CN115611816A - Method for efficiently preparing 5-aryl (hetero) ring modified uracil derivative - Google Patents

Method for efficiently preparing 5-aryl (hetero) ring modified uracil derivative Download PDF

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CN115611816A
CN115611816A CN202110794050.1A CN202110794050A CN115611816A CN 115611816 A CN115611816 A CN 115611816A CN 202110794050 A CN202110794050 A CN 202110794050A CN 115611816 A CN115611816 A CN 115611816A
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程靓
刘安娣
刘利
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Abstract

The invention provides a method for efficiently preparing 5-aryl (hetero) ring modified uracil derivatives. Uracil/uridine or derivatives thereof are used as raw materials, and 5-aryl (hetero) ring substituted uracil/uridine derivatives are obtained through one-step photocatalytic coupling reaction. The invention takes simple and easily obtained uracil/uridine as raw materials, does not need to perform pre-functionalization on the C5 position, and can realize the synthesis of 5-aryl (hetero) ring substituted uracil derivatives through one-step photocatalytic coupling reaction.

Description

Method for efficiently preparing 5-aryl (hetero) ring modified uracil derivative
Technical Field
The invention relates to a method for efficiently preparing 5-aryl (hetero) ring modified uracil derivatives, belonging to the field of organic synthesis.
Background
5-substituted pyrimidine nucleosides, which are important nucleoside derivatives, exhibit a wide range of biological activities and play important roles not only in many biological processes but also as important raw materials for the preparation of drug molecules, and the modification thereof by chemical means is a hot spot of the next study. Among them, 5-ar (hetero) uracil is commonly used as a potential drug due to its unique pharmacological and biological activities and is an important raw material for the preparation of antiviral drugs, antitumor drugs, anticancer drugs, anti-inflammatory drugs, etc. (arch.pharm.chem.life sci.2017,350, e1700023; ACS med.chem.lett.2015,6,1150, eur.j.med.chem.,2018,145,413, bioorg.med.chem.2008, 18, 3344. In addition, modified uracils are structurally similar to natural nucleosides and therefore form stable watson-crick base pairs with natural nucleosides, and the presence of aryl groups can enhance conjugation and increase fluorescence properties, and are therefore often used as fluorescent probes, which, when specifically inserted into an oligonucleotide chain, can detect nucleic Acids and interactions between nucleic Acids and proteins or small molecules by changes in their optical properties, making a great contribution to the diagnosis and treatment of diseases (j.org.chem.2018, 83,20,12711 j.am.chem.soc.2018,140, 12622. During the last decades, researchers have conducted extensive research into the synthesis of 5-aryl (hetero) substituted uracils and their derivatives. The current major methods include: 1) Suzuki-Miyaura coupling reaction, stille coupling reaction, and Negishi reaction of C5 activated uracil and activated aryl (hetero) ring, etc. (bioorg.med.chem.2015, 23,5764; J.am.chem.Soc.2005,127,10784; j.am.chem.soc.2006,128, 5334); 2) Coupling/substitution reactions between activated uracil bases and non-activated aryl (hetero) rings (helv.chim.acta., 2015,98,953; synthesis 2010,22,3927); 3) Non-activated bases and activated aromatic (hetero) rings (eur.j.org.chem.2009, 3698; science 2012,337,1644).
Although these methods can provide target molecules with high yield and selectivity, the reaction is usually carried out in toxic organic solvents and often requires high temperature, and in addition, the steps of C-H activation of coupled substrates, protection of groups and deprotection make the experimental process more cumbersome and do not meet the requirements of green chemistry. Although the photocatalytic chemical synthesis reaction has strong reactivity and mild conditions, the selectivity is poor, and the product is often a mixture. The electrochemical synthesis is realized by the transfer of electrons, the electrons can be used as clean energy, and the electrochemical synthesis has the advantages of strong reaction selectivity, high atom economy, less side reactions and high reaction rate, thereby having high practical value. To date, the technology for preparing biaryl compounds by cross-coupling has been greatly developed, and the search for a transition metal-free and mild-condition synthesis route is a research hotspot in recent years. In order to improve atom economy and meet the requirements of green chemistry, environment-friendly solvents and active substrates or catalysts are required to be searched. Therefore, it will be the direction of future research to implement direct arylation of non-activated substrates instead of cross-coupling reactions.
Disclosure of Invention
The invention aims to provide a method for preparing 5-aryl (hetero) ring modified uracil derivatives. The invention develops a simpler and more universal method, which takes uracil/uridine which is simple and easy to obtain as a raw material, does not need to perform pre-functionalization on the C5 position, and realizes the synthesis of the 5-aryl (hetero) ring substituted uracil derivative through one-step photocatalytic coupling reaction.
The method for preparing the 5-aryl (hetero) ring modified uracil derivative provided by the invention is characterized in that uracil/uridine or derivatives thereof are used as raw materials, and the 5-aryl (hetero) ring substituted uracil/uridine derivative is obtained through one-step photocatalytic coupling reaction.
Specifically, the method comprises the following steps:
in the presence of a photosensitizer and under the illumination of LED, enabling a compound shown in a formula I to react with a compound shown in a formula II to obtain a compound shown in a formula III,
Figure BDA0003162157350000021
in the formula I, R 1 、R 2 Each independently selected from H, C1-C6 straight chain or branched chain alkyl (specifically can be-CH) 3 )
Figure BDA0003162157350000022
When R is 1 、R 2 When the compounds are methyl, the compound shown in the formula I is 1,3-dimethyl uracil;
when R is 1 Is composed of
Figure BDA0003162157350000023
R 2 When the compound is H, the compound shown as the formula I is uridine;
when R is 1 Is composed of
Figure BDA0003162157350000031
R 2 When the compound is H, the compound shown in the formula I is 2' -deoxyuridine;
in the formula II, the reaction mixture is shown in the specification,
Figure BDA0003162157350000032
represents substituted or unsubstituted aromatic group, and the aromatic group can be benzene ring, quinolyl and 1H-pyrazolyl.
The substituent in the substituted aryl group can be selected from C1-C6 straight chain or branched chain alkyl (specifically, methyl), C1-C6 alkoxy (specifically, methoxy), nitro, halogen (specifically, F, cl or Br), halogen substituted C1-C6 straight chain or branched chain alkyl (specifically, trifluoromethyl), and five-membered or six-membered ring (specifically, five-membered or six-membered ring) formed by two adjacent carbon atoms on the aryl group through at least one heteroatom
Figure BDA0003162157350000033
At least one of (a) and (b),
the compound represented by formula II may specifically be: any one of 2-bromophenyl diazonium tetrafluoroborate, 2-chlorophenyl diazonium tetrafluoroborate, 3-methylphenyl diazonium tetrafluoroborate, 3-trifluoromethylphenyl diazonium tetrafluoroborate, 3-chlorophenyl diazonium tetrafluoroborate, 3,4-methylenedioxyphenyl diazonium tetrafluoroborate, 4-trifluoromethylphenyl diazonium tetrafluoroborate, 3-bromophenyl diazonium tetrafluoroborate, 4-methoxyphenyl diazonium tetrafluoroborate, 4-chlorophenyl diazonium tetrafluoroborate, 4-methylphenyl diazonium tetrafluoroborate, phenyl diazonium tetrafluoroborate, 1H-pyrazole-3-diazonium tetrafluoroborate, 3-quinoline diazonium tetrafluoroborate, 3-nitro-4-chlorophenyl diazonium tetrafluoroborate, 3-fluorophenyl diazonium tetrafluoroborate, 4-fluorophenyl diazonium tetrafluoroborate, and 4-nitrophenyl diazonium tetrafluoroborate;
in the formula III, R 1 、R 2 In the same formula I as R 1 、R 2 ，
Figure BDA0003162157350000034
In the same formula II
Figure BDA0003162157350000035
The photosensitizer can be at least one of eosin Y disodium salt, 4,4 '-bis (N, N-dimethylamino) benzophenone, anthraquinone, tris (2,2' -bipyridyl) ruthenium chloride hexahydrate, riboflavin, proflavine sulfate, 9-mesitylene-2,7, 10-trimethylacridine perchlorate, acid red 94, hematoporphyrin dihydrochloride and rhodamine B.
The reaction is carried out in water;
the reaction is carried out in an inert atmosphere, and the inert atmosphere can be specifically provided by argon;
the reaction is carried out under the condition of adding additives, wherein the additives can be NaBr, liCl, naCl, KCl and CaCl 2 ,MgCl 2 ,ZnCl 2 ,CuCl 2 ,NaSO 4 At least one of (1).
The mol ratio of the compound shown in the formula I to the compound shown in the formula II, the photosensitizer and the additive can be: 20:1:0.025:1.
the wavelength of the LED light may be 365-530nm, specifically 470nm, the power may be 3W,
the reaction is carried out at room temperature, and the reaction time can be 18h-60h, and specifically can be 18h.
The invention develops a simpler and more universal method, which takes uracil/uridine which is simple and easy to obtain as a raw material, does not need to carry out pre-functionalization on the C5 position, and can realize the synthesis of the 5-aryl (hetero) ring substituted uracil derivative through one-step photocatalytic coupling reaction.
Drawings
FIG. 1 is a reaction scheme of the present invention.
Detailed Description
The experimental procedures used in the following examples are all conventional procedures unless otherwise specified.
Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.
The aryldiazonium tetrafluoroborates used in the following examples were prepared by the following method:
the first synthesis method of the aryl diazo tetrafluoroborate comprises the following steps: aromatic amine and its derivatives (1 eq) were dissolved in water (2 mL) and ethanol (1 mL) in a 50mL round bottom flask, and aqueous tetrafluoroborate solution (48 w%,2.6 eq) was added. If the aromatic amine and its derivatives are not dissolved, water or ethanol is added dropwise until a homogeneous solution is obtained. After stirring for 15 minutes, an aqueous solution of sodium nitrite (1.0 eq) was added dropwise, and after completion of the addition, the mixture was stirred for a further 1 hour at below 0 ℃. And adding anhydrous ether into the reaction system after the reaction is finished, performing suction filtration on the precipitated solid, re-dissolving the obtained crude product in a minimum amount of acetone, and adding the anhydrous ether for recrystallization to obtain a purified product. The product was stored at-20 ℃ protected from light.
The second synthesis method of the aryl diazo tetrafluoroborate comprises the following steps: the second method for synthesizing the diazo compound corresponds mainly to the first method. Tert-butyl nitrite (2.0 equivalents) was added dropwise instead of aqueous sodium nitrite solution using ethanol as solvent, the temperature was kept at 0 ℃ all the time, and then the reaction mixture was stirred at 0 ℃ for another one hour. And adding anhydrous ether into the reaction system after the reaction is finished, performing suction filtration on the precipitated solid, re-dissolving the obtained crude product in a minimum amount of acetone, and adding the anhydrous ether for recrystallization to obtain a purified product. The product was stored at-20 ℃ protected from light.
Examples 1,
A10 mL Schlenk tube was charged with 1,3-dimethyluracil (280.3mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25% mmol), phenyldiazotetrafluoroborate (19.2mg, 0.1mmol), evacuated three times, protected with an argon balloon, 1mL water was added via syringe, and stirred at room temperature for 18h under a 470nm 3W LED lamp. The reaction mixture was added with a few drops of a saturated aqueous sodium bicarbonate solution, spin-dried, dissolved in ethyl acetate, stirred on silica gel and subjected to column chromatography (n-hexane: ethyl acetate = 5:1) to give 1,3-dimethyl-5-phenyluracil as a white solid in 12.6mg at 58.3% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000051
1 H NMR(300MHz,CDCl 3 )δ7.53–7.45(m,2H),7.43–7.31(m,3H),7.29(s,1H),3.47(s,3H),3.43(s,3H).
13 C NMR(101MHz,CDCl 3 )δ162.5,151.6,140.5,133.0,128.6,128.4,128.0,114.5,37.2,28.4.
HRMS(APCI)calcd for C12H13N2O2(M+H) + :217.0972,Found 217.0977.
the reaction can also be carried out under the following conditions of the photosensitizer (corresponding to the corresponding light source), and the reaction procedure is the same as in example 1
Item(s) Photosensitizers Light source (nm) Yield of the product
1 4,4' -bis (N, N-dimethylamino) benzophenone 365 7.4％
2 Benzophenones as herbicides 365 11.6％
3 Anthraquinone 365 18.5％
4 Riboflavin 470 24.1％
5 Tris (2,2' -bipyridine) ruthenium chloride hexahydrate 470 20.4％
6 Proflavine sulphate 470 33.3％
7 9-trimethyl-2,7, 10-trimethylacridine perchlorate 470 32.4％
8 Acid Red 94 530 20.8％
9 Hematoporphyrin dihydrochloride 530 15.3％
10 Eosin Y disodium salt 530 28.7％
11 Rhodamine B 530 6.9％
The reaction can also be carried out with the addition of the following additives, the procedure being as in example 1
Item(s) Additive agent Yield of
1 LiCl 59.2％
2 ZnCl 2 65.2％
3 CuCl 2 37.5％
4 NaCl 54.6％
5 CaCl 2 53.2％
6 MgCl 2 55.0％
7 Na 2 SO 4 56.9％
8 KCl 52.7％
Examples 2,
A10 mL Schlenk tube was charged with 1,3-dimethyluracil (280.3mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25 mmol), 4-methylphenyldiazotetrafluoroborate (20.6 mg, 0.1mmol), evacuated three times, under argon balloon protection, 1mL of water was added with a syringe and stirred at room temperature for 18h under a 470nm 3W LED lamp. The reaction mixture was added with a few drops of a saturated aqueous sodium bicarbonate solution, spin-dried, dissolved in ethyl acetate, stirred on silica gel and subjected to column chromatography (n-hexane: ethyl acetate = 5:1) to give 1,3-dimethyl-5-p-tolyluracil as a white solid in 12.3mg, 53.5% yield. The structural formula of the product and the characterization data thereof are as follows:
Figure BDA0003162157350000061
1 H NMR(400MHz,DMSO-d 6 )δ7.93(s,1H),7.45(d,J＝7.8Hz,2H),7.18(d,J＝7.8Hz,2H),3.38(s,3H),3.23(s,3H),2.31(s,3H).
13 C NMR(126MHz,DMSO-d 6 )δ161.8,151.0,142.1,136.3,130.5,128.6,127.9,111.4,36.5,27.8,20.7.
HRMS(EI)calcd for C13H14N2O2(M) + :230.1055,found 230.1053.
examples 3,
To a 10mL Schlenk tube was added 1,3-dimethyluracil (280.3mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25 mmol), 4-methoxyphenyl diazotetrafluoroborate (22.2mg, 0.1mmol), evacuated three times, under argon balloon protection, 1mL water was added with syringe, stirred at room temperature for 18h under 470nm 3W LED lamp. The reaction mixture was added with a few drops of a saturated aqueous sodium bicarbonate solution, spin-dried, dissolved in ethyl acetate, stirred on silica gel and subjected to column chromatography (n-hexane: ethyl acetate = 5:1) to give 1,3-dimethyl-5-p-methoxyphenyluracil as a white solid, 15.6mg in 63.4% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000062
1 H NMR(300MHz,CDCl 3 )δ7.42(d,J＝8.7Hz,2H),7.23(s,1H),6.91(d,J＝8.7Hz,2H),3.82(s,3H),3.45(s,3H),3.41(s,3H).
13 C NMR(101MHz,CDCl 3 )δ162.7,159.5,151.6,139.7,129.6,125.4,114.3,114.0,55.5,37.2,28.4.
HRMS(APCI)calcd for C13H15N2O3(M+H) + :247.1077,found 247.1075.
examples 4,
A10 mL Schlenk tube was charged with 1,3-dimethyluracil (280.3mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25% mmol), 4-nitrophenyldiazonium tetrafluoroborate (23.7mg, 0.1mmol), evacuated three times, under argon balloon protection, 1mL of water was added via syringe, and stirred at room temperature for 18h under 470nm 3W LED lamp. The reaction mixture was added with a few drops of a saturated aqueous sodium bicarbonate solution, spin-dried, dissolved in ethyl acetate, stirred on silica gel and subjected to column chromatography (n-hexane: ethyl acetate = 5:1) to give 1,3-dimethyl-5-p-nitrophenyluracil as a yellow solid, 18.5mg, in 70.9% yield. The structural formula of the product and the characterization data thereof are as follows:
Figure BDA0003162157350000071
1 H NMR(300MHz,CDCl 3 )δ8.24(d,J＝8.9Hz,2H),7.73(d,J＝8.9Hz,2H),7.46(s,1H),3.53(s,3H),3.44(s,3H).
13 C NMR(126MHz,CDCl 3 )δ161.8,151.3,147.2,141.9,139.8,128.9,123.9,112.3,37.6,28.5.
HRMS(APCI)calcd for C12H12N3O4(M+H) + :262.0822,found 262.0820.
examples 5,
A10 mL Schlenk tube was charged with 1,3-dimethyluracil (280.3mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25 mmol), 4-fluorophenyldiazotetrafluoroborate (21.0mg, 0.1mmol), evacuated three times, under argon balloon protection, 1mL of water was added via syringe, and stirred at room temperature for 18h under 470nm 3W LED lamp. The reaction mixture was added with a few drops of saturated aqueous sodium bicarbonate solution, spun-dried, dissolved in ethyl acetate, stirred over silica gel and subjected to column chromatography (n-hexane: ethyl acetate = 5:1) to give 1,3-dimethyl-5-p-fluorophenyluracil as a white solid, 16.4mg, 70.1% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000072
1 H NMR(500MHz,CDCl 3 )δ7.50–7.43(m,2H),7.27(s,1H),7.11–7.04(m,2H),3.48(s,3H),3.42(s,3H).
13 C NMR(126MHz,CDCl 3 )δ162.5,161.6(d,J＝247.1Hz),151.6,140.4,130.1(d,J＝8.2Hz),129.0(d,J＝3.6Hz),115.5(d,J＝21.8Hz),113.7,37.3,28.4.
19 F NMR(377MHz,CDCl 3 )δ-114.0.
HRMS(APCI)calcd for C12H12FN2O2(M+H) + :235.0877,found 235.0873.
examples 6,
A10 mL Schlenk tube was charged with 1,3-dimethyluracil (280.3mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25 mmol), 4-chlorophenyldiazotetrafluoroborate (22.6 mg, 0.1mmol), evacuated three times, under argon balloon protection, 1mL of water was added with a syringe and stirred at room temperature for 18h under a 470nm 3W LED lamp. The reaction mixture was added with a few drops of a saturated aqueous sodium bicarbonate solution, spin-dried, dissolved in ethyl acetate, stirred on silica gel and subjected to column chromatography (n-hexane: ethyl acetate = 5:1) to give 1,3-dimethyl-5-p-chlorophenyl uracil as a white solid, 18.1mg in 72.1% yield. The structural formula of the product and the characterization data thereof are as follows:
Figure BDA0003162157350000081
1 H NMR(500MHz,DMSO-d 6 )δ8.06(s,1H),7.61(d,J＝8.5Hz,2H),7.45(d,J＝8.4Hz,2H),3.39(s,3H),3.24(s,3H).
13 C NMR(126MHz,DMSO-d6)δ161.6,150.9,143.0,132.4,131.7,129.6,128.1,110.1,36.5,27.8.
HRMS(APCI)calcd for C12H12ClN2O2(M+H) + :251.0582,found 251.0581.
examples 7,
A10 mL Schlenk tube was charged with 1,3-dimethyluracil (280.3mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25 mmol), 4-trifluoromethylphenyldiazotetrafluoroborate (26.0mg, 0.1mmol), evacuated three times, under argon balloon protection, 1mL of water was added via syringe, and stirred at room temperature for 18h under 470nm 3W LED lamp. The reaction mixture was added with a few drops of a saturated aqueous sodium bicarbonate solution, spin-dried, dissolved in ethyl acetate, stirred on silica gel and subjected to column chromatography (n-hexane: ethyl acetate = 5:1) to give 1,3-dimethyl-5-p-trifluoromethylphenyluracil as a white solid, 19.6mg in 69.0% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000082
1 H NMR(400 MHz,DMSO-d 6 )δ8.16(s,1H),7.83(d,J＝8.3 Hz,2H),7.73(d,J＝8.3 Hz,2H),3.41(s,3H),3.25(s,3H).
13 C NMR(101 MHz,DMSO-d 6 )δ161.5,150.8,143.8,137.8,128.4,127.1(q,J＝31.9Hz),124.8(q,J＝3.7 Hz),123.0(d,J＝271.7 Hz),109.8,36.6,27.7.
19 F NMR(377 MHz,DMSO-d 6 )δ-60.9.
HRMS(APCI)calcd for C13H12F3N2O2(M+H) + :285.0845,found 285.0843.
examples 8,
A Schlenk tube of 10mL was charged with 1,3-dimethyluracil (280.3 mg,2 mmol), sodium bromide (10.3 mg,0.1 mmol), eosin Y disodium salt (1.73 mg,0.25 mmol), 3-fluorophenyldiazotetrafluoroborate (21.0 mg,0.1 mmol), degassed three times, under argon balloon protection, added 1mL of water via syringe, and stirred at room temperature for 18h under 470nm 3W LED lamp. The reaction mixture was added with a few drops of saturated aqueous sodium bicarbonate solution, spin-dried, dissolved in ethyl acetate, stirred on silica gel and subjected to column chromatography (n-hexane: ethyl acetate = 5:1) to give 1,3-dimethyl-5- (3-fluorophenyl) uracil as a white solid, 18.0mg in 76.9% yield. The structural formula of the product and the characterization data thereof are as follows:
Figure BDA0003162157350000091
1 H NMR(500 MHz,DMSO-d 6 )δ8.12(s,1H),7.49–7.38(m,3H),7.16–7.09(m,1H),3.39(s,3H),3.24(s,3H).
13 C NMR(126 MHz,DMSO-d 6 )δ161.9(d,J＝242.1Hz),161.5,150.8,143.4,135.9(d,J＝8.6 Hz),129.9(d,J＝8.6 Hz),123.8(d,J＝3.2 Hz),114.5(d,J＝22.7 Hz),113.7(d,J＝20.9 Hz),109.9,36.6,27.8.
19 F NMR(377 MHz,DMSO-d 6 )δ-113.7.
HRMS(APCI)calcd for C12H12FN2O2(M+H) + :235.0877,found 235.0877.
examples 9,
A Schlenk tube of 10mL was charged with 1,3-dimethyluracil (280.3 mg,2 mmol), sodium bromide (10.3 mg,0.1 mmol), eosin Y disodium salt (1.73 mg,0.25 mmol), 3-chlorophenyldiazotetrafluoroborate (22.6 mg,0.1 mmol), evacuated three times, argon balloon protected, 1mL water was added via syringe, and stirred at room temperature for 18h under 470nm 3W LED lamp. The reaction mixture was added with a few drops of saturated aqueous sodium bicarbonate solution, spun dry, dissolved in ethyl acetate, stirred on silica gel and column chromatographed (n-hexane: ethyl acetate = 5:1) to give 1,3-dimethyl-5- (3-chlorophenyl) uracil as a white solid, 17.4mg, 69.3% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000101
1 H NMR(400MHz,DMSO-d 6 )δ8.13(s,1H),7.68(t,J＝2.0Hz,1H),7.57(d,J＝7.7Hz,1H),7.42(t,J＝7.8Hz,1H),7.39–7.34(m,1H),3.40(s,3H),3.24(s,3H).
13 C NMR(101MHz,DMSO-d 6 )δ161.5,150.8,143.4,135.6,132.7,129.8,127.5,126.8,126.4,109.7,36.5,27.7.
HRMS(APCI)calcd for C12H12ClN2O2(M+H) + :251.0582,found 251.0581.
examples 10,
To a 10mL Schlenk tube was added 1,3-dimethyluracil (280.3mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25 mmol), 3-bromophenyl diazotetrafluoroborate (27.1mg, 0.1mmol), evacuated three times, under argon balloon protection, 1mL water was added with syringe, stirred at room temperature for 18h under 470nm 3W LED lamp. The reaction mixture was added with a few drops of saturated aqueous sodium bicarbonate solution, spin-dried, dissolved in ethyl acetate, stirred on silica gel and subjected to column chromatography (n-hexane: ethyl acetate = 5:1) to give 1,3-dimethyl-5- (3-bromophenyl) uracil as a white solid, 18.4mg in 62.4% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000102
1 H NMR(300MHz,DMSO-d 6 )δ8.12(s,1H),7.81(s,1H),7.61(d,J＝8.1Hz,1H),7.49(d,J＝7.6Hz,1H),7.35(t,J＝8.0Hz,1H),3.40(s,3H),3.25(s,3H).
13 C NMR(101MHz,DMSO-d 6 )δ161.5,150.8,143.4,135.9,130.3,130.1,129.7,126.8,121.3,109.7,36.5,27.7.
HRMS(APCI)calcd for C12H12BrN2O2(M+H) + :295.0077,found 295.0072.
examples 11,
A10 mL Schlenk tube was charged with 1,3-dimethyluracil (280.3mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25 mmol), 2-chlorophenyldiazotetrafluoroborate (22.6 mg, 0.1mmol), evacuated three times, under argon balloon protection, 1mL of water was added with a syringe and stirred at room temperature for 18h under a 470nm 3W LED lamp. The reaction mixture was added with a few drops of saturated aqueous sodium bicarbonate solution, spin-dried, dissolved in ethyl acetate, stirred on silica gel and subjected to column chromatography (n-hexane: ethyl acetate = 5:1) to give 1,3-dimethyl-5- (2-chlorophenyl) uracil as a white solid, 18.1mg in 72.1% yield. The structural formula of the product and the characterization data thereof are as follows:
Figure BDA0003162157350000111
1 H NMR(400MHz,DMSO-d 6 )δ7.87(s,1H),7.51(d,J＝7.2Hz,1H),7.37(m,3H),3.36(s,3H),3.33(s,3H).
13 C NMR(101MHz,DMSO-d6)δ161.0,151.2,143.7,133.9,132.6,132.5,129.7,129.2,126.9,110.7,36.4,27.7.
HRMS(ESI)calcd for C12H12ClN2O2(M+H) + :251.0582,found 251.0584.
examples 12,
A10 mL Schlenk tube was charged with 1,3-dimethyluracil (280.3mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25 mmol), 2-bromophenyl diazotetrafluoroborate (27.1mg, 0.1mmol), evacuated three times, under argon balloon protection, 1mL of water was added with a syringe and stirred at room temperature for 18h under 470nm 3W LED lamp. The reaction mixture was added with a few drops of saturated aqueous sodium bicarbonate solution, spin-dried, dissolved in ethyl acetate, stirred on silica gel and subjected to column chromatography (n-hexane: ethyl acetate = 5:1) to give 1,3-dimethyl-5- (2-bromophenyl) -uracil as a white solid, 16.1mg in 54.6% yield. The structural formula of the product and the characterization data thereof are as follows:
Figure BDA0003162157350000112
1 H NMR(400MHz,DMSO-d 6 )δ7.86(s,1H),7.69(d,J＝8.4Hz,1H),7.42(td,J＝7.3,1.2Hz,1H),7.35–7.29(m,2H),3.37(s,3H),3.23(s,3H).
13 C NMR(101MHz,DMSO-d 6 )δ161.0,151.2,143.6,134.5,132.6,132.3,129.9,127.5,124.7,112.6,36.4,27.7.
HRMS(ESI)calcd for C12H12BrN2O2(M+H) + :295.0077,found 295.0079.
examples 13,
A10 mL Schlenk tube was charged with 1,3-dimethyluracil (280.3mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25 mmol), 3-nitro-4-chlorophenyldiazotetrafluoroborate (27.1mg, 0.1mmol), evacuated three times, under argon balloon protection, 1mL of water was added via syringe, and stirred at room temperature for 18h under 470nm 3W LED lamp. The reaction mixture was added with a few drops of a saturated aqueous sodium bicarbonate solution, spin-dried, dissolved in ethyl acetate, stirred on silica gel and subjected to column chromatography (n-hexane: ethyl acetate = 5:1) to give 5- (4-chloro-3-nitrophenyl) -1,3-dimethyluracil as a white solid, 18.6mg, in 62.8% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000121
1 H NMR(300MHz,CDCl 3 )δ8.07(d,J＝2.2Hz,1H),7.77(dd,J＝8.5,2.2Hz,1H),7.56(d,J＝8.5Hz,1H),7.45(s,1H),3.53(s,3H),3.43(s,3H).
13 C NMR(126MHz,CDCl 3 )δ161.8,151.2,148.0,141.5,133.2,132.8,132.0,126.3,124.9,111.1,37.6,28.5.
HRMS(APCI)calcd for C12H11ClN3O4(M+H) + :296.0433,found 296.0429.
examples 14,
To a 10mL Schlenk tube was added 1,3-dimethyluracil (280.3mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25 mmol), 3,4-methylenedioxyphenyl diazotetrafluoroborate (23.6mg, 0.1mmol), evacuated three times, under argon balloon protection, 1mL water was added with syringe, and stirred at room temperature for 18h under 470nm 3W LED lamp. The reaction mixture was added with a few drops of saturated aqueous sodium bicarbonate solution, spun dry, dissolved in ethyl acetate, stirred on silica gel and subjected to column chromatography (n-hexane: ethyl acetate = 5:1) to give 5- (3,4-methylenedioxyphenyl) -1,3-dimethyluracil as a white solid 15.4mg in 59.2% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000122
1 H NMR(300MHz,CDCl 3 )δ7.23(s,1H),7.03(d,J＝1.8Hz,1H),6.94–6.79(m,2H),5.97(s,2H),3.46(s,3H),3.42(s,3H).
13 C NMR(126MHz,CDCl 3 )δ162.6,151.6,147.9,147.6,140.0,126.9,121.9,114.4,109.3,108.5,101.3,37.2,28.4.
HRMS(APCI)calcd for C13H13N2O4(M+H) + :261.0870,found 261.0868.
examples 15,
To a 10mL Schlenk tube was added 1,3-dimethyluracil (280.3mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25 mmol), 3-quinolinium diazotetrafluoroborate (24.3mg, 0.1mmol), evacuated three times, under argon balloon protection, 1mL water was added with syringe, stirred at room temperature for 18h under 470nm 3W LED lamp. The reaction mixture was added with a few drops of a saturated aqueous sodium bicarbonate solution, spin-dried, dissolved in ethyl acetate, stirred on silica gel and subjected to column chromatography (n-hexane: ethyl acetate = 5:1) to give 5- (3-quinolyl) -1,3-dimethyluracil as a white solid, 20.3mg in 76.0% yield. The structural formula of the product and the characterization data thereof are as follows:
Figure BDA0003162157350000131
1 H NMR(300MHz,CDCl 3 )δ8.99(d,J＝2.3Hz,1H),8.48(d,J＝2.4Hz,1H),8.12(d,J＝8.4Hz,1H),7.86(dt,J＝8.0,1.1Hz,1H),7.73(ddd,J＝8.4,6.9,1.5Hz,1H),7.57(ddd,J＝8.2,6.9,1.2Hz,1H),7.52(s,1H),3.55(s,3H),3.47(s,3H).
13 C NMR(126MHz,CDCl 3 )δ162.3,151.4,148.9,146.3,141.4,136.3,130.4,128.5,128.3,127.9,127.6,126.3,110.9,37.6,28.6.
HRMS(APCI)calcd for C15H14N3O2(M+H) + :268.1081,found 268.1079.
examples 16,
To a 10mL Schlenk tube was added 1,3-dimethyluracil (280.3mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25 mmol), 1H-pyrazole-3-diazotetrafluoroborate (18.2mg, 0.1mmol), evacuated three times, under argon balloon protection, 1mL water was added with a syringe, and stirred at room temperature for 18H under 470nm 3W LED lamp. The reaction mixture was added with a few drops of a saturated aqueous sodium bicarbonate solution, spin-dried, dissolved in ethyl acetate, stirred on silica gel and subjected to column chromatography (n-hexane: ethyl acetate = 5:1) to give 5- (1H-pyrazol-3-yl) -1,3-dimethyluracil as a white solid, 14.1mg in 68.8% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000132
1 H NMR(300 MHz,CDCl 3 )δ8.40(s,1H),7.80(s,1H),7.59(d,J＝2.1 Hz,1H),6.55(d,J＝2.1 Hz,1H),3.51(s,3H),3.44(s,3H).
13 C NMR(101 MHz,CDCl 3 )δ162.2,150.9,139.8,138.4,136.7,104.7,101.5,37.6,28.4.
HRMS(ESI)calcd for C9H11N4O2(M+H) + :207.0877,found 207.0878.
examples 17,
To a Schlenk tube of 10mL was added uridine (488.4 mg,2 mmol), sodium bromide (10.3 mg,0.1 mmol), eosin Y disodium salt (1.73 mg,0.25% mmol), phenyl diazotetrafluoroborate (19.2 mg,0.1 mmol), degassed three times, under argon balloon protection, 1mL of water was added with a syringe, and stirred at room temperature for 18h under a 3W LED lamp of 470 nm. To the reaction was added 10mL saturated aqueous sodium bicarbonate, extracted three times with ethyl acetate (10 ml x 3), the organic phases combined, concentrated, dissolved with a small amount of methanol, and thin layer chromatography (dichloromethane: methanol = 6:1) afforded 5-phenyluridine 7.6 mg as a white solid in 23.8% yield. The structural formula of the product and the characterization data thereof are as follows:
Figure BDA0003162157350000141
1 H NMR(300 MHz,DMSO-d 6 )δ11.52(s,1H),8.28(s,1H),7.59–7.51(m,2H),7.41–7.26(m,3H),5.85(d,J＝4.9 Hz,1H),5.43(d,J＝5.5 Hz,1H),5.23(t,J＝4.7 Hz,1H),5.10(d,J＝5.3 Hz,1H),4.15(q,J＝5.0 Hz,1H),4.04(q,J＝5.0 Hz,1H),3.94–3.85(m,1H),3.71–3.55(m,2H).
13 C NMR(101 MHz,DMSO-d 6 )δ162.1,150.2,138.1,133.1 128.1,127.9,127.1,113.4,88.3,84.7,73.9,69.6,60.4.
HRMS(ESI)calcd for C15H15N2O6(M-H) - :319.0936,found 319.0932.
examples 18,
To a Schlenk tube of 10mL was added 2' -deoxyuridine (456.4 mg,2 mmol), sodium bromide (10.3 mg,0.1 mmol), eosin Y disodium salt (1.73 mg,0.25 mmol), phenyldiazotetrafluoroborate (19.2 mg,0.1 mmol), purged three times, under argon balloon protection, 1mL of water was added with a syringe, and stirred at room temperature for 18h under 470nm 3W LED lamp. To the reaction solution was added 10mL saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 ml × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and thin layer chromatography (dichloromethane: methanol = 6:1) gave 12.9mg of 2' -deoxy-5-phenyluridine as a white solid in 42.4% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000151
1 H NMR(300MHz,DMSO-d 6 )δ11.49(s,1H),8.21(s,1H),7.62–7.49(m,2H),7.42–7.25(m,3H),6.24(t,J＝6.6Hz,1H),5.29(d,J＝4.2Hz,1H),5.15(t,J＝4.9Hz,1H),4.35–4.23(m,1H),3.82(q,J＝3.3Hz,1H),3.68–3.51(m,2H),2.31–2.11(m,2H).
13 C NMR(101MHz,DMSO-d 6 )δ162.1,149.9,138.0,133.2,128.1,127.9,127.1,113.4,87.5,84.5,70.2,61.0,40.1.
HRMS(ESI)calcd for C15H15N2O5(M-H) - :303.0986,found 303.0983.
examples 19,
To a 10mL Schlenk tube were added uridine (488.4 mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25 mmol, vol.), 4-methylphenyldiazotetrafluoroborate (20.6 mg, 0.1mmol), the gas was evacuated three times, 1mL of water was added by syringe under protection of argon balloon, and the mixture was stirred at room temperature for 18h under 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and thin layer chromatography (dichloromethane: methanol = 6:1) gave 12.6mg of 5- (4-methylphenyl) uridine as a white solid in 39.4% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000152
1 H NMR(300MHz,DMSO-d 6 )δ11.47(s,1H),8.22(s,1H),7.43(d,J＝8.1Hz,2H),7.16(d,J＝7.9Hz,2H),5.84(d,J＝4.8Hz,1H),5.40(d,J＝5.5Hz,1H),5.19(t,J＝4.6Hz,1H),5.07(d,J＝5.2Hz,1H),4.13(q,J＝5.1Hz,1H),4.03(q,J＝4.9Hz,1H),3.92–3.84(m,1H),3.70–3.54(m,2H),2.30(s,3H).
13 C NMR(101MHz,DMSO-d 6 )δ162.1,150.2,137.6,136.4,130.2,128.7,127.8,113.4,88.2,84.7,74.0,69.7,60.4,20.7.
HRMS(ESI)calcd for C16H17N2O6(M-H) - :333.1092,found 333.1091.
examples 20,
To a 10mL Schlenk tube were added uridine (488.4 mg, 2mmol), sodium bromide (10.3 mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25% mmol), 4-chlorophenyldiazotetrafluoroborate (22.6 mg, 0.1mmol), vented three times, protected with an argon balloon, 1mL of water was added via syringe, and stirred at room temperature for 18h under a 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and thin layer chromatography (dichloromethane: methanol = 6:1) gave 5- (4-chlorophenyl) uridine as a white solid 15.4mg in 41.6% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000161
1 H NMR(300MHz,DMSO-d 6 )δ11.55(s,1H),8.36(s,1H),7.59(d,J＝8.6Hz,2H),7.41(d,J＝8.6Hz,2H),5.83(d,J＝4.4Hz,1H),5.45(d,J＝5.4Hz,1H),5.28(t,J＝4.6Hz,1H),5.11(d,J＝5.3Hz,1H),4.14(q,J＝5.0Hz,1H),4.05(q,J＝5.0Hz,1H),3.94–3.85(m,1H),3.74–3.54(m,2H).
13 C NMR(101MHz,DMSO-d 6 )δ161.9,150.0,138.5,132.0,131.7,129.5,128.1,112.1,88.5,84.6,74.1,69.4,60.2.
HRMS(ESI)calcd for C15H14ClN2O6(M-H) - :353.0546,found 353.0545.
examples 21,
To a 10mL Schlenk tube was added 2' -deoxyuridine (456.4 mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25% mmol), 4-chlorophenyldiazotetrafluoroborate (22.6 mg, 0.1mmol), the gas was evacuated three times, 1mL of water was added with a syringe under the protection of an argon balloon, and the mixture was stirred at room temperature for 18h under a 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and subjected to thin layer chromatography (dichloromethane: methanol = 6:1) to give 17.0mg of 2' -deoxy-5- (4-chlorophenyl) uridine as a white solid in 50.3% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000171
1 H NMR(400MHz,DMSO-d 6 )δ11.52(s,1H),8.28(s,1H),7.59(d,J＝8.4Hz,2H),7.41(d,J＝8.4Hz,2H),6.22(t,J＝6.6Hz,1H),5.28(s,1H),5.16(s,1H),4.30(s,1H),3.86–3.79(m,1H),3.68–3.54(m,2H),2.31–2.12(m,2H).
13 C NMR(101MHz,DMSO-d 6 )δ161.9,149.8,138.4,132.1,131.8,129.5,128.1,112.1,87.5,84.6,70.1,60.9,40.0.
HRMS(ESI)calcd for C15H14ClN2O5(M-H) - :337.0597,found 337.0595.
examples 22,
To a 10mL Schlenk tube were added uridine (488.4 mg, 2mmol), sodium bromide (10.3 mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25 mmol), 4-methoxyphenyldiazotetrafluoroborate (22.2 mg, 0.1mmol), the gas was purged three times, under argon balloon protection, 1mL of water was added with a syringe, and the mixture was stirred at room temperature for 18h under a 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and subjected to thin layer chromatography (dichloromethane: methanol = 6:1) to give 5- (4-methoxyphenyl) uridine 18.2mg as a white solid in 52.0% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000172
1 H NMR(400MHz,DMSO-d 6 )δ11.45(s,1H),8.18(s,1H),7.48(d,J＝8.8Hz,2H),6.92(d,J＝8.9Hz,2H),5.85(d,J＝4.9Hz,1H),5.41(d,J＝5.9Hz,1H),5.21(t,J＝5.0Hz,1H),5.09(d,J＝5.7Hz,1H),4.14(q,J＝5.0Hz,1H),4.04(q,J＝4.7Hz,1H),3.88(q,J＝2.9Hz,1H),3.76(s,3H),3.69–3.57(m,2H).
13 C NMR(101MHz,DMSO-d 6 )δ162.2,158.5,150.2,137.0,129.1,125.3,113.6,113.2,88.2,84.7,73.9,69.7,60.4,55.1.
HRMS(ESI)calcd for C16H17N2O7(M-H) - :349.1041,found 349.1041.
examples 23,
To a 10mL Schlenk tube was added 2' -deoxyuridine (456.4 mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25% mmol), 4-methoxyphenyl diazotetrafluoroborate (22.2mg, 0.1mmol), the gas was evacuated three times, 1mL of water was added by syringe under the protection of argon balloon, and the mixture was stirred at room temperature for 18h under 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and subjected to thin layer chromatography (dichloromethane: methanol = 6:1) to give 13.8mg of 2' -deoxy-5- (4-methoxyphenyl) uridine as a white solid in 41.3% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000181
1 H NMR(300MHz,DMSO-d 6 )δ11.45(s,1H),8.10(s,1H),7.48(d,J＝8.8Hz,2H),6.93(d,J＝8.9Hz,2H),6.23(t,J＝6.7Hz,1H),5.26(d,J＝4.2Hz,1H),5.10(t,J＝4.8Hz,1H),4.34–4.24(m,1H),3.81(q,J＝3.3Hz,1H),3.76(s,3H),3.66–3.54(m,2H),2.30–2.08(m,2H).
13 C NMR(101MHz,DMSO-d 6 )δ162.3,158.6,150.0,137.0,129.1,125.5,113.6,113.3,87.5,84.4,70.3,61.1,55.1,40.0.
HRMS(ESI)calcd for C16H17N2O6(M-H) - :333.1092,found 333.1092.
examples 24,
To a 10mL Schlenk tube were added uridine (488.4mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25 mmol), 4-trifluoromethylphenyldiazotetrafluoroborate (26.0mg, 0.1mmol), the gas was evacuated three times, under the protection of an argon balloon, 1mL of water was added by syringe, and the mixture was stirred at room temperature for 18h under a 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and thin layer chromatography (dichloromethane: methanol = 6:1) gave 5- (4-trifluoromethylphenyl) uridine 22.1mg as a white solid in a yield of 57.0%. The structural formula of the product and the characterization data thereof are as follows:
Figure BDA0003162157350000191
1 H NMR(300MHz,DMSO-d 6 )δ11.61(s,1H),8.51(s,1H),7.81(d,J＝8.4Hz,2H),7.71(d,J＝8.6Hz,2H),5.84(d,J＝4.1Hz,1H),5.49(d,J＝5.3Hz,1H),5.34(t,J＝4.6Hz,1H),5.13(d,J＝5.3Hz,1H),4.15(q,J＝4.8Hz,1H),4.07(q,J＝5.0Hz,1H),3.96–3.87(m,1H),3.77–3.55(m,2H).
13 C NMR(101MHz,DMSO-d 6 )δ162.3,150.4,139.8,137.7,128.8,127.9(d,J＝31.9Hz),125.4(d,J＝3.7Hz),124.7(d,J＝272.2Hz),112.4,89.0,84.9,74.6,69.7,60.4.
19 F NMR(377MHz,DMSO-d 6 )δ-61.0.
HRMS(ESI)calcd for C16H14F3N2O6(M-H) - :387.0809,found 387.0811.
examples 25,
To a 10mL Schlenk tube was added 2' -deoxyuridine (456.4 mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25% mmol), 4-trifluoromethylphenyldiazotetrafluoroborate (26.0mg, 0.1mmol), the gas was evacuated three times, under the protection of an argon balloon, 1mL of water was added by syringe, and stirred at room temperature for 18h under a 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and subjected to thin layer chromatography (dichloromethane: methanol = 6:1) to give 23.5mg of 2' -deoxy-5- (4-trifluoromethylphenyl) uridine as a white solid in 60.6% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000192
1 H NMR(300MHz,DMSO-d 6 )δ11.60(s,1H),8.42(s,1H),7.80(d,J＝8.4Hz,2H),7.71(d,J＝8.5Hz,2H),6.22(t,J＝6.4Hz,1H),5.33(d,J＝4.3Hz,1H),5.25(t,J＝4.8Hz,1H),4.27-4.37(m,1H),3.84(q,J＝3.3Hz,1H),3.57-3.69(m,2H),2.15-2.31(m,2H).
13 C NMR(101MHz,DMSO-d 6 )δ161.9,149.8,139.4,137.5,128.3,127.4(d,J＝31.2Hz),124.9(d,J＝3.7Hz),124.3(d,J＝271.8Hz),111.8,87.6,84.8,70.0,60.8,40.3.
19 F NMR(377MHz,DMSO-d 6 )δ-61.0.
HRMS(ESI)calcd for C16H14F3N2O5(M-H) - :371.0860,found 371.0860.
examples 26,
To a 10mL Schlenk tube were added uridine (488.4 mg, 2mmol), sodium bromide (10.3 mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25% mmol), 3-bromophenyl diazotetrafluoroborate (27.1mg, 0.1mmol), vented three times, protected with an argon balloon, 1mL of water was added via syringe, and stirred at room temperature for 18h under a 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and thin layer chromatography (dichloromethane: methanol = 6:1) gave 20.9mg of 5- (3-bromophenyl) uridine as a white solid in 52.4% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000201
1 H NMR(300MHz,DMSO-d 6 )δ11.59(s,1H),8.35(s,1H),7.81(t,J＝1.9Hz,1H),7.59–7.46(m,2H),7.32(t,J＝7.9Hz,1H),5.83(d,J＝4.5Hz,1H),5.44(d,J＝5.6Hz,1H),5.24(t,J＝4.9Hz,1H),5.09(d,J＝5.6Hz,1H),4.15(q,J＝4.7Hz,1H),4.05(q,J＝5.0Hz,1H),3.93–3.85(m,1H),3.74–3.55(m,2H).
13 C NMR(101MHz,DMSO-d 6 )δ161.9,150.0,138.9,135.5,130.4,130.2,129.8,126.6,121.3,111.8,88.6,84.7,74.0,69.3,60.2.
HRMS(ESI)calcd for C15H14BrN2O6(M-H) - :397.0041,found 397.0032.
examples 27,
To a 10mL Schlenk tube was added 2' -deoxyuridine (456.4 mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25% mmol), 4-trifluoromethylphenyldiazotetrafluoroborate (27.1mg, 0.1mmol), the gas was purged three times, under the protection of an argon balloon, 1mL of water was added by syringe, and stirred at room temperature for 18h under a 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and subjected to thin layer chromatography (dichloromethane: methanol = 6:1) to give 18.8mg of 2' -deoxy-5- (4-trifluoromethylphenyl) uridine as a white solid in 49.2% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000211
1 H NMR(400MHz,DMSO-d 6 )δ11.52(s,1H),8.28(s,1H),7.82(t,J＝2.0Hz,1H),7.56–7.45(m,2H),7.33(t,J＝7.9Hz,1H),6.22(t,J＝6.5Hz,1H),5.29(s,1H),5.16(t,J＝5.0Hz,1H),4.34–4.27(m,1H),3.82(q,J＝3.4Hz,1H),3.67–3.55(m,2H),2.34–2.12(m,2H).
13 C NMR(101MHz,DMSO-d 6 )δ161.9,149.8,138.8,135.6,130.4,130.3,129.8,126.6,121.3,111.8,87.6,84.7,70.0,60.8,40.1.
HRMS(ESI)calcd for C15H14BrN2O5(M-H) - :381.0092,found 381.0099.
examples 28,
To a 10mL Schlenk tube were added uridine (488.4mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25% mmol), 3-fluorophenyldiazotetrafluoroborate (21.0mg, 0.1mmol), the gas was purged three times, under the protection of an argon balloon, 1mL of water was added by syringe, and the mixture was stirred at room temperature for 18h under a 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and thin layer chromatography (dichloromethane: methanol = 6:1) gave 13.4mg of 5- (3-fluorophenyl) uridine as a white solid in 37.9% yield. The structural formula of the product and the characterization data thereof are as follows:
Figure BDA0003162157350000212
1 H NMR(500MHz,DMSO-d 6 )δ11.53(s,1H),8.39(s,1H),7.51–7.35(m,3H),7.12(m,1H),5.83(d,J＝4.4Hz,1H),5.46(s,1H),5.32(s,1H),5.14(s,1H),4.15(t,J＝5.0Hz,1H),4.06(t,J＝5.0Hz,1H),3.92–3.86(m,1H),3.69(d,J＝12.1Hz,1H),3.60(d,J＝12.2Hz,1H).
13 C NMR(126MHz,DMSO-d 6 )δ161.9,161.9(d,J＝242.1Hz),150.0,138.9,135.5,130.0(d,J＝8.6Hz),123.6(d,J＝2.7Hz),114.5(d,J＝22.7Hz),113.8(d,J＝20.9Hz),111.9(d,J＝3.2Hz),88.5,84.7,74.1,69.4,60.2.
19 F NMR(377MHz,DMSO-d 6 )δ-113.5.
HRMS(ESI)calcd for C15H14FN2O6(M-H) - :337.0841,found 337.0842.
examples 29,
To a 10mL Schlenk tube was added 2' -deoxyuridine (456.4 mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25% mmol), 3-fluoromethylphenyldiazotetrafluoroborate (21.0mg, 0.1mmol), the gas was evacuated three times, under the protection of an argon balloon, 1mL of water was added by syringe, and the mixture was stirred at room temperature for 18h under a 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and subjected to thin layer chromatography (dichloromethane: methanol = 6:1) to give 14.0mg of 2' -deoxy-5- (3-fluorophenyl) uridine as a white solid in 41.4% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000221
1 H NMR(300MHz,DMSO-d 6 )δ11.56(s,1H),8.31(s,1H),7.52–7.34(m,3H),7.22–7.07(m,1H),6.22(t,J＝6.5Hz,1H),5.29(d,J＝4.3Hz,1H),5.19(t,J＝4.9Hz,1H),4.30(m,1H),3.82(q,J＝3.3Hz,1H),3.75–3.54(m,2H),2.38–2.09(m,2H).
13 C NMR(101MHz,DMSO-d 6 )δ161.9(d,J＝242.1Hz),161.9,149.8,138.8,135.5(d,J＝8.8Hz),130.0(d,J＝8.8Hz),123.6(d,J＝2.6Hz),114.4(d,J＝22.7Hz),113.8(d,J＝20.9Hz),111.9(d,J＝2.6Hz),87.6,84.6,70.1,60.8,40.0.
19 F NMR(377MHz,DMSO-d 6 )δ-113.5.
HRMS(ESI)calcd for C15H14FN2O5(M-H) - :321.0892,found 321.0891.
examples 30,
To a 10mL Schlenk tube was added uridine (488.4mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25% mmol), 3,4-methylenedioxyphenyldiazotetrafluoroborate (23.6mg, 0.1mmol), evacuated three times, protected with an argon balloon, 1mL of water was added by syringe, and stirred at room temperature for 18h under a 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and subjected to thin layer chromatography (dichloromethane: methanol = 6:1) to give 12.6mg of 5- (3,4-methylenedioxyphenyl) uridine as a white solid in 34.6% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000231
1 H NMR(300MHz,DMSO-d 6 )δ11.48(s,1H),8.16(s,1H),7.09(s,1H),7.03(dd,J＝8.2,1.7Hz,1H),6.90(d,J＝8.1Hz,1H),6.02(s,2H),5.83(d,J＝5.0Hz,1H),5.43(d,J＝5.5Hz,1H),5.24(t,J＝5.0Hz,1H),5.13(d,J＝5.2Hz,1H),4.14(q,J＝5.0Hz,1H),4.04(q,J＝4.8Hz,1H),3.87(q,J＝2.9Hz,1H),3.70–3.52(m,2H).
13 C NMR(101MHz,DMSO-d 6 )δ162.1,150.1,147.0,146.5,137.5,126.8,121.5,113.2,108.5,108.1,101.0,88.2,84.8,73.9,69.7,60.4.
HRMS(ESI)calcd for C16H15N2O8(M-H) - :363.0834,found 363.0828.
examples 31,
To a 10mL Schlenk tube was added 2' -deoxyuridine (456.4 mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25% mmol), 3,4-methylenedioxyphenyldiazotetrafluoroborate (23.6 mg, 0.1mmol), evacuated three times, under argon balloon protection, 1mL of water was added by syringe, and stirred at room temperature for 18h under 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and subjected to thin layer chromatography (dichloromethane: methanol = 6:1) to give 12.7mg of 2' -deoxy-5- (3,4-methylenedioxyphenyl) uridine as a white solid in a yield of 36.5%. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000241
1 H NMR(300MHz,DMSO-d 6 )δ11.46(s,1H),8.09(s,1H),7.09(s,1H),7.08–6.98(m,1H),6.90(d,J＝8.1Hz,1H),6.22(t,J＝6.7Hz,1H),6.02(s,2H),5.25(d,J＝4.1Hz,1H),5.10(t,J＝5.0Hz,1H),4.28(t,J＝4.9Hz,1H),3.81(q,J＝3.6Hz,1H),3.67–3.50(m,2H),2.38–2.08(m,2H).
13 C NMR(101MHz,DMSO-d 6 )δ162.1,149.9,150.0,146.5,137.3,126.9,121.5,113.3,108.5,108.0,101.0,87.5,84.4,70.3,61.0,40.0.
HRMS(ESI)calcd for C16H15N2O7(M-H) - :347.0885,found 347.0880.
examples 32,
To a 10mL Schlenk tube were added uridine (488.4 mg, 2mmol), sodium bromide (10.3 mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25% mmol), 3-chlorophenyldiazotetrafluoroborate (22.6 mg, 0.1mmol), vented three times, protected with an argon balloon, 1mL of water was added via syringe, and stirred at room temperature for 18h under a 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and thin layer chromatography (dichloromethane: methanol = 6:1) gave 19.8mg of 5- (3-chlorophenyl) uridine as a white solid in 55.8% yield. The structural formula of the product and the characterization data thereof are as follows:
Figure BDA0003162157350000242
1 H NMR(300MHz,DMSO-d 6 )δ11.59(s,1H),8.37(s,1H),7.67(t,J＝1.8Hz,1H),7.50(dt,J＝7.2,1.8Hz,1H),7.45–7.31(m,2H),5.83(d,J＝4.4Hz,1H),5.45(d,J＝5.4Hz,1H),5.28(t,J＝4.9Hz,1H),5.12(d,J＝5.4Hz,1H),4.16(q,J＝4.9Hz,1H),4.06(q,J＝5.0Hz,1H),3.94–3.84(m,1H),3.75–3.54(m,2H).
