CN110372708B - Synthesis method of 5H-benzo [ c ] imidazo [1,2-a ] azepin-6-carboxylic acid compound - Google Patents
Synthesis method of 5H-benzo [ c ] imidazo [1,2-a ] azepin-6-carboxylic acid compound Download PDFInfo
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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
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, C1-4Alkyl or C1-4Alkoxy radical, R2Is hydrogen, C1-4Alkyl radical, C1-4Alkoxy, phenyl or substituted phenyl, R3Is C1-16Alkyl 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 C1-4Alkyl radical, C1-4Alkoxy 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, C1-4Alkyl radical, C1-4Alkoxy, phenyl or substituted phenyl, R3Is C1-16Alkyl 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 C1-4Alkyl radical, C1-4Alkoxy 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,2JC-F=21.5Hz),118.4(d,2JC-F=23.6Hz),124.0,126.4,127.2(d,4JC-F=2.6Hz),128.4,128.8,129.6,131.3(d,3JC-F=8.0Hz),132.6(d,3JC-F=9.3Hz),134.6,138.4,140.7,143.6,162.0(d,1JC-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,1JC-F=270.9Hz),125.0,126.5,128.4,128.8,128.9(q,2JC-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,2JC-F=22.7Hz),118.7(d,2JC-F=14.3Hz),124.5,124.8(d,4JC-F=3.3Hz),126.5,128.4,128.8,129.9,130.2(d,3JC-F=9.3Hz),132.17(d,3JC-F=9.6Hz),132.20,134.9,140.7,143.3(d,4JC-F=2.1Hz),160.5(d,1JC-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,1JC-F=270.5Hz),124.8,125.0(q,3JC-F=3.6Hz),125.1(q,3JC-F=2.9Hz),126.4,128.4,128.8,130.0(q,2JC-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,2JC-F=22.8Hz),118.8(d,3JC-F=11.6Hz),123.3,126.5,128.0,128.36,128.39,128.4,128.9,129.7(d,3JC-F=7.8Hz),130.2,133.6,135.7,138.1(d,4JC-F=5.3Hz),138.4(d,2JC-F=14.9Hz),140.7,159.7(d,1JC-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,2JC-F=20.6Hz),120.1,126.4,126.8(d,3JC-F=8.1Hz),128.4,128.8,129.0,129.1,130.2,130.4,130.7,131.1(d,4JC-F=2.7Hz),132.8,133.1,139.7,140.4,140.7,144.6,161.7(d,1JC-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,2JC-F=21.5Hz),118.4(d,2JC-F=22.4Hz),124.0,127.3,129.5,131.3(d,3JC-F=9.3Hz),132.6(d,3JC-F=6.9Hz),134.7,138.3,143.6,161.9(d,1JC-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,2JC-F=21.4Hz),118.4(d,2JC-F=22.9Hz),124.1,127.5(d,4JC-F=2.6Hz),129.3,131.2(d,3JC-F=8.4Hz),132.7(d,3JC-F=9.2Hz),134.4,138.3,143.6,161.9(d,1JC-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 (4)
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, C1-4Alkyl or C1-4Alkoxy radical, R2Is hydrogen, C1-4Alkyl radical, C1-4Alkoxy, phenyl or substituted phenyl, R3Is C1-16Alkyl, phenyl or substituted phenyl, wherein the substituents on the benzene ring of the substituted phenyl are fluorine, chlorine, bromine and C1-4Alkyl radical, C1-4Alkoxy 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, C1-4Alkyl radical, C1-4Alkoxy, phenyl or substituted phenyl, R3Is C1-16Alkyl, phenyl or substituted phenyl, wherein the substituents on the benzene ring of the substituted phenyl are fluorine, chlorine, bromine and C1-4Alkyl radical, C1-4Alkoxy 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.
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