CN113429424A - Preparation method of [1,2,4] oxadiazino indoline-3-ketone derivative - Google Patents
Preparation method of [1,2,4] oxadiazino indoline-3-ketone derivative Download PDFInfo
- Publication number
- CN113429424A CN113429424A CN202110832402.8A CN202110832402A CN113429424A CN 113429424 A CN113429424 A CN 113429424A CN 202110832402 A CN202110832402 A CN 202110832402A CN 113429424 A CN113429424 A CN 113429424A
- Authority
- CN
- China
- Prior art keywords
- phenylethynyl
- compound
- ethynyl
- nitrobenzene
- room temperature
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/10—Spiro-condensed systems
Abstract
The invention discloses a preparation method of a [1,2,4] oxadiazino indoline-3-ketone derivative, which comprises the following steps: (1) mixing an o-nitroacetophenone compound, a catalyst and a first organic solvent, and reacting at room temperature for 3-6 h; (2) adding alpha-halogenated hydroxamate compound, sodium carbonate and hexafluoroisopropanol into the material obtained in the step (1), and reacting at room temperature for 10-12 h; or mixing the o-nitroacetophenone compound, a catalyst, the alpha-halogenated hydroxamate compound, sodium carbonate and hexafluoroisopropanol, and reacting at 55-65 ℃ for 10-12 h. The invention can synthesize the [1,2,4] oxadiazino indoline-3-ketone derivative with various substituent groups which is difficult to synthesize by other methods, and has profound significance from the organic chemistry perspective.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of a [1,2,4] oxadiazino indoline-3-ketone derivative.
Background
The fused ring indoline-3-ketone compound plays an important role in indole alkaloid family due to the attractive molecular structure and potential biological activity, and researches show that some fused ring indoline-3-ketone compounds have various biological activities and fluorescence properties and have potential application values in the aspects of drug molecule synthesis and luminescent material development; on the other hand, the [1,2,4] oxadiazine derivative has important application value in the aspects of weeding, diuresis and inflammation diminishing. Therefore, the research on the [1,2,4] oxadiazinyl [2,3-a ] indole-2, 10(3H) -diketone derivative and the synthesis method thereof have important values and are widely concerned by researchers in related fields.
The traditional synthesis method of fused ring indoline-3-ketone generally involves complex biosynthesis and oxidative rearrangement of indole alkaloid, and has complicated steps and low economy. The development of a novel synthetic method based on various biological activities and fluorescence properties of the fused ring indoline-3-ketone compound is of great significance.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides a preparation method of a [1,2,4] oxadiazino indoline-3-ketone derivative.
The technical scheme of the invention is as follows:
a preparation method of [1,2,4] oxadiazino indoline-3-ketone derivatives comprises the following steps:
(1) mixing an o-nitroacetophenone compound, a catalyst and a first organic solvent, reacting for 3-6h at room temperature, adding an alpha-halogenated hydroxamate compound, alkali and hexafluoroisopropanol, and reacting for 10-12h at room temperature; or mixing an o-nitroacetophenone compound, a catalyst, an alpha-halogenated hydroxamate compound, sodium carbonate and hexafluoroisopropanol, and reacting at 55-65 ℃ for 10-12 h;
(2) removing the solvent from the material obtained in the step (1), and purifying by column chromatography to obtain the [1,2,4] oxadiazino indoline-3-ketone derivative;
the [1,2,4]]The structural formula of the oxadiazino indoline-3-ketone derivative is shown in the specification
The structural formula of the o-nitroacetophenone compound is shown in the specification
The structural formula of the alpha-halogenated hydroxamate compound is shown in the specification
R is as defined above1Is hydrogen, halogen, alkyl, aryl, substituted aryl, acyl, amino, nitro or alkoxy, R is2Is alkyl, aryl, substituted aryl or heterocycle, the above R3And R4Are each alkyl, or R as defined above3And R4Form a cycloalkyl group, R mentioned above5Is alkyl or alkenyl.
In a preferred embodiment of the present invention, said R1Is H, methyl, methoxy, F, CF3Or
In a preferred embodiment of the present invention: the R is2Is phenyl, substituted phenyl or
The substituent on the substituted phenyl is methoxy, ethyl, tBu and NO2Br, F, N or phenyl.
In a preferred embodiment of the present invention, said R5Is Bn, methyl or propenyl.
In a preferred embodiment of the present invention, the o-nitroacetophenone compound is 2- (phenylethynyl) nitrobenzene, 3-nitro-4- (phenylethynyl) toluene, 3-nitro-4- (phenylethynyl) anisole, 2- (phenylethynyl) -5-fluoronitrobenzene, methyl 3-nitro-4- (phenylethynyl) benzoate, 2- (phenylethynyl) -5-trifluoromethylnitrobenzene, 3- (phenylethynyl) -4-nitrobenzylether, 2- (phenylethynyl) -4-fluoronitrobenzene, 2-nitro-3- (phenylethynyl) toluene, 4-nitro-5- (phenylethynyl) -1, 2-xylene, xylene, 2- ((4-methoxyphenyl) ethynyl) -nitrobenzene, 2- ((4-ethylphenyl) ethynyl) -nitrobenzene, 2- ((4-tert-butylphenyl) ethynyl) -nitrobenzene, 2- ((4-nitrophenyl) ethynyl) -nitrobenzene, 2- ((4-bromophenyl) ethynyl) -nitrobenzene, 2- ((3-fluorophenyl) ethynyl) -nitrobenzene, 2- ((2-nitrophenyl) ethynyl) pyridine, 4- ((2-nitrophenyl) ethynyl) -1,1' -biphenyl or 3- ((2-nitrophenyl) ethynyl) thiophene.
Further preferably, the α -halohydroxamate compound is N- (benzyloxy) -2-bromo-2-methylpropanamide, 2-bromo-N-methoxy-2-methylpropanamide, N- (allyloxy) -2-bromo-2-methylpropanamide, or N- (benzyloxy) -1-bromocyclohexane-1-carboxamide.
In a preferred embodiment of the invention, the catalyst is gold trichloride, palladium dichloride, palladium acetate, bis-acetonitrile palladium dichloride, bis (dibenzylideneacetone) palladium, bis-triphenylphosphine palladium dichloride, gold tribromide or triphenylphosphine gold monochloride.
In a preferred embodiment of the present invention, the first organic solvent is toluene, acetonitrile or dichloromethane.
In a preferred embodiment of the invention, the base is sodium carbonate, triethylamine, 4-dimethylaminopyridine, sodium hydroxide or 1, 8-diazabicyclo [5.4.0] undec-7-ene.
In a preferred embodiment of the present invention, the ratio of the o-nitroacetophenone compound, the catalyst, the α -halohydroxamate compound, the base and the hexafluoroisopropanol is 0.1 to 0.2mmol:0.01 to 0.02mmol:0.1 to 0.5mmol:0.2 to 1.0mmol:1.0 to 2.0 mL.
The invention has the beneficial effects that:
1. the invention can synthesize the [1,2,4] oxadiazino indoline-3-ketone derivative with various substituent groups which is difficult to synthesize by other methods, and has profound significance from the organic chemistry perspective.
