CN110396094B - Quinolinone heteroaromatic ring compound and derivative and synthetic method thereof - Google Patents

Quinolinone heteroaromatic ring compound and derivative and synthetic method thereof Download PDF

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CN110396094B
CN110396094B CN201810371557.4A CN201810371557A CN110396094B CN 110396094 B CN110396094 B CN 110396094B CN 201810371557 A CN201810371557 A CN 201810371557A CN 110396094 B CN110396094 B CN 110396094B
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quinolinone
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CN110396094A (en
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姜雪峰
丁冬
朱国浩
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East China 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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    • 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
    • C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
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    • 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
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    • 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
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    • C07D491/12—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 three hetero rings
    • C07D491/14—Ortho-condensed systems
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    • C07D491/12—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 three hetero rings
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Abstract

The invention discloses a quinolinone heteroaromatic ring compound and a synthesis method of derivatives thereof. The invention relates to a method for preparing quinolinone heteroaromatic ring compound shown in formula (2) and derivatives thereof by utilizing palladium-catalyzed intramolecular alkyne cyclization and intermolecular carbon monoxide insertion reaction of a compound shown in formula (1). The method has the advantages of mild reaction conditions, simple reaction operation, high atom economy and wide substrate application range, and can quickly and efficiently prepare a series of quinolinone heteroaromatic ring compounds substituted by different functional groups.

Description

Quinolinone heteroaromatic ring compound and derivative and synthetic method thereof
Technical Field
The invention belongs to the technical field of organic compound process application, and particularly relates to a quinolinone heteroaromatic ring compound and a synthesis method thereof.
Background
The compounds containing quinolinone structure all have biological and physiological activities, and some are important pharmaceutical intermediates, such as 6-hydroxy-3, 4-dihydro-2 (1H) quinolinone, which is an important intermediate for synthesizing cilostazol (trade name pletal) and is used for treating stable intermittent claudication (clinical manifestation and typical symptoms of atherosclerosis around occlusion). In particular, certain quinolinone heteroaromatic compounds have unique anticoagulant, antibacterial, anti-inflammatory and osteoporosis treatment activities. Therefore, it is very important to find a method with mild conditions, simple operation and wide substrate range for preparing the quinolinone heteroaromatic ring compound.
Figure BDA0001638616170000011
Quinolinone-containing heteroaromatic ring compound and application thereof
In the prior art, methods for synthesizing quinolinone and heteroaromatic compounds have certain limitations, such as pre-functionalization of reaction substrates, high temperature of reaction conditions, toxic and dangerous reagents used in the reaction, and low reaction efficiency.
Therefore, it is particularly important to find a method for synthesizing quinolinone heteroaromatic ring compounds, which is efficient, has high atom utilization rate, is environment-friendly, has mild conditions, and is economically applicable.
Disclosure of Invention
The invention overcomes the defects of the traditional construction method and innovatively provides a method for efficiently synthesizing quinolinone heteroaromatic ring compounds and derivatives thereof based on intramolecular alkyne cyclization tandem carbonyl insertion reaction. The invention relates to a method for preparing quinolinone heteroaromatic ring compound shown in formula (2) and derivatives thereof by utilizing palladium-catalyzed intramolecular alkyne cyclization and intermolecular carbon monoxide insertion reaction of a compound shown in formula (1). The method has the advantages of mild reaction conditions, simple reaction operation, high atom economy and wide substrate application range, and can quickly and efficiently prepare a series of quinolinone heteroaromatic ring compounds substituted by different functional groups.
The invention provides a quinolinone heteroaromatic ring compound and a derivative thereof, wherein the structure of the quinolinone heteroaromatic ring compound is shown as a formula (2):
Figure BDA0001638616170000012
Figure BDA0001638616170000021
in the formula, R1、R2、R3、R4、R5、R6、R7、R8、R9Each independently selected from hydrogen, halogen, C1-20Alkyl radical, C1-20Alkoxy radical, C1-20Ester group, benzyl group, C1-20Alkoxy-substituted benzyl, C6-12Aryl substituted C1-20Alkyl, amino acid derivatives, menthol derivatives;
or R1、R2、R3、R4、R5、R6、R7、R8、R9Any two ofThe carbon-carbon bonds (single or double) connected with the carbon-carbon bonds form C together4-C10An alkyl group;
or R1、R2、R3、R4、R5、R6、R7、R8、R9Wherein any two adjacent carbon-carbon bonds (single bond or double bond) connected with the same form C6-C30An aryl group;
x is N, O, COOH, C6-C12Aryl substituted C1-20An alkoxy group.
Preferably, R1、R2、R3、R4、R5、R6、R7、R8、R9Each independently selected from hydrogen, F, Cl, Br, C1-6Alkyl radical, C1-6Alkoxy radical, C1-8Ester group, benzyl group, C1-6Alkoxy-substituted benzyl, C6-12Aryl substituted C1-6Alkyl, amino acid derivatives, menthol derivatives;
or R1、R2、R3、R4、R5、R6、R7、R8、R9Wherein any two adjacent carbon-carbon bonds (single bond or double bond) connected with the same form C4-C10An alkyl group;
or R1、R2、R3、R4、R5、R6、R7、R8、R9Wherein any two adjacent carbon-carbon bonds (single bond or double bond) connected with the same form C6-C30And (4) an aryl group.
X is N, O, COOH, C6-C10Aryl substituted C1-6An alkoxy group.
Further preferably, R1Selected from benzyl, C1-6Alkyl, p-methoxybenzyl; r2Selected from hydrogen; r3Selected from hydrogen, C1-8An ester group; r4Selected from hydrogen, bromine, C1-6Alkoxy radical, C1-6Alkyl, amino acid derivatives; r5Selected from hydrogen; r6Selected from hydrogen; r7Is selected from C1-6Alkyl, F, Cl, Br; r8Selected from hydrogen; r9Selected from hydrogen.
Or, R3And R4Together form C5-C10An alkyl group; r1And R9Together form C4-C10An alkyl group; r6And R7Together form C6-C30An aryl group; r2And R5Together form C4-C10Alkyl and C6-C30An aryl group;
x is N, O, COOH, C6-C8Aryl substituted C1-6An alkoxy group.
In the present invention, R1、R2、R3、R4、R5、R6、R7、R8、R9Including but not limited to the above groups.
The quinolinone heteroaromatic ring compound and the derivative thereof comprise:
Figure BDA0001638616170000022
Figure BDA0001638616170000031
the invention also provides a synthesis method of the quinolinone heteroaromatic ring compound and the derivative thereof, which comprises the following steps of taking a tolane derivative shown in the formula (1) and carbon monoxide as reaction raw materials in a solvent, and reacting in the presence of a palladium catalyst, a ligand and an oxidant to obtain the quinolinone heteroaromatic ring compound shown in the formula (2) and the derivative thereof, wherein the reaction process is shown in the reaction formula (a):
Figure BDA0001638616170000032
Figure BDA0001638616170000041
in the formulae, R1、R2、R3、R4、R5、R6、R7、R8、R9Each independently selected from hydrogen, halogen, C1-20Alkyl radical, C1-20Alkoxy radical, C1-20Ester group, benzyl group, C1-20Alkoxy-substituted benzyl, C6-12Aryl substituted C1-20Alkyl, amino acid derivatives, menthol derivatives;
or R1、R2、R3、R4、R5、R6、R7、R8、R9Wherein any two adjacent carbon-carbon bonds (single bond or double bond) connected with the same form C4-C10An alkyl group;
or R1、R2、R3、R4、R5、R6、R7、R8、R9Wherein any two adjacent carbon-carbon bonds (single bond or double bond) connected with the same form C6-C30An aryl group;
x is N, O, COOH, C6-C12Aryl substituted C1-20An alkoxy group.
Preferably, R1、R2、R3、R4、R5、R6、R7、R8、R9Each independently selected from hydrogen, F, Cl, Br, C1-6Alkyl radical, C1-6Alkoxy radical, C1-8Ester group, benzyl group, C1-6Alkoxy-substituted benzyl, C6-12Aryl substituted C1-6Alkyl, amino acid derivatives, menthol derivatives;
or R1、R2、R3、R4、R5、R6、R7、R8、R9Wherein any two adjacent carbon-carbon bonds (single bond or double bond) connected with the same form C4-C10An alkyl group;
or R1、R2、R3、R4、R5、R6、R7、R8、R9Wherein any two adjacent carbon-carbon bonds (single bond or double bond) connected with the same form C6-C30And (4) an aryl group.
X is N, O, COOH, C6-C10Aryl substituted C1-6An alkoxy group.
Further preferably, R1Selected from benzyl, C1-6Alkyl, p-methoxybenzyl; r2Selected from hydrogen; r3Selected from hydrogen, C1-8An ester group; r4Selected from hydrogen, bromine, C1-6Alkoxy radical, C1-6Alkyl, amino acid derivatives; r5Selected from hydrogen; r6Selected from hydrogen; r7Is selected from C1-6Alkyl, F, Cl, Br; r8Selected from hydrogen; r9Selected from hydrogen;
or, R3And R4Together form C5-C10An alkyl group; r1And R9Together form C4-C10An alkyl group; r6And R7Together form C6-C30An aryl group; r2And R5Together form C4-C10Alkyl and C6-C30An aryl group;
x is N, O, COOH, C6-C8Aryl substituted C1-6An alkoxy group.
In the present invention, R1、R2、R3、R4、R5、R6、R7、R8、R9Including but not limited to the above groups.
The invention also provides the following compounds prepared by the method:
Figure BDA0001638616170000042
Figure BDA0001638616170000051
according to the reaction formula (a), the invention uses a tolane compound shown in the formula (1) as a starting material, uses carbon monoxide as a carbonyl source, and reacts in a solvent in the presence of a palladium catalyst, a ligand and an oxidant to obtain the quinolinone heteroaromatic ring compound shown in the formula (2) and a derivative thereof.
In the present invention, the carbon monoxide is a carbonyl source.
In the invention, the palladium catalyst is selected from one or more of palladium acetate, palladium trifluoroacetate, palladium dichloride, bis (acetonitrile) palladium dichloride and the like; preferably, palladium trifluoroacetate.
In the invention, the ligand is selected from one or more of 2,2 ' -bipyridyl, 4 ' -dimethoxy-2, 2 ' -bipyridyl, pyridine-2-formic acid, 1, 10-phenanthroline, 2, 9-dimethyl-4, 7-diphenyl-1, 10-phenanthroline, 1, 10-phenanthroline-5, 6-diketone and the like; preferably, 2, 9-dimethyl-4, 7-diphenyl-1, 10-phenanthroline or 1, 10-phenanthroline-5, 6-diketone.
In the invention, the oxidant is selected from one or more of air, silver acetate, silver trifluoroacetate, silver carbonate, copper acetate, potassium persulfate, tert-butyl hydroperoxide, p-benzoquinone and the like; preferably, p-benzoquinone.
In the invention, the solvent is one or more of methanol, ethanol, isopropanol, tert-butanol, water, DMSO, DMF, DMA, acetonitrile, acetone, tetrahydrofuran, toluene, dichloromethane, 1, 2-dichloroethane, chloroform and the like; preferably, it is acetonitrile.
In the invention, the reaction temperature is 10-60 ℃; preferably, it is carried out at 20-40 ℃.
In the invention, the reaction time is 1-10 hours; preferably, it is 2 to 8 hours.
In the invention, the pressure of the carbon monoxide is 1-20 atm; preferably 1 atm.
In the invention, the mole percentage of the palladium catalyst is 0.5-50 mol%; preferably 10 mol%, based on the molar amount of the compound of formula (1).
In the invention, the mole percentage of the ligand is 0.5-50 mol%; preferably 10 mol%, based on the molar amount of the compound of formula (1).
In the invention, the mole percentage of the oxidant is 100-400 mol%; preferably 150 mol%, based on the molar amount of the compound of formula (1).
The invention has the following advantages: the reaction is efficient, and the yield is high; carbon monoxide is used as a carbonyl source, and is cheap and economical; the reaction condition is mild, and strong acid and strong alkali are not needed; the reaction substrate is easy to prepare. The invention takes a tolane derivative which is easy to prepare as a reaction raw material, takes carbon monoxide as a carbonyl source, and carries out ring-closure carbonyl-insertion tandem reaction under the action of a palladium catalyst, a ligand and an oxidant to obtain the quinolinone heteroaromatic ring compound. The method has the advantages of simple reaction operation, mild reaction conditions, high atom economy, wide substrate application range, and capability of quickly and efficiently preparing a series of quinolinone and heteroaromatic ring compounds substituted by different functional groups.
Detailed Description
The present invention will be described in further detail with reference to the following specific examples, but the present invention is not limited to the following examples. Variations and advantages that may occur to those skilled in the art may be incorporated into the invention without departing from the spirit and scope of the inventive concept, and the scope of the appended claims is intended to be protected. The procedures, conditions, reagents, experimental methods and the like for carrying out the present invention are general knowledge and common general knowledge in the art except for the contents specifically mentioned below, and the present invention is not particularly limited. The data given in the examples below include specific operating and reaction conditions and products. The purity of the product was identified by nuclear magnetism.
The synthesis reaction of the quinolinone heteroaromatic ring compound and the derivative thereof comprises the following steps:
as shown in the reaction formula (a), the synthetic reaction of the invention is to add the tolane derivative of the formula (1), a palladium catalyst, a ligand, an oxidant and an organic solvent into a reaction bottle, and stir a reaction system for 2 to 6 hours at 25 ℃ under a CO atmosphere; after the reaction is finished, directly adding silica gel for spin drying, and separating by column chromatography to obtain the target product.
The quinolinone heteroaromatic ring compounds shown in table 1 are all products synthesized by the method of the invention, and no published documents disclose the compounds.
TABLE 1 novel quinolinone heteroaromatic ring compounds of the present invention
Figure BDA0001638616170000071
Figure BDA0001638616170000081
Figure BDA0001638616170000091
Example 1
Synthesis of compound 2 a:
Figure BDA0001638616170000092
1a (29.9mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 1, 10-phenanthroline dione (2.1mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon for three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 2 hours. After the TLC detection reaction, the solvent was dried by evaporation and column chromatography was used to isolate 2a in 87% yield (28.3mg) as a white solid.1H NMR(400MHz,CDCl3)δ8.42–8.25(m,1H),8.19(dd,J＝7.9,1.2Hz,1H),7.68(m,1H),7.57–7.38(m,4H),7.38–7.14(m,5H),5.71(s,2H).13C NMR(100MHz,CDCl3)δ159.8,157.7,155.5,138.9,136.6,130.7,128.9,127.3,126.6,126.2,124.6,124.5,122.5,122.4,122.4,116.0,113.1,111.4,110.2,45.7.IR(KBr)1651,1579,1452,1183,1110,758,748.HRMS(EI)Calcd for C22H15NO2325.1103,Found 325.1105.
Example 2
Synthesis of compound 2 b:
Figure BDA0001638616170000093
the reaction solution was cooled and washed with 1b (32.9mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 1, 10-phenanthroline dione (2.1mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon for three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 2 hours. After the TLC detection reaction, the solvent was dried by evaporation and column chromatography was used to isolate 2b in 81% yield (28.8mg) as a white solid.1H NMR(400MHz,CDCl3)δ8.35-8.33(m,1H),8.19(d,J＝8.0Hz,1H),7.69-7.67(m,1H),7.50-7.46(m,4H),7.33(t,J＝8.0Hz,1H),7.22(d,J＝8.0Hz,2H),6.84(d,J＝12.0Hz,2H),5.65(s,2H),3.75(s,3H).13C NMR(100MHz,CDCl3)δ159.8,158.9,157.6,155.5,138.9,130.7,128.7,128.0,126.2,124.6,124.5,122.4,122.3,116.0,114.3,113.1,111.4,110.2,55.3,55.2,45.1.IR(KBr)1657,1481,1189,1109,767,751,741.HRMS(EI)Calcd for C23H17NO3355.1208,Found 355.1210.
Example 3
Synthesis of compound 2 c:
Figure BDA0001638616170000101
1c (40.8mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 1, 10-phenanthroline dione (2.1mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon for three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 2 hours. After the TLC detection reaction, the solvent was dried by evaporation and column chromatography was used to isolate 2c in 72% yield (29.1mg) as a white solid.1H NMR(400MHz,CDCl3)δ8.47(s,1H),8.17-8.15(m,1H),7.57-7.42(m,3H),7.33(d,J＝8.0Hz,1H),7.31-7.26(m,6H),5.70(s,2H).13C NMR(100MHz,CDCl3)δ159.4,158.4,154.2,129.1,136.5,131.2,129.1,128.9,127.4,126.6,126.5,125.1,122.6,122.4,117.8,116.1,112.8,109.4,45.7.IR(KBr)1662,1498,1444,1246,1183,1140,873,803,747,728,521.HRMS(EI)Calcd for C22H14NO2Br 403.0208,Found403.0206.
Example 4
Synthesis of compound 2 d:
Figure BDA0001638616170000102
1d (33.4mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 1, 10-phenanthroline dione (2.1mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon for three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 2 hours. After TLC detection, the solvent was dried by evaporation and column chromatography gave 74% yield (26.6mg) as a white solid in 2 d.1H NMR(400MHz,CDCl3)δ8.21(s,1H),8.06(d,J＝4.0Hz,1H),7.50(d,J＝12.0Hz,1H),7.34-7.32(m,1H),7.24-7.22(m,2H),7.20-7.17(m,6H),5.60(s,2H).13C NMR(100MHz,CDCl3)δ159.5,158.6,153.8,139.1,131.2,130.3,128.9,127.4,126.6,126.4,126.0,122.7,122.4,122.0,116.1,112.8,112.4,109.6,45.7.IR(KBr)1658,1447,1384,1183,1130,863,805,748,728.HRMS(EI)Calcd for C22H14NO2Cl 359.0713,Found 359.0717.
Example 5
Synthesis of compound 2 e:
Figure BDA0001638616170000111
1e (32.9mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 1, 10-phenanthroline dione (2.1mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon for three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 2 hours. After the TLC detection reaction, the solvent was dried by spinning and separated by column chromatography to give 2e in 65% yield (23.1mg) as a brown solid.1H NMR(400MHz,CDCl3)δ8.09-8.07(m,1H),7.73(d,J＝4.0Hz,1H),7.48(d,J＝8.0Hz,1H),7.41-7.39(m,1H),7.34(d,J＝8.0Hz,1H),7.26-7.16(m,6H),6.99-6.97(m,1H),5.63(s,2H),3.86(s,3H).13C NMR(100MHz,CDCl3)δ160.0,158.2,157.2,150.3,138.8,136.7,130.6,128.9,127.3,126.6,125.3,122.5,122.3,116.0,115.5,113.3,112.0,110.4,104.0,56.0,45.7.IR(KBr)1658,1618,1484,1456,1448,1266,1186,1141,781,751.HRMS(EI)Calcd for C23H17NO3355.1208,Found 355.1213.
Example 6
Synthesis of compound 2 f:
Figure BDA0001638616170000112
1f (37.1mg, 0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 1, 10-phenanthroline dione (2.1mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon for three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 2 hours. After the TLC detection reaction, the solvent was dried by spinning and separated by column chromatography to give 2f in 92% yield (36.6mg) as a yellow solid.1H NMR(400MHz,CDCl3)δ8.38(d,J＝8.0Hz,1H),7.35-7.27(m,7H),5.73(s,2H),4.48(q,J＝12.0Hz,2H),1.49(s,3H).13C NMR(125MHz,CDCl3)δ166.3,159.6,155.0,139.3,136.4,131.5,128.9,128.8,128.5,127.4,126.6,125.9,122.7,121.8,116.1,112.9,112.7,109.8,61.3,45.7,14.4.IR(KBr)1713,1669,1444,1421,1281,1233,759,729,696.HRMS(EI)Calcd for C25H19NO4397.1314,Found 397.1317.
Example 7
Synthesis of Compound 2 g:
Figure BDA0001638616170000121
1g (339.9mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 1, 10-phenanthroline dione (2.1mg,0.01mmol), benzoquinone (16.2mg0.15mmol) were added to the reaction tube in sequence, then replaced three times with a CO balloon and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 2 hours. After the TLC detection reaction, the solvent was dried by spinning and separated by column chromatography to obtain 2g of a white solid with a yield of 78% (31.1 mg).1H NMR(400MHz,CDCl3)δ8.35(s,1H),8.34-8.19(m,1H),7.71(d,J＝8.0Hz,1H),7.55-7.44(m,2H),7.35-7.29(m,1H),7.27-7.25(m,6H),5.71(s,2H),3.60-3.36(m,4H),1.28-1.15(m,6H).13C NMR(100MHz,CDCl3)δ170.9,159.6,158.5,155.5,139.0,136.5,133.9,131.1,128.9,127.4,126.6,125.2,124.5,122.7,122.4,120.3,116.1,112.9,111.8,110.0,45.7,43.6,39.4,14.3,13.0.IR(KBr)2974,1651,1621,1453,1284,1128,1080,757,700.HRMS(EI)Calcd for C27H24N2O3424.1718,Found424.1790.
Example 8
Synthesis of compound 2 h:
Figure BDA0001638616170000122
1h (23.5mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 1, 10-phenanthroline dione (2.1mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon for three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 2 hours. After TLC detection reaction, the solvent was dried by spinning, and column chromatography was used to obtain a white solid with a yield of 76% (19.9mg) for 2 h.1H NMR(400MHz,CDCl3)δ8.33-8.31(m,1H),7.81(d,J＝8.0Hz,1H),7.66-7.65(m,1H),7.63-7.45(m,2H),7.44-7.38(m,1H),7.37-7.23(m,1H),4.56(d,J＝8.0Hz,2H),3.52(s,2H).13C NMR(125MHz,CDCl3)δ157.3,155.7,142.2,131.0,125.9,125.0,124.5,124.3,123.4,122.3,118.3,112.5,111.4,109.6,46.3,27.9.IR(KBr)2931,1645,1605,1455,1434,1413,1196,1146,746,729.HRMS(EI)Calcd for C17H11NO2261.0790,Found261.0787.
Example 9
Synthesis of compound 2 i:
Figure BDA0001638616170000131
1i (24.9mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 1, 10-phenanthroline dione (2.1mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon for three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 2 hours. After the TLC detection reaction, the solvent was dried by spinning, and 2i was isolated by column chromatography in 51% yield (14.0mg) as a white solid.1H NMR(400MHz,CDCl3)δ8.32-8.01(m,1H),7.66(d,J＝4.0Hz,1H),7.65-7.64(m,1H),7.46-7.43(m,2H),7.39(d,J＝4.0Hz,1H),7.38-7.25(m,2H),4.37(t,J＝8.0Hz,2H),3.06(t,J＝8.0Hz,2H),2.22-2.16(m,2H).13C NMR(100MHz,CDCl3)δ159.3,157.5,155.4,136.2,130.1,126.0,125.9,124,6,124.3,122.3,122.0,120.1,112.6,111.3,110.0,42.1,28.2,20.9.IR(KBr)2944,1647,1580,1454,1446,1287,1145,1127,772,746.HRMS(EI)Calcd for C18H13NO2275.0946,Found 275.0945.
Example 10
Synthesis of compound 2 j:
Figure BDA0001638616170000132
1j (31.3mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 1, 10-phenanthroline dione (2.1mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon for three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 2 hours. After the TLC detection reaction, the solvent was dried by spinning and separated by column chromatography to give 2j in 78% yield (26.5mg) as a white solid.1H NMR(400MHz,CDCl3)δ8.34-8.32(m,1H),7.97(s,1H),7.67-7.65(m,1H),7.49-7.45(m,2H),7.31-7.23(m,7H),5.69(s,2H),2.45(s,3H).13C NMR(100MHz,CDCl3)δ159.7,157.6,155.5,137.0,136.8,132.2,132.0,128.8,127.2,126.6,126.1,124.7,124.5,122.3,122.0,115.9,113.0,110.1,45.6,20.7.IR(KBr)1651,1526,1432,1241,1180,1121,820,750,738.HRMS(EI)Calcd for C23H17NO2339.1259,Found 339.1258.
Example 11
Synthesis of compound 2 k:
Figure BDA0001638616170000141
1k (31.3mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 1, 10-phenanthroline dione (2.1mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon for three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 2 hours. After the TLC detection reaction, the solvent was dried by spinning and separated by column chromatography to give 2k as a white solid with a yield of 75% (25.5 mg).1H NMR(400MHz,CDCl3)δ8.32-8.30(m,1H),8.05(d,J＝8.0Hz,1H),7.66-7.64(m,1H),7.47-7.42(m,2H),7.33-7.21(m,6H),7.14(d,J＝8.0Hz,1H),5.68(s,2H),2.41(s,3H).13C NMR(100MHz,CDCl3)δ159.9,158.0,155.4,141.5,139.1,136.8,128.8,127.2,126.6,125.9,124.8,124.4,123.9,122.2,116.1,111.3,110.8,109.3,45.6,22.4.IR(KBr)1655,1566,1495,1453,1253,1184,1130,803,752,731.HRMS(EI)Calcd for C23H17NO2339.1259,Found 339.1256.
Example 12
Synthesis of compound 2 l:
Figure BDA0001638616170000142
1l (31.7mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 1, 10-phenanthroline dione (2.1mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon for three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 2 hours. After the TLC detection reaction, the solvent was dried by evaporation and separated by column chromatography to give 2l as a white solid with a yield of 58% (19.9 mg).1H NMR(400MHz,CDCl3)δ8.35(t,J＝4.0Hz,1H),7.85-7.83(m,1H),7.69(d,J＝8.0Hz,1H),7.53-7.46(m,2H),7.39-7.36(m,1H),7.33-7.29(m,2H),7.26-7.19(m,4H),5.70(s,2H).19F NMR(375MHz,CDCl3)δ-119.5.13C NMR(100MHz,CDCl3)δ159.4,158.0(d,1JC-F＝242.0Hz),156.7,155.6,136.4,135.3(d,4JC-F＝3.0Hz),128.9,127.4,126.7,126.5,124.7,124.4,122.5,118.5(d,2JC-F＝24.0Hz),117.9(d,3JC-F＝8.0Hz),113.9(d,3JC-F＝10.0Hz),111.5,111.1,107.8(d,2JC-F＝24.0Hz),45.9.IR(KBr)1661,1569,1454,1283,1250,1181,1124,871,812,753.HRMS(EI)Calcd for C22H14NO2F 343.1009,Found343.1010.
Example 13
Synthesis of compound 2 m:
Figure BDA0001638616170000151
1m (33.4mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 1, 10-phenanthroline dione (2.1mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon for three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 2 hours. After the TLC detection reaction, the solvent was dried by spinning and separated by column chromatography to obtain 2m, which was 81% yield (29.1mg) as a white solid.1H NMR(500MHz,CDCl3)δ8.3(d,J＝4.0Hz,1H),8.16(s,1H),7.49(s,1H),7.35-7.32(m,2H),7.31-7.23(m,7H),5.69(s,2H).13C NMR(100MHz,CDCl3)δ159.4,156.3,155.6,137.2,136.2,130.7,128.9,127.5,126.7,126.5,124.7,124.3,122.5,121.7,117.5,114.1,111.5,111.0,45.8.IR(KBr)1653,1450,1280,1187,1136,961,805,760,699.HRMS(EI)Calcd for C22H14NO2Cl 359.0713,Found 359.0714.
Example 14
Synthesis of compound 2 n:
Figure BDA0001638616170000152
1n (37.8mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 1, 10-phenanthroline dione (2.1mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon for three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 2 hours. After the TLC detection reaction, the solvent was dried by spinning, and the product was isolated by column chromatography to give 81% yield (34.0mg) as a white solid.1H NMR(400MHz,CDCl3)δ7.95(d,J＝7.9Hz,1H),7.76(d,J＝8.4Hz,2H),7.40(t,J＝9.1Hz,3H),7.29(t,J＝7.6Hz,1H),7.22(d,J＝7.7Hz,1H),6.53(s,1H),4.01(s,3H).13C NMR(100MHz,CDCl3)δ149.84,148.34,135.33,131.15,131.12,130.93,128.92,128.23,126.11,125.67,124.04,121.22,101.01,62.82.IR(KBr)1653,1450,1439,1280,1187,1133,958,760,735,698.HRMS(EI)Calcd for C22H14NO2Br 403.0208,Found403.0214.
Example 15
Synthesis of compound 2 o:
Figure BDA0001638616170000161
1o (43.0mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 1, 10-phenanthroline dione (2.1mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon for three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 2 hours. After the TLC detection reaction, the solvent was dried by spinning, and 2o was isolated by column chromatography with a yield of 40% (18.2mg) as a white solid.1H NMR(400MHz,CDCl3)δ8.31-8.28(m,1H),7.55-7.51(m,1H),7.45-7.24(m,8H),6.77-6.73(m,2H),6.57-6.46(m,2H),6.08(dd,J＝8.0,4.0Hz,1H),5.82(dd,J＝8.0,4.0Hz,2H),4.65(t,J＝12Hz,1H),3.75-3.70(m,1H),3.17-2.98(m,5H),2.83-2.76(m,1H).13C NMR(100MHz,CDCl3)δ159.2,156.8,155.4,139.3,138.9,137.8,136.8,132.4,132.3,131.8,131.0,130.7,128.9,127.3,126.9,126.4,125.3,122.9,122.5,122.3,115.9,113.1,112.8,46.0,35.5,35.2,34.3,29.7.IR(KBr)2928,1650,1495,1416,1145,1135,961,934,757,727.HRMS(EI)Calcd for C32H25NO2455.1885,Found455.1883.
Example 16
Synthesis of compound 2 p:
Figure BDA0001638616170000171
1p (50.1mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 1, 10-phenanthroline dione (2.1mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon for three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 2 hours. After the TLC detection reaction, the solvent was dried by evaporation and separated by column chromatography to give 2p in 72% yield (37.9mg) as a brown solid.1H NMR(400MHz,CDCl3)δ8.18-8.16(m,1H),8.09(s,1H),7.60(d,J＝8.0Hz,1H),7.52-7.49(m,1H),7.41(d,J＝8.0Hz,1H),7.32-7.22(m,7H),5.70(s,2H),5.05(d,J＝8.0Hz,1H),4.66(d,J＝8.0Hz,1H),3.78(s,3H),3.33-3.19(s,2H),1.41(s,9H).13C NMR(100MHz,CDCl3)δ172.3,159.7,158.0,154.8,138.9,136.6,132.7,130.8,128.8,127.4,127.3,126.6,125.0,122.9,122.5,122.3,116.0,113.1,111.4,110.0,54.9,52.4,45.6,38.4,28.3.IR(KBr)2976,1746,1697,1662,1522,1455,1168,1137,1056,750,728.HRMS(EI)Calcd for C31H30N2O6526.2104,Found 526.2106.
Example 17
Synthesis of compound 2 q:
Figure BDA0001638616170000172
1q (48.2mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 1, 10-phenanthroline dione (2.1mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon for three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 2 hours. After the TLC detection reaction, the solvent was dried by spinning and separated by column chromatography to give 2q, 58% yield (29.4mg) as a white solid.1H NMR(500MHz,CDCl3)δ9.0(s,1H),8.26-8.20(m,2H),7.32(d,J＝4.0Hz,1H),7.53(t,J＝4.0Hz,1H),7.45(d,J＝8.0Hz,1H),7.38-7.23(m,8H),5.73(s,2H),5.05-5.00(s,1H),2.14-2.11(m,1H),2.03-1.99(m,1H),1.76-1.73(m,2H),1.63-1.58(m,3H),1.25-1.12(m,3H),0.94-0.92(m,7H),0.82(d,J＝4.0Hz,3H).13C NMR(100MHz,CDCl3)δ172.3,159.7,158.0,154.8,138.9,136.6,132.7,130.8,128.8,127.4,127.3,126.6,125.0,122.9,122.5,122.3,116.0,113.1,111.4,110.0,54.9,52.4,45.6,38.4,28.3.IR(KBr)2936,1726,1653,1443,1151,1106,786,753,728.HRMS(EI)Calcd for C33H33NO4507.2410,Found 507.2411
Example 18
Synthesis of compound 2 r:
Figure BDA0001638616170000181
1r (29.8mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 2, 9-dimethyl-4, 7-diphenyl-1, 10-phenanthroline (3.6mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 6 hours. After TLC detection, the solvent was dried by spinning and separated by column chromatography to give 2r as a white solid with a yield of 75% (24.3 mg).1H NMR(300MHz,DMSO-d6)δ12.67(s,1H),8.30(dd,J＝10.9,7.6Hz,2H),7.67(d,J＝8.0Hz,1H),7.58–7.47(m,2H),7.46–7.13(m,8H),5.70(s,2H).13C NMR(100MHz,DMSO-d6)δ164.5,145.2,143.1,142.9,134.8,133.8,132.1,131.7,129.9,129.5,128.1,127.1,126.5,126.1,121.5,118.5,117.0,110.9,49.2.IR(KBr)1622,1501,1372,1138,1039,954,757,748.HRMS(EI)Calcd for C22H16N2O 324.1263,Found324.1268.
Example 19
Synthesis of compound 2 s:
Figure BDA0001638616170000182
1s (33.3mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 2, 9-dimethyl-4, 7-diphenyl-1, 10-phenanthroline (3.6mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon for three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 6 hours. After the TLC detection reaction, the solvent was dried by evaporation and separated by column chromatography to give 61% yield (21.9mg) as a yellow solid.1H NMR(500MHz,DMSO-d6)δ12.86(s,1H),8.30(dd,J＝7.8,1.0Hz,1H),8.22(d,J＝2.0Hz,1H),7.68(d,J＝8.6Hz,1H),7.53(ddd,J＝18.4,12.8,4.7Hz,2H),7.43(dd,J＝8.6,2.2Hz,1H),7.37(t,J＝7.3Hz,1H),7.33–7.21(m,4H),5.68(s,2H).13C NMR(125MHz,DMSO-d6)δ159.6,141.6,138.6,138.0,136.9,130.5,129.1,127.4,127.0,126.3,126.2,124.7,123.5,122.5,120.3,116.9,113.9,113.5,105.6,44.5.IR(KBr)1641,1425,1372,1141,1032,951,781,747.HRMS(EI)Calcd for C22H15N2O 358.0873,Found358.0871.
Example 20
Synthesis of compound 2 t:
Figure BDA0001638616170000191
1t (33.3mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 2, 9-dimethyl-4, 7-diphenyl-1, 10-phenanthroline (3.6mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 6 hours. After the TLC detection reaction, the solvent was dried by spinning and separated by column chromatography to obtain 2t, 54% yield (19.4mg) as a yellow solid.1H NMR(500MHz,DMSO-d6)δ12.74(s,1H),8.42(d,J＝2.3Hz,1H),8.27(d,J＝7.8Hz,1H),7.67(d,J＝8.2Hz,1H),7.53(dd,J＝9.1,2.3Hz,1H),7.50–7.39(m,2H),7.37–7.26(m,3H),7.22(dd,J＝12.5,7.3Hz,3H),5.67(s,2H).13C NMR(125MHz,DMSO-d6)δ164.3,143.9,143.1,142.5,141.8,134.3,133.9,132.2,131.6,131.4,130.0,129.6,127.4,126.7,123.5,119.9,117.2,111.5,49.3.IR(KBr)1631,1455,1384,1158,1047,964,780,745.HRMS(EI)Calcd for C22H15N2OCl 358.0873,Found 358.0877.
Example 21
Synthesis of compound 2 u:
Figure BDA0001638616170000192
1u (32.7mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 1, 10-phenanthroline dione (2.1mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon for three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 6 hours. After the TLC detection reaction, the solvent was dried by spinning and separated by column chromatography to obtain 2u, 89% yield (31.4mg) as a white solid.1H NMR(500MHz,CDCl3)δ9.64(d,J＝8.1Hz,1H),8.40(ddd,J＝34.0,8.0,1.2Hz,2H),7.89(ddd,J＝8.5,7.4,1.5Hz,1H),7.67–7.58(m,1H),7.55(ddd,J＝8.6,7.2,1.5Hz,1H),7.38–7.29(m,4H),7.25(dd,J＝8.0,5.3Hz,3H),5.66(s,2H).13C NMR(125MHz,CDCl3)δ160.8,160.2,155.0,138.5,136.0,135.7,134.7,132.7,130.0,129.0,128.9,127.5,127.3,126.5,124.2,122.9,120.6,115.1,113.8,104.9,46.3.IR(KBr)1756,1643,1452,1302,1135,1098,1019,761,753,700.HRMS(EI)Calcd for C23H15NO3353.1052,Found353.1055.
Example 22
Synthesis of compound 2 v:
Figure BDA0001638616170000201
1v (37.7mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 1, 10-phenanthroline dione (2.1mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon for three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 6 hours. After the TLC detection reaction was complete, the solvent was dried by evaporation and column chromatography was used to isolate 2v as a 67% yield (27.0mg) yellow solid.1H NMR(400MHz,CDCl3)δ8.32(d,J＝7.9Hz,1H),8.24(dd,J＝15.4,8.6Hz,2H),7.97(d,J＝8.6Hz,1H),7.86(d,J＝8.1Hz,1H),7.62(t,J＝7.5Hz,1H),7.50(dd,J＝11.7,7.2Hz,2H),7.31–7.18(m,7H),5.66(s,2H).13C NMR(100MHz,CDCl3)δ160.5,160.4,155.3,138.9,137.1,136.2,134.5,132.6,130.7,130.0,129.5,128.9,128.1,127.8,127.5,126.6,125.3,124.2,123.5,122.9,120.5,115.1,114.1,106.6,46.7.IR(KBr)1743,1621,1432,1288,1130,1088,836,757,746.HRMS(EI)Calcd for C27H17NO3403.1208,Found403.1209.
Example 23
Synthesis of compound 2 w:
Figure BDA0001638616170000211
1w (35.6mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 1, 10-phenanthroline dione (2.1mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon for three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 6 hours. After TLC detection, the solvent was dried by evaporation and separated by column chromatography to give 2w as a 90% yield (34.4mg) yellow solid.1H NMR(500MHz,CDCl3)δ9.40(d,J＝8.1Hz,1H),8.34–8.24(m,1H),8.06(d,J＝7.9Hz,1H),7.59–7.52(m,1H),7.50–7.44(m,1H),7.39(dd,J＝11.2,4.0Hz,1H),7.26(ddd,J＝17.7,12.7,7.5Hz,7H),5.60(s,2H),4.07(s,3H).13C NMR(125MHz,CDCl3)δ161.0,153.5,146.5,138.4,136.3,132.1,131.5,128.9,128.7,128.4,127.4,126.9,126.5,123.9,123.8,122.6,121.3,114.7,114.1,104.6,63.1,46.1.IR(KBr)1728,1638,1453,1379,1048,751,740,698.HRMS(EI)Calcd for C24H18N2O3382.1317,Found 382.1322.
Example 24
Synthesis of compound 2 x:
Figure BDA0001638616170000212
1X (32.7mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 2, 9-dimethyl-4, 7-diphenyl-1, 10-phenanthroline (3.6mg,0.01mmol)mmol), benzoquinone (16.2mg,0.15mmol) were added to the reaction tube in sequence, then replaced three times with a CO balloon, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 6 hours. After the TLC reaction was completed, the solvent was dried by spinning, and separated by column chromatography to give 2 ×, yield 77% (27.2mg) as a yellow solid.1H NMR(500MHz,CDCl3)δ8.26(dd,J＝8.1,0.9Hz,1H),7.70(d,J＝1.4Hz,1H),7.46(ddd,J＝8.5,7.2,1.3Hz,1H),7.37(d,J＝7.9Hz,1H),7.35–7.29(m,2H),7.27(dd,J＝8.2,1.0Hz,1H),7.26–7.23(m,3H),7.21(dd,J＝8.3,1.6Hz,1H),7.08(d,J＝8.2Hz,1H),5.62(s,2H),5.15(s,2H),2.42(s,3H).13C NMR(125MHz,CDCl3)δ159.7,155.4,139.4,137.4,136.3,131.8,131.1,130.1,128.9,128.4,127.4,126.9,126.6,124.6,122.2,121.2,117.9,115.8,64.6,46.2,21.1.IR(KBr)1638,1593,1453,1396,1027,757,731,698.HRMS(EI)Calcd for C24H19NO2353.1416,Found 353.1420.
Example 25
Synthesis of compound 2 y:
Figure BDA0001638616170000221
1y (35.7mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 2, 9-dimethyl-4, 7-diphenyl-1, 10-phenanthroline (3.6mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 6 hours. After the TLC detection reaction, the solvent was dried by evaporation and column chromatography was used to isolate 2y as a 63% yield (24.2mg) yellow solid.1H NMR(500MHz,CDCl3)δ8.18(d,J＝8.1Hz,1H),7.48–7.42(m,1H),7.38–7.29(m,4H),7.26–7.23(m,3H),6.72(s,1H),6.04(s,2H),5.61(s,2H),5.12(s,2H).13C NMR(125MHz,CDCl3)δ159.7,153.8,149.5,142.7,139.4,137.7,136.3,130.1,128.9,127.3,126.6,126.6,122.4,122.2,117.7,115.9,113.9,107.1,101.8,100.2,64.8,46.2.IR(KBr)2921,1643,1571,1447,1386,1019,826,751,744.HRMS(EI)Calcd for C24H17NO4383.1158,Found 383.1153.
Example 26
Synthesis of compound 2 z:
Figure BDA0001638616170000222
1z (36.3mg,0.1mmol), Pd (TFA)2(3.3mg,0.01mmol), 2, 9-dimethyl-4, 7-diphenyl-1, 10-phenanthroline (3.6mg,0.01mmol), benzoquinone (16.2mg,0.15mmol) were sequentially added to the reaction tube, then replaced with a CO balloon three times, and acetonitrile (1mL) was added. The reaction system was reacted at room temperature for 6 hours. After the TLC detection reaction, the solvent was dried by spinning and separated by column chromatography to give 2z in 82% yield (31.9mg) as a yellow solid.1H NMR(400MHz,CDCl3)δ7.90(dd,J＝15.8,8.4Hz,2H),7.69(d,J＝8.4Hz,1H),7.56(d,J＝8.2Hz,1H),7.47–7.26(m,10H),7.06–6.96(m,1H),5.75(d,J＝13.7Hz,1H),5.68(s,2H),4.64(d,J＝13.7Hz,1H).13C NMR(100MHz,CDCl3)δ160.0,157.8,139.3,137.7,136.4,132.4,130.5,130.1,128.9,128.9,128.5,127.4,126.7,125.9,124.7,124.3,121.2,118.4,117.9,115.7,115.5,64.8,46.4.IR(KBr)1624,1461,1382,1018,840,753,738.HRMS(EI)Calcd for C27H19NO2389.1416,Found 389.1418.
The protection of the present invention is not limited to the above embodiments. Variations and advantages that may occur to those skilled in the art may be incorporated into the invention without departing from the spirit and scope of the inventive concept, and the scope of the appended claims is intended to be protected.

Claims (4)

1. A synthesis method of quinolinone heteroaromatic ring compounds is characterized in that in a solvent, tolane derivatives shown in formula (1) and carbon monoxide are used as reaction raw materials, and in the presence of a palladium catalyst, a ligand and an oxidant, the quinolinone heteroaromatic ring compounds shown in formula (2) are obtained through reaction,
wherein the palladium catalyst is any one or any combination of palladium acetate, palladium trifluoroacetate, palladium dichloride and bis (acetonitrile) palladium dichloride; the ligand is selected from any one or any combination of 2,2 ' -bipyridyl, 4 ' -dimethoxy-2, 2 ' -bipyridyl, pyridine-2-formic acid, 1, 10-phenanthroline, 2, 9-dimethyl-4, 7-diphenyl-1, 10-phenanthroline and 1, 10-phenanthroline-5, 6-diketone; the oxidant is selected from benzoquinone; the solvent is acetonitrile;
the mole percentage of the palladium catalyst is 0.5-50 mol%; the mole percentage of the ligand is 0.5-50 mol%; the mole percentage of the oxidant is 100-400 mol%; wherein the mol% in mole percent is based on the molar usage of the compound of formula (1);
the reaction process is shown as a reaction formula (a):
Figure FDA0003164182850000011
in the reaction formula (a),
wherein R is1Selected from the group consisting of: benzyl radical, C1-20Alkoxy-substituted benzyl;
R2、R3、R4、R5、R6each independently selected from the group consisting of: hydrogen, halogen, C1-20Alkyl radical, C1-20Alkoxy radical, C1-20Ester group, benzyl group, C1-20Alkoxy-substituted benzyl, C6-12Aryl substituted C1-20An alkyl group;
R7、R8、R9each independently selected from the group consisting of: hydrogen, halogen, C1-20An alkyl group;
x in the formula (1) is COOH; x in the formula (2) is COO.
2. The method of synthesis according to claim 1, wherein the temperature of the reaction is 10-60 ℃.
3. The synthesis method of claim 1, wherein the pressure of carbon monoxide is 1 to 20 atm.
4. A synthesis method of quinolinone heteroaromatic ring compounds is characterized in that 35.6mg of 1w and 3.3mg of Pd (TFA))22.1mg of 1, 10-phenanthroline dione and 16.2mg of benzoquinone are sequentially added into a reaction tube, then CO balloon replacement is carried out for three times, 1mL of acetonitrile is added, a reaction system is reacted for 6 hours at room temperature to obtain 2w of yellow solid, and the reaction process is shown as the following reaction formula:
Figure FDA0003164182850000021
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WO2012099129A1 (en) * 2011-01-17 2012-07-26 国立大学法人 長崎大学 Compound having anti-cancer activity

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