CN110372708B

CN110372708B - Synthesis method of 5H-benzo [ c ] imidazo [1,2-a ] azepin-6-carboxylic acid compound

Info

Publication number: CN110372708B
Application number: CN201910787861.1A
Authority: CN
Inventors: 张新迎; 张凌华; 徐园双; 范学森
Original assignee: Henan Normal University
Current assignee: Henan Normal University
Priority date: 2019-08-26
Filing date: 2019-08-26
Publication date: 2021-07-09
Anticipated expiration: 2039-08-26
Also published as: CN110372708A

Abstract

The invention discloses a 5H-benzo [ 2 ]c]Imidazo [1,2-a]Aza derivativesThe synthetic method of the cycloheptene-6-carboxylic acid compounds comprises the step of synthesizing 5 through the tandem reaction between 2-aryl imidazole or 2-heteroaryl imidazole compounds and 2-methyl alkenyl propiolactone compoundsH-benzo [ 2 ]c]Imidazo [1,2-a]The invention has the advantages of simple operation, mild condition, wide substrate application range and the like, and is suitable for industrial production.

Description

Synthesis method of 5H-benzo [ c ] imidazo [1,2-a ] azepin-6-carboxylic acid compound

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing 5H-benzo [ c ] imidazo [1,2-a ] azepin-6-carboxylic acid compounds.

Background

It is well known that natural or synthetic azepinenes and their benzo derivatives often possess significant biological and pharmaceutical activity. On the other hand, imidazole is an important structural unit of a plurality of natural products, clinical drugs, azacyclo-carbene and the like, and has important application value in the fields of organic chemistry, pharmaceutical chemistry, material chemistry and the like. Given the importance of the structural backbones of benzazepines and imidazoles, it is reasonable to believe that hybrid molecules containing both these advantageous structural units will likely exhibit enhanced or synergistic biological or physical properties, thereby providing new ideas and opportunities for the development of highly potent drugs and novel materials. It should be noted that although the hybrid molecules have a wide application prospect, an effective preparation method is still lacking at present. Therefore, the research and development of a novel method for synthesizing the 5H-benzo [ c ] imidazo [1,2-a ] azepin-6-carboxylic acid compound by using cheap and easily available raw materials through simple and convenient operation steps have important theoretical significance and important application value.

Disclosure of Invention

The invention provides a synthesis method of 5H-benzo [ c ] imidazo [1,2-a ] azepin-6-carboxylic acid compounds, which synthesizes the 5H-benzo [ c ] imidazo [1,2-a ] azepin-6-carboxylic acid compounds through the series reaction between 2-aryl imidazole or 2-heteroaryl imidazole compounds and 2-methylene propiolactone compounds, has the advantages of simple and convenient 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 5H-benzo [ c ] imidazo [1,2-a ] azepin-6-carboxylic acid compound is characterized by comprising the following specific synthesis processes: dissolving 2-aryl imidazole or 2-heteroaryl imidazole compounds 1 and 2-methylene propiolactone compounds 2 in a solvent, adding a catalyst and an oxidant, and reacting at 80-120 ℃ to obtain 5H-benzo [ c ] imidazo [1,2-a ] azepin-6-carboxylic acid compounds 3, wherein the reaction equation in the synthesis method is as follows:

wherein R is¹Is hydrogen, fluorine, chlorine, bromine, trifluoromethyl, C_1-4Alkyl or C_1-4Alkoxy radical, R²Is hydrogen, C_1-4Alkyl radical, C_1-4Alkoxy, phenyl or substituted phenyl, R³Is C_1-16Alkyl or substituted alkyl, phenyl or substituted phenyl, wherein the substituent of the substituted alkyl is phenyl or substituted phenyl, and the substituents on the benzene ring of the substituted phenyl are fluorine, chlorine, bromine and C_1-4Alkyl radical, C_1-4Alkoxy or cyano, X is C or N, the catalyst is dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, dichlorobis (4-methylisopropylphenyl) ruthenium (II), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer or pentamethylcyclopentadienyl rhodium (III) acetate, the oxidant is silver acetate or silver carbonate, and the solvent is 1, 2-dichloroethane, methanol, hexafluoroisopropanol, toluene, acetonitrile, dichloromethane or 1, 4-dioxane.

More preferably, the dosage ratio of the 2-aryl imidazole or 2-heteroaryl imidazole compounds 1, the 2-methylene propiolactone compounds 2, the catalyst and the oxidant is 1:1-2:0.025: 1-2.

A method for synthesizing 5H-benzo [ c ] imidazo [1,2-a ] azepin-6-carboxylic acid compounds is characterized by comprising the following specific synthetic processes: dissolving a 2-aryl imidazole compound 4 and a 2-methylene propiolactone compound 2 in a solvent, adding a catalyst and an oxidant, and reacting at 80-120 ℃ to obtain a 5H-benzo [ c ] imidazo [1,2-a ] azepin-6-carboxylic acid compound 5, wherein the reaction equation in the synthetic method is as follows:

wherein R is²Is hydrogen, C_1-4Alkyl radical, C_1-4Alkoxy, phenyl or substituted phenyl, R³Is C_1-16Alkyl or substituted alkyl, phenyl or substituted phenyl, wherein the substituent of the substituted alkyl is phenyl or substituted phenyl, and the substituents on the benzene ring of the substituted phenyl are fluorine, chlorine, bromine and C_1-4Alkyl radical, C_1-4Alkoxy or cyano, the catalyst is dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, dichlorobis (4-methylisopropylphenyl) ruthenium (II), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer or pentamethylcyclopentadienyl rhodium (III) acetate, the oxidant is silver acetate or silver carbonate, and the solvent is 1, 2-dichloroethane, methanol, hexafluoroisopropanol, toluene, acetonitrile, dichloromethane or 1, 4-dioxane.

More preferably, the ratio of the 2-arylimidazole compound 4 to the 2-methylalkenylpropanolide compound 2 to the amount of the catalyst to the amount of the oxidant is 1:1-2:0.025: 1-2.

Compared with the prior art, the invention has the following advantages: (1) the synthetic process is simple and efficient, and the 5H-benzo [ c ] imidazo [1,2-a ] azepin-6-carboxylic acid compound is directly obtained through one-pot series reaction; (2) the reaction condition is mild, and the operation is simple and convenient; (3) the application range of the substrate is wide. Therefore, the invention provides a simple, efficient, economical and practical novel method for synthesizing 5H-benzo [ c ] imidazo [1,2-a ] azepin-6-carboxylic acid 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 resistant tube were added 1a (43.3mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure resistant tube was sealed and placed in a 100 ℃ oil bath to react for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3a as a white solid (72.4mg, 73%). The characterization data for this compound are as follows:¹H NMR(600MHz,DMSO-d₆)δ:1.78-1.87(m,2H),2.18-2.23(m,1H),2.41-2.46(m,1H),5.62(t,J＝6.6Hz,1H),6.96(d,J＝7.2Hz,2H),7.12(t,J＝7.2Hz,1H),7.17-7.18(m,3H),7.45-7.48(m,2H),7.54(t,J＝7.8Hz,1H),7.62(d,J＝7.2Hz,1H),7.87(s,1H),8.17(d,J＝7.8Hz,1H),13.28(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:32.2,34.4,54.7,124.0,126.4,128.4,128.8,128.9,129.6,130.3,130.48,130.51,132.7,133.4,139.6,140.8,144.3,167.3.HRMS calcd for C₂₁H₁₇N₂O₂:329.1296[M-H]^-,found:329.1296。

example 2

To a 15mL pressure resistant tube were added 1a (43.3mg,0.3mmol), 1, 2-dichloroethane (3mL), 2a (56.5mg,0.3mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (50.1mg,0.3mmol) in that order, and then the pressure resistant tube was sealed and placed in an oil bath at 100 ℃ for reaction for 10 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3a as a white solid (30.7mg, 31%).

Example 3

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol), methanol (3mL), 2a (56.5mg,0.3mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (50.1mg,0.3mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3a (24.8mg, 25%) as a white solid.

Example 4

To a 15mL pressure resistant tube were added 1a (43.3mg,0.3mmol), hexafluoroisopropanol (3mL), 2a (56.5mg,0.3mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (50.1mg,0.3mmol) in that order, and then the pressure resistant tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3a as a white solid (25.8mg, 26%).

Example 5

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol), toluene (3mL), 2a (56.5mg,0.3mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (50.1mg,0.3mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3a (29.7mg, 30%) as a white solid.

Example 6

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol), acetonitrile (3mL), 2a (56.5mg,0.3mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (50.1mg,0.3mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3a as a white solid (11.9mg, 12%).

Example 7

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol), dichloromethane (3mL), 2a (56.5mg,0.3mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (50.1mg,0.3mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3a as a white solid (32.7mg, 33%).

Example 8

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol), 1, 4-dioxane (3mL), 2a (56.5mg,0.3mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (50.1mg,0.3mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3a as a white solid (13.9mg, 14%).

Example 9

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol), dichloromethane (3mL), 2a (56.5mg,0.3mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver carbonate (82.7mg,0.3mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3a as a white solid (17.8mg, 18%).

Example 10

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol), dichloromethane (3mL), 2a (56.5mg,0.3mmol), dichlorobis (4-methylisopropylphenyl) ruthenium (II) (4.6mg,0.0075mmol) and silver acetate (50.1mg,0.3mmol) in that order, and the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3a as a white solid (10.9mg, 11%).

Example 11

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol), dichloromethane (3mL), 2a (56.5mg,0.3mmol), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer (6.0mg,0.0075mmol) and silver acetate (50.1mg,0.3mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 10 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3a as a white solid (9.9mg, 10%).

Example 12

To a 15mL pressure resistant tube were added 1a (43.3mg,0.3mmol), dichloromethane (3mL), 2a (56.5mg,0.3mmol), pentamethylcyclopentadienyl rhodium (III) acetate (2.7mg,0.0075mmol) and silver acetate (50.1mg,0.3mmol) in that order, and then the pressure resistant tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3a as a white solid (30.7mg, 31%).

Example 13

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol), dichloromethane (3mL), 2a (56.5mg,0.3mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol) and silver acetate (75.1mg,0.45mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3a as a white solid (54.5mg, 55%).

Example 14

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol), dichloromethane (3mL), 2a (56.5mg,0.3mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol) and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3a as a white solid (63.4mg, 64%).

Example 15

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol), dichloromethane (3mL), 2a (112.9mg,0.6mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol) and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3a as a white solid (66.4mg, 67%).

Example 16

To a 15mL pressure resistant tube were added 1a (43.3mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure resistant tube was sealed and placed in an 80 ℃ oil bath to react for 10 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3a as a white solid (64.4mg, 65%).

Example 17

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 120 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3a as a white solid (62.4mg, 63%).

Example 18

To a 15mL pressure tube were added 1b (47.5mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3b as a white solid (70.3mg, 68%). The characterization data for this compound are as follows:¹H NMR(600MHz,DMSO-d₆)δ:1.73-1.85(m,2H),2.15-2.19(m,1H),2.36(s,3H),2.39-2.44(m,1H),5.55-5.57(m,1H),6.95(d,J＝7.2Hz,2H),7.10-7.12(m,2H),7.18(t,J＝7.8Hz,2H),7.34(d,J＝8.4Hz,1H),7.39-7.41(m,2H),7.78(s,1H),8.03(d,J＝7.8Hz,1H),13.13(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:21.0,32.2,34.4,54.6,123.8,126.4,128.0,128.4,128.8,129.4,130.3,131.3,132.9,133.1,138.5,139.8,140.8,144.4,167.3.HRMS calcd for C₂₂H₁₉N₂O₂:343.1452[M-H]^-,found:343.1450。

example 19

To a 15mL pressure tube were added 1c (60.1mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3c as a white solid (77.7mg, 67%). The characterization data for this compound are as follows:¹H NMR(600MHz,DMSO-d₆)δ:1.33(s,9H),1.75-1.85(m,2H),2.16-2.21(m,1H),2.39-2.44(m,1H),5.54-5.57(m,1H),6.97(d,J＝7.2Hz,2H),7.10-7.13(m,2H),7.19(t,J＝7.2Hz,2H),7.38(s,1H),7.56(dd,J₁＝7.8Hz,J₂＝1.8Hz,1H),7.61(d,J＝1.8Hz,1H),7.87(s,1H),8.07(d,J＝8.4Hz,1H),13.09(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:31.4,32.2,34.4,34.9,54.6,123.8,126.5,127.6,128.0,128.5,128.7,128.8,129.4,129.5,130.1,132.7,140.3,140.8,144.3,151.5,167.4.HRMS calcd for C₂₅H₂₅N₂O₂:385.1922[M-H]^-,385.1920。

example 20

To a 15mL pressure tube were added 1d (52.3mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol) and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction is finished, cooling to room temperature, carrying out suction filtration, spin-drying and passingSilica gel column separation (dichloromethane/methanol/acetic acid-30/1/0.1) gave product 3d as a white solid (68.1mg, 63%). The characterization data for this compound are as follows:¹H NMR(600MHz,DMSO-d₆)δ:1.77-1.85(m,2H),2.17-2.22(m,1H),2.41-2.46(m,1H),3.84(s,3H),5.55-5.58(m,1H),6.96(d,J＝7.2Hz,2H),7.11-7.13(m,3H),7.19(t,J＝7.2Hz,2H),7.22(d,J＝1.8Hz,1H),7.39(s,1H),7.84(s,1H),8.05(d,J＝9.0Hz,1H),13.24(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:32.2,34.2,54.6,55.9,116.4,117.1,123.1,123.5,126.4,128.4,128.7,128.8,130.5,132.0,133.4,139.7,140.8,144.2,159.6,167.3.HRMS calcd for C₂₂H₁₉N₂O₃:359.1401[M-H]^-,found:359.1401。

example 21

To a 15mL pressure tube were added 1e (48.6mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3e (57.5mg, 55%) as a white solid. The characterization data for this compound are as follows:¹H NMR(600MHz,DMSO-d₆)δ:1.76-1.90(m,2H),2.19-2.24(m,1H),2.42-2.48(m,1H),5.61-5.64(m,1H),6.97(d,J＝7.2Hz,2H),7.13(t,J＝7.2Hz,1H),7.17-7.21(m,3H),7.40(td,J₁＝8.4Hz,J₂＝2.4Hz,1H),7.45(s,1H),7.56(dd,J₁＝9.6Hz,J₂＝2.4Hz,1H),7.86(s,1H),8.17-8.20(m,1H),13.38(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:32.2,34.4,54.6,117.6(d,²J_C-F＝21.5Hz),118.4(d,²J_C-F＝23.6Hz),124.0,126.4,127.2(d,⁴J_C-F＝2.6Hz),128.4,128.8,129.6,131.3(d,³J_C-F＝8.0Hz),132.6(d,³J_C-F＝9.3Hz),134.6,138.4,140.7,143.6,162.0(d,¹J_C-F＝244.5Hz),167.1.¹⁹F NMR(565MHz,DMSO-d₆)δ:-113.43.HRMS calcd for C₂₁H₁₆FN₂O₂:347.1207[M-H]^-,found:347.1197。

example 22

To a 15mL pressure tube were added 1f (53.6mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3f as a white solid (69.0mg, 63%). The characterization data for this compound are as follows:¹H NMR(400MHz,DMSO-d₆)δ:1.73-1.87(m,2H),2.14-2.21(m,1H),2.39-2.47(m,1H),5.58-5.62(m,1H),6.96(d,J＝7.2Hz,2H),7.12(t,J＝7.2Hz,1H),7.17-7.21(m,3H),7.47(s,1H),7.57(d,J＝6.4Hz,1H),7.77(d,J＝2.0Hz,1H),7.82(s,1H),8.12(d,J＝6.0Hz,1H),13.24(br s,1H).¹³C NMR(150MHz,CF₃CO₂D)δ:30.6,31.2,57.8,119.0,120.4,124.0,126.6,127.5,128.4,127.9,131.6,132.2,132.8,132.9,137.9,140.7,140.8,141.5,169.0.HRMS calcd for C₂₁H₁₆ClN₂O₂:363.0906[M-H]^-,found:363.0904。

example 23

To a 15mL pressure resistant tube were added 1g (66.9mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure resistant tube was sealed and placed in a 100 ℃ oil bathAnd reacting for 10 hours. After the reaction was completed, it was cooled to room temperature, filtered with suction, dried by spinning, and separated by silica gel column (dichloromethane/methanol/acetic acid: 30/1/0.1) to obtain 3g (83.5mg, 68%) of the product as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,DMSO-d₆)δ:1.74-1.88(m,2H),2.14-2.22(m,1H),2.39-2.47(m,1H),5.57-5.61(m,1H),6.97(d,J＝7.2Hz,2H),7.12(t,J＝7.2Hz,1H),7.17-7.21(m,3H),7.46(s,1H),7.70(dd,J₁＝8.4Hz,J₂＝2.0Hz,1H),7.82(s,1H),7.90(d,J＝2.0Hz,1H),8.05(d,J＝8.4Hz,1H),13.26(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:32.1,34.6,54.7,121.8,124.4,126.5,128.4,128.8,129.6,129.9,130.7,132.4,133.0,134.5,134.8,138.3,140.7,143.5,167.1.HRMS calcd for C₂₁H₁₆BrN₂O₂:407.0401[M-H]^-,found:407.0397。

example 24

To a 15mL pressure tube were added 1h (63.7mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to rt, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give the product as a white solid for 3h (61.0mg, 51%). The characterization data for this compound are as follows:¹H NMR(600MHz,DMSO-d₆)δ:1.75-1.78(m,1H),1.85-1.89(m,1H),2.18-2.21(m,1H),2.42-2.47(m,1H),5.64-5.66(m,1H),6.97(d,J＝7.2Hz,2H),7.12(t,J＝7.2Hz,1H),7.19(t,J＝7.2Hz,2H),7.24(s,1H),7.54(s,1H),7.85(d,J＝7.8Hz,1H),7.96(s,1H),8.07(s,1H),8.33(d,J＝7.8Hz,1H),13.33(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:32.1,34.8,54.9,124.3(q,¹J_C-F＝270.9Hz),125.0,126.5,128.4,128.8,128.9(q,²J_C-F＝29.6Hz),129.7,130.4,131.0,133.8,134.8,138.3,140.6,143.1,167.1.¹⁹F NMR(376MHz,DMSO-d₆)δ:-61.19.HRMS calcd for C₂₂H₁₆F₃N₂O₂:397.1169[M-H]^-,found:397.1169。

example 25

To a 15mL pressure tube were added 1i (47.5mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3i (48.6mg, 47%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,DMSO-d₆)δ:1.76-1.86(m,2H),2.17-2.24(m,1H),2.37-2.44(m,4H),5.57(t,J＝7.6Hz,1H),6.96(d,J＝7.2Hz,2H),7.10-7.13(m,2H),7.19(t,J＝7.2Hz,2H),7.28(d,J＝8.0Hz,1H),7.41(s,1H),7.49(d,J＝7.6Hz,1H),7.81(s,1H),7.96(s,1H),13.07(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:21.5,32.2,34.4,54.7,123.9,126.4,127.9,128.4,128.8,129.2,129.5,129.8,130.4,132.8,139.6,140.2,140.8,144.3,167.4.HRMS calcd for C₂₂H₁₉N₂O₂:343.1452[M-H]^-,found:343.1445。

example 26

To a 15mL pressure tube were added 1j (52.3mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 10 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 (dichloromethane/methanol/acetic acid: 30/1/0.1) to yield product 3j (29.2mg, 27%) as a white solid and product 3j' (30.3mg, 28%) as a white solid.

Characterization data for compound 3j are as follows:¹H NMR(400MHz,DMSO-d₆)δ:1.77-1.84(m,2H),2.16-2.24(m,1H),2.37-2.45(m,1H),3.87(s,3H),5.55-5.59(m,1H),6.97(d,J＝7.2Hz,2H),7.04(dd,J₁＝8.8Hz,J₂＝2.8Hz,1H),7.10-7.14(m,2H),7.19(t,J＝7.2Hz,2H),7.42(s,1H),7.56(d,J＝8.8Hz,1H),7.64(d,J＝2.8Hz,1H),7.80(s,1H),12.95(br s,1H).¹³C NMR(150MHz,CF₃CO₂D)δ:30.5,31.3,55.2,58.0,114.2,118.5,120.1,122.4,123.9,124.2,126.5,127.5,127.7,128.4,135.7,138.2,141.9,142.3,169.7.HRMS calcd for C₂₂H₁₉N₂O₃:359.1401[M-H]^-,found:359.1402。

characterization data for compound 3j' are as follows:¹H NMR(400MHz,DMSO-d₆)δ:1.78-1.87(m,2H),2.15-2.23(m,1H),2.39-2.47(m,1H),3.92(s,3H),5.58-5.62(m,1H),6.96(d,J＝6.8Hz,2H),7.10-7.20(m,5H),7.43(d,J＝0.8Hz,1H),7.51(t,J＝8.0Hz,1H),7.75(d,J＝8.0Hz,1H),8.12(s,1H),13.11(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:32.2,33.7,54.3,56.6,110.9,119.4,121.1,123.9,126.4,128.4,128.8,129.5,131.65,131.69,132.2,133.5,140.8,144.0,157.8,167.4.HRMS calcd for C₂₂H₁₉N₂O₃:359.1401[M-H]^-,found:359.1401。

