CN116813593A - 3-aminoquinoxalinone compound and synthesis method thereof - Google Patents
3-aminoquinoxalinone compound and synthesis method thereof Download PDFInfo
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- -1 3-aminoquinoxalinone compound Chemical class 0.000 title claims abstract description 20
- 238000001308 synthesis method Methods 0.000 title abstract description 7
- FFRYUAVNPBUEIC-UHFFFAOYSA-N quinoxalin-2-ol Chemical compound C1=CC=CC2=NC(O)=CN=C21 FFRYUAVNPBUEIC-UHFFFAOYSA-N 0.000 claims abstract description 33
- 238000006243 chemical reaction Methods 0.000 claims abstract description 22
- 239000003054 catalyst Substances 0.000 claims abstract description 19
- 239000002904 solvent Substances 0.000 claims abstract description 16
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000007800 oxidant agent Substances 0.000 claims abstract description 13
- 239000012363 selectfluor Substances 0.000 claims abstract description 12
- 230000001590 oxidative effect Effects 0.000 claims abstract description 11
- 238000001816 cooling Methods 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims abstract description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 230000002194 synthesizing effect Effects 0.000 claims description 9
- QBBADXPVZMYLKN-UHFFFAOYSA-N 3-amino-1h-quinoxalin-2-one Chemical compound C1=CC=C2NC(=O)C(N)=NC2=C1 QBBADXPVZMYLKN-UHFFFAOYSA-N 0.000 claims description 5
- 230000035484 reaction time Effects 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 3
- 229910000365 copper sulfate Inorganic materials 0.000 claims description 3
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical group [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 3
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 claims description 3
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 claims description 2
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 claims description 2
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 claims description 2
- 238000005576 amination reaction Methods 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract description 2
- 231100000956 nontoxicity Toxicity 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 238000001514 detection method Methods 0.000 description 14
- 239000007787 solid Substances 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 230000001699 photocatalysis Effects 0.000 description 3
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 238000007112 amidation reaction Methods 0.000 description 2
- 150000003851 azoles Chemical class 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 238000007146 photocatalysis Methods 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 238000010499 C–H functionalization reaction Methods 0.000 description 1
- 150000001335 aliphatic alkanes Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000011941 photocatalyst Substances 0.000 description 1
- 239000003504 photosensitizing agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
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Abstract
The invention belongs to the technical field of organic synthesis, and particularly relates to a 3-aminoquinoxalinone compound and a synthesis method thereof. Adding N-methyl protected quinoxalinone, pyrazole, selectfluor oxidant and catalyst into a reaction tube, adding solvent, stirring for reaction in an air atmosphere, cooling to room temperature, separating and purifying to obtain the target product. Pyrazole is an amination reagent which has wide application, low cost, easy obtainment and no toxicity, the invention has wide sources of raw materials, low cost, mild synthesis conditions and high product yield of 63-89 percent, and is suitable for wide application.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a 3-aminoquinoxalinone compound and a synthesis method thereof.
Background
Because of the important medicinal value of the nitrogen-containing heterocycle, the construction of the nitrogen-containing heterocycle is one of the hot spots of organic chemistry research, and the quinoxalinone-2 (1H) -ketone has remarkable biological activity and excellent chemical property as an important nitrogen-containing heterocycle compound, wherein 3-substituted quinoxalinone derivatives are increasingly attracting attention of chemists due to the remarkable biological activity.
In recent years, various methods of direct C3-H functionalization of quinoxalinones have been developed, including alkylation, arylation, amidation, phosphorylation, alkoxylation, and the like, usingTo construct 3-substituted quinoxalinone derivatives. Along with the development of photocatalysis and transition metal catalysis C-H activation methods, a high-efficiency method for constructing the aminated quinoxalinone derivative is realized. For example, in 2016, the Li subject group reported a copper-catalyzed amination of quinoxalinone compounds with primary and secondary alkanes, synthesizing a series of 3-aminoquinoxalinone derivatives. But the process needs to be carried out at high temperatures. In addition, other mild amination strategies, including metal-free or photocatalytic methods, have made tremendous progress in this area. In 2019, the Yuan problem group was K 2 S 2 O 8 In the presence of (2), the direct C-3 amidation reaction of the quinoxalinone compound catalyzed by copper is realized by microwave assistance. In recent years, visible light catalysis has been one of the fastest growing fields in organic chemistry. Under the condition of no external photosensitizer, the Li subject group in 2020 realizes the C-N coupling reaction of quinoxalinone compounds and azole compounds under photocatalysis. PhI (OAc) was reported by the Watchera and Guo subject groups, respectively, 2021 2 And PhI (OTFA) 2 A method for C-H amination of mediated quinoxalinone derivatives and azoles. However, most of the existing methods involve higher reaction temperatures, excessive amounts of strong oxidants, or expensive photocatalysts, which not only increase the cost of the reaction, but also reduce the atomic economy and environmental friendliness of the reaction.
