CN116574089A - Synthesis method of 3, 3-disubstituted indolone or 4, 4-disubstituted isoquinoline dione compound - Google Patents
Synthesis method of 3, 3-disubstituted indolone or 4, 4-disubstituted isoquinoline dione compound Download PDFInfo
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- CN116574089A CN116574089A CN202310475635.6A CN202310475635A CN116574089A CN 116574089 A CN116574089 A CN 116574089A CN 202310475635 A CN202310475635 A CN 202310475635A CN 116574089 A CN116574089 A CN 116574089A
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- disubstituted
- indolone
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- -1 3, 3-disubstituted indolone Chemical class 0.000 title claims abstract description 68
- 238000001308 synthesis method Methods 0.000 title abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 29
- 239000000654 additive Substances 0.000 claims abstract description 21
- 230000000996 additive effect Effects 0.000 claims abstract description 21
- 238000000034 method Methods 0.000 claims abstract description 16
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 13
- 229940126214 compound 3 Drugs 0.000 claims abstract description 8
- QVLTVILSYOWFRM-UHFFFAOYSA-L CC1=C(C)C(C)([Rh](Cl)Cl)C(C)=C1C Chemical class CC1=C(C)C(C)([Rh](Cl)Cl)C(C)=C1C QVLTVILSYOWFRM-UHFFFAOYSA-L 0.000 claims abstract description 7
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 7
- 229940125904 compound 1 Drugs 0.000 claims abstract description 6
- 229940125782 compound 2 Drugs 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 claims description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 4
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical group OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 claims description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 4
- 239000001632 sodium acetate Substances 0.000 claims description 4
- 235000017281 sodium acetate Nutrition 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 3
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 2
- ZOAIGCHJWKDIPJ-UHFFFAOYSA-M caesium acetate Chemical compound [Cs+].CC([O-])=O ZOAIGCHJWKDIPJ-UHFFFAOYSA-M 0.000 claims description 2
- CZKMPDNXOGQMFW-UHFFFAOYSA-N chloro(triethyl)germane Chemical group CC[Ge](Cl)(CC)CC CZKMPDNXOGQMFW-UHFFFAOYSA-N 0.000 claims description 2
- XIXADJRWDQXREU-UHFFFAOYSA-M lithium acetate Chemical compound [Li+].CC([O-])=O XIXADJRWDQXREU-UHFFFAOYSA-M 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- 235000011056 potassium acetate Nutrition 0.000 claims description 2
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 claims description 2
- 229940071536 silver acetate Drugs 0.000 claims description 2
- 229910001494 silver tetrafluoroborate Inorganic materials 0.000 claims description 2
- KZJPVUDYAMEDRM-UHFFFAOYSA-M silver;2,2,2-trifluoroacetate Chemical compound [Ag+].[O-]C(=O)C(F)(F)F KZJPVUDYAMEDRM-UHFFFAOYSA-M 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 7
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000010523 cascade reaction Methods 0.000 abstract description 3
- 125000000524 functional group Chemical group 0.000 abstract description 3
- 238000005580 one pot reaction Methods 0.000 abstract description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 48
- 238000004009 13C{1H}-NMR spectroscopy Methods 0.000 description 44
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000012512 characterization method Methods 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 150000005624 indolones Chemical class 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- HSYLTRBDKXZSGS-UHFFFAOYSA-N silver;bis(trifluoromethylsulfonyl)azanide Chemical compound [Ag+].FC(F)(F)S(=O)(=O)[N-]S(=O)(=O)C(F)(F)F HSYLTRBDKXZSGS-UHFFFAOYSA-N 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- GYPOFOQUZZUVQL-UHFFFAOYSA-N 2h-isoquinolin-3-one Chemical class C1=CC=C2C=NC(O)=CC2=C1 GYPOFOQUZZUVQL-UHFFFAOYSA-N 0.000 description 1
- QGNQEODJYRGEJX-UHFFFAOYSA-N 4h-isoquinoline-1,3-dione Chemical class C1=CC=C2C(=O)NC(=O)CC2=C1 QGNQEODJYRGEJX-UHFFFAOYSA-N 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- XFBVBWWRPKNWHW-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=N[C]3C(CC)=CC=CC3=C21 XFBVBWWRPKNWHW-UHFFFAOYSA-N 0.000 description 1
- 229960005293 etodolac Drugs 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical class C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000004007 neuromodulation Effects 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
Abstract
The invention discloses a method for synthesizing 3, 3-disubstituted indolone and 4, 4-disubstituted isoquinoline dione compounds, belonging to the technical field of organic synthesis. Taking 2-aryloxy-1H-benzo [ d ] imidazole compound 1 and 3-diazonium-2-indolone compound or 4-diazonium-1, 3-isoquinoline dione compound 2 as raw materials, and reacting in an organic solvent in the presence of dichloro (pentamethyl cyclopentadienyl) rhodium (III) dimer and an additive to obtain 3, 3-disubstituted indolone or 4, 4-disubstituted isoquinoline dione compound 3. The synthesis method is realized by one-pot tandem reaction of 2-aryloxy-1H-benzo [ d ] imidazole and 3-diazonium-2-indolone or 4-diazonium-1, 3-isoquinolinedione, has the advantages of readily available raw materials, unique reaction path, simple synthesis steps, good functional group tolerance and the like, and has wider application prospect.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing 3, 3-disubstituted indolone and 4, 4-disubstituted isoquinoline dione compounds.
Background
3, 3-disubstituted indolones and 4, 4-disubstituted isoquinolinedione structural skeletons are widely found in natural products and synthetic compounds, and many compounds containing these structural units have remarkable biological activities such as anticancer, antihypertensive, cardiovascular protection, neuromodulation, and the like. In addition, 3-disubstituted indolone and 4, 4-disubstituted isoquinolinedione derivatives are key intermediates for synthesizing fine chemicals such as indole or quinoline perfumes, dyes and luminescent materials.
In view of the importance of 3, 3-disubstituted indolones and 4, 4-disubstituted isoquinolinediones, a number of reliable and efficient preparation processes have been developed successively. However, these known methods, although also applicable to the preparation of 3, 3-disubstituted indolones or 4, 4-disubstituted isoquinolinediones, are limited to the case where the substituents are the same, but the synthesis of indolones or isoquinolinediones is still lacking when the substituents are different at this position. In addition, the existing literature synthesis method still has the problems of excessive functionalization of the substrate, low efficiency, complicated steps, large amount of byproducts and the like.
Based on the background, the research and development of a novel method for synthesizing 3, 3-disubstituted indolone and 4, 4-disubstituted isoquinolinedione compounds by a simple and efficient way from cheap and easily available substrates have important theoretical significance and application value.
Disclosure of Invention
The invention solves the technical problem of providing a 3, 3-disubstituted indolone and 4, 4-disubstituted isoquinoline dione compound and a novel synthesis method thereof. Taking 2-aryloxy-1H-benzo [ d ] imidazole compound 1 and 3-diazonium-2-indolone compound or 4-diazonium-1, 3-isoquinoline dione compound 2 as raw materials, and reacting in an organic solvent in the presence of dichloro (pentamethyl cyclopentadienyl) rhodium (III) dimer and additive A to obtain 3, 3-disubstituted indolone or 4, 4-disubstituted isoquinoline dione compound 3. The synthesis method is realized by one-pot tandem reaction of 2-aryloxy-1H-benzo [ d ] imidazole and 3-diazonium-2-indolone or 4-diazonium-1, 3-isoquinolinedione, has the advantages of readily available raw materials, unique reaction path, simple synthesis steps, good functional group tolerance and the like, and has wider application prospect.
The invention provides a 3, 3-disubstituted indolone compound or a 4, 4-disubstituted isoquinoline dione compound, which has the structural general formula:
wherein R is 1 Is hydrogen, C 1-4 Alkyl or halogen, R 2 Is hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy or halogen, R 3 Is hydrogen, C 1-4 Alkyl, phenyl or substituted phenyl, the substituent on the phenyl ring of the substituted phenyl being C 1-4 Alkyl, C 1-4 Alkoxy or halogen, R 4 Is hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy or halogen. n=0 is a 3, 3-disubstituted indolone compound; n=1 is 4, 4-disubstituted isoquinolinediones.