example 27

To a 15mL pressure tube were added 1k (48.6mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction is finished, the reaction product is cooled to room temperature, filtered by suction, dried by spinning, and separated by silica gel column (dichloromethane/methanol/acetic acid: 30/1/0.1) to obtain a white solid product 3k (65.8mg, 63%). The characterization data for this compound are as follows:¹H NMR(600MHz,DMSO-d₆)δ:1.77-1.92(m,2H),2.18-2.23(m,1H),2.42-2.47(m,1H),5.64-5.67(m,1H),6.97(d,J＝7.8Hz,2H),7.12(t,J＝7.2Hz,1H),7.18-7.20(m,3H),7.35(t,J＝9.6Hz,1H),7.49(s,1H),7.57-7.60(m,1H),7.93(s,1H),7.99(d,J＝8.4Hz,1H),13.38(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:32.1,34.2,54.6,115.2(d,²J_C-F＝22.7Hz),118.7(d,²J_C-F＝14.3Hz),124.5,124.8(d,⁴J_C-F＝3.3Hz),126.5,128.4,128.8,129.9,130.2(d,³J_C-F＝9.3Hz),132.17(d,³J_C-F＝9.6Hz),132.20,134.9,140.7,143.3(d,⁴J_C-F＝2.1Hz),160.5(d,¹J_C-F＝248.7Hz),166.9.¹⁹F NMR(565MHz,DMSO-d₆)δ:-113.75.HRMS calcd for C₂₁H₁₆FN₂O₂:347.1201[M-H]^-,found:347.1200。

example 28

To a 15mL pressure resistant tube were added 1l (63.7mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure resistant tube was sealed and placed in a 100 ℃ oil bath to react for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give the product as a white solid, 3l (35.9mg, 30%). The characterization data for this compound are as follows:¹H NMR(400MHz,DMSO-d₆)δ:1.74-1.92(m,2H),2.19-2.26(m,1H),2.41-2.46(m,1H),5.63-5.67(m,1H),6.96(d,J＝7.2Hz,2H),7.11(t,J＝7.2Hz,1H),7.16-7.20(m,3H),7.52(s,1H),7.79(d,J＝8.0Hz,1H),7.85-7.89(m,2H),8.35(s,1H),13.38(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:32.1,34.8,54.9,124.3(q,¹J_C-F＝270.5Hz),124.8,125.0(q,³J_C-F＝3.6Hz),125.1(q,³J_C-F＝2.9Hz),126.4,128.4,128.8,130.0(q,²J_C-F＝32.1Hz),130.2,131.0,133.87,133.91,136.0,137.8,140.6,143.1,167.1.¹⁹F NMR(565MHz,DMSO-d₆)δ:-61.63.HRMS calcd for C₂₂H₁₆F₃N₂O₂:397.1169[M-H]^-,found:397.1168。

example 29

To a 15mL pressure tube were added 1m (48.6mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid: 30/1/0.1) to give the product as a white solid, 3m (63.8mg, 61%). The characterization data for this compound are as follows:¹H NMR(600MHz,DMSO-d₆)δ:1.77-1.85(m,2H),2.24-2.28(m,1H),2.41-2.46(m,1H),5.58-5.61(m,1H),6.96(d,J＝7.8Hz,2H),7.12(t,J＝7.2Hz,1H),7.18-7.21(m,3H),7.39-7.43(m,2H),7.47-7.51(m,2H),7.83(s,1H),13.26(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:32.2,33.4,54.3,118.1(d,²J_C-F＝22.8Hz),118.8(d,³J_C-F＝11.6Hz),123.3,126.5,128.0,128.36,128.39,128.4,128.9,129.7(d,³J_C-F＝7.8Hz),130.2,133.6,135.7,138.1(d,⁴J_C-F＝5.3Hz),138.4(d,²J_C-F＝14.9Hz),140.7,159.7(d,¹J_C-F＝251.1Hz),166.9.¹⁹F NMR(376MHz,DMSO-d₆)δ:-110.76.HRMS calcd for C₂₁H₁₆FN₂O₂:347.1201[M-H]^-,found:347.1206。

example 30

To a 15mL pressure resistant tube were added 1n (43.5mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure resistant tube was sealed and placed in a 100 ℃ oil bath to react for 10 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give the product 3n (41.8mg, 42%) as a white solid. The characterization data for this compound are as follows:¹H NMR(600MHz,DMSO-d₆)δ:1.72-1.79(m,1H),1.84-1.90(m,1H),2.14-2.18(m,1H),2.41-2.46(m,1H),5.66-5.69(m,1H),6.97(d,J＝7.8Hz,2H),7.12(t,J＝7.8Hz,1H),7.19(t,J＝7.2Hz,2H),7.27(s,1H),7.60(s,1H),7.90(s,1H),8.01(d,J＝5.4Hz,1H),8.62(d,J＝4.8Hz,1H),8.82(s,1H),13.31(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:32.1,35.3,55.2,121.3,125.3,125.7,126.5,128.4,128.8,130.8,134.8,136.4,136.6,140.6,142.2,150.5,153.7,167.0.HRMS calcd for C₂₀H₁₆N₃O₂:330.1248[M-H]^-,found:330.1241。

example 31

To a 15mL pressure tube were added 1o (47.5mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give the product 3o as a white solid (67.2mg, 65%). The characterization data for this compound are as follows:¹H NMR(400MHz,DMSO-d₆)δ:1.73-1.81(m,2H),2.18-2.25(m,4H),2.40-2.47(m,1H),5.48-5.52(m,1H),6.95(d,J＝7.2Hz,2H),7.11(t,J＝7.2Hz,1H),7.16-7.20(m,3H),7.44-7.53(m,2H),7.61(d,J＝7.2Hz,1H),7.82(s,1H),8.06(d,J＝6.8Hz,1H),13.12(br s,1H).¹³C NMR(100MHz,DMSO-d₆)δ:13.8,32.2,34.4,54.6,120.8,126.4,128.4,128.7,128.8,129.0,129.9,130.3,130.5,132.8,133.2,137.4,139.5,140.8,143.1,167.2.HRMS calcd for C₂₂H₁₉N₂O₂:343.1452[M-H]^-,found:343.1447。

example 32

To a 15mL pressure tube were added 1p (66.1mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give the product 3p as a white solid (85.4mg, 70%). The characterization data for this compound are as follows:¹H NMR(400MHz,DMSO-d₆)δ:1.82-1.91(m,2H),2.24-2.31(m,1H),2.45-2.49(m,1H),5.62-5.66(m,1H),6.96-6.98(m,2H),7.09-7.13(m,1H),7.16-7.20(m,2H),7.25(t,J＝7.2Hz,1H),7.41(t,J＝7.6Hz,2H),7.50(td,J₁＝7.6Hz,J₂＝1.2Hz,1H),7.57(td,J₁＝7.6Hz,J₂＝1.2Hz,1H),7.65(d,J＝7.2Hz,1H),7.86-7.89(m,3H),7.95(s,1H),8.24(dd,J₁＝7.6Hz,J₂＝0.8Hz,1H),13.21(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:32.3,34.4,55.0,120.4,124.9,126.5,127.1,128.4,128.8,129.03,129.06,129.1,130.3,130.4,130.7,132.8,133.1,134.6,139.7,140.7,141.3,144.5,167.3.HRMS calcd for C₂₇H₂₁N₂O₂:405.1609[M-H]^-,found:405.1600。

example 33

To a 15mL pressure tube were added 1q (70.3mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give the product 3q as a white solid (90.8mg, 72%). The characterization data for this compound are as follows:¹H NMR(400MHz,DMSO-d₆)δ:1.81-1.90(m,2H),2.23-2.36(m,4H),2.44-2.48(m,1H),5.59-5.63(m,1H),6.96-6.98(m,2H),7.09-7.12(m,1H),7.16-7.22(m,4H),7.49(td,J₁＝7.2Hz,J₂＝1.2Hz,1H),7.56(td,J₁＝7.6Hz,J₂＝1.6Hz,1H),7.63(d,J＝7.2Hz,1H),7.74(d,J＝8.4Hz,2H),7.87(s,1H),7.88(s,1H),8.22(dd,J₁＝7.6Hz,J₂＝1.2Hz,1H),13.17(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:21.3,32.3,34.4,54.9,119.9,124.9,126.5,128.4,128.8,129.0,129.1,129.6,130.3,130.4,130.6,131.8,132.8,133.1,136.2,139.7,140.7,141.4,144.3,167.3.HRMS calcd for C₂₈H₂₃N₂O₂:419.1765[M-H]^-,found:419.1774。

example 34

To a 15mL pressure tube were added 1r (82.9mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol) and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid: 30/1/0.1) to give the product 3r (101.3mg, 73%) as a white solid. The characterization data for this compound are as follows:¹H NMR(600MHz,DMSO-d₆)δ:1.30(s,9H),1.81-1.89(m,2H),2.24-2.29(m,1H),2.45-2.49(m,1H),5.60-5.63(m,1H),6.97(d,J＝7.2Hz,2H),7.11(t,J＝6.6Hz,1H),7.18(t,J＝7.2Hz,2H),7.42(d,J＝8.4Hz,2H),7.49(t,J＝7.2Hz,1H),7.56(t,J＝7.8Hz,1H),7.63(d,J＝7.8Hz,1H),7.77(d,J＝8.4Hz,2H),7.87(s,1H),7.88(s,1H),8.23(d,J＝7.8Hz,1H),13.17(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:31.7,32.2,34.4,34.7,54.9,120.0,124.7,125.8,126.5,128.4,128.8,129.0,129.1,130.3,130.4,130.6,131.8,132.8,133.1,139.7,140.7,141.4,144.4,149.5,167.3.HRMS calcd for C₃₁H₂₉N₂O₂:461.2235[M-H]^-,found:461.2239。

example 35

To a 15mL pressure resistant tube were added 1s (71.5mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure resistant tube was sealed and placed in a 100 ℃ oil bath to react for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give the product as a white solid, 3s (82.8mg, 65%). The characterization data for this compound are as follows:¹H NMR(400MHz,DMSO-d₆)δ:1.84-1.91(m,2H),2.26-2.33(m,1H),2.46-2.52(m,1H),5.64-5.68(m,1H),6.97(d,J＝6.8Hz,2H),7.10-7.13(m,1H),7.18(t,J＝6.8Hz,2H),7.26(t,J＝8.8Hz,2H),7.51(td,J₁＝7.6Hz,J₂＝1.2Hz,1H),7.58(td,J₁＝7.2Hz,J₂＝1.2Hz,1H),7.66(d,J＝7.6Hz,1H),7.90-7.95(m,4H),8.26(d,J＝7.6Hz,1H),13.21(br s,1H).¹³C NMR(100MHz,DMSO-d₆)δ:32.3,34.3,55.0,115.9(d,²J_C-F＝20.6Hz),120.1,126.4,126.8(d,³J_C-F＝8.1Hz),128.4,128.8,129.0,129.1,130.2,130.4,130.7,131.1(d,⁴J_C-F＝2.7Hz),132.8,133.1,139.7,140.4,140.7,144.6,161.7(d,¹J_C-F＝242.1Hz),167.3.¹⁹F NMR(376MHz,DMSO-d₆)δ:-115.85.HRMS calcd for C₂₇H₂₀FN₂O₂:423.1514[M-H]^-,found:423.1520。

example 36

To a 15mL pressure tube were added 1t (76.4mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol) and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid: 30/1/0.1) to give the product 3t (97.9mg, 74%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,DMSO-d₆)δ:1.80-1.91(m,2H),2.24-2.31(m,1H),2.45-2.49(m,1H),5.61-5.65(m,1H),6.96-6.98(m,2H),7.09-7.12(m,1H),7.16-7.19(m,2H),7.45-7.47(m,2H),7.50(td,J₁＝7.2Hz,J₂＝1.6Hz,1H),7.57(td,J₁＝7.6Hz,J₂＝1.2Hz,1H),7.65(d,J＝7.2Hz,1H),7.85-7.88(m,3H),8.00(s,1H),8.22(dd,J₁＝8.0Hz,J₂＝1.2Hz,1H),13.21(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:32.3,34.3,55.1,120.8,126.4,126.6,128.4,128.8,129.0,129.1,129.2,130.1,130.4,130.7,131.4,132.8,133.1,133.5,139.7,140.1,140.7,144.7,167.2.HRMS calcd for C₂₇H₂₀ClN₂O₂:439.1219[M-H]^-,found:439.1227。

example 37

To a 15mL pressure tube were added 1u (89.7mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath to react for 10 h. After the reaction is finishedCool to room temperature, filter with suction, spin-dry, and isolate over a silica gel column (dichloromethane/methanol/acetic acid 30/1/0.1) to give the product 3u as a white solid (104.8mg, 72%). The characterization data for this compound are as follows:¹H NMR(400MHz,DMSO-d₆)δ:1.82-1.91(m,2H),2.24-2.32(m,1H),2.45-2.49(m,1H),5.62-5.66(m,1H),6.97(d,J＝7.2Hz,2H),7.11(t,J＝7.2Hz,1H),7.17(t,J＝6.8Hz,2H),7.51(t,J＝7.2Hz,1H),7.55-7.61(m,3H),7.65(d,J＝7.2Hz,1H),7.82(d,J＝8.4Hz,2H),7.89(s,1H),8.01(s,1H),8.23(d,J＝7.6Hz,1H),13.26(br s,1H).¹³C NMR(100MHz,DMSO-d₆)δ:32.3,34.3,55.1,119.9,120.8,126.4,126.9,128.4,128.8,129.1,129.2,130.1,130.4,130.7,132.0,132.8,133.2,133.8,139.6,140.1,140.7,144.7,167.3.HRMS calcd for C₂₇H₂₀BrN₂O₂:483.0714[M-H]^-,found:483.0723。

example 38

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol), dichloromethane (3mL), 2b (63.1mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol) and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give the product 3v (55.9mg, 66%) as a white solid. The characterization data for this compound are as follows:¹HNMR(600MHz,DMSO-d₆)δ:0.69(t,J＝7.2Hz,3H),0.86-0.91(m,1H),1.03-1.15(m,3H),1.46-1.52(m,2H),5.50(t,J＝8.4Hz,1H),7.11(s,1H),7.44-7.46(m,2H),7.51(t,J＝7.2Hz,1H),7.60(d,J＝7.2Hz,1H),7.82(s,1H),8.12(d,J＝7.8Hz,1H),13.14(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:14.1,21.8,28.3,32.5,54.9,124.1,128.76,128.82,128.9,129.4,129.5,130.3,130.4,130.6,132.70,132.74,133.5,139.4,139.5,144.2,167.4.HRMS calcd for C₁₇H₁₇N₂O₂:281.1296[M-H]^-,found:281.1301。

example 39

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol), dichloromethane (3mL), 2c (69.4mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol) and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give the product as a white solid, 3w (60.5mg, 68%). The characterization data for this compound are as follows:¹HNMR(400MHz,DMSO-d₆)δ:0.73(t,J＝6.8Hz,3H),0.90-0.95(m,1H),1.00-1.09(m,5H),1.46-1.51(m,2H),5.51(t,J＝7.6Hz,1H),7.11(d,J＝0.4Hz,1H),7.44-7.53(m,3H),7.59-7.61(m,1H),7.82(s,1H),8.11-8.13(m,1H),13.15(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:14.1,22.2,25.6,30.7,32.7,54.9,124.06,124.10,128.7,128.8,128.9,129.4,129.5,130.3,130.4,130.6,132.7,133.5,139.4,139.5,144.2,167.3.HRMS calcd for C₁₈H₁₉N₂O₂:295.1452[M-H]^-,found:295.1452。

example 40

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol), dichloromethane (3mL), 2d (75.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give the product 3x (62.4mg, 67%) as a white solid. The characterization data for this compound are as follows:¹HNMR(600MHz,DMSO-d₆)δ:0.76(t,J＝7.2Hz,3H),0.89-0.91(m,1H),1.04-1.14(m,7H),1.46-1.50(m,2H),5.50(t,J＝7.8Hz,1H),7.11(s,1H),7.44-7.47(m,2H),7.51(t,J＝7.2Hz,1H),7.60(d,J＝7.2Hz,1H),7.81(s,1H),8.11(d,J＝7.8Hz,1H),13.15(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:14.3,22.2,25.9,28.2,31.4,32.7,54.9,124.0,128.78,128.84,129.4,130.2,130.5,130.6,132.7,133.6,139.4,144.2,167.4.HRMS calcd for C₁₉H₂₁N₂O₂:309.1609[M-H]^-,found:309.1600。

EXAMPLE 41

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol), dichloromethane (3mL), 2e (88.3mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol) and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid 30/1/0.1) to give product 3y (67.0mg, 66%) as a white solid. The characterization data for this compound are as follows:¹HNMR(400MHz,DMSO-d₆)δ:0.81(t,J＝6.8Hz,3H),0.90-0.91(m,1H),1.06-1.20(m,11H),1.46-1.49(m,2H),5.50(t,J＝7.6Hz,1H),7.11(s,1H),7.44-7.53(m,3H),7.60(d,J＝7.2Hz,1H),7.81(s,1H),8.12(d,J＝7.6Hz,1H),13.15(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:14.4,22.5,25.9,28.5,28.8,29.0,31.6,32.7,54.9,124.1,128.8,129.4,129.5,130.3,130.4,130.6,132.7,133.5,139.4,139.5,144.2,167.3.HRMS calcd for C₂₁H₂₅N₂O₂:337.1922[M-H]^-,found:337.1922。

example 42

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol), dichloromethane (3mL), 2f (107.3mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol) and silver acetate (100.1mg,0.6mmol), the pressure tube was then sealed and placed in an oil bath at 100 ℃ for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3z (74.2mg, 65%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,DMSO-d₆)δ:0.82-0.91(m,4H),1.05-1.25(m,17H),1.45-1.49(m,2H),5.50(t,J＝7.6Hz,1H),7.10(s,1H),7.43-7.52(m,3H),7.59(d,J＝7.2Hz,1H),7.81(s,1H),8.12(d,J＝7.6Hz,1H),13.15(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:14.4,22.5,25.9,28.5,29.06,29.14,29.4,31.7,32.6,54.9,124.0,128.7,128.8,129.4,129.5,130.2,130.4,130.6,132.7,133.5,139.4,139.5,144.2,167.3.HRMS calcd for C₂₄H₃₁N₂O₂:379.2391[M-H]^-,found:379.2391。

example 43

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol), dichloromethane (3mL), 2g (109.9mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol) and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 hours. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give the product 3aa (71.9mg, 62%) as a white solid. The characterization data for this compound are as follows:¹HNMR(600MHz,DMSO-d₆)δ:0.33(d,J＝6.6Hz,1.5H),0.63(d,J＝6.6Hz,1.5H),1.09-1.12(m,6H),1.78-1.86(m,1H),1.91-1.93(m,0.5H),2.03-2.07(m,0.5H),2.13-2.17(m,0.5H),2.60-2.63(m,0.5H),2.71-2.79(m,1H),5.33-5.36(m,1H),6.58(d,J＝7.8Hz,1H),6.75(d,J＝8.4Hz,1H),6.98(d,J＝8.4Hz,1H),7.03(d,J＝7.8Hz,1H),7.11(s,0.5H),7.15(s,0.5H),7.46-7.52(m,2H),7.55-7.58(m,1H),7.60(d,J＝7.8Hz,0.5H),7.67-7.69(m,0.5H),7.88(s,0.5H),7.95(s,0.5H),8.07-8.09(m,0.5H),8.17(d,J＝7.8Hz,0.5H),13.19(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:15.8,16.1,24.29,24.31,24.34,33.37,33.40,38.3,38.6,38.7,39.2,59.6,59.7,124.6,124.7,126.6,126.7,128.6,128.7,128.8,128.90,128.93,129.3,129.5,130.3,130.6,130.68,130.74,130.8,132.3,132.4,133.2,133.4,137.2,137.5,139.3,139.6,146.4,146.5,167.7,167.8.HRMS calcd for C₂₅H₂₅N₂O₂:385.1922[M-H]^-,found:385.1922。

example 44

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol), dichloromethane (3mL), 2h (68.5mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol) and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid 30/1/0.1) to give product 3bb (58.3mg, 66%) as a white solid. The characterization data for this compound are as follows:¹H NMR(600MHz,DMSO-d₆)δ:1.01-1.05(m,1H),1.12-1.18(m,1H),1.24-1.43(m,4H),1.52-1.58(m,2H),2.04-2.10(m,1H),5.31(d,J＝10.8Hz,1H),7.12(s,1H),7.46(t,J＝7.8Hz,1H),7.50-7.53(m,2H),7.62(d,J＝7.2Hz,1H),7.88(s,1H),8.13(d,J＝7.2Hz,1H),13.20(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:24.4,24.9,29.2,30.1,42.9,58.8,124.2,128.78,128.82,129.2,130.3,130.6,130.7,132.7,133.2,139.5,144.2,167.8.HRMS calcd for C₁₈H₁₇N₂O₂:293.1296[M-H]^-,found:293.1293。

example 45

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol) and methylene chloride in that order(3mL), 2i (78.4mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol) and silver acetate (100.1mg,0.6mmol), the pressure tube was then sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid: 30/1/0.1) to give the product as a white solid, 3cc (52.2mg, 55%). The characterization data for this compound are as follows:¹HNMR(400MHz,DMSO-d₆)δ:2.72(dd,J₁＝13.2Hz,J₂＝9.2Hz,1H),2.81(dd,J₁＝13.2Hz,J₂＝6.4Hz,1H),5.70-5.74(m,1H),6.82(dd,J₁＝7.6Hz,J₂＝1.6Hz,2H),6.93(d,J＝0.8Hz,1H),7.03(d,J＝0.8Hz,1H),7.12-7.19(m,3H),7.51(td,J₁＝7.2Hz,J₂＝1.2Hz,1H),7.58(td,J₁＝7.6Hz,J₂＝1.6Hz,1H),7.68(d,J＝7.2Hz,1H),7.88(s,1H),8.20(dd,J₁＝7.6Hz,J₂＝1.2Hz,1H),13.04(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:38.6,56.5,123.8,127.1,128.7,128.9,129.0,129.2,130.47,130.50,130.9,132.8,136.9,139.7,144.3,167.1.HRMS calcd for C₂₀H₁₅N₂O₂:315.1139[M-H]^-,found:315.1121。

example 46

To a 15mL pressure tube were added 1a (43.3mg,0.3mmol), dichloromethane (3mL), 2j (83.3mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol) and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give the product 3dd as a white solid (40.3mg, 41%). The characterization data for this compound are as follows:¹HNMR(400MHz,DMSO-d₆)δ:6.90(d,J＝8.0Hz,2H),7.02(s,1H),7.25(d,J＝1.2Hz,1H),7.36(td,J₁＝7.6Hz,J₂＝1.6Hz,1H),7.43(td,J₁＝7.6Hz,J₂＝1.6Hz,1H),7.53(d,J＝6.8Hz,1H),7.65(d,J＝8.4Hz,2H),7.83(d,J＝1.2Hz,1H),8.02-8.05(m,2H),13.52(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:56.3,110.9,118.8,124.5,126.8,128.8,129.0,130.2,130.3,130.7,132.1,132.8,132.9,141.5,144.6,145.1,167.7.HRMS calcd for C₂₀H₁₂N₃O₂:326.0935[M-H]^-,found:326.0930。

example 47

To a 15mL pressure tube were added 1b (47.5mg,0.3mmol), dichloromethane (3mL), 2c (69.4mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol) and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 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 (dichloromethane/methanol/acetic acid: 30/1/0.1) to give the product as a white solid in 3ee (56.8mg, 61%). The characterization data for this compound are as follows:¹HNMR(400MHz,DMSO-d₆)δ:0.73(t,J＝6.8Hz,3H),0.88-0.92(m,1H),1.02-1.08(m,5H),1.44-1.48(m,2H),2.37(s,3H),5.47(t,J＝7.6Hz,1H),7.07(s,1H),7.33(d,J＝8.0Hz,1H),7.40-7.42(m,2H),7.75(s,1H),8.00(d,J＝8.0Hz,1H),13.02(br s,1H).¹³C NMR(150MHz,CF₃CO₂D)δ:11.8,19.6,21.4,25.1,30.1,30.5,58.2,118.0,119.8,123.6,128.1,130.5,131.5,132.5,133.8,142.4,142.7,145.8,169.8.HRMS calcd for C₁₉H₂₁N₂O₂:309.1609[M-H]^-,found:309.1613。

example 48

To a 15mL pressure tube were added 1b (47.5mg,0.3mmol), dichloromethane (3mL), 2h (68.5mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) in that orderRhodium (III) dimer (4.7mg,0.0075mmol) and silver acetate (100.1mg,0.6mmol), and the pressure tube was sealed and placed in an oil bath at 100 ℃ for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give the product as a white solid, 3ff (37.0mg, 40%). The characterization data for this compound are as follows:¹H NMR(400MHz,DMSO-d₆)δ:1.01-1.55(m,8H),2.06-2.08(m,1H),2.37(s,3H),5.26(d,J＝10.8Hz,1H),7.06(s,1H),7.32(d,J＝7.6Hz,1H),7.42(s,1H),7.46(s,1H),7.80(s,1H),8.01(d,J＝8.0Hz,1H),13.08(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:21.0,24.4,24.9,29.2,30.1,42.8,58.7,123.9,128.3,128.8,129.1,130.5,131.2,132.9,133.0,138.3,139.6,144.3,167.8.HRMS calcd for C₁₉H₁₉N₂O₂:307.1452[M-H]^-,found:307.1449。

example 49

To a 15mL pressure tube were added 1e (48.6mg,0.3mmol), dichloromethane (3mL), 2c (69.4mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol) and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give the product 3gg as a white solid (50.0mg, 53%). The characterization data for this compound are as follows:¹HNMR(600MHz,DMSO-d₆)δ:0.73(t,J＝7.2Hz,3H),0.90-0.92(m,1H),1.03-1.10(m,5H),1.47-1.50(m,2H),5.50(t,J＝7.8Hz,1H),7.10(s,1H),7.36-7.39(m,1H),7.46(s,1H),7.55(d,J＝9.6Hz,1H),7.80(s,1H),8.12-8.15(m,1H),13.18(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:14.1,22.2,25.6,30.7,32.7,54.8,117.6(d,²J_C-F＝21.5Hz),118.4(d,²J_C-F＝22.4Hz),124.0,127.3,129.5,131.3(d,³J_C-F＝9.3Hz),132.6(d,³J_C-F＝6.9Hz),134.7,138.3,143.6,161.9(d,¹J_C-F＝245.1Hz),167.2.¹⁹F NMR(376MHz,DMSO-d₆)δ:-113.63.HRMS calcd for C₁₈H₁₈FN₂O₂:313.1358[M-H]^-,found:313.1358。

example 50

To a 15mL pressure tube were added 1e (48.6mg,0.3mmol), dichloromethane (3mL), 2h (68.5mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol) and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give the product 3hh (45.9mg, 49%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,DMSO-d₆)δ:0.99-1.06(m,1H),1.11-1.46(m,5H),1.50-1.62(m,2H),2.03-2.10(m,1H),5.30(d,J＝10.8Hz,1H),7.10(d,J＝0.8Hz,1H),7.37(td,J₁＝8.4Hz,J₂＝2.8Hz,1H),7.50(d,J＝0.8Hz,1H),7.56(dd,J₁＝10.0Hz,J₂＝2.4Hz,1H),7.85(s,1H),8.13-8.16(m,1H),13.28(br s,1H).¹³C NMR(100MHz,DMSO-d₆)δ:24.4,24.9,29.2,30.1,43.0,58.6,117.6(d,²J_C-F＝21.4Hz),118.4(d,²J_C-F＝22.9Hz),124.1,127.5(d,⁴J_C-F＝2.6Hz),129.3,131.2(d,³J_C-F＝8.4Hz),132.7(d,³J_C-F＝9.2Hz),134.4,138.3,143.6,161.9(d,¹J_C-F＝243.4Hz),167.6.¹⁹F NMR(376MHz,DMSO-d₆)δ:-113.66.HRMS calcd for C₁₈H₁₆FN₂O₂:311.1201[M-H]^-,found:311.1201。

example 51

To a 15mL pressure tube were added 1p (66.1mg,0.3mmol), dichloromethane (3mL), 2c (69.4mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol) and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 3ii as a white solid (82.7mg, 74%). The characterization data for this compound are as follows:¹H NMR(400MHz,DMSO-d₆)δ:0.72(t,J＝6.4Hz,3H),1.01-1.18(m,6H),1.54-1.57(m,2H),5.61(t,J＝7.2Hz,1H),7.25(t,J＝7.2Hz,1H),7.41(t,J＝7.2Hz,2H),7.50(t,J＝7.2Hz,1H),7.58(t,J＝7.2Hz,1H),7.65(d,J＝7.6Hz,1H),7.89-7.92(m,3H),7.98(s,1H),8.30(d,J＝7.6Hz,1H),13.23(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:14.1,22.2,25.7,30.8,32.6,55.3,120.4,124.9,127.0,129.0,130.3,130.4,130.7,132.8,133.3,134.6,139.5,141.2,144.5,167.4.HRMS calcd for C₂₄H₂₃N₂O₂:371.1765[M-H]^-,found:371.1765。

example 52

To a 15mL pressure tube were added 1p (66.1mg,0.3mmol), dichloromethane (3mL), 2h (68.5mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol) and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give the product 3jj (62.2mg, 56%) as a white solid. The characterization data for this compound are as follows:¹H NMR(400MHz,DMSO-d₆)δ:1.09-1.15(m,1H),1.18-1.45(m,5H),1.54-1.58(m,2H),2.09-2.16(m,1H),5.33(d,J＝11.2Hz,1H),7.23(t,J＝7.2Hz,1H),7.39(t,J＝7.6Hz,2H),7.47-7.51(m,1H),7.54-7.58(m,1H),7.65(d,J＝7.2Hz,1H),7.84(d,J＝7.6Hz,2H),7.91(s,1H),8.03(s,1H),8.23(d,J＝7.2Hz,1H),13.18(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:24.4,24.9,29.3,30.2,59.1,120.6,124.8,127.0,128.98,129.02,130.4,130.5,130.8,132.8,133.0,134.6,139.5,141.1,144.5,167.8.HRMS calcd for C₂₄H₂₁N₂O₂:369.1609[M-H]^-,found:369.1608。

example 53

To a 15mL pressure tube were added 4a (58.3mg,0.3mmol), dichloromethane (3mL), 2a (84.7mg,0.45mmol), dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer (4.7mg,0.0075mmol), and silver acetate (100.1mg,0.6mmol) in that order, and then the pressure tube was sealed and placed in a 100 ℃ oil bath for reaction for 10 h. After the reaction was complete, it was cooled to room temperature, filtered with suction, spin-dried, and separated on a silica gel column (dichloromethane/methanol/acetic acid-30/1/0.1) to give product 5a (62.8mg, 55%) as a white solid. The characterization data for this compound are as follows:¹H NMR(600MHz,DMSO-d₆)δ:1.76-1.80(m,2H),2.26-2.31(m,1H),2.42-2.47(m,1H),5.69(t,J＝7.8Hz,1H),6.84(d,J＝7.8Hz,2H),7.04-7.10(m,3H),7.30(s,1H),7.47(s,1H),7.59-7.64(m,2H),7.67(d,J＝8.4Hz,1H),7.94(s,1H),7.97-7.99(m,2H),8.99(d,J＝8.4Hz,1H),13.17(br s,1H).¹³C NMR(150MHz,DMSO-d₆)δ:32.0,32.3,54.8,122.9,126.4,127.4,127.8,128.0,128.3,128.35,128.38,128.4,128.5,128.8,129.0,129.1,129.3,129.4,129.6,129.7,131.3,134.1,135.8,139.5,139.6,140.8,142.1,166.9.HRMS calcd for C₂₅H₁₉N₂O₂:379.1452[M-H]^-,found:379.1450。

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 method for synthesizing 5H-benzo [ c ] imidazo [1,2-a ] azepin-6-carboxylic acid compounds is characterized by comprising the following specific synthetic processes: dissolving 2-aryl imidazole or 2-heteroaryl imidazole compounds 1 and 2-methylene propiolactone compounds 2 in a solvent, adding a catalyst and an oxidant, and reacting at 80-120 ℃ to obtain 5H-benzo [ c ] imidazo [1,2-a ] azepin-6-carboxylic acid compounds 3, wherein the reaction equation in the synthesis method is as follows:

wherein R is¹Is hydrogen, fluorine, chlorine, bromine, trifluoromethyl, C_1-4Alkyl or C_1-4Alkoxy radical, R²Is hydrogen, C_1-4Alkyl radical, C_1-4Alkoxy, phenyl or substituted phenyl, R³Is C_1-16Alkyl, phenyl or substituted phenyl, wherein the substituents on the benzene ring of the substituted phenyl are fluorine, chlorine, bromine and C_1-4Alkyl radical, C_1-4Alkoxy or cyano, X is CH or N, the catalyst is dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, dichlorobis (4-methylisopropylphenyl) ruthenium (II), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer or pentamethylcyclopentadienyl rhodium (III) acetate, the oxidant is silver acetate or silver carbonate, and the solvent is 1, 2-dichloroethane, methanol, hexafluoroisopropanol, toluene, acetonitrile, dichloromethane or 1, 4-dioxane.

2. The method for synthesizing 5H-benzo [ c ] imidazo [1,2-a ] azepin-6-carboxylic acid compounds according to claim 1, characterized in that: the dosage ratio of the 2-aryl imidazole or 2-heteroaryl imidazole compounds 1, the 2-methyl alkenyl propiolactone compounds 2, the catalyst and the oxidant is 1:1-2:0.025: 1-2.

3. A method for synthesizing 5H-benzo [ c ] imidazo [1,2-a ] azepin-6-carboxylic acid compounds is characterized by comprising the following specific synthetic processes: dissolving a 2-aryl imidazole compound 4 and a 2-methylene propiolactone compound 2 in a solvent, adding a catalyst and an oxidant, and reacting at 80-120 ℃ to obtain a 5H-benzo [ c ] imidazo [1,2-a ] azepin-6-carboxylic acid compound 5, wherein the reaction equation in the synthetic method is as follows:

wherein R is²Is hydrogen, C_1-4Alkyl radical, C_1-4Alkoxy, phenyl or substituted phenyl, R³Is C_1-16Alkyl, phenyl or substituted phenyl, wherein the substituents on the benzene ring of the substituted phenyl are fluorine, chlorine, bromine and C_1-4Alkyl radical, C_1-4Alkoxy or cyano, the catalyst is dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, dichlorobis (4-methylisopropylphenyl) ruthenium (II), dichloro (pentamethylcyclopentadienyl) iridium (III) dimer or pentamethylcyclopentadienyl rhodium (III) acetate, the oxidant is silver acetate or silver carbonate, and the solvent is 1, 2-dichloroethane, methanol, hexafluoroisopropanol, toluene, acetonitrile, dichloromethane or 1, 4-dioxane.

4. The method for synthesizing 5H-benzo [ c ] imidazo [1,2-a ] azepin-6-carboxylic acid compounds according to claim 3, characterized in that: the mass ratio of the 2-arylimidazole compound 4 to the 2-methylene propiolactone compound 2 to the catalyst to the oxidant is 1:1-2:0.025: 1-2.