Disclosure of Invention
In order to overcome the defects, the invention aims to provide a 3-aminoquinoxalinone compound and a synthesis method thereof.
In order to achieve the above purpose, the invention adopts the following technical scheme:
a3-aminoquinoxalinone compound has a chemical structural formula:
R 1 is H, mono-or dihalogen substituted, mono-or di-C 1-4 Alkyl substitution, -CF 3 Or benzoyl, R 2 H, C of a shape of H, C 1-4 Alkyl, ethynyl, benzyl orAnd a benzyl group.
Preferably, the substituted benzyl is-F, -Cl, -Br, -I, C 1-4 Alkyl, C 1-4 Benzyl with any one, two, three or four of alkoxy, trifluoromethyl, trifluoromethoxy, nitro and cyano substituents substituted on the benzene ring.
A synthetic method of a 3-aminoquinoxalinone compound comprises the following steps:
adding N-methyl protected quinoxalinone, pyrazole, selectfluor oxidant and catalyst into a reaction tube, adding solvent, stirring for reaction in an air atmosphere, cooling to room temperature, separating and purifying to obtain the target product.
Preferably, the molar usage ratio of pyrazole to N-methyl protected quinoxalinone is 1.5-2:1.
preferably, the catalyst is copper sulfate, copper triflate, copper iodide, copper bromide or copper acetate.
Preferably, the molar usage ratio of the catalyst to the N-methyl protected quinoxalinone is 0.1-0.15:1.
Preferably, the molar usage ratio of the SelectFluor oxidant to the N-methyl protected quinoxalinone is 1.5-2:1.
Preferably, the solvent is methanol or acetonitrile, and the dosage ratio of the solvent to the N-methyl protected quinoxalinone is 10-15mL:1mmol.
Preferably, the reaction temperature is 40-60 ℃ and the reaction time is 3-5h.
The chemical reaction formula of the synthesis method of the 3-aminoquinoxalinone compound is as follows:
R 1 is H, mono-or dihalogen substituted, mono-or di-C 1-4 Alkyl substitution, -CF 3 Or benzoyl, R 2 H, C of a shape of H, C 1-4 Alkyl, propynyl, benzyl or substituted benzyl.
Preferably, the takingThe substituted benzyl is-F, -Cl, -Br, -I, C 1-4 Alkyl, C 1-4 Benzyl with any one, two, three or four of alkoxy, trifluoromethyl, trifluoromethoxy, nitro and cyano substituents substituted on the benzene ring.
The invention has the positive beneficial effects that:
1. under the copper catalysis condition, N-methyl protected quinoxalinone and pyrazole are used as amination reagents to synthesize 3-amino quinoxalinone compounds, N-methyl protected quinoxalinone, pyrazole, selectfluor oxidant and catalyst are added into a reaction tube to react under the atmosphere of air, then a gas-mass spectrometer (GC-MS) is used for detecting whether a target product is generated or not, a peak which accords with the molecular weight of the product is obtained, after the generation of the product is determined, the reaction liquid is separated and purified, and the catalyst is used for preparing the catalyst 1 H NMR、 13 Characterization by C NMR demonstrated that the target product was indeed present. Pyrazole is an amination reagent which has wide application, low cost, easy obtainment and no toxicity, the invention has wide sources of raw materials, low cost, mild synthesis conditions and high product yield of 63-89 percent, and is suitable for wide application.
Detailed Description
The invention will be further described with reference to the following embodiments.
A3-aminoquinoxalinone compound has a chemical structural formula:
R 1 is H, mono-or dihalogen substituted, mono-or di-C 1-4 Alkyl substitution, -CF 3 Or benzoyl, R 2 H, C of a shape of H, C 1-4 Alkyl, propynyl, benzyl or substituted benzyl.
Further, the substituted benzyl is-F, -Cl, -Br, -I, C 1-4 Alkyl, C 1-4 Any one, two, three or four groups of alkoxy, trifluoromethyl, trifluoromethoxy, nitro and cyano substituent groups are substituted benzyl on the benzene ring, and the details are shown in table 1.
TABLE 1 3-aminoquinoxalinones of examples 1-17
Wherein, the target product structure detection data of example 1: yellow solid; m.p. =142-144 ℃. 1 H NMR(400MHz,CDCl 3 ,ppm):δ9.08(d,J＝2.7Hz,1H),8.10(dd,J＝8.0Hz,1.3Hz,1H),7.88(d,J＝1.6Hz,1H),7.57-7.52(m,1H),7.40-7.36(m,1H),7.34-7.32(m,1H),6.50(dd,J＝2.7Hz,1.6Hz,1H),3.80(s,3H)； 13 C NMR(100MHz,CDCl 3 ,ppm):δ150.6,143.3,142.5,131.1,132.5,131.2,130.1,130.0,124.5,113.6,108.2,29.9.MS(ESI)(m/z):227.1[M+H] + 。
Example 2 target product structure detection data: yellow solid; m.p. =114-115 ℃. 1 H NMR(400MHz,CDCl 3 ,ppm):δ9.10(d,J＝2.7Hz,1H),8.05(dd,J＝8.8Hz,1.6Hz,1H),7.89(d,J＝1.6Hz,1H),7.60-7.56(m,1H),7.42-7.38(m,2H),6.51(dd,J＝2.7Hz,1.6Hz,1H),4.44(q,J＝7.2Hz,2H),1.44(t,J＝7.2Hz,3H). 13 C NMR(100MHz,CDCl 3 ,ppm):δ150.1,143.4,142.6,133.2,131.6,131.5,130.5,130.1,124.4,113.5,108.2,38.3,12.4.MS(ESI)(m/z):241.1[M+H] + 。
Example 3 target product structure detection data: yellow liquid; 1 H NMR(400MHz,CDCl 3 ,ppm):δ9.10(d,J＝2.7Hz,1H),8.04(dd,J＝8.0Hz,1.2Hz,1H),7.89(d,J＝1.6Hz,1H),7.59-7.55(m,1H),7.41-7.35(m,2H),6.5(dd,J＝2.7Hz,1.6Hz,1H),4.38-4.34(m,2H),1.84-1.76(m,2H),1.57-1.47(m,2H),1.02(t,J＝7.3Hz,3H). 13 CNMR(100MHz,CDCl 3 ,ppm):δ150.4,143.3,142.6,133.2,131.8,131.6,130.5,130.0,124.4,113.7,108.2,43.1,29.3,20.3,13.8.HRMS(ESI)calcd for C 15 H 16 N 4 O[M+H] + 269.1397,found 269.1395。
example 4 target product structure detection data: yellow solid; m.p. =209-211 ℃. 1 H NMR(400MHz,CDCl 3 ,ppm):δ9.08(d,J＝2.7Hz,1H),8.05(dd,J＝8.1Hz,1.3Hz,1H),7.90(d,J＝1.6Hz,1H),7.64-7.59(m,1H),7.52-7.50(m,1H),7.46-7.42(m,1H),6.52(dd,J＝2.7Hz,1.6Hz,1H),5.17(d,J＝2.5Hz,2H),2.34(t,J＝2.5Hz,1H). 13 C NMR(100MHz,CDCl 3 ,ppm):δ149.9,143.6,142.4,133.2,131.5,131.1,130.4,130.2,125.0,114.1,108.5,76.3,73.7,32.3.MS(ESI)(m/z):251.1[M+H] + 。
Example 5 target product structure detection data: yellow solid; m.p. =138-140 ℃. 1 H NMR(400MHz,CDCl 3 ,ppm):δ9.14(d,J＝2.7Hz,1H),8.06(dd,J＝8.0Hz,1.4Hz,1H),7.92(d,J＝1.6Hz,1H),7.49-7.46(m,1H),7.39-7.28(m,7H),6.53(dd,J＝2.7Hz,1.6Hz,1H),5.63(s,2H). 13 C NMR(100MHz,CDCl 3 ,ppm):δ150.9,143.5,142.7,134.7,133.3,132.0,131.6,130.4,130.1,129.1,128.0,126.8,124.7,114.4,108.4,46.7.MS(ESI)(m/z):303.1[M+H] + 。
Example 6 target product structure detection data: yellow solid; m.p. =182-184 ℃. 1 H NMR(400MHz,CDCl 3 ,ppm):δ9.12(d,J＝2.7Hz,1H),8.08(dd,J＝7.9Hz,1.3Hz,1H),7.92(d,J＝1.6Hz,1H),7.46-7.41(m,1H),7.40-7.36(m,1H),7.27-7.25(m,1H),7.20-7.16(m,1H),7.09-7.06(m,1H),7.05-7.01(m,1H),6.61(like d,1H),6.52(dd,J＝2.7Hz,1.6Hz,1H),5.55(s,2H),2.51(s,3H). 13 C NMR(100MHz,CDCl 3 ,ppm):δ150.7,143.5,142.6,135.0,133.4,132.1,131.9,131.6,130.7,130.3,130.2,127.6,126.6,124.7,124.3,114.5,108.4,44.8,19.3.HRMS(ESI)calcd for C 19 H 16 N 4 [M+H] + 317.1397,found 317.1394。
Example 10 target product structure detection data: yellow solid; m.p. =173-175 ℃. 1 HNMR(400MHz,CDCl 3 ,ppm):δ9.08(d,J＝2.7Hz,1H),8.06(dd,J＝8.0Hz,1.4Hz,1H),7.92(d,J＝1.6Hz,1H),7.60-7.57(m,2H),7.49-7.44(m,1H),7.40-7.36(m,3H).7.22(dd,J＝8.4Hz,1.0Hz,1H),6.52(dd,J＝2.7Hz,1.6Hz,1H),5.56(s,2H). 13 C NMR(100MHz,CDCl 3 ,ppm):δ150.7,143.6,142.6,138.7,133.2,131.7,131.5,130.5,130.3(q,J＝32.8Hz),130.2,127.1,126.1(q,J＝3.7Hz,),125.0,123.8(q,J＝270.5Hz),114.0,108.5,46.2. 19 F NMR(376MHz,CDCl 3 ,ppm):δ-62.7.HRMS(ESI)calcd for C 19 H 13 F 3 N 4 O[M+H] + 371.1114,found 371.1114。
Example 11 target product structure detection data: yellow solid; m.p. =191-193 ℃. 1 HNMR(400MHz,CDCl 3 ,ppm):δ9.17(d,J＝2.7Hz,1H),8.10(d,J＝8.3Hz,1H),7.93-7.89(m,2H),7.84-7.81(m,2H),7.74(dd,J＝8.3Hz,1.6Hz,1H),7.66-7.62(m,1H),7.55-7.51(m,2H),6.55(dd,J＝2.7Hz,1.6Hz,1H),3.87(s,3H). 13 C NMR(100MHz,CDCl 3 ,ppm):δ195.4,150.7,144.1,143.9,138.2,137.0,133.8,133.6,133.0,132.5,130.1,129.8,128.6,126.2,115.4,108.9,30.2.HRMS(ESI)calcd for C 19 H 14 N 4 O 2 [M+H] + 331.1190,found 331.1187。
Example 12 target product structure detection data: yellow solid; m.p. =185-187 ℃. 1 HNMR(400MHz,CDCl 3 ,ppm):δ9.10(d,J＝2.7Hz,1H),8.34(d,J＝1.2Hz,1H),7.92(d,J＝1.6Hz,1H),7.79(dd,J＝8.8Hz,1.2Hz,1H),7.47(d,J＝8.8Hz,1H),6.54(dd,J＝2.7Hz,1.6Hz,1H),3.86(s,3H). 13 C NMR(100MHz,CDCl 3 ,ppm):δ150.6,144.0,143.5,134.7,133.3,130.8,127.6(q,J＝4.1Hz),127.0(q,J＝33.5Hz),126.3(q,J＝3.5Hz),123.6(q,J＝270.4Hz),114.4,108.9,30.2. 19 F NMR(376MHz,CDCl 3 ,ppm):δ-62.2.HRMS(ESI)calcd for C 13 H 9 F 3 N 4 O[M+H] + 295.0801,found 295.0801。
Example 13 target product structure detection data: yellow solid; m.p. =184-186 ℃. 1 HNMR(400MHz,CDCl 3 ,ppm):δ9.08(d,J＝2.7Hz,1H),7.90-7.87(m,2H),7.53-7.50(m,2H),6.52(dd,J＝2.7Hz,1.6Hz,1H),3.80(s,3H). 13 C NMR(100MHz,CDCl 3 ,ppm):δ150.4,143.7,142.7,133.5,133.3,131.3,130.2,128.0,124.1,116.8,108.6,30.1.MS(ESI)(m/z):327.0[M+Na] + ,633.1[2M+2+Na] + 。
Example 14 target product structure detection data: yellow solid; m.p. =165-167 ℃. 1 HNMR(400MHz,CDCl 3 ,ppm):δ9.04(d,J＝2.6Hz,1H),7.87-7.85(m,2H),7.19-7.17(m,1H),7.01(s,1H),6.48(dd,J＝2.7Hz,1.6Hz,1H),3.76(s,3H),2.48(s,3H). 13 C NMR(100MHz,CDCl 3 ,ppm):δ150.6,143.1,141.8,141.0,133.0,132.4,129.8,129.2,125.9,113.7,108.0,29.7,22.1.HRMS(ESI)calcd for C 13 H 12 N 4 O[M+H] + 241.1084,found 241.1085。
Example 15 target product structure detection data: yellow solid; m.p. =202-204 ℃. 1 HNMR(400MHz,CDCl 3 ,ppm):δ9.05(d,J＝2.6Hz,1H),7.86(d,J＝1.6Hz,1H),7.76(s,1H),7.09(s,1H),6.49(dd,J＝2.6Hz,1.6Hz,1H),3.77(s,3H),2.40(s,3H),2.33(s,3H). 13 C NMR(100MHz,CDCl 3 ,ppm):δ150.6,143.0,141.9,140.2,133.6,133.0,130.6,130.2,129.5,114.2,107.9,29.8,20.6,19.3.MS(ESI)(m/z):255.1[M+H] + 。
Example 16 target product structure detection data: yellow solid; m.p. =235-237 ℃. 1 HNMR(400MHz,CDCl 3 ,ppm):δ9.06(d,J＝2.7Hz,1H),7.88(d,J＝1.6Hz,1H),7.82(dd,J＝10.2Hz,8.2Hz,1H),7.16(dd,J＝11.1Hz,7.0Hz,1H),6.51(dd,J＝2.7Hz,1.6Hz,1H),3.76(s,3H). 13 C NMR(100MHz,CDCl 3 ,ppm):δ151.3(dd,J＝252.6Hz,14.5Hz),150.2,147.3(dd,J＝246.7Hz,13.9Hz),143.8,142.7,133.3,129.7(d,J＝6.9Hz),127.6(dd,J＝9.9Hz,3.3Hz),117.6(dd,J＝18.7Hz,2.0Hz),108.6,102.4(d,J＝23.2Hz),30.5. 19 F NMR(376MHz,CDCl 3 ,ppm):δ-130.2,-130.3,-140.0,-140.1.MS(ESI)(m/z):263.1[M+H] + 。
Example 17 target product structure detection data: yellow solid; m.p. =211-213 ℃. 1 HNMR(400MHz,DMSO-d 6 ,ppm):δ12.94(s,1H),8.91(d,J＝2.6Hz,1H),7.87(d,J＝1.6Hz,1H),7.78(dd,J＝8.0Hz,1.0Hz,1H),7.57-7.52(m,1H),7.38-7.33(m,2H),6.57(dd,J＝2.6Hz,1.6Hz,1H). 13 C NMR(100MHz,DMSO,ppm):δ150.7,143.7,142.3,132.8,131.6,130.4,129.8,128.1,123.9,115.2,107.7.HRMS(ESI)calcd for C 11 H 8 N 4 O[M+H] + 213.0771,found 213.0768。
One of the synthetic methods of the 3-aminoquinoxalinone compounds of any one of the above examples 1-17, comprises the steps of:
adding N-methyl protected quinoxalinone, pyrazole, selectfluor oxidant and catalyst into a reaction tube, adding solvent, stirring for reaction in an air atmosphere, cooling to room temperature, separating and purifying to obtain the target product.
Further, the molar amount of pyrazole to N-methyl protected quinoxalinone was 0.3mmol, 0.2mmol, respectively, in a molar ratio of 1.5:1.
further, the catalyst is copper sulfate.
Further, the molar usage ratio of the catalyst to the N-methyl protected quinoxalinone is 0.15:1.
Further, the molar ratio of SelectFluor oxidant to N-methyl protected quinoxalinone was 1.5:1.
Further, the solvent is acetonitrile, and the dosage ratio of the solvent to the N-methyl protected quinoxalinone is 10mL:1mmol.
Further, the reaction temperature was 40℃and the reaction time was 4 hours.
The second method for synthesizing a 3-aminoquinoxalinone compound according to any one of examples 1-17, comprising the steps of:
adding N-methyl protected quinoxalinone, pyrazole, selectfluor oxidant and catalyst into a reaction tube, adding solvent, stirring for reaction in an air atmosphere, cooling to room temperature, separating and purifying to obtain the target product.
Further, the molar amount of pyrazole and N-methyl protected quinoxalinone was 0.4mmol and 0.2mmol, respectively, in a molar ratio of 2:1:.
Further, the catalyst is copper acetate.
Further, the molar usage ratio of the catalyst to the N-methyl protected quinoxalinone is 0.1:1.
Further, the molar ratio of SelectFluor oxidant to N-methyl protected quinoxalinone was 1.5:1.
Further, the solvent is acetonitrile, and the dosage ratio of the solvent to the N-methyl protected quinoxalinone is 15mL:1mmol.
Further, the reaction temperature was 50℃and the reaction time was 6 hours.
The third synthesis method of the 3-aminoquinoxalinone compound of any one of the above examples 1-17, comprising the steps of:
adding N-methyl protected quinoxalinone, pyrazole, selectfluor oxidant and catalyst into a reaction tube, adding solvent, stirring for reaction in an air atmosphere, cooling to room temperature, separating and purifying to obtain the target product.
Further, the molar amount of pyrazole to N-methyl protected quinoxalinone was 0.3mmol, 0.2mmol, respectively, in a molar ratio of 1.5:1.
further, the catalyst is copper acetate.
Further, the molar usage ratio of the catalyst to the N-methyl protected quinoxalinone is 0.1:1.
Further, the molar ratio of SelectFluor oxidant to N-methyl protected quinoxalinone was 2:1.
Further, the solvent is methanol, and the dosage ratio of the solvent to the N-methyl protected quinoxalinone is 10mL:1mmol.
Further, the reaction temperature was 60℃and the reaction time was 3 hours.
Finally, it is noted that the above-mentioned embodiments are merely for illustrating the technical solution of the present invention, and that other modifications and equivalents thereof by those skilled in the art should be included in the scope of the claims of the present invention without departing from the spirit and scope of the technical solution of the present invention.
Claims (9)
1. A3-aminoquinoxalinone compound is characterized in that the chemical structural formula is as follows:
R 1 is H, mono-or dihalogen substituted, mono-or di-C 1-4 Alkyl substitution, -CF 3 Or benzoyl, R 2 H, C of a shape of H, C 1-4 Alkyl, propynyl, benzyl or substituted benzyl.
2. The 3-aminoquinoxalinone compound according to claim 1, wherein said substituted benzyl is-F, -Cl, -Br, -I, C 1-4 Alkyl, C 1-4 Benzyl with any one, two, three or four of alkoxy, trifluoromethyl, trifluoromethoxy, nitro and cyano substituents substituted on the benzene ring.
3. A method for synthesizing the 3-aminoquinoxalinone compound according to claim 1 or 2, comprising the steps of:
adding N-methyl protected quinoxalinone, pyrazole, selectfluor oxidant and catalyst into a reaction tube, adding solvent, stirring for reaction in an air atmosphere, cooling to room temperature, separating and purifying to obtain the target product.
4. The method for synthesizing 3-aminoquinoxalinone compound according to claim 3, wherein the molar ratio of pyrazole to N-methyl protected quinoxalinone is 1.5-2:1.
5. the method for synthesizing a 3-aminoquinoxalinone compound according to claim 3, wherein the catalyst is copper sulfate, copper trifluoromethane sulfonate, copper iodide, copper bromide or copper acetate.
6. The method for synthesizing 3-aminoquinoxalinone compound according to claim 3, wherein the molar ratio of said catalyst to said N-methyl protected quinoxalinone is 0.1-0.15:1.
7. The method for synthesizing 3-aminoquinoxalinone according to claim 3, wherein the molar ratio of the Selectfluor oxidizing agent to the N-methyl protected quinoxalinone is 1.5-2:1.
8. The method for synthesizing 3-aminoquinoxalinone compound according to claim 3, wherein the solvent is methanol or acetonitrile, and the dosage ratio of the solvent to the N-methyl protected quinoxalinone is 10-15mL:1mmol.
9. The method for synthesizing 3-aminoquinoxalinone compound according to claim 3, wherein the reaction temperature is 40-60 ℃ and the reaction time is 3-5h.
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