The invention also provides a synthetic method of the 3, 3-disubstituted indolone compound and the 4, 4-disubstituted isoquinolone compound, which adopts the following technical scheme:
the synthesis method of the 3, 3-disubstituted indolone and 4, 4-disubstituted isoquinoline dione compounds comprises the following operations: taking 2-aryloxy-1H-benzo [ d ] imidazole compound 1 and 3-diazonium-2-indolone compound or 4-diazonium-1, 3-isoquinoline dione compound 2 as raw materials, and reacting in an organic solvent in the presence of dichloro (pentamethyl cyclopentadienyl) rhodium (III) dimer and additive A to obtain 3, 3-disubstituted indolone or 4, 4-disubstituted isoquinoline dione compound 3. The reaction equation is expressed as:
wherein: r is R 1 Is hydrogen, C 1-4 Alkyl or halogen, R 2 Is hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy or halogen, R 3 Is hydrogen, C 1-4 Alkyl, phenyl or substituted phenyl, the substituent on the phenyl ring of the substituted phenyl being C 1-4 Alkyl, C 1-4 Alkoxy or halogen, R 4 Is hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy or halogen. n=0 is a 3, 3-disubstituted indolone compound; n=1 is 4, 4-disubstituted isoquinolinediones.
Further, in the above technical scheme, the additive a is sodium acetate, lithium acetate, potassium acetate or cesium acetate.
Further, in the above technical scheme, the organic solvent is 2, 2-trifluoroethanol, hexafluoroisopropanol, methanol, 1, 2-dichloroethane, acetonitrile or a mixed solvent of any two solvents thereof.
Further, in the technical scheme, the molar ratio of the 2-aryloxy-1H-benzo [ d ] imidazole compound 1, the 3-diazonium-2-indolone compound or the 4-diazonium-1, 3-isoquinolinedione compound 2, dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer to the additive A is 1:1-2:0.02-0.03:1-2.
Further, in the above technical solution, the additive further includes a silver salt additive B; the silver salt additive B is silver hexafluoroantimonate, silver trifluoromethane sulfonate, silver tetrafluoroborate, silver bistrifluoromethane sulfonyl imide, silver acetate or silver trifluoroacetate. In the actual reaction process, the silver salt additive is additionally added, so that the reaction yield can be obviously improved.
Further, in the technical scheme, the mol ratio of the additive A to the additive B is 1-2:0.1-0.3.
Further, in the above technical scheme, the reaction temperature is 25-100 ℃.
Further, in the above technical scheme, the reaction is performed under an air atmosphere.
The invention has the beneficial effects that:
compared with the prior art, the invention has the following advantages: (1) The synthesis process is simple and efficient, and 3, 3-disubstituted indolone compounds or 4, 4-disubstituted isoquinolone compounds with different substituents can be conveniently synthesized by one-pot tandem reaction of the 2-aryloxy-1H-benzo [ d ] imidazole compounds and 3-diazonium-2-indolone or 4-diazonium-1, 3-isoquinolone compounds, and the economy of reaction atoms is high; (2) raw materials are cheap and easy to obtain; (3) the reaction condition is mild, and the operation is simple; and (4) the substrate has wide application range and good functional group tolerance.
Drawings
FIG. 1 is An X-ray single crystal diffraction pattern of compound 3An in example 4;
FIG. 2 is an X-ray single crystal diffraction pattern of compound 3Av in example 4.
Detailed Description
The above-described matters of the present invention will be described in further detail by way of examples, but it should not be construed that the scope of the above-described subject matter of the present invention is limited to the following examples, and all techniques realized based on the above-described matters of the present invention are within the scope of the present invention.
Example 1
Into a 15mL reaction tube, the compound 1a, 2A, dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp. Times. Cl) 2 ] 2 ) The catalyst, the additive and the organic solvent are sealed under the air condition, and the reaction tube is placed in a heating module to be heated and stirred for reaction. After the reaction was completed, the mixture was cooled to room temperature, suction filtration was performed, the filtrate was concentrated, and silica gel column separation (petroleum ether/ethyl acetate=3/1) was performed to obtain a white solid product 3Aa.
By changing the reaction conditions of the solvent, the additive, the material ratio and the like, the reaction results are as follows:
TABLE 1 Synthesis of 3Aa under different conditions a
Example 2
1a (42.1 mg,0.2 mmol), 2A (52.0 mg,0.3 mmol) and [ RhCp ] Cl were added sequentially to a 15mL pressure-resistant tube 2 ] 2 (3.1 mg,0.005 mmol), silver bis (trifluoromethanesulfonyl) imide (15.5 mg,0.04 mmol), sodium acetate (24 mg,0.3 mmol) and 2, 2-trifluoroethanol (2 mL), the reaction tube was then sealed and placed in a 60 ℃ heating module with stirring to react for 1h. After the reaction was completed, the reaction system was cooled to room temperature, filtered through celite, and the filtrate was concentrated and separated by a silica gel column (petroleum ether/ethyl acetate=3/1) to give a white solid product 3Aa (61.1 mg, 86%). Characterization data for this compound were: 1 H NMR(600MHz,DMSO-d 6 ):δ12.16(s,1H),9.68(s,1H),7.56(d,J＝7.8Hz,1H),7.50(d,J＝7.8Hz,1H),7.34(d,J＝7.8Hz,1H),7.30(t,J＝7.8Hz,1H),7.17(t,J＝7.8Hz,1H),7.13-7.11(m,2H),7.06-7.04(m,2H),6.74-6.72(m,2H),6.60(d,J＝7.2Hz,1H),3.22(s,3H). 13 C{ 1 H}NMR(150MHz,DMSO-d 6 ):δ175.9,155.2,151.2,144.2,142.7,135.6,130.9,129.5,129.4,128.5,127.3,126.7,122.7,122.6,121.6,119.4,119.2,116.3,112.4,108.6,57.5,27.1.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 18 N 3 O 2 356.1394；Found 356.1392.
example 3
1a (42.1 mg,0.2 mmol), 2B (60.4 mg,0.3 mmol) and [ RhCp ] Cl were added sequentially to a 15mL pressure-resistant tube 2 ] 2 (3.1 mg,0.005 mmol), silver bis (trifluoromethanesulfonyl) imide (15.5 mg,0.04 mmol), sodium acetate (24 mg,0.3 mmol) and 2, 2-trifluoroethanol (2 mL), the reaction tube was then sealed and placed in a 60 ℃ heating module with stirring to react for 1h. After the reaction was completed, the reaction system was cooled to room temperatureFiltration through celite, concentration of the filtrate, and column separation over silica gel (petroleum ether/ethyl acetate=2/1) afforded product 3Ba (61.3 mg, 80%) as a white solid. Characterization data for this compound were: 1 H NMR(400MHz,DMSO-d 6 ):δ12.31(br s,1H),9.88(s,1H),8.15(d,J＝7.2Hz,1H),7.61(t,J＝7.2Hz,1H),7.55-7.49(m,3H),7.22-7.13(m,4H),6.85(t,J＝7.2Hz,1H),6.79-6.74(m,2H),3.32(s,3H). 13 C{ 1 H}NMR(150MHz,DMSO-d 6 ):δ172.7,164.6,154.2,151.4,142.5,140.8,135.7,133.6,130.4,130.3,129.8,129.6,128.0,127.7,125.0,123.3,122.0,119.6,119.4,116.2,112.6,57.4,27.8.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 18 N 3 O 3 384.1343；Found 384.1340.
example 4
Method and procedure according to example 2 or example 3 a,b By changing the reactant 1 and the reactant 2, various 3, 3-disubstituted indolone or 4, 4-disubstituted isoquinoline dione compounds 3 are synthesized, and specific results are as follows:
representative product characterization data are as follows:
3-(2-Hydroxyphenyl)-1-methyl-3-(5/6-methyl-1H-benzo[d]imidazol-2-yl)indolin-2-one(3Ab):1H NMR(600MHz,DMSO-d 6 ):δ12.01(s,1H),9.66(s,1H),7.42(d,J＝7.8Hz,0.6H),7.38-7.35(m,0.8H),7.32-7.28(m,2.6H),7.11(td,J 1 ＝7.8Hz,J 2 ＝1.2Hz,1H),7.05-7.03(m,2H),7.00(d,J＝8.4Hz,0.4H),6.94(d,J＝8.4Hz,0.6H),6.73-6.70(m,2H),6.57-6.56(m,1H),3.22(s,3H),2.39(s,1.8H),2.37(s,1.2H). 13 C{ 1 H}NMR(150MHz,DMSO-d 6 ):δ176.0,155.2,150.9,150.5,144.2,143.1,140.8,135.9,133.6,132.0,130.9,130.4,129.6,129.4,128.5,127.5,126.7,124.1,123.2,122.5,119.4,118.9,118.8,116.3,112.1,111.9,108.6,57.4,27.1,21.85,21.75.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 20 N 3 O 2 370.1550；Found 370.1555.
3-(5,6-Dimethyl-1H-benzo[d]imidazol-2-yl)-3-(2-hydroxyphenyl)-1-methylindolin-2-one(3Ac): 1 H NMR(400MHz,DMSO-d 6 ):δ11.91(br s,1H),9.66(s,1H),7.31-7.27(m,4H),7.10(t,J＝7.6Hz,1H),7.05-7.01(m,2H),6.73-6.69(m,2H),6.54(d,J＝7.6Hz,1H),3.22(s,3H),2.27(s,6H). 13 C{ 1 H}NMR(150MHz,DMSO-d 6 ):δ176.1,155.2,150.0,144.2,141.3,134.2,131.3,130.9,129.9,129.6,129.3,128.4,127.6,126.7,122.5,119.3,119.2,116.2,112.3,108.5,57.4,27.1,20.5.HRMS(ESI)m/z:[M+H] + Calcd for C 24 H 22 N 3 O 2 384.1707；Found 384.1705.
3-(5,6-Dichloro-1H-benzo[d]imidazol-2-yl)-3-(2-hydroxyphenyl)-1-methylindolin-2-one(3Ad):1H NMR(400MHz,DMSO-d 6 ):δ12.48(br s,1H),9.74(s,1H),7.88(br s,1H),7.69(br s,1H),7.37(d,J＝7.2Hz,1H),7.33(t,J＝7.6Hz,1H),7.17-7.13(m,1H),7.08-7.05(m,2H),6.77-6.74(m,2H),6.61(d,J＝7.6Hz,1H),3.24(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ175.4,155.3,154.2,144.1,142.3,135.1,130.5,129.6,129.3,128.8,126.9,126.7,125.2,124.3,122.8,120.5,119.5,116.4,113.5,108.8,57.5,27.2.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 16 Cl 2 N 3 O 2 424.0614；Found 424.0604.
3-(1H-Benzo[d]imidazol-2-yl)-3-(2-hydroxy-5-methylphenyl)-1-methylindolin-2-one(3Ae): 1 H NMR(600MHz,DMSO-d 6 ):δ12.16(br s,1H),9.44(s,1H),7.55-7.51(m,2H),7.39(d,J＝7.2Hz,1H),7.29(t,J＝7.2Hz,1H),7.16-7.13(m,2H),7.06-7.03(m,2H),6.93(d,J＝7.8Hz,1H),6.64(d,J＝7.8Hz,1H),6.47(s,1H),3.22(s,3H),2.08(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ175.9,153.1,151.4,144.1,142.7,135.6,131.1,129.82,129.80,128.5,127.8,126.9,126.7,122.6,121.6,119.2,116.3,112.4,108.6,57.6,27.1,20.8.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 20 N 3 O 2 370.1550；Found 370.1556.
3-(1H-Benzo[d]imidazol-2-yl)-3-(2-hydroxy-5-methoxyphenyl)-1-methylindolin-2-one(3Af): 1 H NMR(600MHz,DMSO-d 6 ):δ12.17(br s,1H),9.21(s,1H),7.56-7.50(m,2H),7.39-7.38(m,1H),7.31-7.30(m,1H),7.17-7.14(m,2H),7.06-7.05(m,2H),6.75(d,J＝7.2Hz,1H),6.65(d,J＝8.4Hz,1H),6.17(s,1H),3.54(s,3H),3.22(s,3H). 13 C{ 1 H}NMR(150MHz,DMSO-d 6 ):δ175.7,152.3,151.1,149.1,144.2,142.6,135.6,130.7,128.6,128.0,126.7,122.8,122.6,121.7,119.2,116.7,116.4,113.4,112.3,108.7,57.5,55.8,27.1.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 20 N 3 O 3 386.1499；Found 386.1497.
3-(1H-Benzo[d]imidazol-2-yl)-3-(5-fluoro-2-hydroxyphenyl)-1-methylindolin-2-one(3Ag): 1 H NMR(600MHz,DMSO-d 6 ):δ12.26(br s,1H),9.75(s,1H),7.59-7.53(m,2H),7.42(d,J＝6.6Hz,1H),7.34-7.32(m,1H),7.19-7.16(m,2H),7.09-7.06(m,2H),7.01(td,J 1 ＝8.4Hz,J 2 ＝3.0Hz,1H),6.74(dd,J 1 ＝9.0Hz,J 2 ＝4.8Hz,1H),6.41(dd,J 1 ＝10.2Hz,J 2 ＝3.6Hz,1H),3.24(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ175.3,155.6(d, 1 J C-F ＝232.6Hz),151.7,150.7,144.2,142.7,135.6,130.4,128.8,128.4(d, 3 J C-F ＝7.0Hz),126.6,122.9,122.8,121.8,119.3,117.2(d, 3 J C-F ＝8.0Hz),116.0(d, 2 J C-F ＝25.2Hz),115.7(d, 2 J C-F ＝23.1Hz),112.4,108.8,57.3,27.1. 19 F NMR(376MHz,DMSO-d 6 ):δ-125.41–-125.47(m).HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 17 FN 3 O 2 374.1299；Found 374.1295.
3-(1H-Benzo[d]imidazol-2-yl)-3-(5-chloro-2-hydroxyphenyl)-1-methylindolin-2-one(3Ah): 1 H NMR(600MHz,DMSO-d 6 ):δ12.27(s,1H),10.09(s,1H),7.60(d,J＝7.8Hz,1H),7.53(d,J＝7.2Hz,1H),7.44(d,J＝7.2Hz,1H),7.34(t,J＝7.8Hz,1H),7.23(dd,J＝9.0Hz,J＝2.4Hz,1H),7.21-7.16(m,2H),7.10-7.07(m,2H),6.78(d,J＝9.0Hz,1H),6.63(d,J＝2.4Hz,1H),3.25(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ175.2,154.5,150.6,144.2,142.7,135.5,130.3,129.3,129.1,129.0,128.8,126.6,122.9,122.84,122.79,121.8,119.3,118.0,112.4,108.8,57.3,27.2.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 17 ClN 3 O 2 390.1004；Found 390.1000.
3-(1H-Benzo[d]imidazol-2-yl)-3-(5-bromo-2-hydroxyphenyl)-1-methylindolin-2-one(3Ai): 1 H NMR(600MHz,DMSO-d 6 ):δ12.25(s,1H),10.10(s,1H),7.58(d,J＝7.8Hz,1H),7.52(d,J＝7.8Hz,1H),7.43(d,J＝7.2Hz,1H),7.34-7.31(m,2H),7.19(t,J＝7.2Hz,1H),7.14(t,J＝7.2Hz,1H),7.08-7.06(m,2H),6.74-6.71(m,2H),3.23(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ175.2,154.9,150.6,144.2,142.7,135.5,132.2,131.8,130.4,129.6,128.8,126.6,122.9,122.8,121.8,119.3,118.6,112.4,110.3,108.8,57.3,27.2.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 17 Br N 3 O 2 434.0499；Found 434.0503.
3-(1H-Benzo[d]imidazol-2-yl)-3-(2-hydroxy-4-methylphenyl)-1-methylindolin-2-one(3Aj): 1 H NMR(600MHz,DMSO-d 6 ):δ12.13(s,1H),9.56(s,1H),7.56(d,J＝7.8Hz,1H),7.50(d,J＝7.8Hz,1H),7.35(d,J＝7.8Hz,1H),7.29(t,J＝7.8Hz,1H),7.16(t,J＝7.8Hz,1H),7.12(t,J＝7.8Hz,1H),7.05-7.02(m,2H),6.57-6.54(m,2H),6.49(d,J＝7.8Hz,1H),3.22(s,3H),2.17(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ176.0,155.1,151.4,144.1,142.7,138.9,135.6,131.1,129.4,128.4,126.7,124.5,122.7,122.6,121.6,120.1,119.2,116.9,112.4,108.6,57.3,27.1,21.1.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 20 N 3 O 2 370.1550；Found 370.1551.
3-(1H-Benzo[d]imidazol-2-yl)-3-(2-hydroxy-4-methoxyphenyl)-1-methylindolin-2-one(3Ak): 1 H NMR(400MHz,DMSO-d 6 ):δ12.12(br s,1H),9.71(s,1H),7.52-7.50(m,2H),7.34(d,J＝7.2Hz,1H),7.30(t,J＝7.6Hz,1H),7.14(br s,2H),7.07-7.03(m,2H),6.50(d,J＝8.8Hz,1H),6.34(dd,J＝8.8Hz,J＝2.4Hz,1H),6.28(d,J＝2.4Hz,1H),3.65(s,3H),3.22(s,3H). 13 C{ 1 H}NMR(150MHz,DMSO-d 6 ):δ176.1,160.4,156.3,151.5,144.0,142.7,135.6,131.3,130.1,128.4,126.6,122.6,121.6,121.1,119.8,119.2,118.9,112.3,108.6,104.7,102.3,57.0,55.5,27.1.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 20 N 3 O 3 386.1499；Found 386.1497.
3-(1H-Benzo[d]imidazol-2-yl)-3-(4-chloro-2-hydroxyphenyl)-1-methylindolin-2-one(3Al): 1 H NMR(600MHz,DMSO-d 6 ):δ12.21(br s,1H),10.28(s,1H),7.56-7.51(m,2H),7.36(d,J＝7.2Hz,1H),7.33-7.31(m,1H),7.16-7.15(m,2H),7.08-7.05(m,2H),6.84(dd,J 1 ＝8.4Hz,J 2 ＝2.4Hz,1H),6.76(d,J＝2.4Hz,1H),6.64(d,J＝8.4Hz,1H),3.23(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ175.4,156.3,150.8,144.2,142.7,135.6,133.4,131.0,130.5,128.7,126.61,126.58,122.9,122.8,121.7,119.33,119.26,116.0,112.4,108.8,57.1,27.1.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 17 ClN 3 O 2 390.1004；Found 390.1002.
3-(1H-Benzo[d]imidazol-2-yl)-3-(4-bromo-2-hydroxyphenyl)-1-methylindolin-2-one(3Am): 1 H NMR(600MHz,DMSO-d 6 ):δ12.19(br s,1H),10.25(s,1H),7.55(d,J＝7.8Hz,1H),7.49(d,J＝7.8Hz,1H),7.35-7.31(m,2H),7.18-7.12(m,2H),7.08-7.05(m,2H),6.96(dd,J 1 ＝8.4Hz,J 2 ＝1.8Hz,1H),6.88(d,J＝1.8Hz,1H),6.56(d,J＝8.4Hz,1H),3.23(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ175.4,156.4,150.7,144.2,142.7,135.6,132.5,131.3,130.4,128.7,127.0,126.6,122.8,122.7,122.2,121.7,119.3,118.8,112.4,108.8,57.1,27.1.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 17 BrN 3 O 2 434.0499；Found 434.0490.
3-(1H-Benzo[d]imidazol-2-yl)-3-(2-fluoro-6-hydroxyphenyl)-1-methylindolin-2-one(3An): 1 H NMR(400MHz,DMSO-d 6 ):δ12.33(br s,1H),10.23(s,1H),7.44(br s,2H),7.35-7.31(m,2H),7.18-7.03(m,5H),6.63-6.58(m,2H),3.16(s,3H). 13 C{ 1 H}NMR(150MHz,DMSO-d 6 ):δ174.7,162.0(d, 1 J C-F ＝244.2Hz),157.5,152.2,144.1,142.7,136.0,130.5,129.9(d, 3 J C-F ＝11.6Hz),128.9,126.3,122.9,122.3,121.2,119.0,114.4(d, 2 J C-F ＝13.1Hz),112.7,111.8,108.9,107.2(d, 2 J C-F ＝24.8Hz),54.4,27.1. 19 F{ 1 H}NMR(565MHz,DMSO-d 6 ):δ-110.30(dd,J 1 ＝11.7Hz,J 2 ＝6.4Hz).HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 20 N 3 O 3 374.1299；Found 374.1308.
3-(1H-Benzo[d]imidazol-2-yl)-3-(2-hydroxy-3-methoxyphenyl)-1-methylindolin-2-one(3Ao): 1 H NMR(400MHz,DMSO-d 6 ):δ12.15(br s,1H),8.88(s,1H),7.52(br s,2H),7.37(d,J＝7.6Hz,1H),7.30(t,J＝7.6Hz,1H),7.15(brs,2H),7.07-7.04(m,2H),6.91(d,J＝8.0Hz,1H),6.70(t,J＝8.0Hz,1H),6.23(d,J＝7.6Hz,1H),3.71(s,3H),3.22(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ175.7,151.4,148.3,144.6,144.1,142.7,135.6,131.0,128.6,127.2,126.7,122.6,121.7,121.6,121.2,119.5,119.1,112.3,112.0,108.7,57.5,56.4,27.1.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 20 N 3 O 3 386.1499；Found 386.1497.
3-(1H-Benzo[d]imidazol-2-yl)-3-(3-fluoro-2-hydroxyphenyl)-1-methylindolin-2-one(3Ap): 1 H NMR(400MHz,DMSO-d 6 ):δ12.23(br s,1H),9.97(s,1H),7.54(br s,2H),7.37(d,J＝7.2Hz,1H),7.35-7.31(m,1H),7.16-7.06(m,5H),6.79-6.74(m,1H),6.47(d,J＝8.0Hz,1H),3.25(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ175.4,152.2(d, 1 J C-F ＝237.0Hz),150.1,144.0,143.0(d, 2 J C-F ＝16.4Hz),142.6,135.5,130.5,130.3(d, 4 J C-F ＝1.9Hz),128.8,126.6,125.0,122.8,121.6,119.5(d, 3 J C-F ＝6.9Hz),119.3,118.4,115.9(d, 2 J C-F ＝17.9Hz),112.3,108.9,57.5(d, 4 J C-F ＝3.2Hz),27.2. 19 F NMR(376MHz,DMSO-d 6 ):δ-135.30–-135.34(m).HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 17 FN 3 O 2 374.1299；Found 374.1297.
3-(1H-Benzo[d]imidazol-2-yl)-3-(3-chloro-2-hydroxyphenyl)-1-methylindolin-2-one(3Aq): 1 H NMR(400MHz,DMSO-d 6 ):δ12.24(br s,1H),9.81(br s,1H),7.54(br s,2H),7.38-7.32(m,3H),7.16-7.06(m,4H),6.82(t,J＝8.0Hz,1H),6.63(d,J＝8.0Hz,1H),3.26(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ175.7,151.1,151.0,144.0,142.7,135.6,130.3,130.1,129.9,128.9,128.5,126.6,122.9,122.7,122.0,121.7,120.9,119.2,112.4,109.1,57.9,27.2.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 17 Cl N 3 O 2 390.1004；Found 390.1002.
3-(1H-Benzo[d]imidazol-2-yl)-3-(3-hydroxynaphthalen-2-yl)-1-methylindolin-2-one(3Ar): 1 H NMR(600MHz,DMSO-d 6 ):δ12.30(br s,1H),10.11(s,1H),7.67(d,J＝8.4Hz,1H),7.63(d,J＝7.8Hz,1H),7.58-7.55(m,2H),7.43-7.38(m,2H),7.34(t,J＝7.8Hz,1H),7.28(s,1H),7.24-7.20(m,3H),7.11-7.05(m,3H),3.29(s,3H). 13 C{ 1 H}NMR(150MHz,DMSO-d 6 ):δ175.8,153.6,151.2,144.3,142.8,135.7,134.5,130.9,130.1,129.2,128.7,128.2,127.7,127.0,126.6,125.8,123.7,122.8,122.7,121.7,119.3,112.4,110.2,108.8,58.1,27.2.HRMS(ESI)m/z:[M+H] + Calcd for C 26 H 20 N 3 O 2 406.1550；Found 406.1552.
3-(1H-Benzo[d]imidazol-2-yl)-3-(2-hydroxyphenyl)-1,5-dimethylindolin-2-one(3As): 1 H NMR(600MHz,DMSO-d 6 ):δ12.12(br s,1H),9.66(s,1H),7.57(d,J＝7.8Hz,1H),7.50(d,J＝7.2Hz,1H),7.17-7.10(m,5H),6.94(d,J＝7.8Hz,1H),6.74-6.72(m,2H),6.60(d,J＝7.2Hz,1H),3.20(s,3H),2.27(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ175.9,155.2,151.3,142.7,141.9,135.6,131.4,130.9,129.6,129.4,128.8,127.5,127.2,122.7,121.6,119.4,119.2,116.4,112.4,108.4,57.6,27.1,21.3.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 20 N 3 O 2 370.1550；Found 370.1551.3-(1H-Benzo[d]imidazol-2-yl)-3-(2-hydroxyphenyl)-5-methoxy-1-methylindolin-2-one(3At): 1 H NMR(400MHz,DMSO-d 6 ):δ12.16(br s,1H),9.68(s,1H),7.57-7.50(m,2H),7.15-7.12(m,3H),6.98-6.96(m,2H),6.89(d,J＝8.4Hz,1H),6.75-6.74(m,2H),6.63(d,J＝7.2Hz,1H),3.69(s,3H),3.20(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ175.5,155.7,155.4,151.3,142.7,137.8,135.6,132.3,129.54,129.49,127.2,122.7,121.6,119.4,119.2,116.4,114.4,112.3,108.9,57.9,55.9,27.2.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 20 N 3 O 3 386.1499；Found 386.1504.
3-(1H-Benzo[d]imidazol-2-yl)-5-fluoro-3-(2-hydroxyphenyl)-1-methylindolin-2-one(3Au): 1 H NMR(400MHz,DMSO-d 6 ):δ12.23(br s,1H),9.76(s,1H),7.55(br s,2H),7.20-7.13(m,5H),7.09-7.06(m,1H),6.77-6.74(m,2H),6.61(d,J＝6.8Hz,1H),3.23(s,3H). 13 C{ 1 H}NMR(150MHz,DMSO-d 6 ):δ175.5,158.8(d, 1 J C-F ＝234.5Hz),155.2,150.6,142.6,140.5,135.5,132.7(d, 3 J C-F ＝7.7Hz),129.7,129.6,126.7,122.9,121.7,121.1,119.5,119.3,118.9,116.3,114.8(d, 2 J C-F ＝23.0Hz),114.3(d, 2 J C-F ＝25.7Hz),112.4,109.5(d, 3 J C-F ＝8.0Hz),57.8,27.3. 19 F NMR(376MHz,DMSO-d 6 ):δ-113.08–-113.14(m).HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 17 FN 3 O 2 374.1299；Found 374.1301.
3-(1H-Benzo[d]imidazol-2-yl)-5-chloro-3-(2-hydroxyphenyl)-1-methylindolin-2-one(3Av): 1 H NMR(400MHz,DMSO-d 6 ):δ12.26(s,1H),9.80(s,1H),7.61(d,J＝7.6Hz,1H),7.51(d,J＝7.6Hz,1H),7.39(dd,J 1 ＝8.4Hz,J 2 ＝2.0Hz,1H),7.33(d,J＝2.0Hz,1H),7.21-7.12(m,3H),7.10(d,J＝8.4Hz,1H),6.77-6.74(m,2H),6.62-6.60(m,1H),3.23(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ175.5,155.2,150.5,143.2,142.6,135.6,132.9,129.8,129.6,128.5,126.65,126.55,126.4,122.9,121.8,119.6,119.3,116.3,112.4,110.2,57.6,27.3.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 17 Cl N 3 O 2 390.1004；Found 390.1003.
3-(1H-Benzo[d]imidazol-2-yl)-5-bromo-3-(2-hydroxyphenyl)-1-methylindolin-2-one(3Aw): 1 H NMR(600MHz,DMSO-d 6 ):δ12.24(brs,1H),9.78(s,1H),7.60(d,J＝7.8Hz,1H),7.52(dd,J 1 ＝8.4Hz,J 2 ＝1.8Hz,1H),7.50(d,J＝8.4Hz,1H),7.42(d,J＝1.8Hz,1H),7.19-7.14(m,3H),7.07(d,J＝8.4Hz,1H),6.77-6.75(m,2H),6.60(d,J＝7.2Hz,1H),3.22(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ175.4,155.2,150.5,143.6,142.6,135.7,133.2,131.3,129.8,129.6,129.1,126.7,122.9,121.8,119.6,119.3,116.3,114.3,112.4,110.8,57.5,27.2.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 17 BrN 3 O 2 434.0499；Found 434.0493.
3-(1H-Benzo[d]imidazol-2-yl)-3-(2-hydroxyphenyl)-6-methoxy-1-methylindolin-2-one(3Ax): 1 H NMR(600MHz,DMSO-d 6 ):δ12.13(br s,1H),9.67(s,1H),7.57-7.51(m,2H),7.25(d,J＝7.8Hz,1H),7.16-7.13(m,3H),6.74-6.72(m,3H),6.62(br s,2H),3.81(s,3H),3.24(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ176.4,160.4,155.2,151.6,145.3,142.7,135.7,129.4,129.3,127.6,127.3,122.8,122.6,121.6,119.4,119.1,116.3,112.3,107.1,96.2,57.0,55.9,27.2.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 20 N 3 O 3 386.1499；Found 386.1501.
3-(1H-Benzo[d]imidazol-2-yl)-6-fluoro-3-(2-hydroxyphenyl)-1-methylindolin-2-one(3Ay): 1 H NMR(400MHz,DMSO-d 6 ):δ12.21(br s,1H),9.75(s,1H),7.55(br s,2H),7.32(dd,J 1 ＝8.0Hz,J 2 ＝5.6Hz,1H),7.15-7.11(m,3H),7.05(dd,J 1 ＝9.2Hz,J 2 ＝2.0Hz,1H),6.87-6.82(m,1H),6.76-6.73(m,2H),6.58(d,J＝8.0Hz,1H),3.23(s,3H). 13 C{ 1 H}NMR(150MHz,DMSO-d 6 ):δ176.2,163.0(d, 1 J C-F ＝241.4Hz),155.1,150.9,145.9(d, 3 J C-F ＝12.2Hz),142.6,135.7,129.54,129.49,127.9(d, 3 J C-F ＝10.1Hz),127.2,126.6,122.8,121.7,119.5,119.2,116.3,112.4,108.4(d, 2 J C-F ＝22.8Hz),97.4(d, 2 J C-F ＝28.7Hz),57.0,27.3. 19 F NMR(376MHz,DMSO-d 6 ):δ-113.09–-113.16(m).HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 17 FN 3 O 2 374.1299；Found 374.1303.
3-(1H-Benzo[d]imidazol-2-yl)-6-chloro-3-(2-hydroxyphenyl)-1-methylindolin-2-one(3Az): 1 H NMR(400MHz,DMSO-d 6 ):δ12.23(br s,1H),9.76(s,1H),7.57(d,J＝7.6Hz,1H),7.50(d,J＝7.6Hz,1H),7.30(d,J＝8.0Hz,1H),7.23(d,J＝1.6Hz,1H),7.18-7.09(m,4H),6.76-6.73(m,2H),6.58(d,J＝6.8Hz,1H),3.24(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ176.0,155.1,150.5,145.7,142.6,135.7,133.2,129.7,129.6,129.5,127.9,126.9,122.9,122.2,121.7,119.5,119.3,116.3,112.4,109.1,57.1,27.3.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 17 ClN 3 O 2 390.1004；Found 390.1000.
3-(1H-Benzo[d]imidazol-2-yl)-6-bromo-3-(2-hydroxyphenyl)-1-methylindolin-2-one(3Aaa): 1 H NMR(400MHz,DMSO-d 6 ):δ12.23(br s,1H),9.75(s,1H),7.55-7.50(m,2H),7.34(s,1H),7.26-7.22(m,2H),7.16-7.12(m,3H),6.74(t,J＝8.0Hz,2H),6.57(d,J＝7.2Hz,1H),3.23(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ175.8,155.1,150.4,145.8,142.5,135.7,130.2,129.6,129.5,128.3,126.8,125.2,122.9,121.8,121.5,119.5,119.2,116.2,112.4,111.8,57.2,27.3.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 17 BrN 3 O 2 434.0499；Found 434.0495.
3-(1H-Benzo[d]imidazol-2-yl)-3-(2-hydroxyphenyl)-1,7-dimethylindolin-2-one(3Aab): 1 H NMR(400MHz,DMSO-d 6 ):δ12.16(br s,1H),9.71(s,1H),7.55(br s,2H),7.19-7.12(m,4H),7.06(d,J＝7.6Hz,1H),6.94(t,J＝7.6Hz,1H),6.76-6.74(m,2H),6.61(d,J＝8.0Hz,1H),3.52(s,3H),2.59(s,3H). 13 C{ 1 H}NMR(150MHz,DMSO-d 6 ):δ176.6,155.2,151.4,142.7,141.8,135.6,132.1,131.4,129.5,129.4,127.6,124.9,122.7,122.4,121.6,119.6,119.4,119.2,116.4,112.4,57.0,30.2,19.1.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 20 N 3 O 2 370.1550；Found 370.1553.
3-(1H-Benzo[d]imidazol-2-yl)-7-chloro-3-(2-hydroxyphenyl)-1-methylindolin-2-one(3Aac): 1 H NMR(400MHz,DMSO-d 6 ):δ12.27(s,1H),9.84(s,1H),7.58(d,J＝7.6Hz,1H),7.51(d,J＝7.6Hz,1H),7.31(d,J＝8.0Hz,1H),7.25(d,J＝7.2Hz,1H),7.21-7.13(m,3H),7.05(t,J＝7.6Hz,1H),6.77-6.72(m,2H),6.57(d,J＝7.6Hz,1H),3.56(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ176.4,155.0,150.2,142.6,139.9,135.7,133.7,130.5,129.7,129.6,127.1,126.0,123.8,123.0,121.8,119.5,119.3,116.2,114.3,112.5,57.2,30.4.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 17 Cl N 3 O 2 390.1004；Found 390.1001.
3-(1H-Benzo[d]imidazol-2-yl)-3-(2-hydroxyphenyl)indolin-2-one(3Aad): 1 H NMR(600MHz,DMSO-d 6 ):δ12.11(br s,1H),10.73(s,1H),9.69(s,1H),7.57-7.52(m,2H),7.33(d,J＝7.2Hz,1H),7.22(t,J＝7.8Hz,1H),7.16-7.13(m,3H),6.98(t,J＝7.8Hz,1H),6.91(d,J＝7.8Hz,1H),6.77-6.74(m,2H),6.64(d,J＝7.8Hz,1H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ177.5,155.5,151.7,142.7,135.5,131.9,129.6,129.4,128.4,127.3,126.9,122.6,121.9,121.6,119.4,119.1,118.4,116.4,112.3,109.6,58.1.HRMS(ESI)m/z:[M+H] + Calcd for C 21 H 16 N 3 O 2 342.1237；Found 342.1233.
4-(1H-Benzo[d]imidazol-2-yl)-4-(2-hydroxyphenyl)-2-methylisoquinoline-1,3(2H,4H)-dione(3Ba): 1 H NMR(400MHz,DMSO-d 6 ):δ12.31(br s,1H),9.88(s,1H),8.15(d,J＝7.2Hz,1H),7.61(t,J＝7.2Hz,1H),7.55-7.49(m,3H),7.22-7.13(m,4H),6.85(t,J＝7.2Hz,1H),6.79-6.74(m,2H),3.32(s,3H). 13 C{ 1 H}NMR(150MHz,DMSO-d 6 ):δ172.7,164.6,154.2,151.4,142.5,140.8,135.7,133.6,130.4,130.3,129.8,129.6,128.0,127.7,125.0,123.3,122.0,119.6,119.4,116.2,112.6,57.4,27.8.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 18 N 3 O 3 384.1343；Found 384.1340.
4-(5,6-Dimethyl-1H-benzo[d]imidazol-2-yl)-4-(2-hydroxyphenyl)-2-methylisoquin oline-1,3(2H,4H)-dione(3Bb): 1 H NMR(600MHz,DMSO-d 6 ):δ12.02(br,1H),9.84(s,1H),8.14(d,J＝7.8Hz,1H),7.60(t,J＝7.2Hz,1H),7.52-7.50(m,1H),7.29(s,2H),7.20(t,J＝7.2Hz,1H),7.11(d,J＝7.2Hz,1H),6.84(t,J＝7.2Hz,1H),6.742-6.737(m,2H),3.32(s,3H),2.27(s,6H). 13 C{ 1 H}NMR(150MHz,DMSO-d 6 ):δ172.7,164.7,154.2,150.3,141.2,140.9,134.2,133.5,131.9,130.4,130.3,130.2,129.7,129.6,128.0,127.7,124.9,119.5,119.3,116.2,112.5,57.4,27.8,20.4.HRMS(ESI)m/z:[M+H] + Calcd for C 25 H 22 N 3 O 3 412.1656；Found 412.1653.4-(1H-Benzo[d]imidazol-2-yl)-4-(2-hydroxy-5-methylphenyl)-2-methylisoquinoline-1,3(2H,4H)-dione(3Bc): 1 H NMR(400MHz,DMSO-d 6 ):δ12.31(s,1H),9.63(s,1H),8.14(d,J＝7.6Hz,1H),7.60(t,J＝7.6Hz,1H),7.54-7.48(m,3H),7.21(t,J＝7.6Hz,1H),7.17-7.11(m,2H),7.01(d,J＝8.0Hz,1H),6.64(d,J＝8.0Hz,1H),6.62(s,1H),3.30(s,3H),2.16(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ172.7,164.7,152.0,151.5,142.5,140.9,135.6,133.5,130.4,130.1,130.0,128.0,127.8,127.6,124.9,123.3,121.9,119.6,116.1,112.6,57.4,27.8,20.9.HRMS(ESI)m/z:[M+H] + Calcd for C 24 H 20 N 3 O 3 398.1499；Found 398.1506.
4-(1H-Benzo[d]imidazol-2-yl)-4-(5-fluoro-2-hydroxyphenyl)-2-methylisoquinolin e-1,3(2H,4H)-dione(3Bd): 1 H NMR(400MHz,DMSO-d 6 ):δ12.40(br s,1H),9.94(s,1H),8.17(d,J＝7.6Hz,1H),7.64(t,J＝7.6Hz,1H),7.55-7.52(m,3H),7.22-7.20(m,2H),7.16(d,J＝7.6Hz,1H),7.09(td,J 1 ＝8.4Hz,J 2 ＝2.8Hz,1H),6.76(dd,J 1 ＝8.8Hz,J 2 ＝4.8Hz,1H),6.67(dd,J 1 ＝10.0Hz,J 2 ＝2.8Hz,1H),3.33(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ172.1,164.5,155.5(d, 1 J C-F ＝232.9Hz),150.9,150.7(d, 4 J C-F ＝2.3Hz),142.5,140.2,135.6,133.8,131.3(d, 3 J C-F ＝7.0Hz),130.1,128.3,127.9,125.0,123,5,122.1,119.7,117.5(d, 3 J C-F ＝8.0Hz),116.5(d, 2 J C-F ＝24.9Hz),116.0(d, 2 J C-F ＝22.6Hz),112.6,57.3,27.8. 19 F NMR(376MHz,DMSO-d 6 ):δ-125.04–-125.10(m).HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 17 FN 3 O 3 402.1248；Found 402.1252.
4-(1H-Benzo[d]imidazol-2-yl)-4-(5-chloro-2-hydroxyphenyl)-2-methylisoquinoline-1,3(2H,4H)-dione(3Be): 1 H NMR(400MHz,DMSO-d 6 ):δ12.38(s,1H),10.27(s,1H),8.17-8.15(m,1H),7.67-7.63(m,1H),7.58-7.52(m,3H),7.30(dd,J 1 ＝8.4Hz,J 2 ＝2.4Hz,1H),7.25-7.16(m,3H),6.79-6.77(m,2H),3.32(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ172.1,164.5,153.4,150.7,142.5,140.1,135.6,133.8,131.9,130.0,129.6,129.2,128.3,127.9,125.0,123.5,122.9,122.2,119.7,117.8,112.7,57.3,27.9.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 17 ClN 3 O 3 418.0953；Found418.0952.
4-(1H-Benzo[d]imidazol-2-yl)-4-(5-bromo-2-hydroxyphenyl)-2-methylisoquinoline-1,3(2H,4H)-dione(3Bf): 1 H NMR(600MHz,DMSO-d 6 ):δ12.37(s,1H),10.28(s,1H),8.15(d,J＝8.4Hz,1H),7.65(t,J＝7.8Hz,1H),7.57-7.52(m,3H),7.41(dd,J 1 ＝8.4Hz,J 2 ＝1.8Hz,1H),7.23(t,J＝7.8Hz,1H),7.18-7.14(m,2H),6.89(d,J＝1.8Hz,1H),6.73(d,J＝8.4Hz,1H),3.31(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ172.1,164.5,153.8,150.7,142.5,140.1,135.5,133.9,132.6,132.4,131.9,130.0,128.3,127.9,125.0,123.5,122.2,119.7,118.4,112.7,110.4,57.3,27.9.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 17 BrN 3 O 3 462.0448；Found 462.0442.
4-(1H-Benzo[d]imidazol-2-yl)-4-(2-hydroxy-4-methylphenyl)-2-methylisoquinolin e-1,3(2H,4H)-dione(3Bg): 1 H NMR(600MHz,DMSO-d 6 ):δ12.28(br s,1H),9.76(s,1H),8.15(d,J＝7.8Hz,1H),7.61(t,J＝7.8Hz,1H),7.55-7.53(m,2H),7.51(t,J＝7.8Hz,1H),7.19-7.15(m,3H),6.67(s,2H),6.57(s,1H),3.32(s,3H),2.23(s,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ172.8,164.7,154.1,151.6,142.5,141.0,139.3,135.6,133.5,130.4,129.4,128.0,127.7,127.6,124.9,123.2,121.9,120.0,119.4,116.8,112.5,57.2,27.8,21.2.HRMS(ESI)m/z:[M+H] + Calcd for C 24 H 20 N 3 O 3 398.1499；Found 398.1494.
4-(1H-Benzo[d]imidazol-2-yl)-4-(2-hydroxyphenyl)-2-isopropylisoquinoline-1,3(2H,4H)-dione(3Bh): 1 H NMR(400MHz,DMSO-d 6 ):δ12.26(s,1H),9.83(s,1H),8.12(d,J＝7.6Hz,1H),7.60-7.56(m,1H),7.55-7.53(m,2H),7.49(t,J＝7.6Hz,1H),7.22-7.17(m,2H),7.12(t,J＝7.6Hz,1H),7.07(d,J＝7.6Hz,1H),6.81(t,J＝7.6Hz,1H),6.76(d,J＝8.4Hz,1H),6.67(d,J＝7.6Hz,1H),5.16-5.06(m,1H),1.42(d,J＝7.2Hz,3H),1.36(d,J＝6.8Hz,3H). 13 C{ 1 H}NMR(100MHz,DMSO-d 6 ):δ172.3,164.7,154.3,151.5,142.6,140.7,135.6,133.3,130.4,130.0,129.7,129.5,127.9,127.8,125.6,123.2,121.9,119.6,119.2,116.2,112.6,58.0,45.5,20.3,19.3.HRMS(ESI)m/z:[M+H] + Calcd for C 25 H 22 N 3 O 3 412.1656；Found 412.1659.4-(1H-Benzo[d]imidazol-2-yl)-4-(2-hydroxyphenyl)-2-(4-methoxyphenyl)isoquino line-1,3(2H,4H)-dione(3Bi): 1 H NMR(600MHz,DMSO-d 6 ):δ12.23(s,1H),10.06(s,1H),8.13(d,J＝7.8Hz,1H),7.66(t,J＝7.8Hz,1H),7.59(d,J＝7.8Hz,1H),7.54-7.52(m,2H),7.22-7.21(m,3H),7.15(t,J＝7.8Hz,1H),7.09(d,J＝7.8Hz,2H),7.03(d,J＝7.8Hz,2H),6.84(t,J＝7.8Hz,1H),6.79(d,J＝8.4Hz,1H),6.75(d,J＝7.2Hz,1H),3.79(s,3H). 13 C{ 1 H}NMR(150MHz,DMSO-d 6 ):δ172.5,164.7,159.4,154.3,151.4,142.6,140.8,135.7,133.8,130.6,130.4,130.1,129.8,129.5,128.8,128.1,128.0,125.2,123.3,122.0,119.6,119.4,116.4,114.7,112.7,58.0,55.9.HRMS(ESI)m/z:[M+H] + Calcd for C 29 H 22 N 3 O 4 476.1605；Found 476.1623.
example 5
The 3, 3-disubstituted indolone compound and 4, 4-disubstituted isoquinolone compound synthesized by the invention can perform a series of reactions, thereby synthesizing derivatives thereof. For example:
in a round bottom flask, 3Aa (71.1 mg,0.2 mmol) and 1, 2-dichloroethane (2 mL) were added, and to the resulting solution were added N, N' -dicyclohexylcarbodiimide (41.3 mg,0.2 mmol), 4-dimethylaminopyridine (4.9 mg,0.04 mmol) and ibuprofen (41.3 mg,0.2 mmol), and the system was reacted at 25℃for 12 hours. After the reaction is finished, water is added to quench the reaction, dichloromethane is used for extraction for three times, the organic phases are combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was subjected to silica gel column separation (petroleum ether/ethyl acetate=3/1) to give two isomers 4-1 (50.9 mg, 47%) and 4-2 (29.8 mg, 27%) of product 4. The product characterization data are as follows: isomer 4-1: 1 H NMR(400MHz,CDCl 3 ):δ10.14(s,1H),7.80-7.78(m,1H),7.52(d,J＝7.2Hz,1H),7.39-7.37(m,1H),7.31(t,J＝7.6Hz,1H),7.27-7.23(m,2H),7.21-7.15(m,2H),7.05-7.00(m,3H),6.91(d,J＝8.0Hz,2H),6.86-6.82(m,3H),3.35-3.27(m,4H),2.41(d,J＝6.8Hz,2H),1.85-1.79(m,1H),1.48(d,J＝7.2Hz,3H),0.88(d,J＝6.8Hz,6H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ176.0,172.1,149.8,148.1,142.9,142.5,140.9,136.4,134.1,131.1,129.9,129.5,129.4,129.2,129.0,127.3,127.1,126.0,124.0,123.5,123.4,122.2,120.2,111.2,108.5,57.0,45.0,44.6,30.2,27.0,22.4,18.5.HRMS(ESI)m/z:[M+H] + Calcd for C 35 H 34 N 3 O 3 544.2595; fond 544.2601 isomer 4-2: 1 H NMR(400MHz,CDCl 3 ):δ10.08(s,1H),7.80-7.78(m,1H),7.62(d,J＝7.2Hz,1H),7.40-7.35(m,2H),7.24-7.16(m,5H),7.09(3H,overlapping with CHCl 3 ),7.03(t,J＝8.0Hz,1H),6.92(d,J＝7.6Hz,1H),6.80(dd,J 1 ＝8.0Hz,J 2 ＝1.2Hz,1H),6.76(d,J＝8.0Hz,1H),3.37(s,3H),3.20(q,J＝7.2Hz,1H),2.44(d,J＝7.2Hz,2H),1.86-1.81(m,1H),0.98(d,J＝7.2Hz,3H),0.89(d,J＝6.8Hz,6H). 13 C{ 1 H}NMR(400MHz,CDCl 3 ):δ175.7,171.7,149.8,148.5,143.0,142.7,140.9,136.9,134.0,131.2,129.71,129.65,129.6,129.3,129.0,127.6,127.0,126.0,124.1,123.6,123.4,122.2,120.2,111.2,108.4,57.2,45.1,44.5,30.2,27.0,22.4,17.9.HRMS(ESI)m/z:[M+H] + Calcd for C 35 H 34 N 3 O 3 544.2595；Found 544.2585.
in a round bottom flask, 3Aa (71.1 mg,0.2 mmol) and 1, 2-dichloroethane (2 mL) were added, and to the resulting solution were added N, N' -dicyclohexylcarbodiimide (41.3 mg,0.2 mmol), 4-dimethylaminopyridine (4.9 mg,0.04 mmol) and etodolac (57.5 mg,0.2 mmol), and the system was reacted at 25℃for 12 hours. After the reaction is finished, water is added to quench the reaction, dichloromethane is used for extraction for three times, the organic phases are combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was subjected to silica gel column separation (petroleum ether/ethyl acetate=3/1) to give two isomers 5-1 (51.1 mg, 41%) and 5-2 (61.3 mg, 49%) of product 5. The product characterization data are as follows: isomer 5-1: 1 H NMR(600MHz,CDCl 3 ):δ10.14(s,1H),8.50(s,1H),7.72(d,J＝7.8Hz,1H),7.43(d,J＝7.2Hz,1H),7.38(d,J＝7.8Hz,1H),7.34-7.31(m,2H),7.18-7.11(m,3H),7.09(t,J＝7.8Hz,1H),7.03(d,J＝6.6Hz,1H),6.99(d,J＝8.4Hz,1H),6.79(d,J＝7.8Hz,1H),6.69(t,J＝7.8Hz,1H),6.59(d,J＝7.8Hz,1H),6.56(t,J＝7.2Hz,1H),4.03-4.00(m,1H),3.88-3.85(m,1H),3.31(s,3H),2.85-2.80(m,2H),2.77-2.74(m,3H),2.52(d,J＝17.4Hz,1H),2.06-2.02(m,1H),1.94-1.90(m,1H),1.32(t,J＝7.8Hz,3H),0.80(t,J＝7.8Hz,3H). 13 C{ 1 H}NMR(600MHz,CDCl 3 ):δ175.9,170.3,149.1,147.4,142.8,142.1,135.0,134.7,133.8,131.5,130.3,129.4,129.0,128.7,127.2,126.6,126.2,123.81,123.78,123.6,122.3,120.3,120.1,119.7,115.9,111.1,108.4,108.2,74.4,60.7,57.0,42.0,30.5,27.1,24.0,22.5,13.7,7.6.HRMS(ESI)m/z:[M+H] + Calcd for C 39 H 37 N 4 O 4 625.2809; fond 625.2780 isomer 5-2: 1 H NMR(600MHz,CDCl 3 ):δ10.10(s,1H),8.54(s,1H),7.76(d,J＝7.2Hz,1H),7.58(d,J＝7.8Hz,1H),7.38-7.34(m,3H),7.28(t,J＝7.8Hz,1H),7.23-7.18(m,3H),7.11(t,J＝7.8Hz,1H),7.07(t,J＝7.2Hz,1H),7.02(d,J＝7.2Hz,1H),6.91-6.90(m,2H),6.82(d,J＝7.8Hz,1H),4.04-4.01(m,1H),3.88-3.85(m,1H),3.20(s,3H),2.90(d,J＝16.8Hz,1H),2.85-2.82(m,3H),2.73-2.70(m,1H),2.49(d,J＝16.8Hz,1H),1.98-1.94(m,1H),1.74-1.71(m,1H),1.33(t,J＝7.8Hz,3H),0.68(t,J＝7.8Hz,3H). 13 C{ 1 H}NMR(600MHz,CDCl 3 ):δ175.8,170.1,149.3,147.5,142.9,142.6,134.63,134.56,133.9,131.3,130.3,129.33,129.27,129.2,127.4,126.7,126.5,126.1,124.0,123.6,123.5,122.3,120.7,120.3,119.8,116.0,111.1,109.2,108.6,74.6,60.7,56.9,42.6,31.0,26.9,24.1,22.4,13.9,7.6.HRMS(ESI)m/z:[M+H] + Calcd for C 39 H 37 N 4 O 4 625.2809；Found 625.2806.
the foregoing embodiments illustrate the basic 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 above-described embodiments, and that the above-described embodiments and descriptions are merely illustrative of the principles of the present invention, and various changes and modifications may be made without departing from the scope of the principles of the invention, which are defined in the appended claims.
Claims (9)
1. A3, 3-disubstituted indolone compound or a 4, 4-disubstituted isoquinolinedione compound has the structural general formula:
wherein: r is R 1 Is hydrogen, C 1-4 Alkyl or halogen, R 2 Is hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy or halogen, R 3 Is hydrogen, C 1-4 Alkyl, phenyl or substituted phenyl, the substituent on the phenyl ring of the substituted phenyl being C 1-4 Alkyl, C 1-4 Alkoxy or halogen, R 4 Is hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy or halogen; n=0 is a 3, 3-disubstituted indolone compound; n=1 is 4, 4-disubstituted isoquinolinediones.
2. The method for synthesizing 3, 3-disubstituted indolone compounds and 4, 4-disubstituted isoquinolinedione compounds according to claim 1, comprising the following operations: taking 2-aryloxy-1H-benzo [ d ] imidazole compound 1 and 3-diazonium-2-indolone compound or 4-diazonium-1, 3-isoquinoline dione compound 2 as raw materials, and reacting in an organic solvent in the presence of dichloro (pentamethyl cyclopentadienyl) rhodium (III) dimer and additive A to obtain 3, 3-disubstituted indolone or 4, 4-disubstituted isoquinoline dione compound 3; the reaction equation is expressed as:
wherein: r is R 1 -R 4 The substituents are as defined in claim 1.
3. The method for synthesizing 3, 3-disubstituted indolone compounds and 4, 4-disubstituted isoquinolinedione compounds according to claim 2, characterized in that: the additive A is sodium acetate, lithium acetate, potassium acetate or cesium acetate.
4. The method for synthesizing 3, 3-disubstituted indolone compounds and 4, 4-disubstituted isoquinolinedione compounds according to claim 2, characterized in that: the organic solvent is 2, 2-trifluoroethanol, hexafluoroisopropanol, methanol, 1, 2-dichloroethane, acetonitrile or a mixed solvent of any two solvents.
5. The method for synthesizing 3, 3-disubstituted indolone compounds and 4, 4-disubstituted isoquinolinedione compounds according to claim 2, characterized in that: the molar ratio of the 2-aryloxy-1H-benzo [ d ] imidazole compound 1, 3-diazonium-2-indolone compound or 4-diazonium-1, 3-isoquinolinedione compound 2, dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer to the additive A is 1:1-2:0.02-0.03:1-2.
6. The method for synthesizing 3, 3-disubstituted indolone compounds and 4, 4-disubstituted isoquinolinedione compounds according to claim 2, characterized in that: the additive also comprises a silver salt additive B; the silver salt additive B is silver hexafluoroantimonate, silver trifluoromethane sulfonate, silver tetrafluoroborate, silver bistrifluoromethane sulfonyl imide, silver acetate or silver trifluoroacetate.
7. The method for synthesizing 3, 3-disubstituted indolone compounds and 4, 4-disubstituted isoquinolinedione compounds according to claim 6, characterized in that: the mol ratio of the additive A to the additive B is 1-2:0.1-0.3.
8. The method for synthesizing 3, 3-disubstituted indolone compounds and 4, 4-disubstituted isoquinolinedione compounds according to claim 2, characterized in that: the reaction temperature is 25-100 ℃.
9. The method for synthesizing 3, 3-disubstituted indolone compounds and 4, 4-disubstituted isoquinolinedione compounds according to any one of claims 2 to 8, characterized in that: the reaction was carried out under an air atmosphere.
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