetramethylthiourea in a [3+2] cycloaddition reaction as evidence.

[0053] In this invention, the alkali 1 is one or more of K2CO3, NaOH, KOH, tBuOLi, tBuONa, tBuOK, LiHMDS, and LDA, preferably KOH or tBuOK; the alkali 2 is one or more of K2CO3, NaOH, KOH, tBuOLi, tBuONa, tBuOK, LiHMDS, and LDA, preferably LiHMDS.

[0054] In this invention, the solvent is one or more of methanol, ethanol, tetrahydrofuran, toluene, acetonitrile, ethyl acetate, dioxane, dichloromethane, diethyl ether, and petroleum ether; preferably, toluene or acetonitrile is used as the solvent.

[0055] In this invention, the volume of the solvent used is 0.5-10 mL; preferably, it is 1 mL.

[0056] In this invention, the temperature of the oxidation reaction is -20 to 80°C; preferably, it is room temperature.

[0057] In this invention, the oxidation reaction takes 2-36 hours; preferably, it takes 12 hours.

[0058] In this invention, the amount of the polysubstituted diene or nucleophile is 1-20 equivalents of the raw material; preferably, it is 5 equivalents.

[0059] The structural formulas of the [4+2] cycloaddition products that are captured by furan twice in succession include the following:

[0060]

[0061]

[0062] The pyridyne-benzyne diaromaticyne precursor protected by this invention is the first proposed concept of a pyridyne-aromaticyne diaromaticyne, and similar structures with other heteroatoms are extremely difficult to obtain. Technical challenges of this invention:

[0063] 1) For the first time, pyridine periodide was used as a pyridyne precursor to generate pyridyne under mild conditions;

[0064] 2) For the first time, cyclic pyridine high-iodide salt was used as a precursor for diaromaticynes, which can generate aromaticynes twice in succession through [4+2] cycloaddition, thus efficiently and rapidly constructing N-PAHs;

[0065] 3) Cyclic pyridine periodontium salts, as aromatic yne precursors, have a single nucleophilic addition selectivity, and the nucleophilic addition site is opposite to that of conventional aromatic yne precursors;

[0066] 4) This paper first proposed that the nucleophilic addition selectivity of aromatic yne directed groups is induced by aromatic yne directing groups, providing a feasible approach for the study of highly selective nucleophilic addition of aromatic yne;

[0067] 5) Iodine atoms have a large atomic radius and weak electron binding ability. They can not only serve as a good leaving group to generate aromatic yne, but also stabilize aromatic yne through hyperconjugation and regulate nucleophilic selective sites through push-pull effects.

[0068] 6) Pyridine periodide, as a precursor of this type of aromatic yne, has very gentle formation conditions, very simple synthesis conditions, and wide functional group compatibility, and has very broad potential application value.

[0069] The beneficial effects of this invention include: This invention proposes for the first time the concept of pyridine-benzyne biaromatic yne precursor, designs the first pyridine-benzyne biaromatic yne precursor, has mild reaction conditions, simple reaction operation, good reaction selectivity, and rich reaction types, and has great practical and research value. Detailed Implementation

[0070] The present invention will be further described in detail below with reference to specific embodiments. Except for the contents specifically mentioned below, the processes, conditions, and experimental methods for implementing the present invention are all common knowledge and general knowledge in the art, and the present invention does not have any particular limitations.

[0071] Example 1

[0072] Synthesis of Compound 1

[0073] Using 2-chloro-3-aminopyridine (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to give 2-aryl-3-aminopyridine. Subsequently, at -40 °C, 2-aryl-3-iodopyridine was diazotized by tBuONO (1.3 equiv.) in the presence of TfOH (4.0 equiv.) and iodinated by TBAI (1.3 equiv.) to give 2-aryl-3-iodopyridine. 2-aryl-3-iodopyridine was oxidized by mCPBA (1.75 equiv.) in the presence of TfOH (4.0 equiv.) at 0 °C using DCM as a solvent, and stirred at room temperature until a solid precipitated. After the reaction was complete, the solvent was evaporated to dryness. The mixture was washed with Et2O and filtered to obtain the product, diarylcyclic pyridine high iodide salt 1.

[0074] The characterization results of compound 1 are as follows:

[0075] 1 H NMR(500MHz,DMSO-d6)δ8.98–9.02(m,1H),8.59(d,J=8.3Hz,1H),8.50–8.43(m,1H),8.29(d,J =8.1Hz,1H),7.92(t,J=7.4Hz,1H),7.85(dd,J=10.7,4.7Hz,1H),7.76(dd,J=8.3,4.6Hz,1H). 13 C NMR (125MHz, DMSO-d6) δ 157.50, 151.44, 139.36, 139.21, 133.04, 130.86, 130.24, 128.36, 125.90, 121.8, 120.8 (q, J = 320.0Hz), 119.6.

[0076] Example 2

[0077] Synthesis of Compound 2

[0078] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently...

[0079] At -40℃, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) yielded 2-aryl-3-iodopyridine compounds under the action of TfOH (4.0 equiv.) at 0℃. The 2-aryl-3-iodopyridine compounds were then oxidized with mCPBA (1.75 equiv.) at 0℃ using DCM as solvent and under the action of TfOH (4.0 equiv.). The mixture was stirred at room temperature until a solid precipitated, and the solvent was evaporated to dryness after the reaction was complete. The mixture was washed with Et₂O and filtered to give the product, diarylcyclic pyridine periodic salt 2.

[0080] The characterization results of compound 2 are as follows:

[0081] 1 H NMR(500MHz,CD3OD)δ8.95(d,J=4.3Hz,1H),8.49(dd,J=8.4,1.1Hz,1H),8.36–8.42( m,1H),8.00(s,1H),7.74(d,J=7.8Hz,1H),7.67(dd,J=8.2,4.6Hz,1H),2.58(s,3H). 13 CNMR(125MHz,CD3OD)δ159.6,153.0,146.3,140.0,138.5,133.4,131.0,130.1,126 .6,121.8(q,J=316.3Hz),121.6,119.1,21.9.IR(neat)1286,1160,992,795,633cm - 1 .HRMS(ESI)m / z:(M) + Calculated for C 12 H9IN + 293.9774; Found 293.9774.

[0082] Example 3

[0083] Synthesis of Compound 3

[0084] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently, at -40 °C, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) were carried out in the presence of TfOH (4.0 equiv.) to yield 2-aryl-3-iodopyridine compounds. 2-aryl-3-iodopyridine compounds were oxidized by mCPBA (1.75 equiv.) at 0 °C with TfOH (4.0 equiv.) as solvent. The mixture was stirred at room temperature until a solid precipitated. After the reaction was complete, the solvent was evaporated to dryness. The mixture was washed with Et2O and filtered to obtain the product, diaryl cyclic pyridine periodide 3.

[0085] The characterization results of compound 3 are as follows: 1 H NMR (400MHz, DMSO-d6) δ8.97(dd,J=4.6,1.1Hz,1H),8.57(dd,J=8.3,1.2Hz,1H),8.36(d,J=8.2Hz ,1H),8.29(d,J=1.6Hz,1H),7.97(dd,J=8.2,1.6Hz,1H),7.72(dd,J=8.3,4.6Hz,1H),1.39(s,9H). 13 C NMR(100MHz,DMSO-d6)δ157.4,156.5,151.4,139.2,136.9,128.5,128.0,126.4,125.6,122.4,1 22.29,120.7(q,J=320.0Hz),119.4,35.8,30.9.IR(neat)1280,1224,1161,1024,991,795,633cm -1 .HRMS(ESI)m / z:(M) + Calculated for C 15 H 15 IN + 336.0244; Found 336.0237.

[0086] Example 4

[0087] Synthesis of Compound 4

[0088] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently, at -40 °C, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) were carried out in the presence of TfOH (4.0 equiv.) to yield 2-aryl-3-iodopyridine compounds. 2-aryl-3-iodopyridine compounds were oxidized by mCPBA (1.75 equiv.) at 0 °C with TfOH (4.0 equiv.) as solvent. The mixture was stirred at room temperature until a solid precipitated. After the reaction was complete, the solvent was evaporated to dryness. The mixture was washed with Et2O and filtered to obtain the product, diaryl cyclic pyridine periodic salt 4.

[0089] The characterization results of compound 4 are as follows:

[0090] 1 H NMR (400MHz, DMSO-d6) δ8.98(d,J=4.5Hz,1H),8.57(d,J=8.3Hz,1H),8.42(d,J=7.5H z,1H),8.38(s,1H),8.02(d,J=7.6Hz,1H),7.74(dd,J=8.2,4.6Hz,1H),0.35(s,9H). 13 C NMR (400MHz, DMSO-d6) δ157.7,151.5,147.1,139.7,139.3,135.2,134.2,127.9,126.1,1 22.5,120.7(q,J=320.0Hz),119.5,-1.3.IR(neat)1281,1221,1162,1025,833,752,632cm -1 .HRMS(ESI)m / z:(M) + Calculated for C 14 H 15 INSi + 352.0013; Found 352.0011.

[0091] Example 5

[0092] Synthesis of Compound 5

[0093] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently, at -40 °C, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) were carried out in the presence of TfOH (4.0 equiv.) to yield 2-aryl-3-iodopyridine compounds. 2-aryl-3-iodopyridine compounds were oxidized by mCPBA (1.75 equiv.) at 0 °C with TfOH (4.0 equiv.) as solvent. The mixture was stirred at room temperature until a solid precipitated. After the reaction was complete, the solvent was evaporated to dryness. The mixture was washed with Et2O and filtered to obtain the product, diaryl cyclic pyridine periodic salt 5.

[0094] The characterization results of compound 5 are as follows:

[0095] 1 H NMR (500MHz, DMSO-d6) δ8.89(dd,J=4.6,1.0Hz,1H),8.52(d,J=8.3Hz,1H),8.24(d,J=8.7Hz,1H ),7.80(d,J=2.3Hz,1H),7.64(dd,J=8.3,4.6Hz,1H),7.43(dd,J=8.7,2.3Hz,1H),3.92(s,3H). 13 C NMR (125MHz, DMSO-d6) δ161.8,156.6,150.7,138.5,131.3,128.4,124.1,122.8,120.2(q ,J=320.0Hz),118.4,117.5,113.9,55.7.IR(neat)1285,1210,1117,1024,960,837,633cm -1 .HRMS(ESI)m / z:(M) + Calculated for C 12 H9INO + 309.9723; Found 309.9755.