2. The method has the advantages of easily available raw materials, high yield, mild reaction conditions, short reaction time, wide substrate range, strong reaction specificity, simple and green post-treatment.
3. The [1,2,4] oxadiazinoindolin-3-one derivative obtained by the method has fluorescence property and low cytotoxicity, has potential application value in the field of nucleic acid dyes, and has specific effects shown in figure 1.
Drawings
FIG. 1 is a fluorescence emission spectrum of a portion of the products of the present invention, wherein the numbers represent specific products, such as 1 for product 1 obtained in example 1 and 2 for product 2 obtained in example 16.
FIG. 2 is an agarose gel electrophoresis of product 7 of example 21 of the present invention as a DNA dye.
Detailed Description
The technical solution of the present invention will be further illustrated and described below with reference to the accompanying drawings by means of specific embodiments.
Example 1
Preparation of product 1:
0.20mmol of 2- (phenylethynyl) nitrobenzene and 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene and reacted at room temperature for 3 hours, and then 0.50mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 1.0mmol of sodium carbonate and 1.0mL of hexafluoroisopropanol were added and reacted at room temperature for 12 hours. The reaction solution is extracted by water/dichloromethane (25mL/25mL), an organic phase is collected and concentrated, column chromatography purification is carried out to obtain 67.3mg of a target product, the yield is 81%, and the structural representation of the compound is as follows:1H NMR(400MHz,CDCl3)δ7.77(d,J＝8.1Hz,1H),7.65(t,J＝7.7Hz.,1H),7.52–7.44(m,4H),7.40–7.28(m,7H),7.11(t,J＝7.5Hz,1H),5.01(d,J＝8.8Hz,1H),4.86(d,J＝8.8Hz,1H),1.59(d,J＝4.4Hz,6H).13C NMR(100MHz,CDCl3)δ189.7,168.9,158.6,137.6,133.9,133.8,129.9,129.4,128.8,128.6,128.3,127.7,125.4,122.8,119.1,113.7,87.0,84.0,77.6,27.6,24.9.HRMS(ESI)m/z calcd for C25H22N2O4[M+Na]+437.1472,found437.1474。
example 2
Preparation of product 1:
0.10mmol of 2- (phenylethynyl) nitrobenzene, 0.01mmol of palladium dichloride, 0.10mmol of N- (benzyloxy) -2-bromo-2-methylpropionamide and 0.20mmol of sodium carbonate are added into a reaction tube containing 2.0mL of hexafluoroisopropanol and reacted at 60 ℃ for 12 hours, the reaction solution is extracted with water/dichloromethane (25mL/25mL), the organic phase is collected and concentrated, and after purification by column chromatography, the target product is obtained in a yield of 45% (structural characterization same as example 1).
Example 3
Preparation of product 1:
0.10mmol of 2- (phenylethynyl) nitrobenzene, 0.01mmol of palladium acetate, 0.10mmol of N- (benzyloxy) -2-bromo-2-methylpropionamide, and 0.20mmol of sodium carbonate were added to a reaction tube containing 2.0mL of hexafluoroisopropanol, and reacted at 60 ℃ for 12 hours, the reaction mixture was extracted with water/dichloromethane (25mL/25mL), the organic phase was collected and concentrated, and after purification by column chromatography, the objective product was obtained in 41% yield (structural characteristics same as in example 1).
Example 4
Preparation of product 1:
0.10mmol of 2- (phenylethynyl) nitrobenzene, 0.01mmol of bis-acetonitrile palladium dichloride, 0.10mmol of N- (benzyloxy) -2-bromo-2-methylpropionamide, and 0.20mmol of sodium carbonate were added to a reaction tube containing 2.0mL of hexafluoroisopropanol, reacted at 60 ℃ for 12 hours, the reaction solution was extracted with water/dichloromethane (25mL/25mL), the organic phase was collected, concentrated, and purified by column chromatography to obtain the objective product in a yield of 40% (structural characterization same as example 1).
Example 5
Preparation of product 1:
0.10mmol of 2- (phenylethynyl) nitrobenzene, 0.01mmol of bis (dibenzylideneacetone) palladium, 0.10mmol of N- (benzyloxy) -2-bromo-2-methylpropionamide and 0.20mmol of sodium carbonate were added to a reaction tube containing 2.0mL of hexafluoroisopropanol, reacted at 60 ℃ for 12 hours, the reaction solution was extracted with water/dichloromethane (25mL/25mL), the organic phase was collected, concentrated, purified by column chromatography, and the objective product was obtained in a yield of 40% (structural characterization same as in example 1).
Example 6
Preparation of product 1:
0.10mmol of 2- (phenylethynyl) nitrobenzene, 0.01mmol of bis triphenylphosphine palladium dichloride, 0.10mmol of N- (benzyloxy) -2-bromo-2-methylpropionamide, and 0.20mmol of sodium carbonate were added to a reaction tube containing 2.0mL hexafluoroisopropanol, and reacted at 60 ℃ for 12 hours, the reaction solution was extracted with water/dichloromethane (25mL/25mL), the organic phase was collected and concentrated, and after purification by column chromatography, the objective product was obtained in a yield of 40% (structural characterization same as example 1).
Example 7
Preparation of product 1:
0.10mmol of 2- (phenylethynyl) nitrobenzene, 0.01mmol of bis-acetonitrile palladium dichloride, 0.20mmol of N- (benzyloxy) -2-bromo-2-methylpropionamide, and 0.40mmol of triethylamine were added to a reaction tube containing 2.0mL of hexafluoroisopropanol, and reacted at 60 ℃ for 12 hours, and the reaction solution was extracted with water/dichloromethane (25mL/25mL), and the organic phase was collected, concentrated, and purified by column chromatography to obtain the objective product in a yield of 45% (structural characterization same as example 1).
Example 8
Preparation of product 1:
0.10mmol of 2- (phenylethynyl) nitrobenzene, 0.01mmol of bis-acetonitrile palladium dichloride, 0.20mmol of N- (benzyloxy) -2-bromo-2-methylpropionamide, and 0.40mmol of 4-dimethylaminopyridine were added to a reaction tube containing 2.0mL of hexafluoroisopropanol, reacted at 60 ℃ for 12 hours, the reaction solution was extracted with water/dichloromethane (25mL/25mL), the organic phase was collected, concentrated, and purified by column chromatography to obtain the objective product in a yield of 53% (structural characterization same as example 1).
Example 9
Preparation of product 1:
0.10mmol of 2- (phenylethynyl) nitrobenzene, 0.01mmol of bis-acetonitrile palladium dichloride, 0.20mmol of N- (benzyloxy) -2-bromo-2-methylpropionamide, and 0.40mmol of sodium hydroxide were added to a reaction tube containing 2.0mL of hexafluoroisopropanol, reacted at 60 ℃ for 12 hours, the reaction solution was extracted with water/dichloromethane (25mL/25mL), the organic phase was collected and concentrated, and after purification by column chromatography, the objective product was obtained in a yield of 40% (structural characterization same as example 1).
