CN114874212B - Preparation method of pentacyclic compound containing benzimidazole - Google Patents
Preparation method of pentacyclic compound containing benzimidazole Download PDFInfo
- Publication number
- CN114874212B CN114874212B CN202210611856.7A CN202210611856A CN114874212B CN 114874212 B CN114874212 B CN 114874212B CN 202210611856 A CN202210611856 A CN 202210611856A CN 114874212 B CN114874212 B CN 114874212B
- Authority
- CN
- China
- Prior art keywords
- compound
- benzimidazole
- pentacyclic
- nmr
- cdcl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- 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
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a preparation method of pentacyclic compound containing benzimidazole, which comprises the following steps: under the action of a catalyst, an oxidant and an additive, the benzimidazole compound (II) and the maleimide compound (III) react in a solvent, and after the reaction is finished, the pentacyclic compound (I) is obtained through post-treatment. The benzimidazole and maleimide react to obtain the pentacyclic structure containing benzimidazole and maleimide structural units, the operation is simple, the yield is high, and the obtained structure can be used as a potential drug molecular unit.
Description
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 a very important class of organic intermediates, and are important building blocks for many drugs. For example, the first line drug Omeprazole (Omeprazole, 5-methoxy-2- [ [ (4-methoxy-3, 5-dimethyl-2-pyridinyl) methyl) for the treatment of gastric disorders]Sulfinyl group]-1H-benzimidazole), mainly for duodenal ulcers and jejunum-mugwort syndrome, but also for gastric ulcers and reflux esophagitis; intravenous injection can be used for treating acute hemorrhage of peptic ulcer, and can be used together with amoxicillin He Kelin or metronidazole and clarithromycin to kill helicobacter pylori
D.；/>
E.；
ak,T.；Habinovec,I.；Parlov />
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), 2092-2099). Telmisartan (telmihartan, 4'- [ (1, 4' -dimethyl-2 '-propyl [2,6' -di-1H-benzimidazole) as a first-line antihypertensive drug]-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.; pershadsingh, h.a.; speth, r.c.; karamyan, v.t.; carvalho, p.b.; avery, m.a., design, synthesis, and Docking Studies of Novel Benzimidazoles for the Treatment of Metabolic syndrome, journal of Medicinal Chemistry 2010,53 (3), 1076-1085). At present, the research on the medicaments containing benzimidazole structural units mainly comprises two aspects, namely, modifying the medicaments containing the benzimidazole structural units which are marketed, and searching for medicaments with better curative effects; secondly, based on the pathological characteristics of certain diseases and the mechanism of action of the medicines, the medicines containing benzimidazole structural units with novel structures are designed, synthesized and screened. Therefore, the development of new potential drug structures containing benzimidazole building blocks is an important development direction for future benzimidazole drug research. In addition, many benzimidazole compounds have better fluorescence properties and are widely applied to the fields of optical electronic devices, DNA diagnostics, photochemical sensors, dyes, fluorescent brighteners, 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 structural analogs Enzastaurin (Zeston, A.G., mikelman, S.R., kennedy, R.T., gnegy, M.E., PKCβ Inhibitors Attenuate Amphetamine-Stimulated Dopamine Efflux.ACS Chemical Neuroscience 2016,7 (6), 757-766), and Ruboxicstaurin (Zeston, A.G., carpenter, C., kim, Y., low, M.J., kennedy, R.T., gnegy, M.E., ruboxistaurin Reduces Cocaine-Stimulated Increases in Extracellular Dopamine by Modifying Dopamine-Autorecep Activity.ACS Chemical Neuroscience 2019,10 (4), 1960-1969) have entered clinical studies with good antitumor activity.
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 process for preparing a benzimidazole-containing pentacyclic compound, comprising:
under the action of a catalyst, an oxidant and an additive, the benzimidazole compound (II) and the maleimide compound (III) react in a solvent, and after the reaction is finished, the pentacyclic compound (I) is obtained through post-treatment;
the reaction formula is as follows:
wherein R is 1 H, C of a shape of H, C 1 ～C 4 Alkyl, C 1 ～C 4 Alkoxy, halogen or trifluoromethyl;
R 2 is C 1 ～C 4 Alkyl, benzyl, substituted or unsubstituted phenyl, the substituents on said phenyl being selected from C 1 ～C 4 Alkyl, C 1 ～C 4 Alkoxy or halogen.
Preferably, said R 1 Is H, methyl, methoxy, F, cl or trifluoromethyl.
Preferably, said R 2 Is methyl, tert-butyl, benzyl, substituted or unsubstituted phenyl, the substituents on the phenyl groups being selected from methylMethoxy or Cl.
Preferably, the catalyst is [ Cp. RhCl ] 2 ] 2 And AgSbF 6 The molar ratio of the two is 1:0.5-2.
Preferably, the oxidizing agent is AgOAc.
Preferably, the additive is CsOAc.
Preferably, the benzimidazole compound is represented by mole: maleimide compound: oxidizing agent: additive = 1:1.2 to 1.5:2 to 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:
compared with the prior art, the invention has the beneficial effects that:
the benzimidazole and maleimide are reacted to obtain the pentacyclic structure containing the benzimidazole and maleimide structural units, the operation is simple, the yield is high, and the obtained structure can be used as a potential drug molecular unit.
Drawings
FIG. 1 is a graph showing the bacteriostatic effect of the compound of test example 1 according to the present invention.
Detailed Description
The general operation mode is as follows:
to 25mL of a tube sealer with magnetic stirring was added benzimidazole compound (II) (0.2 mmol), maleimide compound (III) (0.3 mmol), and [ Cp. Rhol ] 2 ] 2 (0.01mol),AgSbF 6 (0.02mol),AgOAc(66.8mg,0.4mmol),CsOAc(38.4mg,0.2 mmol), DCE (2.0 mL) was mixed well. The tube was sealed under nitrogen, heated to 120℃and stirred for 12h. The resulting reaction mixture was cooled to room temperature, diluted with ethyl acetate and the product was separated by column chromatography on silica gel (ethyl acetate: petroleum ether=1:2, v/v)) to give product I.
The reaction formula is as follows:
examples 1 to 19
One of the compounds 3a to 3j, 4b to 4j, respectively, obtained according to the above general method, had the following structure and yield:
example 20 (amplification reaction)
To 250mL of a tube sealer with magnetic stirring was added benzimidazole compound (1 a) (1.156 g,6 mmol), maleimide compound (2 a) (1.37 g,9 mmol), [ Cp ] RhCl 2 ] 2 (0.3mol),AgSbF 6 (0.6 mol), agOAc (2.0 g,12 mmol), csOAc (1.152 g,6 mmol), DCE (60 mL), were mixed well. The tube was sealed under nitrogen, heated to 120℃and stirred for 12h. The resulting reaction mixture was cooled to room temperature, diluted with ethyl acetate, and the product was separated by silica gel column chromatography (ethyl acetate: petroleum ether=1:2, v/v)) to give product 3a (1.471 g, yield 71%).
The reaction formula is as follows:
test example 1 antibacterial Activity assay
The formula of the culture medium comprises: 3.0g of agar, 1.5g of sodium chloride, 1.5g of peptone and 0.75g of yeast extract.
(1) Weighing: agar, sodium chloride, peptone, yeast extract and the like are accurately weighed according to the formula of the culture medium and placed into a blue-mouth bottle.
(2) Dissolving: 150ml of primary water was added to the flask, and the flask was shaken to dissolve the water.
(3) Binding: binding with kraft paper or newspaper.
(4) And (3) sterilization: the culture medium is placed in a sterilizing pot, sterilized for 20min at 121 ℃ under 0.1 MPa.
The antibacterial effect of the sample was tested, the synthesized compound 3e was dissolved in DCM to prepare a 30mg/ml and 10mg/ml sample solution, the oxford cup method was used to perform the experiment, the bacteria solution (E.coli) was inoculated onto the sterile plate with the medium poured in, the oxford cup was placed after the coating, and the wells numbered 1,2,3,4 were each filled with a negative control solution (20. Mu.l water), a positive control solution (20. Mu.l 1mg/ml amoxicillin solution), 20. Mu.l 10mg/ml sample solution, and 20. Mu.l 30mg/ml sample solution. The results of the culture observation are shown in FIG. 1, and the diameters of inhibition zones of the small holes numbered 1,2,3 and 4 are respectively 0cm,2.3cm and 2.2cm.
Characterization data for the fraction of compounds obtained are as follows:
58.7mg,85% of Compound (3 a); 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(100MHz,DMSO-d 6 ) Delta 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) theory: c (C) 21 H 19 N 3 O 2 345.1477, calculated: 345.1480.
55.3mg,77% of compound (3 b); 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 )δ174.9,173.4,145.9,143.8,141.4,135.0,130.0,128.2,126.5,125.7,123.4,123.2,121.7,119.6,110.7,59.8,53.3,41.9,28.2,21.7; HRMS (EI) theory: c (C) 22 H 21 N 3 O 2 359.1634, calculated: 359.1638.
61.5mg,82% of compound (3 c); 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 ) Delta 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) theory: c (C) 22 H 21 N 3 O 3 375.1583, calculated: 375.1585.
54.8mg,73% of compound (3 d); 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 ) Delta 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) theory: c (C) 22 H 21 N 3 O 3 375.1583, calculated: 375.1589.
compound (3 e) 65.3mg,75%; 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 ) Delta 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) theory: c (C) 24 H 25 N 3 O 5 435.1794, calculated: 435.1794.
60.1mg,70% of compound (3 f); 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(100MHz,CDCl 3 ) 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=268.1 Hz), 120.2,119.9,110.9,60.2,53.1,41.7,28.1; HRMS (EI) theory: c (C) 22 H 18 F 3 N 3 O 3 429.1300, calculated: 429.1304.
45.8mg,63% of Compound (3 g); 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 )δ174.3,173.1,164.0(d, 1 J C-F ＝251.1Hz,Ar-F),145.0,143.7,135.0,129.0(d, 2 J C-F ＝9.0Hz,Ar-F),128.2(d, 2 J C-F ＝8.0Hz,Ar-F),123.7,123.4,120.9,119.7,116.8(d, 2 J C-F ＝22.1Hz,Ar-F),114.9(d, 2 J C-F =24.0 hz, ar-F), 110.8,60.2,53.1,41.8,28.2; HRMS (EI) theory: c (C) 21 H 18 FN 3 O 2 363.1383, calculated: 363.1390.
48.4mg,57% of compound (3 h); 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 ) Delta 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) theory: c (C) 21 H 18 BrN 3 O 2 423.0582, calculated: 423.0583.
43.0mg,52% of compound (3 i); 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 )δ174.1,172.9,144.1,143.8,135.0,132.3(q, 2 J C-F ＝32.9Hz),127.6,127.1,126.2,125.9,125.2,124.4,123.8,123.6(q, 1 J C-F ＝275.0Hz),120.1,1112,60.3,53.1,41.6,28.1; HRMS (EI) theory: c (C) 22 H 18 FN 3 O 2 413.1351, calculated: 413.1354.
42.7mg,54% of Compound (3 j); 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 ) Delta 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) theory: c (C) 25 H 21 N 3 O 2 395.1634, calculated: 395.1639.
49.7mg,82% of Compound (4 b); 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 ) Delta 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) theory: c (C) 18 H 13 N 3 O 2 303.1008, calculated: 303.1012.
49.5mg,78% of compound (4 c); 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(100MHz,DMSO-d 6 ) Delta 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) theory: c (C) 19 H 15 N 3 O 2 317.1164, calculated: 317.1170.
51.6mg,68% of Compound (4 d); 1 H NMR(400MHz,DMSO-d 6 )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)； 13 C NMR(100MHz,DMSO-d 6 )δ175.1,173.9,146.0,143.9,135.9,135.6,131.2,129.2,129.1,128.7,128.4,128.2,128.1,125.6,124.7,123.5,123.3,119.6,112.5,53.4,42.8,42.1; HRMS (EI) theory: c (C) 24 H 17 N 3 O 2 379.1321, calculated: 379.1322.
52.6mg,72% of Compound (4 e); 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 ) Delta 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) theory: c (C) 23 H 15 N 3 O 2 365.1164, calculated: 365.1167.
57.7mg,73% of compound (4 f); 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 ) Delta 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) theory: c (C) 24 H 17 N 3 O 3 395.1270, calculated: 395.1273.
61.4mg,75% of Compound (4 g); 1 H NMR(400MHz,CDCl 3 )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)； 13 C NMR(100MHz,CDCl 3 ) Delta 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) theory: c (C) 24 H 15 N 3 O 4 409.1063, calculated: 409.1069.
Claims (5)
1. a process for preparing a benzimidazole-containing pentacyclic compound, comprising:
under the action of a catalyst, an oxidant and an additive, the benzimidazole compound (II) and the maleimide compound (III) react in a solvent, and after the reaction is finished, the pentacyclic compound (I) is obtained through post-treatment;
the reaction formula is as follows:
wherein R is 1 H, C of a shape of H, C 1 ~C 4 Alkyl, C 1 ~C 4 Alkoxy, halogen or trifluoromethyl;
R 2 is C 1 ~C 4 Alkyl, benzyl, substituted or unsubstituted phenyl, the substituents on said phenyl being selected from C 1 ~C 4 Alkyl, C 1 ~C 4 Alkoxy or halogen;
the catalyst is [ Cp ] RhCl 2 ] 2 And AgSbF 6 The molar ratio of the two is 1:0.5-2;
the oxidant is AgOAc;
the additive is CsOAc;
the solvent is DCE;
the reaction temperature is 100-130 ℃, and the reaction time is 10-24 hours.
2. The method for preparing a pentacyclic benzimidazole compound according to claim 1, wherein R 1 Is H, methyl, methoxy, F, cl or trifluoromethyl.
3. The method for preparing a pentacyclic benzimidazole compound according to claim 1, wherein R 2 Is methyl, tert-butyl, benzyl, substituted or unsubstituted phenyl, the substituents on said phenyl being selected from methyl, methoxy or Cl.
4. The method for producing a pentacyclic benzimidazole compound according to claim 1, wherein the benzimidazole compound is represented by a molar amount: maleimide compound: oxidizing agent: additive = 1: 1.2-1.5: 2-2.2: 1 to 1.1.
5. The method for preparing a pentacyclic compound containing benzimidazole according to claim 1, wherein the pentacyclic compound has the following structure:
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110652955.5A CN113307808A (en) | 2021-06-11 | 2021-06-11 | Preparation method of pentacyclic compound containing benzimidazole |
| CN2021106529555 | 2021-06-11 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114874212A CN114874212A (en) | 2022-08-09 |
| CN114874212B true CN114874212B (en) | 2023-04-21 |
Family
ID=77378477
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110652955.5A Pending CN113307808A (en) | 2021-06-11 | 2021-06-11 | Preparation method of pentacyclic compound containing benzimidazole |
| CN202210611856.7A Active CN114874212B (en) | 2021-06-11 | 2022-05-31 | Preparation method of pentacyclic compound containing benzimidazole |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110652955.5A Pending CN113307808A (en) | 2021-06-11 | 2021-06-11 | Preparation method of pentacyclic compound containing benzimidazole |
Country Status (1)
| Country | Link |
|---|---|
| CN (2) | CN113307808A (en) |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108250202B (en) * | 2018-01-15 | 2019-10-25 | 陕西师范大学 | 2,3- disubstituted benzenes and imidazo [1,2-a] pyrimidines and its preparation method and application |
-
2021
- 2021-06-11 CN CN202110652955.5A patent/CN113307808A/en active Pending
-
2022
- 2022-05-31 CN CN202210611856.7A patent/CN114874212B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN113307808A (en) | 2021-08-27 |
| CN114874212A (en) | 2022-08-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2596013C (en) | Benzoimidazole derivatives and pharmaceutical composition comprising the same | |
| AU2006346931B2 (en) | 6-1H-imidazo-quinazoline and quinolines derivatives, new potent analgesics and anti-inflammatory agents | |
| JP3256513B2 (en) | Benzimidazole cyclooxygenase-2 inhibitor | |
| JP5061097B2 (en) | Fused heterocyclic compounds | |
| US9199965B2 (en) | Benzoimidazole derivatives and pharmaceutical composition comprising the same | |
| CA2977750A1 (en) | 4-methoxy pyrrole derivatives or salts thereof for preventing or treating gastrointestinal damage | |
| KR20110060910A (en) | 3h-imidazo[4,5-b]pyridine-6-carboxamides as anti-inflammatory agents | |
| CN106946790B (en) | A kind of preparation method of 1,2- substituted benzimidazole analog derivative | |
| CN107973779A (en) | A kind of N-（2- pyridines/pyrimidine radicals）The preparation method of indole derivatives | |
| JP3439643B2 (en) | Benzimidazole compounds | |
| CN114874212B (en) | Preparation method of pentacyclic compound containing benzimidazole | |
| KR101320752B1 (en) | Novel method for preparing benzoimidazole derivatives | |
| CN116947854A (en) | Preparation method of imidazo [2,1-a ] isoquinoline compound | |
| CN113845509B (en) | Synthetic method of indolyl-substituted spiro [ cyclobutane-1,1' -indene ] compound | |
| EP2970210B1 (en) | Pyrazolylbenzo[d]imidazole derivatives | |
| JPH0376318B2 (en) | ||
| CN109897033A (en) | A kind of method synthesizing imidazo containing iodine [1,2a] pyridine compounds and their | |
| CN106749220B (en) | 6 '-substituted benzimidazole -4- substituent methyl indole derivatives of one kind and its preparation and application | |
| CN106749319B (en) | 6 '-- 5-substituent methyl of substituted benzimidazole indole derivatives of one kind and its preparation and application | |
| CN109400629A (en) | Indoles spirooxazine heterocycle compound and preparation method thereof | |
| CN111116464B (en) | (E) -4- (pyridylformylhydrazono) -N-phenylbenzamide antitumor compounds | |
| CN108586436A (en) | Bishydrazide derivative of one kind skeleton containing indoles and its preparation method and application | |
| CN109810112A (en) | A kind of preparation method of indoles simultaneously [2,1-a] phthalazine derivatives | |
| CN108530445A (en) | A kind of synthetic method of 3- cyanoimidazoles simultaneously [1,5-a] quinoline compound | |
| CN103145710B (en) | The synthetic method of indole-imidazole compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |