CN113307808A - Preparation method of pentacyclic compound containing benzimidazole - Google Patents

Preparation method of pentacyclic compound containing benzimidazole Download PDF

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CN113307808A
CN113307808A CN202110652955.5A CN202110652955A CN113307808A CN 113307808 A CN113307808 A CN 113307808A CN 202110652955 A CN202110652955 A CN 202110652955A CN 113307808 A CN113307808 A CN 113307808A
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compound
benzimidazole
pentacyclic
nmr
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缪琳
姚金忠
周宏伟
邓成
李唱唱
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Jiaxing University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
    • C07D471/14—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
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Abstract

The invention discloses a preparation method of a pentacyclic compound containing benzimidazole, which comprises the following steps: under the action of a catalyst, an oxidant and an additive, a benzimidazole compound (II) and a maleimide compound (III) react in a solvent, and after the reaction is finished, the pentacyclic compound (I) is obtained through post-treatment. The method utilizes the reaction of benzimidazole and maleimide to obtain a pentacyclic structure containing benzimidazole and maleimide structural units, has simple operation and high yield, and the obtained structure can be used as a potential drug molecular unit.

Description

Preparation method of pentacyclic compound containing benzimidazole
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a preparation method of a pentacyclic compound containing benzimidazole.
Background
Benzimidazole compounds are very important organic intermediates and are important structural units of a plurality of medicines. For example, Omeprazole (5-methoxy-2- [ [ (4-methoxy-3, 5-dimethyl-2-pyridyl) methyl group), a first-line drug for the treatment of gastric diseases]Sulfinyl group]-1H-benzimidazole) primarily for duodenal ulcers and zollinger-ellison syndrome, but also for gastric ulcers and reflux esophagitis; intravenous injection can be usedTreatment of acute hemorrhage of peptic ulcer by combining with amoxicillin and clindamycin or with metronidazole and clarithromycin to kill helicobacter pylori: (
Figure BDA0003112467200000011
D.；
Figure BDA0003112467200000012
E.；
Figure BDA0003112467200000013
ak,T.；Habinovec,I.；Parlov
Figure BDA0003112467200000014
J.；Novak,P.,Monitoring and Quantification of Omeprazole Synthesis Reaction by In-Line Raman Spectroscopy and Characterization of the Reaction Components.Organic Process Research&Development 2016,20(12), 2092-. First-line antihypertensive drug Telmisartan (Telmisartan, 4'- [ (1,4' -dimethyl-2 '-propyl [2,6' -di-1H-benzimidazole)]-1' -yl) methyl]- [1,1' -Biphenyl group]-2-carboxylic acid), a specific angiotensin ii receptor (AT type i) antagonist, for the treatment of essential hypertension (Mizuno, c.s.; chittiboyina, a.g.; shah, f.h.; patny, A.; kurtz, t.w.; pershadingh, h.a.; speth, R.C.; karayman, v.t.; carvalho, p.b.; avery, M.A., Design, Synthesis, and Docking students of Novel leather Synthesis for the Treatment of metallic Synthesis 2010,53(3),1076, 1085). At present, the research on the medicine containing the benzimidazole structural unit mainly comprises two aspects, namely, the medicine which contains the benzimidazole structural unit and is on the market is modified to search the medicine with better curative effect; secondly, the method designs, synthesizes and screens the medicine containing the benzimidazole structural unit with novel structure by taking the pathological characteristics of certain diseases and the mechanism of the medicine for playing the role as the basis. Therefore, the development of new potential drug structures containing benzimidazole structural units is a major development direction of future benzimidazole drug research. In addition, many benzimidazole compounds also have good fluorescence properties and are widely applied to photoelectricityThe field of sub-devices, DNA diagnosis, photochemical sensors, dyes, fluorescent whitening agents, fluorescent coatings, laser dyes, organic electroluminescent devices (ELDs), and the like.
On the other hand, maleimide alkaloids are also a promising class of antitumor compounds, and their structural analogs Enzastaurin (Zestos, A.G.; Mikelman, S.R.; Kennedy, R.T.; Gnegy, M.E., PKC. beta. Inhibitors attachment Amphylamine-immobilized dopamide efficacy. ACS Chemical Neuroscience 2016,7(6), 757-ketone 766), and Ruboxistaurin (Zestos, A.G.; Carpenter, C.; Kim, Y.; Low, M.J.; Kennedy, R.T.; Gnegy, M.E., Ruboxistaurin resin-immobilized peptides in Extracellular polysaccharide), 1969, and their clinical activities have been studied by International patent publication No. 9, Inc. 10.
Disclosure of Invention
The invention provides a preparation method of a pentacyclic compound containing benzimidazole, which has high yield and high substrate adaptability, and the obtained product contains a pentacyclic structure of benzimidazole and maleimide structural units.
A method for preparing a pentacyclic compound containing benzimidazole, which is characterized by comprising the following steps:
under the action of a catalyst, an oxidant and an additive, a benzimidazole compound (II) and a maleimide compound (III) react in a solvent, and after the reaction is finished, a pentacyclic compound (I) is obtained through post-treatment;
the reaction formula is as follows:
Figure BDA0003112467200000021
wherein R is1Is H, C1～C4Alkyl radical, C1～C4Alkoxy, halogen or trifluoromethyl;
R2is C1～C4Alkyl, benzyl, substituted or unsubstituted phenyl, the substituents on the phenyl being selected from C1～C4Alkyl radical, C1～C4Alkoxy or halogen.
Preferably, R is1Is H, methyl, methoxy, F, Cl or trifluoromethyl.
Preferably, R is2Is methyl, tert-butyl, benzyl, substituted or unsubstituted phenyl, and the substituent on the phenyl is selected from methyl, methoxy or Cl.
Preferably, the catalyst is [ Cp + RhCl ]2]2And AgSbF6The molar ratio of the two is 1: 0.5-2.
Preferably, the oxidant is AgOAc.
Preferably, the additive is CsOAc.
Preferably, the benzimidazole compound: maleimide compound: oxidizing agent: additive 1: 1.2-1.5: 2-2.2: 1 to 1.1.
Preferably, the solvent is DCE.
Preferably, the reaction temperature is 100-130 ℃, and the reaction time is 10-24 h.
Preferably, the pentacyclic compound has the following structure:
Figure BDA0003112467200000031
Figure BDA0003112467200000041
compared with the prior art, the invention has the beneficial effects that:
the method utilizes the reaction of benzimidazole and maleimide to obtain the pentacyclic structure containing benzimidazole and maleimide structural units, has simple operation and high yield, and the obtained structure can be used as a potential drug molecular unit.
Detailed Description
The general operation mode is as follows:
to 25mL of a sealed tube with magnetic stirring were added benzimidazole compound (II) (0.2mmol), maleimide compound (III) (0.3mmol), [ Cp ] RhCl2]2(0.01mol),AgSbF6(0.02mol), AgOAc (66.8mg,0.4mmol), CsOAc (38.4mg,0.2mmol), DCE (2.0mL), mixed well. Sealing the tube, protecting with nitrogen, heating to 120 deg.C, and stirring for 12 hr. The resulting reaction mixture was cooled to room temperature, diluted with ethyl acetate, and the product was isolated by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:2, v/v)) to give product I.
The reaction formula is as follows:
Figure BDA0003112467200000051
examples 1 to 19
According to the general method, one of the compounds 3a to 3j and 4b to 4j is obtained, and the structure and the yield are as follows:
Figure BDA0003112467200000052
Figure BDA0003112467200000061
example 20 (amplification reaction)
To 250mL of a sealed tube with magnetic stirring were added benzimidazole compound (1a) (1.156g,6mmol), maleimide compound (2a) (1.37g,9mmol), [ Cp ] RhCl2]2(0.3mol),AgSbF6(0.6mol), AgOAc (2.0g,12mmol), CsOAc (1.152g,6mmol), DCE (60 mL.) were mixed well. Sealing the tube, protecting with nitrogen, heating to 120 deg.C, and stirring for 12 hr. The resulting reaction mixture was cooled to room temperature, diluted with ethyl acetate, and the product was isolated by silica gel column chromatography (ethyl acetate: petroleum ether ═ 1:2, v/v)) to give product 3a (1.471g, yield 71%).
The reaction formula is as follows:
Figure BDA0003112467200000062
the characterization data of the partial compounds obtained are as follows:
58.7mg, 85% of Compound (3 a);1H NMR(400MHz,DMSO-d6)δ8.29(d,J＝7.4Hz,1H),7.85(d,J＝7.4Hz,1H),7.77-7.73(m,2H),7.61-7.53(m,2H),7.37-7.28(m,2H),6.12(d,J＝9.7Hz,1H),4.80(d,J＝9.7Hz,1H),1.49(s,9H)；13C NMR(100MHz,DMSO-d6) δ 175.9,174.8,145.9,143.9,135.8,131.2,129.2,128.6,128.1,125.7,124.8,123.4,123.1,119.6,112.1,58.9,53.5,42.4, 28.2; hrms (ei) theoretical value: c21H19N3O2345.1477, calculated as: 345.1480.
55.3mg, 77% of the compound (3 b);1H NMR(400MHz,CDCl3)δ8.31(d,J＝7.2Hz,1H),7.80(d,J＝7.3Hz,1H),7.67(s,2H),7.31-7.26(m,3H),5.48(d,J＝10.3Hz,1H),4.47(d,J＝8.7Hz,1H),2.44(s,3H),1.55(s,9H)；13C NMR(100MHz,CDCl3) δ 174.9,173.4,145.9,143.8,141.4,135.0,130.0,128.2,126.5,125.7,123.4,123.2,121.7,119.6,110.7,59.8,53.3,41.9,28.2, 21.7; hrms (ei) theoretical value: c22H21N3O2359.1634, calculated as: 359.1638.
61.5mg, 82% of Compound (3 c);1H NMR(400MHz,CDCl3)δ8.28(d,J＝8.7Hz,1H),7.75-7.73(m,1H),7.56-7.54(m,1H),7.33(s,1H),7.27-7.25(m,2H),6.98(d,J＝8.6Hz,1H),5.36(d,J＝9.8Hz,1H),4.40(d,J＝9.8Hz,1H),3.87(s,3H),1.53(s,9H)；13C NMR(100MHz,CDCl3) δ 174.8,173.4,161.6,146.0,143.9,140.0,128.4,127.6,123.2,123.1,119.4,117.3,115.5,112.4,110.5,59.9,55.5,53.2,42.1, 28.2; hrms (ei) theoretical value: c22H21N3O3375.1583, calculated as: 375.1585.
54.8mg, 73% of the compound (3 d);1H NMR(400MHz,CDCl3)δ7.88(d,J＝2.8Hz,1H),7.82-7.80(m,1H),7.75(d,J＝8.7Hz,1H),7.65-7.63(m,1H),7.35-7.30(m,2H),7.05(dd,J＝8.7,2.8Hz,1H),5.45(d,J＝9.8Hz,1H),4.44(d,J＝9.8Hz,1H),3.92(s,3H),1.54(s,9H)；13C NMR(100MHz,CDCl3) δ 175.2,173.4,160.1,145.8,143.7,135.2,129.1,125.7,123.8,123.4,119.8,119.0,118.7,110.7,108.6,59.8,55.7,53.4,41.7, 28.2; hrms (ei) theoretical value: c22H21N3O3375.1583, calculated as: 375.1589.
65.3mg, 75% of the compound (3 e);1H NMR(400MHz,CDCl3)δ8.05-8.03(m,1H),7.78-7.76(m,1H),7.69(s,1H),7.31-7.28(m,2H),5.24(d,J＝8.0Hz,1H),4.77(d,J＝8.0Hz,1H),4.11(s,3H),3.99(s,3H),3.96(s,3H),1.50(s,9H)；13C NMR(100MHz,CDCl3) δ 174.4,172.8,154.6,152.1,146.8,144.2,143.9,134.7,123.6,123.3,120.3,119.4,113.3,112.8,104.0,61.6,60.9,59.7,56.6,56.4,39.7, 28.1; hrms (ei) theoretical value: c24H25N3O5435.1794, calculated as: 435.1794.
60.1mg, 70% of the compound (3 f);1H NMR(400MHz,DMSO-d6)δ8.33(d,J＝8.6Hz,1H),7.75-7.67(m,3H),7.49(d,J＝8.6Hz,1H),7.32-7.23(m,2H),6.04(d,J＝9.8Hz,1H),4.80(d,J＝9.9Hz,1H),1.45(s,9H)；13C NMR(100MHz,CDCl3) δ 174.2,173.0,150.6,144.5,143.7,135.0,128.6,127.7,124.0,123.6,123.1,121.5,120.5(q, J ═ 268.1Hz),120.2,119.9,110.9,60.2,53.1,41.7, 28.1; hrms (ei) theoretical value: c22H18F3N3O3429.1300, calculated as: 429.1304.
45.8mg, 63% of Compound (3 g);1H NMR(400MHz,CDCl3)δ8.40-8.36(m,1H),7.78-7.77(m,1H),7.60-7.58(m,2H),7.33-7.31(m,2H),7.20-7.16(m,1H),5.41(d,J＝10.0Hz,1H),4.44(d,J＝10.0Hz,1H),1.55(s,9H)；13CNMR(100MHz,CDCl3)δ174.3,173.1,164.0(d,1JC-F＝251.1Hz,Ar-F),145.0,143.7,135.0,129.0(d,2JC-F＝9.0Hz,Ar-F),128.2(d,2JC-F＝8.0Hz,Ar-F),123.7,123.4,120.9,119.7,116.8(d,2JC-F＝22.1Hz,Ar-F),114.9(d,2JC-F24.0Hz, Ar-F),110.8,60.2,53.1,41.8, 28.2; hrms (ei) theoretical value: c21H18FN3O2363.1383, meterCalculating the value: 363.1390.
48.4mg, 57% of compound (3 h);1H NMR(400MHz,CDCl3)δ8.37(d,J＝8.5Hz,1H),7.89(s,1H),7.60(d,J＝8.2Hz,1H),7.69(d,J＝7.9Hz,1H),7.44(d,J＝8.0Hz,1H),7.38-7.30(m,2H),5.55(d,J＝8.4Hz,1H),4.53(d,J＝10.7Hz,1H),1.56(s,9H)；13C NMR(100MHz,CDCl3) δ 174.2,173.0,144.7,143.5,137.0,134.9,129.6,128.1,128.0,127.2,124.0,123.6,122.9,119.7,111.0,60.2,53.1,41.6,28.3, 28.2; hrms (ei) theoretical value: c21H18BrN3O2423.0582, calculated as: 423.0583.
43.0mg, 52% of Compound (3 i);1H NMR(400MHz,CDCl3)δ8.45(d,J＝8.2Hz,1H),8.12(s,1H),7.78(d,J＝7.2Hz,1H),7.68(d,J＝8.2Hz,1H),7.63(d,J＝7.6Hz,1H),7.33-7.31(m,2H),5.41(d,J＝9.9Hz,1H),4.48(d,J＝10.0Hz,1H),1.53(s,9H)；13C NMR(100MHz,CDCl3)δ174.1,172.9,144.1,143.8,135.0,132.3(q,2JC-F＝32.9Hz),127.6,127.1,126.2,125.9,125.2,124.4,123.8,123.6(q,1JC-F275.0Hz),120.1,111.2,60.3,53.1,41.6, 28.1; hrms (ei) theoretical value: c22H18FN3O2413.1351, calculated as: 413.1354.
42.7mg, 54% of the compound (3 j);1H NMR(400MHz,CDCl3)δ9.13(d,J＝8.4Hz,1H),8.04-7.96(m,3H),7.80-7.76(m,1H),7.68-7.64(m,1H),7.42(d,J＝8.5Hz,1H),7.36-7.30(m,2H),7.19-7.18(m,1H),3.53(d,J＝18.4Hz,1H),3.35(d,J＝18.4Hz,1H),1.53(s,9H)；13C NMR(100MHz,CDCl3) δ 173.5,173.1,158.3,145.0,133.9,131.8,130.4,128.6,128.3,127.9,127.7,125.6,125.2,123.8,122.9,121.5,117.3,108.1,66.5,60.5,38.7, 28.4; hrms (ei) theoretical value: c25H21N3O2395.1634, calculated as: 395.1639.
49.7mg, 82% of the compound (4 b);1H NMR(400MHz,CDCl3)δ8.39-8.37(m,1H),7.89-7.87(m,1H),7.79-7.77(m,1H),7.71-7.69(m,1H),7.48-7.46(m,2H),7.33-7.31(m,2H),5.57(d,J＝9.8Hz,1H),4.63(d,J＝9.8Hz,1H),3.03(s,3H)；13C NMR(100MHz,CDCl3) δ 174.0,172.3,145.5,143.6,134.8,130.9,129.2,128.2,126.1,125.9,124.2,123.8,123.6,120.0,111.1,53.1,41.5, 25.7; hrms (ei) theoretical value: c18H13N3O2303.1008, calculated as: 303.1012.
49.5mg, 78% of Compound (4 c);1H NMR(400MHz,DMSO-d6)δ8.30(d,J＝7.4Hz,1H),7.90-7.84(m,2H),7.75(d,J＝7.8Hz,1H),7.62-7.53(m,2H),7.38-7.30(m,2H),6.16(d,J＝9.6Hz,1H),4.94(d,J＝9.6Hz,1H),3.49(m,2H),1.08(t,J＝7.1Hz,3H)；13C NMR(100MHz,DMSO-d6) δ 175.1,173.7,145.9,143.9,135.6,131.1,129.1,128.6,128.5,125.6,124.6,123.4,123.2,120.0,112.4,53.4,41.9,34.4, 12.9; hrms (ei) theoretical value: c19H15N3O2317.1164, calculated as: 317.1170.
51.6mg, 68% of the compound (4 d);1H NMR(400MHz,DMSO-d6)δ8.36-8.34(m,1H),7.91-7.89(m,2H),7.80-7.79(m,1H),7.63-7.60(m,2H),7.40-7.28(m,7H),6.34(d,J＝9.0Hz,1H),5.09(d,J＝9.2Hz,1H),4.70(s,2H)；13CNMR(100MHz,DMSO-d6) δ 175.1,173.9,146.0,143.9,135.9,135.6,131.2,129.2,129.1,128.7,128.4,128.2,128.1,125.6,124.7,123.5,123.3,119.6,112.5,53.4,42.8, 42.1; hrms (ei) theoretical value: c24H17N3O2379.1321, calculated as: 379.1322.
52.6mg, 72% of Compound (4 e);1H NMR(400MHz,CDCl3)δ8.48-8.46(m,1H),7.97-7.95(m,1H),7.84-7.82(m,1H),7.76-7.74(m,1H),7.54-7.52(m,2H),7.46-7.34(m,5H),7.29-7.25(m,2H),5.83(d,J＝9.4Hz,1H),4.84(d,J＝9.8Hz,1H)；13C NMR(100MHz,CDCl3) δ 173.0,171.4,145.6,143.9,134.9,130.9,129.3,129.2,129.1,128.1,126.0,125.9,124.5,123.8,123.5,119.8,111.0,53.2, 41.7; hrms (ei) theoretical value: c23H15N3O2365.1164, calculated as: 365.1167.
57.7mg, 73% of the compound (4 f);1H NMR(400MHz,CDCl3)δ8.47-8.45(m,1H),7.96-7.94(m,1H),7.83-7.81(m,1H),7.76-7.74(m,1H),7.54-7.51(m,2H),7.36-7.34(m,2H),7.20-7.18(m,2H),6.95-6.93(m,2H),5.81(d,J＝9.8Hz,1H),4.82(d,J＝9.8Hz,1H),3.80(s,3H)；13C NMR(100MHz,CDCl3) δ 173.2,171.5,159.8,145.6,143.9,135.0,131.1,129.4,128.1,127.3,126.1,126.0,124.6,123.8,123.5,123.4,119.9,114.5,111.0,55.5,53.3, 41.7; hrms (ei) theoretical value: c24H17N3O3395.1270, calculated as: 395.1273.
61.4mg, 75% of Compound (4 g);1H NMR(400MHz,CDCl3)δ8.46-8.44(m,1H),7.94-7.91(m,1H),7.83-7.80(m,1H),7.73-7.71(m,1H),7.52-7.50(m,2H),7.35-7.32(m,2H),6.84-6.81(m,1H),6.73-6.70(m,2H),5.99(s,2H),5.77(d,J＝9.8Hz,1H),4.79(d,J＝9.8Hz,1H)；13C NMR(100MHz,CDCl3) δ 173.2,171.5,148.1,145.5,143.8,134.9,130.9,129.3,128.0,126.0,125.9,124.4,124.2,123.7,123.5,120.0,119.8,111.0,108.3,107.2,101.9,53.1, 41.6; hrms (ei) theoretical value: c24H15N3O4409.1063, calculated as: 409.1069.

Claims (10)

1. a method for preparing a pentacyclic compound containing benzimidazole, which is characterized by comprising the following steps:
under the action of a catalyst, an oxidant and an additive, a benzimidazole compound (II) and a maleimide compound (III) react in a solvent, and after the reaction is finished, a pentacyclic compound (I) is obtained through post-treatment;
the reaction formula is as follows:
Figure FDA0003112467190000011
wherein R is1Is H, C1～C4Alkyl radical, C1～C4Alkoxy, halogen or trifluoromethyl;
R2is C1～C4Alkyl, benzyl, substituted or unsubstituted phenyl, the substituents on the phenyl being selected from C1～C4Alkyl radical, C1～C4Alkoxy or halogen.
2. The method for preparing a benzimidazole-containing pentacyclic compound of claim 1, wherein R is1Is H, methyl, methoxy, F, Cl or trifluoromethyl.
3. The method for preparing a benzimidazole-containing pentacyclic compound of claim 1, wherein R is2Is methyl, tert-butyl, benzyl, substituted or unsubstituted phenyl, and the substituent on the phenyl is selected from methyl, methoxy or Cl.
4. The method of claim 1, wherein the catalyst is [ Cp RhCl ™2]2And AgSbF6The molar ratio of the two is 1: 0.5-2.
5. The method according to claim 1, wherein the oxidizing agent is AgOAc.
6. The method of claim 1, wherein the additive is CsOAc.
7. The process for producing a benzimidazole-containing pentacyclic compound according to claim 1, wherein the benzimidazole compound is one of, based on a molar amount: maleimide compound: oxidizing agent: additive 1: 1.2-1.5: 2-2.2: 1 to 1.1.
8. The method of claim 1, wherein the solvent is DCE.
9. The method for preparing the pentacyclic compound comprising benzimidazole according to claim 1, wherein the reaction temperature is 100-130 ℃ and the reaction time is 10-24 h.
10. The method of claim 1, wherein the pentacyclic compound has the following structure:
Figure FDA0003112467190000021
Figure FDA0003112467190000031
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Citations (1)

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CN108250202A (en) * 2018-01-15 2018-07-06 陕西师范大学 2,3- disubstituted benzenes and imidazo [1,2-a] pyrimidines and its preparation method and application

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