[0096] Example 6

[0097] Synthesis of Compound 6

[0098] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently...

[0099] At -40℃, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) yielded 2-aryl-3-iodopyridine compounds under the action of TfOH (4.0 equiv.) at 0℃. The 2-aryl-3-iodopyridine compounds were then oxidized with mCPBA (1.75 equiv.) at 0℃ using DCM as solvent and under the action of TfOH (4.0 equiv.). The mixture was stirred at room temperature until a solid precipitated, and the solvent was evaporated to dryness after the reaction was complete. The mixture was washed with Et₂O and filtered to give the product, diarylcyclic pyridine periodide 6.

[0100] The characterization results of compound 6 are as follows:

[0101] 1 H NMR(500MHz,DMSO-d6)δ9.01(d,J=3.6Hz,1H),8.94(s,1H),8.88(d,J=8.2Hz, 1H), 8.59 (d, J = 8.1Hz, 1H), 8.21 (d, J = 8.0Hz, 1H), 7.80 (dd, J = 8.3, 4.6Hz, 1H). 13 C NMR (125MHz, DMSO-d6) δ156.0,151.4,143.2,139.2,131.4(q,J=32.5Hz),128.3,127.5,127.2 ,126.4,125.1,123.5(q,J=271.3Hz),123.0.IR(neat)1223,1180,1131,1016,788,629,575cm -1 .HRMS(ESI)m / z:(M) + Calculated for C 12 H6F3IN + 347.9492; Found 347.9479.

[0102] Example 7

[0103] Synthesis of Compound 7

[0104] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently, at -40 °C, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) were carried out in the presence of TfOH (4.0 equiv.) to yield 2-aryl-3-iodopyridine compounds. 2-aryl-3-iodopyridine compounds were oxidized by mCPBA (1.75 equiv.) at 0 °C with TfOH (4.0 equiv.) as solvent. The mixture was stirred at room temperature until a solid precipitated. After the reaction was complete, the solvent was evaporated to dryness. The mixture was washed with Et2O and filtered to obtain the product, diaryl cyclic pyridine periodic salt 7.

[0105] The characterization results of compound 7 are as follows:

[0106] 1 H NMR (500MHz, CD3OD) δ8.99(dd,J=4.6,1.1Hz,1H),8.58(d,J=8.6Hz,1H),8.53(dd,J=8.4,1 .1Hz,1H),8.17(d,J=1.0Hz,1H),7.86(dd,J=8.6,1.1Hz,1H),7.74(dd,J=8.4,4.6Hz,1H). 13 C NMR (125MHz, CD3OD) δ158.1,153.2,152.6,152.6,140.1,140.0,131.4,127.3,125.5,123.5,121.8(q,J= 257.5Hz),121.7(q,J=316.3Hz),121.6,120.3.IR(neat)1263,1224,1167,1024,997,799,631,625,574cm -1 .HRMS(ESI)m / z:(M) + Calculated for C 12 H6F3INO + 363.9441; Found 363.9433.

[0107] Example 8

[0108] Synthesis of Compound 8

[0109] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently...

[0110] At -40℃, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) under the action of TfOH (4.0 equiv.) yielded 2-aryl-3-iodopyridine compounds. Using DCM as solvent, the 2-aryl-3-iodopyridine compounds were oxidized with mCPBA (1.75 equiv.) at 0℃ under the action of TfOH (4.0 equiv.). The mixture was stirred at room temperature until a solid precipitated, and the solvent was evaporated to dryness after the reaction was complete. The mixture was washed with Et₂O and filtered to give the product, diarylcyclic pyridine periodide 8.

[0111] The characterization results of compound 8 are as follows:

[0112] 1 H NMR (400MHz, DMSO-d6) δ8.97(d,J=4.6Hz,1H),8.56(d,J=8.3Hz,1H),8.41(dd,J=8.6,5.3Hz,1H),8.11–8.01(m,1H),7.72–7.83(m,2H). 13 C NMR (100MHz, DMSO-d6) δ163.5(d,J=252.0Hz),156.3,151.5,139.2,136.1,129.8(d,J=9.0Hz),125.8,122.5(d,J=10.0Hz),120 .7(q,J=320.0Hz),120.0,119.2(d,J=23.0Hz),117.5(d,J=27.0Hz).IR(neat)1280,1220,1128,1022,957,836,732,633,571cm -1 .HRMS(ESI)m / z:(M) + Calculated for C 11 H6FIN + 297.9523; Found 297.9515.

[0113] Example 9

[0114] Synthesis of Compound 9

[0115] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently, at -40 °C, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) were carried out in the presence of TfOH (4.0 equiv.) to yield 2-aryl-3-iodopyridine compounds. 2-aryl-3-iodopyridine compounds were oxidized by mCPBA (1.75 equiv.) at 0 °C with TfOH (4.0 equiv.) as solvent. The mixture was stirred at room temperature until a solid precipitated. After the reaction was complete, the solvent was evaporated to dryness. The mixture was washed with Et2O and filtered to obtain the product, diaryl cyclic pyridine periodide 9.

[0116] The characterization results of compound 9 are as follows:

[0117] 1 H NMR(500MHz,DMSO-d6)δ8.98(d,J=3.9Hz,1H),8.57(d,J=8.1Hz,1H),8.35(d,J=8 .3Hz,1H),8.24(d,J=1.1Hz,1H),7.99–7.90(m,1H),7.77(dd,J=8.2,4.6Hz,1H). 13 CNMR(125MHz,DMSO-d6)δ156.3,151.5,139.2,138.4,136.6,131.3,129.5,129.2,126 .1,122.49,120.7(q,J=320.0Hz),120.10.IR(neat)1232,1159,1094,994,793,630cm -1 .HRMS(ESI)m / z:(M) + Calculated for C 11 H6ClIN + 313.9228; Found 313.9256.

[0118] Example 10

[0119] Synthesis of Compound 10

[0120] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently, at -40 °C, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) were carried out in the presence of TfOH (4.0 equiv.) to yield 2-aryl-3-iodopyridine compounds. 2-aryl-3-iodopyridine compounds were oxidized by mCPBA (1.75 equiv.) in DCM solvent at 0 °C with TfOH (4.0 equiv.). The mixture was stirred at room temperature until a solid precipitated. After the reaction was complete, the solvent was evaporated to dryness. The mixture was washed with Et2O and filtered to obtain the product, diaryl cyclic pyridine periodic salt 10.

[0121] The characterization results of compound 10 are as follows:

[0122] 1 H NMR (500MHz, DMSO-d6) δ8.97(d,J=3.2Hz,1H),8.61(d,J=7.0Hz,1H),8.26(s,1H),8.18(d,J=7.7Hz,1H),7.79–7.60(m,2H),2.54(s,3H). 13 C NMR (125MHz, DMSO-d6) δ157.4,151.3,141.0,139.3,139.2,133.8,129.8,128.4,125.7,1 20.7(q,J=320.0Hz),120.1,118.7,20.7.IR(neat)1224,1156,1025,983,854,791,631cm -1 .HRMS(ESI)m / z:(M) + Calculated for C 12 H9IN + 293.9774; Found 293.9774.

[0123] Example 11

[0124] Synthesis of Compound 11

[0125] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently, at -40 °C, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) were carried out in the presence of TfOH (4.0 equiv.) to yield 2-aryl-3-iodopyridine compounds. 2-aryl-3-iodopyridine compounds were oxidized by mCPBA (1.75 equiv.) at 0 °C with TfOH (4.0 equiv.) as solvent. The mixture was stirred at room temperature until a solid precipitated. After the reaction was complete, the solvent was evaporated to dryness. The mixture was washed with Et2O and filtered to obtain the product, diaryl cyclic pyridine periodic salt 11.

[0126] The characterization results of compound 11 are as follows:

[0127] 1 H NMR (500MHz, DMSO-d6) δ8.88(d,J=3.8Hz,1H),8.49(d,J=8.0Hz,1H),8.01(d,J=8.9H z,1H),7.76(s,1H),7.66(dd,J=7.9,4.5Hz,1H),7.33(d,J=8.7Hz,1H),3.88(s,3H). 13 C NMR(125MHz,DMSO-d6)δ161.8,157.3,151.8,141.1,139.6,131.3,126.4,121.0,121.0(q, J=318.8Hz),119.9,112.1,110.9,56.4.IR(neat)1276,1222,1163,1024,1007,796,634cm -1 .HRMS(ESI)m / z:(M) + Calculated for C 12 H9INO + 309.9723; Found 309.9755.

[0128] Example 12

[0129] Synthesis of Compound 12

[0130] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently, at -40 °C, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) were carried out in the presence of TfOH (4.0 equiv.) to yield 2-aryl-3-iodopyridine compounds. 2-aryl-3-iodopyridine compounds were oxidized by mCPBA (1.75 equiv.) in DCM solvent at 0 °C with TfOH (4.0 equiv.). The mixture was stirred at room temperature until a solid precipitated. After the reaction was complete, the solvent was evaporated to dryness. The mixture was washed with Et2O and filtered to obtain the product, diaryl cyclic pyridine periodic salt 12.

[0131] The characterization results of compound 12 are as follows:

[0132] 1 H NMR(400MHz,CD3OD)δ9.01(d,J=4.5Hz,1H),8.75(s,1H),8.53(d,J=8.3Hz,1H),8 .24(d,J=8.6Hz,1H),8.09(d,J=8.4Hz,1H),7.70–7.81(m,3H),7.45–7.58(m,3H). 13 CNMR(100MHz,CD3OD)δ159.4,153.1,145.8,141.7,140.1,139.7,133.0,131.4,130.4,130.0 ,128.3,128.3,127.2,120.2,119.8,119.6.IR(neat)1287,1233,1156,1029,990,757,696cm -1 .HRMS(ESI)m / z:(M) + Calculated for C 17 H 11 IN + 355.9931; Found 355.9944.

[0133] Example 13

[0134] Synthesis of Compound 13

[0135] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently, at -40 °C, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) were carried out in the presence of TfOH (4.0 equiv.) to yield 2-aryl-3-iodopyridine compounds. 2-aryl-3-iodopyridine compounds were oxidized by mCPBA (1.75 equiv.) in DCM solvent at 0 °C with TfOH (4.0 equiv.). The mixture was stirred at room temperature until a solid precipitated. After the reaction was complete, the solvent was evaporated to dryness. The mixture was washed with Et2O and filtered to obtain the product, diaryl cyclic pyridine periodic salt 13.