Example 10
Preparation of product 1:
0.10mmol of 2- (phenylethynyl) nitrobenzene, 0.01mmol of bis-acetonitrile palladium dichloride, 0.20mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 0.40mmol of 1, 8-diazabicyclo [5.4.0] undec-7-ene were added to a reaction tube containing 2.0mL of hexafluoroisopropanol and reacted at 60 ℃ for 12 hours, the reaction solution was extracted with water/dichloromethane (25mL/25mL), the organic phase was collected and concentrated, and after purification by column chromatography, the objective product was obtained in a yield of 45% (structural characterization same as in example 1).
Example 11
Preparation of product 1:
0.20mmol of 2- (phenylethynyl) nitrobenzene, 0.02mmol of bisacetonitrildichloropalladium were added to a reaction tube containing 0.50mL of acetonitrile, reacted at 100 ℃ for 12 hours, and then added with 0.40mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 0.8mmol of sodium carbonate, 2.0mL of hexafluoroisopropanol, and reacted at room temperature for 12 hours. The reaction solution was extracted with water/dichloromethane (25mL/25mL), the organic phase was collected, concentrated, and purified by column chromatography to obtain the objective product (structural characterization same as in example 1) in a yield of 70%.
Example 12
Preparation of product 1:
0.20mmol of 2- (phenylethynyl) nitrobenzene, 0.02mmol of bis-acetonitrile palladium dichloride were added to a reaction tube containing 0.50mL of dichloromethane and reacted at 100 ℃ for 12h, followed by addition of 0.40mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 0.8mmol of sodium carbonate, 2.0mL of hexafluoroisopropanol and reaction at room temperature for 12 h. The reaction solution was extracted with water/dichloromethane (25mL/25mL), the organic phase was collected, concentrated, and purified by column chromatography to obtain the objective product in 44% yield (structural characterization same as in example 1).
Example 13
Preparation of product 1:
0.20mmol of 2- (phenylethynyl) nitrobenzene, 0.02mmol of bis-acetonitrile palladium dichloride were added to a reaction tube containing 0.50mL of toluene, reacted at 100 ℃ for 12h, then added with 0.40mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 0.8mmol of sodium carbonate, 2.0mL of hexafluoroisopropanol, and reacted at room temperature for 12 h. The reaction solution was extracted with water/dichloromethane (25mL/25mL), the organic phase was collected, concentrated, and purified by column chromatography to obtain the objective product (structural characterization same as in example 1) in a yield of 47%.
Example 14
Preparation of product 1:
0.20mmol of 2- (phenylethynyl) nitrobenzene, 0.01mmol of gold tribromide were added to a reaction tube containing 0.50mL of toluene and reacted at room temperature for 3 hours, and then 0.50mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 1mmol of sodium carbonate, 1.0mL of hexafluoroisopropanol were added and reacted at room temperature for 12 hours. The reaction solution was extracted with water/dichloromethane (25mL/25mL), the organic phase was collected, concentrated, and purified by column chromatography to obtain the objective product (structural characterization same as example 1) in a yield of 76%.
Example 15
Preparation of product 1:
0.20mmol of 2- (phenylethynyl) nitrobenzene and 0.01mmol of triphenylphosphine gold monochloride were added to a reaction tube containing 0.50mL of toluene and reacted at room temperature for 3 hours, and then 0.50mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 1mmol of sodium carbonate and 1.0mL of hexafluoroisopropanol were added and reacted at room temperature for 12 hours. The reaction solution was extracted with water/dichloromethane (25mL/25mL), the organic phase was collected, concentrated, and purified by column chromatography to obtain the objective product (structural characterization same as example 1) in a yield of 37%.
Example 16
Preparation of product 2:
0.20mmol of 3-nitro-4- (phenylethynyl) toluene and 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene, and reacted at room temperature for 3 hours, followed by addition of 0.50mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 1.0mmol of sodium carbonate and 1.0mL of hexafluoroisopropanol, and reacted at room temperature for 12 hours. The reaction solution is extracted by water/dichloromethane (25mL/25mL), an organic phase is collected and concentrated, column chromatography purification is carried out to obtain 64.2mg of a target product, the yield is 75%, and the structural representation of the compound is as follows:1H NMR(400MHz,CDCl3)δ7.66(d,J＝7.9Hz,1H),7.51–7.45(m,4H),7.39–7.34(m,3H),7.31(dd,J＝5.1,1.9Hz,3H),7.15(s,1H),6.93(d,J＝7.9Hz,1H),5.01(d,J＝8.8Hz,1H),4.86(d,J＝8.8Hz,1H),2.47(s,3H),1.59(d,J＝10.5Hz,6H).13C NMR(100MHz,CDCl3)δ189.2,168.9,159.1,149.8,134.0,134.0,129.9,129.3,128.8,128.6,128.3,127.7,125.2,124.4,117.0,113.8,86.9,84.2,77.6,27.6,24.9,22.7.HRMS(ESI)m/z calcd for C26H24N2O4[M+Na]+451.1628,found 451.1629。
example 17
Preparation of product 3:
0.20mmol of 3-nitro-4- (phenylethynyl) anisole and 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene, and reacted at room temperature for 3 hours, followed by addition of 0.50mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 1.0mmol of sodium carbonate and 1.0mL of hexafluoroisopropanol, and reacted at room temperature for 12 hours. The reaction solution is extracted by water/dichloromethane (25mL/25mL), an organic phase is collected and concentrated, column chromatography purification is carried out to obtain 70.6mg of a target product, the yield is 81%, and the structural representation of the compound is as follows:1H NMR(400MHz,CDCl3)δ7.69(d,J＝8.6Hz,1H),7.51–7.45(m,4H),7.41–7.34(m,3H),7.34–7.28(m,3H),6.72(d,J＝2.1Hz,1H),6.63(dd,J＝8.7,2.1Hz,1H),5.01(d,J＝8.8Hz,1H),4.87(d,J＝8.8Hz,1H),3.92(s,3H),1.63(s,3H),1.57(s,3H).13C NMR(100MHz,CDCl3)δ187.5,168.8,168.0,161.0,134.2,134.0,129.9,129.3,128.8,128.6,128.3,127.6,127.1,112.0,111.4,96.5,87.2,84.1,77.6,56.0,27.8,24.8.HRMS(ESI)m/z calcd for C26H24N2O5[M+Na]+467.1577,found 467.1574。
example 18
Preparation of product 4:
0.20mmol of 2- (phenylethynyl) -5-fluoronitrobenzene and 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene, reacted at room temperature for 3 hours, and then added with 0.50mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 1.0mmol of sodium carbonate and 1.0mL of hexafluoroisopropanol, and reacted at room temperatureAnd (4) 12 h. The reaction solution is extracted by water/dichloromethane (25mL/25mL), an organic phase is collected and concentrated, column chromatography purification is carried out to obtain 57.6mg of a target product, the yield is 68%, and the structural representation of the compound is as follows:1H NMR(400MHz,CDCl3)δ7.76(dd,J＝8.5,5.3Hz,1H),7.47(td,J＝5.6,5.1,2.3Hz,4H),7.42–7.35(m,3H),7.31(dd,J＝4.9,1.9Hz,3H),6.97(dd,J＝8.8,2.1Hz,1H),6.78(td,J＝8.7,2.2Hz,1H),5.01(d,J＝8.9Hz,1H),4.86(d,J＝8.9Hz,1H),1.62(s,3H),1.57(s,3H).13C NMR(100MHz,CDCl3)δ187.7,169.2(d,JC-F＝259.4Hz),168.9,160.4(d,JC-F＝13.6Hz),133.8,133.5,130.0,129.5,128.9,128.7,128.3,128.0(d,JC-F＝12.0Hz),127.6,114.9(d,JC-F＝1.5Hz),110.9(d,JC-F＝24.6Hz),100.2(d,JC-F＝27.5Hz),87.6,83.9,77.7,27.6,24.7.19F NMR(376MHz,CDCl3)δ-95.8.HRMS(ESI)m/z calcd for C25H21FN2O4[M+Na]+455.1378,found 455.1377。
example 19
Preparation of product 5:
0.20mmol of 3-nitro-4- (phenylethynyl) benzoic acid methyl ester, 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene, reacted at room temperature for 3 hours, and then added with 0.50mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 1.0mmol of sodium carbonate, 1.0mL of hexafluoroisopropanol, and reacted at room temperature for 12 hours. The reaction solution is extracted by water/dichloromethane (25mL/25mL), an organic phase is collected and concentrated, column chromatography purification is carried out to obtain 77.0mg of target product, the yield is 82%, and the structural representation of the compound is as follows:1H NMR(400MHz,CDCl3)δ7.97(s,1H),7.81–7.73(m,2H),7.50–7.46(m,2H),7.46–7.42(m,2H),7.41–7.36(m,3H),7.33–7.28(m,3H),4.99(d,J＝8.9Hz,1H),4.86(d,J＝8.9Hz,1H),3.98(s,3H),1.59(s,6H).13C NMR(100MHz,CDCl3)δ189.4,169.1,165.5,158.2,138.2,133.7,133.3,130.0,129.6,128.9,128.7,128.4,128.3,127.7,125.4,123.6,121.9,114.6,87.3,84.4,77.7,52.9,27.5,24.7.HRMS(ESI)m/z calcd for C27H24N2O6[M+Na]+495.1527,found 495.1523。
example 20
Preparation of product 6:
0.20mmol of 2- (phenylethynyl) -5-trifluoromethylnitrobenzene and 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene, reacted at room temperature for 3 hours, and then added with 0.50mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 1.0mmol of sodium carbonate and 1.0mL of hexafluoroisopropanol, and reacted at room temperature for 12 hours. The reaction solution is extracted by water/dichloromethane (25mL/25mL), an organic phase is collected and concentrated, and the target product of 78.1mg is obtained by column chromatography purification, the yield is 81%, and the structural representation of the compound is as follows:1H NMR(400MHz,CDCl3)δ7.84(d,J＝8.0Hz,1H),7.57(s,1H),7.51–7.36(m,7H),7.36–7.27(m,4H),5.00(d,J＝8.9Hz,1H),4.85(d,J＝8.9Hz,1H),1.60(d,J＝3.5Hz,6H).13C NMR(100MHz,CDCl3)δ188.9,169.0,158.1,138.8(q,JC-F＝32.7Hz),133.7,133.1,130.0,129.7,128.9,128.7,128.3,127.7,126.3,123.1(q,JC-F＝273.7Hz),121.2,119.2(q,JC-F＝3.5Hz),110.4(q,JC-F＝4.0Hz),87.6,84.1,77.8,27.5,24.7.19FNMR(376MHz,CDCl3)δ-63.6.HRMS(ESI)m/z calcd for C26H21F3N2O4[M+Na]+505.1346,found 505.1350。
example 21
Preparation of product 7:
0.20mmol of 3- (phenylethynyl) -4-nitrobenzylether, 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene, reacted at room temperature for 3 hours, and then 0.50mmol of gold trichloride was addedN- (benzyloxy) -2-bromo-2-methylpropanamide, 1.0mmol of sodium carbonate, 1.0mL of hexafluoroisopropanol, and reacted at room temperature for 12 h. The reaction solution was extracted with water/dichloromethane (25mL/25mL), the organic phase was collected, concentrated, and purified by column chromatography to give 66.4mg of the target product (whose effect as DNA dye is shown in fig. 2), with a yield of 76%, and the structure of the compound was characterized as follows:1H NMR(400MHz,CDCl3)δ7.53–7.48(m,2H),7.48–7.44(m,2H),7.38–7.34(m,3H),7.33–7.28(m,4H),7.26(s,1H),7.20(d,J＝2.5Hz,1H),5.02(d,J＝8.9Hz,1H),4.97(d,J＝8.9Hz,1H),3.85(s,3H),1.65(s,3H),1.52(s,3H).13C NMR(100MHz,CDCl3)δ192.2,169.6,157.3,153.4,134.1,134.0,129.9,129.4,128.7,128.6,128.3,127.8,126.9,122.9,118.1,105.9,86.5,85.3,55.9,26.9,24.8.HRMS(ESI)m/z calcd for C26H24N2O5[M+Na]+467.1577,found 467.1579。
example 22
Preparation of product 8:
0.20mmol of 2- (phenylethynyl) -4-fluoronitrobenzene and 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene and reacted at room temperature for 3 hours, and then 0.50mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 1.0mmol of sodium carbonate and 1.0mL of hexafluoroisopropanol were added and reacted at room temperature for 12 hours. The reaction solution is extracted by water/dichloromethane (25mL/25mL), an organic phase is collected and concentrated, column chromatography purification is carried out to obtain 61.8mg of a target product, the yield is 72%, and the structural representation of the compound is as follows:1H NMR(400MHz,CDCl3)δ7.51–7.46(m,2H),7.46–7.40(m,3H),7.40–7.33(m,5H),7.33–7.28(m,3H),5.00(d,J＝8.9Hz,1H),4.91(d,J＝8.9Hz,1H),1.61(s,3H),1.55(s,3H).13C NMR(100MHz,CDCl3)δ190.1(d,JC-F＝2.9Hz),169.3,159.1(d,JC-F＝246.2Hz),155.0,130.0,129.6,128.8,128.7,128.3,127.7,125.3(d,JC-F＝25.3Hz),121.4(d,JC-F＝7.5Hz),116.6(d,JC-F＝7.8Hz),110.9(d,JC-F＝23.6Hz),27.3,24.8.19F NMR(376MHz,CDCl3)δ-117.9.HRMS(ESI)m/z calcd for C25H21FN2O4[M+Na]+455.1378,found455.1381。
example 23
Preparation of product 9:
0.20mmol of 2-nitro-3- (phenylethynyl) toluene and 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene, and reacted at room temperature for 3 hours, followed by addition of 0.50mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 1.0mmol of sodium carbonate and 1.0mL of hexafluoroisopropanol, and reacted at room temperature for 12 hours. The reaction solution is extracted by water/dichloromethane (25mL/25mL), an organic phase is collected and concentrated, column chromatography purification is carried out to obtain 79.1mg of a target product, the yield is 84%, and the structural representation of the compound is as follows:1H NMR(400MHz,CDCl3)δ7.65(d,J＝7.5Hz,1H),7.55(dd,J＝6.3,2.6Hz,2H),7.50–7.43(m,3H),7.35–7.26(m,7H),5.29(d,J＝9.0Hz,1H),5.08(d,J＝9.0Hz,1H),2.45(s,3H),1.87(s,3H),1.44(s,3H).13C NMR(100MHz,CDCl3)δ197.8,171.5,156.3,138.5,134.5,134.2,132.1,129.7,129.5,128.5,128.4,128.3,128.1,127.9,127.8,122.4,88.5,83.2,77.8,24.7,23.5,16.1.HRMS(ESI)m/z calcd for C26H24N2O4[M+Na]+451.1628,found451.1627。
example 24
Preparation of product 10:
0.20mmol of 4-nitro-5- (phenylethynyl) -1, 2-xylene, 0.01mmol of gold trichloride was added to a reaction tube containing 0.50mL of toluene, reacted at room temperature for 3 hours, and then 0.50mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 1.0mmol of sodium carbonate, 1.0mL of hexafluoroisopropanol were added and reacted at room temperature for 12 hours. The reaction mixture was washed with water/dichloromethane (25 mL/2)5mL), collecting an organic phase, concentrating, and purifying by column chromatography to obtain 51.2mg of a target product, wherein the yield is 58%, and the structural representation of the compound is as follows:1H NMR(400MHz,CDCl3)δ7.53(s,1H),7.47(dd,J＝6.5,2.7Hz,4H),7.39–7.33(m,3H),7.33–7.27(m,3H),7.16(s,1H),5.00(d,J＝8.8Hz,1H),4.86(d,J＝8.8Hz,1H),2.38(s,3H),2.29(s,3H),1.58(s,6H).13C NMR(100MHz,CDCl3)δ189.9,169.1,157.6,148.7,134.2,134.1,132.6,129.9,129.2,128.7,128.5,128.3,127.7,125.2,118.1,115.3,86.3,84.8,77.5,27.5,24.9,21.5,19.5.HRMS(ESI)m/z calcd for C27H26N2O4[M+Na]+465.1785,found 465.1786。
example 25
Preparation of product 11:
0.20mmol of 2- ((4-methoxyphenyl) ethynyl) -nitrobenzene, 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene, reacted at room temperature for 3h, and then 0.50mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 1.0mmol of sodium carbonate, 1.0mL of hexafluoroisopropanol were added, and reacted at room temperature for 12 h. The reaction solution is extracted by water/dichloromethane (25mL/25mL), an organic phase is collected and concentrated, 73.4mg of target product is obtained by column chromatography purification, the yield is 83%, and the structural representation of the compound is as follows:1H NMR(400MHz,CDCl3)δ7.78(d,J＝7.7Hz,1H),7.66(t,J＝7.5Hz,1H),7.52–7.42(m,4H),7.39–7.30(m,4H),7.13(t,J＝7.5Hz,1H),6.91(d,J＝8.8Hz,2H),5.01(d,J＝8.8Hz,1H),4.87(d,J＝8.8Hz,1H),3.81(s,3H),1.60(s,6H).13C NMR(100MHz,CDCl3)δ190.0,168.9,160.3,158.5,137.5,133.9,129.9,129.1,128.8,128.3,125.6,125.4,122.8,119.2,114.1,113.9,113.8,86.9,83.8,77.6,55.3,27.6,24.9,HRMS(ESI)m/zcalcd for C26H24N2O5[M+Na]+467.1577,found 467.1576。
example 26
Preparation of product 12:
0.20mmol of 2- ((4-ethylphenyl) ethynyl) -nitrobenzene, 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene, reacted at room temperature for 3 hours, and then 0.50mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 1.0mmol of sodium carbonate, 1.0mL of hexafluoroisopropanol were added, and reacted at room temperature for 12 hours. The reaction solution is extracted by water/dichloromethane (25mL/25mL), an organic phase is collected and concentrated, column chromatography purification is carried out to obtain 63.7mg of a target product, the yield is 70%, and the structural representation of the compound is as follows:1H NMR(400MHz,CDCl3)δ7.76(d,J＝7.7Hz,1H),7.67–7.61(m,1H),7.46(dd,J＝6.4,3.1Hz,2H),7.39(d,J＝8.3Hz,2H),7.36–7.27(m,4H),7.20(d,J＝8.3Hz,2H),7.10(t,J＝7.6Hz,1H),5.00(d,J＝8.8Hz,1H),4.85(d,J＝8.8Hz,1H),2.63(q,J＝7.6Hz,2H),1.58(s,6H),1.21(t,J＝7.6Hz,3H).13C NMR(100MHz,CDCl3)δ189.9,169.0,158.6,145.6,137.5,133.9,130.9,129.9,128.8,128.3,128.2,127.6,125.4,122.7,119.2,113.7,86.9,84.0,77.6,28.6,27.6,24.9,15.2.HRMS(ESI)m/z calcd for C27H26N2O4[M+Na]+465.1785,found 465.1789。
example 27
Preparation of product 13:
0.20mmol of 2- ((4-tert-butylphenyl) ethynyl) -nitrobenzene, 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene, reacted at room temperature for 3 hours, and then 0.50mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 1.0mmol of sodium carbonate, 1.0mL of hexafluoroisopropanol were added, and reacted at room temperature for 12 hours. The reaction solution is extracted by water/dichloromethane (25mL/25mL), an organic phase is collected and concentrated, column chromatography purification is carried out to obtain 71.5mg of a target product, the yield is 76%, and the structural representation of the compound is as follows:1H NMR(400MHz,CDCl3)δ7.76(d,J＝7.7Hz,1H),7.64(t,J＝7.7Hz,1H),7.47(dd,J＝6.4,2.7Hz,2H),7.43–7.36(m,4H),7.35–7.27(m,4H),7.10(t,J＝7.5Hz,1H),5.00(d,J＝8.9Hz,1H),4.86(d,J＝8.9Hz,1H),1.59(d,J＝4.3Hz,6H),1.29(s,9H).13C NMR(100MHz,CDCl3)δ189.9,168.9,158.6,152.3,137.5,133.9,130.6,130.0,128.8,128.3,127.3,125.7,125.4,122.7,119.2,113.7,86.9,83.9,77.6,34.6,31.2,27.6,24.9.HRMS(ESI)m/z calcd for C29H30N2O4[M+Na]+493.2098,found 493.2099。
example 28
Preparation of product 14:
0.20mmol of 2- ((4-nitrophenyl) ethynyl) -nitrobenzene, 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene, reacted at room temperature for 3 hours, and then 0.50mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 1.0mmol of sodium carbonate, 1.0mL of hexafluoroisopropanol were added, and reacted at room temperature for 12 hours. The reaction solution is extracted by water/dichloromethane (25mL/25mL), an organic phase is collected and concentrated, column chromatography purification is carried out to obtain 48.1mg of a target product, the yield is 52%, and the structural representation of the compound is as follows:1H NMR(400MHz,CDCl3)δ8.21(d,J＝8.7Hz,2H),7.77(t,J＝8.5Hz,3H),7.70(t,J＝7.7Hz,1H),7.47(dd,J＝6.3,2.8Hz,2H),7.39(d,J＝8.2Hz,1H),7.36–7.30(m,3H),7.16(t,J＝7.5Hz,1H),5.04(d,J＝8.7Hz,1H),4.84(d,J＝8.7Hz,1H),1.60(s,3H),1.55(s,3H).13C NMR(100MHz,CDCl3)δ188.4,168.6,158.7,148.4,140.8,138.1,133.5,130.0,129.1,129.1,128.4,125.8,123.6,123.3,118.6,113.8,87.4,82.9,77.9,27.6,24.8.HRMS(ESI)m/z calcd for C25H21N3O6[M+Na]+482.1323,found 482.1321。
example 29
Preparation of product 15:
0.20mmol of 2- ((4-bromophenyl) ethynyl) -nitrobenzene, 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene, reacted at room temperature for 3 hours, and then 0.50mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 1.0mmol of sodium carbonate, 1.0mL of hexafluoroisopropanol, and reacted at room temperature for 12 hours. The reaction solution is extracted by water/dichloromethane (25mL/25mL), an organic phase is collected and concentrated, column chromatography purification is carried out to obtain 72.2mg of a target product, the yield is 78%, and the structural representation of the compound is as follows:1H NMR(400MHz,CDCl3)δ7.76(d,J＝7.7Hz,1H),7.69–7.63(m,1H),7.53–7.44(m,4H),7.44–7.38(m,2H),7.38–7.29(m,4H),7.12(t,J＝7.5Hz,1H),5.01(d,J＝8.8Hz,1H),4.83(d,J＝8.8Hz,1H),1.58(s,3H),1.56(s,3H).13C NMR(100MHz,CDCl3)δ189.1,168.8,158.6,137.8,133.7,132.9,131.8,129.9,129.5,128.9,128.3,125.5,123.9,123.0,118.9,113.8,87.1,83.4,77.8,27.6,24.8.HRMS(ESI)m/z calcd for C25H21BrN2O4[M+Na]+515.0577,found 515.0582。
example 30
Preparation of product 16:
0.20mmol of 2- ((3-fluorophenyl) ethynyl) -nitrobenzene, 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene, reacted at room temperature for 3 hours, and then added with 0.50mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 1.0mmol of sodium carbonate, 1.0mL of hexafluoroisopropanol, and reacted at room temperature for 12 hours. The reaction solution is extracted by water/dichloromethane (25mL/25mL), an organic phase is collected and concentrated, column chromatography purification is carried out to obtain 50.1mg of a target product, the yield is 58%, and the structural representation of the compound is as follows:1H NMR(400MHz,CDCl3)δ7.77(d,J＝7.7Hz,1H),7.66(t,J＝7.7Hz,1H),7.51–7.42(m,2H),7.39–7.24(m,7H),7.16–7.02(m,2H),5.01(d,J＝8.8Hz,1H),4.85(d,J＝8.8Hz,1H),1.58(d,J＝3.5Hz,6H).13C NMR(100MHz,CDCl3)δ188.9,168.7,162.7(d,JC-F＝246.7Hz),158.6,137.8,136.2(d,JC-F＝7.3Hz),133.8,130.2(d,JC-F＝8.1Hz),129.9,128.9,128.3,125.6,123.5(d,JC-F＝3.1Hz),123.0,118.9,116.5(d,JC-F＝21.0Hz),115.2(d,JC-F＝23.7Hz),113.8,87.1,83.2(d,JC-F＝2.2Hz),77.8,27.6,24.9.19F NMR(376MHz,CDCl3)δ-111.8.HRMS(ESI)m/z calcd for C25H21FN2O4[M+Na]+455.1378,found 455.1376。
example 31
Preparation of product 17
0.20mmol of 2- ((2-nitrophenyl) ethynyl) pyridine and 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene, and reacted at room temperature for 3 hours, followed by addition of 0.50mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 1.0mmol of sodium carbonate and 1.0mL of hexafluoroisopropanol, and reacted at room temperature for 12 hours. The reaction solution is extracted by water/dichloromethane (25mL/25mL), an organic phase is collected and concentrated, column chromatography purification is carried out to obtain 51.6mg of a target product, the yield is 62%, and the structural representation of the compound is as follows:1H NMR(400MHz,CDCl3)δ8.64(d,J＝4.5Hz,1H),7.78(d,J＝7.7Hz,1H),7.72(td,J＝7.8,1.5Hz,1H),7.63(t,J＝7.7Hz,1H),7.48–7.35(m,3H),7.32–7.25(m,5H),7.11(t,J＝7.5Hz,1H),5.04(d,J＝9.0Hz,1H),4.89(d,J＝9.0Hz,1H),1.63(s,3H),1.59(s,3H).13C NMR(100MHz,CDCl3)δ189.5,170.5,158.9,153.2,149.8,137.5,136.9,134.0,130.1,128.7,128.2,125.4,123.9,122.9,122.8,119.5,113.5,86.9,84.3,77.8,27.6,24.5.HRMS(ESI)m/z calcd for C24H21N3O4[M+Na]+438.1424,found 438.1421。
example 32
Preparation of product 18
0.20mmol of 4- ((2-nitrophenyl) ethynyl) -1,1' -biphenyl, 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene, reacted at room temperature for 3 hours, and then 0.50mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 1.0mmol of sodium carbonate, 1.0mL of hexafluoroisopropanol were added, and reacted at room temperature for 12 hours. The reaction solution is extracted by water/dichloromethane (25mL/25mL), an organic phase is collected and concentrated, column chromatography purification is carried out to obtain 79.9mg of a target product, the yield is 82%, and the structural representation of the compound is as follows:1H NMR(400MHz,CDCl3)δ7.80(d,J＝7.7Hz,1H),7.69–7.63(m,1H),7.63–7.53(m,6H),7.54–7.48(m,2H),7.43(t,J＝7.5Hz,2H),7.39–7.29(m,5H),7.13(t,J＝7.5Hz,1H),5.06(d,J＝8.8Hz,1H),4.90(d,J＝8.8Hz,1H),1.62(s,6H).13CNMR(100MHz,CDCl3)δ189.7,168.9,158.6,142.3,140.4,137.6,133.8,132.7,129.9,128.8,128.7,128.3,128.1,127.5,127.4,127.2,125.5,122.9,119.1,113.7,87.0,83.9,77.7,27.6,24.9.HRMS(ESI)m/zcalcd for C31H26N2O4[M+Na]+513.1785,found 513.1783。
example 33
Preparation of product 19
0.20mmol of 3- ((2-nitrophenyl) ethynyl) thiophene, 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene, reacted at room temperature for 3 hours, and then added with 0.50mmol of N- (benzyloxy) -2-bromo-2-methylpropanamide, 1.0mmol of sodium carbonate, 1.0mL of hexafluoroisopropanol, and reacted at room temperature for 12 hours. The reaction solution is extracted by water/dichloromethane (25mL/25mL), an organic phase is collected and concentrated, column chromatography purification is carried out to obtain 79.0mg of a target product, the yield is 90%, and the structural representation of the compound is as follows:1H NMR(400MHz,CDCl3)δ7.80–7.70(m,2H),7.64(t,J＝7.7Hz,1H),7.51(dd,J＝7.0,2.1Hz,2H),7.41–7.28(m,6H),7.10(t,J＝7.8Hz,1H),4.94(d,J＝8.8Hz,1H),4.89(d,J＝8.8Hz,1H),1.59(s,3H),1.56(s,3H).13C NMR(100MHz,CDCl3)δ188.7,168.6,158.4,137.6,134.0,133.8,129.9,128.8,128.4,126.7,126.3,126.0,125.5,122.9,119.0,113.9,86.9,81.1,77.9,27.4,24.8.HRMS(ESI)m/zcalcd for C23H20N2O4S[M+Na]+443.1036,found 443.1035。
example 34
Preparation of product 20
0.20mmol of 2- (phenylethynyl) nitrobenzene and 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene and reacted at room temperature for 3 hours, and then 0.50mmol of 2-bromo-N-methoxy-2-methylpropanamide, 1.0mmol of sodium carbonate and 1.0mL of hexafluoroisopropanol were added and reacted at room temperature for 12 hours. The reaction solution is extracted by water/dichloromethane (25mL/25mL), an organic phase is collected and concentrated, column chromatography purification is carried out to obtain 33.2mg of a target product, the yield is 49%, and the structural representation of the compound is as follows:1H NMR(400MHz,CDCl3)δ7.80(d,J＝7.7Hz,1H),7.65(t,J＝7.7Hz,1H),7.47–7.36(m,5H),7.34(d,J＝8.2Hz,1H),7.12(t,J＝7.5Hz,1H),3.77(s,3H),1.57(d,J＝3.8Hz,6H).13C NMR(100MHz,CDCl3)δ189.9,168.7,158.7,137.7,133.6,129.5,128.7,127.6,125.4,122.9,119.0,113.9,86.9,83.7,63.8,27.5,24.8.HRMS(ESI)m/zcalcd for C19H18N2O4[M+Na]+361.1159,found 361.1163。
example 35
Preparation of product 21
0.20mmol of 2- (phenylethynyl) nitrobenzene and 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene and reacted at room temperature for 3 hours, and then 0.50mmol of N- (allyloxy) -2-bromo-2-methylpropanamide, 1.0mmol of sodium carbonate and 1.0mL of hexafluoroisopropanol were added and reacted at room temperature for 12 hours. Extracting the reaction solution with water/dichloromethane (25mL/25mL), collecting organic phase, concentrating, and purifying by column chromatography to obtain 40.4mg target productYield was 55%, and the structure of the compound is characterized as follows:1H NMR(400MHz,CDCl3)δ7.78(d,J＝7.7Hz,1H),7.64(t,J＝7.7Hz,1H),7.47(dd,J＝6.7,2.9Hz,2H),7.43–7.36(m,3H),7.34(d,J＝8.2Hz,1H),7.12(t,J＝7.5Hz,1H),5.99(dt,J＝10.5,6.7Hz,1H),5.30–5.17(m,2H),4.50(dd,J＝9.5,7.9Hz,1H),4.35(dd,J＝10.7,6.4Hz,1H),1.56(d,J＝2.3Hz,6H).13C NMR(100MHz,CDCl3)δ189.9,169.1,158.7,137.6,133.8,131.2,129.4,128.6,127.6,125.3,122.9,121.0,119.2,113.8,87.0,84.0,77.4,27.6,24.8.HRMS(ESI)m/zcalcd for C21H20N2O4[M+Na]+387.1315,found387.1313。
example 36
Preparation of product 22
0.20mmol of 2- (phenylethynyl) nitrobenzene and 0.01mmol of gold trichloride were added to a reaction tube containing 0.50mL of toluene and reacted at room temperature for 3 hours, and then 0.50mmol of N- (benzyloxy) -1-bromocyclohexane-1-carboxamide, 1.0mmol of sodium carbonate and 1.0mL of hexafluoroisopropanol were added and reacted at room temperature for 12 hours. The reaction solution is extracted by water/dichloromethane (25mL/25mL), an organic phase is collected and concentrated, column chromatography purification is carried out to obtain 46.0mg of a target product, the yield is 51%, and the structural representation of the compound is as follows:1H NMR(400MHz,CDCl3)δ7.77(d,J＝7.7Hz,1H),7.65(t,J＝7.7Hz,1H),7.53–7.40(m,5H),7.40–7.34(m,3H),7.34–7.27(m,3H),7.14(t,J＝7.5Hz,1H),5.02(d,J＝8.8Hz,1H),4.86(d,J＝8.8Hz,1H),2.14–2.04(m,1H),1.98–1.87(m,3H),1.76–1.57(m,5H),1.38(ddd,J＝16.4,12.7,6.7Hz,1H).13C NMR(100MHz,CDCl3)δ190.3,169.0,158.5,137.6,133.9,133.8,129.9,129.4,128.8,128.6,128.3,127.7,125.4,123.2,119.8,113.4,87.9,84.1,77.6,33.5,33.3,24.7,21.4,20.9.HRMS(ESI)m/zcalcd for C28H26N2O4[M+Na]+477.1785,found 477.1784。
the above description is only a preferred embodiment of the present invention, and therefore should not be taken as limiting the scope of the invention, which is defined by the appended claims.
Claims (10)
1. A method for preparing a [1,2,4] oxadiazinoindolin-3-one derivative is characterized in that: the method comprises the following steps:
(1) mixing an o-nitroacetophenone compound, a catalyst and a first organic solvent, reacting for 3-6h at room temperature, adding an alpha-halogenated hydroxamate compound, alkali and hexafluoroisopropanol, and reacting for 10-12h at room temperature; or mixing an o-nitroacetophenone compound, a catalyst, an alpha-halogenated hydroxamate compound, sodium carbonate and hexafluoroisopropanol, and reacting at 55-65 ℃ for 10-12 h;
(2) removing the solvent from the material obtained in the step (1), and purifying by column chromatography to obtain the [1,2,4] oxadiazino indoline-3-ketone derivative;
the [1,2,4]]The structural formula of the oxadiazino indoline-3-ketone derivative is shown in the specification
The structural formula of the o-nitroacetophenone compound is shown in the specification
The structural formula of the alpha-halogenated hydroxamate compound is shown in the specification
R is as defined above1Is hydrogen, halogen, alkyl, aryl, substituted aryl, acyl, amino, nitro or alkoxy, R is2Is alkyl, aryl, substituted aryl or heterocycle, the above R3And R4Are each alkyl, or R as defined above3And R4Form a cycloalkyl group, R mentioned above5Is alkyl or alkenyl.
2. The method of claim 1, wherein: the R is1Is H, methyl, methoxy, F, CF3Or
3. The method of claim 1, wherein: the R is2Is phenyl, substituted phenyl or
The substituent on the substituted phenyl is methoxy, ethyl, tBu and NO2Br, F, N or phenyl.
