CN111138430A

CN111138430A - Method for synthesizing imidazole-containing fused heterocyclic compound

Info

Publication number: CN111138430A
Application number: CN202010083616.5A
Authority: CN
Inventors: 沈娜娜; 李彬; 范学森; 张新迎; 杨玉洁
Original assignee: Henan Normal University
Current assignee: Henan Normal University
Priority date: 2020-02-10
Filing date: 2020-02-10
Publication date: 2020-05-12

Abstract

The invention discloses a method for synthesizing imidazole-containing fused heterocyclic compounds, which comprises the steps of synthesizing 3-formyl-2-aryl imidazo [1,2-a]Pyridine or 3-formyl-2-heteroaryl imidazo [1,2-a]Pyridine compounds, 5-formyl-6-arylimidazo [2,1-b]Thiazole or 5-formyl-6-heteroarylimidazo [2,1-b]Thiazole compound or 3-formyl-2-arylbenzo [2 ], [ solution of a salt of a carboxylic acidd]Imidazo [2,1-b]Thiazole or 3-formyl-2-heteroarylbenzo [2 ]d]Imidazo [2,1-b]The thiazole compound and the cyclic α -diazo-1, 3-diketone compound are subjected to a series reaction to synthesize a target product, namely the imidazole fused heterocyclic compound.

Description

Method for synthesizing imidazole-containing fused heterocyclic compound

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of imidazole-containing fused heterocyclic compounds.

Background

Imidazole is an important nitrogen-containing heterocyclic compound and has biological activities of resisting cancer, malaria, tumor, bacteria, virus and the like. Furthermore, imidazoles are also the main building blocks of many natural products and organic functional molecules. The imidazopyridine compound is a special imidazole-containing fused heterocyclic compound and has wide application in the fields of pharmaceutical chemistry, material science and the like. In the field of medicinal chemistry, there are currently a number of marketed drugs containing an imidazopyridine skeleton, such as: zolpidem (Zolpidem), Olprinone (Olprinone), thalipidem (Saripideem), necopiden (Necopidem), and the like. In addition, the compounds also have biological activities of diminishing inflammation, resisting bacteria, resisting viruses, resisting tumors and the like; in the field of material science, imidazopyridine compounds are widely applied to biological probes, fluorescent dyes, photoelectric materials and the like. In view of the importance of the compounds, researchers develop various methods for synthesizing imidazole-containing fused heterocyclic compounds, but the developed methods have the defects of difficult obtainment of raw materials, multiple reaction steps, harsh reaction conditions, high environmental factors and the like, so that the application of the developed methods in actual production is limited to a certain extent. Therefore, research and development of a novel method for synthesizing the imidazole-containing fused heterocyclic compound from cheap and easily available raw materials under mild reaction conditions through simple operation steps have important theoretical significance and important application value.

Disclosure of Invention

The technical problem solved by the invention is to provide a synthesis method of imidazole-fused heterocyclic compounds, the synthesis method synthesizes target products of imidazole-fused heterocyclic compounds through the series reaction between 3-formyl-2-aryl imidazo [1,2-a ] pyridine or 3-formyl-2-heteroaryl imidazo [1,2-a ] pyridine compounds, 5-formyl-6-aryl imidazo [2,1-b ] thiazole or 5-formyl-6-heteroaryl imidazo [2,1-b ] thiazole compounds or 3-formyl-2-aryl benzo [ d ] imidazo [2,1-b ] thiazole compounds or 3-formyl-2-heteroaryl benzo [ d ] imidazo [2,1-b ] thiazole compounds and cyclic α -diazo-1, 3-diketone compounds, and the method has the advantages of simple operation, mild conditions, wide substrate application range and the like, and is suitable for industrial production.

The invention adopts the following technical scheme for solving the technical problems, and the synthesis method of the imidazole-containing fused heterocyclic compound is characterized in that the specific synthesis process comprises the steps of dissolving 3-formyl-2-aryl imidazo [1,2-a ] pyridine or 3-formyl-2-heteroaryl imidazo [1,2-a ] pyridine compound 1 and cyclic α -diazo-1, 3-diketone compound 2 in a solvent, adding a catalyst and an additive, and reacting at 80-140 ℃ to obtain the target product imidazole-containing fused heterocyclic compound 3, wherein the reaction equation in the synthesis method is as follows:

wherein R is¹Is hydrogen, fluorine, chlorine, bromine, trifluoromethyl, methyl or methoxy, R²Is 2-thienyl, 1-naphthyl, phenyl or substituted phenyl, the substituent in the substituted phenyl is fluorine, chlorine, bromine, methyl, methoxy, trifluoromethyl or phenyl, R³Is 1, 2-phenyl, 1, 8-naphthyl, C_2-6Alkyl, monosubstituted C_2-6Alkyl or disubstituted C_2-6Alkyl radical, the monosubstituted C_2-6Alkyl or disubstituted C_2-6The substituent in the alkyl group being C_1-6The catalyst is dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, bis (hexafluoroantimonate) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III), bis (pentamethylcyclopentadienyl) rhodium (III) diacetate (pentamethylcyclopentadienyl) rhodium (III) or dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, and the additive is zinc acetate, silver hexafluoroantimonate, sodium acetate, potassium acetate, cesium acetate, copper acetate, acetic acid, trimethylacetic acid, 2,4, 6-trimethylbenzoic acid, 1-adamantanic acid or trifluoroacetic acid.

More preferably, the ratio of the amount of the 3-formyl-2-arylimidazo [1,2-a ] pyridine or 3-formyl-2-heteroarylimidazo [1,2-a ] pyridine compound 1 to the amount of the cyclic α -diazo-1, 3-dione compound 2 to the amount of the catalyst and the additive is 1:1-2:0.05: 0-3.

More preferably, the ratio of the amount of the 3-formyl-2-arylimidazo [1,2-a ] pyridine or 3-formyl-2-heteroarylimidazo [1,2-a ] pyridine compound 1 to the amount of the cyclic α -diazo-1, 3-dione compound 2 to the amount of the catalyst and the additive is 1:1-2:0.05: 0.1-3.

A synthetic method of imidazole-containing fused heterocyclic compounds is characterized in that the specific synthetic process comprises the steps of dissolving 5-formyl-6-aryl imidazo [2,1-b ] thiazole or 5-formyl-6-heteroaryl imidazo [2,1-b ] thiazole compounds 1 and cyclic α -diazo-1, 3-diketone compounds 2 in a solvent, adding a catalyst and an additive, and reacting at 80-140 ℃ to obtain target products, namely imidazole-containing fused heterocyclic compounds 3, wherein the reaction equation in the synthetic method is as follows:

wherein R is¹Is 2-thienyl, 1-naphthyl, phenyl or substituted phenyl, the substituent in the substituted phenyl is fluorine, chlorine, bromine, methyl, methoxy, trifluoromethyl or phenyl, R²Is 1, 2-phenyl, 1, 8-naphthyl, C_2-6Alkyl, monosubstituted C_2-6Alkyl or disubstituted C_2-6Alkyl radical, the monosubstituted C_2-6Alkyl or disubstituted C_2-6The substituent in the alkyl group being C_1-6The catalyst is dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, bis (hexafluoroantimonate) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III), bis (pentamethylcyclopentadienyl) rhodium (III) diacetate (pentamethylcyclopentadienyl) rhodium (III) or dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, and the additive is zinc acetate, silver hexafluoroantimonate, sodium acetate, potassium acetate, cesium acetate, copper acetate, acetic acid, trimethylacetic acid, 2,4, 6-trimethylbenzoic acid, 1-adamantanic acid or trifluoroacetic acid.

Further preferably, the ratio of the amount of the 5-formyl-6-arylimidazo [2,1-b ] thiazole or 5-formyl-6-heteroarylimidazo [2,1-b ] thiazole compound 1, the cyclic α -diazo-1, 3-dione compound 2, the catalyst and the additive is 1:1-2:0.05: 0-3.

Further preferably, the ratio of the amount of the 5-formyl-6-arylimidazo [2,1-b ] thiazole or 5-formyl-6-heteroarylimidazo [2,1-b ] thiazole compound 1, the cyclic α -diazo-1, 3-dione compound 2, the catalyst and the additive is 1:1-2:0.05: 0.1-3.

A synthetic method of imidazole-containing fused heterocyclic compounds is characterized in that the specific synthetic process comprises the steps of dissolving 3-formyl-2-aryl benzo [ d ] imidazo [2,1-b ] thiazole or 3-formyl-2-heteroaryl benzo [ d ] imidazo [2,1-b ] thiazole compounds 1 and cyclic α -diazo-1, 3-diketone compounds 2 in a solvent, adding a catalyst and an additive, and reacting at 80-140 ℃ to obtain target products, namely imidazole-containing fused heterocyclic compounds 3, wherein the reaction equation in the synthetic method is as follows:

Further preferably, the ratio of the amount of the 3-formyl-2-arylbenzo [ d ] imidazo [2,1-b ] thiazole or 3-formyl-2-heteroarylbenzo [ d ] imidazo [2,1-b ] thiazole compound 1 to the amount of the cyclic α -diazo-1, 3-dione compound 2 to the amount of the catalyst and the additive is 1:1-2:0.05: 0-3.

Further preferably, the ratio of the amount of the 3-formyl-2-arylbenzo [ d ] imidazo [2,1-b ] thiazole or 3-formyl-2-heteroarylbenzo [ d ] imidazo [2,1-b ] thiazole compound 1 to the amount of the cyclic α -diazo-1, 3-dione compound 2 to the amount of the catalyst and the additive is 1:1-2:0.05: 0.1-3.

Compared with the prior art, the invention has the following advantages: (1) the raw materials are cheap and easy to obtain or easy to prepare; (2) the synthesis process is a one-pot series reaction, is simple and efficient, and avoids resource waste and environmental pollution; (3) the reaction condition is mild, and the operation is simple and convenient; (4) the atom economy of the reaction is high; (5) the application range of the substrate is wide. Therefore, the invention provides a simple, high-efficiency, economical and practical novel method for synthesizing imidazole-containing fused heterocyclic compounds.

Detailed Description

The present invention is described in further detail below with reference to examples, but it should not be construed that the scope of the above subject matter of the present invention is limited to the following examples, and that all the technologies realized based on the above subject matter of the present invention belong to the scope of the present invention.

Example 1

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (6mg,0.01mmol), and zinc acetate (37mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 120 ℃ oil bath for reaction for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and isolated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to yield the product 3aa (5mg, 8%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.89(t,J＝6.8Hz,2H),3.47(t,J＝6.8Hz,2H),3.76(s,3H),6.96(t,J＝6.8Hz,1H),7.46-7.50(m,1H),7.62-7.66(m,1H),7.68-7.71(m,1H),7.82(d,J＝9.2Hz,1H),8.40(s,1H),8.50(d,J＝6.8Hz,1H),8.80-8.84(m,2H).¹³C NMR(100MHz,CDCl₃)δ:28.7,36.3,52.0,112.1,113.5,118.1,122.4,123.1,124.7,126.88,126.93,127.6,129.0,129.20,129.25,144.2,149.2,173.7,200.6.HRMS calcd forC₂₀H₁₇N₂O₃:333.1239[M+H]⁺,found:333.1228。

example 2

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (6mg,0.01mmol), and acetic acid (12mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in an oil bath at 120 ℃ for reaction for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and isolated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to yield the product 3aa (34mg, 51%) as a white solid.

Example 3

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (6mg,0.01mmol), and potassium acetate (20mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 120 ℃ oil bath for reaction for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and isolated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to yield the product 3aa (22mg, 33%) as a white solid.

Example 4

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (6mg,0.01mmol), and sodium acetate (16mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 120 ℃ oil bath for reaction for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and isolated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to yield the product 3aa (19mg, 28%) as a white solid.

Example 5

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (6mg,0.01mmol), and cesium acetate (38mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 120 ℃ oil bath for reaction for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and isolated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to yield the product 3aa (15mg, 22%) as a white solid.

Example 6

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (6mg,0.01mmol), and copper acetate (40mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 120 ℃ oil bath for reaction for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and isolated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to yield the product 3aa (7mg, 10%) as a white solid.

Example 7

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (6mg,0.01mmol), and silver hexafluoroantimonate (7mg,0.02mmol) in that order, and then the pressure tube was sealed and placed in a 120 ℃ oil bath for reaction for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and isolated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to yield the product 3aa (28mg, 42%) as a white solid.

Example 8

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (6mg,0.01mmol), and trimethylacetic acid (20mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 120 ℃ oil bath for reaction for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and isolated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to yield the product 3aa (31mg, 46%) as a white solid.

Example 9

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (6mg,0.01mmol), and trifluoroacetic acid (23mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 120 ℃ oil bath for reaction for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and isolated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to yield the product 3aa (25mg, 37%) as a white solid.

Example 10

To a 15mL pressure resistant tube were added 1a (44mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (6mg,0.01mmol), and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure resistant tube was sealed and placed in an oil bath at 120 ℃ for reaction for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and isolated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to yield the product 3aa (41mg, 62%) as a white solid.

Example 11

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (6mg,0.01mmol), and 1-adamantanecarboxylic acid (36mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 120 ℃ oil bath for reaction for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and isolated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to yield the product 3aa (29mg, 44%) as a white solid.

Example 12

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 120 ℃ oil bath to react for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and isolated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to yield the product 3aa (52mg, 78%) as a white solid.

Example 13

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), pentamethylcyclopentadienyl rhodium (III) diacetate (7mg,0.01mmol), and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 120 ℃ oil bath for reaction for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and isolated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to yield the product 3aa (33mg, 50%) as a white solid.

Example 14

To a 15mL pressure resistant tube were added 1a (44mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer (8mg,0.01mmol), and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure resistant tube was sealed and placed in an oil bath at 120 ℃ for reaction for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and isolated on a silica gel column (vol: petroleum ether/ethyl acetate 2/1) to give the product 3aa (37mg, 55%) as a white solid.

Example 15

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and isolated on a silica gel column (vol: petroleum ether/ethyl acetate 2/1) to give the product 3aa (56mg, 84%) as a white solid.

Example 16

To a 15mL pressure resistant tube were added 1a (44mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol), and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure resistant tube was sealed and placed in an 80 ℃ oil bath to react for 12 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and isolated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to yield the product 3aa (44mg, 67%) as a white solid.

Example 17

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and the pressure tube was sealed and placed in an oil bath at 140 ℃ for reaction for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and isolated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to yield the product 3aa (47mg, 71%) as a white solid.

Example 18

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL) and bis (hexafluoroantimonate) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 12 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and isolated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to yield the product 3aa (21mg, 32%) as a white solid.

Example 19

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2b (41mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (vol.: petroleum ether/ethyl acetate: 2/1) to give the product 3ab (57mg, 82%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,DMSO-d₆)δ:1.99-2.06(m,2H),2.49-2.52(m,2H),3.32(t,J＝7.2Hz,2H),3.63(s,3H),7.24(t,J＝6.8Hz,1H),7.68-7.76(m,3H),7.91(d,J＝8.8Hz,1H),8.75(d,J＝7.6Hz,1H),8.88(d,J＝8.4Hz,1H),9.17(s,1H),9.36(d,J＝6.8Hz,1H).¹³C NMR(100MHz,DMSO-d₆)δ:20.4,33.2,51.8,112.6,116.8,117.7,123.2,123.3,126.8,127.0,127.3,127.6,127.7,128.2,129.3,130.6,143.7,149.3,173.7,202.7.HRMS calcd for C₂₁H₁₉N₂O₃:347.1396[M+H]⁺,found:347.1371。

example 20

To a 15mL pressure resistant tube were added 1a (44mg,0.2mmol), 2c (46mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, thenThen the pressure pipe is sealed and placed in an oil bath at 100 ℃ for reaction for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, dried by spinning, and separated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to give the product 3ac (59mg, 82%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:1.78-1.84(m,2H),1.86-1.93(m,2H),2.42(t,J＝7.2Hz,2H),3.17(t,J＝7.2Hz,2H),3.67(s,3H),7.01(td,J₁＝6.8Hz,J₂＝1.2Hz,1H),7.51(ddd,J₁＝9.2Hz,J₂＝6.4Hz,J₃＝1.2Hz,1H),7.65-7.74(m,2H),7.86(d,J＝9.2Hz,1H),8.35(s,1H),8.59(d,J＝6.8Hz,1H),8.80(d,J＝7.6Hz,1H),8.85(dd,J₁＝8.0Hz,J₂＝1.2Hz,1H).¹³C NMR(100MHz,CDCl₃)δ:24.6,24.7,33.9,41.5,51.6,112.1,113.1,118.2,122.6,123.2,124.8,126.95,126.99,127.03,127.6,129.1,129.3,129.9,144.1,149.2,174.0,202.8.HRMS calcd for C₂₂H₂₁N₂O₃:361.1552[M+H]⁺,found:361.1552。

example 21

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2d (50mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (vol: petroleum ether/ethyl acetate 2/1) to give the product 3ad (64mg, 85%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:1.24(s,6H),2.58(s,2H),3.33(s,2H),3.60(s,3H),6.99(td,J₁＝6.8Hz,J₂＝0.8Hz,1H),7.49(ddd,J₁＝9.2Hz,J₂＝6.8Hz,J₃＝1.2Hz,1H),7.65-7.74(m,2H),7.85(d,J＝9.2Hz,1H),8.44(s,1H),8.61(d,J＝6.4Hz,1H),8.70-8.72(m,1H),8.86(dd,J₁＝8.0Hz,J₂＝1.2Hz,1H).¹³C NMR(100MHz,CDCl₃)δ:28.6,33.7,44.7,50.9,51.2,112.0,113.1,118.1,122.5,123.3,124.8,126.8,126.9,127.1,127.4,129.0,129.1,131.6,143.8,149.1,172.9,203.2.HRMS calcd forC₂₃H₂₃N₂O₃:375.1709[M+H]⁺,found:375.1709。

example 22

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2e (46mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol), and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried and separated on a silica gel column (vol.: petroleum ether/ethyl acetate 2/1) to give the product 3ae as a white solid (62mg, 86%). The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:1.11(d,J＝6.8Hz,3H),2.39-2.51(m,2H),2.74-2.86(m,2H),3.42-3.46(m,1H),3.72(s,3H),6.99(t,J＝6.8Hz,1H),7.49(t,J＝8.0Hz,1H),7.65-7.72(m,2H),8.84(d,J＝9.2Hz,1H),8.59(s,1H),8.64(d,J＝6.4Hz,1H),8.82-8.84(m,1H),8.92(d,J＝8.0Hz,1H).¹³C NMR(100MHz,CDCl₃)δ:20.1,28.1,40.9,48.3,51.6,112.2,114.5,117.9,122.6,123.2,125.0,126.9,127.0,127.7,128.9,129.3,129.5,144.0,149.2,173.4,202.0.HRMS calcd for C₂₂H₂₁N₂O₃:361.1552[M+H]⁺,found:361.1549。

example 23

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2f (64mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 12 h. To be reversedAfter this reaction had ended, it was cooled to room temperature, filtered off with suction, spin-dried and isolated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to give the product 3af (67mg, 79%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.77(dd,J₁＝15.6Hz,J₂＝6.8Hz,1H),2.90(dd,J₁＝15.6Hz,J₂＝7.6Hz,1H),3.37(dd,J₁＝16.0Hz,J₂＝8.0Hz,1H),3.60-3.65(m,4H),3.92-4.00(m,1H),6.96(t,J＝6.8Hz,1H),7.16-7.28(m,5H),7.44-7.48(m,1H),7.55-7.59(m,1H),7.66(t,J＝7.2Hz,1H),7.80(d,J＝9.2Hz,1H),8.26(s,1H),8.48(d,J＝6.8Hz,1H),8.60(d,J＝8.4Hz,1H),8.79(d,J＝8.0Hz,1H).¹³C NMR(100MHz,CDCl₃)δ:38.9,40.5,48.0,51.7,112.1,113.7,118.0,122.5,123.1,124.9,126.88,126.94,127.0,127.5,128.7,129.2,129.3,129.4,143.0,144.1,149.2,172.6,201.1.HRMScalcd for C₂₇H₂₃N₂O₃:423.1709[M+H]⁺,found:423.1709。

example 24

To a 15mL pressure resistant tube were added 1a (44mg,0.2mmol), 2g (73mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure resistant tube was sealed and placed in a 100 ℃ oil bath to react for 12 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to give the product 3ag (70mg, 77%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.74(dd,J₁＝16.0Hz,J₂＝6.8Hz,1H),2.87(dd,J₁＝15.6Hz,J₂＝7.6Hz,1H),3.34(dd,J₁＝15.6Hz,J₂＝8.4Hz,1H),3.60-3.66(m,4H),3.72(s,3H),3.87-3.95(m,1H),6.79(d,J＝8.8Hz,2H),7.00(td,J₁＝6.8Hz,J₂＝1.2Hz,1H),7.14(d,J＝8.4Hz,2H),7.50(ddd,J₁＝9.2Hz,J₂＝6.8Hz,J₃＝1.6Hz,1H),7.57-7.62(m,1H),7.68(td,J₁＝7.6Hz,J₂＝0.8Hz,1H),7.84(d,J＝9.2Hz,1H),8.28(s,1H),8.54(d,J＝6.8Hz,1H),8.60(d,J＝8.0Hz,1H),8.82(dd,J₁＝8.0Hz,J₂＝0.8Hz,1H).¹³C NMR(100MHz,CDCl₃)δ:38.3,40.7,48.4,51.7,55.2,112.1,113.7,114.1,118.1,122.6,123.1,124.9,126.91,126.94,127.5,128.5,129.2,129.3,129.6,134.9,144.0,149.2,158.5,172.7,201.5.HRMS calcd for C₂₈H₂₅N₂O₄:453.1814[M+H]⁺,found:453.1813。

example 25

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2h (68mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol), and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (vol/vol: petroleum ether/ethyl acetate 2/1) to give the product 3ah (66mg, 76%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.27(s,3H),2.76(dd,J₁＝16.0Hz,J₂＝7.2Hz,1H),2.89(dd,J₁＝15.6Hz,J₂＝8.0Hz,1H),3.38(dd,J₁＝15.6Hz,J₂＝8.0Hz,1H),3.61-3.66(m,4H),3.90-3.97(m,1H),7.02(t,J＝6.8Hz,1H),7.07(d,J＝8.0Hz,2H),7.13(d,J＝7.6Hz,2H),7.50-7.54(m,1H),7.59-7.63(m,1H),7.69(t,J＝7.6Hz,1H),7.87(d,J＝8.8Hz,1H),8.31(s,1H),8.56(d,J＝6.8Hz,1H),8.63(d,J＝8.4Hz,1H),8.83(d,J＝8.4Hz,1H).¹³C NMR(100MHz,CDCl₃)δ:21.0,38.6,40.5,48.3,51.7,112.1,113.7,118.2,122.6,123.1,124.8,126.94,126.96,126.99,127.3,127.5,129.2,129.35,129.41,129.6,136.6,140.0,144.1,149.3,172.7,201.4.HRMS calcd for C₂₈H₂₅N₂O₃:437.1865[M+H]⁺,found:437.1862。

example 26

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2i (70mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (volume ratio: petroleum ether/ethyl acetate: 2/1) to give the product 3ai as a white solid (69mg, 78%). The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.73(dd,J₁＝16.0Hz,J₂＝7.2Hz,1H),2.87(dd,J₁＝16.0Hz,J₂＝8.0Hz,1H),3.34(dd,J₁＝16.0Hz,J₂＝8.8Hz,1H),3.64-3.69(m,4H),3.92-3.99(m,1H),6.92-6.98(m,2H),7.00(td,J₁＝6.8Hz,J₂＝1.2Hz,1H),7.18-7.23(m,2H),7.50(ddd,J₁＝9.2Hz,J₂＝6.8Hz,J₃＝1.2Hz,1H),7.57-7.66(m,1H),7.66-7.70(m,1H),7.84(d,J＝9.2Hz,1H),8.35(s,1H),8.56(d,J＝6.8Hz,1H),8.59(d,J＝8.4Hz,1H),8.82(dd,J₁＝8.4Hz,J₂＝0.8Hz,1H).¹³C NMR(100MHz,CDCl₃)δ:38.1,40.6,48.0,51.8,112.1,113.7,115.5(d,²J_C-F＝21.3Hz),118.1,122.5,123.1,124.8,126.86,126.94,127.6,129.0(d,³J_C-F＝8.1Hz),129.2,129.3,138.6(d,⁴J_C-F＝3.3Hz),144.2,149.3,161.7(d,¹J_C-F＝243.9Hz),172.5,200.9.¹⁹F NMR(376MHz,CDCl₃)δ:-115.8.HRMS calcd for C₂₇H₂₂FN₂O₃:441.1614[M+H]⁺,found:441.1610。

example 27

Sequentially adding into a 15mL pressure resistant tube1a (44mg,0.2mmol), 2j (75mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonate) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol), the pressure tube was then sealed and placed in a 100 ℃ oil bath for reaction for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (vol: petroleum ether/ethyl acetate 2/1) to give the product 3aj (72mg, 79%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.73(dd,J₁＝16.0Hz,J₂＝7.2Hz,1H),2.87(dd,J₁＝15.6Hz,J₂＝7.6Hz,1H),3.34(dd,J₁＝16.0Hz,J₂＝8.8Hz,1H),3.62-3.67(m,4H),3.91-3.98(m,1H),7.01(td,J₁＝6.8Hz,J₂＝1.2Hz,1H),7.16-7.19(m,2H),7.22-7.25(m,2H),7.50(ddd,J₁＝9.2Hz,J₂＝6.8Hz,J₃＝1.2Hz,1H),7.58-7.62(m,1H),7.69(td,J₁＝7.6Hz,J₂＝1.2Hz,1H),7.84(d,J＝9.2Hz,1H),8.32(s,1H),8.55(d,J＝6.8Hz,1H),8.60(d,J＝8.4Hz,1H),8.82(dd,J₁＝8.0Hz,J₂＝0.8Hz,1H).¹³C NMR(100MHz,CDCl₃)δ:38.2,40.4,47.8,51.8,112.2,113.7,118.1,122.5,123.2,124.8,126.8,126.9,127.0,127.6,128.8,128.9,129.22,129.25,129.33,132.7,141.5,144.2,149.3,172.4,200.8.HRMS calcd for C₂₇H₂₂ClN₂O₃:457.1319[M+H]⁺,found:457.1319。

example 28

To a 15mL pressure resistant tube were added 1a (44mg,0.2mmol), 2k (88mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure resistant tube was sealed and placed in a 100 ℃ oil bath to react for 12 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (vol.: petroleum ether/ethyl acetate: 2/1) to give the product 3ak (73mg, 73%) as a white solid. Characterization number of the CompoundThe following is provided:¹H NMR(400MHz,CDCl₃)δ:2.73(dd,J₁＝16.0Hz,J₂＝7.2Hz,1H),2.87(dd,J₁＝16.0Hz,J₂＝7.6Hz,1H),3.34(dd,J₁＝16.0Hz,J₂＝8.4Hz,1H),3.60-3.66(m,4H),3.89-3.96(m,1H),6.98-7.02(m,1H),7.12(d,J＝8.4Hz,2H),7.38(d,J＝8.4Hz,2H),7.50(ddd,J₁＝9.2Hz,J₂＝6.8Hz,J₃＝0.8Hz,1H),7.58-7.62(m,1H),7.66-7.70(m,1H),7.83(d,J＝9.2Hz,1H),8.29(s,1H),8.54(d,J＝7.2Hz,1H),8.60(d,J＝8.8Hz,1H),8.80-8.82(m,1H).¹³C NMR(100MHz,CDCl₃)δ:38.3,40.3,47.8,51.8,112.2,113.7,118.1,120.8,122.5,123.2,124.8,126.8,126.9,127.0,127.6,129.18,129.24,129.30,129.33,131.8,142.0,144.1,149.3,172.3,200.7.HRMS calcd for C₂₇H₂₂BrN₂O₃:501.0814[M+H]⁺,found:501.0797。

example 29

To a 15mL pressure resistant tube were added 1a (44mg,0.2mmol), 2l (85mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure resistant tube was sealed and placed in a 100 ℃ oil bath to react for 12 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, dried by spinning, and separated on a silica gel column (volume ratio: petroleum ether/ethyl acetate: 2/1) to give the product 3al (79mg, 81%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.76(dd,J₁＝16.0Hz,J₂＝7.2Hz,1H),2.91(dd,J₁＝16.0Hz,J₂＝7.6Hz,1H),3.39(dd,J₁＝16.0Hz,J₂＝8.4Hz,1H),3.66-3.71(m,4H),4.00-4.07(m,1H),6.99(t,J＝6.8Hz,1H),7.37(d,J＝8.0Hz,2H),7.48-7.54(m,3H),7.59(t,J＝8.0Hz,1H),7.68(t,J＝7.6Hz,1H),7.83(d,J＝9.2Hz,1H),8.32(s,1H),8.52(d,J＝6.8Hz,1H),8.59(d,J＝8.8Hz,1H),8.81(d,J＝8.4Hz,1H).¹³C NMR(150MHz,CDCl₃)δ:38.5,40.2,47.5,51.9,112.2,113.7,118.1,122.5,123.2,124.1(q,¹J_C-F＝270.45Hz),124.8,125.7(q,³J_C-F＝8.4Hz),126.8,126.9,127.0,127.6,128.0,129.0,129.2,129.3(q,²J_C-F＝32.55Hz),129.4,144.2,147.2,149.4,172.2,200.4.¹⁹F NMR(376MHz,CDCl₃)δ:-62.5.HRMS calcd for C₂₈H₂₂F₃N₂O₃:491.1583[M+H]⁺,found:491.1597。

example 30

To a 15mL pressure resistant tube were added 1a (44mg,0.2mmol), 2m (79mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure resistant tube was sealed and placed in a 100 ℃ oil bath to react for 12 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to give the product 3am as a white solid (72mg, 76%). The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.96(dd,J₁＝15.6Hz,J₂＝6.8Hz,1H),3.05(dd,J₁＝16.0Hz,J₂＝8.0Hz,1H),3.54-3.60(m,4H),3.77(dd,J₁＝16.0Hz,J₂＝7.2Hz,1H),4.84-4.90(m,1H),6.91(t,J＝6.8Hz,1H),7.35(t,J＝8.0Hz,1H),7.41-7.47(m,4H),7.55(t,J＝7.6Hz,1H),7.63-7.68(m,2H),7.79-8.81(m,2H),8.13(s,1H),8.17(d,J＝8.8Hz,1H),8.26(d,J＝6.4Hz,1H),8.64(d,J＝8.4Hz,1H),8.78(d,J＝8.0Hz,1H).¹³C NMR(150MHz,CDCl₃)δ:40.0,47.4,51.8,112.0,113.7,118.0,122.4,123.0,123.1,124.8,125.4,125.7,126.4,126.8,126.9,127.47,127.53,129.0,129.2,129.3,129.4,131.2,134.1,139.2,144.0,149.2,172.7,201.2.HRMS calcd for C₃₁H₂₅N₂O₃:473.1865[M+H]⁺,found:473.1856。

example 31

To a 15mL pressure resistant tube were added 1a (44mg,0.2mmol), 2n (66mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure resistant tube was sealed and placed in a 100 ℃ oil bath to react for 12 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (vol: petroleum ether/ethyl acetate 2/1) to give the product 3an (61mg, 71%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.84(dd,J₁＝15.6Hz,J₂＝6.8Hz,1H),2.93(dd,J₁＝16.0Hz,J₂＝7.6Hz,1H),3.46(dd,J₁＝16.0Hz,J₂＝7.6Hz,1H),3.64-3.69(m,4H),4.28-4.35(m,1H),6.87-6.89(m,2H),6.98(t,J＝6.8Hz,1H),7.14(t,J＝2.8Hz,1H),7.48(t,J＝8.0Hz,1H),7.61(t,J＝7.6Hz,1H),7.68(t,J＝7.6Hz,1H),7.82(d,J＝9.2Hz,1H),8.34(s,1H),8.53(d,J＝6.4Hz,1H),8.71(d,J＝8.4Hz,1H),8.80(d,J＝8.0Hz,1H).¹³C NMR(150MHz,CDCl₃)δ:34.2,41.3,48.6,51.9,112.1,113.9,118.0,122.5,123.1,123.7,124.6,124.9,126.88,126.92,127.0,127.6,129.1,129.30,129.33,144.1,146.5,149.3,172.3,200.4.HRMS calcd for C₂₅H₂₁N₂O₃S:429.1273[M+H]⁺,found:429.1281。

example 32

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2o (52mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (vol.: petroleum ether/ethyl acetate 2/1) to give the product 3ao as a white solid (68mg, 89%). Characterization of the CompoundThe data are as follows:¹H NMR(400MHz,CDCl₃)δ:3.39(s,3H),6.86(t,J＝6.8Hz,1H),7.40-7.44(m,1H),7.59-7.67(m,3H),7.74-7.81(m,3H),7.91(s,1H),7.99(d,J＝7.2Hz,1H),8.30(d,J＝6.8Hz,1H),8.86-8.88(m,1H),917-9.20(m,1H).¹³C NMR(100MHz,CDCl₃)δ:52.5,112.0,117.0,118.0,122.3,123.1,125.0,126.9,127.1,127.4,127.9,128.6,129.1,129.4,130.0,130.16,130.21,130.5,132.0,142.9,144.7,149.5,167.1,197.4.HRMS calcd for C₂₄H₁₇N₂O₃:381.1239[M+H]⁺,found:381.1224。

example 33

To a 15mL pressure tube were added 1a (44mg,0.2mmol), 2p (67mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol), and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (vol/vol: petroleum ether/ethyl acetate 2/1) to give the product 3ap as a white solid (53mg, 62%). The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:3.49(s,3H),6.96-6.70(m,1H),7.46(d,J＝7.60Hz,1H),7.53(ddd,J₁＝9.2Hz,J₂＝6.8Hz,J₃＝1.2Hz,1H),7.62-7.68(m,3H),7.75-7.79(m,1H),7.92(d,J＝9.2Hz,1H),8.03(dd,J₁＝7.2Hz,J₂＝1.2Hz,1H),8.06(dd,J₁＝8.0Hz,J₂＝1.2Hz,1H),8.11(dd,J₁＝8.0Hz,J₂＝1.2Hz,1H),8.52(d,J＝6.8Hz,1H),8.57(s,1H),8.86(d,J＝8.4Hz,1H),8.95-8.97(m,1H).¹³C NMR(150MHz,CDCl₃)δ:52.1,112.0,117.1,118.2,123.0,123.3,124.9,125.1,125.7,126.9,127.0,127.4,128.1,129.3,129.5,130.27,130.34,130.5,131.5,132.5,134.8,139.2,144.6,149.4,169.5,197.8.HRMS calcd for C₂₈H₁₉N₂O₃:431.1396[M+H]⁺,found:431.1393。

example 34

To a 15mL pressure tube were added 1b (60mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to give the product 3ba (66mg, 81%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.88(t,J＝6.8Hz,2H),3.46(t,J＝6.8Hz,2H),3.75(s,3H),6.86-6.90(m,1H),7.36-7.42(m,2H),7.47-7.51(m,2H),7.73-7.78(m,3H),7.92(dd,J₁＝8.8Hz,J₂＝2.0Hz,1H),8.37(s,1H),8.41(d,J＝6.8Hz,1H),8.80(d,J＝8.4Hz,1H),9.09(d,J＝2.0Hz,1H).¹³C NMR(100MHz,CDCl₃)δ:28.7,36.1,52.0,112.0,114.2,117.9,122.4,123.6,124.8,125.1,125.7,126.1,127.5,127.6,128.6,128.9,129.3,129.6,140.1,141.1,144.0,149.3,173.7,200.4.HRMS calcd forC₂₆H₂₁N₂O₃:409.1552[M+H]⁺,found:409.1550。

example 35

To a 15mL pressure tube were added 1c (50mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (vol.: petroleum ether/ethyl acetate: 2/1) to give the product 3ca (64mg, 88%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.89(t,J＝6.8Hz,2H),3.49(t,J＝6.8Hz,2H),3.76(s,3H),3.96(s,3H),6.96(t,J＝6.8Hz,1H),7.33(dd,J₁＝8.8Hz,J₂＝2.4Hz,1H),7.48(t,J＝7.6Hz,1H),7.79(d,J＝9.2Hz,1H),8.44(s,1H),8.47-8.49(m,2H),8.69(d,J＝8.8Hz,1H).¹³C NMR(100MHz,CDCl₃)δ:28.7,35.9,51.9,55.4,106.8,111.9,114.6,117.8,118.3,121.4,121.6,124.5,124.8,126.9,129.4,131.1,144.7,149.5,159.5,173.7,200.2.HRMS calcd for C₂₁H₁₉N₂O₄:363.1345[M+H]⁺,found:363.1345。

example 36

To a 15mL pressure tube were added 1d (47mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, dried by spinning, and separated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to give the product 3da (57mg, 82%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.55(s,3H),2.88(t,J＝6.8Hz,2H),3.45(t,J＝6.4Hz,2H),3.76(s,3H),6.91-6.94(m,1H),7.42-7.47(m,1H),7.50(dd,J₁＝8.0Hz,J₂＝1.2Hz,1H),7.77(d,J＝9.2Hz,1H),8.33(s,1H),8.44(d,J＝7.2Hz,1H),8.60(s,1H),8.66(d,J＝8.4Hz,1H).¹³C NMR(100MHz,CDCl₃)δ:22.3,28.7,36.2,52.0,111.9,113.6,117.9,122.0,122.9,124.7,124.8,126.2,128.4,128.8,129.1,129.4,137.5,144.1,149.2,173.7,200.7.HRMS calcd for C₂₁H₁₉N₂O₃:347.1396[M+H]⁺,found:347.1388。

example 37

Sequentially adding into a 15mL pressure resistant tube1e (48mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonate) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol), the pressure tube was then sealed and placed in a 100 ℃ oil bath for reaction for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (vol: petroleum ether/ethyl acetate 2/1) to give product 3ea as a white solid (54mg, 77%). The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.90(t,J＝6.4Hz,2H),3.49(t,J＝6.4Hz,2H),3.77(s,3H),7.00-7.04(m,1H),7.39-7.44(m,1H),7.51-7.55(m,1H),7.80(d,J＝9.2Hz,1H),8.50-8.53(m,2H),8.66(dd,J₁＝12.4Hz,J₂＝2.8Hz,1H),8.75(dd,J₁＝9.2Hz,J₂＝6.4Hz,1H).¹³C NMR(100MHz,CDCl₃)δ:28.6,35.7,52.0,111.8(d,²J_C-F＝24.9Hz),112.2,115.2,116.3(d,²J_C-F＝24.6Hz),118.0,122.1,123.5,124.9,125.2(d,³J_C-F＝9.5Hz),127.1(d,⁴J_C-F＝4Hz),129.7,130.6(d,³J_C-F＝10.5Hz),144.5,149.6,162.3(d,¹J_C-F＝242.8Hz),173.7,199.7.¹⁹F NMR(376MHz,CDCl₃)δ:-111.5.HRMS calcd forC₂₀H₁₆FN₂O₃:351.1145[M+H]⁺,found:351.1136。

example 38

To a 15mL pressure tube were added 1f (51mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 12 h. After the reaction was complete, the reaction mixture was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (volume ratio: petroleum ether/ethyl acetate: 2/1) to give the product 3fa as a white solid (58mg, 79%). The characterization data for this compound are as follows:¹H NMR(400MHz,DMSO-d₆)δ:2.81(t,J＝6.4Hz,2H),3.58(t,J＝6.4Hz,2H),3.68(s,3H),7.22(t,J＝6.8Hz,1H),7.68-7.73(m,2H),7.87(d,J＝9.2Hz,1H),8.64(d,J＝8.8Hz,1H),8.99(s,1H),9.27(s,1H),9.33(d,J＝6.4Hz,1H).¹³C NMR(150MHz,DMSO-d₆)δ:28.8,35.8,51.9,112.8,117.6,118.9,123.5,125.0,125.1,125.5,126.2,127.1,127.8,130.0,131.2,132.8,143.8,149.7,173.6,200.6.HRMScalcd for C₂₀H₁₆ClN₂O₃:367.0849[M+H]⁺,found:367.0834。

example 39

To a 15mL pressure resistant tube were added 1g (60mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure resistant tube was sealed and placed in a 100 ℃ oil bath to react for 12 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, dried by spinning, and separated on a silica gel column (volume ratio: petroleum ether/ethyl acetate: 2/1) to give product 3ga (63mg, 77%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.90(t,J＝6.4Hz,2H),3.47(t,J＝6.4Hz,2H),3.79(s,3H),7.03(td,J₁＝6.8Hz,J₂＝0.8Hz,1H),7.53(ddd,J₁＝9.2Hz,J₂＝6.8Hz,J₃＝1.2Hz,1H),7.67(dd,J₁＝8.4Hz,J₂＝1.6Hz,1H),7.76(d,J＝9.2Hz,1H),8.40(s,1H),8.46(d,J＝6.8Hz,1H),8.55(d,J＝8.8Hz,1H),9.02(d,J＝2.0Hz,1H).¹³CNMR(100MHz,CDCl₃)δ:28.6,35.8,52.0,112.4,114.9,118.0,122.4,124.5,124.9,125.1,126.9,129.2,129.8,130.0,130.1,144.0,149.5,173.7,199.8.HRMS calcd forC₂₀H₁₆BrN₂O₃:411.0344[M+H]⁺,found:411.0323。

example 40

To a 15mL pressure tube were added 1h (58mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (vol: petroleum ether/ethyl acetate 2/1) to give the product 3ha (59mg, 74%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.93(t,J＝6.4Hz,2H),3.51(t,J＝6.4Hz,2H),3.78(s,3H),7.03(td,J₁＝6.8Hz,J₂＝0.8Hz,1H),7.51-7.55(m,1H),7.78-7.83(m,2H),8.50(d,J＝6.8Hz,1H),8.53(s,1H),8.83(d,J＝8.8Hz,1H),9.21(s,1H).¹³C NMR(100MHz,CDCl₃)δ:28.6,35.9,52.0,112.6,115.1,118.2,122.6(q,³J_C-F＝2.3Hz),123.3,123.9,124.5(q,¹J_C-F＝270.5Hz),124.8(q,³J_C-F＝4.6Hz),124.9,128.2,128.26,128.30,129.2(q,²J_C-F＝31.7Hz),129.9,143.7,149.6,173.7,199.9.¹⁹F NMR(376MHz,CDCl₃)δ:-61.8.HRMS calcd for C₂₁H₁₆F₃N₂O₃:401.1113[M+H]⁺,found:401.1106。

EXAMPLE 41

To a 15mL pressure tube were added 1i (47mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 12 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (vol. ratio: petroleum ether/ethyl acetate: 2/1) to give the product 3ia (58mg, 84%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.60(s,3H),2.87(t,J＝6.8Hz,2H),3.45(t,J＝6.8Hz,2H),3.75(s,3H),6.92-6.95(m,1H),7.43-7.47(m,2H),7.79(d,J＝9.2Hz,1H),8.31(s,1H),8.46(d,J＝6.4Hz,1H),8.58(s,1H),8.73(d,J＝8.4Hz,1H).¹³C NMR(100MHz,CDCl₃)δ:21.6,28.7,36.1,51.9,111.9,112.7,118.0,122.48,122.53,124.7,126.8,126.9,127.2,128.8,129.0,129.6,137.0,143.8,149.1,173.7,200.5.HRMS calcd for C₂₁H₁₉N₂O₃:347.1396[M+H]⁺,found:347.1387。

example 42

To a 15mL pressure tube were added 1j (48mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to give product 3ja (53mg, 76%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.90(t,J＝6.4Hz,2H),3.48(t,J＝6.4Hz,2H),3.76(s,3H),7.02(td,J₁＝6.8Hz,J₂＝0.8Hz,1H),7.41(dd,J₁＝11.4Hz,J₂＝8.0Hz,1H),7.51(ddd,J₁＝9.2Hz,J₂＝6.8Hz,J₃＝1.2Hz,1H),7.56(td,J₁＝8.0Hz,J₂＝5.6Hz,1H),7.93(d,J＝9.2Hz,1H),8.48(s,1H),8.57(d,J＝6.8Hz,1H),8.59(d,J＝9.6Hz,1H).¹³C NMR(100MHz,CDCl₃)δ:28.6,36.5,52.0,112.48,112.55(d,²J_C-F＝19.7Hz),114.2,116.8(d,²J_C-F＝12.8Hz),118.7,122.6(d,⁴J_C-F＝4Hz),123.3,124.4,127.4(d,³J_C-F＝8.4Hz),128.9(d,⁴J_C-F＝2Hz),129.3,131.3(d,³J_C-F＝4.1Hz),141.4(d,⁴J_C-F＝4Hz),149.3(d,³J_C-F＝4.1Hz),159.5(d,¹J_C-F＝254.2Hz),173.6,200.7.¹⁹F NMR(376MHz,CDCl₃)δ:-113.1.HRMS calcd for C₂₀H₁₆FN₂O₃:351.1145[M+H]⁺,found:351.1138。

example 43

To a 15mL pressure tube were added 1k (51mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 12 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (vol: petroleum ether/ethyl acetate: 2/1) to give the product 3ka as a white solid (59mg, 80%). The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.90(t,J＝6.4Hz,2H),3.44(t,J＝6.8Hz,2H),3.78(s,3H),7.37(dd,J₁＝9.6Hz,J₂＝1.2Hz,1H),7.58-7.69(m,3H),8.22(s,1H),8.40(s,1H),8.67(d,J＝8.0Hz,1H),8.71(d,J＝8.4Hz,1H).¹³C NMR(100MHz,CDCl₃)δ:28.6,36.3,52.0,113.1,118.3,120.1,122.2,122.8,123.0,126.7,126.9,127.1,127.7,129.0,129.7,130.3,144.1,147.1,173.7,200.6.HRMS calcd forC₂₀H₁₆ClN₂O₃:367.0849[M+H]⁺,found:367.0848。

example 44

To a 15mL pressure resistant tube were added 1l (50mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure resistant tube was sealed and placed in a 100 ℃ oil bath to react for 12 hours. After the reaction was complete, the reaction mixture was cooled to room temperature, filtered under suction, dried by spinning, and separated by means of a silica gel column (volume ratio: petroleum ether/ethyl acetate: 2/1) to give 3l of a white solid producta (60mg, 83%). The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.88(t,J＝6.4Hz,2H),3.46(t,J＝6.4Hz,2H),3.75(s,3H),3.93(s,3H),6.61(dd,J₁＝7.2Hz,J₂＝2.4Hz,1H),7.00(d,J＝2.4Hz,1H),7.59-7.67(m,2H),8.24(d,J＝7.6Hz,1H),8.32(s,1H),8.72-8.74(m,1H),8.88(d,J＝8.0Hz,1H).¹³C NMR(100MHz,CDCl₃)δ:28.7,36.0,51.9,55.8,94.7,107.3,113.4,122.1,122.9,125.0,126.2,126.5,126.9,127.3,127.4,129.1,144.6,151.4,161.2,173.8,200.2.HRMS calcd for C₂₁H₁₉N₂O₄:363.1345[M+H]⁺,found:363.1342。

example 45

To a 15mL pressure tube were added 1m (48mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 12 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried and separated on a silica gel column (vol.: petroleum ether/ethyl acetate 2/1) to give the product 3ma (58mg, 83%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.89(t,J＝6.4Hz,2H),3.44(t,J＝6.4Hz,2H),3.76(s,3H),6.84(td,J₁＝7.2Hz,J₂＝4.4Hz,1H),7.14(dd,J₁＝10.4Hz,J₂＝8.0Hz,1H),7.61(td,J₁＝8.0Hz,J₂＝1.6Hz.1H),7.66-7.70(m,1H),8.26(d,J＝6.4Hz,1H),8.29(s,1H),8.70(d,J＝8.4Hz,1H),8.84(d,J＝8.0Hz,1H).¹³C NMR(100MHz,CDCl₃)δ:28.6,36.4,52.0,111.0(d,³J_C-F＝6.9Hz),111.3(d,²J_C-F＝16.9Hz),113.2,121.1(d,⁴J_C-F＝5.3Hz),123.1,123.3,126.7,126.9,127.1,127.7,129.1,130.2,141.6(d,²J_C-F＝27.4Hz),143.6,151.5(d,¹J_C-F＝252.3Hz),173.6,200.8.¹⁹F NMR(376MHz,CDCl₃)δ:-127.7.HRMS calcd for C₂₀H₁₆FN₂O₃:351.1145[M+H]⁺,found:351.1135。

example 46

To a 15mL pressure resistant tube were added 1n (54mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol), and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure resistant tube was sealed and placed in a 100 ℃ oil bath to react for 12 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (vol.: petroleum ether/ethyl acetate 2/1) to give the product 3na (61mg, 80%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.87(t,J＝6.4Hz,2H),3.42(t,J＝6.4Hz,2H),3.78(s,3H),6.81(t,J＝6.4Hz,1H),7.23-7.27(m,1H),7.49-7.54(m,2H),7.60(d,J＝9.2Hz,1H),7.98-8.00(m,1H),8.05(d,J＝7.2Hz,1H),8.20(s,1H),8.25(d,J＝6.8Hz,1H),9.15(s,1H),9.37(s,1H).¹³C NMR(100MHz,CDCl₃)δ:28.7,35.7,52.0,112.3,115.4,117.5,120.8,121.5,124.3,124.8,125.8,126.3,126.8,126.9,128.02,128.04,128.5,129.2,131.3,132.4,144.2,148.6,173.8,200.0.HRMS calcd forC₂₄H₁₉N₂O₃:383.1396[M+H]⁺,found:383.1385。

example 47

To a 15mL pressure tube were added 1o (46mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 12 hours. After the reaction is finished, cooling to room temperature, carrying out suction filtration, spin-drying, and separating by a silica gel column (volume ratio: petroleum ether/ethyl acetate)2/1) gave the product 3oa (44mg, 65%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.89(t,J＝6.8Hz,2H),3.55(t,J＝6.8Hz,2H),3.76(s,3H),7.01(td,J₁＝6.8Hz,J₂＝0.8Hz,1H),7.54(ddd,J₁＝9.2Hz,J₂＝6.4Hz,J₃＝1.2Hz,1H),7.67(d,J＝5.6Hz,1H),7.80(d,J＝9.2Hz,1H),8.49(s,1H),8.51(d,J＝5.6Hz,1H),8.56(d,J＝7.2Hz,1H).¹³C NMR(100MHz,CDCl₃)δ:28.6,34.3,52.0,111.5,112.1,118.2,123.8,125.4,125.5,126.1,127.6,130.4,131.5,136.6,143.1,150.4,173.7,197.6.HRMS calcd for C₁₈H₁₅N₂O₃S:339.0803[M+H]⁺,found:339.0801。

example 48

To a 15mL pressure tube were added 1p (46mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol) and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 12 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (volume ratio: petroleum ether/ethyl acetate 2/1) to give the product 3pa (50mg, 74%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.87(t,J＝6.8Hz,2H),3.41(t,J＝6.8Hz,2H),3.75(s,3H),6.91(d,J＝4.4Hz,1H),7.55-7.59(m,1H),7.62-7.66(m,1H),7.72(d,J＝4.8Hz,1H),8.19(s,1H),8.63(dd,J₁＝8.0Hz,J₂＝0.8Hz,1H),8.76(d,J＝8.4Hz,1H).¹³C NMR(100MHz,CDCl₃)δ:28.6,34.3,52.0,112.5,113.7,117.6,122.4,123.5,126.61,126.65,126.8,126.9,128.0,128.6,146.9,157.1,173.7,200.7.HRMScalcd for C₁₈H₁₅N₂O₃S:339.0803[M+H]⁺,found:339.0786。

example 49

To a 15mL pressure resistant tube were added 1q (56mg,0.2mmol), 2a (37mg,0.3mmol), methanol (1mL), bis (hexafluoroantimonic acid) triethylenenitrile (pentamethylcyclopentadienyl) rhodium (III) (8mg,0.01mmol), and 2,4, 6-trimethylbenzoic acid (33mg,0.2mmol) in that order, and then the pressure resistant tube was sealed and placed in a 100 ℃ oil bath to react for 12 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, dried by spinning, and separated on a silica gel column (volume ratio: petroleum ether/ethyl acetate: 2/1) to give the product 3qa (63mg, 87%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,CDCl₃)δ:2.90(t,J＝6.4Hz,2H),3.45(t,J＝6.4Hz,2H),3.78(s,3H),7.29(t,J＝7.6Hz,1H),7.40(t,J＝8.0Hz,1H),7.46(t,J＝8.0Hz,1H),7.50(t,J＝7.6Hz,1H),7.63(d,J＝8.0Hz,1H),7.77(d,J＝8.0Hz,1H),8.24(s,1H),8.48(d,J＝8.4Hz,1H),8.59(d,J＝8.4Hz,1H).¹³C NMR(100MHz,CDCl₃)δ:28.7,36.5,52.0,112.7,113.1,122.2,124.30,124.33,124.81,126.2,126.3,126.71,126.76,126.79,127.6,129.2,129.5,132.4,146.5,155.4,173.7,200.9.HRMS calcd forC₂₂H₁₇N₂O₃S:389.0960[M+H]⁺,found:389.0954。

the foregoing embodiments have described the general principles, principal features and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are merely illustrative of the principles of the present invention, and that various changes and modifications may be made without departing from the scope of the principles of the present invention, and the invention is intended to be covered by the appended claims.

Claims

1. A synthetic method of imidazole-containing fused heterocyclic compounds is characterized in that the specific synthetic process comprises the steps of dissolving 3-formyl-2-aryl imidazo [1,2-a ] pyridine or 3-formyl-2-heteroaryl imidazo [1,2-a ] pyridine compounds 1 and cyclic α -diazo-1, 3-diketone compounds 2 in a solvent, adding a catalyst and an additive, and reacting at 80-140 ℃ to obtain target products, namely imidazole-containing fused heterocyclic compounds 3, wherein the reaction equation in the synthetic method is as follows:

2. The method for synthesizing imidazole-containing fused heterocyclic compounds according to claim 1, wherein the ratio of the amounts of the 3-formyl-2-arylimidazo [1,2-a ] pyridine or 3-formyl-2-heteroarylimidazo [1,2-a ] pyridine compound 1, the cyclic α -diazo-1, 3-dione compound 2, the catalyst and the additive is 1:1-2:0.05: 0-3.

3. The method for synthesizing imidazole-containing fused heterocyclic compounds according to claim 1, wherein the ratio of the amounts of the 3-formyl-2-arylimidazo [1,2-a ] pyridine or 3-formyl-2-heteroarylimidazo [1,2-a ] pyridine compound 1, the cyclic α -diazo-1, 3-dione compound 2, the catalyst and the additive is 1:1-2:0.05: 0.1-3.

4. A synthetic method of imidazole-containing fused heterocyclic compounds is characterized in that the specific synthetic process comprises the steps of dissolving 5-formyl-6-aryl imidazo [2,1-b ] thiazole or 5-formyl-6-heteroaryl imidazo [2,1-b ] thiazole compounds 1 and cyclic α -diazo-1, 3-diketone compounds 2 in a solvent, adding a catalyst and an additive, and reacting at 80-140 ℃ to obtain target products, namely imidazole-containing fused heterocyclic compounds 3, wherein the reaction equation in the synthetic method is as follows:

5. The method for synthesizing imidazole-containing fused heterocyclic compounds according to claim 4, wherein the ratio of the amounts of the 5-formyl-6-arylimidazo [2,1-b ] thiazole or 5-formyl-6-heteroarylimidazo [2,1-b ] thiazole compound 1, the cyclic α -diazo-1, 3-dione compound 2, the catalyst and the additive is 1:1-2:0.05: 0-3.

6. The method for synthesizing imidazole-containing fused heterocyclic compounds according to claim 4, wherein the ratio of the amounts of the 5-formyl-6-arylimidazo [2,1-b ] thiazole or 5-formyl-6-heteroarylimidazo [2,1-b ] thiazole compound 1, the cyclic α -diazo-1, 3-dione compound 2, the catalyst and the additive is 1:1-2:0.05: 0.1-3.

7. A synthetic method of imidazole-containing fused heterocyclic compounds is characterized in that the specific synthetic process comprises the steps of dissolving 3-formyl-2-aryl benzo [ d ] imidazo [2,1-b ] thiazole or 3-formyl-2-heteroaryl benzo [ d ] imidazo [2,1-b ] thiazole compounds 1 and cyclic α -diazo-1, 3-diketone compounds 2 in a solvent, adding a catalyst and an additive, and reacting at 80-140 ℃ to obtain target products, namely imidazole-containing fused heterocyclic compounds 3, wherein the reaction equation in the synthetic method is as follows:

wherein R is¹Is 2-thienyl, 1-naphthyl, phenyl or substituted phenyl, the substituent in the substituted phenyl is fluorine, chlorine, bromine, methyl, methoxy, trifluoromethyl or phenyl, R²Is 1, 2-phenyl, 1, 8-naphthyl, C_2-6Alkyl, monosubstituted C_2-6Alkyl or disubstituted C_2-6Alkyl radical, the monosubstituted C_2-6Alkyl or disubstituted C_2-6The substituent in the alkyl group being C_1-6Alkyl, phenyl, substituted phenyl, 2-thienyl or 1-naphthyl, the substituent in the substituted phenyl is fluorine, chlorine, bromine, trifluoromethyl, methyl or methoxy, the solvent is methanol, the catalyst is dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, bis (hexafluoroantimonate) triacetonitrile (pentamethylcyclopentadienyl) rhodium (III), pentamethylcyclopentadienyl rhodium (III) diacetate or dichloro (pentamethylcyclopentadienyl) iridium (III) dimer, and the additive is zinc acetate, silver hexafluoroantimonate, acetateSodium, potassium acetate, cesium acetate, copper acetate, acetic acid, trimethylacetic acid, 2,4, 6-trimethylbenzoic acid, 1-adamantanic acid, or trifluoroacetic acid.

8. The method for synthesizing imidazole-containing fused heterocyclic compounds according to claim 7, wherein the ratio of the amounts of the 3-formyl-2-arylbenzo [ d ] imidazo [2,1-b ] thiazole or 3-formyl-2-heteroarylbenzo [ d ] imidazo [2,1-b ] thiazole compound 1, the cyclic α -diazo-1, 3-dione compound 2, the catalyst and the additive is 1:1-2:0.05: 0-3.

9. The method for synthesizing imidazole-containing fused heterocyclic compounds according to claim 7, wherein the ratio of the amounts of the 3-formyl-2-arylbenzo [ d ] imidazo [2,1-b ] thiazole or 3-formyl-2-heteroarylbenzo [ d ] imidazo [2,1-b ] thiazole compound 1, the cyclic α -diazo-1, 3-dione compound 2, the catalyst and the additive is 1:1-2:0.05: 0.1-3.