CN108640914B - Method for synthesizing isoindole [2,1-b ] isoquinoline-5, 7-diketone compound - Google Patents

Method for synthesizing isoindole [2,1-b ] isoquinoline-5, 7-diketone compound Download PDF

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CN108640914B
CN108640914B CN201810355807.5A CN201810355807A CN108640914B CN 108640914 B CN108640914 B CN 108640914B CN 201810355807 A CN201810355807 A CN 201810355807A CN 108640914 B CN108640914 B CN 108640914B
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isoindole
isoquinoline
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isoquinolinone
oac
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郭胜海
王芳
范学森
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Henan Normal University
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    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
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Abstract

The invention discloses a method for synthesizing isoindole [2,1-b]A method for preparing isoquinoline-5, 7-diketone compounds, belonging to the technical field of organic synthesis. Technique of the inventionThe key point of the scheme is that NH-isoquinolinone compounds, organic solvent, catalyst, oxidant and alkali are added into a reaction tube in turn or NH-isoquinolinone compounds, organic solvent, catalyst and oxidant are added into the reaction tube in turn, vacuumizing and CO charging are carried out for three times, then the reaction is heated and stirred in an oil bath at 120 ℃, T L C is followed to monitor the completion of the reaction, and the isoindole [2,1-b]Isoquinoline-5, 7-diketone compounds. The invention overcomes the defects of the prior synthetic method of the compounds such as high toxicity and explosiveness of reactants, poor reaction selectivity, long synthetic route and the like, and is a method for synthesizing isoindole [2,1-b]The efficient method for synthesizing the isoquinoline-5, 7-diketone compound has the advantages of easy preparation of raw materials, simple reaction operation, wide applicability of substrates, high yield and the like.

Description

Method for synthesizing isoindole [2,1-b ] isoquinoline-5, 7-diketone compound
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing isoindole [2,1-b ] isoquinoline-5, 7-diketone compounds.
Background
The compound containing the isoindole isoquinoline skeleton not only widely exists in natural products and synthetic drugs with important biological activity, but also shows good fluorescence performance, attracts more and more researchers' attention and research in recent years, wherein, the isoindole [2,1-b ] isoquinoline-5, 7-diketone is a very important isoindole isoquinoline compound with potential fluorescence performance and has wide application prospect in the research fields of biological imaging, organic light emitting diodes (O L ED) and the like.
Disclosure of Invention
The technical problem to be solved by the invention is to provide a method for synthesizing the isoindole [2,1-b ] isoquinoline-5, 7-diketone compound, which has the advantages of easily obtained starting materials, simple reaction operation, wide substrate applicability, high yield and no need of high-pressure equipment.
The invention adopts the following technical scheme for solving the technical problems, and the method for synthesizing the isoindole [2,1-b ] isoquinoline-5, 7-diketone compound is characterized by comprising the following specific steps of sequentially adding NH-isoquinolinone compound 1, an organic solvent, a catalyst, an oxidant and alkali into a reaction tube or sequentially adding NH-isoquinolinone compound 1, an organic solvent, a catalyst and an oxidant into the reaction tube, vacuumizing and filling CO for three times, then placing the reaction tube in an oil bath at 120 ℃ for heating and stirring reaction, and tracking and monitoring the reaction completion by T L C to prepare the isoindole [2,1-b ] isoquinoline-5, 7-diketone compound 2, wherein the reaction equation in the synthesis process is as follows:
Figure BDA0001634568440000011
wherein R is1Is hydrogen, methyl, methoxy, fluorine, chlorine or bromine, R2Is hydrogen, methyl, fluorine or chlorine, R3Is hydrogen, methyl, phenyl, 4-methylphenyl, 3-methylphenyl, 4-fluorophenyl, 4-chlorophenyl, 2-chlorophenyl or thiophen-2-yl, and the catalyst is Pd (OAc)2、PdCl2、Pd(OTFA)2Or Pd (PPh)3)2Cl2The oxidant is AgOTFA, Cu (OAc)2、Cu(OTf)2、K2S2O8、AgOAc、Cu(OTFA)2、O2Or BQ (1,4-benzoquinone, p-benzoquinone) and Na as base2CO3、K2CO3、K3PO4DBU, DABCO or Et3N, the organic solvent is chlorobenzene, toluene or o-xylene.
Further preferably, the oxidant is AgOTFA, Cu (OAc)2、Cu(OTf)2、K2S2O8、AgOAc、Cu(OTFA)2Or when BQ is adopted, the feeding molar ratio of the NH-isoquinolinone compound, the catalyst, the oxidant and the alkali is 1.0:0.1:2.0: 0.5.
Synthetic isoindole [2,1-b]The method for preparing the isoquinoline-5, 7-diketone compound is characterized by comprising the following specific steps: NH-isoquinolinone 1o, chlorobenzene, Pd (OAc) are added into a reaction tube in sequence2AgOTFA and Na2CO3Vacuumizing and filling CO three times, heating in 120 deg.C oil bath while stirring for reaction, and tracking and monitoring the reaction at T L C to obtain isoindole [2,1-b ]]Isoquinoline-5, 7-diketone 2o, and the reaction equation in the synthesis process is as follows:
Figure BDA0001634568440000021
the invention overcomes the defects of high toxicity, explosive property, poor reaction selectivity, long synthesis route and the like of reactants in the existing synthesis method of the compounds, is an efficient method for synthesizing the isoindole [2,1-b ] isoquinoline-5, 7-diketone compounds, and has the advantages of easy preparation of raw materials, simple reaction operation, wide substrate applicability, high yield and the like.
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
Figure BDA0001634568440000022
Into a schlenk reaction tube of 15m L, NH-isoquinolinone 1a (118.8mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added in order2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃, heating and stirring for 15h, after the reaction is finished, quenching the reaction by using a saturated ammonium chloride solution, extracting by using dichloromethane, washing an organic phase by using deionized water and saturated salt solution, and adding anhydrous sodium sulfate for drying. Filtering, concentrating under reduced pressure, separating and purifying with silica gel column (eluent is dichloromethane/ethyl acetate with volume ratio of 10/1) to obtain yellow solid isoindole [2,1-b]Isoquinoline-5, 7-dione 2a (105mg, 81%). The characterization data for this compound are as follows:1H NMR(CDCl3,600MHz)6.26(d,J＝7.8Hz,1H),7.05(d,J＝7.8Hz,1H),7.26(t,J＝7.8Hz,1H),7.35-7.37(m,3H),7.44-7.47(m,1H),7.50-7.53(m,1H),7.56-7.58(m,3H),7.91(d,J＝7.2Hz,1H),8.51(d,J＝7.2Hz,1H)；13C NMR(CDCl3,150MHz)119.8,123.7,125.4,126.5,127.9,128.2,128.5,129.2,129.3,129.8,129.9,130.3,131.5,133.8,133.9,134.3,135.2,137.4,159.8,165.4.HRMS(ESI)calcd for C22H13NNaO2[M+Na]+346.0838,found 346.0862。
example 2
The procedure described in example 1 was followed to add NH-isoquinolinone 1a (118.8mg,0.4mmol), chlorobenzene (2m L), PdCl in succession to a 15m L schlenk reaction tube2(7.1mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃ and heating and stirring for 15h to prepare the isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (63mg, 49%).
Example 3
According to the method described in example 1, NH-isoquinolinone 1a (118.8mg,0.4mmol), chlorobenzene (2m L), Pd (OTFA) are added successively to a 15m L schlenk reaction tube2(13.3mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃ and heating and stirring for 15h to prepare the isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (86mg, 66%).
Example 4
The procedure described in example 1 was followed to add NH-isoquinolinone 1a (118.8mg,0.4mmol), chlorobenzene (2m L), Pd (PPh) sequentially into a 15m L schlenk reaction tube3)2Cl2(28.1mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃ and heating and stirring for 15h to prepare the isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (61mg, 47%).
Example 5
The procedure described in example 1 was followed to add NH-isoquinolinone 1a (118.8mg,0.4mmol), chlorobenzene (2m L), [ Cp + RhCl ] in succession to a 15m L schlenk reaction tube2]2(24.7mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃ and heating and stirring for 15h to obtain the isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (0mg, 0%).
Example 6
By the method described in example 1, at 15m LTo the schlenk reaction tube were successively added NH-isoquinolinone 1a (118.8mg,0.4mmol), chlorobenzene (2m L), Pd (OAc)2(9.0mg,0.04mmol)，Cu(OAc)2(145.5mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃ and heating and stirring for 15h to prepare the isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (60mg, 47%).
Example 7
The procedure was as described in example 1, NH-isoquinolinone 1a (118.8mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，Cu(OTf)2(289.3mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃ and heating and stirring for 15h to prepare the isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (20mg, 15%).
Example 8
The procedure was as described in example 1, NH-isoquinolinone 1a (118.8mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，K2S2O8(216.3mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃ and heating and stirring for 15h to prepare the isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (79mg, 61%).
Example 9
The procedure was as described in example 1, NH-isoquinolinone 1a (118.8mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOAc(133.5mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃ and heating and stirring for 15h to prepare the isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (76mg, 59%).
Example 10
The procedure was as described in example 1, NH-isoquinolinone 1a (118.8mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，Cu(OTFA)2(231.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuum pumping and CO charging three times,then placing the mixture in an oil bath at the temperature of 120 ℃ for heating and stirring for 15 hours to prepare the isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (27mg, 21%).
Example 11
The procedure was as described in example 1, NH-isoquinolinone 1a (118.8mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，Na2CO3(21.2mg,0.2mmol), evacuation and CO/O filling2(2:1) three times, then placing the mixture in an oil bath at the temperature of 120 ℃, heating and stirring the mixture for 15 hours to prepare the isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (8mg, 6%).
Example 12
The procedure was as described in example 1, NH-isoquinolinone 1a (118.8mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，BQ(86.5mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃ and heating and stirring for 15h to prepare the isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (51mg, 39%).
Example 13
The procedure was as described in example 1, NH-isoquinolinone 1a (118.8mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，K2CO3(27.6mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃ and heating and stirring for 15h to prepare the isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (70mg, 54%).
Example 14
The procedure was as described in example 1, NH-isoquinolinone 1a (118.8mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，K3PO4(42.5mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃ for heating and stirring for 15h to prepare the isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (66mg, 51%).
Example 15
The procedure described in example 1 was followed to add NH-isoquinolinone 1a (118.8mg,0.4mmol), chlorobenzene (0.4 mmol) in succession to a 15m L schlenk reaction tube2mL)，Pd(OAc)2(9.0mg,0.04mmol), AgOTFA (176.7mg,0.8mmol), DBU (30.4mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃ to heat and stir for 15h to obtain isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (93mg, 72%).
Example 16
The procedure was as described in example 1, NH-isoquinolinone 1a (118.8mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol), AgOTFA (176.7mg,0.8mmol), DABCO (22.4mg,0.2mmol), vacuumizing and CO charging three times, then placing in a 120 ℃ oil bath to heat and stir for 15h to obtain isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (41mg, 32%).
Example 17
The procedure was as described in example 1, NH-isoquinolinone 1a (118.8mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol), AgOTFA (176.7mg,0.8mmol), TEA (20.2mg,0.2mmol), vacuumizing and CO charging three times, then placing in an oil bath at 120 ℃ to heat and stir for 15h to obtain isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (77mg, 59%).
Example 18
According to the method described in example 1, NH-isoquinolinone 1a (118.8mg,0.4mmol), toluene (2m L), Pd (OAc) are added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃ and heating and stirring for 15h to prepare the isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (65mg, 50%).
Example 19
According to the method described in example 1, NH-isoquinolinone 1a (118.8mg,0.4mmol), o-xylene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃ and heating and stirring for 15h to prepare the isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (32mg, 25%).
Example 20
The process as described in example 1NH-isoquinolinone 1a (118.8mg,0.4mmol), DMSO (2m L), Pd (OAc) are added in sequence to a schlenk reaction tube of 15m L2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃ and heating and stirring for 15h to obtain the isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (0mg, 0%).
Example 21
According to the method described in example 1, NH-isoquinolinone 1a (118.8mg,0.4mmol), DMF (2m L), Pd (OAc) are added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃ and heating and stirring for 15h to obtain the isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (0mg, 0%).
Example 22
NH-isoquinolinone 1a (118.8mg,0.4mmol), chlorobenzene (2m L), AgOTFA (176.7mg,0.8mmol), Na were added successively to a 15m L schlenk reaction tube as described in example 12CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃ and heating and stirring for 15h to obtain the isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (0mg, 0%).
Example 23
The procedure was as described in example 1, NH-isoquinolinone 1a (118.8mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃ and heating and stirring for 15h to prepare the isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (6mg, 4%).
Example 24
The procedure was as described in example 1, NH-isoquinolinone 1a (118.8mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol) and AgOTFA (176.7mg,0.8mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃ and heating and stirring for 15h to prepare the isoindole [2,1-b ]]Isoquinoline-5, 7-dione 2a (71mg, 55%).
Example 25
Figure BDA0001634568440000061
The procedure was as described in example 1, NH-isoquinolinone 1b (136.8mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃, heating and stirring for 15h, after the reaction is finished, quenching the reaction by using a saturated ammonium chloride solution, extracting by using dichloromethane, washing an organic phase by using deionized water and saturated salt solution, and adding anhydrous sodium sulfate for drying. Filtering, concentrating under reduced pressure, separating and purifying with silica gel column (eluent is dichloromethane/ethyl acetate with volume ratio of 10/1) to obtain yellow solid isoindole [2,1-b]Isoquinoline-5, 7-dione 2b (101mg, 75%). The characterization data for this compound are as follows:1H NMR(CDCl3,400MHz)2.35(s,3H),6.28(d,J＝8.0Hz,1H),6.87(s,1H),7.30-7.34(m,2H),7.40-7.43(m,3H),7.63-7.65(m,3H),7.97(d,J＝7.6Hz,1H),8.45(d,J＝8.0Hz,1H)；13C NMR(CDCl3,150MHz)22.0,119.9,123.7,125.3,125.5,126.6,128.2,129.2,129.3,129.8,130.4,131.6,134.0,134.3,135.2,137.4,144.8,159.7,165.4(two13Csignals were not observed).HRMS(ESI)calcd for C23H15NNaO2[M+Na]+360.0995,found360.1011。
example 26
Figure BDA0001634568440000071
The procedure was as described in example 1, NH-isoquinolinone 1c (124.4mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃, heating and stirring for 15h, after the reaction is finished, quenching the reaction by using a saturated ammonium chloride solution, extracting by using dichloromethane, washing an organic phase by using deionized water and saturated salt solution, and adding anhydrous sodium sulfate for drying. FiltrationConcentrating under reduced pressure, separating and purifying with silica gel column (eluent is dichloromethane/ethyl acetate with volume ratio of 10/1) to obtain yellow solid isoindole [2,1-b]Isoquinoline-5, 7-dione 2c (110.5mg, 82%). The characterization data for this compound are as follows:1H NMR(CDCl3,400MHz)2.48(s,3H),6.32(d,J＝7.6Hz,1H),7.01(d,J＝8.0Hz,1H),7.32(t,J＝7.6Hz,1H),7.38-7.43(m,4H),7.62-7.63(m,3H),7.97(d,J＝7.6Hz,1H),8.38(s,1H)；13C NMR(CDCl3,150MHz)21.3,120.0,123.5,125.3,126.5,127.7,128.1,129.1,129.2,129.6,129.7,130.3,130.6,134.0,134.3,135.0,135.3,139.0,159.8,165.4(one13C signal was not observed).HRMS(ESI)calcd for C23H16NO2[M+H]+338.1176,found 338.1176。
example 27
Figure BDA0001634568440000072
The procedure was as described in example 1, NH-isoquinolinone 1d (124.4mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃, heating and stirring for 15h, after the reaction is finished, quenching the reaction by using a saturated ammonium chloride solution, extracting by using dichloromethane, washing an organic phase by using deionized water and saturated salt solution, and adding anhydrous sodium sulfate for drying. Filtering, concentrating under reduced pressure, separating and purifying with silica gel column (eluent is dichloromethane/ethyl acetate with volume ratio of 10/1) to obtain yellow solid isoindole [2,1-b]Isoquinoline-5, 7-dione 2d (96mg, 71%). The characterization data for this compound are as follows:1H NMR(CDCl3,600MHz)2.97(s,3H),6.26(d,J＝7.8Hz,1H),6.97(d,J＝7.8Hz,1H),7.27(d,J＝7.2Hz,1H),7.30-7.33(m,1H),7.39-7.42(m,4H),7.62-7.63(m,3H),7.94(d,J＝7.8Hz,1H)；13C NMR(CDCl3,150MHz)24.1,120.0,123.6,125.16,125.21,125.7,128.4,129.1,129.7,130.4,131.3,132.3,132.8,134.1,134.5,134.7,138.9,144.2,160.7,165.5(one13C signal was not observed).HRMS(ESI)calcd for C23H15NNaO2[M+Na]+360.0995,found 360.0996。
example 28
Figure BDA0001634568440000081
The procedure was as described in example 1, NH-isoquinolinone 1e (130.8mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃, heating and stirring for 15h, after the reaction is finished, quenching the reaction by using a saturated ammonium chloride solution, extracting by using dichloromethane, washing an organic phase by using deionized water and saturated salt solution, and adding anhydrous sodium sulfate for drying. Filtering, concentrating under reduced pressure, separating and purifying with silica gel column (eluent is dichloromethane/ethyl acetate with volume ratio of 10/1) to obtain yellow solid isoindole [2,1-b]Isoquinoline-5, 7-dione 2e (95mg, 67%). The characterization data for this compound are as follows:1H NMR(CDCl3,400MHz)3.76(s,3H),6.31(d,J＝7.6Hz,1H),6.50(d,J＝2.0Hz,1H),7.05(dd,J＝2.0,8.8Hz,1H),7.32(t,J＝7.6Hz,1H),7.40-7.43(m,3H),7.62-7.63(m,3H),7.97(d,J＝7.6Hz,1H),8.51(d,J＝8.8Hz,1H)；13C NMR(CDCl3,150MHz)55.5,110.2,115.2,119.6,121.1,123.7,125.3,128.4,129.2,129.8,129.9,130.3,131.5,132.2,133.8,134.2,135.1,139.6,159.4,164.0,165.3.HRMS(ESI)calcd for C23H16NO3[M+H]+354.1125,found 354.1135。
example 29
Figure BDA0001634568440000091
The procedure was as described in example 1, NH-isoquinolinone 1f (126.0mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in a 120 ℃ oil bath for heating and stirring for 15h, after the reaction is finished,the reaction was quenched with a saturated ammonium chloride solution, extracted with dichloromethane, and the organic phase was washed with deionized water and saturated brine, and dried over anhydrous sodium sulfate. Filtering, concentrating under reduced pressure, separating and purifying with silica gel column (eluent is dichloromethane/ethyl acetate with volume ratio of 10/1) to obtain yellow solid isoindole [2,1-b]Isoquinoline-5, 7-dione 2f (111mg, 74%). The characterization data for this compound are as follows:1H NMR(CDCl3,600MHz)6.35(d,J＝8.4Hz,1H),6.75(d,J＝9.6Hz,1H),7.20(t,J＝8.4Hz,1H),7.35(t,J＝7.8Hz,1H),7.42-7.47(m,3H),7.65(m,3H),7.98(d,J＝7.2Hz,1H),8.57(t,J＝7.2Hz,1H)；13C NMR(CDCl3,150MHz)112.5(d,J＝23.1Hz,1C),116.4(d,J＝23.0Hz,1C),118.9(d,J＝3.3Hz,1C),123.9,124.2,125.4,128.2,129.5,130.0,130.2,130.3,132.3(d,J＝11.0Hz,1C),132.8,133.2,134.5,134.9,140.2(d,J＝9.8Hz,1C),158.8,165.1,166.3(d,J＝253.8Hz,1C).HRMS(ESI)calcd for C22H13FNO2[M+H]+342.0925,found 342.0922。
example 30
Figure BDA0001634568440000092
According to the method described in example 1, 1g (132.4mg,0.4mmol) of NH-isoquinolinone, chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃, heating and stirring for 15h, after the reaction is finished, quenching the reaction by using a saturated ammonium chloride solution, extracting by using dichloromethane, washing an organic phase by using deionized water and saturated salt solution, and adding anhydrous sodium sulfate for drying. Filtering, concentrating under reduced pressure, separating and purifying with silica gel column (eluent is dichloromethane/ethyl acetate with volume ratio of 10/1) to obtain yellow solid isoindole [2,1-b]Isoquinoline-5, 7-dione 2g (113mg, 79%). The characterization data for this compound are as follows:1H NMR(CDCl3,400MHz)6.32(d,J＝8.0Hz,1H),7.06(d,J＝1.2Hz,1H),7.35(t,J＝7.6Hz,1H),7.41-7.43(m,2H),7.45(s,1H),7.48(m,1H),7.65-7.67(m,3H),7.98(d,J＝7.2Hz,1H),8.50(d,J＝8.4Hz,1H)；13C NMR(CDCl3,150MHz)118.6,123.9,125.4,126.0,126.1,128.1,128.7,129.5,130.0,130.27,130.28,130.8,132.8,133.1,134.5,134.9,138.9,140.7,158.9,165.1.HRMS(ESI)calcd for C22H13ClNO2[M+H]+358.0629,found358.0630。
example 31
Figure BDA0001634568440000101
The procedure was as described in example 1, NH-isoquinolinone 1h (132.4mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃, heating and stirring for 15h, after the reaction is finished, quenching the reaction by using a saturated ammonium chloride solution, extracting by using dichloromethane, washing an organic phase by using deionized water and saturated salt solution, and adding anhydrous sodium sulfate for drying. Filtering, concentrating under reduced pressure, separating and purifying with silica gel column (eluent is dichloromethane/ethyl acetate with volume ratio of 10/1) to obtain yellow solid isoindole [2,1-b]Isoquinoline-5, 7-dione 2h (93mg, 65%). The characterization data for this compound are as follows:1H NMR(CDCl3,400MHz)6.26(d,J＝8.0Hz,1H),7.02(d,J＝7.6Hz,1H),7.33(t,J＝7.6Hz,1H),7.39-7.46(m,4H),7.52(d,J＝7.6Hz,1H),7.63-7.65(m,3H),7.98(d,J＝7.6Hz,1H)；13C NMR(CDCl3,150MHz)118.8,123.9,124.1,125.3,125.8,128.3,129.4,129.9,130.2,130.4,132.0,132.2,133.2,133.8,134.4,134.5,137.7,140.4,157.8,165.0.HRMS(ESI)calcd for C22H12ClNNaO2[M+Na]+380.0449,found 380.0446。
example 32
Figure BDA0001634568440000102