4. The method of claim 1, wherein: the R is5Is Bn, methyl or propenyl.
5. The method of claim 1, wherein: the o-nitroacetophenone compound is 2- (phenylethynyl) nitrobenzene, 3-nitro-4- (phenylethynyl) toluene, 3-nitro-4- (phenylethynyl) anisole, 2- (phenylethynyl) -5-fluoronitrobenzene, 3-nitro-4- (phenylethynyl) methyl benzoate, 2- (phenylethynyl) -5-trifluoromethylnitrobenzene, 3- (phenylethynyl) -4-nitrobenzyl ether, 2- (phenylethynyl) -4-fluoronitrobenzene, 2-nitro-3- (phenylethynyl) toluene, 4-nitro-5- (phenylethynyl) -1, 2-xylene, 2- ((4-methoxyphenyl) ethynyl) -nitrobenzene, methyl benzoate, ethyl benzoate, and the like, 2- ((4-ethylphenyl) ethynyl) -nitrobenzene, 2- ((4-tert-butylphenyl) ethynyl) -nitrobenzene, 2- ((4-nitrophenyl) ethynyl) -nitrobenzene, 2- ((4-bromophenyl) ethynyl) -nitrobenzene, 2- ((3-fluorophenyl) ethynyl) -nitrobenzene, 2- ((2-nitrophenyl) ethynyl) pyridine, 4- ((2-nitrophenyl) ethynyl) -1,1' -biphenyl or 3- ((2-nitrophenyl) ethynyl) thiophene.
6. The method of claim 7, wherein: the alpha-halo hydroxamate compound is N- (benzyloxy) -2-bromo-2-methylpropanamide, 2-bromo-N-methoxy-2-methylpropanamide, N- (allyloxy) -2-bromo-2-methylpropanamide, or N- (benzyloxy) -1-bromocyclohexane-1-carboxamide.
7. The method of claim 1, wherein: the catalyst is gold trichloride, palladium dichloride, palladium acetate, bis-acetonitrile palladium dichloride, bis (dibenzylideneacetone) palladium, bis-triphenylphosphine palladium dichloride, gold tribromide or triphenylphosphine gold monochloride.
8. The method of claim 1, wherein: the first organic solvent is toluene, acetonitrile or dichloromethane.
9. The method of claim 1, wherein: the base is sodium carbonate, triethylamine, 4-dimethylaminopyridine, sodium hydroxide or 1, 8-diazabicyclo [5.4.0] undec-7-ene.
10. The production method according to any one of claims 1 to 8, characterized in that: the proportion of the o-nitroacetophenone compound, the catalyst, the alpha-halogenated hydroxamate compound, the alkali and the hexafluoroisopropanol is 0.1-0.2mmol, 0.01-0.02mmol, 0.1-0.5mmol, 0.2-1.0mmol and 1.0-2.0 mL.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110832402.8A CN113429424B (en) | 2021-07-22 | 2021-07-22 | Preparation method of [1,2,4] oxadiazino indoline-3-ketone derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110832402.8A CN113429424B (en) | 2021-07-22 | 2021-07-22 | Preparation method of [1,2,4] oxadiazino indoline-3-ketone derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113429424A true CN113429424A (en) | 2021-09-24 |
| CN113429424B CN113429424B (en) | 2022-06-07 |
Family
ID=77761453
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110832402.8A Active CN113429424B (en) | 2021-07-22 | 2021-07-22 | Preparation method of [1,2,4] oxadiazino indoline-3-ketone derivative |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113429424B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999064426A1 (en) * | 1998-06-10 | 1999-12-16 | G.D. Searle & Co. | Heterobicyclic and tricyclic nitric oxide synthase inhibitors |
| CN107382899A (en) * | 2017-07-06 | 2017-11-24 | 华侨大学 | A kind of polysubstituted benzo-oxazine derivative of 2 hydroxyl 1,4 |
-
2021
- 2021-07-22 CN CN202110832402.8A patent/CN113429424B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999064426A1 (en) * | 1998-06-10 | 1999-12-16 | G.D. Searle & Co. | Heterobicyclic and tricyclic nitric oxide synthase inhibitors |
| CN107382899A (en) * | 2017-07-06 | 2017-11-24 | 华侨大学 | A kind of polysubstituted benzo-oxazine derivative of 2 hydroxyl 1,4 |
Non-Patent Citations (1)
| Title |
|---|
| ZHANNA V. CHIRKOVA，等: "Synthesis of substituted [1,2,4]oxadiazino[2,3-a]indole-7,8-dicarbonitriles", 《MENDELEEV COMMUN.》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113429424B (en) | 2022-06-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN114105978A (en) | Oxindole compound and preparation method and application thereof | |
| CN111646990A (en) | Preparation method of 3, 4-bridged ring indole compound and synthesis method of Rucaparib | |
| CN114195711A (en) | Preparation method of quinoline-4 (1H) -ketone compound | |
| CN113429424B (en) | Preparation method of [1,2,4] oxadiazino indoline-3-ketone derivative | |
| WO2022156025A1 (en) | SYNTHESIS METHOD FOR 4-(2,2,2-TRICHLOROETHYL)-β-LACTAM DERIVATIVE | |
| CN115260080B (en) | Preparation method of indole-3-formamide compound | |
| CN113735756A (en) | Method for synthesizing chiral 3, 3-disubstituted isoindolinone compound by rhodium catalysis | |
| CN113912609B (en) | Preparation method of natural alkaloid tryptanthrin and derivatives thereof | |
| CN114014802B (en) | Method for synthesizing enamide by dehydrogenation coupling of palladium catalyst | |
| CN115215814A (en) | Synthetic method of isoxazolidine compounds | |
| CN112694430B (en) | Preparation method of 1, 5-dihydro-2H-pyrrole-2-ketone compound | |
| CN113387886B (en) | 2-aminodibenzo [ c, e ] azepine compound and synthetic method thereof | |
| CN110540516B (en) | Preparation method of 1-sulfonylmethyl-3, 4-dihydronaphthalene | |
| CN113651788A (en) | 3-amine alkyl chromone compound and preparation method thereof | |
| CN113511986A (en) | Preparation method of aryl acetonitrile derivative | |
| CN109810114A (en) | A kind of method of microwave atmospheric synthesis camptothecine compounds | |
| CN115286628B (en) | Preparation method of indolo [2,1a ] isoquinoline compound | |
| CN112239456B (en) | Preparation method of substituted 2, 3-dihydroquinolone compound | |
| CN110467613B (en) | Reaction method for alkylation of imide cation intramolecular amide by nickel catalysis | |
| CN115353514B (en) | Fluoro-pyridopyrimidinone compounds and synthesis method thereof | |
| CN112939830B (en) | Nucleophilic reaction method of alkenyl thioether to o-methylene benzoquinone | |
| CN113429407B (en) | Simple synthesis method of 1-alkyl-3-aryl substituted indolizine compound | |
| CN115304557B (en) | Enamine derivative and preparation method thereof | |
| CN113754544B (en) | Preparation method of polysubstituted (E) -trifluoromethyl olefin | |
| CN110204456B (en) | Polysubstituted naphthalene derivative and synthesis method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |