CN104140415B - Alpha, beta unsaturated ketone compounds containing benzo five-membered unsaturated heterocycle structures as well as preparation method and application of compounds - Google Patents

Alpha, beta unsaturated ketone compounds containing benzo five-membered unsaturated heterocycle structures as well as preparation method and application of compounds Download PDF

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CN104140415B
CN104140415B CN201410242125.5A CN201410242125A CN104140415B CN 104140415 B CN104140415 B CN 104140415B CN 201410242125 A CN201410242125 A CN 201410242125A CN 104140415 B CN104140415 B CN 104140415B
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ethyl
ketone
alkene
propane
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CN104140415A (en
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李卓荣
吴林韬
王真
金洁
易红
季兴跃
薛司徒
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Institute of Medicinal Biotechnology of CAMS
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • C07—ORGANIC CHEMISTRY
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    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C07D235/12—Radicals substituted by oxygen atoms
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/06—Benzimidazoles; Hydrogenated benzimidazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
    • C07D235/14—Radicals substituted by nitrogen atoms
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/56—Benzoxazoles; Hydrogenated benzoxazoles with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/64—Benzothiazoles with only hydrocarbon or substituted hydrocarbon radicals attached in position 2
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Abstract

The invention provides alpha, beta unsaturated ketone compounds containing benzo five-membered unsaturated heterocycle structures as well as a preparation method and an application and use of the compounds. The alpha, beta unsaturated ketone compounds containing the benzo five-membered unsaturated heterocycle structures have the structure of a formula (I). In addition, the invention further provides a method for preparing the compounds and a pharmaceutical composition containing the components as active components. In vitro activity tests show that the compounds provided by the invention show a remarkable inhibiting effect on tumor cells. Therefore, the invention lays a foundation for lucubrating and developing anti-tumor medicines in the future and meanwhile further provides a new technical means for treating tumor diseases.

Description

α containing benzo five-membered unsaturated heterocycle structure, beta unsaturated ketone class compound and its Preparation method and application
Technical field
The present invention relates to a class contains the α of benzo five-membered unsaturated heterocycle structure, beta unsaturated ketone class compound or it is medicinal Salt, and disclose the described α containing benzo five-membered unsaturated heterocycle structure, the system of beta unsaturated ketone class compound or pharmaceutically acceptable salt thereof Preparation Method, the invention still further relates to the described α containing benzo five-membered unsaturated heterocycle structure, beta unsaturated ketone class compound or its medicine With application in antitumor for the salt and containing such compound as active component pharmaceutical composition.
Background technology
In recent years, chemotherapy of tumors achieved suitable progress, and tumor patient life span is obviously prolonged, particularly dialogue The treatment of blood disease, malignant lymphoma etc. has a breakthrough, but to harm human life and health most serious, account for malignant tumour more than 90% The treatment of solid tumor fail to reach satisfied effect.Pharmacy man and oncologist more and more profoundly recognize：Tumour to be improved The curative effect for the treatment of, it is necessary to set about from the mechanism of tumor development, could obtain new breakthrough progress.In recent years, molecular weight tumor Learn, the development of molecular pharmacology makes tumour essence progressively illustrate；Quickly screening, combinatorial chemistry, genetic engineering etc. are advanced on a large scale The invention of technology and application acceleration drug development process；The research and development of antineoplastic have been enter into brand-new epoch.
The development strategy of current antineoplastic have following some：1. to account for based on the solid tumor of malignant tumour more than 90% Attack object；2. find active component from natural products；3. it is directed to the mechanism of tumor development, find new molecular action (enzyme, acceptor, gene) target spot；4. quickly screen (High-through put screening) on a large scale；5. the leading of new technology Enter and apply：Combinatorial chemistry, structure biology, CAD, genetic engineering, DNA chip, pharmacogenomics (work( Energy genomics is combined with pharmacology) etc..
Antineoplastic just from traditional cytotoxic drug, send out by the new type antineoplastic medicine to the too many levels effect for mechanism Exhibition, the novel targets of antitumor action of concern and corresponding new antitumoral agent or means have both at home and abroad at present：1. turned with cell signal Leading molecule is target spot：Including protein tyrosine kinase inhibitor, farnesyl transferase inhibitor, MAPK signal transduction pathway inhibitor, Cell cycle regulating agent；2. with new vessels as target spot：Angiogensis inhibitor；3. reduce cancer cell to come off, adhere to and substrate Membrane degradation：Antimetastatic agents；4. with Telomerase as target spot：Telomerase inhibitor；5. it is directed to tumor cell drug resistance：Reversal agent of drug resistance；⑥ Promote malignant cell to ripe differentiation：Differentiating inducer；7. specific killing cancer cell：(antibody or toxin) targeted therapy；8. strengthen The curative effect of radiation and chemotherapy：Oncotherapy sensitizer；9. improve or adjust body's immunity：BRM；10. it is directed to Oncogene and tumor suppressor gene：Gene therapy imports wild type tumor suppressor gene, suicide gene, overriding resistance gene and antisense oligonucleotides Though acid, the research of oncogene engineering have made great progress, the medicine clinically using at present lacks specificity, generally There is more serious side effect.
Oncogene MDM2 (mouse double minute chromosome 2) is the gene from the double minute chromosome of conversion mouse cell lines such as Cahilly The gene finding in amplification, is second in 3 genes cloning on this chromosome, in mouse and people's (homologous gene HDM2 there is expression in a lot of tissues), and have different mRNA splicing forms.Oncogene screening finds, MDM2 is excessive It is injected into meeting trigger cell growth in athymic mouse body in the mouse cell of expression out of control, thus display MDM2 is a kind of cancer base Cause.The albumen of MDM2 coding can combine and suppress the function of p53 with suppressor gene protein p53, and more than 30% sarcoma has MDM2 Amplification, though the no gene magnification of the human tumor of about 5%-10% has MDM2 to over-express.In recent years to oncogene and suppression cancer base The further investigation of cause makes the specific aim of oncotherapy greatly reinforce, and makes that exploitation is new and effective, low toxicity cancer therapy drug is possibly realized.
The present invention on the basis of the studies above, according to tumour cell correlation molecule study mechanism latest developments and to front The analysis of phase experimental data, further design, synthesis and screening a series of can with below general formula represent containing benzo five-membered The α of unsaturated heterocycle structure, beta unsaturated ketone class compound (formula I), through system architecture transformation and structure activity study, carry Highly-water-soluble, metabolic stability, improve activity further, provide new guide structure for oncotherapy, for developing further New type antineoplastic medicine lays the foundation.
Content of the invention
The invention provides having the α containing benzo five-membered unsaturated heterocycle structure of formula (I) structure, beta unsaturated ketone Class compound and its pharmaceutical salts, such compound has anti-tumour cell proliferative activity, can be used for treating cancer.
Present invention also offers the system of the described α containing benzo five-membered unsaturated heterocycle structure, beta unsaturated ketone class compound Preparation Method.
Present invention also offers the described α containing benzo five-membered unsaturated heterocycle structure, beta unsaturated ketone class compound are being controlled Treat cancer and the application of the relative patient aspect being led to by cancer.
Present invention also offers can treating cancer pharmaceutical composition, this pharmaceutical composition with above-mentioned containing benzo five-membered not The α of saturated heterocyclic structure, beta unsaturated ketone class compound or pharmaceutically acceptable salt thereof are as active component.
Major design synthesis of the present invention is substituted with diverse location on benzo five-membered unsaturated heterocycle (3-, 4-, 5-, 6-) α, the benzimidazole of beta unsaturated ketone, benzothiazole or benzothiazole be parent nucleus the compound shown in formula I and in 2- position Introduce the compound group with substituted α, beta unsaturated ketone structure.Discuss and be connected with alkyl, halogen on benzo five-membered unsaturated heterocycle The different substituents such as element, alkoxyl, hydroxyl, and 2- position introduces the α with different replacements, beta unsaturated ketone structure resists to compound The impact of tumor promotion.Designed target compound structure, can on the benzo unsaturated heterocycle in formula I as shown in formula I With with substituents such as alkyl, alkoxyl, hydroxyls.
The invention provides having the benzo five-membered unsaturated heterocycle compound or pharmaceutically acceptable salt thereof of structure as shown in formula I,
X represents O or S or NH or N-R or CH2, wherein R is alkyl or the replacement alkyl of 1-5 carbon；
R1Represent following group：H, hydroxyl, the saturation of 1-18 carbon or unsaturated alkyl (C1-18), alkoxyl, halogen, mercapto Base or substituted sulfhydryl；
R2Represent following group：H, hydroxyl, the saturation of 1-18 carbon or unsaturated alkyl (C1-18), alkoxyl, halogen, mercapto Base or substituted sulfhydryl；
R3Represent following group：H, hydroxyl, the saturation of 1-18 carbon or unsaturated alkyl (C1-18), alkoxyl, halogen, mercapto Base or substituted sulfhydryl；
R4Represent following group：H, hydroxyl, the saturation of 1-18 carbon or unsaturated alkyl (C1-18), alkoxyl, halogen, mercapto Base or substituted sulfhydryl；
R5Represent following group：H, cyclohexyl, phenyl or substituted phenyl, pyridine radicals or substituted pyridinyl, furyl or Substituted furan base, thienyl substituted thiophene base, pyrrole radicals or substituted azole base；
Described in defined above：
" halogen " may refer to chlorine, bromine and three kinds of elements of iodine.
Substituted sulfhydryl is the sulfydryl of the replacement of the alkyl containing 1-5 carbon it is preferred that described substituted sulfhydryl is sulphomethyl Or thio-ethyl.
The α containing benzo five-membered unsaturated heterocycle structure, beta unsaturated ketone class compound or its medicine being provided according to the present invention With salt, its corresponding benzimidazole/azoles/thiazole or Benzazole compounds, nude mice Anticancer effect in vivo result of study shows, The compound of the present invention has the obvious effect suppressing people's HCT116 cell.
As non-limiting example, the α containing benzo five-membered unsaturated heterocycle structure of the present invention, beta unsaturated ketone Class compound can be selected from particular compound listed by table 1：
Present invention also offers the synthetic method of formula (I) related compound.
Intermediate (III) is obtained first using method shown in route 1, wherein, M is amino, hydroxyl or sulfydryl；R1, R2, R3, R4Definition with claim 1, route 1：
Synthetic method is：With the aniline (II) of replacement as initiation material, select organic acid such as lactic acid to be solvent, add inorganic Acid, example hydrochloric acid, obtain III after intensification stirring reaction.Further, described intermediate (III) can be reacted as follows respectively and be obtained Corresponding generalformula-compound：
A：When in Formulas I structure, X is NH, O and S, intermediate (III) can be reacted as follows obtains corresponding formula I chemical combination Thing；R1, R2, R3, R4, R5Definition with claim 1；
Intermediate (III) in acidic aqueous solution oxidized dose as chromium trioxide oxidation after in the presence of alkali with replace aldehyde Isolate and purify after reaction and obtain target compound IV.
B：When in Formulas I structure, X is N-R, intermediate (III) can be reacted as follows obtains corresponding generalformula-compound, its In, R1, R2, R3, R4, R5Definition with claim 1；
Present invention also offers the pharmaceutical composition containing described compound, can the above-mentioned chemical combination containing therapeutically effective amount Thing or its pharmaceutical salts are active component, and contain one or more pharmaceutically acceptable carrier.
The type I compound of the present invention and pharmaceutical composition can be used for preparing antineoplastic.
The pharmaceutical composition that the present invention provides can be the various administrations of the conventional production process preparation according to pharmaceutical field Formulation, for example, make active component mix with one or more carrier, is then made into required formulation.For example can be by compound The mixture tablets of itself or itself and pharmaceutically acceptable excipient, diluent etc., capsule, the form of granule, powder or syrup Oral administration or in the form of injection non-oral administration.The pharmaceutical composition of the present invention preferably comprises weight than for 0.1%- 99.5% active component, most preferably weight is than the active component for 0.5%-99.5%.Above-mentioned preparation can be by routine Prepared by pharmaceutical methods.The example of available medicinal adjuvant includes excipient (such as carbohydrate derivative such as lactose, sucrose, glucose, sweet Dew sugar alcohol and D-sorbite；Starch derivatives such as cornstarch, potato starch, dextrin and CMS；Cellulose derivative is such as Avicel cellulose, hydroxypropyl cellulose, carboxymethylcellulose calcium, calcium carboxymethylcellulose, sodium carboxymethylcellulose；Arabic gum；Right The sugared acid anhydride of rotation；Silicate derivative such as Neusilin US2；Phosphate derivative such as calcium phosphate；Carbonate derivative such as calcium carbonate；Sulphur Acid salt derivant such as calcium sulfate etc.), adhesive (such as gelatin, polyvinylpyrrolidone and polyethylene glycol), disintegrant (for example fine Dimension plain derivative such as sodium carboxymethylcellulose, polyvinylpyrrolidone), lubricant (for example talcum, calcium stearate, magnesium stearate, Spermaceti, boric acid, Sodium Benzoate, leucine), stabilizer (methyl p-hydroxybenzoate, propylparaben etc.), flavouring (for example conventional sweetener, acid and spices etc.), diluent and parenteral solution are with solvent (such as water, ethanol and glycerine etc.).
Specific embodiment
According to foregoing route and method, can stablize, repeatable synthesize obtain the compounds of this invention.Tie below Close specific embodiment to further describe the present invention, advantages of the present invention and feature will be with description and apparent.But it is real It is only exemplary for applying example, does not constitute any restriction to the scope of the present invention.It will be understood by those skilled in the art that To modify to the details of technical solution of the present invention and form or can replace under without departing from the spirit and scope of the present invention, but this A little modifications and replacement each fall within protection scope of the present invention.
Effect experiment
Test an anti tumor activity in vitro test
With the anti tumor activity in vitro test model having built, detailed process is：Take 96 porocyte culture plates, in every hole Plus 100 μ l contain 5000 target cells nutrient solution (the DMEM nutrient solution containing 10% calf serum), at 37 DEG C, 5%CO2Culture In case, culture allows cell attachment for 24 hours.With 5 times of successives diluted compounds storing solution (100mM) of DMEM nutrient solution, every hole adds 0.1ml liquid, 3 repeating holes of each dilution factor.3 blank control wells, every hole adds 0.1ml DMEM nutrient solution.At 37 DEG C, 5% CO2Incubator in cultivate 48 hours.Every hole adds 20 μ l MTT dye liquors, at 37 DEG C, 5%CO2Saturation vapour carbon dioxide culture Continue culture 3～4 hours in case.Every hole adds the DMSO solution of 150 μ l, and vibration on the oscillator mixes 5min, allows reduzate Fully dissolve.Put and measure optical density (OD) value, Detection wavelength 570nm on enzyme connection detector.With OD value, sample dilution is mapped, Standard of comparison curve and testing sample curve can try to achieve the content of cell factor in testing sample, and result is as shown in table 1.
The structure of table 1 invention compound and anti tumor activity in vitro
Embodiment 1:The system of 1- (7- chloro- 1H- benzimidazolyl-2 radicals-ethyl) -3- phenyl-propane -2- alkene -1- ketone (compound 1) Standby
5.4g (0.05mol) o-phenylenediamine, 4.5g (0.05mol) lactic acid and 4mol/L is added in the round-bottomed flask of 50mL Hydrochloric acid 20mL, is heated to reflux 1.5h, is cooled to room temperature.It is neutralized to purple litmus paper with concentrated ammonia liquor to redden, suction filtration goes out solid, use Water recrystallizes (63%).In the three-neck flask of 50mL add 2- (Alpha-hydroxy) ethyl benzo imidazole 3.24g (0.02mol) and The glacial acetic acid of 15mL, is heated to when 90 DEG C dripping CrO in three-neck flask3The aqueous solution, after completion of dropping, at 105 DEG C of temperature control Then reactant liquor is poured in the beaker filling 200mL water by stirring reaction 10min, stirring a moment, suction filtration, and filtrate is extracted with chloroform Take 3 times, chloroform layer is merged, anhydrous magnesium sulfate is dried, filtrate rotation is evaporated to obtain yellow solid, with re crystallization from toluene, yield： 63%, 50ml round-bottomed flask adds 95% ethanol and 3.20g (0.02mol) the 2- acetyl group benzimidazole of 20ml, stirring About 10min makes solid be completely dissolved, and adds the sodium hydrate aqueous solution of 8ml10%, and stirring is lower to add 0.02mol benzaldehyde, After a period of time, system separates out a large amount of solids, detects reaction end with TLC, has reacted rear suction filtration and obtained solid, yield:77%
1HNMR(CDCl3)δ:10.50 (brs, 1H), 8.06 (dd, J=15.9Hz, J=55.2Hz, 2H), 7.96 (d, J= 8.07Hz, 1H), 7.69 (d, J=7.93Hz, 2H), 7.45-7.38 (m, 5H) MS (EI+)m/z:249[M]+.
Embodiment 2：1-'s (1H- benzimidazolyl-2 radicals-ethyl) -3- (2- bromophenyl) propane -2- alkene -1- ketone (compound 2) Preparation
With compound 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo miaow Azoles -2- ethyl) -3- (2- bromophenyl) propane -2- alkene -1- ketone (51%).
1HNMR(CDCl3)δ:11.77(brs,1H),8.73(s,1H),8.62-8.59(d,1H),7.94-7.92(t, 2H),7.77-7.75(t,1H),7.71-7.70(d,1H),7.48(s,2H),7.40-7.39(t,1H),7.32-7.30(d, 1H)MS(EI+)m/z:326[M]+.
Embodiment 3：1-'s (1H- benzimidazolyl-2 radicals-ethyl) -3- (3- pyridine radicals) propane -2- alkene -1- ketone (compound 3) Preparation
With compound 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo miaow Azoles -2- ethyl) -3- (3- pyridine radicals) propane -2- alkene -1- ketone (78%)
1HNMR(CDCl3) 9.31 (brs, 1H), 8.02 (dd, J=15.9Hz, J=55.2Hz, 2H), 7.88 (d, J= 8.07Hz, 1H), 7.60 (d, J=7.93Hz, 2H), 7.17-7.02 (m, 5H) MS (EI+)m/z:249[M]+.
Embodiment 4：1- (1H- benzimidazolyl-2 radicals-ethyl) -3- (1H, 2- pyrrole radicals) propane -2- alkene -1- ketone (compound 4) Preparation
With compound 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo miaow Azoles -2- ethyl) -3- (1H, 2- pyrrole radicals) propane -2- alkene -1- ketone (86%)
1HNMR(CDCl3)δ:10.20 (brs, 1H), 9.28 (brs, 1H), 7.86 (d, J=7.96Hz, 1H), 7.82 (s, 2H),7.47-7.42(m,3H),7.00(s,1H),6.74(s,1H),6.34(s,1H)MS(EI+)m/z:237[M]+.
Embodiment 5：1-'s (1H- benzimidazolyl-2 radicals-ethyl) -3- (3- fluorophenyl) propane -2- alkene -1- ketone (compound 5) Preparation
With compound 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo miaow Azoles -2- ethyl) -3- (3- fluorophenyl) propane -2- alkene -1- ketone (44%).
1HNMR(CDCl3)δ:9.87(brs,1H),8.73(s,1H),8.62-8.59(d,1H),7.93(t,2H),7.86- 7.81(t,1H),7.75-7.72(d,1H),7.60(s,1H),7.52-7.49(t,1H),7.47-7.45(d,1H),7.40(s, 1H)MS(EI+)m/z:266[M]+.
Embodiment 6：1- (1H- benzimidazolyl-2 radicals-ethyl) -3- (1- methyl, 2- pyrrole radicals) propane -2- alkene -1- ketone (chemical combination Thing 6) preparation
With compound 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo miaow Azoles -2- ethyl) -3- (1- methyl, 2- pyrrole radicals) propane -2- alkene -1- ketone (46%)
1HNMR(CDCl3)δ:9.26 (brs, 1H), 7.79 (d, J=7.96Hz, 1H), 7.60 (s, 2H), 7.45-7.43 (m,3H),7.00(s,1H),6.58(s,1H),6.26(s,1H),3.28(s,3H)MS(EI+)m/z:251[M]+.
Embodiment 7：1- (1H- benzimidazolyl-2 radicals-ethyl) -3- (3- aminomethyl phenyl) propane -2- alkene -1- ketone (compound 7) Preparation
With compound 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo miaow Azoles -2- ethyl) -3- (3- aminomethyl phenyl) propane -2- alkene -1- ketone (60%).
1HNMR(CDCl3)δ:9.87(brs,1H),8.73(s,1H),8.62-8.59(d,1H),7..70(t,2H), 7.54-7.52 (t, 1H), 7.71-7.70 (d, 1H), 7.48 (s, 1H), 7.32-7.30 (d, 1H), 7.07 (s, 1H), 3.28 (s, 3H)MS(EI+)m/z:262[M]+.
Embodiment 8:1- (1H- benzimidazolyl-2 radicals-ethyl) -3- (2- aminomethyl phenyl) propane -2- alkene -1- ketone (compound 8) Preparation
With compound 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo miaow Azoles -2- ethyl) -3- (2- aminomethyl phenyl) propane -2- alkene -1- ketone (43%).
1HNMR(CDCl3)δ:11.77(brs,1H),7.93(s,1H),7.72-7.69(d,1H),7.47(s,2H), 7.40-7.38(t,1H),7.30-7.27(d,1H),7.15(s,2H),7.03-6.99(t,1H),6.88(s,1H),4.17(s, 3H)MS(EI+)m/z:262[M]+.
Embodiment 9：1-'s (1H- benzimidazolyl-2 radicals-ethyl) -3- (2- fluorophenyl) propane -2- alkene -1- ketone (compound 9) Preparation
With compound 2- acetyl benzimidazole as raw material, according to embodiment 1 method reaction obtain 1- (1H- benzimidazole- 2- ethyl) -3- (2- fluorophenyl) propane -2- alkene -1- ketone (89%).
1HNMR(CDCl3)δ:9.87(brs,1H),8.73(s,1H),8.62-8.59(d,1H),7.93(t,2H),7.86- 7.81(t,1H),7.70-7.68(d,1H),7.60(s,1H),7.50(s,1H),7.47-7.45(d,1H),7.40(s,1H)MS (EI+)m/z:266[M]+.
Embodiment 10：1- (1H- benzimidazolyl-2 radicals-ethyl) -3- (3- chlorphenyl) propane -2- alkene -1- ketone (compound 10)； Preparation
With compound 2- acetyl benzimidazole as raw material, according to embodiment 1 method reaction obtain 1- (1H- benzimidazole- 2- ethyl) -3- (3- chlorphenyl) propane -2- alkene -1- ketone (81%)
1HNMR(CDCl3)δ:9.87(brs,1H),8.73(s,1H),8.62-8.59(d,1H),7.93(t,2H),7.80- 7.77(t,1H),7.71-7.68(d,1H),7.60(s,1H),7.52-7.49(t,1H),7.47-7.45(d,1H),7.37(s, 1H)MS(EI+)m/z:282[M]+.
Embodiment 11：1- (1H- benzimidazolyl-2 radicals-ethyl) -3- (3- bromophenyl) propane -2- alkene -1- ketone (compound 11) Preparation
With compound 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo miaow Azoles -2- ethyl) -3- (3- bromophenyl) propane -2- alkene -1- ketone (93%).
1HNMR(CDCl3)δ:10.12(brs,1H),8.90(s,1H),8.21-8.18(d,1H),7.77(t,2H), 7.69-7.66(t,1H),7.60-7.57(d,1H),7.54(s,1H),7.50-7.47(t,1H),7.40(s,1H),7.35(s, 1H)MS(EI+)m/z:326[M]+.
Embodiment 12:1- (1H- benzimidazolyl-2 radicals-ethyl) -3- (4- fluorophenyl) propane -2- alkene -1- ketone (compound 12) Preparation
With compound 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo miaow Azoles -2- ethyl) -3- (4- fluorophenyl) propane -2- alkene -1- ketone (85%).
1HNMR(CDCl3)δ:10.50 (brs, 1H), 8.17 (dd, J=15.9Hz, J=55.2Hz, 2H), 7.98 (d, J= 8.07Hz, 1H), 7.72 (d, J=7.93Hz, 2H), 7.56-7.54 (m, 5H) MS (EI+)m/z:266[M]+.
Embodiment 13:1- (1H- benzimidazolyl-2 radicals-ethyl) -3- (4- bromophenyl) propane -2- alkene -1- ketone (compound 13) Preparation
With compound 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo miaow Azoles -2- ethyl) -3- (4- bromophenyl) propane -2- alkene -1- ketone (59%).
1HNMR(CDCl3)δ:11.70 (brs, 1H), 8.03 (dd, J=15.9Hz, J=12Hz, 2H), 7.90 (d, J= 8.07Hz, 1H), 7.72 (d, J=7.93Hz, 2H), 7.47-7.44 (m, 5H) MS (EI+)m/z:326[M]+.
Embodiment 14:1- (1H- benzimidazolyl-2 radicals-ethyl) -3- (2- methoxyphenyl) propane -2- alkene -1- ketone (compound 14) preparation
With compound 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo miaow Azoles -2- ethyl) -3- (2- methoxyphenyl) propane -2- alkene -1- ketone (90%).
1HNMR(CDCl3)δ:11.77(brs,1H),7.93(s,1H),7.72-7.69(d,1H),7.47(s,2H), 7.40-7.38(t,1H),7.30-7.27(d,1H),7.15(s,2H),7.03-6.99(t,1H),6.88(s,1H),3.77(s, 3H)MS(EI+)m/z:278[M]+.
Embodiment 15:1- (1H- benzimidazolyl-2 radicals-ethyl) -3- (3- methoxyphenyl) propane -2- alkene -1- ketone (compound 15) preparation
With compound 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo miaow Azoles -2- ethyl) -3- (3- methoxyphenyl) propane -2- alkene -1- ketone (77%).
1HNMR(CDCl3)δ:9.89 (brs, 1H), 7.64 (s, 1H), 7.50 (d, J=8.07Hz, 2H), 7.47 (s, 1H), 7.40-7.38 (t, J=7.93,1H), 7.30-7.27 (d, J=7.2,1H), 7.15 (s, 2H), 7.11-7.00 (t, 1H), 6.67(s,1H),3.01(s,3H).MS(EI+)m/z:278[M]+.
Embodiment 16:1- (1H- benzimidazolyl-2 radicals-ethyl) -3- (2- thienyl) propane -2- alkene -1- ketone (compound 16) Preparation
With compound 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo miaow Azoles -2- ethyl) -3- (2- thienyl) propane -2- alkene -1- ketone (71%).
1HNMR(CDCl3)δ:8.09 (d, J=15.69Hz, 1H), 7.93 (d, J=8.15Hz, 1H), 7.69 (d, J= 15.69Hz, 1H), 7.56 (s, 1H), 7.47-7.37 (m, 3H), 6.81 (d, J=3.27Hz, 1H), 6.53 (dd, J= 1.63Hz, J=3.08Hz, 1H) MS (EI+)m/z:254[M]+.
Embodiment 17:1- (1H- benzimidazolyl-2 radicals-ethyl) -3- (4- methylthiophenyi) propane -2- alkene -1- ketone (chemical combination Thing 17) preparation
With compound 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo miaow Azoles -2- ethyl) -3- (4- methylthiophenyi) propane -2- alkene -1- ketone (71%).
1HNMR(CDCl3)δ:10.47(brs,1H),8.08-7.96(m,3H),7.83-7.34(m,7H),2.41(s,3H) MS(EI+)m/z:294[M]+.
Embodiment 18:1- (1H- benzimidazolyl-2 radicals-ethyl) -3- (4- aminomethyl phenyl) propane -2- alkene -1- ketone (compound 18) preparation
With compound 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo miaow Azoles -2- ethyl) -3- (4- aminomethyl phenyl) propane -2- alkene -1- ketone (51%).
1HNMR(CDCl3)δ:9.70 (brs, 1H), 8.12 (dd, J=15.9Hz, J=12Hz, 2H), 7.80 (d, J= 8.07Hz, 1H), 7.72 (d, J=7.93Hz, 2H), 7.31-7.26 (m, 5H), 2.01 (s, 3H) MS (EI+)m/z:262[M]+.
Embodiment 19:The system of 1- (1H- benzimidazolyl-2 radicals-ethyl) -3- cyclohexyl propane -2- alkene -1- ketone (compound 19) Standby
With compound 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo miaow Azoles -2- ethyl) -3- cyclohexyl propane -2- alkene -1- ketone (84%).
1HNMR(CDCl3)δ:9.70 (brs, 1H), 7.70 (d, J=8.07Hz, 2H), 7.28 (d, J=7.93Hz, 2H), 6.87-6.80 (m, 2H), 2.11 (d, J=7.2Hz, 1H), 2.11 (d, J=7.2Hz, 1H), 1.56-1.52 (m, 4H), 1.46- 1.22(m,4H),1.37-1.30(m,4H)m/z:254[M]+.
Embodiment 20:The preparation of 1- (1H- benzimidazolyl-2 radicals-ethyl) -3- phenyl-propane -2- alkene -1- ketone (compound 20)
With compound 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo miaow Azoles -2- ethyl) -3- phenyl-propane -2- alkene -1- ketone (84%).
1HNMR(CDCl3)δ:11.01 (brs, 1H), 7.84 (s, 1H), 7.73-7.70 (d, J=7.93Hz1H), 7.47 (s, 2H), 7.40-7.38 (t, 1H), 7.25-7.21 (d, J=7.93Hz2H), 7.18 (s, 2H), 7.10-7.06 (t, 1H), 6.88(s,1H)MS(EI+)m/z:248[M]+.
Embodiment 21:1- (1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (compound 21) Preparation
With compound for 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo Imidazoles -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (80%).
1HNMR(CDCl3)δ:8.17 (s, 1H), 7.72 (d, J=8.15Hz, 1H), 7.59 (d, J=15.69Hz, 1H), 7.51 (s, 1H), 7.42-7.35 (m, 3H), 6.81 (d, J=3.27Hz, 1H), 6.53 (dd, J=1.63Hz, J=3.08Hz, 1H)MS(EI+)m/z:238[M]+.
Embodiment 22:1- (1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (compound 22) Preparation
With compound for 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo Imidazoles -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (45%).
1HNMR(CDCl3)δ:9.50 (brs, 1H), 8.12 (dd, J=15.9Hz, J=12Hz, 2H), 7.80 (d, J= 8.07Hz, 1H), 7.72 (d, J=7.93Hz, 2H), 7.66-7.59 (m, 5H) m/z:282[M]+.
Embodiment 23:1- (1H- benzimidazolyl-2 radicals-ethyl) -3- (4- dimethylamino phenyl) propane -2- alkene -1- ketone (chemical combination Thing 23) preparation
With compound for 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo Imidazoles -2- ethyl) -3- (4- dimethylamino phenyl) propane -2- alkene -1- ketone (47%).
1HNMR(CDCl3)δ:9.12 (brs, 1H), 8.26 (d, J=12Hz, 2H), 7.74 (d, J=8.07Hz, 1H), 7.63 (d, J=7.2Hz, 2H), 7.57 (s, 1H), 7.49-7.46 (m, 3H), 6.77 (d, J=3.27Hz, 1H), 2.85 (s, 6H)MS(EI+)m/z:291[M]+.
Embodiment 24:The preparation of 1,3- bis- (1H- benzimidazolyl-2 radicals-ethyl) propane -2- alkene -1- ketone (compound 24)
With compound for 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1,3- bis- (1H- Benzimidazolyl-2 radicals-ethyl) propane -2- alkene -1- ketone (53%).
1HNMR(CDCl3)δ:9.70 (brs, 2H), 7.70 (d, J=8.07Hz, 4H), 7.28 (d, J=7.93Hz, 4H), 6.87-6.80(m,2H)MS(EI+)m/z:288[M]+.
Embodiment 25:1- (1H- benzimidazolyl-2 radicals-ethyl) -3- (4- methoxyphenyl) propane -2- alkene -1- ketone (compound 25) preparation
With compound for 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo Imidazoles -2- ethyl) -3- (4- methoxyphenyl) propane -2- alkene -1- ketone (55%).
1HNMR(CDCl3)δ:9.89 (brs, 1H), 8.23 (d, J=12Hz, 2H), 7.80 (d, J=8.07Hz, 1H), 7.53 (d, J=7.93Hz, 2H), 7.31-7.28 (m, 5H), 3.03 (s, 3H) MS (EI+)m/z:278[M]+.
Embodiment 26:1- (1H- benzimidazolyl-2 radicals-ethyl) -3- (3- nitrobenzophenone) propane -2- alkene -1- ketone (compound 26) preparation
With compound 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo miaow Azoles -2- ethyl) -3- (3- nitrobenzophenone) propane -2- alkene -1- ketone (77%).
1HNMR(CDCl3)δ:9.69(brs,1H),8.70(s,1H),8.24-8.20(d,1H),7.80(t,2H),7.68 (s, 1H), 7.60-7.57 (d, J=5.1Hz1H), 7.54 (s, 1H), 7.50-7.47 (t, 1H), 7.40 (s, 1H), 7.35 (s, 1H)MS(EI+)m/z:293[M]+.
Embodiment 27:1- (7- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) -3- phenyl-propane -2- alkene -1- ketone (compound 27) Preparation
6.1g (0.05mol) 3- methylbenzene -1,2- diamines, 4.5g (0.05mol) lactic acid is added in the round-bottomed flask of 50mL And 4mol/L hydrochloric acid 20mL, it is heated to reflux 3h, be cooled to room temperature.It is neutralized to purple litmus paper with concentrated ammonia liquor to redden, suction filtration Go out solid, recrystallize (72%) with water.1- (7- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) alcohol is added in the three-neck flask of 50mL The glacial acetic acid of 3.52g (0.02mol) and 15mL, is heated to when 90 DEG C dripping CrO in three-neck flask3The aqueous solution, drip Bi Hou, stirring reaction 20min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, in stirring a moment, take out Filter, filtrate, with chloroform extraction 3 times, chloroform layer is merged, and anhydrous magnesium sulfate is dried, and filtrate rotation is evaporated to obtain yellow solid, uses first Benzene recrystallizes, yield：84%, 50ml round-bottomed flask adds 95% ethanol and 3.48g (0.02mol) 1- (the 7- first of 20ml Base -1H- benzimidazolyl-2 radicals-ethyl) ketone, stir about 10min makes solid be completely dissolved, adds the NaOH water of 8ml10% Solution, stirring is lower to add 0.02mol benzaldehyde, and after a period of time, system separates out a large amount of solids, detects reaction end with TLC, instead Rear suction filtration has been answered to obtain solid, yield:80%
1HNMR(CDCl3)δ:8.76 (brs, 1H), 7.91 (d, J=12Hz, 2H), 7.80 (d, J=8.07Hz, 1H), 7.53 (d, J=7.93Hz, 2H), 7.31-7.28 (m, 5H), 2.47 (s, 3H) MS (EI+)m/z:262[M]+.
Embodiment 28:1- (7- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (is changed Compound 28) preparation
With compound 1- (7- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 27 Obtain 1- (7- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (45%).
1HNMR(CDCl3)δ:8.94 (brs, 1H), 7.83 (d, J=12Hz, 2H), 7.45 (d, J=7.93Hz, 2H), 7.31-7.28(m,5H),2.47(s,3H)MS(EI+)m/z:296[M]+.
Embodiment 29:1- (7- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (is changed Compound 29) preparation
With compound 1- (7- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 27 Obtain 1- (7- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (59%).
1HNMR(CDCl3)δ:9.50 (brs, 1H), 8.17 (s, 1H), 7.96 (d, J=8.07Hz, 1H), 7.58 (d, J= 7.93Hz,2H),7.41-7.37(m,5H),2.13(s,3H)MS(EI+)m/z:263[M]+.
Embodiment 30:1- (7- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (is changed Compound 30) preparation
With compound 1- (7- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 27 Obtain 1- (7- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (43%).
1HNMR(CDCl3)δ:9.12 (brs, 1H), 8.34 (s, 1H), 7.67 (d, J=8.07Hz, 1H), 7.49 (d, J= 7.93Hz,2H),7.41-7.30(m,5H),2.24(s,3H)MS(EI+)m/z:263[M]+.
Embodiment 31:1- (7- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (is changed Compound 31) preparation
With compound 1- (7- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 27 Obtain 1- (7- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (43%).
1HNMR(CDCl3)δ:8.17 (s, 1H), 7.72 (d, J=8.15Hz, 1H), 7.59 (d, J=15.69Hz, 1H), 7.51 (s, 1H), 7.42-7.35 (m, 3H), 6.53 (dd, J=1.63Hz, J=3.08Hz, 1H), 2.18 (s, 3H) MS (EI+) m/z:252[M]+.
Embodiment 32:1- (6- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) -3- phenyl-propane -2- alkene -1- ketone (compound 32) Preparation
6.1g (0.05mol) 4- methylbenzene -1,2- diamines, 4.5g (0.05mol) lactic acid is added in the round-bottomed flask of 50mL And 4mol/L hydrochloric acid 20mL, it is heated to reflux 3h, be cooled to room temperature.It is neutralized to purple litmus paper with concentrated ammonia liquor to redden, suction filtration Go out solid, recrystallize (57%) with water.1- (6- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) alcohol is added in the three-neck flask of 50mL The glacial acetic acid of 3.52g (0.02mol) and 15mL, is heated to when 90 DEG C dripping CrO in three-neck flask3The aqueous solution, drip Bi Hou, stirring reaction 20min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, in stirring a moment, take out Filter, filtrate, with chloroform extraction 3 times, chloroform layer is merged, and anhydrous magnesium sulfate is dried, and filtrate rotation is evaporated to obtain yellow solid, uses first Benzene recrystallizes, yield：89%, 50ml round-bottomed flask adds 95% ethanol and 3.48g (0.02mol) 1- (the 6- first of 20ml Base -1H- benzimidazolyl-2 radicals-ethyl) ketone, stir about 10min makes solid be completely dissolved, adds the NaOH water of 8ml10% Solution, stirring is lower to add 0.02mol benzaldehyde, and after a period of time, system separates out a large amount of solids, detects reaction end with TLC, instead Rear suction filtration has been answered to obtain solid, yield:76%.
1HNMR(CDCl3)δ:8.61 (brs, 1H), 7.91 (d, J=12Hz, 2H), 7.80 (d, J=8.07Hz, 1H), 7.53(s,1H),7.49(s,1H),7.35-7.26(m,5H),2.20(s,3H)MS(EI+)m/z:262[M]+.
Embodiment 33:1- (6- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (is changed Compound 33) preparation
With compound 1- (7- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 27 Obtain 1- (6- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (83%).
1HNMR(CDCl3)δ:8.37 (s, 1H), 7.64 (d, J=8.15Hz, 1H), 7.60 (d, J=12Hz, 1H), 7.51 (s, 1H), 7.42-7.35 (m, 3H), 7.18 (d, J=3.27Hz, 1H), 6.53 (dd, J=1.63Hz, J=3.08Hz, 1H) MS (EI+)m/z:252[M]+.
Embodiment 34:1- (6- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (is changed Compound 34) preparation
With compound 1- (7- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 27 Obtain 1- (6- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (32%).
1HNMR(CDCl3)δ:9.31 (brs, 1H), 8.02 (dd, J=15.9Hz, J=55.2Hz, 2H), 7.88 (d, J= 8.07Hz, 1H), 7.37 (d, J=7.93Hz, 2H), 7.14-7.09 (m, 4H), 2.71 (s, 3H) MS (EI+)m/z:263[M]+.
Embodiment 35:1- (6- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (is changed Compound 35) preparation
With compound 1- (7- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 27 Obtain 1- (6- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (61%).
1HNMR(CDCl3)δ:9.50 (brs, 1H), 8.12 (dd, J=15.9Hz, J=12Hz, 2H), 7.80 (d, J= 8.07Hz, 1H), 7.72 (d, J=7.93Hz, 1H), 7.66-7.59 (m, 5H), 2.86 (s, 3H) MS (EI+)m/z:296[M]+.
Embodiment 36:1- (6- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (is changed Compound 36) preparation
With compound 1- (7- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 27 Obtain 1- (6- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone
1HNMR(CDCl3)δ:10.50 (brs, 1H), 8.06 (dd, J=15.9Hz, J=55.2Hz, 1H), 7.96 (d, J= 8.07Hz, 1H), 7.69 (d, J=7.93Hz, 2H), 7.45-7.38 (m, 5H), 2.55 (s, 3H) MS (EI+)m/z:263[M]+.
Embodiment 37:1- (1H- benzimidazolyl-2 radicals-ethyl) -3- (4- hydroxy phenyl) propane -2- alkene -1- ketone (compound 37) preparation
With compound 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo miaow Azoles -2- ethyl) -3- (4- hydroxy phenyl) propane -2- alkene -1- ketone (52%).
1HNMR(CDCl3)δ:9.71 (brs, 1H), 8.91 (brs, 1H), 8.17 (d, J=12Hz, 2H), 7.80 (d, J= 8.07Hz, 1H), 7.72 (d, J=7.93Hz, 1H), 7.35-7.26 (m, 5H), MS (EI+)m/z:264[M]+.
Embodiment 38:1- (1H- benzimidazolyl-2 radicals-ethyl) -3- (1H-3 pyrrole radicals) propane -2- alkene -1- ketone (compound 38) preparation
With compound 2- acetyl group benzimidazole as raw material, the method reaction according to embodiment 1 obtains 1- (1H- benzo miaow Azoles -2- ethyl) -3- (1H-3 pyrrole radicals) propane -2- alkene -1- ketone (53%).
1HNMR(CDCl3)δ:10.20 (brs, 1H), 9.28 (brs, 1H), 7.86 (d, J=7.96Hz, 1H), 7.82 (s, 2H), 7.47-7.42 (m, 3H), 7.00 (s, 1H), 6.74 (s, 1H), 6.34 (s, 1H), 2.80 (d, J=7.8Hz2H), 2.53 (d, J=7.8Hz2H) MS (EI+)m/z:239[M]+.
Embodiment 39:The system of 1- (benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (compound 39) Standby
Addition 6.25g (0.05mol) 2- amino benzo mercaptan in the round-bottomed flask of 50mL, 22.5g (0.25mol) lactic acid, It is heated to reflux 6h, be cooled to room temperature.It is neutralized to purple litmus paper with concentrated ammonia liquor to redden, suction filtration goes out solid, is tied with petroleum ether again Brilliant (78%).The ice of 1- (benzothiazole -2- ethyl) alcohol 3.58g (0.02mol) and 20mL is added in the three-neck flask of 50mL Acetic acid, is heated to when 90 DEG C dripping CrO in three-neck flask3The aqueous solution, after completion of dropping, stirring reaction at 105 DEG C of temperature control Then reactant liquor is poured in the beaker filling 200mL water by 20min, stirring a moment, suction filtration, and filtrate, will with chloroform extraction 3 times Chloroform layer merges, and anhydrous magnesium sulfate is dried, and filtrate rotation is evaporated to obtain yellow solid, with re crystallization from toluene, yield：81%, 95% ethanol and 3.54g (0.02mol) 1- (benzothiazole -2- ethyl) ketone of 20ml, stir about is added in 50ml round-bottomed flask 10min makes solid be completely dissolved, and adds the sodium hydrate aqueous solution of 8ml10%, and stirring is lower to add 0.02mol2- pyridine first Aldehyde, after a period of time, system separates out a large amount of solids, detects reaction end with TLC, has reacted rear suction filtration and obtained solid, yield:92%
1HNMR(CDCl3)δ:8.28 (d J=8.4Hz, 2H), 7.75 (d, J=8.4Hz, 1H), 7.69 (d, J= 7.93Hz,2H),7.45-7.38(m,5H),MS(EI+)m/z:266[M]+.
Embodiment 40:The system of 1- (benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (compound 40) Standby
With compound 1- (benzothiazole -2- ethyl) ketone as raw material, the method reaction according to embodiment 39 obtains 1- (benzo Thiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (68%).
1HNMR(CDCl3)δ:8.02 (d, J=9.0Hz, 2H), 7.81 (d, J=8.07Hz, 1H), 7.37 (d, J= 7.93Hz,2H),7.14-7.07(m,5H),MS(EI+)m/z:266[M]+.
Embodiment 41:1-'s (benzothiazole -2- ethyl) -3- (2- aminomethyl phenyl) propane -2- alkene -1- ketone (compound 41) Preparation
With compound 1- (benzothiazole -2- ethyl) ketone as raw material, the method reaction according to embodiment 39 obtains 1- (benzo Thiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (59%).
1HNMR(CDCl3)δ:7.93(s,1H),7.72-7.69(d,1H),7.47(s,2H),7.40-7.38(t,1H), 7.30-7.27(d,1H),7.15(s,2H),7.03-6.99(t,1H),6.88(s,1H),3.77(s,3H)MS(EI+)m/z: 279[M]+.
Embodiment 42:The system of 1- (benzothiazole -2- ethyl) -3- (2- fluorophenyl) propane -2- alkene -1- ketone (compound 42) Standby
With compound 1- (benzothiazole -2- ethyl) ketone as raw material, the method reaction according to embodiment 39 obtains 1- (benzo Thiazole -2- ethyl) -3- (2- fluorophenyl) propane -2- alkene -1- ketone (85%)
1HNMR(CDCl3)δ:8.73(s,1H),8.60-8.55(d,1H),7.93(t,2H),7.86-7.81(t,1H), 7.70-7.68(d,1H),7.60(s,1H),7.50(s,1H),7.47-7.45(d,1H),7.40(s,1H),MS(EI+)m/z: 283[M]+.
Embodiment 43:The system of 1- (benzothiazole -2- ethyl) -3- (3- chlorphenyl) propane -2- alkene -1- ketone (compound 43) Standby
With compound 1- (benzothiazole -2- ethyl) ketone as raw material, the method reaction according to embodiment 39 obtains 1- (benzo Thiazole -2- ethyl) -3- (3- chlorphenyl) propane -2- alkene -1- ketone (79%).
1HNMR(CDCl3)δ:8.73(s,1H),8.62-8.59(d,1H),7.93(t,2H),7.80-7.77(t,1H), 7.71-7.68(d,1H),7.60(s,1H),7.52-7.49(t,1H),7.47-7.45(d,1H),7.37(s,1H)MS(EI+) m/z:299[M]+.
Embodiment 44:The system of 1- (benzothiazole -2- ethyl) -3- (3- bromophenyl) propane -2- alkene -1- ketone (compound 44) Standby
With compound 1- (benzothiazole -2- ethyl) ketone as raw material, the method reaction according to embodiment 39 obtains 1- (benzo Thiazole -2- ethyl) -3- (3- bromophenyl) propane -2- alkene -1- ketone (92%).
1HNMR(CDCl3)δ:8.90(s,1H),8.21-8.18(d,1H),7.77(t,2H),7.69-7.66(t,1H), 7.60-7.57(d,1H),7.54(s,1H),7.50-7.47(t,1H),7.40(s,1H),7.35(s,1H)MS(EI+)m/z: 344[M]+.
Embodiment 45:1- (benzothiazole -2- ethyl) -3- (3- methoxyphenyl) propane -2- alkene -1- ketone (compound 45) Preparation
With compound 1- (benzothiazole -2- ethyl) ketone as raw material, the method reaction according to embodiment 39 obtains 1- (benzo Thiazole -2- ethyl) -3- (3- methoxyphenyl) propane -2- alkene -1- ketone (51%).
1HNMR(CDCl3)δ:7.64 (s, 1H), 7.50 (d, J=8.07Hz, 2H), 7.47 (s, 1H), 7.40-7.38 (t, J =7.93,1H), 7.30-7.27 (d, J=7.2,1H), 7.15 (s, 2H), 7.11-7.00 (t, 1H), 6.67 (s, 1H), 3.01 (s,3H)MS(EI+)m/z:295[M]+.
Embodiment 46:The preparation of 1- (benzothiazole -2- ethyl) -3- phenyl-propan -2- alkene -1- ketone (compound 46)
With compound 1- (benzothiazole -2- ethyl) ketone as raw material, the method reaction according to embodiment 39 obtains 1- (benzo Thiazole -2- ethyl) -3- phenyl-propan -2- alkene -1- ketone (67%).
1HNMR(CDCl3)δ:7.84 (s, 1H), 7.73-7.70 (d, J=7.93Hz1H), 7.47 (s, 2H), 7.40-7.38 (t, 1H), 7.25-7.21 (d, J=7.93Hz2H), 7.18 (s, 2H), 7.10-7.06 (t, 1H), 6.88 (s, 1H), MS (EI+) m/z:265[M]+.
Embodiment 47:The system of 1- (benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (compound 47) Standby
5.45g (0.05mol) Ortho-Aminophenol, 22.5g (0.25mol) lactic acid, heating is added in the round-bottomed flask of 50mL Backflow 6h, is cooled to room temperature.It is neutralized to purple litmus paper with concentrated ammonia liquor to redden, suction filtration goes out solid, is recrystallized with petroleum ether (78%).The ice vinegar of 1- (benzothiazole -2- ethyl) alcohol 3.26g (0.02mol) and 20mL is added in the three-neck flask of 50mL Acid, is heated to when 90 DEG C dripping CrO in three-neck flask3The aqueous solution, after completion of dropping, stirring reaction at 105 DEG C of temperature control Then reactant liquor is poured in the beaker filling 200mL water by 20min, stirring a moment, suction filtration, and filtrate, will with chloroform extraction 3 times Chloroform layer merges, and anhydrous magnesium sulfate is dried, and filtrate rotation is evaporated to obtain yellow solid, with re crystallization from toluene, yield：81%, 95% ethanol and 3.22g (0.02mol) 1- (benzothiazole -2- ethyl) ketone of 20ml, stir about is added in 50ml round-bottomed flask 10min makes solid be completely dissolved, and adds the sodium hydrate aqueous solution of 8ml10%, and stirring is lower to add 0.02mol2- pyridine first Aldehyde, after a period of time, system separates out a large amount of solids, detects reaction end with TLC, has reacted rear suction filtration and obtained solid, yield:73%
1HNMR(CDCl3)δ:8.37 (d J=8.4Hz, 2H), 7.89 (d, J=8.4Hz, 1H), 7.77 (d, J= 7.93Hz,2H),7.45-7.38(m,5H),MS(EI+)m/z:250[M]+.
Embodiment 48:The system of 1- (benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (compound 48) Standby
With compound 1- (benzothiazole -2- ethyl) ketone as raw material, the method reaction according to embodiment 47 obtains 1- (benzo Azoles -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (82%).
1HNMR(CDCl3)δ:8.41 (d, J=9.0Hz, 2H), 7.86 (d, J=8.07Hz, 1H), 7.49 (d, J= 7.93Hz,2H),7.14-7.07(m,5H).MS(EI+)m/z:250[M]+.
Embodiment 49:1-'s (benzothiazole -2- ethyl) -3- (2- aminomethyl phenyl) propane -2- alkene -1- ketone (compound 49) Preparation
With compound 1- (benzothiazole -2- ethyl) ketone as raw material, the method reaction according to embodiment 47 obtains 1- (benzo Azoles -2- ethyl) -3- (2- aminomethyl phenyl) propane -2- alkene -1- ketone (63%).
1HNMR(CDCl3)δ:7.97(s,1H),7.74-7.68(d,1H),7.51(s,2H),7.42-7.39(t,1H), 7.30-7.27(d,1H),7.15(s,2H),7.03-6.99(t,1H),6.88(s,1H),3.69(s,3H)MS(EI+)m/z: 263[M]+.
Embodiment 50:The system of 1- (benzothiazole -2- ethyl) -3- (2- fluorophenyl) propane -2- alkene -1- ketone (compound 50) Standby
With compound 1- (benzothiazole -2- ethyl) ketone as raw material, the method reaction according to embodiment 47 obtains 1- (benzo Azoles -2- ethyl) -3- (2- fluorophenyl) propane -2- alkene -1- ketone (75%).
1HNMR(CDCl3)δ:8.89(s,1H),8.67-8.60(d,1H),7.85(t,2H),7.81-7.76(t,1H), 7.70-7.68(d,1H),7.60(s,1H),7.50(s,1H),7.47-7.45(d,1H),7.40(s,1H)MS(EI+)m/z: 267[M]+.
Embodiment 51:The system of 1- (benzothiazole -2- ethyl) -3- (3- chlorphenyl) propane -2- alkene -1- ketone (compound 51) Standby
With compound 1- (benzothiazole -2- ethyl) ketone as raw material, the method reaction according to embodiment 47 obtains 1- (benzo Azoles -2- ethyl) -3- (3- chlorphenyl) propane -2- alkene -1- ketone (89%).
1HNMR(CDCl3)δ:8.73(s,1H),8.62-8.59(d,1H),7.93(t,2H),7.80-7.77(t,1H), 7.71-7.68(d,1H),7.60(s,1H),7.52-7.49(t,1H),7.47-7.45(d,1H),7.37(s,1H).MS(EI+) m/z:283[M]+.
Embodiment 52:The system of 1- (benzothiazole -2- ethyl) -3- (3- bromophenyl) propane -2- alkene -1- ketone (compound 52) Standby
With compound 1- (benzothiazole -2- ethyl) ketone as raw material, the method reaction according to embodiment 47 obtains 1- (benzo Azoles -2- ethyl) -3- (3- bromophenyl) propane -2- alkene -1- ketone (89%).
1HNMR(CDCl3)δ:8.77(s,1H),8.24-8.20(d,1H),7.87(t,2H),7.70-7.66(t,1H), 7.60-7.57(d,1H),7.54(s,1H),7.50-7.47(t,1H),7.33(s,1H),7.20(s,1H).MS(EI+)m/z: 327[M]+.
Embodiment 53:1- (benzothiazole -2- ethyl) -3- (3- methoxyphenyl) propane -2- alkene -1- ketone (compound 53) Preparation
With compound 1- (benzothiazole -2- ethyl) ketone as raw material, the method reaction according to embodiment 47 obtains 1- (benzo Azoles -2- ethyl) -3- (3- methoxyphenyl) propane -2- alkene -1- ketone (51%).
1HNMR(CDCl3)δ:7.73 (s, 1H), 7.52 (d, J=8.07Hz, 2H), 7.47 (s, 1H), 7.40-7.38 (t, J =7.93,1H), 7.30-7.27 (d, J=7.2,1H), 7.19 (s, 2H), 7.11-7.06 (t, 1H), 6.67 (s, 1H), 3.01 (s,3H),MS(EI+)m/z:279[M]+.
Embodiment 54:The preparation of 1- (benzothiazole -2- ethyl) -3- phenyl-propan -2- alkene -1- ketone (compound 54)
With compound 1- (benzothiazole -2- ethyl) ketone as raw material, the method reaction according to embodiment 47 obtains 1- (benzo Azoles -2- ethyl) -3- (3- methoxyphenyl) propane -2- alkene -1- ketone (57%)
1HNMR(CDCl3)δ:7.84 (s, 1H), 7.73-7.70 (d, J=7.93Hz1H), 7.47 (s, 2H), 7.40-7.38 (t, 1H), 7.25-7.21 (d, J=7.93Hz2H), 7.18 (s, 2H), 7.10-7.06 (t, 1H), 6.88 (s, 1H), MS (EI+) m/z:249[M]+.
Embodiment 55:1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (is changed Compound 55) preparation
Addition 6.20g (0.05mol) 2,3- diaminophenol in the round-bottomed flask of 50mL, 22.5g (0.25mol) lactic acid, It is heated to reflux 6h, be cooled to room temperature.It is neutralized to purple litmus paper with concentrated ammonia liquor to redden, suction filtration goes out solid, is tied with petroleum ether again Brilliant (78%).In the three-neck flask of 50mL add 2- (1- ethoxy) -3- benzimidazole -4- alcohol 3.56g (0.02mol) and The glacial acetic acid of 20mL, is heated to when 90 DEG C dripping CrO in three-neck flask3The aqueous solution, after completion of dropping, at 105 DEG C of temperature control Then reactant liquor is poured in the beaker filling 200mL water by stirring reaction 20min, stirring a moment, suction filtration, and filtrate is extracted with chloroform Take 3 times, chloroform layer is merged, anhydrous magnesium sulfate is dried, filtrate rotation is evaporated to obtain yellow solid, with re crystallization from toluene, yield： 81%, add in 50ml round-bottomed flask 95% ethanol of 20ml and 3.22g (0.02mol) 1- (7- hydroxyl -1H- benzimidazole - 2- ethyl) ketone, stir about 10min makes solid be completely dissolved, adds the sodium hydrate aqueous solution of 8ml10%, stirs lower addition 0.02mol2- pyridine carboxaldehyde, after a period of time, system separates out a large amount of solids, detects reaction end with TLC, has reacted rear suction filtration and obtained Solid, yield:94%
1HNMR(CDCl3)δ:10.07 (brs, 1H), 9.14 (brs, 1H), 8.37 (d, J=8.4Hz, 2H), 7.89 (d, J =8.4Hz, 1H), 7.77 (s, 1H), 7.45-7.38 (m, 5H), MS (EI+)m/z:265[M]+.
Embodiment 56:1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (is changed Compound 56) preparation
With compound 1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 55 Obtain 1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (58%)
1HNMR(CDCl3)δ:10.13 (brs, 1H), 9.75 (brs, 1H), 8.41 (d, J=9.0Hz, 2H), 7.86 (d, J =8.07Hz, 1H), 7.49 (d, J=7.93Hz, 1H), 7.14-6.97 (m, 5H) .MS (EI+)m/z:265[M]+.
Embodiment 57:1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- aminomethyl phenyl) propane -2- alkene -1- ketone The preparation of (compound 57)
With compound 1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 55 Obtain 1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- aminomethyl phenyl) propane -2- alkene -1- ketone (84%)
1HNMR(CDCl3)δ:9.79(brs,1H),9.22(brs,1H),7.97(s,1H),7.74-7.68(d,1H), 7.51(s,2H),7.42-7.39(t,1H),7.30-7.27(d,1H),7.15(s,1H),7.03-6.99(t,1H),6.73(s, 1H),3.69(s,3H).MS(EI+)m/z:278[M]+.
Embodiment 58:1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- fluorophenyl) propane -2- alkene -1- ketone (is changed Compound 58) preparation
With compound 1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 55 Obtain 1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- fluorophenyl) propane -2- alkene -1- ketone (89%)
1HNMR(CDCl3)δ:11.13(brs,1H),9.75(brs,1H),8.74(s,1H),8.64-8.60(d,1H), 7.85(t,2H),7.81-7.76(t,1H),7.70-7.68(d,1H),7.60(s,1H),7.50(s,1H),6.73(s,1H)MS (EI+)m/z:282[M]+.
Embodiment 59:1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (3- chlorphenyl) propane -2- alkene -1- ketone (is changed Compound 59) preparation
With compound 1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 55 Obtain 1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (3- chlorphenyl) propane -2- alkene -1- ketone (54%)
1HNMR(CDCl3)δ:11.39(brs,1H),9.61(brs,1H),8.73(s,1H),8.62-8.59(d,1H), 7.93(t,2H),7.80-7.77(t,1H),7.71-7.68(d,1H),7.60(s,1H),7.52-7.49(t,1H),6.46(s, 1H).MS(EI+)m/z:298[M]+.
Embodiment 60:1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (3- bromophenyl) propane -2- alkene -1- ketone (is changed Compound 60) preparation
With compound 1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 55 Obtain 1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (3- bromophenyl) propane -2- alkene -1- ketone (87%)
1HNMR(CDCl3)δ:10.65(brs,1H),9.34(brs,1H),8.77(s,1H),8.24-8.20(d,1H), 7.87(t,2H),7.70-7.66(t,1H),7.60-7.57(d,1H),7.54(s,1H),7.33(s,1H),6.50(s,1H) .MS(EI+)m/z:342[M]+.
Embodiment 61:1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (3- methoxyphenyl) propane -2- alkene -1- ketone The preparation of (compound 61)
With compound 1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 55 Obtain 1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (3- bromophenyl) propane -2- alkene -1- ketone (49%)
1HNMR(CDCl3)δ:10.70 (brs, 1H), 9.15 (brs, 1H), 7.73 (s, 1H), 7.52 (d, J=8.07Hz, 2H), 7.44 (s, 1H), 7.40-7.38 (t, J=7.93,1H), 7.30-7.27 (d, J=7.2,1H), 7.23 (s, 2H), 6.67 (s,1H),3.01(s,3H),MS(EI+)m/z:294[M]+.
Embodiment 62:1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- phenyl-propane -2- alkene -1- ketone (compound 62) Preparation
With compound 1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 55 Obtain 1- (7- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- phenyl-propane -2- alkene -1- ketone (60%)
1HNMR(CDCl3)δ:9.79 (brs, 1H), 9.22 (brs, 1H), 7.84 (s, 1H), 7.73-7.70 (d, J= 7.93Hz1H), 7.47 (s, 2H), 7.40-7.38 (t, 1H), 7.25-7.21 (d, J=7.93Hz2H), 7.18 (s, 2H), 6.36 (s,1H),MS(EI+)m/z:264[M]+.
Embodiment 63:1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (is changed Compound 63) preparation
Addition 6.20g (0.05mol) 3,4- diaminophenol in the round-bottomed flask of 50mL, 22.5g (0.25mol) lactic acid, It is heated to reflux 6h, be cooled to room temperature.It is neutralized to purple litmus paper with concentrated ammonia liquor to redden, suction filtration goes out solid, is tied with petroleum ether again Brilliant (78%).In the three-neck flask of 50mL add 2- (1- ethoxy) -3- benzimidazole -5- alcohol 3.56g (0.02mol) and The glacial acetic acid of 20mL, is heated to when 90 DEG C dripping CrO in three-neck flask3The aqueous solution, after completion of dropping, at 105 DEG C of temperature control Then reactant liquor is poured in the beaker filling 200mL water by stirring reaction 20min, stirring a moment, suction filtration, and filtrate is extracted with chloroform Take 3 times, chloroform layer is merged, anhydrous magnesium sulfate is dried, filtrate rotation is evaporated to obtain yellow solid, with re crystallization from toluene, yield： 81%, add in 50ml round-bottomed flask 95% ethanol of 20ml and 3.22g (0.02mol) 1- (6- hydroxyl -1H- benzimidazole - 2- ethyl) ketone, stir about 10min makes solid be completely dissolved, adds the sodium hydrate aqueous solution of 8ml10%, stirs lower addition 0.02mol2- pyridine carboxaldehyde, after a period of time, system separates out a large amount of solids, detects reaction end with TLC, has reacted rear suction filtration and obtained Solid, yield:87%
1HNMR(CDCl3)δ:10.11 (brs, 1H), 9.15 (brs, 1H), 8.46 (d, J=8.4Hz, 2H), 7.81 (d, J =8.4Hz, 1H), 7.45-7.38 (m, 5H), 6.72 (s, 1H), MS (EI+)m/z:265[M]+.
Embodiment 64:1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (is changed Compound 64) preparation
With compound 1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 63 Obtain 1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (74%)
1HNMR(CDCl3)δ:10.18 (brs, 1H), 9.66 (brs, 1H), 8.52 (d, J=9.0Hz, 2H), 7.81 (d, J =8.07Hz, 1H), 7.14-6.97 (m, 5H), 6.49 (d, J=7.93Hz, 1H) .MS (EI+)m/z:265[M]+.
Embodiment 65:1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- aminomethyl phenyl) propane -2- alkene -1- ketone The preparation of (compound 65)
With compound 1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 63 Obtain 1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- aminomethyl phenyl) propane -2- alkene -1- ketone (73%).
1HNMR(CDCl3)δ:9.84(brs,1H),9.20(brs,1H),7.87(s,1H),7.74-7.68(d,1H), 7.51(s,2H),7.42-7.39(t,1H),7.30-7.27(d,1H),6.45(s,1H),7.03-6.99(t,1H),6.73(s, 1H),3.69(s,3H).MS(EI+)m/z:278[M]+.
Embodiment 66:1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- fluorophenyl) propane -2- alkene -1- ketone (is changed Compound 66) preparation
With compound 1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 63 Obtain 1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- fluorophenyl) propane -2- alkene -1- ketone (87%).
1HNMR(CDCl3)δ:11.77(brs,1H),9.34(brs,1H),8.34(s,1H),8.21(s,1H),7.87(t, 2H),7.81-7.76(t,1H),7.73(s,1H),7.60(s,1H),7.50(s,1H),6.73(s,1H)MS(EI+)m/z:282 [M]+.
Embodiment 67:1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (3- chlorphenyl) propane -2- alkene -1- ketone (is changed Compound 67) preparation
With compound 1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 63 Obtain 1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (3- chlorphenyl) propane -2- alkene -1- ketone (82%).
1HNMR(CDCl3)δ:11.46(brs,1H),9.89(brs,1H),8.73(s,1H),8.54(s,1H),7.87(t, 2H),7.80-7.77(t,1H),7.62(s,1H),7.60(s,1H),7.52-7.49(t,1H),6.46(s,1H).MS(EI+) m/z:298[M]+.
Embodiment 68:1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (3- bromophenyl) propane -2- alkene -1- ketone (is changed Compound 68) preparation
With compound 1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 63 Obtain 1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (3- bromophenyl) propane -2- alkene -1- ketone (80%).
1HNMR(CDCl3)δ:10.34(brs,1H),9.21(brs,1H),8.77(s,1H),8.27(s,1H),7.87(t, 2H),7.70-7.66(t,1H),7.52(s,1H),7.54(s,1H),7.33(s,1H),6.50(s,1H).MS(EI+)m/z: 342[M]+.
Embodiment 69:1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (3- methoxyphenyl) propane -2- alkene -1- ketone The preparation of (compound 69)
With compound 1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 63 Obtain 1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (3- methoxyphenyl) propane -2- alkene -1- ketone (80%).
1HNMR(CDCl3)δ:11.27 (brs, 1H), 9.43 (brs, 1H), 7.73 (s, 1H), 7.52 (d, J=8.07Hz, 2H), 7.49 (s, 1H), 7.40-7.38 (t, J=7.93,1H), 7.35 (s, J=7.2,1H), 7.23 (s, 2H), 6.67 (s, 1H),3.01(s,3H),MS(EI+)m/z:294[M]+.
Embodiment 70:1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- phenyl-propane -2- alkene -1- ketone (compound 70) Preparation
With compound 1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 63 Obtain 1- (6- hydroxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- phenyl-propane -2- alkene -1- ketone (69%).
1HNMR(CDCl3)δ:9.79 (brs, 1H), 9.22 (brs, 1H), 7.84 (s, 1H), 7.73-7.70 (d, J= 7.93Hz1H), 7.47 (s, 2H), 7.40-7.38 (t, 1H), 7.25-7.21 (d, J=7.93Hz2H), 7.18 (s, 2H), 6.36 (s,1H),MS(EI+)m/z:264[M]+.
Embodiment 71:1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (is changed Compound 71) preparation
5.4g (0.05mol) o-phenylenediamine, 4.5g (0.05mol) lactic acid and 4mol/L is added in the round-bottomed flask of 50mL Hydrochloric acid 20mL, is heated to reflux 1.5h, is cooled to room temperature.It is neutralized to purple litmus paper with concentrated ammonia liquor to redden, suction filtration goes out solid, use Water recrystallizes (63%).In the three-neck flask of 50mL add 2- (Alpha-hydroxy) ethyl benzo imidazole 3.24g (0.02mol) and The glacial acetic acid of 15mL, is heated to when 90 DEG C dripping CrO in three-neck flask3The aqueous solution, after completion of dropping, at 105 DEG C of temperature control Then reactant liquor is poured in the beaker filling 200mL water by stirring reaction 10min, stirring a moment, suction filtration, and filtrate is extracted with chloroform Take 3 times, chloroform layer is merged, anhydrous magnesium sulfate is dried, filtrate rotation is evaporated to obtain yellow solid, with re crystallization from toluene, yield： 64%.Add 1.6g2- acetyl group benzimidazole, 2mol/L NaOH solution 15mL in the three-neck flask of 50mL, then to flask In drip 1.3mL bromoethane, rapidly three-neck flask is put into after dripping and in ice bath, is cooled to 0 DEG C, after 5min, separate out a large amount of solids, Suction filtration, washing, dry to obtain yellow solid, yield:79%, 50ml round-bottomed flask adds 95% ethanol and the 3.20g of 20ml (0.02mol) 1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone, stir about 10min makes solid be completely dissolved, adds The sodium hydrate aqueous solution of 8ml10%, stirring is lower to add 0.02mol2- pyridine carboxaldehyde, and after a period of time, system precipitation is solid in a large number Body, detects reaction end with TLC, has reacted rear suction filtration and has obtained solid, yield:86%
1HNMR(CDCl3)δ:8.12 (d J=8.4Hz, 2H), 7.80 (d, J=8.4Hz, 1H), 7.68 (d, J= 7.93Hz,2H),7.45-7.38(m,5H),3.77-3.70(m,2H),1.51(s,3H)MS(EI+)m/z:277[M]+.
Embodiment 72:1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (is changed Compound 72) preparation
With compound 1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 71 Obtain 1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (46%).
1HNMR(CDCl3)δ:8.41 (d, J=9.0Hz, 2H), 7.86 (d, J=8.07Hz, 1H), 7.49 (d, J= 7.93Hz,2H),7.14-7.07(m,5H),3.64-3.61(m,2H),1.37(s,3H)MS(EI+)m/z:277[M]+.
Embodiment 73:1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- aminomethyl phenyl) propane -2- alkene -1- ketone The preparation of (compound 73)
With compound 1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 71 Obtain 1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- aminomethyl phenyl) propane -2- alkene -1- ketone (75%).
1HNMR(CDCl3)δ:7.97(s,1H),7.74-7.68(d,1H),7.51(s,2H),7.42-7.39(t,1H), 7.30-7.27(d,1H),7.15(s,2H),7.03-6.99(t,1H),6.88(s,1H),3.69(s,3H),3.57-3.52(m, 2H),1.41(s,3H)MS(EI+)m/z:290[M]+.
Embodiment 74:1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- fluorophenyl) propane -2- alkene -1- ketone (is changed Compound 74) preparation
With compound 1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 71 Obtain 1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- fluorophenyl) propane -2- alkene -1- ketone (68%).
1HNMR(CDCl3)δ:8.89(s,1H),8.67-8.60(d,1H),7.97(t,2H),7.81-7.76(t,1H), 7.70-7.68(d,1H),7.57(s,1H),7.50(s,1H),7.47-7.45(d,1H),7.40(s,1H),3.57-3.52(m, 2H),1.41(s,3H)MS(EI+)m/z:294[M]+.
Embodiment 75:1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (3- chlorphenyl) propane -2- alkene -1- ketone (is changed Compound 75) preparation
With compound 1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 71 Obtain 1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- fluorophenyl) propane -2- alkene -1- ketone (87%).
1HNMR(CDCl3)δ:8.67(s,1H),8.62(s,1H),7.93(t,2H),7.80-7.77(t,1H),7.71- 7.68(d,1H),7.60(s,1H),7.52-7.49(t,1H),7.47-7.45(d,1H),7.37(s,1H).3.76-3.72(m, 2H),1.67(s,3H).MS(EI+)m/z:310[M]+.
Embodiment 76:1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (3- bromophenyl) propane -2- alkene -1- ketone (is changed Compound 76) preparation
With compound 1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 71 Obtain 1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (3- bromophenyl) propane -2- alkene -1- ketone (93%).
1HNMR(CDCl3)δ:8.77(s,1H),8.24-8.20(d,1H),7.87(t,2H),7.70-7.66(t,1H), 7.60-7.57(d,1H),7.54(s,1H),7.50-7.47(t,1H),7.33(s,1H),7.20(s,1H).3.81-3.77(m, 2H),1.55(s,3H).MS(EI+)m/z:354[M]+.
Embodiment 77:1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (3- methoxyphenyl) propane -2- alkene -1- ketone The preparation of (compound 77)
With compound 1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 71 Obtain 1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (3- methoxyphenyl) propane -2- alkene -1- ketone (76%).
1HNMR(CDCl3)δ:7.73 (s, 1H), 7.52 (d, J=8.07Hz, 2H), 7.47 (s, 1H), 7.40-7.38 (t, J =7.93,1H), 7.30-7.27 (d, J=7.2,1H), 7.19 (s, 2H), 7.11-7.06 (t, 1H), 6.67 (s, 1H), 3.65- 3.60(m,2H),3.14(s,3H),1.37(s,3H).MS(EI+)m/z:306[M]+.
Embodiment 78:1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- phenyl-propan -2- alkene -1- ketone (compound 78) preparation
With compound 1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method reaction of embodiment 71 Obtain 1- (1- ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- phenyl-propan -2- alkene -1- ketone (94%).
1HNMR(CDCl3)δ:7.84 (s, 1H), 7.73-7.70 (d, J=7.93Hz1H), 7.47 (s, 2H), 7.40-7.38 (t, 1H), 7.25-7.21 (d, J=7.93Hz2H), 7.18 (s, 2H), 7.10-7.06 (t, 1H), 6.88 (s, 1H), 3.51- 3.47(m,2H),1.39(s,3H).MS(EI+)m/z:276[M]+.
Embodiment 79:1- (7- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) -3 phenyl-propan -2- alkene -1- ketone (compound 79) preparation
6.9g (0.05mol) 3- methoxybenzene -1,2- diamines, 4.5g (0.05mol) breast is added in the round-bottomed flask of 50mL Acid and 4mol/L hydrochloric acid 20mL, are heated to reflux 3h, are cooled to room temperature.It is neutralized to purple litmus paper with concentrated ammonia liquor to redden, take out Leach solid, recrystallize (68%) with water.1- (7- methoxyl group -1H- benzimidazolyl-2 radicals-second is added in the three-neck flask of 50mL Base) alcohol 3.84g (0.02mol) and 15mL glacial acetic acid, be heated to when 90 DEG C dripping CrO in three-neck flask3The aqueous solution, drip Add after finishing, stirring reaction 20min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, stirring sheet Carve, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, anhydrous magnesium sulfate is dried, filtrate rotation is evaporated to obtain yellow solid, With re crystallization from toluene, yield：71%, 50ml round-bottomed flask adds 95% ethanol and 3.8g (0.02mol) 1- (7- of 20ml Methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) ketone, stir about 10min makes solid be completely dissolved, adds the hydroxide of 8ml10% Sodium water solution, stirring is lower to add 0.02mol benzaldehyde, and after a period of time, system separates out a large amount of solids, with TLC detection reaction eventually Point, has reacted rear suction filtration and has obtained solid, yield:84%.
1HNMR(CDCl3)δ:8.53 (brs, 1H), 7.97 (d, J=12Hz, 2H), 7.80 (d, J=8.07Hz, 1H), 7.53 (d, J=7.93Hz, 2H), 7.33-7.26 (m, 5H), 3.47 (s, 3H) MS (EI+)m/z:278[M]+.
Embodiment 80:1- (7- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone The preparation of (compound 80)
With compound 1- (7- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl), as raw material, the method according to embodiment 79 is anti-for ketone 1- (7- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (94%) should be obtained.
1HNMR(CDCl3)δ:9.15 (brs, 1H), 7.53 (d, J=12Hz, 2H), 7.37 (d, J=7.93Hz, 2H), 7.31-7.26(m,5H),3.71(s,3H)MS(EI+)m/z:312[M]+.
Embodiment 81:1- (7- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone The preparation of (compound 81)
With compound 1- (7- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl), as raw material, the method according to embodiment 79 is anti-for ketone 1- (7- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (70%) should be obtained.
1HNMR(CDCl3)δ:8.59 (brs, 1H), 8.00 (s, 1H), 7.89 (d, J=8.07Hz, 1H), 7.47 (d, J= 7.93Hz,2H),7.40-7.35(m,5H),3.03(s,3H)MS(EI+)m/z:279[M]+.
Embodiment 82:1- (7- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone The preparation of (compound 82)
With compound 1- (7- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl), as raw material, the method according to embodiment 79 is anti-for ketone 1- (7- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (61%) should be obtained.
1HNMR(CDCl3)δ:9.01 (brs, 1H), 7.79 (s, 1H), 7.52 (d, J=8.07Hz, 1H), 7.47 (d, J= 7.93Hz,2H),7.41-7.30(m,5H),3.90(s,3H)MS(EI+)m/z:279[M]+.
Embodiment 83:1- (7- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone The preparation of (compound 83)
With compound 1- (7- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl), as raw material, the method according to embodiment 79 is anti-for ketone 1- (7- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (61%) should be obtained.
1HNMR(CDCl3)δ:8.87 (brs, 1H), 7.62 (d, J=8.15Hz, 1H), 7.53 (d, J=12Hz, 1H), 7.47 (s, 1H), 7.39-7.30 (m, 3H), 6.66 (dd, J=1.63Hz, J=3.08Hz, 1H), 3.87 (s, 3H) MS (EI+) m/z:268[M]+.
Embodiment 84:1- (7- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- phenyl-propan -2- alkene -1- ketone (compound 83) preparation
7.6g (0.05mol) 3- ethoxybenzene -1,2- diamines, 4.5g (0.05mol) breast is added in the round-bottomed flask of 50mL Acid and 4mol/L hydrochloric acid 20mL, are heated to reflux 3h, are cooled to room temperature.It is neutralized to purple litmus paper with concentrated ammonia liquor to redden, take out Leach solid, recrystallize (73%) with water.1- (7- ethyoxyl -1H- benzimidazolyl-2 radicals-second is added in the three-neck flask of 50mL Base) alcohol 4.12g (0.02mol) and 15mL glacial acetic acid, be heated to when 90 DEG C dripping CrO in three-neck flask3The aqueous solution, drip Add after finishing, stirring reaction 20min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, stirring sheet Carve, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, anhydrous magnesium sulfate is dried, filtrate rotation is evaporated to obtain yellow solid, With re crystallization from toluene, yield：71%, 50ml round-bottomed flask adds 95% ethanol and 4.08g (0.02mol) 1- of 20ml (7- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) ketone, stir about 10min makes solid be completely dissolved, adds the hydrogen-oxygen of 8ml10% Change sodium water solution, stirring is lower to add 0.02mol benzaldehyde, and after a period of time, system separates out a large amount of solids, with TLC detection reaction eventually Point, has reacted rear suction filtration and has obtained solid, yield:84%.
1HNMR(CDCl3)δ:8.93 (brs, 1H), 7.94 (d, J=12Hz, 2H), 7.78 (d, J=8.07Hz, 1H), 7.59 (d, J=7.93Hz, 2H), 7.33-7.26 (m, 5H), 3.61 (s, 2H), 1.56 (s, 3H) MS (EI+)m/z:292[M]+.
Embodiment 85:1- (7- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone The preparation of (compound 85)
With compound 1- (7- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl), as raw material, the method according to embodiment 79 is anti-for ketone 1- (7- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (61%) should be obtained.
1HNMR(CDCl3)δ:9.01 (brs, 1H), 7.66 (d, J=12Hz, 2H), 7.40 (d, J=7.93Hz, 2H), 7.35-7.29(m,5H),3.58(s,2H),1.13(s,3H)MS(EI+)m/z:326[M]+.
Embodiment 86:1- (7- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone The preparation of (compound 86)
With compound 1- (7- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl), as raw material, the method according to embodiment 79 is anti-for ketone 1- (7- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (78%) should be obtained.
1HNMR(CDCl3)δ:8.89 (brs, 1H), 8.02 (s, 1H), 7.87 (d, J=8.07Hz, 1H), 7.53 (d, J= 7.93Hz,2H),7.41-7.37(m,5H),3.36(s,2H),1.25(s,3H)MS(EI+)m/z:293[M]+.
Embodiment 87:1- (7- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone The preparation of (compound 87)
With compound 1- (7- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl), as raw material, the method according to embodiment 79 is anti-for ketone 1- (7- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (88%) should be obtained.
1HNMR(CDCl3)δ:9.15 (brs, 1H), 8.29 (s, 1H), 7.53 (d, J=8.07Hz, 1H), 7.46 (d, J= 7.93Hz,2H),7.39-7.32(m,5H),3.76(s,2H),1.38(s,3H)MS(EI+)m/z:293[M]+.
Embodiment 88:1- (7- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone The preparation of (compound 88)
With compound 1- (7- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl), as raw material, the method according to embodiment 79 is anti-for ketone 1- (7- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (73%) should be obtained.
1HNMR(CDCl3)δ:8.79 (brs, 1H), 7.82 (d, J=8.15Hz, 1H), 7.59 (d, J=15.69Hz, 1H), 7.51 (s, 1H), 7.42-7.35 (m, 3H), 6.53 (dd, J=1.63Hz, J=3.08Hz, 1H), 3.53 (s, 2H), 1.66 (s, 3H)MS(EI+)m/z:282[M]+.
Embodiment 89:1- (6- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) -3- phenyl-propane -2- alkene -1- ketone (compound 89) preparation
7.6g (0.05mol) 3- ethoxybenzene -1,2- diamines, 4.5g (0.05mol) breast is added in the round-bottomed flask of 50mL Acid and 4mol/L hydrochloric acid 20mL, are heated to reflux 3h, are cooled to room temperature.It is neutralized to purple litmus paper with concentrated ammonia liquor to redden, take out Leach solid, recrystallize (79%) with water.1- (7- ethyoxyl -1H- benzimidazolyl-2 radicals-second is added in the three-neck flask of 50mL Base) alcohol 4.12g (0.02mol) and 15mL glacial acetic acid, be heated to when 90 DEG C dripping CrO in three-neck flask3The aqueous solution, drip Add after finishing, stirring reaction 20min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, stirring sheet Carve, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, anhydrous magnesium sulfate is dried, filtrate rotation is evaporated to obtain yellow solid, With re crystallization from toluene, yield：74%, 50ml round-bottomed flask adds 95% ethanol and 4.08g (0.02mol) 1- of 20ml (7- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) ketone, stir about 10min makes solid be completely dissolved, adds the hydrogen-oxygen of 8ml10% Change sodium water solution, stirring is lower to add 0.02mol benzaldehyde, and after a period of time, system separates out a large amount of solids, with TLC detection reaction eventually Point, has reacted rear suction filtration and has obtained solid, yield:76%.
1HNMR(CDCl3)δ:8.77 (brs, 1H), 7.86 (d, J=12Hz, 2H), 7.75 (d, J=8.07Hz, 1H), 7.53(s,1H),7.47(s,1H),7.27-7.20(m,5H),2.14(s,3H)MS(EI+)m/z:278[M]+.
Embodiment 90:1- (6- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone The preparation of (compound 90)
With compound 1- (6- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl), as raw material, the method according to embodiment 89 is anti-for ketone 1- (6- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (76%) should be obtained.
1HNMR(CDCl3)δ:9.13 (brs, 1H), 8.27 (dd, J=15.9Hz, J=12Hz, 2H), 7.75 (d, J= 8.07Hz, 1H), 7.53 (d, J=7.93Hz, 1H), 7.46-7.38 (m, 5H), 2.15 (s, 3H) MS (EI+)m/z:282[M]+.
Embodiment 91:1- (6- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone The preparation of (compound 91)
With compound 1- (6- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl), as raw material, the method according to embodiment 89 is anti-for ketone 1- (6- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (83%) should be obtained.
1HNMR(CDCl3)δ:10.87 (brs, 1H), 8.19 (dd, J=15.9Hz, J=55.2Hz, 1H), 7.85 (d, J= 8.07Hz, 1H), 7.60 (d, J=7.9Hz, 2H), 7.47-7.41 (m, 5H), 2.26 (s, 3H) MS (EI+)m/z:279[M]+.
Embodiment 92:1- (6- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone The preparation of (compound 92)
With compound 1- (6- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl), as raw material, the method according to embodiment 89 is anti-for ketone 1- (6- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (83%) should be obtained.
1HNMR(CDCl3)δ:9.38 (brs, 1H), 8.26 (dd, J=15.9Hz, J=55.2Hz, 2H), 7.75 (d, J= 8.07Hz, 1H), 7.41 (d, J=7.93Hz, 2H), 7.20-7.13 (m, 4H), 2.06 (s, 3H) MS (EI+)m/z:279[M]+.
Embodiment 93:1- (6- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone The preparation of (compound 93)
With compound 1- (6- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl), as raw material, the method according to embodiment 89 is anti-for ketone 1- (6- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (83%) should be obtained.
1HNMR(CDCl3)δ:8.97 (s, 1H), 7.79 (d, J=8.15Hz, 1H), 7.62 (d, J=12Hz, 1H), 7.53 (s, 1H), 7.47-7.40 (m, 3H), 7.10 (d, J=3.27Hz, 1H), 6.45 (dd, J=1.63Hz, J=3.08Hz, 1H), 2.37(s,3H)MS(EI+)m/z:268[M]+.
Embodiment 94:1- (6- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- phenyl-propane -2- alkene -1- ketone (compound 94) preparation
7.6g (0.05mol) 4- ethoxybenzene -1,2- diamines, 4.5g (0.05mol) breast is added in the round-bottomed flask of 50mL Acid and 4mol/L hydrochloric acid 20mL, are heated to reflux 3h, are cooled to room temperature.It is neutralized to purple litmus paper with concentrated ammonia liquor to redden, take out Leach solid, recrystallize (72%) with water.1- (6- ethyoxyl -1H- benzimidazolyl-2 radicals-second is added in the three-neck flask of 50mL Base) alcohol 4.12g (0.02mol) and 15mL glacial acetic acid, be heated to when 90 DEG C dripping CrO in three-neck flask3The aqueous solution, drip Add after finishing, stirring reaction 20min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, stirring sheet Carve, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, anhydrous magnesium sulfate is dried, filtrate rotation is evaporated to obtain yellow solid, With re crystallization from toluene, yield：80%, 50ml round-bottomed flask adds 95% ethanol and 4.08g (0.02mol) 1- of 20ml (6- methoxyl group -1H- benzimidazolyl-2 radicals-ethyl) ketone, stir about 10min makes solid be completely dissolved, adds the hydrogen-oxygen of 8ml10% Change sodium water solution, stirring is lower to add 0.02mol benzaldehyde, and after a period of time, system separates out a large amount of solids, with TLC detection reaction eventually Point, has reacted rear suction filtration and has obtained solid, yield:85%.
1HNMR(CDCl3)δ:8.90 (brs, 1H), 7.87 (d, J=12Hz, 2H), 7.71 (d, J=8.07Hz, 1H), 7.62(s,1H),7.40(s,1H),7.39-7.30(m,5H),3.47(s,2H),1.75(s,3H)MS(EI+)m/z:292[M]+.
Embodiment 95:1- (6- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (3- chlorphenyl)-propane -2- alkene -1- ketone The preparation of (compound 95)
With compound 1- (6- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl), as raw material, the method according to embodiment 89 is anti-for ketone 1- (6- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (3- chlorphenyl)-propane -2- alkene -1- ketone (77%) should be obtained.
1HNMR(CDCl3)δ:9.77 (brs, 1H), 8.03 (dd, J=15.9Hz, J=12Hz, 2H), 7.92 (d, J= 8.07Hz, 1H), 7.80 (d, J=7.93Hz, 1H), 7.54-7.48 (m, 5H), 3.13 (s, 2H), 1.26 (s, 3H) MS (EI+) m/z:326[M]+.
Embodiment 96:1- (6- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals)-propane -2- alkene -1- ketone The preparation of (compound 96)
With compound 1- (6- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl), as raw material, the method according to embodiment 89 is anti-for ketone 1- (6- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals)-propane -2- alkene -1- ketone (67%) should be obtained.
1HNMR(CDCl3)δ:11.13 (brs, 1H), 8.24 (dd, J=15.9Hz, J=55.2Hz, 1H), 7.90 (d, J= 8.07Hz, 1H), 7.78 (d, J=7.93Hz, 2H), 7.47-7.40 (m, 5H), 3.28 (s, 2H), 1.37 (s, 3H) MS (EI+) m/z:293[M]+.
Embodiment 97:1- (6- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals)-propane -2- alkene -1- ketone The preparation of (compound 97)
With compound 1- (6- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl), as raw material, the method according to embodiment 89 is anti-for ketone 1- (6- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals)-propane -2- alkene -1- ketone (89%) should be obtained.
1HNMR(CDCl3)δ:9.75 (brs, 1H), 8.22 (dd, J=15.9Hz, J=55.2Hz, 2H), 7.63 (d, J= 8.07Hz, 1H), 7.40 (d, J=7.93Hz, 2H), 7.17-7.12 (m, 4H)), 3.45 (s, 2H), 1.23 (s, 3H) MS (EI+) m/z:263[M]+.
Embodiment 98:1- (6- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl)-propane -2- alkene -1- ketone The preparation of (compound 98)
With compound 1- (6- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl), as raw material, the method according to embodiment 89 is anti-for ketone 1- (6- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl)-propane -2- alkene -1- ketone (80%) should be obtained.
1HNMR(CDCl3)δ:9.57 (brs, 1H), 7.79 (d, J=8.15Hz, 1H), 7.63 (d, J=12Hz, 1H), 7.28 (s, 1H), 7.40-7.32 (m, 3H), 7.09 (d, J=3.27Hz, 1H), 6.31 (dd, J=1.63Hz, J=3.08Hz, 1H),3.58(s,2H),1.79(s,3H)MS(EI+)m/z:282[M]+.
Embodiment 99:1- (7- chloro- 1H- benzimidazolyl-2 radicals-ethyl) -3-'s phenyl-propane -2- alkene -1- ketone (compound 99) Preparation
Addition 0.14g (0.001mol) 3- chlorobenzene -1 in the round-bottomed flask of 50mL, 2- diamines, 0.9g (0.01mol) lactic acid, It is heated to reflux 3h under nitrogen protection, be cooled to room temperature.It is neutralized to purple litmus paper with saturated sodium bicarbonate aqueous solution to redden, take out Leach solid, recrystallize (51%) with water.1- (7- chloro- 1H- benzimidazolyl-2 radicals-ethyl) alcohol is added in the three-neck flask of 50mL The glacial acetic acid of 0.196g (0.001mol) and 10mL, is heated to being slowly added dropwise CrO in three-neck flask when 90 DEG C3The aqueous solution, After completion of dropping, stirring reaction 5min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, stirring sheet Carve, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, anhydrous magnesium sulfate is dried, filtrate rotation is evaporated to obtain pale yellow colored solid Body, with ethyl alcohol recrystallization, yield：63%. 95% ethanol and the 0.194g adding 10ml in 50ml round-bottomed flask (0.001mol) 1- (7- chloro- 1H- benzimidazolyl-2 radicals-ethyl) ketone, stir about 10min makes solid be completely dissolved, adds The sodium hydrate aqueous solution of 8ml10%, stirring is lower to add 0.0015mol benzaldehyde, and after a period of time, system separates out a large amount of solids, Detect reaction end with TLC, reacted rear suction filtration and obtained solid, yield:61%
1HNMR(CDCl3)δ:13.20 (brs, 1H), 7.91 (d, J=12Hz, 2H), 7.80 (d, J=8.07Hz, 1H), 7.53 (d, J=7.93Hz, 2H), 7.31-7.28 (m, 5H) MS (EI+)m/z:282[M]+.
Embodiment 100:1- (7- chloro- 1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (chemical combination Thing 100) preparation
With compound 1- (7- chloro- 1H- benzimidazolyl-2 radicals-ethyl), ketone as raw material, react by the method according to embodiment 99 To 1- (7- chloro- 1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (52%).
1HNMR(CDCl3)δ:12.17 (brs, 1H), 7.76 (d, J=12Hz, 2H), 7.45 (d, J=7.93Hz, 2H), 7.31-7.28(m,5H)MS(EI+)m/z:316[M]+.
Embodiment 101:1- (7- chloro- 1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 101) preparation
With compound 1- (7- chloro- 1H- benzimidazolyl-2 radicals-ethyl), ketone as raw material, react by the method according to embodiment 99 To 1- (7- chloro- 1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (63%).
1HNMR(CDCl3)δ:10.62 (brs, 1H), 7.95 (s, 1H), 7.72 (d, J=8.07Hz, 1H), 7.53 (d, J= 7.93Hz,2H),7.32-7.28(m,5H)MS(EI+)m/z:283[M]+.
Embodiment 102:1- (7- chloro- 1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 102) preparation
With compound 1- (7- chloro- 1H- benzimidazolyl-2 radicals-ethyl), ketone as raw material, react by the method according to embodiment 99 To 1- (7- chloro- 1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (51%).
1HNMR(CDCl3)δ:9.79 (brs, 1H), 8.34 (s, 1H), 7.60 (d, J=8.07Hz, 1H), 7.38 (d, J= 7.93Hz,2H),7.30-7.27(m,5H)MS(EI+)m/z:283[M]+.
Embodiment 103:1- (7- chloro- 1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (chemical combination Thing 103) preparation
With compound 1- (7- chloro- 1H- benzimidazolyl-2 radicals-ethyl), ketone as raw material, react by the method according to embodiment 99 To 1- (7- chloro- 1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (55%).
1HNMR(CDCl3)δ:9.70 (s, 1H), 7.94 (d, J=8.15Hz, 1H), 7.56 (d, J=15.69Hz, 1H), 7.51 (s, 1H), 7.31-7.24 (m, 3H), 6.73 (dd, J=1.63Hz, J=3.08Hz, 1H) MS (EI+)m/z:272[M]+.
Embodiment 104:1- (6- chloro- 1H- benzimidazolyl-2 radicals-ethyl) -3- phenyl-propane -2- alkene -1- ketone (compound 104) Preparation
Addition 0.14g (0.001mol) 4- chlorobenzene -1 in the round-bottomed flask of 50mL, 2- diamines, 0.9g (0.01mol) lactic acid, It is heated to reflux 3h under nitrogen protection, be cooled to room temperature.It is neutralized to purple litmus paper with saturated sodium bicarbonate aqueous solution to redden, take out Leach solid, recrystallize (51%) with water.1- (6- chloro- 1H- benzimidazolyl-2 radicals-ethyl) alcohol is added in the three-neck flask of 50mL The glacial acetic acid of 0.196g (0.001mol) and 10mL, is heated to being slowly added dropwise CrO in three-neck flask when 90 DEG C3The aqueous solution, After completion of dropping, stirring reaction 5min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, stirring sheet Carve, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, anhydrous magnesium sulfate is dried, filtrate rotation is evaporated to obtain pale yellow colored solid Body, with ethyl alcohol recrystallization, yield：63%. 95% ethanol and the 0.194g adding 10ml in 50ml round-bottomed flask (0.001mol) 1- (6- chloro- 1H- benzimidazolyl-2 radicals-ethyl) ketone, stir about 10min makes solid be completely dissolved, adds The sodium hydrate aqueous solution of 8ml10%, stirring is lower to add 0.0015mol benzaldehyde, and after a period of time, system separates out a large amount of solids, Detect reaction end with TLC, reacted rear suction filtration and obtained solid, (57%).
1HNMR(CDCl3)δ:8.77 (brs, 1H), 7.91 (d, J=12Hz, 2H), 7.6 (d, J=8.07Hz, 1H), 7.53 (s,1H),7.49(s,1H),7.35-7.26(m,5H)MS(EI+)m/z:282[M]+.
Embodiment 105:1- (6- chloro- 1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (chemical combination Thing 105) preparation
With compound 1- (6- chloro- 1H- benzimidazolyl-2 radicals-ethyl), ketone as raw material, react by the method according to embodiment 104 To 1- (6- chloro- 1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (76%).
1HNMR(CDCl3)δ:8.37 (s, 1H), 7.64 (d, J=8.15Hz, 1H), 7.60 (d, J=12Hz, 1H), 7.50 (s, 1H), 7.37-7.28 (m, 3H), 7.02 (d, J=3.27Hz, 1H), 6.47 (dd, J=1.63Hz, J=3.08Hz, 1H) MS (EI+)m/z:272[M]+.
Embodiment 106:1- (6- chloro- 1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 106) preparation
With compound 1- (6- chloro- 1H- benzimidazolyl-2 radicals-ethyl), ketone as raw material, react by the method according to embodiment 104 To 1- (6- chloro- 1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (42%).
1HNMR(CDCl3)δ:9.31 (brs, 1H), 8.02 (dd, J=15.9Hz, J=55.2Hz, 2H), 7.88 (d, J= 8.07Hz, 1H), 7.37 (d, J=7.93Hz, 2H), 7.14-7.09 (m, 4H) MS (EI+)m/z:283[M]+.
Embodiment 107:1- (6- chloro- 1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (chemical combination Thing 107) preparation
With compound 1- (6- chloro- 1H- benzimidazolyl-2 radicals-ethyl), ketone as raw material, react by the method according to embodiment 104 To 1- (6- chloro- 1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (73%).
1HNMR(CDCl3)δ:9.79 (brs, 1H), 8.38 (dd, J=15.9Hz, J=12Hz, 2H), 7.92 (d, J= 8.07Hz, 1H), 7.84 (d, J=7.93Hz, 1H), 7.70-7.61 (m, 5H) MS (EI+)m/z:316[M]+.
Embodiment 108:1- (6- chloro- 1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 108) preparation
With compound 1- (6- chloro- 1H- benzimidazolyl-2 radicals-ethyl), ketone as raw material, react by the method according to embodiment 104 To 1- (6- chloro- 1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (79%).
1HNMR(CDCl3)δ:11.06 (brs, 1H), 8.06 (d, J=12Hz, 1H), 7.84 (d, J=8.07Hz, 1H), 7.73 (d, J=7.93Hz, 2H), 7.56-7.49 (m, 5H) MS (EI+)m/z:283[M]+.
Embodiment 109:1- (7- bromo- 1H- benzimidazolyl-2 radicals-ethyl) -3- phenyl-propane -2- alkene -1- ketone (compound 109) Preparation
0.185g (0.001mol) 3- bromobenzene -1,2- diamines, 0.9g (0.01mol) breast is added in the round-bottomed flask of 50mL Acid, is heated to reflux 3h under nitrogen protection, is cooled to room temperature.It is neutralized to purple litmus paper with saturated sodium bicarbonate aqueous solution to become Red, suction filtration goes out solid, recrystallizes (51%) with water.1- (7- bromo- 1H- benzimidazolyl-2 radicals-second is added in the three-neck flask of 50mL Base) alcohol 0.24g (0.001mol) and 10mL glacial acetic acid, be heated to being slowly added dropwise CrO in three-neck flask when 90 DEG C3Water-soluble Liquid, after completion of dropping, stirring reaction 5min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, stir Mix a moment, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, anhydrous magnesium sulfate is dried, filtrate rotation is evaporated yellowish Color solid, with ethyl alcohol recrystallization, yield：63%. 95% ethanol and the 0.238g adding 10ml in 50ml round-bottomed flask (0.001mol) 1- (7- bromo- 1H- benzimidazolyl-2 radicals-ethyl) ketone, stir about 10min makes solid be completely dissolved, adds The sodium hydrate aqueous solution of 8ml10%, stirring is lower to add 0.0015mol benzaldehyde, and after a period of time, system separates out a large amount of solids, Detect reaction end with TLC, reacted rear suction filtration and obtained solid, yield:62%
1HNMR(CDCl3)δ:11.74 (brs, 1H), 7.95 (d, J=12Hz, 2H), 7.82 (d, J=8Hz, 1H), 7.67 (d, J=7.93Hz, 2H), 7.49-7.40 (m, 5H) MS (EI+)m/z:326[M]+.
Embodiment 110:1- (7- bromo- 1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (chemical combination Thing 110) preparation
With compound 1- (7- bromo- 1H- benzimidazolyl-2 radicals-ethyl), ketone as raw material, react by the method according to embodiment 109 To 1- (7- bromo- 1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (45%).
1HNMR(CDCl3)δ:11.32 (brs, 1H), 7.82 (d, J=12Hz, 2H), 7.63 (d, J=7.93Hz, 2H), 7.39-7.32(m,5H)MS(EI+)m/z:361.9[M]+.
Embodiment 111:1- (7- bromo- 1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 111) preparation
With compound 1- (7- bromo- 1H- benzimidazolyl-2 radicals-ethyl), ketone as raw material, react by the method according to embodiment 109 To 1- (7- bromo- 1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (75%).
1HNMR(CDCl3)δ:10.62 (brs, 1H), 7.88 (s, 1H), 7.75 (d, J=8.07Hz, 1H), 7.62 (d, J= 7.93Hz,2H),7.52-7.48(m,5H)MS(EI+)m/z:327[M]+.
Embodiment 112:1- (7- bromo- 1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 112) preparation
With compound 1- (7- bromo- 1H- benzimidazolyl-2 radicals-ethyl), ketone as raw material, react by the method according to embodiment 109 To 1- (7- bromo- 1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (49%).
1HNMR(CDCl3)δ:9.47 (brs, 1H), 8.57 (s, 1H), 7.64 (d, J=8.07Hz, 1H), 7.46 (d, J= 7.93Hz,2H),7.39-7.32(m,5H)MS(EI+)m/z:327[M]+.
Embodiment 113:1- (7- bromo- 1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (chemical combination Thing 113) preparation
With compound 1- (7- bromo- 1H- benzimidazolyl-2 radicals-ethyl), ketone as raw material, react by the method according to embodiment 109 To 1- (7- bromo- 1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (52%).
1HNMR(CDCl3)δ:9.85 (s, 1H), 7.93 (d, J=8.15Hz, 1H), 7.56 (d, J=15.69Hz, 1H), 7.51 (s, 1H), 7.37-7.30 (m, 3H), 6.90 (d, J=3.08Hz, 1H) MS (EI+)m/z:315.9[M]+.
Embodiment 114:1- (6- bromo- 1H- benzimidazolyl-2 radicals-ethyl) -3- phenyl-propane -2- alkene -1- ketone (compound 114) Preparation
0.185g (0.001mol) 4- bromobenzene -1,2- diamines, 0.9g (0.01mol) breast is added in the round-bottomed flask of 50mL Acid, is heated to reflux 3h under nitrogen protection, is cooled to room temperature.It is neutralized to purple litmus paper with saturated sodium bicarbonate aqueous solution to become Red, suction filtration goes out solid, recrystallizes (51%) with water.1- (6- bromo- 1H- benzimidazolyl-2 radicals-second is added in the three-neck flask of 50mL Base) alcohol 0.24g (0.001mol) and 10mL glacial acetic acid, be heated to being slowly added dropwise CrO in three-neck flask when 90 DEG C3Water-soluble Liquid, after completion of dropping, stirring reaction 5min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, stir Mix a moment, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, anhydrous magnesium sulfate is dried, filtrate rotation is evaporated yellowish Color solid, with ethyl alcohol recrystallization, yield：63%.95% ethanol and the 0.238g of 10ml is added in 50ml round-bottomed flask (0.001mol) 1- (6- bromo- 1H- benzimidazolyl-2 radicals-ethyl) ketone, stir about 10min makes solid be completely dissolved, adds The sodium hydrate aqueous solution of 8ml10%, stirring is lower to add 0.0015mol benzaldehyde, and after a period of time, system separates out a large amount of solids, Detect reaction end with TLC, reacted rear suction filtration and obtained solid (52%).
1HNMR(CDCl3)δ:8.93 (brs, 1H), 7.85 (d, J=12Hz, 2H), 7.61 (d, J=8.07Hz, 1H), 7.57(s,1H),7.40(s,1H),7.31-7.27(m,5H)MS(EI+)m/z:326[M]+.
Embodiment 115:1- (6- bromo- 1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (chemical combination Thing 115) preparation
With compound 1- (6- bromo- 1H- benzimidazolyl-2 radicals-ethyl), ketone as raw material, react by the method according to embodiment 114 To 1- (6- bromo- 1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (66%).
1HNMR(CDCl3)δ:8.42 (s, 1H), 7.73 (d, J=8.15Hz, 1H), 7.66 (d, J=12Hz, 1H), 7.52 (s, 1H), 7.39-7.32 (m, 3H), 7.17 (d, J=3.27Hz, 1H), 6.62 (d, J=3.08Hz, 1H) MS (EI+)m/z: 315.9[M]+.
Embodiment 116:1- (6- bromo- 1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 116) preparation
With compound 1- (6- bromo- 1H- benzimidazolyl-2 radicals-ethyl), ketone as raw material, react by the method according to embodiment 114 To 1- (6- bromo- 1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (32%).
1HNMR(CDCl3)δ:9.42 (brs, 1H), 8.13 (d, J=15.9Hz, 2H), 7.70 (d, J=8.07Hz, 1H), 7.32 (d, J=7.93Hz, 2H), 7.18-7.11 (m, 4H) MS (EI+)m/z:327[M]+.
Embodiment 117:1- (6- bromo- 1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (chemical combination Thing 117) preparation
With compound 1- (6- bromo- 1H- benzimidazolyl-2 radicals-ethyl), ketone as raw material, react by the method according to embodiment 114 To 1- (6- bromo- 1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (61%).
1HNMR(CDCl3)δ:9.84 (brs, 1H), 8.32 (d J=12Hz, 2H), 7.89 (d, J=8.07Hz, 1H), 7.76 (d, J=7.93Hz, 1H), 7.65-7.60 (m, 5H) MS (EI+)m/z:361.9[M]+.
Embodiment 118:1- (6- bromo- 1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 118) preparation
With compound 1- (6- bromo- 1H- benzimidazolyl-2 radicals-ethyl), ketone as raw material, react by the method according to embodiment 114 To 1- (6- bromo- 1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (68%).
1HNMR(CDCl3)δ:10.86 (brs, 1H), 8.25 (d, J=12Hz, 1H), 7.89 (d, J=8.07Hz, 1H), 7.71 (d, J=7.93Hz, 2H), 7.50-7.46 (m, 5H) MS (EI+)m/z:327[M]+.
Embodiment 119:1- (7- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- phenyl-propane -2- alkene -1- ketone (chemical combination Thing 119) preparation
7.7g (0.05mol) 3- sulphomethyl benzene -1,2- diamines, 4.5g (0.05mol) is added in the round-bottomed flask of 50mL Lactic acid and 4mol/L hydrochloric acid 20mL, are heated to reflux 3h, are cooled to room temperature.It is neutralized to purple litmus paper with concentrated ammonia liquor to redden, Suction filtration goes out solid, recrystallizes (72%) with water.In the three-neck flask of 50mL add 1- (7- sulphomethyl -1H- benzimidazole - 2- ethyl) alcohol 4.16g (0.02mol) and 15mL glacial acetic acid, be heated to when 90 DEG C dripping CrO in three-neck flask3Water-soluble Liquid, after completion of dropping, stirring reaction 20min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, stir Mix a moment, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, anhydrous magnesium sulfate is dried, filtrate rotation is evaporated to obtain yellow Solid, with re crystallization from toluene, yield：80%, 50ml round-bottomed flask adds 95% ethanol and the 4.12g of 20ml (0.02mol) 1- (7- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone, stir about 10min makes solid be completely dissolved, adds The sodium hydrate aqueous solution of 8ml10%, stirring is lower to add 0.02mol benzaldehyde, and after a period of time, system separates out a large amount of solids, uses TLC detects reaction end, has reacted rear suction filtration and has obtained solid, yield:72%
1HNMR(CDCl3)δ:8.96 (brs, 1H), 7.98 (d, J=12Hz, 2H), 7.83 (d, J=8.07Hz, 1H), 7.66 (d, J=7.93Hz, 2H), 7.39-7.31 (m, 5H), 3.19 (s, 3H) MS (EI+)m/z:294[M]+.
Embodiment 120:1- (7- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- The preparation of ketone (compound 120)
With compound 1- (7- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method for embodiment 119 Reaction obtains 1- (7- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (49%).
1HNMR(CDCl3)δ:9.15 (brs, 1H), 7.91 (d, J=12Hz, 2H), 7.50 (d, J=7.93Hz, 2H), 7.39-7.32(m,5H),3.26(s,3H)MS(EI+)m/z:328[M]+.
Embodiment 121:1- (7- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- The preparation of ketone (compound 121)
With compound 1- (7- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method for embodiment 119 Reaction obtains 1- (7- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (59%).
1HNMR(CDCl3)δ:9.78 (brs, 1H), 8.06 (s, 1H), 7.90 (d, J=8.07Hz, 1H), 7.53 (d, J= 7.93Hz,2H),7.49-7.42(m,5H),3.36(s,3H)MS(EI+)m/z:295[M]+.
Embodiment 122:1- (7- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- The preparation of ketone (compound 122)
With compound 1- (7- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method for embodiment 119 Reaction obtains 1- (7- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (43%).
1HNMR(CDCl3)δ:9.35 (brs, 1H), 8.76 (s, 1H), 7.58 (d, J=8.07Hz, 1H), 7.43 (d, J= 7.93Hz,2H),7.39-7.33(m,5H),3.34(s,3H)MS(EI+)m/z:295[M]+.
Embodiment 123:1- (7- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- The preparation of ketone (compound 123)
With compound 1- (7- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method for embodiment 119 Reaction obtains 1- (7- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (60%).
1HNMR(CDCl3)δ:8.49 (s, 1H), 7.68 (d, J=8.15Hz, 1H), 7.52 (d, J=15.69Hz, 1H), 7.47 (s, 1H), 7.36-7.30 (m, 3H), 6.69 (d, J=3.08Hz, 1H), 3.35 (s, 3H) MS (EI+)m/z:284[M]+.
Embodiment 124:1- (6- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- phenyl-propane -2- alkene -1- ketone (chemical combination Thing 124) preparation
7.7g (0.05mol) 4- sulphomethyl benzene -1,2- diamines, 4.5g (0.05mol) is added in the round-bottomed flask of 50mL Lactic acid and 4mol/L hydrochloric acid 20mL, are heated to reflux 3h, are cooled to room temperature.It is neutralized to purple litmus paper with concentrated ammonia liquor to redden, Suction filtration goes out solid, recrystallizes (72%) with water.In the three-neck flask of 50mL add 1- (6- sulphomethyl -1H- benzimidazole - 2- ethyl) alcohol 4.16g (0.02mol) and 15mL glacial acetic acid, be heated to when 90 DEG C dripping CrO in three-neck flask3Water-soluble Liquid, after completion of dropping, stirring reaction 20min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, stir Mix a moment, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, anhydrous magnesium sulfate is dried, filtrate rotation is evaporated to obtain yellow Solid, with re crystallization from toluene, yield：80%, 50ml round-bottomed flask adds 95% ethanol and the 4.12g of 20ml (0.02mol) 1- (6- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone, stir about 10min makes solid be completely dissolved, adds The sodium hydrate aqueous solution of 8ml10%, stirring is lower to add 0.02mol benzaldehyde, and after a period of time, system separates out a large amount of solids, uses TLC detects reaction end, has reacted rear suction filtration and has obtained solid (61%).
1HNMR(CDCl3)δ:8.96 (brs, 1H), 787 (d, J=12Hz, 2H), 7.75 (d, J=8.07Hz, 1H), 7.59 (s,1H),7.40(s,1H),7.37-7.31(m,5H),3.38(s,3H)MS(EI+)m/z:294[M]+.
Embodiment 125:1- (6- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- The preparation of ketone (compound 125)
With compound 1- (6- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method for embodiment 124 Reaction obtains 1- (6- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (76%).
1HNMR(CDCl3)δ:8.70 (s, 1H), 7.73 (d, J=8.15Hz, 1H), 7.65 (d, J=12Hz, 1H), 7.59 (s, 1H), 7.47-7.42 (m, 3H), 7.20 (d, J=3.27Hz, 1H), 6.69 (d, J=3.08Hz, 1H) MS (EI+)m/z: 284[M]+.
Embodiment 126:1- (6- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- The preparation of ketone (compound 126)
With compound 1- (6- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method for embodiment 124 Reaction obtains 1- (6- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (69%).
1HNMR(CDCl3)δ:9.62 (brs, 1H), 8.37 (d, J=15.9Hz, 2H), 7.79 (d, J=8.07Hz, 1H), 7.42 (d, J=7.93Hz, 2H), 7.20-7.16 (m, 4H), 3.30 (s, 3H) MS (EI+)m/z:295[M]+.
Embodiment 127:1- (6- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- The preparation of ketone (compound 127)
With compound 1- (6- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method for embodiment 124 Reaction obtains 1- (6- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (61%).
1HNMR(CDCl3)δ:9.39 (brs, 1H), 8.26 (d, J=12Hz, 2H), 7.87 (d, J=8.07Hz, 1H), 7.79 (d, J=7.93Hz, 1H), 7.60-7.52 (m, 5H), 3.37 (s, 3H) MS (EI+)m/z:328[M]+.
Embodiment 128:1- (6- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- The preparation of ketone (compound 128)
With compound 1- (6- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method for embodiment 124 Reaction obtains 1- (6- sulphomethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (53%).
1HNMR(CDCl3)δ:9.98 (brs, 1H), 8.23 (d, J=12Hz, 1H), 7.87 (d, J=8.07Hz, 1H), 7.74 (d, J=7.93Hz, 2H), 7.49-7.42 (m, 5H), 3.41 (s, 3H) MS (EI+)m/z:295[M]+.
Embodiment 129:1- (7- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- phenyl-propane -2- alkene -1- ketone (chemical combination Thing 129) preparation
8.4g (0.05mol) 3- thio-ethyl benzene -1,2- diamines, 4.5g (0.05mol) is added in the round-bottomed flask of 50mL Lactic acid and 4mol/L hydrochloric acid 20mL, are heated to reflux 3h, are cooled to room temperature.It is neutralized to purple litmus paper with concentrated ammonia liquor to redden, Suction filtration goes out solid, recrystallizes (72%) with water.In the three-neck flask of 50mL add 1- (7- thio-ethyl -1H- benzimidazole - 2- ethyl) alcohol 4.44g (0.02mol) and 15mL glacial acetic acid, be heated to when 90 DEG C dripping CrO in three-neck flask3Water-soluble Liquid, after completion of dropping, stirring reaction 20min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, stir Mix a moment, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, anhydrous magnesium sulfate is dried, filtrate rotation is evaporated to obtain yellow Solid, with re crystallization from toluene, yield：80%, 50ml round-bottomed flask adds 95% ethanol and the 4.4g (0.02mol) of 20ml 1- (7- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone, stir about 10min makes solid be completely dissolved, adds 8ml10%'s Sodium hydrate aqueous solution, stirring is lower to add 0.02mol benzaldehyde, and after a period of time, system separates out a large amount of solids, anti-with TLC detection Answer terminal, reacted rear suction filtration and obtained solid.Yield:71%.
1HNMR(CDCl3)δ:9.73 (brs, 1H), 8.01 (d, J=12Hz, 2H), 7.67 (d, J=8.07Hz, 1H), 7.53 (d, J=7.93Hz, 2H), 7.39-7.31 (m, 5H), 3.89 (s, 2H), 1.77 (s, 3H) MS (EI+)m/z:308[M]+.
Embodiment 130:1- (7- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- The preparation of ketone (compound 130)
With compound 1- (7- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method for embodiment 129 Reaction obtains 1- (7- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (61%).
1HNMR(CDCl3)δ:9.79 (brs, 1H), 7.82 (d, J=12Hz, 2H), 7.43 (d, J=7.93Hz, 2H), 7.30-7.25(m,5H),3.96(s,2H),2.08(s,3H)MS(EI+)m/z:342[M]+.
Embodiment 131:1- (7- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- The preparation of ketone (compound 131)
With compound 1- (7- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method for embodiment 129 Reaction obtains 1- (7- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (78%).
1HNMR(CDCl3)δ:9.37 (brs, 1H), 8.27 (s, 1H), 7.93 (d, J=8.07Hz, 1H), 7.60 (d, J= 7.93Hz,2H),7.43-7.39(m,5H),3.99(s,2H),1.79(s,3H)MS(EI+)m/z:309[M]+.
Embodiment 132:1- (7- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- The preparation of ketone (compound 132)
With compound 1- (7- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method for embodiment 129 Reaction obtains 1- (7- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (71%).
1HNMR(CDCl3)δ:9.80 (brs, 1H), 8.34 (s, 1H), 7.61 (d, J=8.07Hz, 1H), 7.40 (d, J= 7.93Hz,2H),7.32-7.28(m,5H),4.19(s,2H),1.83(s,3H)MS(EI+)m/z:309[M]+.
Embodiment 133:1- (7- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- The preparation of ketone (compound 133)
With compound 1- (7- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method for embodiment 129 Reaction obtains 1- (7- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (73%).
1HNMR(CDCl3)δ:8.99 (brs, 1H), 7.74 (d, J=8.15Hz, 1H), 7.60 (d, J=15.69Hz, 1H), 7.53 (s, 1H), 7.41-7.36 (m, 3H), 6.24 (dd, J=1.63Hz, J=3.08Hz, 1H), 3.76 (s, 2H), 1.35 (s, 3H)MS(EI+)m/z:298[M]+.
Embodiment 134:1- (6- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- phenyl-propane -2- alkene -1- ketone (chemical combination Thing 134) preparation
8.4g (0.05mol) 4- thio-ethyl benzene -1,2- diamines, 4.5g (0.05mol) is added in the round-bottomed flask of 50mL Lactic acid and 4mol/L hydrochloric acid 20mL, are heated to reflux 3h, are cooled to room temperature.It is neutralized to purple litmus paper with concentrated ammonia liquor to redden, Suction filtration goes out solid, recrystallizes (72%) with water.In the three-neck flask of 50mL add 1- (6- thio-ethyl -1H- benzimidazole - 2- ethyl) alcohol 4.44g (0.02mol) and 15mL glacial acetic acid, be heated to when 90 DEG C dripping CrO in three-neck flask3Water-soluble Liquid, after completion of dropping, stirring reaction 20min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, stir Mix a moment, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, anhydrous magnesium sulfate is dried, filtrate rotation is evaporated to obtain yellow Solid, with re crystallization from toluene, yield：80%, 50ml round-bottomed flask adds 95% ethanol and the 4.4g (0.02mol) of 20ml 1- (6- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone, stir about 10min makes solid be completely dissolved, adds 8ml10%'s Sodium hydrate aqueous solution, stirring is lower to add 0.02mol benzaldehyde, and after a period of time, system separates out a large amount of solids, anti-with TLC detection Answer terminal, reacted rear suction filtration and obtained solid.Yield:79%.
1HNMR(CDCl3)δ:9.37 (brs, 1H), 7.89 (d, J=12Hz, 2H), 7.69 (d, J=8.07Hz, 1H), 7.53(s,1H),7.41(s,1H),7.37-7.30(m,5H),3.96(s,2H),1.75(s,3H)MS(EI+)m/z:308[M]+.
Embodiment 135:1- (6- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- The preparation of ketone (compound 135)
With compound 1- (6- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method for embodiment 134 Reaction obtains 1- (6- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (77%).
1HNMR(CDCl3)δ:9.93 (brs, 1H), 8.03 (dd, J=15.9Hz, J=12Hz, 2H), 7.90 (d, J= 8.07Hz, 1H), 7.86 (d, J=7.93Hz, 1H), 7.52-7.46 (m, 5H), 3.68 (s, 2H), 1.37 (s, 3H) MS (EI+) m/z:298[M]+.
Embodiment 136:1- (6- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- The preparation of ketone (compound 136)
With compound 1- (6- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method for embodiment 134 Reaction obtains 1- (6- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (67%).
1HNMR(CDCl3)δ:11.26 (brs, 1H), 8.37 (d, J=15.9Hz, 1H), 7.83 (d, J=8.07Hz, 1H), 7.75 (d, J=7.93Hz, 2H), 7.45-7.39 (m, 5H), 3.90 (s, 2H), 1.76 (s, 3H) MS (EI+)m/z:309[M]+.
Embodiment 137:1- (6- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- The preparation of ketone (compound 137)
With compound 1- (6- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method for embodiment 134 Reaction obtains 1- (6- ethyoxyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (4- pyridine radicals)-propane -2- alkene -1- ketone (89%).
1HNMR(CDCl3)δ:9.63 (brs, 1H), 8.17 (d, J=12Hz, 2H), 7.77 (d, J=8.07Hz, 1H), 7.35 (d, J=7.93Hz, 2H), 7.10-7.04 (m, 4H)), 3.62 (s, 2H), 1.79 (s, 3H) MS (EI+)m/z:342[M]+.
Embodiment 138:1- (6- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- The preparation of ketone (compound 138)
With compound 1- (6- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) ketone as raw material, according to the method for embodiment 134 Reaction obtains 1- (6- thio-ethyl -1H- benzimidazolyl-2 radicals-ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (80%).
1HNMR(CDCl3)δ:9.62 (brs, 1H), 7.71 (d, J=8.15Hz, 1H), 7.65 (d, J=12Hz, 1H), 7.53 (s, 1H), 7.40-7.32 (m, 3H), 7.02 (d, J=3.27Hz, 1H), 6.49 (d, J=9Hz, 1H), 3.93 (s, 2H),2.06(s,3H)MS(EI+)m/z:309[M]+.
Embodiment 139:1- (7- chloro- 1H- benzothiazole -2- ethyl) -3- phenyl-propane -2- alkene -1- ketone (compound 139) Preparation
0.143g (0.001mol) 2- amino -6- chlorophenol, 0.9g (0.01mol) breast is added in the round-bottomed flask of 50mL Acid, is heated to reflux 3h under nitrogen protection, is cooled to room temperature.It is neutralized to purple litmus paper with saturated sodium bicarbonate aqueous solution to become Red, suction filtration goes out solid, recrystallizes (51%) with water.1- (7- chloro- 1H- benzothiazole -2- second is added in the three-neck flask of 50mL Base) alcohol 0.197g (0.001mol) and 10mL glacial acetic acid, be heated to being slowly added dropwise CrO in three-neck flask when 90 DEG C3Water Solution, after completion of dropping, stirring reaction 5min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, Stirring a moment, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, and anhydrous magnesium sulfate is dried, and filtrate rotation is evaporated light Yellow solid, with ethyl alcohol recrystallization, yield：63%. 95% ethanol and the 0.195g adding 10ml in 50ml round-bottomed flask (0.001mol) 1- (7- chloro- 1H- benzothiazole -2- ethyl) ketone, stir about 10min makes solid be completely dissolved, adds The sodium hydrate aqueous solution of 8ml10%, stirring is lower to add 0.0015mol benzaldehyde, and after a period of time, system separates out a large amount of solids, Detect reaction end with TLC, reacted rear suction filtration and obtained solid (52%).
1HNMR(CDCl3)δ:7.96 (d, J=12Hz, 2H), 7.72 (d, J=8.07Hz, 1H), 7.48 (d, J= 7.93Hz,2H),7.23-7.19(m,5H)MS(EI+)m/z:283[M]+.
Embodiment 140:1- (7- chloro- 1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (chemical combination Thing 140) preparation
With compound 1- (7- chloro- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 139 To 1- (7- chloro- 1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (75%).
1HNMR(CDCl3)δ:7.87 (d, J=12Hz, 2H), 7.40 (d, J=7.93Hz, 2H), 7.32-7.29 (m, 5H) MS(EI+)m/z:317[M]+.
Embodiment 141:1- (7- chloro- 1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 141) preparation
With compound 1- (7- chloro- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 139 To 1- (7- chloro- 1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (57%).
1HNMR(CDCl3)δ:7.95 (s, 1H), 7.72 (d, J=8.07Hz, 1H), 7.53 (d, J=7.93Hz, 2H), 7.32-7.28(m,5H)MS(EI+)m/z:284[M]+.
Embodiment 142:1- (7- chloro- 1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 142) preparation
With compound 1- (7- chloro- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 139 To 1- (7- chloro- 1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (47%).
1HNMR(CDCl3)δ:8.76 (s, 1H), 7.71 (d, J=8Hz, 1H), 7.40 (d, J=7.93Hz, 2H), 7.33- 7.29(m,5H)MS(EI+)m/z:284[M]+.
Embodiment 143:1- (7- chloro- 1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (chemical combination Thing 143) preparation
With compound 1- (7- chloro- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 139 To 1- (7- chloro- 1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (58%).
1HNMR(CDCl3)δ:7.95 (d, J=8.15Hz, 1H), 7.68d, J=12Hz, 1H), 7.47 (s, 1H), 7.33- 7.29 (m, 3H), 6.87 (d, J=7.2Hz, 1H) MS (EI+)m/z:273[M]+.
Embodiment 144:1- (6- chloro- 1H- benzothiazole -2- ethyl) -3- phenyl-propane -2- alkene -1- ketone (compound 144) preparation,
0.143g (0.001mol) 2- amino -5- chlorophenol, 0.9g (0.01mol) breast is added in the round-bottomed flask of 50mL Acid, is heated to reflux 3h under nitrogen protection, is cooled to room temperature.It is neutralized to purple litmus paper with saturated sodium bicarbonate aqueous solution to become Red, suction filtration goes out solid, recrystallizes (51%) with water.1- (6- chloro- 1H- benzothiazole -2- second is added in the three-neck flask of 50mL Base) alcohol 0.197g (0.001mol) and 10mL glacial acetic acid, be heated to being slowly added dropwise CrO in three-neck flask when 90 DEG C3Water Solution, after completion of dropping, stirring reaction 5min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, Stirring a moment, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, and anhydrous magnesium sulfate is dried, and filtrate rotation is evaporated light Yellow solid, with ethyl alcohol recrystallization, yield：63%. 95% ethanol and the 0.195g adding 10ml in 50ml round-bottomed flask (0.001mol) 1- (6- chloro- 1H- benzothiazole -2- ethyl) ketone, stir about 10min makes solid be completely dissolved, adds The sodium hydrate aqueous solution of 8ml10%, stirring is lower to add 0.0015mol benzaldehyde, and after a period of time, system separates out a large amount of solids, Detect reaction end with TLC, reacted rear suction filtration and obtained solid.Yield:57%.
1HNMR(CDCl3)δ:7.87 (d, J=12Hz, 2H), 7.70 (d, J=7.2Hz, 1H), 7.52 (s, 1H), 7.49 (s,1H),7.30-7.24(m,5H)MS(EI+)m/z:283[M]+.
Embodiment 145:1- (6- chloro- 1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (chemical combination Thing 145) preparation
With compound 1- (6- chloro- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 144 To 1- (6- chloro- 1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (76%).
1HNMR(CDCl3)δ:7.73 (d, J=8.4Hz, 1H), 7.68 (d, J=12Hz, 1H), 7.50 (s, 1H), 7.32- 7.29 (m, 3H), 6.92 (d, J=3.27Hz, 1H), 6.51 (d, J=7.2Hz, 1H) MS (EI+)m/z:273[M]+.
Embodiment 146:1- (6- chloro- 1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 146) preparation
With compound 1- (6- chloro- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 144 To 1- (6- chloro- 1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (77%).
1HNMR(CDCl3)δ:8.15 (d, J=15.6Hz, 2H), 7.83 (d, J=8.4Hz, 1H), 7.44 (d, J= 7.93Hz,2H),7.10-7.02(m,4H)MS(EI+)m/z:284[M]+.
Embodiment 147:1- (6- chloro- 1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (chemical combination Thing 147) preparation
With compound 1- (6- chloro- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 144 To 1- (6- chloro- 1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (61%).
1HNMR(CDCl3)δ:8.41 (dJ=12Hz, 2H), 7.90 (d, J=8.4Hz, 1H), 7.86 (d, J=7.93Hz, 1H),7.52-7.47(m,5H)MS(EI+)m/z:317[M]+.
Embodiment 148:1- (6- chloro- 1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 148) preparation
With compound 1- (6- chloro- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 144 To 1- (6- chloro- 1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (67%).
1HNMR(CDCl3)δ:8.19 (d, J=12Hz, 1H), 7.86 (d, J=8.07Hz, 1H), 7.77 (d, J= 7.93Hz,2H),7.42-7.37(m,5H)MS(EI+)m/z:284[M]+.
Embodiment 149:1- (7- chloro- 1H- benzothiazole -2- ethyl) -3- phenyl-propane -2- alkene -1- ketone (compound 149) Preparation
0.159g (0.001mol) 2- amino -6- chlorothio-phenol, 0.9g (0.01mol) breast is added in the round-bottomed flask of 50mL Acid, is heated to reflux 3h under nitrogen protection, is cooled to room temperature.It is neutralized to purple litmus paper with saturated sodium bicarbonate aqueous solution to become Red, suction filtration goes out solid, recrystallizes (51%) with water.1- (7- chloro- 1H- benzothiazole -2- second is added in the three-neck flask of 50mL Base) alcohol 0.213g (0.001mol) and 10mL glacial acetic acid, be heated to being slowly added dropwise CrO in three-neck flask when 90 DEG C3Water Solution, after completion of dropping, stirring reaction 5min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, Stirring a moment, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, and anhydrous magnesium sulfate is dried, and filtrate rotation is evaporated light Yellow solid, with ethyl alcohol recrystallization, yield：63%. 95% ethanol and the 0.211g adding 10ml in 50ml round-bottomed flask (0.001mol) 1- (7- chloro- 1H- benzothiazole -2- ethyl) ketone, stir about 10min makes solid be completely dissolved, adds The sodium hydrate aqueous solution of 8ml10%, stirring is lower to add 0.0015mol benzaldehyde, and after a period of time, system separates out a large amount of solids, Detect reaction end with TLC, reacted rear suction filtration and obtained solid, yield:74%
1HNMR(CDCl3)δ:7.81 (d, J=12Hz, 2H), 7.62 (d, J=8.07Hz, 1H), 7.45 (d, J= 7.93Hz,2H),7.17-7.12(m,5H)MS(EI+)m/z:299[M]+.
Embodiment 150:1- (7- chloro- 1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (chemical combination Thing 150) preparation
With compound 1- (7- chloro- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 149 To 1- (7- chloro- 1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (41%).
1HNMR(CDCl3)δ:7.73 (d, J=12Hz, 2H), 7.41 (d, J=7.93Hz, 2H), 7.31-7.27 (m, 5H) MS(EI+)m/z:332.9[M]+.
Embodiment 151:1- (7- chloro- 1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 151) preparation
With compound 1- (7- chloro- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 149 To 1- (7- chloro- 1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (57%).
1HNMR(CDCl3)δ:7.82 (s, 1H), 7.74 (d, J=8.07Hz, 1H), 7.43 (d, J=7.93Hz, 2H), 7.38-7.34(m,5H)MS(EI+)m/z:300[M]+.
Embodiment 152:1- (7- chloro- 1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 152) preparation
With compound 1- (7- chloro- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 149 To 1- (7- chloro- 1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (43%).
1HNMR(CDCl3)δ:8.93 (s, 1H), 7.69 (d, J=8Hz, 1H), 7.42 (d, J=7.93Hz, 2H), 7.31- 7.26(m,5H)MS(EI+)m/z:300[M]+.
Embodiment 153:1- (7- chloro- 1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (chemical combination Thing 153) preparation
With compound 1- (7- chloro- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 149 To 1- (7- chloro- 1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (56%).
1HNMR(CDCl3)δ:7.89 (d, J=8.15Hz, 1H), 7.60 (d, J=12Hz, 1H), 7.52 (s, 1H), 7.31- 7.27 (m, 3H), 6.74 (d, J=7.2Hz, 1H) MS (EI+)m/z:289[M]+.
Embodiment 154:1- (6- chloro- 1H- benzothiazole -2- ethyl) -3- phenyl-propane -2- alkene -1- ketone (compound 154) Preparation
0.159g (0.001mol) 2- amino -5- chlorothio-phenol, 0.9g (0.01mol) breast is added in the round-bottomed flask of 50mL Acid, is heated to reflux 3h under nitrogen protection, is cooled to room temperature.It is neutralized to purple litmus paper with saturated sodium bicarbonate aqueous solution to become Red, suction filtration goes out solid, recrystallizes (51%) with water.1- (6- chloro- 1H- benzothiazole -2- second is added in the three-neck flask of 50mL Base) alcohol 0.213g (0.001mol) and 10mL glacial acetic acid, be heated to being slowly added dropwise CrO in three-neck flask when 90 DEG C3Water Solution, after completion of dropping, stirring reaction 5min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, Stirring a moment, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, and anhydrous magnesium sulfate is dried, and filtrate rotation is evaporated light Yellow solid, with ethyl alcohol recrystallization, yield：63%. 95% ethanol and the 0.211g adding 10ml in 50ml round-bottomed flask (0.001mol) 1- (6- chloro- 1H- benzothiazole -2- ethyl) ketone, stir about 10min makes solid be completely dissolved, adds The sodium hydrate aqueous solution of 8ml10%, stirring is lower to add 0.0015mol benzaldehyde, and after a period of time, system separates out a large amount of solids, Detect reaction end with TLC, reacted rear suction filtration and obtained solid.Yield:57%.
1HNMR(CDCl3)δ:7.92 (d, J=12Hz, 2H), 7.74 (d, J=7.2Hz, 1H), 7.53 (s, 1H), 7.42 (s,1H),7.36-7.30(m,5H)MS(EI+)m/z:299[M]+.
Embodiment 155:1- (6- chloro- 1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (chemical combination Thing 155) preparation
With compound 1- (6- chloro- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 154 To 1- (6- chloro- 1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (83%).
1HNMR(CDCl3)δ:7.79 (d, J=8.4Hz, 1H), 7.62 (d, J=12Hz, 1H), 7.57 (s, 1H), 7.34- 7.30 (m, 3H), 7.17 (d, J=3.27Hz, 1H), 6.69 (d, J=7.2Hz, 1H) MS (EI+)m/z:289[M]+.
Embodiment 156:1- (6- chloro- 1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 156) preparation
With compound 1- (6- chloro- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 154 To 1- (6- chloro- 1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (74%).
1HNMR(CDCl3)δ:8.20 (d, J=15.6Hz, 2H), 7.76 (d, J=8.4Hz, 1H), 7.42 (d, J= 7.93Hz,2H),7.23-7.17(m,4H)MS(EI+)m/z:300[M]+.
Embodiment 157:1- (6- chloro- 1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (chemical combination Thing 154) preparation
With compound 1- (6- chloro- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 154 To 1- (6- chloro- 1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (63%).
1HNMR(CDCl3)δ:8.36 (d, J=12Hz, 2H), 7.95 (d, J=8.4Hz, 1H), 7.79 (d, J=7.93Hz, 1H),7.43-7.39(m,5H)MS(EI+)m/z:332.9[M]+.
Embodiment 158:1- (6- chloro- 1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 158) preparation
With compound 1- (6- chloro- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 154 To 1- (6- chloro- 1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (73%).
1HNMR(CDCl3)δ:8.07 (d, J=12Hz, 1H), 7.83 (d, J=8.07Hz, 1H), 7.63 (d, J= 7.93Hz,2H),7.49-7.43(m,5H)MS(EI+)m/z:300[M]+.
Embodiment 159:1- (7- bromo- 1H- benzothiazole -2- ethyl) -3- phenyl-propane -2- alkene -1- ketone (compound 159) Preparation
0.188g (0.001mol) 2- amino -6- bromophenol, 0.9g (0.01mol) breast is added in the round-bottomed flask of 50mL Acid, is heated to reflux 3h under nitrogen protection, is cooled to room temperature.It is neutralized to purple litmus paper with saturated sodium bicarbonate aqueous solution to become Red, suction filtration goes out solid, recrystallizes (51%) with water.1- (7- bromo- 1H- benzothiazole -2- second is added in the three-neck flask of 50mL Base) alcohol 0.241g (0.001mol) and 10mL glacial acetic acid, be heated to being slowly added dropwise CrO in three-neck flask when 90 DEG C3Water Solution, after completion of dropping, stirring reaction 5min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, Stirring a moment, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, and anhydrous magnesium sulfate is dried, and filtrate rotation is evaporated light Yellow solid, with ethyl alcohol recrystallization, yield：63%. 95% ethanol and the 0.239g adding 10ml in 50ml round-bottomed flask (0.001mol) 1- (7- bromo- 1H- benzothiazole -2- ethyl) ketone, stir about 10min makes solid be completely dissolved, adds The sodium hydrate aqueous solution of 8ml10%, stirring is lower to add 0.0015mol benzaldehyde, and after a period of time, system separates out a large amount of solids, Detect reaction end with TLC, reacted rear suction filtration and obtained solid.Yield:77%
1HNMR(CDCl3)δ:7.79 (d, J=12Hz, 2H), 7.68 (d, J=8.07Hz, 1H), 7.56 (d, J= 7.93Hz,2H),7.21-7.17(m,5H)MS(EI+)m/z:326.9[M]+.
Embodiment 160:1- (7- bromo- 1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (chemical combination Thing 160) preparation
With compound 1- (7- bromo- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 159 To 1- (7- bromo- 1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (58%).
1HNMR(CDCl3)δ:7.86 (d, J=12Hz, 2H), 7.52 (d, J=7.8Hz, 2H), 7.36-7.31 (m, 5H) MS (EI+)m/z:326.9[M]+.
Embodiment 161:1- (7- bromo- 1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 161) preparation
With compound 1- (7- bromo- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 159 To 1- (7- bromo- 1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (59%).
1HNMR(CDCl3)δ:7.84 (s, 1H), 7.70 (d, J=8.4Hz, 1H), 7.49 (d, J=7.8Hz, 2H), 7.40- 7.35(m,5H)MS(EI+)m/z:327.9[M]+.
Embodiment 162:1- (7- bromo- 1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 162) preparation
With compound 1- (7- bromo- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 159 To 1- (7- bromo- 1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (43%).
1HNMR(CDCl3)δ:9.14 (s, 1H), 7.82 (d, J=8Hz, 1H), 7.53 (d, J=7.8Hz, 2H), 7.33- 7.28(m,5H)MS(EI+)m/z:327.9[M]+.
Embodiment 163:1- (7- bromo- 1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (chemical combination Thing 163) preparation
With compound 1- (7- bromo- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 159 To 1- (7- bromo- 1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (71%).
1HNMR(CDCl3)δ:7.93 (d, J=8.4Hz, 1H), 7.79 (d, J=12Hz, 1H), 7.52 (s, 1H), 7.30- 7.25 (m, 3H), 6.86 (d, J=7.2Hz, 1H) MS (EI+)m/z:316.9[M]+.
Embodiment 164:1- (6- bromo- 1H- benzothiazole -2- ethyl) -3- phenyl-propane -2- alkene -1- ketone (compound 164) Preparation
0.188g (0.001mol) 2- amino -5- bromophenol, 0.9g (0.01mol) breast is added in the round-bottomed flask of 50mL Acid, is heated to reflux 3h under nitrogen protection, is cooled to room temperature.It is neutralized to purple litmus paper with saturated sodium bicarbonate aqueous solution to become Red, suction filtration goes out solid, recrystallizes (51%) with water.1- (6- bromo- 1H- benzothiazole -2- second is added in the three-neck flask of 50mL Base) alcohol 0.241g (0.001mol) and 10mL glacial acetic acid, be heated to being slowly added dropwise CrO in three-neck flask when 90 DEG C3Water Solution, after completion of dropping, stirring reaction 5min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, Stirring a moment, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, and anhydrous magnesium sulfate is dried, and filtrate rotation is evaporated light Yellow solid, with ethyl alcohol recrystallization, yield：63%. 95% ethanol and the 0.239g adding 10ml in 50ml round-bottomed flask (0.001mol) 1- (6- bromo- 1H- benzothiazole -2- ethyl) ketone, stir about 10min makes solid be completely dissolved, adds The sodium hydrate aqueous solution of 8ml10%, stirring is lower to add 0.0015mol benzaldehyde, and after a period of time, system separates out a large amount of solids, Detect reaction end with TLC, reacted rear suction filtration and obtained solid.(70%).
1HNMR(CDCl3)δ:7.90 (d, J=12Hz, 2H), 7.71 (d, J=7.2Hz, 1H), 7.56 (s, 1H), 7.44 (s,1H),7.39-7.33(m,5H)MS(EI+)m/z:326.9[M]+.
Embodiment 165:1- (6- bromo- 1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (chemical combination Thing 165) preparation
With compound 1- (6- bromo- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 164 To 1- (6- bromo- 1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (80%).
1HNMR(CDCl3)δ:7.88 (d, J=8.4Hz, 1H), 7.69 (d, J=12Hz, 1H), 7.50 (s, 1H), 7.33- 7.28 (m, 3H), 7.12 (d, J=3.27Hz, 1H), 6.52 (d, J=7.2Hz, 1H) MS (EI+)m/z:316.9[M]+.
Embodiment 166:1- (6- bromo- 1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 166) preparation
With compound 1- (6- bromo- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 164 To 1- (6- bromo- 1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (32%).
1HNMR(CDCl3)δ:8.13 (d, J=15.6Hz, 2H), 7.70 (d, J=8.4Hz, 1H), 7.51 (d, J= 7.8Hz,2H),7.21-7.14(m,4H)MS(EI+)m/z:327.9[M]+.
Embodiment 167:1- (6- bromo- 1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (chemical combination Thing 167) preparation
With compound 1- (6- bromo- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 164 To 1- (6- bromo- 1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (63%).
1HNMR(CDCl3)δ:8.23 (d, J=12Hz, 2H), 7.97 (d, J=8.4Hz, 1H), 7.65 (d, J=7.8Hz, 1H),7.40-7.36(m,5H)MS(EI+)m/z:362.9[M]+.
Embodiment 168:1- (6- bromo- 1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 168) preparation
With compound 1- (6- bromo- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 164 To 1- (6- bromo- 1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone
1HNMR(CDCl3)δ:8.11 (d, J=12Hz, 1H), 7.73 (d, J=8.4Hz, 1H), 7.61 (d, J=7.8Hz, 2H),7.44-7.40(m,5H)MS(EI+)m/z:327.9[M]+.
Embodiment 169:1- (7- bromo- 1H- benzothiazole -2- ethyl) -3- phenyl-propane -2- alkene -1- ketone (compound 169) Preparation
0.204g (0.001mol) 2- amino -6- bromo thiophenol, 0.9g (0.01mol) breast is added in the round-bottomed flask of 50mL Acid, is heated to reflux 3h under nitrogen protection, is cooled to room temperature.It is neutralized to purple litmus paper with saturated sodium bicarbonate aqueous solution to become Red, suction filtration goes out solid, recrystallizes (51%) with water.1- (7- bromo- 1H- benzothiazole -2- second is added in the three-neck flask of 50mL Base) alcohol 0.259g (0.001mol) and 10mL glacial acetic acid, be heated to being slowly added dropwise CrO in three-neck flask when 90 DEG C3Water Solution, after completion of dropping, stirring reaction 5min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, Stirring a moment, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, and anhydrous magnesium sulfate is dried, and filtrate rotation is evaporated light Yellow solid, with ethyl alcohol recrystallization, yield：63%. 95% ethanol and the 0.257g adding 10ml in 50ml round-bottomed flask (0.001mol) 1- (7- bromo- 1H- benzothiazole -2- ethyl) ketone, stir about 10min makes solid be completely dissolved, adds The sodium hydrate aqueous solution of 8ml10%, stirring is lower to add 0.0015mol benzaldehyde, and after a period of time, system separates out a large amount of solids, Detect reaction end with TLC, reacted rear suction filtration and obtained solid, yield:71%
1HNMR(CDCl3)δ:7.70 (d, J=12Hz, 2H), 7.59 (d, J=8.07Hz, 1H), 7.43 (d, J=7.8Hz, 2H),7.19-7.13(m,5H)MS(EI+)m/z:344[M]+.
Embodiment 170:1- (7- bromo- 1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (chemical combination Thing 170) preparation
With compound 1- (7- bromo- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 169 To 1- (7- methyl isophthalic acid H- benzimidazolyl-2 radicals-ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (63%).
1HNMR(CDCl3)δ:7.91 (d, J=12Hz, 2H), 7.63 (d, J=7.8Hz, 2H), 7.24-7.19 (m, 5H) MS (EI+)m/z:378[M]+.
Embodiment 171:1- (7- bromo- 1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 171) preparation
With compound 1- (7- bromo- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 169 To 1- (7- bromo- 1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (54%).
1HNMR(CDCl3)δ:7.76 (s, 1H), 7.58 (d, J=8.4Hz, 1H), 7.40 (d, J=7.8Hz, 2H), 7.37- 7.32(m,5H)MS(EI+)m/z:345[M]+.
Embodiment 172:1- (7- bromo- 1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 172) preparation
With compound 1- (7- bromo- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 169 To 1- (7- bromo- 1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (76%).
1HNMR(CDCl3)δ:9.03 (s, 1H), 7.72 (d, J=8.4Hz, 1H), 7.59 (d, J=7.8Hz, 2H), 7.40- 7.36(m,5H)MS(EI+)m/z:345[M]+.
Embodiment 173:1- (7- bromo- 1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (chemical combination Thing 173) preparation
With compound 1- (7- bromo- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 169 To 1- (7- bromo- 1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone.Yield:55%.
1HNMR(CDCl3)δ:8.06 (d, J=8.4Hz, 1H), 7.77 (d, J=12Hz, 1H), 7.42 (s, 1H), 7.20- 7.17 (m, 3H), 6.65 (d, J=7.2Hz, 1H) MS (EI+)m/z:334[M]+.
Embodiment 174:1- (6- bromo- 1H- benzothiazole -2- ethyl) -3- phenyl-propane -2- alkene -1- ketone (compound 174) Preparation
0.204g (0.001mol) 2- amino -5- bromo thiophenol, 0.9g (0.01mol) breast is added in the round-bottomed flask of 50mL Acid, is heated to reflux 3h under nitrogen protection, is cooled to room temperature.It is neutralized to purple litmus paper with saturated sodium bicarbonate aqueous solution to become Red, suction filtration goes out solid, recrystallizes (51%) with water.1- (6- bromo- 1H- benzothiazole -2- second is added in the three-neck flask of 50mL Base) alcohol 0.259g (0.001mol) and 10mL glacial acetic acid, be heated to being slowly added dropwise CrO in three-neck flask when 90 DEG C3Water Solution, after completion of dropping, stirring reaction 5min at 105 DEG C of temperature control, then reactant liquor is poured in the beaker filling 200mL water, Stirring a moment, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, and anhydrous magnesium sulfate is dried, and filtrate rotation is evaporated light Yellow solid, with ethyl alcohol recrystallization, yield：63%. 95% ethanol and the 0.257g adding 10ml in 50ml round-bottomed flask (0.001mol) 1- (6- bromo- 1H- benzothiazole -2- ethyl) ketone, stir about 10min makes solid be completely dissolved, adds The sodium hydrate aqueous solution of 8ml10%, stirring is lower to add 0.0015mol benzaldehyde, and after a period of time, system separates out a large amount of solids, Detect reaction end with TLC, reacted rear suction filtration and obtained solid.Yield:57%.
1HNMR(CDCl3)δ:7.95 (d, J=12Hz, 2H), 7.63 (d, J=7.2Hz, 1H), 7.59 (s, 1H), 7.37 (s,1H),7.22-7.18(m,5H)MS(EI+)m/z:344[M]+.
Embodiment 175:1- (6- bromo- 1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (chemical combination Thing 175) preparation
With compound 1- (6- bromo- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 174 To 1- (6- bromo- 1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (83%).
1HNMR(CDCl3)δ:7.96 (d, J=8.4Hz, 1H), 7.63 (d, J=12Hz, 1H), 7.51 (s, 1H), 7.20- 7.15 (m, 3H), 7.02 (d, J=7.2Hz, 1H), 6.44 (d, J=7.2Hz, 1H) MS (EI+)m/z:334[M]+.
Embodiment 176:1- (6- bromo- 1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2 alkene -1- ketone (chemical combination Thing 176) preparation
With compound 1- (6- bromo- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 174 To 1- (6- bromo- 1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2 alkene -1- ketone (32%).
1HNMR(CDCl3)δ:8.38 (d, J=15.6Hz, 2H), 7.62 (d, J=8.4Hz, 1H), 7.43 (d, J= 7.8Hz,2H),7.13-7.09(m,4H)MS(EI+)m/z:345[M]+.
Embodiment 177:1- (6- bromo- 1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (chemical combination Thing 177) preparation
With compound 1- (6- bromo- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 174 To 1- (6- bromo- 1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (63%).
1HNMR(CDCl3)δ:8.10 (d, J=12Hz, 2H), 7.86 (d, J=8.4Hz, 1H), 7.55 (d, J=7.8Hz, 1H),7.32-7.28(m,5H)MS(EI+)m/z:378[M]+.
Embodiment 178:1- (6- bromo- 1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (chemical combination Thing 178) preparation
With compound 1- (6- bromo- 1H- benzothiazole -2- ethyl), ketone as raw material, react by the method according to embodiment 174 To 1- (6- bromo- 1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (77%)
1HNMR(CDCl3)δ:8.01 (d, J=12Hz, 1H), 7.69 (d, J=8.4Hz, 1H), 7.53 (d, J=7.8Hz, 2H),7.37-7.34(m,5H)MS(EI+)m/z:345[M]+.
Embodiment 179:1- (7- sulphomethyl -1H- benzothiazole -2- ethyl) -3- phenyl-propane -2- alkene -1- ketone (chemical combination Thing 179) preparation
0.155g (0.001mol) 2- amino -6- sulphomethyl phenol, 0.9g is added in the round-bottomed flask of 50mL (0.001mol) lactic acid and 4mol/L hydrochloric acid 20mL, is heated to reflux 3h under nitrogen protection, is cooled to room temperature.Neutralized with concentrated ammonia liquor Redden to purple litmus paper, suction filtration goes out solid, recrystallize (72%) with water.1- (7- sulphur is added in the three-neck flask of 50mL For methyl isophthalic acid H- benzothiazole -2- ethyl) glacial acetic acid of alcohol 0.209g (0.001mol) and 10mL, it is heated to when 90 DEG C to three necks CrO is dripped in flask3The aqueous solution, after completion of dropping, stirring reaction 10min at 105 DEG C of temperature control, then reactant liquor is poured into Sheng Have in the beaker of 200mL water, stirring a moment, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, and anhydrous magnesium sulfate is done Dry, filtrate rotation is evaporated to obtain yellow solid, with re crystallization from toluene, yield：71%, add 15ml's in 50ml round-bottomed flask 95% ethanol and 0.207g (0.001mol) 1- (7- sulphomethyl -1H- benzothiazole -2- ethyl) ketone, stir about 10min makes solid Body is completely dissolved, and adds the sodium hydrate aqueous solution of 8ml10%, and stirring is lower to add 0.0015mol benzaldehyde, after a period of time System separates out a large amount of solids, detects reaction end with TLC, has reacted rear suction filtration and obtained solid.Yield:53%
1HNMR(CDCl3)δ:7.90 (d, J=12Hz, 2H), 7.75 (d, J=8.4Hz, 1H), 7.61 (d, J=7.8Hz, 2H),7.47(s,1H),7.22-7.18(m,4H),3.23(s,3H)MS(EI+)m/z:295[M]+.
Embodiment 180:1- (7- sulphomethyl -1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- The preparation of ketone (compound 180)
With compound 1- (7- sulphomethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 179 Reaction obtains 1- (7- sulphomethyl -1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (54%).
1HNMR(CDCl3)δ:7.76 (d, J=12Hz, 2H), 7.47 (d, J=7.8Hz, 2H), 7.34-7.29 (m, 5H), 3.88(s,3H)MS(EI+)m/z:329[M]+.
Embodiment 181:1- (7- sulphomethyl -1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- The preparation of ketone (compound 181)
With compound 1- (7- sulphomethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 179 Reaction obtains 1- (7- sulphomethyl -1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (58%).
1HNMR(CDCl3)δ:8.11 (s, 1H), 7.66 (d, J=8.4Hz, 1H), 7.54 (d, J=7.8Hz, 2H), 7.41- 7.36(m,5H),3.78(s,3H)MS(EI+)m/z:296[M]+.
Embodiment 182:1- (7- sulphomethyl -1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- The preparation of ketone (compound 182)
With compound 1- (7- sulphomethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 179 Reaction obtains 1- (7- sulphomethyl -1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (59%).
1HNMR(CDCl3)δ:8.81 (s, 1H), 7.62 (d, J=8.4Hz, 1H), 7.49 (d, J=7.8Hz, 2H), 7.24- 7.19(m,5H),3.86(s,3H)MS(EI+)m/z:296[M]+.
Embodiment 183:1- (7- sulphomethyl -1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- The preparation of ketone (compound 183)
With compound 1- (7- sulphomethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 179 Reaction obtains 1- (7- sulphomethyl -1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (71%).
1HNMR(CDCl3)δ:7.61 (d, J=8.4Hz, 1H), 7.58 (d, J=15.6Hz, 1H), 7.40 (s, 1H), 7.31-7.28(m,3H),6.72(s,1H),3.86(s,3H)MS(EI+)m/z:285[M]+.
Embodiment 184:1- (6- sulphomethyl -1H- benzothiazole -2- ethyl) -3- phenyl-propane -2- alkene -1- ketone (chemical combination Thing 184) preparation
0.155g (0.001mol) 2- amino -5- sulphomethyl phenol, 0.9g is added in the round-bottomed flask of 50mL (0.001mol) lactic acid and 4mol/L hydrochloric acid 20mL, is heated to reflux 3h under nitrogen protection, is cooled to room temperature.Neutralized with concentrated ammonia liquor Redden to purple litmus paper, suction filtration goes out solid, recrystallize (72%) with water.1- (6- sulphur is added in the three-neck flask of 50mL For methyl isophthalic acid H- benzothiazole -2- ethyl) glacial acetic acid of alcohol 0.209g (0.001mol) and 10mL, it is heated to when 90 DEG C to three necks CrO is dripped in flask3The aqueous solution, after completion of dropping, stirring reaction 10min at 105 DEG C of temperature control, then reactant liquor is poured into Sheng Have in the beaker of 200mL water, stirring a moment, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, and anhydrous magnesium sulfate is done Dry, filtrate rotation is evaporated to obtain yellow solid, with re crystallization from toluene, yield：71%, add 15ml's in 50ml round-bottomed flask 95% ethanol and 0.207g (0.001mol) 1- (6- sulphomethyl -1H- benzothiazole -2- ethyl) ketone, stir about 10min makes solid Body is completely dissolved, and adds the sodium hydrate aqueous solution of 8ml10%, and stirring is lower to add 0.0015mol benzaldehyde, after a period of time System separates out a large amount of solids, detects reaction end with TLC, has reacted rear suction filtration and obtained solid.(50%)
1HNMR(CDCl3)δ:7.92 (d, J=12Hz, 2H), 7.70 (d, J=8.4Hz, 1H), 7.59 (s, 1H), 7.40 (s,1H),7.47(s,1H),7.31-7.24(m,4H),3.81(s,3H)MS(EI+)m/z:295[M]+.
Embodiment 185:1- (6- sulphomethyl -1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- The preparation of ketone (compound 185)
With compound 1- (6- sulphomethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 184 Reaction obtains 1- (6- sulphomethyl -1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (71%).
1HNMR(CDCl3)δ:8.61 (s, 1H), 7.89 (d, J=8.4Hz, 1H), 7.60 (d, J=12Hz, 1H), 7.53 (s,1H),7.38-7.33(m,3H),7.23(s,1H),6.77(s,1H)MS(EI+)m/z:285[M]+.
Embodiment 186:1- (6- sulphomethyl -1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- The preparation of ketone (compound 186)
With compound 1- (6- sulphomethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 184 Reaction obtains 1- (6- sulphomethyl -1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (56%).
1HNMR(CDCl3)δ:8.37 (d, J=15.6Hz, 2H), 7.63 (d, J=8.4Hz, 1H), 7.47 (d, J= 7.8Hz,2H),7.18-7.14(m,4H),3.76(s,3H)MS(EI+)m/z:296[M]+.
Embodiment 187:1- (6- sulphomethyl -1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- The preparation of ketone (compound 187)
With compound 1- (6- sulphomethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 184 Reaction obtains 1- (6- sulphomethyl -1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (64%).
1HNMR(CDCl3)δ:8.32 (d, J=12Hz, 2H), 7.96 (d, J=8.4Hz, 1H), 7.79 (d, J=7.8Hz, 1H),7.49-7.44(m,5H),3.83(s,3H)MS(EI+)m/z:329[M]+.
Embodiment 188:1- (6- sulphomethyl -1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- The preparation of ketone (compound 188)
With compound 1- (6- sulphomethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 184 Reaction obtains 1- (6- sulphomethyl -1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (71%).
1HNMR(CDCl3)δ:8.21 (d, J=12Hz, 1H), 7.90 (d, J=8.4Hz, 1H), 7.62 (d, J=7.8Hz, 2H),7.33-7.29(m,5H),3.50(s,3H)MS(EI+)m/z:296[M]+.
Embodiment 189:1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) -3- phenyl-propane -2- alkene -1- ketone (chemical combination Thing 189) preparation
0.169g (0.001mol) 2- amino -6- sulphomethyl phenol, 0.9g is added in the round-bottomed flask of 50mL (0.001mol) lactic acid and 4mol/L hydrochloric acid 20mL, is heated to reflux 3h under nitrogen protection, is cooled to room temperature.Neutralized with concentrated ammonia liquor Redden to purple litmus paper, suction filtration goes out solid, recrystallize (72%) with water.1- (7- sulphur is added in the three-neck flask of 50mL For ethyl -1H- benzothiazole -2- ethyl) glacial acetic acid of alcohol 0.223g (0.001mol) and 10mL, it is heated to when 90 DEG C to three necks CrO is dripped in flask3The aqueous solution, after completion of dropping, stirring reaction 10min at 105 DEG C of temperature control, then reactant liquor is poured into Sheng Have in the beaker of 200mL water, stirring a moment, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, and anhydrous magnesium sulfate is done Dry, filtrate rotation is evaporated to obtain yellow solid, with re crystallization from toluene, yield：62%, add 15ml's in 50ml round-bottomed flask 95% ethanol and 0.221g (0.001mol) 1- (7- sulphomethyl -1H- benzothiazole -2- ethyl) ketone, stir about 10min makes solid Body is completely dissolved, and adds the sodium hydrate aqueous solution of 8ml10%, and stirring is lower to add 0.0015mol benzaldehyde, after a period of time System separates out a large amount of solids, detects reaction end with TLC, has reacted rear suction filtration and obtained solid.Yield:52%.
1HNMR(CDCl3)δ:8.20 (d, J=12Hz, 2H), 7.72 (d, J=8.4Hz, 1H), 7.59 (d, J=7.8Hz, 2H),7.32-7.27(m,5H),3.66(s,2H),1.82(s,3H)MS(EI+)m/z:309[M]+.
Embodiment 190:1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- The preparation of ketone (compound 190)
With compound 1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 189 Reaction obtains 1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (62%).
1HNMR(CDCl3)δ:7.89 (d, J=12Hz, 2H), 7.52 (d, J=7.8Hz, 2H), 7.34-7.29 (m, 5H), 4.12(s,2H),1.97(s,3H)MS(EI+)m/z:343[M]+.
Embodiment 191:1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- The preparation of ketone (compound 191)
With compound 1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 189 Reaction obtains 1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (78%).
1HNMR(CDCl3)δ:8.33 (s, 1H), 7.81 (d, J=8.4Hz, 1H), 7.60 (d, J=7.8Hz, 2H), 7.37- 7.32(m,5H),3.90(s,2H),1.94(s,3H)MS(EI+)m/z:310[M]+.
Embodiment 192:1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- The preparation of ketone (compound 192)
With compound 1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 189 Reaction obtains 1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (70%).
1HNMR(CDCl3)δ:8.39 (s, 1H), 7.82 (d, J=8.4Hz, 1H), 7.43 (d, J=7.8Hz, 2H), 7.23- 7.19(m,5H),4.16(s,2H),1.72(s,3H)MS(EI+)m/z:310[M]+.
Embodiment 193:1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- The preparation of ketone (compound 193)
With compound 1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 189 Reaction obtains 1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (61%).
1HNMR(CDCl3)δ:7.81 (d, J=8.4Hz, 1H), 7.63 (d, J=15.6Hz, 1H), 7.58 (s, 1H), 7.33-7.27(m,3H),6.32(s,1H),3.91(s,2H),1.47(s,3H)MS(EI+)m/z:299[M]+.
Embodiment 194:1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) -3- phenyl-propane -2- alkene -1- ketone (chemical combination Thing 194) preparation
0.169g (0.001mol) 2- amino -5- sulphomethyl phenol, 0.9g is added in the round-bottomed flask of 50mL (0.001mol) lactic acid and 4mol/L hydrochloric acid 20mL, is heated to reflux 3h under nitrogen protection, is cooled to room temperature.Neutralized with concentrated ammonia liquor Redden to purple litmus paper, suction filtration goes out solid, recrystallize (72%) with water.1- (6- sulphur is added in the three-neck flask of 50mL For ethyl -1H- benzothiazole -2- ethyl) glacial acetic acid of alcohol 0.223g (0.001mol) and 10mL, it is heated to when 90 DEG C to three necks CrO is dripped in flask3The aqueous solution, after completion of dropping, stirring reaction 10min at 105 DEG C of temperature control, then reactant liquor is poured into Sheng Have in the beaker of 200mL water, stirring a moment, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, and anhydrous magnesium sulfate is done Dry, filtrate rotation is evaporated to obtain yellow solid, with re crystallization from toluene, yield：62%, add 15ml's in 50ml round-bottomed flask 95% ethanol and 0.221g (0.001mol) 1- (6- sulphomethyl -1H- benzothiazole -2- ethyl) ketone, stir about 10min makes solid Body is completely dissolved, and adds the sodium hydrate aqueous solution of 8ml10%, and stirring is lower to add 0.0015mol benzaldehyde, after a period of time System separates out a large amount of solids, detects reaction end with TLC, has reacted rear suction filtration and obtained solid.Yield:85%.
1HNMR(CDCl3)δ:7.98 (d, J=12Hz, 2H), 7.64 (d, J=8.4Hz, 1H), 7.50 (s, 1H), 7.35 (s,1H),7.20-7.16(m,5H),3.96(s,2H),1.77(s,3H)MS(EI+)m/z:309[M]+.
Embodiment 195:1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (3- chlorphenyl)-propane -2- alkene -1- The preparation of ketone (compound 195)
With compound 1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 194 Reaction obtains 1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (3- chlorphenyl)-propane -2- alkene -1- ketone (71%).
1HNMR(CDCl3)δ:8.75 (d J=12Hz, 2H), 7.93 (d, J=8.4Hz, 1H), 7.80 (d, J=7.8Hz, 1H),7.43-7.38(m,5H),3.78(s,2H),1.56(s,3H)MS(EI+)m/z:299[M]+.
Embodiment 196:1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals)-propane -2- alkene -1- The preparation of ketone (compound 196)
With compound 1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 194 Reaction obtains 1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals)-propane -2- alkene -1- ketone (66%).
1HNMR(CDCl3)δ:8.47 (d, J=15Hz, 1H), 7.87 (d, J=8.4Hz, 1H), 7.72 (d, J=7.8Hz, 2H),7.40-7.36(m,5H),3.81(s,2H),1.96(s,3H)MS(EI+)m/z:310[M]+.
Embodiment 197:1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals)-propane -2- alkene -1- The preparation of ketone (compound 197)
With compound 1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 194 Reaction obtains 1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals)-propane -2- alkene -1- ketone (73%).
1HNMR(CDCl3)δ:8.23 (d, J=12Hz, 2H), 7.76 (d, J=8.4Hz, 1H), 7.46 (d, J=7.8Hz, 2H),7.21-7.18(m,4H)),3.87(s,2H),1.90(s,3H)MS(EI+)m/z:343[M]+.
Embodiment 198:1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (2- furyl)-propane -2- alkene -1- The preparation of ketone (compound 198)
With compound 1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 194 Reaction obtains 1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (2- furyl)-propane -2- alkene -1- ketone (63%).
1HNMR(CDCl3)δ:7.80 (d, J=8.4Hz, 1H), 7.67 (d, J=12Hz, 1H), 7.48 (s, 1H), 7.33- 7.28 (m, 3H), 6.79 (d, J=9Hz, 1H), 3.86 (s, 2H), 2.17 (s, 3H) MS (EI+)m/z:310[M]+.
Embodiment 199:1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) -3- phenyl-propane -2- alkene -1- ketone (chemical combination Thing 199) preparation
0.185g (0.001mol) 2- amino -6- thio-ethyl phenol, 0.9g is added in the round-bottomed flask of 50mL (0.001mol) lactic acid and 4mol/L hydrochloric acid 20mL, is heated to reflux 3h under nitrogen protection, is cooled to room temperature.Neutralized with concentrated ammonia liquor Redden to purple litmus paper, suction filtration goes out solid, recrystallize (63%) with water.1- (7- sulphur is added in the three-neck flask of 50mL For ethyl -1H- benzothiazole -2- ethyl) glacial acetic acid of alcohol 0.239g (0.001mol) and 10mL, it is heated to when 90 DEG C to three necks CrO is dripped in flask3The aqueous solution, after completion of dropping, stirring reaction 10min at 105 DEG C of temperature control, then reactant liquor is poured into Sheng Have in the beaker of 200mL water, stirring a moment, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, and anhydrous magnesium sulfate is done Dry, filtrate rotation is evaporated to obtain yellow solid, with re crystallization from toluene, yield：77%, add 15ml's in 50ml round-bottomed flask 95% ethanol and 0.237g (0.001mol) 1- (7- sulphomethyl -1H- benzothiazole -2- ethyl) ketone, stir about 10min makes solid Body is completely dissolved, and adds the sodium hydrate aqueous solution of 8ml10%, and stirring is lower to add 0.0015mol benzaldehyde, after a period of time System separates out a large amount of solids, detects reaction end with TLC, has reacted rear suction filtration and obtained solid.Yield:79%.
1HNMR(CDCl3)δ:8.27 (d, J=12Hz, 2H), 7.88 (d, J=8.4Hz, 1H), 7.46 (d, J=7.8Hz, 2H),7.21-7.18(m,5H),3.74(s,2H),1.90(s,3H)MS(EI+)m/z:325[M]+.
Embodiment 200:1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- The preparation of ketone (compound 200)
With compound 1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 199 Reaction obtains 1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl) propane -2- alkene -1- ketone (63%).
1HNMR(CDCl3)δ:7.93 (d, J=12Hz, 2H), 7.60 (d, J=7.8Hz, 2H), 7.31-7.27 (m, 5H), 4.06(s,2H),1.88(s,3H)MS(EI+)m/z:359[M]+.
Embodiment 201:1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- The preparation of ketone (compound 201)
With compound 1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 199 Reaction obtains 1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (79%).
1HNMR(CDCl3)δ:8.45 (s, 1H), 7.93 (d, J=8.4Hz, 1H), 7.72 (d, J=7.8Hz, 2H), 7.39- 7.34(m,5H),3.91(s,2H),1.78(s,3H)MS(EI+)m/z:326.
Embodiment 202:1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- The preparation of ketone (compound 202)
With compound 1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 199 Reaction obtains 1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (61%).
1HNMR(CDCl3)δ:8.20 (s, 1H), 7.76 (d, J=8.4Hz, 1H), 7.52 (d, J=7.8Hz, 2H), 7.20- 7.16(m,5H),3.97(s,2H),1.69(s,3H)MS(EI+)m/z:326[M]+.
Embodiment 203:1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- The preparation of ketone (compound 203)
With compound 1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 199 Reaction obtains 1- (7- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (2- furyl) propane -2- alkene -1- ketone (77%).
1HNMR(CDCl3)δ:7.96 (d, J=8.4Hz, 1H), 7.66 (d, J=15.6Hz, 1H), 7.41 (s, 1H), 7.30-7.25(m,3H),6.67(s,1H),3.43(s,2H),1.79(s,3H)MS(EI+)m/z:315[M]+.
Embodiment 204:1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) -3- phenyl-propane -2- alkene -1- ketone (chemical combination Thing 204) preparation
0.185g (0.001mol) 2- amino -5- thio-ethyl benzenethiol, 0.9g is added in the round-bottomed flask of 50mL (0.001mol) lactic acid and 4mol/L hydrochloric acid 20mL, is heated to reflux 3h under nitrogen protection, is cooled to room temperature.Neutralized with concentrated ammonia liquor Redden to purple litmus paper, suction filtration goes out solid, recrystallize (62%) with water.1- (6- sulphur is added in the three-neck flask of 50mL For ethyl -1H- benzothiazole -2- ethyl) glacial acetic acid of alcohol 0.239g (0.001mol) and 10mL, it is heated to when 90 DEG C to three necks CrO is dripped in flask3The aqueous solution, after completion of dropping, stirring reaction 10min at 105 DEG C of temperature control, then reactant liquor is poured into Sheng Have in the beaker of 200mL water, stirring a moment, suction filtration, filtrate, with chloroform extraction 3 times, chloroform layer is merged, and anhydrous magnesium sulfate is done Dry, filtrate rotation is evaporated to obtain yellow solid, with re crystallization from toluene, yield：51%, add 15ml's in 50ml round-bottomed flask 95% ethanol and 0.237g (0.001mol) 1- (6- sulphomethyl -1H- benzothiazole -2- ethyl) ketone, stir about 10min makes solid Body is completely dissolved, and adds the sodium hydrate aqueous solution of 8ml10%, and stirring is lower to add 0.0015mol benzaldehyde, after a period of time System separates out a large amount of solids, detects reaction end with TLC, has reacted rear suction filtration and obtained solid.Yield:62%.
1HNMR(CDCl3)δ:7.92 (d, J=12Hz, 2H), 7.73 (d, J=8.4Hz, 1H), 7.51 (s, 1H), 7.39 (s,1H),7.23-7.17(m,5H),3.83(s,2H),1.64(s,3H)MS(EI+)m/z:325[M]+.
Embodiment 205:1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (2- furyl)-propane -2- alkene -1- The preparation of ketone (compound 205)
With compound 1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 204 Reaction obtains 1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (2- furyl)-propane -2- alkene -1- ketone (77%).
1HNMR(CDCl3)δ:8.60 (d J=12Hz, 2H), 7.95 (d, J=8.4Hz, 1H), 7.81 (d, J=7.8Hz, 1H),7.44-7.37(m,5H),3.62(s,2H),1.59(s,3H)MS(EI+)m/z:315[M]+.
Embodiment 206:1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals)-propane -2- alkene -1- The preparation of ketone (compound 206)
With compound 1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 204 Reaction obtains 1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (4- pyridine radicals)-propane -2- alkene -1- ketone (57%).
1HNMR(CDCl3)δ:8.36 (d, J=15Hz, 1H), 7.94 (d, J=8.4Hz, 1H), 7.60 (d, J=7.8Hz, 2H),7.35-7.29(m,5H),3.96(s,2H),1.87(s,3H)MS(EI+)m/z:326[M]+.
Embodiment 207:1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl)-propane -2- alkene -1- The preparation of ketone (compound 207)
With compound 1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 204 Reaction obtains 1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (4- chlorphenyl)-propane -2- alkene -1- ketone (66%).
1HNMR(CDCl3)δ:8.36 (d, J=12Hz, 2H), 7.70 (d, J=8.4Hz, 1H), 7.42 (d, J=7.8Hz, 2H),7.19-7.13(m,4H)),3.67(s,2H),1.92(s,3H)MS(EI+)m/z:359[M]+.
Embodiment 208:1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals)-propane -2- alkene -1- The preparation of ketone (compound 208)
With compound 1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) ketone as raw material, according to the method for embodiment 204 Reaction obtains 1- (6- thio-ethyl -1H- benzothiazole -2- ethyl) -3- (2- pyridine radicals)-propane -2- alkene -1- ketone (80%).
1HNMR(CDCl3)δ:7.81 (d, J=8.4Hz, 1H), 7.76 (d, J=12Hz, 1H), 7.53 (s, 1H), 7.21- 7.17 (m, 3H), 6.83 (d, J=9Hz, 1H), 3.72 (s, 2H), 2.05 (s, 3H) MS (EI+)m/z:310.3[M]+.
Embodiment 209:The preparation of 1- (3H- indoles -2- ethyl) -3- phenyl-propane -2- alkene -1- ketone (compound 209)
95% ethanol of 0.159g (0.001mol) 2- acetylindole and 15ml, stirring is added in the round-bottomed flask of 50mL About 10min makes solid be completely dissolved, and adds the sodium hydrate aqueous solution of 8ml10%, and stirring is lower to add 0.0015mol benzene first Aldehyde, after a period of time, system separates out a large amount of solids, detects reaction end with TLC, has reacted rear suction filtration and obtained solid.Yield:58%.
1HNMR(CDCl3)δ:7.92 (d, J=12Hz, 2H), 7.73 (d, J=8.4Hz, 1H), 7.51 (s, 1H), 7.39 (s,1H),7.23-7.17(m,5H),3.83(s,2H),1.64(s,3H)MS(EI+)m/z:247[M]+.
Embodiment 210:3- (2- furyl) -1- (3H- indoles -2- ethyl) propane -2- alkene -1- ketone (compound 210) Preparation
With compound 2- acetylindole as raw material, the method reaction according to embodiment 209 obtains 3- (2- furyl) -1- (3H- indoles -2- ethyl) propane -2- alkene -1- ketone (65%).
1HNMR(CDCl3)δ:8.60 (d J=12Hz, 2H), 7.95 (d, J=8.4Hz, 1H), 7.81 (d, J=7.8Hz, 1H),7.44-7.37(m,5H),3.62(s,2H),1.59(s,3H)MS(EI+)m/z:237[M]+.
Embodiment 211:1- (3H- indoles -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (compound 211) Preparation
With compound 2- acetylindole as raw material, the method reaction according to embodiment 209 obtains 1- (3H- indoles -2- second Base) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (54%).
1HNMR(CDCl3)δ:8.36 (d, J=15Hz, 1H), 7.94 (d, J=8.4Hz, 1H), 7.60 (d, J=7.8Hz, 2H),7.35-7.29(m,5H),3.96(s,2H),1.87(s,3H)MS(EI+)m/z:248[M]+.
Embodiment 212:1- (3H- indoles -2- ethyl) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (compound 212) Preparation
With compound 2- acetylindole as raw material, the method reaction according to embodiment 209 obtains 1- (3H- indoles -2- second Base) -3- (4- pyridine radicals) propane -2- alkene -1- ketone (73%).
1HNMR(CDCl3)δ:8.36 (d, J=12Hz, 2H), 7.70 (d, J=8.4Hz, 1H), 7.42 (d, J=7.8Hz, 2H),7.19-7.13(m,4H)),3.67(s,2H),1.92(s,3H)MS(EI+)m/z:281[M]+.
Embodiment 213:1- (3H- indoles -2- ethyl) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (compound 213) Preparation
With compound 2- acetylindole as raw material, the method reaction according to embodiment 209 obtains 1- (3H- indoles -2- second Base) -3- (2- pyridine radicals) propane -2- alkene -1- ketone (61%).
1HNMR(CDCl3)δ:7.81 (d, J=8.4Hz, 1H), 7.76 (d, J=12Hz, 1H), 7.53 (s, 1H), 7.21- 7.17 (m, 3H), 6.83 (d, J=9Hz, 1H), 3.72 (s, 2H), 2.05 (s, 3H) MS (EI+)m/z:248[M]+.

Claims (7)

1. there is the α containing benzo five-membered unsaturated heterocycle structure of structure, beta unsaturated ketone class compound as shown in formula (I) Or its pharmaceutical salts,
Wherein, the described α containing benzo five-membered unsaturated heterocycle structure, beta unsaturated ketone class compound are selected from following compound Formed group：
2. there is in preparation claim 1 α, β insatiable hunger containing benzo five-membered unsaturated heterocycle structure of structure shown in formula (I) With the method for ketone compounds or its pharmaceutical salts it is characterised in that：
Intermediate (III) is obtained first using method shown in route 1, wherein, M is amino, hydroxyl, methyl or sulfydryl；R1, R2, R3, R4Definition with claim 1, route 1：
Synthetic method is：With the aniline (II) of replacement as initiation material, selection lactic acid is solvent, adds hydrochloric acid, heats up stirring instead Should after obtain III；Further, described intermediate (III) is reacted as follows respectively and is obtained corresponding generalformula-compound：
A：In Formulas I structure X be NH, O and, S or CH2When, intermediate (III) is reacted as follows obtains corresponding formula I chemical combination Thing；R1, R2, R3, R4, R5Definition with claim 1；
Intermediate (III) in acidic aqueous solution through chromium trioxide oxidation after in the presence of alkali with replace aldehyde reaction after separate pure Change and obtain target compound I；
B：When in Formulas I structure, X is N-R, intermediate (III) is reacted as follows obtains corresponding generalformula-compound, wherein, R1, R2, R3, R4, R5Definition with claim 1；
Intermediate (III) is connected with alkylating reagent in acidic aqueous solution after chromium trioxide oxidation in the presence of alkali, so Obtain target compound I with replacing to isolate and purify after aldehyde reaction under base catalysis afterwards.
3. there is in claim 1 α containing benzo five-membered unsaturated heterocycle structure of structure, beta unsaturated ketone shown in formula (I) Application in preparing antineoplastic for the class compound or pharmaceutically acceptable salt thereof.
4. one kind contains described in claim 1 it is characterised in that containing in this pharmaceutical composition for antitumor medicine composition There are α, the beta unsaturated ketone class compound or pharmaceutically acceptable salt thereof of benzo five-membered unsaturated heterocycle structure, and contain one or more pharmacy Upper acceptable pharmaceutical adjuvant.
5. pharmaceutical composition as claimed in claim 4, wherein, described α, β containing benzo five-membered unsaturated heterocycle structure are not , as active component, the weight content in this pharmaceutical composition is 0.1%- for saturated ketone compounds or its pharmaceutical salts 99.5%.
6. pharmaceutical composition as claimed in claim 5, wherein, described α, β containing benzo five-membered unsaturated heterocycle structure are not , as active component, the weight content in this pharmaceutical composition is 0.5%- for saturated ketone compounds or its pharmaceutical salts 99.5%.
7. application in preparing antineoplastic for the pharmaceutical composition as described in any one of claim 4-6.
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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3755314A (en) * 1970-12-01 1973-08-28 Delalande Sa Novel 2-acryloyl benzimidazoles, their process of preparation and their therapeutic application
FR2140347B1 (en) * 1971-06-11 1974-08-30 Delalande Sa
FR2160719B1 (en) * 1971-11-23 1975-02-07 Delalande Sa
EP0985683A1 (en) * 1998-09-09 2000-03-15 Fuji Photo Film Co., Ltd. Photosensitive composition and method for manufacturing lithographic printing plate
WO2013002879A1 (en) * 2011-06-29 2013-01-03 President And Fellows Of Harvard College Small molecule cd38 inhibitors and methods of using same

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060074108A1 (en) * 2004-10-04 2006-04-06 Bioderm Research Matrix metalloprotease (MMP) inhibitors and their application in cosmetic and pharmaceutical composition

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3755314A (en) * 1970-12-01 1973-08-28 Delalande Sa Novel 2-acryloyl benzimidazoles, their process of preparation and their therapeutic application
FR2140347B1 (en) * 1971-06-11 1974-08-30 Delalande Sa
FR2160719B1 (en) * 1971-11-23 1975-02-07 Delalande Sa
EP0985683A1 (en) * 1998-09-09 2000-03-15 Fuji Photo Film Co., Ltd. Photosensitive composition and method for manufacturing lithographic printing plate
WO2013002879A1 (en) * 2011-06-29 2013-01-03 President And Fellows Of Harvard College Small molecule cd38 inhibitors and methods of using same

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Synthesis and biological evaluation of some novel-3-(5-substituted benzimidazol-2-yl)-5- arylisoxazolines;Reddy, Vanga Malla et al.;《Chinese Chemical Letters》;20101231;第21卷(第10期);1145-1148 *
The optical properties, synthesis and characterization of novel 5-aryl-3-benzimidazolyl-1-phenyl-pyrazoline derivatives;Cao, Xiao Qun et al.;《Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy》;20120826;第98卷;76-80 *
新型含有苯并咪唑取代基的多取代吡啶类化合物及其配合物的合成与表征;景崤壁等;《有机化学》;20101231;第30卷(第4期);539-545 *

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