13 C NMR(101MHz,DMSO-d 6 )δ161.9,150.0,138.9,135.2,132.8,130.0,127.6,126.9,126.2,111.8,88.6,84.7,74.0,69.4,60.2.
HRMS(ESI)calcd for C15H14ClN2O6(M-H) - :353.0546,found 353.0539.
examples 33,
To a 10mL Schlenk tube was added 2' -deoxyuridine (456.4 mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25% mmol), 3-chlorophenyldiazotetrafluoroborate (22.6 mg, 0.1mmol), the tube was degassed three times, under argon balloon protection, 1mL of water was added via syringe, and the mixture was stirred at room temperature for 18h under a 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and subjected to thin layer chromatography (dichloromethane: methanol = 6:1) to give 17.3mg of 2' -deoxy-5- (3-chlorophenyl) uridine as a white solid in 51.0% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000251
1 H NMR(300MHz,DMSO-d 6 )δ11.57(s,1H),8.28(s,1H),7.67(t,J＝1.9Hz,1H),7.50(dt,J＝7.3,1.7Hz,1H),7.45–7.31(m,2H),6.22(t,J＝6.5Hz,1H),5.27(d,J＝4.3Hz,1H),5.15(t,J＝4.9Hz,1H),4.36–4.25(m,1H),3.82(q,J＝3.3Hz,1H),3.73–3.52(m,2H),2.34–2.10(m,2H).
13 C NMR(101MHz,DMSO-d 6 )δ161.9,149.8,138.8,135.3,132.8,129.9,127.6,126.9,126.2,111.8,87.6,84.7,70.0,60.8,40.1.
HRMS(ESI)calcd for C15H14ClN2O5(M-H) - :337.0597,found 337.0591.
examples 34,
To a 10mL Schlenk tube were added uridine (488.4 mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25 mmol as small as this), 3-trifluoromethylphenyldiazotetrafluoroborate (26.0 mg, 0.1mmol), the gas was evacuated three times, 1mL of water was added by syringe under the protection of argon balloon, and the mixture was stirred at room temperature for 18h under 470nm 3WLED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and thin layer chromatography (dichloromethane: methanol = 6:1) gave 18.5mg of 5- (3-trifluoromethylphenyl) uridine as a white solid in 47.7% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000261
1 H NMR(300MHz,DMSO-d 6 )δ11.63(s,1H),8.44(s,1H),7.97(s,1H),7.82(d,J＝7.7Hz,1H),7.61(m,2H),5.84(d,J＝4.3Hz,1H),5.44(d,J＝5.4Hz,1H),5.23(t,J＝4.9Hz,1H),5.08(d,J＝5.5Hz,1H),4.16(q,J＝4.9Hz,1H),4.07(q,J＝5.1Hz,1H),3.94–3.86(m,1H),3.76–3.55(m,2H).
13 C NMR(101MHz,DMSO-d 6 )δ162.0,150.0,139.2,134.2,131.5,129.3,128.9(d,J＝31.5Hz),124.3,124.2(d,J＝272.5Hz),123.7,111.7,88.7,84.6,74.1,69.3,60.2.
19 F NMR(377MHz,DMSO-d 6 )δ-61.1.
HRMS(ESI)calcd for C16H14F3N2O6(M-H) - :387.0809,found 387.0802.
examples 35,
To a 10mL Schlenk tube was added 2' -deoxyuridine (456.4 mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25% mmol), 3-trifluoromethylphenyldiazotetrafluoroborate (26.0mg, 0.1mmol), the gas was evacuated three times, under the protection of an argon balloon, 1mL of water was added by syringe, and stirred at room temperature for 18h under a 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10ml × 3), and the organic phases were combined, concentrated, dissolved with a small amount of methanol, and subjected to thin layer chromatography (dichloromethane: methanol = 6:1) to give 19.7mg of 2' -deoxy-5- (3-trifluoromethylphenyl) uridine as a white solid in a yield of 53.0%. The structural formula of the product and the characterization data thereof are as follows:
Figure BDA0003162157350000262
1 H NMR(300MHz,DMSO-d 6 )δ11.61(s,1H),8.35(s,1H),7.97(s,1H),7.82(d,J＝7.3Hz,1H),7.69–7.56(m,2H),6.22(t,J＝6.5Hz,1H),5.26(d,J＝4.4Hz,1H),5.13(t,J＝5.0Hz,1H),4.30(m,1H),3.82(q,J＝3.3Hz,1H),3.69–3.52(m,2H),2.35–2.13(m,2H).
13 C NMR(101MHz,DMSO-d 6 )δ162.0,149.8,139.1,134.3,131.5,129.2,128.8,124.4(d,J＝4.0Hz),124.2(d,J＝272.2Hz),123.7,111.7,87.6,84.8,70.0,60.8,40.0.
19 F NMR(377MHz,DMSO-d 6 )δ-61.1.
HRMS(ESI)calcd for C16H14F3N2O5(M-H) - :371.0860,found 371.0852.
examples 36,
To a 10mL Schlenk tube were added uridine (488.4mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25 mmol%; mmol), 3-methylphenyldiazotetrafluoroborate (20.6mg, 0.1mmol), the gas was evacuated three times, 1mL of water was added with a syringe under the protection of an argon balloon, and the mixture was stirred at room temperature for 18h under a 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10ml × 3), and the organic phases were combined, concentrated, dissolved with a small amount of methanol, and subjected to thin layer chromatography (dichloromethane: methanol = 6:1) to give 5- (3-methylphenyl) uridine 10.6mg as a white solid in a yield of 33.3%. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000271
1 H NMR(300MHz,DMSO-d 6 )δ11.49(s,1H),8.24(s,1H),7.35(s,1H),7.33(s,1H),7.24(t,J＝8.0Hz,1H),7.11(d,J＝7.5Hz,1H),5.84(d,J＝4.8Hz,1H),5.43(d,J＝5.5Hz,1H),5.21(t,J＝4.7Hz,1H),5.09(d,J＝5.3Hz,1H),4.13(q,J＝5.2Hz,1H),4.04(q,J＝5.1Hz,1H),3.92–3.85(m,1H),3.73–3.54(m,2H),2.31(s,3H).
13 C NMR(101MHz,DMSO-d 6 )δ162.1,150.2,138.0,137.1,133.0,128.5,128.0,127.8,125.1,113.5,88.3,84.7,74.0,69.6,60.4,21.1.
HRMS(ESI)calcd for C16H17N2O6(M-H) - :333.1092,found 333.1093.
examples 37,
To a 10mL Schlenk tube was added 2' -deoxyuridine (456.4 mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25% mmol), 3-methylphenyldiazotetrafluoroborate (20.6 mg, 0.1mmol), the tube was degassed three times, under the protection of an argon balloon, 1mL of water was added by syringe, and the mixture was stirred at room temperature for 18h under a 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and subjected to thin layer chromatography (dichloromethane: methanol = 6:1) to give 11.2mg of 2' -deoxy-5- (3-methylphenyl) uridine as a white solid in a yield of 33.5%. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000281
1 H NMR(300MHz,DMSO-d 6 )δ11.47(s,1H),8.17(s,1H),7.35(s,1H),7.32(s,1H),7.24(t,J＝7.5Hz,1H),7.10(d,J＝7.6Hz,1H),6.23(t,J＝6.6Hz,1H),5.28(d,J＝4.2Hz,1H),5.13(t,J＝4.9Hz,1H),4.30(m,1H),3.81(q,J＝3.2Hz,1H),3.69–3.51(m,2H),2.31(s,3H),2.27–2.10(m,2H).
13 C NMR(101MHz,DMSO-d 6 )δ162.1,149.9,137.9,137.1,133.1,128.5,128.0,127.8,125.0,113.5,87.5,84.5,70.2,60.9,40.0,21.1.
HRMS(ESI)calcd for C16H17N2O5(M-H) - :317,1143,found 317.1144.
examples 38,
To a 10mL Schlenk tube were added uridine (488.4 mg, 2mmol), sodium bromide (10.3 mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25 mmol, vol.), 2-chlorophenyldiazotetrafluoroborate (22.6 mg, 0.1mmol), the tube was vented three times, 1mL of water was added with a syringe under the protection of an argon balloon, and the mixture was stirred at room temperature for 18h under a 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and thin layer chromatography (dichloromethane: methanol = 6:1) gave 13.2mg of 5- (2-chlorophenyl) uridine as a white solid in 39.1% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000282
1 H NMR(300MHz,DMSO-d 6 )δ11.57(s,1H),8.07(s,1H),7.58–7.45(m,1H),7.37(m,3H),5.85(d,J＝5.3Hz,1H),5.43(d,J＝5.7Hz,1H),5.11(d,J＝5.1Hz,1H),5.03(t,J＝5.0Hz,1H),4.10(q,J＝5.3Hz,1H),3.98(q,J＝4.6Hz,1H),3.90–3.82(m,1H),3.62–3.48(m,2H).
13 C NMR(101MHz,DMSO-d 6 )δ161.4,150.4,139.8,133.7,132.5,132.1,129.6,129.2,127.0,112.7,88.0,84.9,73.8,69.8,60.6.
HRMS(ESI)calcd for C15H14ClN2O6(M-H) - :353.0546,found 353.0546.
examples 39,
To a 10mL Schlenk tube was added 2' -deoxyuridine (456.4 mg, 2mmol), sodium bromide (10.3mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25% mmol), 2-chlorophenyldiazotetrafluoroborate (22.6 mg, 0.1mmol), the tube was degassed three times, under argon balloon protection, 1mL of water was added via syringe, and the mixture was stirred at room temperature for 18h under a 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and subjected to thin layer chromatography (dichloromethane: methanol = 6:1) to give 8.2mg of 2' -deoxy-5- (2-chlorophenyl) uridine as a white solid in 24.3% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000291
1 H NMR(300MHz,DMSO-d 6 )δ11.55(s,1H),8.02(s,1H),7.54–7.45(m,1H),7.45–7.29(m,3H),6.23(t,J＝6.7Hz,1H),5.26(d,J＝4.2Hz,1H),4.95(t,J＝5.0Hz,1H),4.25(q,J＝3.9,3.2Hz,1H),3.79(q,J＝3.3Hz,1H),3.61–3.44(m,2H),2.21–2.11(m,2H).
13 C NMR(101MHz,DMSO-d 6 )δ161.4,150.2,139.6,133.6,132.5,132.1,129.6,129.3,126.9,112.6,87.5,84.4,70.4,61.1,40.1.
HRMS(ESI)calcd for C15H14ClN2O5(M-H) - :337.0597,found 337.0598.
examples 40,
To a 10mL Schlenk tube were added uridine (488.4 mg, 2mmol), sodium bromide (10.3 mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25% mmol), 2-bromophenyl diazotetrafluoroborate (27.1mg, 0.1mmol), vented three times, protected with an argon balloon, 1mL of water was added via syringe, and stirred at room temperature for 18h under a 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and thin layer chromatography (dichloromethane: methanol = 6:1) gave 10.4mg of 5- (2-bromophenyl) uridine as a white solid in 26.1% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000301
1 H NMR(300MHz,DMSO-d 6 )δ11.56(s,1H),8.04(s,1H),7.67(d,J＝7.8Hz,1H),7.46–7.26(m,3H),5.85(d,J＝5.3Hz,1H),5.41(d,J＝5.8Hz,1H),5.09(d,J＝5.1Hz,1H),5.01(t,J＝4.9Hz,1H),4.10(q,J＝5.4Hz,1H),3.98(q,J＝4.8Hz,1H),3.89–3.82(m,1H),3.61–3.48(m,2H).
13 C NMR(400MHz,DMSO-d 6 )δ161.3,150.4,139.7,134.1,132.6,132.4,129.8,127.5,124.4,114.5,88.0,84.9,73.9,69.8,60.6.
HRMS(ESI)calcd for C15H14BrN2O6(M-H) - :397.0041,found 397.0040.
examples 41,
To a 10mL Schlenk tube was added 2' -deoxyuridine (456.4 mg, 2mmol), sodium bromide (10.3 mg, 0.1mmol), eosin Y disodium salt (1.73mg, 0.25% mmol), 2-bromophenyl diazotetrafluoroborate (27.1mg, 0.1mmol), the gas was evacuated three times, 1mL of water was added by syringe under protection of argon balloon, and stirred at room temperature for 18h under 470nm 3W LED lamp. To the reaction solution was added 10mL of saturated aqueous sodium bicarbonate solution, extracted three times with ethyl acetate (10 mL × 3), the organic phases were combined, concentrated, dissolved with a small amount of methanol, and subjected to thin layer chromatography (dichloromethane: methanol = 6:1) to give 12.8mg of 2' -deoxy-5- (2-bromophenyl) uridine as a white solid in 33.4% yield. The structural formula of the product and its characterization data are as follows:
Figure BDA0003162157350000302
1 H NMR(300 MHz,DMSO-d 6 )δ11.55(s,1H),7.98(s,1H),7.67(dd,J＝7.9,1.3 Hz,1H),7.45–7.25(m,3H),6.23(t,J＝6.8 Hz,1H),5.27(d,J＝4.2 Hz,1H),4.94(t,J＝4.9Hz,1H),4.27-4.21(m,1H),3.79(q,J＝3.4 Hz,1H),3.59–3.47(m,2H),2.16(dd,J＝6.8,4.6 Hz,2H).
13 C NMR(101 MHz,DMSO-d 6 )δ161.3,150.1,139.5,134.1,132.6,132.4,129.8,127.5,124.4,114.4,87.5,84.4,70.4,61.1,40.0.
HRMS(ESI)calcd for C15H14BrN2O5(M-H) - :381.0092,found 381.0093。

Claims (7)

1. a method for preparing 5-aryl (hetero) ring modified uracil derivatives comprises the following steps: uracil/uridine or derivatives thereof are used as raw materials, and 5-aryl (hetero) ring substituted uracil/uridine derivatives are obtained through one-step photocatalytic coupling reaction.
2. The method of claim 1, wherein: the method comprises the following steps:
in the presence of a photosensitizer and under the illumination of LED, enabling a compound shown as a formula I to react with a compound shown as a formula II to obtain a compound shown as a formula III,
Figure FDA0003162157340000011
in the formula I, R 1 、R 2 Each independently selected from H, C1-C6 straight or branched chain alkyl,
Figure FDA0003162157340000012
Figure FDA0003162157340000013
in the formula II, the reaction solution is shown in the specification,
Figure FDA0003162157340000014
represents substituted or unsubstituted aromatic group, and the aromatic group is benzene ring, quinolyl and 1H-pyrazolyl;
the substituent in the substituted aryl is selected from C1-C6 straight chain or branched chain alkyl, C1-C6 alkoxy, nitryl, halogen substituted C1-C6 straight chain or branched chain alkyl, and at least one of five-membered or six-membered rings is formed by two adjacent carbon atoms on the aryl through at least one heteroatom.
3. The method of claim 2, wherein: the photosensitizer is eosin Y disodium salt, 4,4 '-bis (N, N-dimethylamino) benzophenone, anthraquinone, tris (2,2' -bipyridine) ruthenium chloride hexahydrate, riboflavin, proflavine sulfate, 9-mesitylene-2,7, 10-trimethylacridine perchlorate, acid red 94, hematoporphyrin dihydrochloride and rhodamine B;
the reaction is carried out in water;
the reaction is carried out in an inert atmosphere.
4. A method according to claim 2 or 3, characterized in that: the reaction is carried out under the condition of adding additives, wherein the additives are NaBr, liCl, naCl, KCl and CaCl 2 ,MgCl 2 ,ZnCl 2 ,CuCl 2 ,NaSO 4 At least one of (1).
5. The method of claim 4, wherein: the mol ratio of the compound shown in the formula I to the compound shown in the formula II, the photosensitizer and the additive is as follows: 20:1:0.025:1.
6. the method according to any one of claims 2-5, wherein: the wavelength of the LED light is 365-530nm, and the power is 3W.
7. The apparatus according to any one of claims 2-6, wherein: the reaction is carried out at room temperature, and the reaction time is 18-60h.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106349170A (en) * 2016-08-02 2017-01-25 东华大学 Preparation method of 1,3-dimethyl-5-phenyluracil
CN112409250A (en) * 2020-11-30 2021-02-26 常州工程职业技术学院 Direct aromatization process of cyanopyridine

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106349170A (en) * 2016-08-02 2017-01-25 东华大学 Preparation method of 1,3-dimethyl-5-phenyluracil
CN112409250A (en) * 2020-11-30 2021-02-26 常州工程职业技术学院 Direct aromatization process of cyanopyridine

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
SHINDE VIDYACHARAN等: "Continuous-Flow Visible Light Organophotocatalysis for Direct Arylation of 2H-Indazoles: Fast Access to Drug Molecules", 《CHEMSUSCHEM》, vol. 12, 5 June 2019 (2019-06-05), pages 2581 - 2586 *
SU JIN KWON等: "Visible Light Photoredox-Catalyzed Arylation of Quinoxalin-2(1H)-ones with Aryldiazonium Salts", 《CHEMISTRYSELECT》, vol. 3, 31 December 2018 (2018-12-31), pages 5824 - 5827 *
TAPAS ADAK等: "Metal-Free, Visible-Light-Enabled Direct C3−H Arylation of Anthranils", 《ORG. LETT.》, vol. 22, 7 July 2020 (2020-07-07), pages 5640 *
王雷雷等: "可见光诱导下喹喔啉-2(1H)-酮与重氮盐的直接C—H 3-芳基化反应", 《CHIN. J. ORG. CHEM.》, vol. 38, 31 December 2018 (2018-12-31), pages 3189 - 3196 *

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