The procedure was as described in example 1, NH-isoquinolinone 1i (150.0mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃, heating and stirring for 15h, after the reaction is finished, quenching the reaction by using a saturated ammonium chloride solution, extracting by using dichloromethane, washing an organic phase by using deionized water and saturated salt solution, and adding anhydrous sodium sulfate for drying. Filtering, concentrating under reduced pressure, separating and purifying with silica gel column (eluent is dichloromethane/ethyl acetate with volume ratio of 10/1) to obtain yellow solid isoindole [2,1-b]Isoquinoline-5, 7-dione 2i (122mg, 76%). The characterization data for this compound are as follows:1H NMR(CDCl3,400MHz)6.33(d,J＝7.6Hz,1H),6.98(d,J＝8.4Hz,1H),7.34(t,J＝7.6Hz,1H),7.39-7.42(m,2H),7.45(t,J＝7.6Hz,1H),7.63-7.68(m,4H),7.98(d,J＝7.6Hz,1H),8.68(d,J＝2.0Hz,1H)；13C NMR(CDCl3,150MHz)119.1,123.0,123.8,125.5,128.0,128.1,129.2,129.4,129.9,130.1,130.3,131.8,133.3,134.6,135.1,136.2,136.9,158.5,165.1(one13C signal was not observed).HRMS(ESI)calcd forC22H12BrNNaO2[M+Na]+423.9944,found 423.9943。
example 33
Figure BDA0001634568440000111
The procedure was as described in example 1, NH-isoquinolinone 1j (130.0mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃, heating and stirring for 15h, after the reaction is finished, quenching the reaction by using a saturated ammonium chloride solution, extracting by using dichloromethane, washing an organic phase by using deionized water and saturated salt solution, and adding anhydrous sodium sulfate for drying. Filtering, concentrating under reduced pressure, separating and purifying with silica gel column (eluent is dichloromethane/ethyl acetate with volume ratio of 10/1) to obtain yellow solid isoindole [2,1-b]Isoquinoline-5, 7-dione 2j (104mg, 74%). The characterization data for this compound are as follows:1H NMR(CDCl3,400MHz)2.39(s,3H),2.54(s,3H),6.29(d,J＝8.4Hz,1H),7.12(d,J＝8.0Hz,1H),7.16(d,J＝8.4Hz,1H),7.29(d,J＝7.6Hz,2H),7.42(d,J＝8.0Hz,2H),7.49(t,J＝7.6Hz,1H),7.56(t,J＝7.6Hz,1H),7.77(s,1H),8.55(d,J＝8.0Hz,1H)；13C NMR(CDCl3,100MHz)21.4,21.5,119.0,123.6,125.3,126.4,127.7,128.1,128.3,129.1,130.2,130.4,130.8,131.7,132.9,133.6,135.5,137.7,139.0,140.5,159.8,165.5.HRMS(ESI)calcd for C24H17NNaO2[M+Na]+374.1151,found 374.1163。
example 34
Figure BDA0001634568440000112
According to the method described in example 1, NH-isoquinolinone 1k (130.0mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) are added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃, heating and stirring for 15h, after the reaction is finished, quenching the reaction by using a saturated ammonium chloride solution, extracting by using dichloromethane, washing an organic phase by using deionized water and saturated salt solution, and adding anhydrous sodium sulfate for drying. Filtering, concentrating under reduced pressure, separating and purifying with silica gel column (eluent is dichloromethane/ethyl acetate with volume ratio of 10/1) to obtain yellow solid isoindole [2,1-b]Isoquinoline-5, 7-dione 2k (101mg, 72%). The characterization data for this compound are as follows:1H NMR(CDCl3,400MHz)2.19(s,3H),2.48(s,3H),6.13(s,1H),7.15(d,J＝7.6Hz,1H),7.21-7.23(m,3H),7.44(d,J＝7.6Hz,1H),7.49-7.54(m,2H),7.57(d,J＝7.2Hz,1H),7.83(d,J＝7.6Hz,1H),8.54(d,J＝7.6Hz,1H)；13C NMR(CDCl3,150MHz)21.5,22.3,119.7,124.3,125.1,125.7,126.5,127.3,127.9,128.3,129.1,129.5,129.8,130.8,130.9,131.5,133.7,133.8,135.7,137.5,139.5,145.4,159.8,165.4.HRMS(ESI)calcd forC24H17NNaO2[M+Na]+374.1151,found 374.1150。
example 35
Figure BDA0001634568440000121
According to the method described in example 1, NH-isoquinolinone 1l (133.2mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) are added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃, heating and stirring for 15h, after the reaction is finished, quenching the reaction by using a saturated ammonium chloride solution, extracting by using dichloromethane, washing an organic phase by using deionized water and saturated salt solution, and adding anhydrous sodium sulfate for drying. Filtering, concentrating under reduced pressure, separating and purifying with silica gel column (eluent is dichloromethane/ethyl acetate with volume ratio of 10/1) to obtain yellow solid isoindole [2,1-b]Isoquinoline-5, 7-dione 2l (111mg, 77%). The characterization data for this compound are as follows:1H NMR(CDCl3,400MHz)6.34-6.37(m,1H),7.07-7.11(m,2H),7.35(t,J＝8.4Hz,2H),7.40-7.43(m,2H),7.54(t,J＝7.6Hz,1H),7.59-7.65(m,2H),8.56(d,J＝7.6Hz,1H)；13CNMR(CDCl3,150MHz)111.8(d,J＝24.0Hz,1C),117.1(d,J＝21.9Hz,2C),118.7,122.2(d,J＝23.0Hz,1C),125.6(d,J＝7.7Hz,1C),126.4,127.3,128.6,129.1,129.4(d,J＝3.3Hz,1C),130.2(d,J＝8.7Hz,1C),131.0(d,J＝2.3Hz,1C),132.3(d,J＝8.7Hz,2C),134.0,137.1,159.3,163.3(d,J＝248.3Hz,1C),163.5(d,J＝252.8Hz,1C),163.9(d,J＝3.3Hz,1C)(one13C signal was not observed).HRMS(ESI)calcd for C22H11F2NNaO2[M+Na]+382.0650,found 382.0656。
example 36
Figure BDA0001634568440000122
According to the method described in example 1, NH-isoquinolinone 1m (146.0mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) are added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃, heating and stirring for 15h, after the reaction is finished, quenching the reaction by using a saturated ammonium chloride solution, extracting by using dichloromethane, and using deionized water and saturated food for an organic phaseWashed with brine and dried by adding anhydrous sodium sulfate. Filtering, concentrating under reduced pressure, separating and purifying with silica gel column (eluent is dichloromethane/ethyl acetate with volume ratio of 10/1) to obtain yellow solid isoindole [2,1-b]Isoquinoline-5, 7-dione 2m (113mg, 72%). The characterization data for this compound are as follows:1H NMR(CDCl3,400MHz)6.34-6.37(m,1H),7.07-7.10(m,2H),7.36(t,J＝8.0Hz,2H),7.43-7.46(m,2H),7.50(t,J＝7.6Hz,1H),7.58-7.62(m,2H),8.50(d,J＝8.0Hz,1H)；13CNMR(CDCl3,150MHz)119.0,124.7,125.4,126.3,127.7,128.9,129.5,129.7,130.2,131.0,131.8,132.0,133.1,134.1,134.7,135.7,136.6,136.8,159.4,163.9.HRMS(ESI)calcd for C22H11Cl2NNaO2[M+Na]+414.0059,found 414.0061。
example 37
Figure BDA0001634568440000131
According to the method described in example 1, NH-isoquinolinone 1n (146.0mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) are added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃, heating and stirring for 15h, after the reaction is finished, quenching the reaction by using a saturated ammonium chloride solution, extracting by using dichloromethane, washing an organic phase by using deionized water and saturated salt solution, and adding anhydrous sodium sulfate for drying. Filtering, concentrating under reduced pressure, separating and purifying with silica gel column (eluent is dichloromethane/ethyl acetate with volume ratio of 10/1) to obtain yellow solid isoindole [2,1-b]Isoquinoline-5, 7-dione 2n (11mg, 7%). The characterization data for this compound are as follows:1H NMR(CDCl3,600MHz)7.01(d,J＝7.8Hz,1H),7.37-7.41(m,2H),7.44(t,J＝7.2Hz,1H),7.47-7.51(m,2H),7.55-7.60(m,3H),8.00(d,J＝7.2Hz,1H),8.57(d,J＝7.2Hz,1H)；13C NMR(CDCl3,150MHz)119.9,124.2,126.9,127.38,127.43,129.0,129.2,129.9,130.1,130.7,131.2,131.9,132.0,132.5,133.7,134.1,135.4,136.2,136.6,138.1,159.8,164.0.HRMS(ESI)calcd for C22H11Cl2NNaO2[M+Na]+414.0059,found 414.0052。
example 38
Figure BDA0001634568440000132
The procedure was as described in example 1, NH-isoquinolinone 1o (123.6mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃, heating and stirring for 15h, after the reaction is finished, quenching the reaction by using a saturated ammonium chloride solution, extracting by using dichloromethane, washing an organic phase by using deionized water and saturated salt solution, and adding anhydrous sodium sulfate for drying. Filtering, concentrating under reduced pressure, separating and purifying with silica gel column (eluent is dichloromethane/ethyl acetate with volume ratio of 10/1) to obtain yellow solid isoindole [2,1-b]Isoquinoline-5, 7-dione 2o (84mg, 63%). The characterization data for this compound are as follows:1H NMR(CDCl3,400MHz)7.22-7.23(m,1H),7.29-7.39(m,4H),7.53(t,J＝7.6Hz,1H),7.63(t,J＝7.6Hz,1H),6.67(d,J＝5.2Hz,1H),8.54(d,J＝8.0Hz,1H)；13C NMR(CDCl3,150MHz)111.3,121.5,126.4,128.2,128.7,128.9,129.5,129.8,131.8,132.7,133.91,133.93,136.7,137.0,146.1,159.0,160.2(one13C signal was not observed).HRMS(ESI)calcd for C18H9NNaO2S2[M+Na]+357.9967,found 357.9968。
example 39
Figure BDA0001634568440000141
The procedure was as described in example 1, NH-isoquinolinone 1p (94.0mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃, heating and stirring for 15h, after the reaction is finished, quenching the reaction by using a saturated ammonium chloride solution,the dichloromethane extraction, organic phase with deionized water and saturated brine washing, adding anhydrous sodium sulfate drying. Filtering, concentrating under reduced pressure, separating and purifying with silica gel column (eluent is dichloromethane/ethyl acetate with volume ratio of 10/1) to obtain yellow solid isoindole [2,1-b]Isoquinoline-5, 7-dione 2p (78mg, 75%). The characterization data for this compound are as follows:1H NMR(CDCl3,400MHz)2.71(s,3H),7.51-7.56(m,2H),7.72-7.78(m,3H),8.02-8.05(m,2H),8.53(d,J＝8.0Hz,1H)；13C NMR(CDCl3,150MHz)13.0,114.6,124.1,124.2,125.6,127.8,128.3,129.3,129.5,131.0,133.8,134.7,135.5,136.9,159.6,165.1(one13Csignal was not observed).HRMS(ESI)calcd for C17H11NNaO2[M+Na]+284.0682,found284.0697。
example 40
Figure BDA0001634568440000142
According to the method described in example 1, NH-isoquinolinone 1q (88.4mg,0.4mmol), chlorobenzene (2m L), Pd (OAc) were added successively to a 15m L schlenk reaction tube2(9.0mg,0.04mmol)，AgOTFA(176.7mg,0.8mmol)，Na2CO3(21.2mg,0.2mmol), vacuumizing and charging CO three times, then placing in an oil bath at 120 ℃, heating and stirring for 15h, after the reaction is finished, quenching the reaction by using a saturated ammonium chloride solution, extracting by using dichloromethane, washing an organic phase by using deionized water and saturated salt solution, and adding anhydrous sodium sulfate for drying. Filtering, concentrating under reduced pressure, separating and purifying with silica gel column (eluent is dichloromethane/ethyl acetate with volume ratio of 10/1) to obtain yellow solid isoindole [2,1-b]Isoquinoline-5, 7-dione 2q (79mg, 80%). The characterization data for this compound are as follows:1H NMR(CDCl3,400MHz)6.92(s,1H),7.46(t,J＝8.0Hz,1H),7.50-7.53(m,2H),7.64(t,J＝7.6Hz,1H),7.70(t,J＝7.2Hz,1H),7.77(d,J＝7.6Hz,1H),7.93(d,J＝8.0Hz,1H),8.42(d,J＝8.0Hz,1H)；13C NMR(CDCl3,150MHz)103.6,120.6,125.5,127.5,127.7,128.2,128.5,129.4,130.5,133.9,134.8,135.0,135.6,159.7,165.1(one13C signal was notobserved).HRMS(ESI)calcd for C16H9NNaO2[M+Na]+270.0525,found 270.0532。
the foregoing embodiments illustrate the principles, principal features and advantages of the invention, and it will be understood by those skilled in the art that the invention is not limited to the foregoing embodiments, which are merely illustrative of the principles of the invention, and that various changes and modifications may be made therein without departing from the scope of the principles of the invention.

Claims (3)

1. Synthesis of isoindole [2,1-b]A process for preparing isoquinoline-5, 7-diketone compounds includes such steps as sequentially adding NH-isoquinolone compound 1, organic solvent, catalyst, oxidant and alkali to reaction tube, vacuumizing, filling CO three times, heating in 120 deg.C oil bath while stirring, and tracking and monitoring by T L C to obtain isoindole [2,1-b]The reaction equation of the isoquinoline-5, 7-diketone compound 2 in the synthesis process is as follows:
Figure DEST_PATH_IMAGE002
wherein R is1Is hydrogen, methyl, methoxy, fluorine, chlorine or bromine, R2Is hydrogen, methyl, fluorine or chlorine, R3Is hydrogen, methyl, phenyl, 4-methylphenyl, 3-methylphenyl, 4-fluorophenyl, 4-chlorophenyl, 2-chlorophenyl or thiophen-2-yl, and the catalyst is Pd (OAc)2、PdCl2、Pd(OTFA)2Or Pd (PPh)3)2Cl2The oxidant is AgOTFA, Cu (OAc)2、Cu(OTf)2、K2S2O8、AgOAc、Cu(OTFA)2、O2Or BQ, the base is Na2CO3、K2CO3、K3PO4DBU, DABCO or Et3N, the organic solvent is chlorobenzene, toluene or o-xylene.
2. The synthetic isoindole [2,1-b]A method for producing isoquinoline-5, 7-diones characterized by: the oxidant is AgOTFA, Cu (OAc)2、Cu(OTf)2、K2S2O8、AgOAc、Cu(OTFA)2Or when BQ is adopted, the feeding molar ratio of the NH-isoquinolinone compound, the catalyst, the oxidant and the alkali is 1.0:0.1:2.0: 0.5.
3. A method for synthesizing a compound 2o is characterized by comprising the following specific steps: NH-isoquinolinone 1o, chlorobenzene, Pd (OAc) are added into a reaction tube in sequence2AgOTFA and Na2CO3Vacuumizing and filling CO for three times, then placing the mixture in an oil bath at 120 ℃ for heating and stirring reaction, tracking and monitoring the completion of the reaction by T L C to obtain a compound 2o, wherein the reaction equation in the synthesis process is as follows:
Figure DEST_PATH_IMAGE004
。
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