CN114890961A - Preparation method of arylation azauracil by visible light catalysis - Google Patents
Preparation method of arylation azauracil by visible light catalysis Download PDFInfo
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- CN114890961A CN114890961A CN202210368300.XA CN202210368300A CN114890961A CN 114890961 A CN114890961 A CN 114890961A CN 202210368300 A CN202210368300 A CN 202210368300A CN 114890961 A CN114890961 A CN 114890961A
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- SSPYSWLZOPCOLO-UHFFFAOYSA-N 6-azauracil Chemical compound O=C1C=NNC(=O)N1 SSPYSWLZOPCOLO-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 238000006254 arylation reaction Methods 0.000 title abstract description 7
- 238000006555 catalytic reaction Methods 0.000 title abstract 2
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 42
- -1 arylated azauracil ketone compounds Chemical class 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 14
- QVCUKHQDEZNNOC-UHFFFAOYSA-N 1,2-diazabicyclo[2.2.2]octane Chemical compound C1CC2CCN1NC2 QVCUKHQDEZNNOC-UHFFFAOYSA-N 0.000 claims description 12
- 238000002390 rotary evaporation Methods 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 238000004440 column chromatography Methods 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- WYXSYVWAUAUWLD-SHUUEZRQSA-N 6-azauridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=N1 WYXSYVWAUAUWLD-SHUUEZRQSA-N 0.000 abstract description 5
- 230000000259 anti-tumor effect Effects 0.000 abstract description 5
- 238000012360 testing method Methods 0.000 abstract description 5
- 150000001875 compounds Chemical class 0.000 abstract description 4
- 238000000034 method Methods 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 239000011941 photocatalyst Substances 0.000 abstract 1
- 239000003504 photosensitizing agent Substances 0.000 abstract 1
- 239000000758 substrate Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
- 238000005481 NMR spectroscopy Methods 0.000 description 19
- 239000012467 final product Substances 0.000 description 10
- 239000003208 petroleum Substances 0.000 description 10
- 238000010898 silica gel chromatography Methods 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 239000000203 mixture Substances 0.000 description 9
- WLHCBQAPPJAULW-UHFFFAOYSA-N 4-methylbenzenethiol Chemical class CC1=CC=C(S)C=C1 WLHCBQAPPJAULW-UHFFFAOYSA-N 0.000 description 3
- 238000011161 development Methods 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- ZOEZJWWVZQPLDF-UHFFFAOYSA-N 1-(disulfanyl)-4-methylbenzene Chemical class CC1=CC=C(SS)C=C1 ZOEZJWWVZQPLDF-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- KDBMAPTVSLWDPH-UHFFFAOYSA-N 4-cyclopropylbenzenethiol Chemical class C1=CC(S)=CC=C1C1CC1 KDBMAPTVSLWDPH-UHFFFAOYSA-N 0.000 description 1
- NIFAOMSJMGEFTQ-UHFFFAOYSA-N 4-methoxybenzenethiol Chemical class COC1=CC=C(S)C=C1 NIFAOMSJMGEFTQ-UHFFFAOYSA-N 0.000 description 1
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- LAWVKJXSUUKJTK-UHFFFAOYSA-N disulfanylbenzene Chemical class SSC1=CC=CC=C1 LAWVKJXSUUKJTK-UHFFFAOYSA-N 0.000 description 1
- 230000005281 excited state Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000005918 in vitro anti-tumor Effects 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000002342 ribonucleoside Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
- C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
- C07D253/06—1,2,4-Triazines
- C07D253/065—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members
- C07D253/07—1,2,4-Triazines having three double bonds between ring members or between ring members and non-ring members with hetero atoms, or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D253/075—Two hetero atoms, in positions 3 and 5
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
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Abstract
The invention discloses a preparation method of arylation azauracil compounds under the action of visible light catalysis. The invention takes azauracil compounds and arylthiophene salt as raw materials, synthesizes a series of arylated azauracil compounds under the condition of no photocatalyst, and has the advantages of mild reaction conditions, simple and convenient operation, no photosensitizer, wide substrate application range and the like. By the method, effective connection of drug molecules and azauridine can be successfully realized, and preliminary tests show that part of compounds have certain antitumor activity.
Description
Technical Field
The invention relates to the fields of chemical synthesis and pharmaceutical chemistry, in particular to a preparation method of an arylation azauracil compound.
Background
An aza-base is a nucleobase derivative that has a structure similar to a standard base except that the carbon atoms at certain sites are replaced with nitrogen atoms, generally with more unique excited state kinetics. Research has shown that azauracil has important application prospect in the biomedical field (Angew. chem. int. Ed.,2021,60, 191), especially ribonucleoside of 6-azauracil has significant antiviral, antitumor and antifungal activity. The development of a novel method for synthesizing azauracil by functional group synthesis further enriches the structural diversity of azauracil and nucleoside, and promotes the further development of the field.
Disclosure of Invention
The invention provides a preparation method of an arylation azauracil compound, and the synthesis method has mild reaction conditions, simple, convenient and safe operation and cheap and easily-obtained raw materials, and is an environment-friendly green synthesis method. By the method, effective connection of drug molecules and azauridine can be successfully realized, and preliminary tests show that part of compounds have certain antitumor activity.
The technical scheme for realizing the invention is as follows:
the preparation method of the arylation azauracil compound is characterized by comprising the following steps: dissolving azauracil compounds and aryl thiene salt in acetonitrile, adding 1, 4-diazabicyclo [2.2.2] octane (DABCO), stirring for 12 hours under blue light irradiation, extracting after the reaction is finished, drying, removing the solvent by rotary evaporation, and separating by column chromatography to obtain the arylated azauracil ketone compounds.
The structural formula of the prepared arylated azauracil compound is as follows:
wherein R is 1 Methyl, fluoro, chloro, bromo, cyclopropyl, benzyl, phenyl, methoxy, etc.; r 2 R 3 Methyl, ethyl, benzyl, allyl, propargyl, and the like;
the structural formula of the azauracil compound is as follows:
wherein R is 2 R 3 Is methyl, ethyl, benzyl, allyl, alkynePropyl, and the like.
The aryl thiene salt has the following structural formula:
wherein R is 1 Methyl, fluoro, chloro, bromo, cyclopropyl, benzyl, phenyl, methoxy, etc.; prepared according to literature reported methods (Nature 2019,567,223).
The solvent is acetonitrile. The molar ratio of the azauracil compound to the arylthiophene salt to the DABCO is 1:2: 3.
The reaction general formula of the preparation method is as follows:
the invention has the beneficial effects that: the invention provides a preparation method of an arylation azauracil compound, which has mild conditions, cheap and easily-obtained raw materials, simple and convenient operation, high yield and no participation of metal and oxidant, can successfully realize effective connection of drug molecules and azauracil nucleoside, and preliminary tests show that part of the compounds have certain antitumor activity.
Description of the drawings:
FIG. 1 is a graph showing the results of an in vitro antitumor activity test of the target product in example 10.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to the following embodiments of the present invention, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be obtained by a person skilled in the art without inventive effort based on the embodiments of the present invention, are within the scope of the present invention.
Example 1
Azauracil (0.1mmol), p-tolylsulfonium salt (0.2mmol) and DABCO (0.3mmol) were charged into an 8mL reaction flask, and the mixture was stirred in a 2mL acetonitrile solution under blue light irradiation for 12 hours, after the reaction was completed, the mixture was extracted, dried, and the solvent was removed by rotary evaporation, and the residue was separated by silica gel column chromatography (petroleum ether: ethyl acetate: 3:1) to obtain a final product in 82% yield.
The specific results are as follows:
White solid(31.4mg,82％)；m.p.130.5–132.1℃； 1 H NMR(400MHz, Chloroform-d)δ7.90(d,J＝8.2Hz,2H),7.59–7.54(m,2H),7.53–7.48(m,2H), 7.41–7.25(m,8H),5.23(s,2H),5.20(s,2H),2.42(s,3H). 13 C NMR(101MHz, Chloroform-d)δ155.5,148.8,141.3,140.3,135.70,135.68,129.6,129.3,129.0, 128.82,128.76,128.6,128.33,128.28,128.1,55.7,44.5,21.4.HRMS(ESI-TOF)m/z: [M+H] + Calcd for C 24 H 22 N 3 O 2 ,384.1707；Found:384.1718。
example 2
Azauracil (0.1mmol), phenylthiosulfonium salt (0.2mmol) and DABCO (0.3mmol) were put into an 8mL reaction flask, and the mixture was stirred in a 2mL acetonitrile solution under blue light irradiation for 12 hours, after the reaction was completed, the mixture was extracted, dried, and the solvent was removed by rotary evaporation, and the residue was separated by silica gel column chromatography (petroleum ether: ethyl acetate 3:1) to obtain a final product with a yield of 72%.
The specific results are as follows:
White solid(26.6mg,72％)；m.p.151.1–152.4℃； 1 H NMR(400MHz, Chloroform-d)δ8.04–7.94(m,2H),7.60–7.55(m,2H),7.53–7.44(m,5H),7.43 –7.32(m,6H),5.23(d,J＝15.5Hz,4H). 13 C NMR(101MHz,Chloroform-d)δ 155.5,148.8,141.2,135.6,135.6,132.0,130.0,129.6,128.84,128.79,128.6,128.4, 128.33,128.28,128.1,55.8,44.5.HRMS(ESI-TOF)m/z:[M+H] + Calcd for C 23 H 20 N 3 O 2 ,370.1550；Found:370.1559。
example 3
Azauracil (0.1mmol), p-methoxyphenyl sulfonium salt (0.2mmol) and DABCO (0.3mmol) were put into an 8mL reaction flask, and stirred in 2mL acetonitrile solution under blue light irradiation for 12 hours, after the reaction was completed, the mixture was extracted, dried, and the solvent was removed by rotary evaporation, and the residue was separated by silica gel column chromatography (petroleum ether: ethyl acetate 3:1) to obtain a final product with a yield of 76%.
The specific results are as follows:
White solid(30.3mg,76％)；m.p.114.3–115.1℃；1H NMR(400MHz, Chloroform-d)δ8.00(d,J＝9.0Hz,2H),7.59–7.54(m,2H),7.49(d,J＝6.5Hz, 2H),7.41–7.33(m,6H),6.97(d,J＝9.0Hz,2H),5.21(d,J＝11.7Hz,4H),3.87(s, 3H). 13 C NMR(101MHz,Chloroform-d)δ161.1,155.6,148.8,140.9,135.7,134.5, 129.9,129.5,128.80,128.76,128.6,128.3,128.1,124.6,113.7,55.6,55.4,44.4. HRMS(ESI-TOF)m/z:[M+H] + Calcd for C 24 H 22 N 3 O 3 ,400.1656；Found: 400.1661。
example 4
Azauracil (0.1mmol), p-cyclopropylphenyl sulfonium salt (0.2mmol) and DABCO (0.3mmol) were put into an 8mL reaction flask, and stirred in 2mL acetonitrile solution under irradiation with blue light for 12 hours, after the reaction was completed, the solvent was extracted, dried and removed by rotary evaporation, and the residue was separated by silica gel column chromatography (petroleum ether: ethyl acetate 3:1) to obtain a final product in a yield of 56%.
The specific results are as follows:
White solid(22.9mg,56％)；m.p.107.4–108.9℃； 1 H NMR(400MHz, Chloroform-d)δ7.90(d,J＝8.4Hz,2H),7.59–7.54(m,2H),7.52–7.45(m,2H), 7.42–7.30(m,6H),7.14(d,J＝8.4Hz,2H),5.21(d,J＝12.4Hz,4H),1.99–1.92 (m,1H),1.09–1.00(m,2H),0.81–0.73(m,2H). 13 C NMR(101MHz, Chloroform-d)δ155.5,148.8,146.6,141.2,135.70,135.67,129.6,129.1,128.83, 128.76,128.6,128.34,128.28,128.1,125.4,55.7,44.4,15.5,9.8.HRMS(ESI-TOF) m/z:[M+H] + Calcd for C 26 H 24 N 3 O 2 ,410.1863；Found:410.1864。
example 5
Azauracil (0.1mmol), p-tert-butylphenyl thiasulfonium salt (0.2mmol) and DABCO (0.3mmol) were charged into an 8mL reaction flask, and the mixture was stirred in a 2mL acetonitrile solution under irradiation with blue light for 12 hours, after the reaction was completed, the mixture was extracted, dried, and the solvent was removed by rotary evaporation, and the residue was separated by silica gel column chromatography (petroleum ether: ethyl acetate 3:1) to obtain a final product with a yield of 75%.
The specific results are as follows:
White solid(31.9mg,75％)；m.p.159.0–159.4℃； 1 H NMR(400MHz, Chloroform-d)δ7.94–7.89(m,2H),7.57–7.55(m,2H),7.50–7.46(m,4H),7.41 –7.30(m,6H),5.21(d,J＝11.2Hz,4H),1.36(s,9H). 13 C NMR(101MHz, Chloroform-d)δ155.6,153.3,148.8,141.3,135.68,135.66,129.6,129.2,128.8, 128.7,128.6,128.3,128.2,128.1,125.3,55.7,44.5,34.8,31.2.HRMS(ESI-TOF) m/z:[M+H] + Calcd for C 27 H 28 N 3 O 2 ,426.2176；Found:426.2180。
example 6
An allyl-substituted azauracil (0.1mmol), p-methylphenylthiasulfonium salt (0.2mmol) and DABCO (0.3mmol) were charged into an 8mL reaction flask, and stirred in 2mL acetonitrile solution under irradiation with blue light for 12 hours, after the reaction was completed, the solvent was extracted, dried, and removed by rotary evaporation, and the residue was separated by silica gel column chromatography (petroleum ether: ethyl acetate 3:1) to obtain the final product in a yield of 57%.
The specific results are as follows:
White solid(16.1mg,57％)；m.p.92.0–92.7℃； 1 H NMR(400MHz, Chloroform-d)δ7.91(d,J＝8.2Hz,2H),7.26(d,J＝8.1Hz,2H),6.08–5.89(m, 2H),5.41–5.26(m,4H),4.67(dd,J＝16.3,6.1Hz,4H),2.42(s,3H). 13 C NMR (101MHz,Chloroform-d)δ155.3,148.3,141.2,140.3,131.5,130.5,129.2,129.0, 128.3,119.3,119.2,54.4,43.2,21.4.HRMS(ESI-TOF)m/z:[M+H] + Calcd for C 16 H 18 N 3 O 2 ,284.1394；Found:284.1400。
example 7
To an 8mL reaction flask, propargyl-substituted azauracil (0.1mmol), p-methylphenylthiosulfonium salt (0.2mmol) and DABCO (0.3mmol) were added, and the mixture was stirred in 2mL acetonitrile solution under irradiation with blue light for 12 hours, after completion of the reaction, the mixture was extracted, dried, and the solvent was removed by rotary evaporation, and the residue was separated by silica gel column chromatography (petroleum ether: ethyl acetate 3:1) to obtain a final product with a yield of 71%.
The specific results are as follows:
White solid(19.8mg,71％)；m.p.149.0–149.7℃； 1 H NMR(400MHz, Chloroform-d)δ7.95(d,J＝8.0Hz,2H),7.27(d,J＝8.4Hz,2H),4.84(dd,J＝30.2, 1.8Hz,4H),2.42(s,4H),2.27(s,1H). 13 C NMR(101MHz,Chloroform-d)δ154.6, 147.5,141.7,140.8,129.1,128.6,128.4,76.8,76.7,73.7,71.7,41.7,30.3,21.5. HRMS(ESI-TOF)m/z:[M+H] + Calcd for C 16 H 14 N 3 O 2 ,280.1081；Found: 280.1079。
example 8
An azauridine (0.1mmol), p-methylphenyl sulfonium salt (0.2mmol) and DABCO (0.3mmol) were put into an 8mL reaction flask, and stirred in 2mL acetonitrile solution under blue light irradiation for 12 hours, after the reaction was completed, the solvent was extracted, dried and removed by rotary evaporation, and the residue was separated by silica gel column chromatography (petroleum ether: ethyl acetate 3:1), whereby the yield of the final product was 51%.
The specific results are as follows:
White solid(23.5mg,51％)；m.p.107.0–107.5℃； 1 H NMR(400MHz, Chloroform-d)δ9.62(s,1H),7.95(d,J＝8.2Hz,2H),7.28(d,J＝8.1Hz,2H),6.42 (d,J＝2.8Hz,1H),5.78(dd,J＝5.3,2.9Hz,1H),5.67–5.59(m,1H),4.39(ddt,J＝ 10.6,7.2,3.2Hz,2H),4.23–4.14(m,1H),2.41(s,3H),2.15(d,J＝7.3Hz,6H), 1.84(s,3H). 13 C NMR(101MHz,Chloroform-d)δ170.6,169.7,169.6,155.3,148.0, 143.4,141.3,129.3,128.4,128.1,88.1,79.1,73.1,70.3,62.8,21.4,20.54,20.50, 20.4.HRMS(ESI-TOF)m/z:[M+Na] + Calcd for C 21 H 23 N 3 NaO 9, 484.1327；Found: 484.1333。
example 9
An azauridine (0.1mmol), p-methylphenyl sulfonium salt (0.2mmol) and DABCO (0.3mmol) were put into an 8mL reaction flask, and stirred in 2mL acetonitrile solution under blue light irradiation for 12 hours, after the reaction was completed, the solvent was extracted, dried and removed by rotary evaporation, and the residue was separated by silica gel column chromatography (petroleum ether: ethyl acetate 3:1), whereby the yield of the final product was 52%.
The specific results are as follows:
White solid(30.4mg,52％)；m.p.129.5–130.2℃； 1 H NMR(400MHz, Chloroform-d)δ9.41(s,1H),8.01–7.93(m,4H),7.74(d,J＝8.2Hz,2H),7.58– 7.52(m,2H),7.39(t,J＝7.8Hz,2H),7.31(d,J＝7.8Hz,2H),6.91(d,J＝8.1Hz, 2H),6.35(d,J＝3.6Hz,1H),5.90(dd,J＝3.6,2.1Hz,1H),5.76(dd,J＝4.6,2.0Hz, 1H),4.81(dt,J＝6.6,4.8Hz,1H),4.70(h,J＝6.8Hz,2H),2.30(s,3H),2.20(s,3H). 13 C NMR(101MHz,Chloroform-d)δ169.9,166.1,165.6,155.3,148.2,143.4,140.7, 133.5,133.2,130.0,129.7,129.4,128.9,128.7,128.5,128.4,128.0,89.7,78.8,76.3, 62.3,21.4,20.7.HRMS(ESI-TOF)m/z:[M+Na] + Calcd for C 31 H 27 N 3 NaO 9, 608.1640；Found:608.1647。
example 10
An azauridine (0.1mmol), a p-methylphenylthisulfonium salt (0.2mmol) and DABCO (0.3mmol) were added to an 8mL reaction flask, and stirred in 2mL acetonitrile solution under irradiation of blue light for 12 hours, after the reaction was completed, extraction, drying and rotary evaporation were performed to remove the solvent, and the residue was separated by silica gel column chromatography (petroleum ether: ethyl acetate 3:1) to obtain the final product in 41% yield. Tests show that the compound shows certain antitumor activity, IC, on Ramos tumor cells 50 8.493 μmol/L (FIG. 1).
The specific results are as follows:
White solid(33.5mg,41％)；m.p.100.0–101.1℃； 1 H NMR(400MHz, Chloroform-d)δ8.66(d,J＝8.7Hz,1H),8.48(dd,J＝4.7,2.0Hz,1H),8.37(s,1H), 8.23–8.18(m,1H),8.13(dd,J＝8.8,2.0Hz,1H),7.99(d,J＝2.1Hz,1H),7.57– 7.53(m,2H),7.50–7.46(m,2H),7.42–7.31(m,6H),6.44(d,J＝2.9Hz,1H),5.78 (dd,J＝5.4,2.9Hz,1H),5.60–5.54(m,1H),5.18(d,J＝2.7Hz,2H),4.42–4.32 (m,2H),4.20–4.14(m,1H),2.14(s,3H),2.12(s,3H),1.86(s,3H). 13 C NMR(101 MHz,Chloroform-d)δ170.4,169.4,169.4,154.9,151.5,148.5,146.6,141.6,140.4, 136.6,135.4,135.1,134.9,131.6,131.0,130.8,130.5,129.7,129.5,129.2,128.6, 128.3,128.0,123.0,121.2,89.2,73.0,70.3,62.9,44.7,20.5,20.4,20.4.HRMS (ESI-TOF)m/z:[M+Na] + Calcd for C 40 H 37 C l2 N 5 NaO 10, 840.1810；Found:840.1815.
the above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (2)
1. A preparation method of arylated azauracil compounds is characterized in that: the preparation steps are as follows: dissolving azauracil compounds and aryl thiene salt in acetonitrile, adding 1, 4-diazabicyclo [2.2.2] octane (DABCO), stirring for 12 hours under blue light irradiation, extracting after the reaction is finished, drying, removing the solvent by rotary evaporation, and separating by column chromatography to obtain the arylated azauracil ketone compounds.
The structural formula of the prepared arylated azauracil compound is as follows:
wherein R is 1 Methyl, fluoro, chloro, bromo, cyclopropyl, benzyl, phenyl, methoxy, etc.; r 2 R 3 Methyl, ethyl, benzyl, allyl, propargyl, and the like;
the structural formula of the azauracil compound is as follows:
wherein R is 2 Is methyl, ethyl, benzyl, allyl, propargyl, or the like, R 3 Methyl, ethyl, benzyl, allyl, propargyl, and the like.
The solvent is acetonitrile.
2. The process for preparing an arylated azauracil compound according to claim 1, wherein: the molar ratio of the azauracil compound to the arylthiophene salt to the DABCO is 1:2: 3.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0873488A (en) * | 1994-09-02 | 1996-03-19 | Noguchi Kenkyusho | Production of 1-(2-deoxyribofuranoyl)pyridazinone derivative |
| CN113683573A (en) * | 2021-10-10 | 2021-11-23 | 郑州大学 | Preparation method of visible light catalyzed benzylation quinoxalinone compound |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0873488A (en) * | 1994-09-02 | 1996-03-19 | Noguchi Kenkyusho | Production of 1-(2-deoxyribofuranoyl)pyridazinone derivative |
| CN113683573A (en) * | 2021-10-10 | 2021-11-23 | 郑州大学 | Preparation method of visible light catalyzed benzylation quinoxalinone compound |
Non-Patent Citations (5)
| Title |
|---|
| ALVAREZ, EVA MARIA等: "Late-Stage Heteroarylation of Hetero(aryl)sulfonium Salts Activated by α-Amino Alkyl Radicals", 《 ANGEWANDTE CHEMIE, INTERNATIONAL EDITION》, vol. 60, pages 13609 - 13613 * |
| KAI SUN等: "A general electron donor–acceptor complex for photoactivation of arenes via thianthrenation", 《CHEM. SCI.》, vol. 13, pages 5659 - 5666 * |
| MILES H. AUKLAND等: "Metal-free photoredox-catalysed formal C–H/C–H coupling of arenes enabled by interrupted Pummerer activation", 《NATURE CATALYSIS》, vol. 3, pages 163 - 169 * |
| YUE ZHAO等: "Photochemical (Hetero-)Arylation of Aryl Sulfonium Salts", 《ORG. LETT. 》, vol. 23, pages 6232 - 6236 * |
| 孟继本等: "1,3-二甲基-5-芳基尿嘧啶的光化学合成", 《化学学报》, vol. 46, pages 890 - 893 * |
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