[0136] The characterization results of compound 13 are as follows:

[0137] 1 H NMR (400MHz, CD3OD) δ8.97 (dd, J=4.6, 1.2Hz, 1H), 8.51 (dd, J=8.4, 1.2Hz, 1H), 8.41 (d, J=2 .4Hz,1H),8.14(d,J=8.8Hz,1H),7.80(dd,J=8.8,2.4Hz,1H),7.73(dd,J=8.4,4.6Hz,1H). 13 C NMR(100MHz,CD3OD)δ158.1,153.2,142.9,140.1,139.2,134.0,132.4,129.8,127.6, 121.7(q,J=317.0Hz),112.0,118.7.IR(neat)1279,1213,1168,1023,961,789,633cm -1 .HRMS(ESI)m / z:(M) + Calculated for C 11 H6ClIN + 313.9228; Found 313.9256.

[0138] Example 14

[0139] Synthesis of Compound 14

[0140] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently, at -40 °C, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) were carried out in the presence of TfOH (4.0 equiv.) to yield 2-aryl-3-iodopyridine compounds. 2-aryl-3-iodopyridine compounds were oxidized by mCPBA (1.75 equiv.) in DCM solvent at 0 °C with TfOH (4.0 equiv.). The mixture was stirred at room temperature until a solid precipitated. After the reaction was complete, the solvent was evaporated to dryness. The mixture was washed with Et2O and filtered to obtain the product, diaryl cyclic pyridine periodic salt 14.

[0141] The characterization results of compound 14 are as follows:

[0142] 1 H NMR (500MHz, DMSO-d6) δ8.48–8.54(m,2H),8.17–8.27(m,4H),7.88(t,J=7.4Hz,1H),7.80(dd,J=10.6,4.7Hz,1H),7.52–7.58(m,3H). 13 C NMR(125MHz,DMSO-d6)δ158.3,157.9,140.2,139.6,137.0,133.6,131.4,131.1,130.6,129.7,129.1 ,127.6,122.7,122.1,121.0(q,J=320.0Hz),117.7.IR(neat)1273,1223,1143,1025,740,632,612cm -1 .HRMS(ESI)m / z:(M) + Calculated for C 17 H 11 IN + 355.9931; Found 355.9944.

[0143] Example 15

[0144] Synthesis of Compound 15

[0145] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently, at -40 °C, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) were carried out in the presence of TfOH (4.0 equiv.) to yield 2-aryl-3-iodopyridine compounds. 2-aryl-3-iodopyridine compounds were oxidized by mCPBA (1.75 equiv.) in DCM at 0 °C with TfOH (4.0 equiv.). The mixture was stirred at room temperature until a solid precipitated. After the reaction was complete, the solvent was evaporated to dryness. The mixture was washed with Et2O and filtered to obtain the product, diaryl cyclic pyridine periodic salt 15.

[0146] The characterization results of compound 15 are as follows:

[0147] 1 H NMR(500MHz,DMSO-d6)δ8.90(d,J=8.6Hz,1H),8.58(dd,J=8.6,5.4Hz,1H),8.42(dd, J=8.1,2.3Hz,1H),8.27–8.32(m,3H),7.75(td,J=8.5,2.4Hz,1H),7.52–7.62(m,3H). 13 C NMR (125MHz, DMSO-d6) δ163.4(d,J=251.3Hz),157.5,156.3,140.0,137.0,136.1,130.3,129.8,129.4(d,J=8.8Hz),129.1,128.8,127.7 ,127.1,126.3(d,J=10.0Hz),121.5,119.9,118.5(d,J=22.5Hz),117.4(d,J=27.5Hz).IR(neat)1550,1359,1192,1071,1024,764,573cm -1 .HRMS(ESI)m / z:(M) + Calculated for C 17 H 10 FIN + 373.9836; Found 373.9833.

[0148] Example 16

[0149] Synthesis of Compound 16

[0150] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently, at -40 °C, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) were carried out in the presence of TfOH (4.0 equiv.) to yield 2-aryl-3-iodopyridine compounds. 2-aryl-3-iodopyridine compounds were oxidized by mCPBA (1.75 equiv.) at 0 °C with TfOH (4.0 equiv.) as solvent. The mixture was stirred at room temperature until a solid precipitated. After the reaction was complete, the solvent was evaporated to dryness. The mixture was washed with Et2O and filtered to obtain the product, diaryl cyclic pyridine periodic salt 16.

[0151] The characterization results of compound 16 are as follows:

[0152] 1 H NMR (500MHz, DMSO-d6) δ8.39(d,J=8.4Hz,1H),7.92(s,1H),7.79(s,1H),7.58(d,J=8.5Hz,1H),4.00(s,3H),2.69(s,3H),2.32(s,3H). 13 C NMR (125MHz, DMSO-d6) δ160.7,159.6,156.8,138.9,138.6,132.5,130.4,125.4,120.7(q,J=32 0.0Hz),116.1,110.6,108.6,56.1,23.9,16.9.IR(neat)1280,1220,1167,1023,999,814,633cm -1 .HRMS(ESI)m / z:(M) + Calculated for C 14 H 13 INO + 338.0036; Found 338.0023.

[0153] Example 17

[0154] Synthesis of Compound 17

[0155] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently, at -40 °C, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) were carried out in the presence of TfOH (4.0 equiv.) to yield 2-aryl-3-iodopyridine compounds. 2-aryl-3-iodopyridine compounds were oxidized by mCPBA (1.75 equiv.) in DCM solvent at 0 °C with TfOH (4.0 equiv.). The mixture was stirred at room temperature until a solid precipitated, and the solvent was evaporated to dryness after the reaction was complete. The mixture was washed with Et2O and filtered to obtain the product, diaryl cyclic pyridine periodic salt 17.

[0156] The characterization results of compound 17 are as follows:

[0157] 1 H NMR (400MHz, DMSO-d6) δ8.36(d,J=8.5Hz,1H),7.78(s,1H),7.72(s,1H),7.53(d,J=8.5Hz,1H),3.97(s,3H),3.93(s,3H),2.68(s,3H). 13 C NMR(100MHz,DMSO-d6)δ160.7,156.9,152.4,151.5,138.8,132.2,124.5,115.8,112.1 ,111.5,109.3,56.3,56.1,23.8.IR(neat)1284,1212,1165,1023,996,869,782,635cm -1 .HRMS(ESI)m / z:(M) + Calculated for C 14 H 13 INO2 + 353.9985; Found 353.9984.

[0158] Example 18

[0159] Synthesis of Compound 18

[0160] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently, at -40 °C, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) were carried out in the presence of TfOH (4.0 equiv.) to yield 2-aryl-3-iodopyridine compounds. 2-aryl-3-iodopyridine compounds were oxidized by mCPBA (1.75 equiv.) at 0 °C with TfOH (4.0 equiv.) as solvent. The mixture was stirred at room temperature until a solid precipitated. After the reaction was complete, the solvent was evaporated to dryness. The mixture was washed with Et2O and filtered to obtain the product, diaryl cyclic pyridine periodic salt 18.

[0161] The characterization results of compound 18 are as follows:

[0162] 1 H NMR (500MHz, DMSO-d6) δ9.65(d,J=11.6Hz,1H),8.42(d,J=7.1Hz,1H),8.09(d,J=8.5Hz,1H),7.81(d,J=8.6Hz,1H),2.58(s,3H). 13 C NMR (125MHz, DMSO-d6) δ158.0 (d, J = 246Hz), 151.9, 145.9, 136.6 (d, J = 10Hz), 131.1, 126.4, 125.8, 123.5 (d, J = 20Hz) ,120.7(q,J=320.0Hz),118.9(d,J=28Hz),117.9,115.1,17.5.IR(neat)1279,1121,1151,1023,997,819,631,611cm -1 .HRMS(ESI)m / z:(M) + Calculated for C 12 H7ClFIN + 345.9290; Found 345.9268.

[0163] Example 19

[0164] Synthesis of Compound 19

[0165] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently, at -40 °C, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) were carried out in the presence of TfOH (4.0 equiv.) to yield 2-aryl-3-iodopyridine compounds. 2-aryl-3-iodopyridine compounds were oxidized by mCPBA (1.75 equiv.) at 0 °C with TfOH (4.0 equiv.) as solvent. The mixture was stirred at room temperature until a solid precipitated. After the reaction was complete, the solvent was evaporated to dryness. The mixture was washed with Et2O and filtered to obtain the product, diaryl cyclic pyridine periodic salt 19.

[0166] The characterization results of compound 19 are as follows:

[0167] 1 H NMR (500MHz, DMSO-d6) δ8.87–8.94(m,1H),8.47–8.55(m,1H),8.15–8.21(m,1H),7.72–7.77(m,1H),7.61–7.69(m,1H),3.96(s,3H),2.34(s,3H). 13 C NMR (125MHz, DMSO-d6) δ160.7,157.4,151.2,139.0,131.4,130.1,129.0,124.5,120.7(q,J=32 0.0Hz),120.3,118.9,110.8,56.2,16.2.IR(neat)1281,1225,1165,1027,900,759,632,572cm - 1 .HRMS(ESI)m / z:(M) + Calculated for C 13 H 11 INO + 323.9880; Found 323.9896.

[0168] Example 20

[0169] Synthesis of Compound 20

[0170] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently, at -40 °C, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) were carried out in the presence of TfOH (4.0 equiv.) to yield 2-aryl-3-iodopyridine compounds. 2-aryl-3-iodopyridine compounds were oxidized by mCPBA (1.75 equiv.) at 0 °C with TfOH (4.0 equiv.) as solvent. The mixture was stirred at room temperature until a solid precipitated. After the reaction was complete, the solvent was evaporated to dryness. The mixture was washed with Et2O and filtered to obtain the product, diaryl cyclic pyridine periodic salt 20.

[0171] The characterization results of compound 20 are as follows:

[0172] 1 H NMR (400MHz, DMSO-d6) δ8.97(d,J=4.0Hz,1H),8.55(d,J=8.3Hz,1H),8.29(s,1H),8.13(s,1H),7.75(dd,J=8.4,4.6Hz,1H),2.51(s,3H). 13 C NMR(100MHz,DMSO-d6)δ156.2,151.5,140.9,139.3,138.9,136.9,131.8,127.5,126.2 ,120.7(q,J=320.0Hz),120.0,119.5,20.6.IR(neat)1279,1213,1166,1019,993,634cm -1 .HRMS(ESI)m / z:(M) + Calculated for C 12 H8ClIN + 327.9384; Found 327.9410.

[0173] Example 21

[0174] Synthesis of Compound 21

[0175] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently, at -40 °C, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) were carried out in the presence of TfOH (4.0 equiv.) to yield 2-aryl-3-iodopyridine compounds. 2-aryl-3-iodopyridine compounds were oxidized by mCPBA (1.75 equiv.) in DCM at 0 °C with TfOH (4.0 equiv.). The mixture was stirred at room temperature until a solid precipitated. After the reaction was complete, the solvent was evaporated to dryness. The mixture was washed with Et2O and filtered to obtain the product, diaryl cyclic pyridine periodic salt 21.

[0176] The characterization results of compound 21 are as follows:

[0177] 1 H NMR (500MHz, DMSO-d6) δ8.92(d,J=4.6Hz,1H),8.52(d,J=8.4Hz,1H),8.29(t,J=8.8Hz,1H),8.16(t,J=7.8Hz,1H),7.76–7.68(m,1H). 13 C NMR (125MHz, DMSO-d6) δ156.1,152.5(dd,J=251.3,13.8Hz),152.0,151.9(dd,J=255.0,13.8Hz),139.65,137.6(d,J=3.8Hz),126.6,121 .0(q,J=320.0Hz),120.6,119.9(d,J=22.5Hz),116.7(d,J=20.0Hz),115.9(d,J=6.3Hz).IR(neat)1223,1158,1010,793,628,611,573cm -1 .HRMS(ESI)m / z:(M) + Calculated for C 11 H5F2IN + 315.9429; Found 315.9492.

[0178] Example 22

[0179] Synthesis of Compound 22

[0180] Using a 2-chloro-3-aminopyridine derivative (10 mmol) as a starting material, toluene, water, and ethanol (v / v / v = 5 / 1 / 5) as a mixed solvent, Pd(dba)₂ (2 mol%) as a catalyst, X-Phos (4 mol%) as a ligand, and Na₂CO₃ (5.0 equiv.) as a base, a substituted arylboronic acid compound (1.3 equiv.) was coupled at 90 °C to yield 2-aryl-3-aminopyridine compounds. Subsequently, at -40 °C, diazotization with tBuONO (1.3 equiv.) and iodination with TBAI (1.3 equiv.) were carried out in the presence of TfOH (4.0 equiv.) to yield 2-aryl-3-iodopyridine compounds. 2-aryl-3-iodopyridine compounds were oxidized by mCPBA (1.75 equiv.) at 0 °C with TfOH (4.0 equiv.) as solvent. The mixture was stirred at room temperature until a solid precipitated. After the reaction was complete, the solvent was evaporated to dryness. The mixture was washed with Et2O and filtered to obtain the product, diaryl cyclic pyridine periodic salt 22.

[0181] The characterization results of compound 22 are as follows:

[0182] 1 H NMR (500MHz, DMSO-d6) δ9.04–8.98(m,1H),8.63–8.58(m,1H),8.55–8.46(m,1H),8.43–8.37(m,1H),7.84–7.79(m,1H). 13 C NMR (125MHz, DMSO-d6) δ155.3,151.6,139.9,139.3,134.9,134.5,131.4,128.7,126. 7,120.8,120.7(q,J=321.3Hz),120.2.IR(neat)1169,1129,1020,997,855,633,572cm -1 .HRMS(ESI)m / z:(M) + Calculated for C 11 H5Cl2IN + 347.8838; Found 347.8862.

[0183] The following embodiments of the present invention refer to the following reaction formulas for the preparation of sulfoxide compounds:

[0184]

[0185] Example 23

[0186] Synthesis of compound 23:

[0187]

[0188] The substrate (0.1 mmol), furan (34 mg, 0.5 mmol), and tBuOK (34 mg, 0.3 mmol) were added to the reaction tube. Toluene was used as the solvent, and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the solvent was evaporated to dryness, and the product was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 23 (22.6 mg, 65%).

[0189] The characterization results of compound 23 are as follows:

[0190] 1 H NMR (400MHz, CDCl3) δ8.39(d,J=4.8Hz,1H),7.96(dd,J=8.0,0.8Hz,1H),7.44(td,J=7.6,1.1Hz,1H),7.22–7.29(m,2 H),7.20(dd,J=5.6,1.6Hz,1H),7.10–7.14(m,1H),7.02(dd,J=5.6,2.0Hz,1H),5.75–5.95(m,1H),5.45–5.62(m,1H). 13 C NMR (100MHz, CDCl3) δ159.1,152.0,146.9,143.5,143.1,143.1,141.5,139.4,130.0,128.2,115.4,96.9,82.0,80.9.HRMS(ESI)m / z:(M+H) + Calculated for C 15 H 11 INO + 347.9880; Found 347.9971.

[0191] Example 24

[0192] Synthesis of compound 24:

[0193]

[0194] The substrate (0.1 mmol), furan (34 mg, 0.5 mmol), and tBuOK (34 mg, 0.3 mmol) were added to the reaction tube. Toluene was used as the solvent, and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 24 (22.4 mg, 62%).

[0195] The characterization results of compound 24 are as follows:

[0196] 1 H NMR(400MHz, CDCl3)δ8.38(d,J=4.8Hz,1H),7.80(s,1H),7.11–7.34(m,4H), 7.02(dd,J=5.6,2.0Hz,1H),5.79(d,J=1.2Hz,1H),5.57(s,1H),2.37(s,3H). 13 C NMR (100MHz, CDCl3) δ159.0,152.0,146.9,143.2,141.5,140.6,140.2,139.8,129.7,129.1,115.3,96.7,82.0,81.0,20.6.HRMS(ESI)m / z:(M+H) + Calculated for C 16 H 13 INO + 362.0036; Found 362.0045. Example 25

[0197] Synthesis of compound 25:

[0198]

[0199] The substrate (0.1 mmol), furan (34 mg, 0.5 mmol), and tBuOK (34 mg, 0.3 mmol) were added to the reaction tube. Toluene was used as the solvent, and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 25 (23.8 mg, 59%).

[0200] The characterization results of compound 25 are as follows:

[0201] 1 H NMR (400MHz, CDCl3) δ8.38(d,J=4.8Hz,1H),7.94(d,J=2.0Hz,1H),7.45(dd,J=8.0,2.0Hz,1H) ,7.14–7.25(m,3H),7.02–7.04(m,1H),5.80(d,J=1.2Hz,1H),5.56–5.65(m,1H),1.34(s,9H). 13C NMR (100MHz, CDCl3) δ159.03,153.47,152.03,146.89,143.21,141.50,140.64,136. 48,129.56,125.47,115.29,96.97,82.03,81.02,34.58,31.15.HRMS(ESI)m / z:(M+H) + Calculated for C 19 H 19 INO + 404.0506; Found 404.0533.

[0202] Example 26

[0203] Synthesis of compound 26:

[0204]

[0205] The substrate (0.1 mmol), furan (34 mg, 0.5 mmol), and tBuOK (34 mg, 0.3 mmol) were added to the reaction tube. Toluene was used as the solvent, and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 26 (23.5 mg, 56%).

[0206] The characterization results of compound 26 are as follows:

[0207] 1 H NMR(400MHz, CDCl3) δ8.39(d,J=4.8Hz,1H),8.06(d,J=0.8Hz,1H),7.48–7.59(m,1H),7.20–7. 28(m,3H),7.02(dt,J=12.0,6.0Hz,1H),5.80(d,J=1.2Hz,1H),5.57–5.62(m,1H),0.31(s,9H). 13 C NMR (100MHz, CDCl3) δ159.2,152.0,146.9,144.0,143.5,143.2,143.1,141.5,133.1,129.5,115.4,97.8,82.0,81.0,-1.3.HRMS(ESI)m / z:(M+H) + Calculated for C 18 H 19 INOSi + 420.0275; Found 420.0351.

[0208] Example 27

[0209] Synthesis of compound 27:

[0210]

[0211] The substrate (0.1 mmol), furan (34 mg, 0.5 mmol), and tBuOK (34 mg, 0.3 mmol) were added to the reaction tube. Toluene was used as the solvent, and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 27 (24.6 mg, 68%).

[0212] The characterization results of compound 27 are as follows:

[0213] 1 H NMR (400MHz, CDCl3) δ8.37(d,J=4.8Hz,1H),7.80(d,J=8.0Hz,1H),7.24–7.28(m,1H),7.21(dd,J=5.6,2.0Hz,1H),7.11(d,J =2.0Hz,1H),7.02(dd,J=5.6,2.0Hz,1H),6.94(dd,J=8.0,2.0Hz,1H),5.79(d,J=1.2Hz,1H),5.56–5.60(m,1H),2.33(s,3H). 13 CNMR (100MHz, CDCl3) δ159.0,152.1,146.9,143.3,143.2,143.1,141.4,139 .0,138.3,131.0,130.9,115.4,92.7,82.0,82.0,20.9.HRMS(ESI)m / z:(M+H) + Calculated for C 16 H 13 INO + 362.0036; Found 362.0039.

[0214] Example 28

[0215] Synthesis of compound 28:

[0216]

[0217] The substrate (0.1 mmol), furan (34 mg, 0.5 mmol) and tBuOK (34 mg, 0.3 mmol) were added to the reaction tube. Toluene was used as the solvent, and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 28 (28.0 mg, 74%).

[0218] The characterization results of compound 28 are as follows:

[0219] 1 H NMR(400MHz, CDCl3) δ8.39(d,J=4.8Hz,1H),7.80(d,J=8.8Hz,1H),7.16–7.35(m,2H),7.03(dd,J=5.6,2 .0Hz,1H),6.85(d,J=3.2Hz,1H),6.73(d,J=8.8Hz,1H),5.81(d,J=1.2Hz,1H),5.58(s,1H),3.80(s,3H). 13 C NMR (100MHz, CDCl3) δ159.86,159.20,151.86,146.94,143.17,141.46,139.9 5,116.78,115.64,115.49,85.30,82.03,80.99,55.47.HRMS(ESI)m / z:(M+H) + Calculated for C 16 H 13 INO2 + 377.9986; Found 378.0062.

[0220] Example 29

[0221] Synthesis of compound 29:

[0222]

[0223] The substrate (0.1 mmol), furan (34 mg, 0.5 mmol), and tBuOK (34 mg, 0.3 mmol) were added to the reaction tube. Toluene was used as the solvent, and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 29 (29.3 mg, 69%).

[0224] The characterization results of compound 29 are as follows:

[0225] 1H NMR(500MHz, CDCl3)δ8.43(d,J=4.8Hz,1H),8.02(d,J=8.0Hz,1H),7.56–7.64(m,2H),7.53(dd,J=20.0,4.0Hz,1H),7.32–7.4 7(m,4H),,7.29(t,J=8.0Hz,1H),7.22(dd,J=5.6,1.6Hz,1H),7.04(dd,J=5.6,2.0Hz,1H),5.82(d,J=1.2Hz,1H),5.64(s,1H). 13 C NMR (125MHz, CDCl3) δ159.3,151.9,147.0,143.8,143.3,143.2,141.6,141.5,139.8,1 39.5,128.9,128.8,128.7,127.9,127.0,115.5,95.5,82.1,81.0.HRMS(ESI)m / z:(M+H) + Calculated for C 21 H 15 INO + 424.0193; Found 424.0221.

[0226] Example 30

[0227] Synthesis of compound 30:

[0228]

[0229] The substrate (0.1 mmol), furan (34 mg, 0.5 mmol) and tBuOK (34 mg, 0.3 mmol) were added to the reaction tube. Toluene was used as the solvent, and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 30 (26.7 mg, 68%).

[0230] The characterization results of compound 30 are as follows:

[0231] 1 H NMR(500MHz, CDCl3)δ8.39(d,J=4.8Hz,1H),7.87(d,J=8.4Hz,1H),7.18–7.33(m,3H) ,7.12(dd,J=8.4,2.4Hz,1H),7.03–7.05(m,1H),5.81(d,J=1.2Hz,1H),5.59(s,1H). 13C NMR (125MHz, CDCl3) δ159.4,150.7,147.2,145.1,143.2,143.0,141.7,140.4,134.7,130.2,130.2,115.8,94.1,82.0,80.9.HRMS(ESI)m / z:(M+H) + Calculated for C 15 H 10 ClINO + 381.9490; Found 381.9568.

[0232] Example 31

[0233] Synthesis of compound 31:

[0234]

[0235] Substrate (0.1 mmol), furan (34 mg, 0.5 mmol) and tBuOK (34 mg, 0.3 mmol) were added to the reaction tube. Toluene was used as the solvent, and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 31 (21.1 mg, 52%).

[0236] The characterization results of compound 31 are as follows:

[0237] 1 H NMR (400MHz, CDCl3) δ7.63(s,1H),7.22(dd,J=5.6,1.6Hz,1H),7.15(d,J=6.4Hz,1H),6.98(dd,J=5.6 ,2.0Hz,1H),6.76(s,1H),5.74(d,J=1.2Hz,1H),5.56(s,1H),3.80(s,3H),2.58(s,3H),2.21(s,3H). 13 C NMR (100MHz, CDCl3) δ159.4,158.0,156.0,151.1,143.3,142.1,140.9,140.3,134 .0,129.3,115.4,112.0,85.2,81.9,81.0,55.4,24.5,15.6.HRMS(ESI)m / z:(M+H) + Calculated for C 18 H 17 INO2 + 406.0299; Found 406.0301.

[0238] Example 32

[0239] Synthesis of compound 32:

[0240]

[0241] The substrate (0.1 mmol), furan (34 mg, 0.5 mmol), and tBuOK (34 mg, 0.3 mmol) were added to the reaction tube. Toluene was used as the solvent, and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the solvent was evaporated to dryness, and the product was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 32 (31.0 mg, 73%).

[0242] The characterization results of compound 32 are as follows:

[0243] 1 H NMR (400MHz, CDCl3) δ7.98–8.08(m,3H),7.71(s,1H),7.30–7.54(m,5H),7.22(d,J= 5.4Hz,1H),7.14(t,J=7.6Hz,1H),7.07(d,J=5.6Hz,1H),5.86(s,1H),5.64(s,1H). 13 CNMR (100MHz, CDCl3) δ160.6,155.0,151.0,143.0,141.5,141.4,139.8,139.0,130. 2,130.0,129.2,128.7,128.2,127.5,112.9,97.1,82.24,81.0.HRMS(ESI)m / z:(M+H) + Calculated for C 21 H 15 INO + 424.0193; Found 424.0162.

[0244] Example 33

[0245] Synthesis of compound 33:

[0246]

[0247] The substrate (0.1 mmol), furan (34 mg, 0.5 mmol) and tBuOK (34 mg, 0.3 mmol) were added to the reaction tube. Toluene was used as the solvent, and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 33 (24.9 mg, 63%).

[0248] The characterization results of compound 33 are as follows:

[0249] 1 H NMR (400MHz, CDCl3) δ8.38 (d, J=4.8Hz, 1H), 7.82 (s, 1H), 7.26–7.28 (m, 2H), 7.20 (dd, J=5. 6,2.0Hz,1H),7.02–7.04(m,1H),5.80(d,J=1.3Hz,1H),5.59(d,J=0.8Hz,1H),2.39(s,3H). 13 C NMR (100MHz, CDCl3) δ159.3,150.7,147.1,143.3,143.0,142.5,141.6,141. 1,138.3,134.8,130.3,115.6,93.9,82.0,80.9,19.4.HRMS(ESI)m / z:(M+H) + Calculated for C 16 H 12 ClINO + 395.9647; Found 395.9648.

[0250] Example 34

[0251] Synthesis of compound 34:

[0252]

[0253] Substrate (0.1 mmol), furan (34 mg, 0.5 mmol) and KOH (28 mg, 0.5 mmol) were added to the reaction tube. MeCN was used as solvent, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was evaporated to dryness, and the product was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 34 (29.9 mg, 79%).

[0254] The characterization results of compound 34 are as follows:

[0255] 1 H NMR (400MHz, CDCl3) δ8.62(dd,J=4.8,1.6Hz,1H),8.25(dd,J=8.0,1.6Hz,1H),7.24(d,J=8.4Hz,1H),7.17(dd,J=5.6,1 .8Hz,1H),7.07–7.12(m,1H),6.97(dd,J=8.0,4.8Hz,1H),6.66(d,J=8.4Hz,1H),6.00(s,1H),5.63(s,1H),3.87(s,3H). 13C NMR (100MHz, CDCl3) δ159.9,153.0,151.6,148.5,147.6,143.0,142.8,135.3,128.7,127.9,123.1,109.4,94.3,82.4,80.1,55.7.HRMS (ESI) m / z: (M) + Calculated for C 16 H 13 INO2 + 377.9986; Found 377.9989. Example 35

[0256] Synthesis of compound 35:

[0257]

[0258] The substrate (0.1 mmol), furan (34 mg, 0.5 mmol) and KOH (28 mg, 0.5 mmol) were added to the reaction tube. MeCN was used as the solvent, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was evaporated to dryness, and the product was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 35 (35.9 mg, 83%).

[0259] The characterization results of compound 35 are as follows:

[0260] 1 H NMR (400MHz, CDCl3) δ8.64(dd,J=4.8,1.4Hz,1H),8.28(dd,J=8.0,1.5Hz,1H),7.28(s,1H),7.19(dd ,J=5.4,1.9Hz,1H),7.08–7.00(m,2H),6.92(dd,J=8.5,0.7Hz,1H),5.99(s,1H),5.59–5.67(m,1H). 13 C NMR (100MHz, CDCl3) δ158.9,152.2,148.7,147.7,143.3,142.1,141.9,141.2,133 .7,128.2,123.7,120.5(q,J=256Hz),118.6,93.9,82.4,80.3.HRMS(ESI)m / z:(M) + Calculated for C 16 H 10 F3INO2 + 431.9703; Found 431.9765.

[0261] Example 36

[0262] Synthesis of compound 36:

[0263]

[0264] The substrate (0.1 mmol), furan (34 mg, 0.5 mmol) and KOH (28 mg, 0.5 mmol) were added to the reaction tube. MeCN was used as the solvent, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was evaporated to dryness, and the product was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 36 (31.6 mg, 76%).

[0265] The characterization results of compound 14 are as follows:

[0266] 1 H NMR (500MHz, CDCl3) δ8.66 (dd, J=4.6, 1.3Hz, 1H), 8.29 (dd, J=8.0, 1.4Hz, 1H), 7.23–7.34 ( m,2H),7.20(dd,J=5.5,1.8Hz,1H),7.02–7.08(m,2H),6.07(s,1H),5.64(d,J=0.8Hz,1H). 13 C NMR (125MHz, CDCl3) δ158.9,150.3,148.7,148.4,147.7,143.7,142.1,137.4,126.5,12 5.0,123.9(q,J=217Hz),123.4(q,J=26Hz),120.7,93.7,81.7,81.6.HRMS(ESI)m / z:(M) + Calculated for C 16 H 10 F3INO + 415.9754; Found 415.9792.

[0267] Example 37

[0268] Synthesis of compound 37:

[0269]

[0270] Substrate (0.1 mmol), furan (34 mg, 0.5 mmol) and KOH (28 mg, 0.5 mmol) were added to the reaction tube. MeCN was used as solvent, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was evaporated to dryness, and the product was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 37 (27.5 mg, 75%).

[0271] The characterization results of compound 37 are as follows:

[0272] 1 H NMR (400MHz, CDCl3) δ8.63(dd,J=4.8,1.4Hz,1H),8.27(dd,J=8.0,1.5Hz,1H),7.16–7.24(m,2H),7.08(dd ,J=5.6,1.8Hz,1H),7.00(dd,J=8.0,4.6Hz,1H),6.77(t,J=8.4Hz,1H),6.03(d,J=0.8Hz,1H),5.63(s,1H). 13 C NMR (100MHz, CDCl3) δ159.2,156.9,154.4,152.7,148.6,147.7,143.2,142.3,133.9,128.6,123.5,113.4,94.1,82.4,79.5.HRMS (ESI) m / z: (M) + Calculated for C 15 H 10 FINO + 365.9786; Found 365.9836.

[0273] Example 38

[0274] Synthesis of compound 38:

[0275]

[0276] The substrate (0.1 mmol), furan (34 mg, 0.5 mmol) and KOH (28 mg, 0.5 mmol) were added to the reaction tube. MeCN was used as the solvent, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was evaporated to dryness, and the product was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 38 (24.1 mg, 63%).

[0277] The characterization results of compound 38 are as follows:

[0278] 1 H NMR (400MHz, CDCl3) δ8.64 (dd, J=4.8, 1.2Hz, 1H), 8.27 (dd, J=8.0, 1.2Hz, 1H), 7.15–7 .22(m,2H),7.11(dd,J=5.6,1.6Hz,1H),6.96–7.05(m,2H),5.94(s,1H),5.64(s,1H). 13C NMR (100MHz, CDCl3) δ159.1,151.2,148.7,147.7,147.4,143.4,142.1,133.3,127.7,126.7,125.2,123.6,93.9,82.8,81.3.HRMS (ESI) m / z: (M) + Calculated for C 15 H 10 ClINO + 381.9490; Found 381.9531.

[0279] Example 39

[0280] Synthesis of compound 39:

[0281]

[0282] The substrate (0.1 mmol), furan (34 mg, 0.5 mmol) and KOH (28 mg, 0.5 mmol) were added to the reaction tube. MeCN was used as the solvent, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was evaporated to dryness, and the product was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 39 (32.6 mg, 85%).

[0283] The characterization results of compound 39 are as follows:

[0284] 1 H NMR (500MHz, CDCl3) δ8.58–8.69(m,1H),8.22–8.31(m,1H),7.16–7.28(m,1H),6.95–7.11(m,3H),6.02(s,1H),5.60(s,1H). 13 C NMR (125MHz, CDCl3) δ158.1,148.6,147.8,146.5,143.7,141.8,136.6,136.5,123.9,114.4,114.3,93.8,82.2,79.7.HRMS(ESI)m / z:(M+H) + Calculated for C 15 H9F2INO + 383.9691; Found 383.9772.

[0285] Example 40

[0286] Synthesis of compound 40:

[0287]

[0288] The substrate (0.1 mmol), furan (34 mg, 0.5 mmol) and KOH (28 mg, 0.5 mmol) were added to the reaction tube. MeCN was used as the solvent, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 40 (33.0 mg, 73%).

[0289] The characterization results of compound 40 are as follows:

[0290] 1 H NMR (400MHz, CDCl3) δ8.64(dd,J=4.8,1.6Hz,1H),8.28(dd,J=8.0,1.6Hz,1H),7.35(s,1H),7.21(dd,J=5.6 ,2.0Hz,1H),7.10(dd,J=5.6,2.0Hz,1H),7.04(dd,J=8.0,4.8Hz,1H),5.90–5.95(m,1H),5.62–5.66(m,1H). 13 C NMR (100MHz, CDCl3) δ158.0,150.0,149.5,148.8,147.8,143.8,141.8,133.9,128.7,127.8,125.5,124.0,93.8,82.8,82.0.HRMS (ESI) m / z: (M) + Calculated for C 15 H9Cl2INO + 415.9100; Found 415.9081.

[0291] Example 41

[0292] Synthesis of compound 41:

[0293]

[0294] The substrate (0.1 mmol), furan (34 mg, 0.5 mmol) and KOH (28 mg, 0.5 mmol) were added to the reaction tube. MeCN was used as the solvent, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was evaporated to dryness, and the product was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 41 (27.4 mg, 70%).

[0295] The characterization results of compound 41 are as follows:

[0296] 1H NMR(500MHz,CD3OD)δ8.56(d,J=4.5Hz,1H),8.41(d,J=8.0Hz,1H),7.05–7. 15(m,3H),6.83(s,1H),6.21(s,1H),5.40(s,1H),3.97(s,3H),2.18(s,3H). 13 C NMR (125MHz, CD3OD) δ161.7,153.5,152.8,149.6,149.5,149.3,143.6,143.3,13 4.8,130.5,129.0,127.7,125.1,96.2,83.1,82.5,60.2,16.4.HRMS(ESI)m / z:(M) + Calculated for C 17 H 15 INO2 + 392.0142; Found 392.0530.

[0297] Example 42

[0298] Synthesis of compound 42:

[0299]

[0300] The substrate (0.1 mmol), furan (34 mg, 0.5 mmol) and KOH (28 mg, 0.5 mmol) were added to the reaction tube. MeCN was used as the solvent, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was evaporated to dryness, and the product was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 42 (35.4 mg, 80%).

[0301] The characterization results of compound 42 are as follows:

[0302] 1 H NMR (501MHz, CDCl3) δ8.30–8.33(m,1H),7.95–8.05(m,2H),7.42–7.51(m,4H),7.36(dd,J=8.8,4.4Hz,1H),7.24(d d,J=5.6,2.0Hz,1H),7.11(dd,J=5.6,2.0Hz,1H),6.79(t,J=8.4Hz,1H),6.04–6.05(m,1H),5.73(d,J=1.6Hz,1H). 13 C NMR (125MHz, CDCl3)δ

[0303] 158.5,156.7,156.4,154.8,153.0,148.6,143.5,142.3,138.1,133.8,129.6,129. 0,128.9,128.9,126.8,120.2,113.1,112.9,91.6,82.6,79.6.HRMS(ESI)m / z:(M+H) + Calculated for C 21 H 14 FINO + 442.0099; Found 442.0173.

[0304] Example 43

[0305] Synthesis of Compound 43

[0306]

[0307] Substrate (0.1 mmol), furan (34 mg, 0.5 mmol) and KOH (28 mg, 0.5 mmol) were added to the reaction tube. MeCN was used as solvent, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was evaporated to dryness, and the product was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 43 (30.8 mg, 73%).

[0308] The characterization results of compound 43 are as follows:

[0309] 1 H NMR (400MHz, CDCl3) δ8.10(d,J=8.0Hz,1H),7.13(d,J=5.6Hz,1H),6.98–7.05(m,1H),6.85(d ,J=8.0Hz,1H),6.67(s,1H),6.09(s,1H),5.56(s,1H),3.97(s,3H),3.85(s,3H),2.54(s,3H). 13 C NMR (100MHz, CDCl3) δ158.8,157.6,148.9,147.7,143.9,143.1,141.7,141.4,136 .5,129.3,123.2,108.7,90.0,81.8,81.1,60.4,56.4,24.0.HRMS(ESI)m / z:(M+H) + Calculated for C 18 H 17 INO3 + 422.0248; Found 422.0278.

[0310] Example 44

[0311] Synthesis of Compound 44

[0312]

[0313] The substrate (0.1 mmol), furan (34 mg, 0.5 mmol) and KOH (28 mg, 0.5 mmol) were added to the reaction tube. MeCN was used as the solvent, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was evaporated to dryness, and the product was separated by column chromatography (PE / EA = 10 / 1) to obtain a pale green liquid 44 (29.8 mg, 72%).

[0314] The characterization results of compound 44 are as follows:

[0315] 1 H NMR(500MHz,MeOD)δ8.25(d,J=8.0Hz,1H),7.23(d,J=4.0Hz,1H),7.13(dd,J=15.0,11.5Hz ,1H),7.06(d,J=8.0Hz,1H),6.97(d,J=10.0Hz,1H),5.94(s,1H),5.56(s,1H),2.52(s,3H). 13 C NMR (125MHz, CDCl3) δ159.5,158.5,157.2,155.2,152.0,149.6,145.1,142.6,135.5,125.7,115.9,114.1,91.1,83.6,82.6,23.6.HRMS (ESI) m / z: (M) + Calculated for C 16 H 11 ClFINO + 413.9552; Found 413.9596.

[0316] Example 45

[0317] Synthesis of Compound 45

[0318]

[0319] The substrate (0.1 mmol), N-methylbenzylamine (61 mg, 0.5 mmol) and tBuOK (112.2 mg, 1.0 mmol) were added to the reaction tube. Toluene was used as the solvent, and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 5 / 1) to obtain a pale green liquid 45 (29 mg, 75%).

[0320] The characterization results of compound 45 are as follows:

[0321] 1 H NMR (400MHz, CDCl3) δ9.53(s,1H),7.63(s,1H),7.59(d,J=9.2Hz,1H),7.54(d,J=8.8Hz,1H),7.38(d,J=8.8Hz,2H),7.02 (s,1H),6.89–6.91(m,3H),5.10(s,2H),4.10(s,3H),4.02-4.04(m,5H),3.95(s,3H),3.81(s,3H),2.87(t,J=5.6Hz,2H). 13 C NMR (100MHz, CDCl3) δ159.38,150.5,148.9,146.5,145.4,144.1,132.7,132.4,132.0,129.3,129.2,122.7 ,122.6,121.0,119.9,116.8,113.9,113.7,71.4,64.0,61.7,57.2,56.1,55.3,35.2.HRMS(ESI)m / z:(M+H) + Calculated for C 28 H 30 NO6476.2068; Found 476.2087.

[0322] Example 46

[0323] Synthesis of Compound 46

[0324]

[0325] The substrate (0.1 mmol), N-methyl-n-butylamine (44 mg, 0.5 mmol) and tBuOK (112.2 mg, 1.0 mmol) were added to the reaction tube. Toluene was used as the solvent, and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 5 / 1) to obtain a pale green liquid 46 (27.0 mg, 63%).

[0326] The characterization results of compound 46 are as follows:

[0327] 1H NMR (400MHz, CDCl3) δ7.92–8.04(m,3H),7.34–7.55(m,5H),7.06(td,J=7.6,1.7Hz,1H),6.86(d,J=2.0Hz,1H),6. 56(d,J=2.0Hz,1H),4.66(s,1H),3.22–3.28(m,2H),1.58–1.74(m,2H),1.38–1.52(m,2H),0.97(t,J=8.0Hz,3H). 13 C NMR (100MHz, CDCl3) δ160.5,157.1,154.7,145.5,139.9,139.8,130.4,129.6,128.8, 128.6,128.2,127.2,106.7,103.6,97.1,42.8,31.4,20.3,13.9.HRMS(ESI)m / z:(M+H) + Calculated for C 21 H 22 IN2+429.0822; Found 429.0893. Example 47

[0328] Synthesis of Compound 47

[0329]

[0330] The substrate (0.1 mmol), N-methyl-3-chloropropane (72 mg, 0.5 mmol), and tBuOK (112.2 mg, 1.0 mmol) were added to the reaction tube. Toluene was used as the solvent, and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 5 / 1) to obtain a pale green liquid 47 (39.4 mg, 84%).

[0331] The characterization results of compound 47 are as follows:

[0332] 1 H NMR (400MHz, CDCl3) δ8.01–8.08(m,2H),7.98(d,J=8.0Hz,1H),7.56(dd,J=8.0,1.6Hz,1H),7.35–7.51(m,4H),7.07(t d,J=8.0,1.6Hz,1H),6.97(d,J=2.4Hz,1H),6.68(d,J=2.4Hz,1H),3.61–3.68(m,4H),3.13(s,3H),2.10–2.21(m,2H). 13C NMR (100MHz, CDCl3) δ160.8,157.6,154.2,146.0,140.4,139.8,130.4,129.4,128.6, 128.5,128.1,127.3,105.9,102.6,97.2,48.8,42.4,38.2,30.0.HRMS(ESI)m / z:(M+H) + Calculated for C 21 H 21 ClIN2 + 463.0433; Found 463.0520.

[0333] Example 48

[0334] Synthesis of Compound 48

[0335]

[0336] The substrate (0.1 mmol), N-methylallylamine (36 mg, 0.5 mmol) and tBuOK (112.2 mg, 1.0 mmol) were added to the reaction tube. Toluene was used as the solvent, and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 5 / 1) to obtain a pale green liquid 48 (32.9 mg, 77%).

[0337] The characterization results of compound 48 are as follows:

[0338] 1 H NMR (400MHz, CDCl3) δ8.03(d,J=7.6Hz,2H),7.97(d,J=8.0Hz,1H),7.55(d,J=7.6Hz,1H),7.34–7.49(m,4H),7.06(t ,J=7.6Hz,1H),6.92(s,1H),6.67(s,1H),5.82–5.92(m,1H),5.17–5.26(m,2H),4.06(d,J=4.4Hz,2H),3.11(s,3H). 13 C NMR (100MHz, CDCl3) δ160.5,157.3,154.6,145.7,139.8,132.1,130.4,129.5,128. 6,128.5,128.1,127.4,116.9,106.1,102.8,97.2,54.1,37.6.HRMS(ESI)m / z:(M+H) + Calculated for C 21 H 20 IN2+ 427.0666; Found 427.0761.

[0339] Example 49

[0340] Synthesis of Compound 49

[0341]

[0342] The substrate (0.1 mmol), 3,4-dichlorothiophenol (90 mg, 0.5 mmol) and tBuOK (112.2 mg, 1.0 mmol) were added to the reaction tube. Toluene was used as the solvent, and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the solvent was evaporated to dryness, and the product was separated by column chromatography (PE / EA = 5 / 1) to give a white solid 49 (45.4 mg, 85%).

[0343] The characterization results of compound 49 are as follows:

[0344] 1 H NMR (500MHz, CDCl3) δ8.03(d,J=7.0Hz,2H),7.96(d,J=8.0Hz,1H),7.72(d,J=2.0Hz,1H),7.39–7.55(m,8H),7.05–7.13(m,2H). 13 C NMR (125MHz, CDCl3) δ160.5,157.1,148.4,144.4,139.9,138.5,135.7,134.0,133.8,133.4,1 31.5,130.5,130.3,129.9,129.4,128.7,128.3,127.2,120.5,117.1,96.6.HRMS(ESI)m / z:(M) + Calculated for C 23 H 15 Cl2INS + 533.9342; Found 533.9343.

[0345] Example 50

[0346] Synthesis of Compound 50

[0347]

[0348] The substrate (0.1 mmol), tert-butanol (37 mg, 0.5 mmol), and tBuOK (112.2 mg, 1.0 mmol) were added to the reaction tube. Toluene was used as the solvent, and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 5 / 1) to obtain a pale green liquid 50 (31.8 mg, 74%).

[0349] The characterization results of compound 50 are as follows:

[0350] 1 H NMR (400MHz, CDCl3) δ8.05(d,J=7.6Hz,2H),7.98(d,J=8.0Hz,1H),7.56(d,J=7.2Hz, 1H),7.37–7.50(m,4H),7.30(s,1H),7.11(t,J=7.6Hz,1H),7.05(s,1H),1.57(s,9H). 13 C NMR(100MHz, CDCl3)δ139.8,130.6,130.0,129.4,128.7,128.2,127.4,114.8,112.5,96.9,29.0,28.8HRMS(ESI)m / z:(M+H) + Calculated for C 21 H 21 INO + 430.0662; Found 430.0687. Example 51

[0351] Synthesis of Compound 51

[0352]

[0353] The substrate (0.1 mmol), 4-methoxyphenol (62 mg, 0.5 mmol) and tBuOK (112.2 mg, 1.0 mmol) were added to the reaction tube. Toluene was used as the solvent, and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 5 / 1) to obtain a pale green liquid 51 (24.0 mg, 50%).

[0354] The characterization results of compound 51 are as follows:

[0355] 1H NMR(400MHz, CDCl3)δ8.03(d,J=7.6Hz,2H),7.96(d,J=8.0Hz,1H),7.37–7.54 (m,5H),7.25–7.28(m,1H),7.01–7.16(m,3H),6.89–6.99(m,3H),3.84(s,3H). 13 C NMR (100MHz, CDCl3) δ166.3,161.9,158.6,157.1,147.4,134.0,130.3,129.8,129.2,128.7 ,128.2,127.3,122.1,117.9,115.2,114.6,110.6,107.5,96.7,55.7.HRMS(ESI)m / z:(M+H) + Calculated for C 24 H 19 INO2 + 480.0455; Found 480.0467.

[0356] Example 52

[0357] Synthesis of Compound 52

[0358]

[0359] The substrate (0.1 mmol), benzyl azide (67 mg, 0.5 mmol) and tBuOK (112.2 mg, 1.0 mmol) were added to the reaction tube. Toluene was used as the solvent, and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 5 / 1) to obtain a pale green liquid 52 (23.0 mg, 47%).

[0360] The characterization results of compound 52 are as follows:

[0361] 1 H NMR (400MHz, CDCl3) δ8.08–8.13(m,3H),7.81(d,J=7.6Hz,1H),7.59(s,1H) ,7.54(t,J=7.6Hz,1H),7.33–7.51(m,8H),7.21(t,J=8Hz,1H),5.92(s,2H). 13C NMR (100MHz, CDCl3) δ154.1,153.0,141.0,140.5,140.5,138.8,138.6,135.9,134.0,131.8,13 0.7,129.3,129.2,128.9,128.8,128.7,127.8,127.68,99.6,96.5,52.6.HRMS(ESI)m / z:(M+H) + Calculated for C 24 H 18 IN4+489.0571;Found 489.0650.

[0362] Example 53

[0363] Synthesis of Compound 53

[0364]

[0365] The substrate (0.1 mmol), 4-methoxyaniline (37 mg, 0.3 mmol) and KOH (28 mg, 0.5 mmol) were added to the reaction tube. MeCN was used as the solvent, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was evaporated to dryness, and the product was separated by column chromatography (PE / EA = 5 / 1) to give a white solid 53 (38.0 mg, 78%).

[0366] The characterization results of compound 53 are as follows:

[0367] 1 H NMR (400MHz, CDCl3) δ8.67(dd,J=4.8,1.6Hz,1H),8.31(dd,J=8.0,1.6Hz,1H),7.30(d,J=8.4Hz,1H),7. 06–7.12(m,2H),7.03(dd,J=8.0,4.8Hz,1H),6.81–6.91(m,3H),6.73(m,1H),6.25(s,1H),3.80(s,3H). 13 C NMR (100MHz, CDCl3) δ159.6,158.1,156.2,150.5,148.7,148.4,144.9,134.0,132.2,126. 5,124.0,123.7,120.8(q,J=178Hz),114.8,110.1,106.8,96.5,55.5.HRMS(ESI)m / z:(M+H) + Calculated for C 19 H 15 F3IN2O2 +487.0125; Found 487.1266. Example 54

[0368] Synthesis of Compound 54

[0369]

[0370] The substrate (0.1 mmol), benzyl azide (40 mg, 0.3 mmol) and KOH (28 mg, 0.5 mmol) were added to the reaction tube. MeCN was used as the solvent, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 5 / 1) to obtain a pale green liquid 54 (30 mg, 75%).

[0371] The characterization results of compound 54 are as follows:

[0372] 1 H NMR (400MHz, CDCl3) δ8.62 (dd, J=4.8, 1.4Hz, 1H), 8.10 (dd, J=8.0, 1.4Hz, 1H), 7.38 (d, J=8.0Hz,1H),7.25–7.30(m,1H),7.00–7.20(m,4H),6.43(d,J=7.6Hz,2H),5.66(s,2H). 13 C NMR (100MHz, CDCl3) δ157.2,148.0,147.4,140.4,140.2,135.1,132.2,130.2,128. 6,128.1,125.7,124.8,124.4,120.7(q,J=258Hz),113.3,97.0.HRMS(ESI)m / z:(M) + Calculated for C 19 H 13 F3IN4O + 497.0081; Found 497.0123.

[0373] Example 55

[0374] Synthesis of Compound 55

[0375]

[0376] The substrate (0.1 mmol), pyridine NO compound (29 mg, 0.3 mmol) and KOH (28 mg, 0.5 mmol) were added to the reaction tube. MeCN was used as the solvent, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was evaporated to dryness, and the product was separated by column chromatography (PE / EA = 5 / 1) to give a white solid 55 (33.5 mg, 73%).

[0377] The characterization results of compound 55 are as follows:

[0378] 1 H NMR (400MHz, CDCl3) δ11.42(s,1H),8.61(d,J=24Hz,2H),8.52(dd,J=4.8,1.6Hz,1H),8.44(dd,J=8 .0,1.5Hz,1H),8.12(d,J=8.8Hz,1H),7.78(d,J=8.0Hz,1H),7.36–7.44(m,1H),6.95–7.08(m,2H). 13 C NMR (100MHz, CDCl3) δ157.2,155.9,151.1,151.0,148.4,148.3,146.5,138.3 ,131.6,123.6,123.1,121.6,120.6,118.9,110.1,91.6.HRMS(ESI)m / z:(M+H) + Calculated for C 17 H 11 F3IN2O2 + 458.9812; Found 458.982.

[0379] Example 56

[0380] Synthesis of Compound 56

[0381]

[0382] The substrate (0.1 mmol), n-butylamine (22 mg, 0.3 mmol) and KOH (28 mg, 0.5 mmol) were added to the reaction tube. MeCN was used as the solvent, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 5 / 1) to obtain a pale green liquid 56 (33.0 mg, 76%).

[0383] The characterization results of compound 56 are as follows:

[0384] 1H NMR (400MHz, CDCl3) δ8.64(dd,J=7.6,3.6Hz,1H),8.30(dd,J=7.2,3.6Hz,1H),7.17(d,J=8.4Hz,1H),7.01(dd,J=8.0,4.8Hz,1H),6.6 0(dd,J=8.4,1.2Hz,1H),6.55(s,1H),3.62(s,1H),3.08(t,J=7.2Hz,2H),1.50–1.58(m,2H),1.29–1.43(m,2H),0.91(t,J=7.2Hz,3H). 13 C NMR (100MHz, CDCl3) δ159.9,151.0,148.8,148.3,147.0,131.6,125.0,123.7,120 .5(q,J=256Hz),107.6,103.6,96.6,43.4,31.1,20.2,13.8..HRMS(ESI)m / z:(M+H) + Calculated for C 16 H 17 F3IN2O + 437.033; Found 437.0431.

[0385] Example 57

[0386] Synthesis of Compound 57

[0387]

[0388] The substrate (0.1 mmol), diphenyl sulfoxide (61 mg, 0.3 mmol) and KOH (28 mg, 0.5 mmol) were added to the reaction tube. MeCN was used as the solvent, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was evaporated to dryness, and the product was separated by column chromatography (PE / EA = 5 / 1) to give a white solid 57 (35.6 mg, 63%).

[0389] The characterization results of compound 57 are as follows:

[0390] 1 H NMR(400MHz, CDCl3)δ8.54(dd,J=4.8,1.2Hz,1H),8.07(dd,J=8.0,1.2Hz,1H),7.84–7.86(m,4H), 7.33–7.56(m,6H),7.33(d,J=8.0Hz,1H),6.85(dd,J=8.0,4.8Hz,1H),6.31(dd,J=8.0,1.6Hz,1H). 13C NMR (100MHz, CDCl3) δ169.7,161.5,151.0,148.2,146.6,136.9,135.6,132.2,13 0.6,129.8,126.5,122.7,121.7,119.1,100.6,97.8,93.4.HRMS(ESI)m / z:(M+H) + Calculated for C 24 H 16 F3INO2S + 565.9893; Found 565.9921.

[0391] Example 58

[0392] Synthesis of Compound 58

[0393]

[0394] The substrate (0.1 mmol), 4-methoxyphenol (37 mg, 0.3 mmol) and KOH (28 mg, 0.5 mmol) were added to the reaction tube. MeCN was used as the solvent, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 5 / 1) to obtain a pale green liquid 58 (33.2 mg, 68%).

[0395] The characterization results of compound 58 are as follows:

[0396] 1 H NMR (400MHz, CDCl3) δ8.64(d,J=4.8Hz,1H),8.21(d,J=8.0Hz,1H),7.33(d,J=8 .4Hz,1H),6.97–7.06(m,4H),6.86(d,J=8.8Hz,2H),6.63(s,1H),3.79(s,3H). 13 C NMR (100MHz, CDCl3) δ159.0,156.8,156.6,150.2,149.1,148.5,148.4,147.7,146.8 ,131.4,131.0,123.8,121.7,115.0,114.0,108.9,97.1,55.6.HRMS(ESI)m / z:(M+H) + Calculated for C 19 H 14 F3INO3 + 487.9965; Found 487.9969.

[0397] Example 59

[0398] Synthesis of Compound 59

[0399]

[0400] The substrate (0.1 mmol), potassium sulfide (33 mg, 0.3 mmol) and KOH (28 mg, 0.5 mmol) were added to the reaction tube. MeCN was used as the solvent, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was evaporated to dryness, and the product was separated by column chromatography (PE / EA = 5 / 1) to obtain a white solid 59 (25.0 mg, 92%).

[0401] The characterization results of compound 59 are as follows:

[0402] 1 H NMR (400MHz, CDCl3) δ8.76(d,J=4.4Hz,1H),8.51(d,J=8.8Hz,1H),8.18(dd,J=8.0,1.2Hz,1H),7.72(s,1H),7.34–7.46(m,2H). 13 C NMR (101MHz, CDCl3) δ151.0,149.2,147.0,140.7,134.1,133.2,130.6,124.1,121.1,120.5(q,J=257Hz),118.7,115.2.HRMS(ESI)m / z:(M+H) + Calculated for C 12 H7F3NOS + 270.0195; Found 270.0231.

[0403] Example 60

[0404] Synthesis of Compound 60

[0405]

[0406] The substrate (0.1 mmol), tetramethylthiourea (40 mg, 0.3 mmol) and KOH (28 mg, 0.5 mmol) were added to the reaction tube. MeCN was used as the solvent, and the reaction was carried out at room temperature for 24 h. After the reaction was completed, the solvent was evaporated to dryness, and the mixture was separated by column chromatography (PE / EA = 5 / 1) to obtain a pale green liquid 60 (38.5 mg, 78%).

[0407] The characterization results of compound 60 are as follows:

[0408] 1H NMR (400MHz, CDCl3) δ8.73–8.82(m,2H),8.34(dd,J=8.4,1.6Hz,1H),7.58–7.66(m,1H),7.50(dd,J=8.4,4.8Hz,1H),3.79(s,6H),3.07(s,6H). 13 C NMR (100MHz, CDCl3) δ162.9,149.59,148.1,146.4,141.1,135.0,133.9,131.5,1 28.8,122.5,121.4,120.1(q,J=260Hz),118.8,118.3,116.1.HRMS(ESI)m / z:(M) + Calculated for C 17 H 18 F3N3OS + 369.1117; Found 369.1165.

[0409] The scope of protection of this invention is not limited to the above embodiments. Any variations and advantages that can be conceived by those skilled in the art without departing from the spirit and scope of this invention are included in this invention and are protected by the appended claims.

Claims

1. A pyridyne-benzyne diaromaticyne precursor, characterized in that, The pyridyne-benzyne diaromatic precursor is a diaryl cyclic highiodide salt, with the structure shown in Formula 1 below: Among them, R 1 R 2 R 3 R 4 R 5 Each of the following is independently selected from one or more of hydrogen, alkyl, alkoxy, trifluoromethyl, trifluoromethoxy, aryl, silyl, and halogen.

2. The pyridyne-benzyne diaromaticyne precursor as described in claim 1, characterized in that, R 1 R 2 R 3 R 4 R 5 The compounds are independently selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, methoxy, trifluoromethoxy, trifluoromethyl, phenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-aldehydephenyl, 4-formylphenyl, as well as thiophene, thiazole, benzothiophene, benzothiazole, benzoisothiazole, dibenzothiophene, phenothiazine, thianthracene, alkoxy, dimethylamino, and halogen.

3. The pyridyne-benzyne diaromaticyne precursor as described in claim 1, characterized in that, The structural formula of the pyridyne-benzyne diaromaticyne precursor includes the following:

4. A method for synthesizing a pyridyne-benzyne diaromaticyne precursor, characterized in that, The method includes the following steps: Step (1): Using substituted 2-halo-3-aminopyridine as raw material, under the conditions of Pd catalyst, solvent, base and ligand, it undergoes Suzuki coupling reaction with polysubstituted arylboronic acid to obtain intermediate 1; Step (2): The intermediate 1 obtained in step (1) is subjected to diazotization in the presence of acid, additives and solvent to replace the amino group with iodine to obtain intermediate 2; Step (3): The intermediate 2 obtained in step (2) is oxidized in the presence of acid, oxidant, and solvent to obtain diarylpyridine periodic salt; the reaction equation is shown below: R contains R 4 R 5 R' contains R 1 R 2 R 3 X is a halogen; where R 1 R 2 R 3 R 4 R 5 The definition is the same as in claim 1.

5. The preparation method as described in claim 3, characterized in that, In step (1), the Pd catalyst is one or more of Pd(OAc)2, Pd(dba)2, Pd2(dba)3, Pd(Ph3P)4, PdCl2, and Pd(MeCN)2Cl2; and / or, the ligand is one or more of Dave-Phos, X-Phos, S-Phos, Ph3P, (Ph2P)2(CH2)2, (Ph2P)2(CH2)3, (Ph2P)2(CH2)4, and tBu-Phos; and / or, the molar ratio of the substituted 2-halo-3-aminopyridine, the base, the Pd catalyst, and the ligand is 1:1-10:0.01-1:0.01-1.

6. The preparation method as described in claim 3, characterized in that, In step (1), the solvent is one or more of PhMe, MeOH, EtOH, H2O, THF, dioxane, EtOAc, MeCN, DCM, and DMF; and / or, the base is one or more of Na2CO3, K2CO3, NaOH, KOH, tBuOLi, tBuONa, tBuOK, LiHMDS, and LDA; and / or, the reaction temperature is room temperature - 120°C.

7. The preparation method as described in claim 3, characterized in that, In step (2), the acid is one or more of H2SO4, HCl, TFA, TfOH, TsOH, and HBF4; and / or, the additive is one or more of NaNO2, KNO2, and tBuONO; and / or, the molar ratio of intermediate 1, acid, additive, and iodine source is 1:1-10:0.5-2:0.5-2.

8. The preparation method as described in claim 3, characterized in that, In step (2), the solvent is one or more of PhMe, MeOH, EtOH, H2O, THF, dioxane, EtOAc, MeCN, DCM, and DMF; and / or, the iodine source used is one or more of NaI, I2, KI, and TBAI; and / or, the reaction temperature is -80–100℃.

9. The preparation method as described in claim 3, characterized in that, In step (3), the oxidant is one or more of H2O2, m-CPBA, and NaIO4; and / or, the acid is one or more of H2SO4, HCl, TFA, TfOH, TsOH, and HBF4; and / or, the solvent is one or more of PhMe, MeOH, EtOH, H2O, THF, dioxane, EtOAc, MeCN, DCM, and DMF; and / or, the reaction temperature is -80–100℃; and / or, the molar ratio of intermediate 2, acid, and oxidant is 1:1–10:1–5.

10. The use of the pyridyne-benzyne biaromaticyne precursor as described in claim 1 in the preparation of multisubstituted pyridines, pyridine heteroatom nucleophilic products, and benzene ring derivatives.

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