CN105503868A - Imidazo heterocycle carbamic acid ester derivate and preparation method and application thereof - Google Patents

Imidazo heterocycle carbamic acid ester derivate and preparation method and application thereof Download PDF

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CN105503868A
CN105503868A CN201610046408.1A CN201610046408A CN105503868A CN 105503868 A CN105503868 A CN 105503868A CN 201610046408 A CN201610046408 A CN 201610046408A CN 105503868 A CN105503868 A CN 105503868A
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compound
imidazoheterocycles
carbamate derivatives
preparation
washing
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汤日元
徐莉
张军荣
廖燕燕
李春远
郑文旭
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South China Agricultural University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
    • B01J23/70—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of the iron group metals or copper
    • B01J23/74—Iron group metals
    • B01J23/745—Iron
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
    • C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials

Abstract

The invention belongs to the field of organic synthetic technology and organic fluorescent materials, and particularly discloses an imidazo heterocycle carbamic acid ester derivate and a preparation method and application thereof. The structural formula of the imidazo heterocycle carbamic acid ester derivate is shown in the description, wherein R is alkyl or CH3O or F or Cl or Br or CN, R can be at any position of the benzene ring and Het is thiazole or benzothiazole or pyridine or pyrimidine. The preparation line of the imidazo heterocycle carbamic acid ester is the technological process with the advantages of being simple, low in cost, environmentally friendly and the like. The cheap ferric salt is adopted as a catalyst, and the imidazo heterocycle carbamic acid ester derivate can be obtained at the normal pressure. No phosgene is involved on the aspect of the technology of obtaining the carbamic acid ester, and the requirement for current world development green chemical industry is met. The synthetized imidazo heterocycle carbamic acid ester derivate has the excellent fluorescence property and can be applied to the field of biological imaging.

Description

A kind of imidazoheterocycles carbamate derivatives and its preparation method and application
Technical field
The invention belongs to technical field of organic synthesis and organic fluorescence materials field, be specifically related to a kind of imidazoheterocycles carbamate derivatives and its preparation method and application.
Background technology
Imidazoheterocycles is a kind of lead compound of excellence, has excellent biological activity.Bioactivity research shows that this compounds has excellent antitumor, anti-inflammatory isoreactivity, be the inhibitor of multiple non-friendly enzyme, multiple imidazoheterocycles class medicine (comprises alpidem, olprinone, necopidem, zolimidineandsaripidem) go on the market.Carbamate is also important active fragments, carbamate insecticides just has 45 kinds.Such as N-methyl carbamic acid-1-naphthalene ester is the sterilant of wide effect, and trade name is SevinCarbaryl; N-(3,4-dichlorophenyl) Urethylane is weedicide.Meanwhile, carbamate also has important application at field of medicaments, and such as urethane is a kind of Hypnotics and sedatives.By imidazoheterocycles skeleton together with the grafting of carbamate fragment; very likely obtain highly active drug molecule; and on the basis of active drug molecule; possesses excellent fluorescence property; this has important using value for bio-imaging field; therefore develop this compounds, and be added on patent protection and be necessary.
Tradition prepare carbamate method mainly with hypertoxic phosgene for raw material, obtain through alcoholysis and ammonia solution.The shortcoming of phosgenation is that phosgene is volatile, hypertoxic, there is serious potential safety hazard, and byproduct hydrogen chloride is serious to equipment corrosion, produces the very high stopping property of equipment Requirement and corrosion resistance nature, involves great expense and to bad environmental.
Summary of the invention
For solving the shortcoming and defect part of prior art, primary and foremost purpose of the present invention is to provide a kind of imidazoheterocycles carbamate derivatives.
Another object of the present invention is to provide a kind of gentleness, non-phosgene prepares the technological method of imidazoheterocycles carbamate derivatives.
Another object of the present invention is the application providing above-mentioned imidazoheterocycles carbamate derivatives.
The object of the invention is achieved through the following technical solutions:
A kind of imidazoheterocycles carbamate derivatives, its structural formula is such as formula shown in (1):
wherein, R is alkyl (alkyl), CH 3o, F, Cl, Br or CN, R can in the optional position of phenyl ring; Het is thiazole, benzothiazole, pyridine or pyrimidine.Et represents ethyl.
Described alkyl (alkyl) is preferably C1-C6 alkyl.
The preparation method of above-mentioned imidazoheterocycles carbamate derivatives, comprises the following steps:
(1) synthesis of Imidazoheterocyclic compounds substrate:
By compound 1 and compound 2 with mol ratio 1:1 under the condition of catalyzer and water, stirring reaction 4 hours at 60 DEG C; Reaction terminates rear cooling, mixed solution AcOEt (ethyl acetate) dilution, washing, extraction, suction filtration after organic phase drying, filtrate revolves steaming, residuum chromatography, organic solvent drip washing, TLC detects, and merge the effluent liquid containing product and revolve steaming, vacuum-drying obtains compound 3;
The structural formula of described compound 1 is het is thiazole, benzothiazole, pyridine or pyrimidine; The structural formula of described compound 2 is the structural formula of compound 3 is
(2) aminating reaction of Imidazoheterocyclic compounds and DEAD (diethyl azodiformate):
By compound 3 and compound 4 (i.e. Compound D EAD) with mol ratio 1:1-2 under catalysts and solvents condition, stirring reaction 12 hours at 40-120 DEG C; Reaction terminates rear cooling, and mixed solution AcOEt dilutes, washing, extraction, suction filtration after organic phase drying, and filtrate revolves steaming, residuum chromatography, organic solvent drip washing, and TLC detects, and merge the effluent liquid containing product and revolve steaming, vacuum-drying obtains compound 5;
(3) preparation of imidazoheterocycles carbamate compounds:
By compound 5, alkali and ethyl bromoacetate 2:2:1 in molar ratio, in a solvent with stirring reaction 1-3 hour at 50-120 DEG C; Reaction terminates rear cooling, the saturated NH of mixed solution 4the quencher of Cl solution, mixed solution AcOEt dilutes, washing, extraction, suction filtration after organic phase drying, filtrate revolves steaming, residuum chromatography, organic solvent drip washing, TLC detects, and merge the effluent liquid containing product and revolve steaming, vacuum-drying obtains target product and described imidazoheterocycles carbamate derivatives.
Step (1) described catalyzer is preferably DABCO (Chinese Isosorbide-5-Nitrae-diazabicylo [2.2.2] octane), and its add-on is the 10mol% of compound 1 molar weight;
Wash preferred saturated aqueous common salt described in step (1) to wash, described drying preferably uses anhydrous magnesium sulfate drying, described suction filtration is preferably with short silicagel column suction filtration, and described chromatography refers to that described organic solvent is preferably petrol ether/ethyl acetate mixed solvent with silica gel column chromatography.
Step (2) described catalyzer is preferably FeCl 3, its add-on is the 10mol% of compound 3 molar weight;
Step (2) described solvent comprises: DMSO (methyl-sulphoxide), CH 3cN (acetonitrile), DCE (1,2-ethylene dichloride), DMA (N, N-N,N-DIMETHYLACETAMIDE), NMP (2-Pyrrolidone), EtOH (ethanol), PhMe (toluene) or DMF (DMF); Be preferably CH 3cN.
Step (2) reaction significant temp is 40 DEG C-120 DEG C, is preferably 80 DEG C.
Washing described in step (2) is preferably with the washing of saturated sodium thiosulfate solution, described drying preferably uses anhydrous magnesium sulfate drying, described suction filtration is preferably with short silicagel column suction filtration, and described chromatography refers to that described organic solvent is preferably petrol ether/ethyl acetate mixed solvent with silica gel column chromatography.
Step (3) described alkali is Cs 2cO 3, Na 2cO 3or K 2cO 3, be preferably Cs 2cO 3.
Step (3) described solvent comprises DMSO, CH 3cN, DCE, DMA, NMP, EtOH, PhMe or DMF, be preferably CH 3cN.
Step (3) described temperature of reaction is preferably 50 DEG C-100 DEG C, is more preferably 80 DEG C.
Wash preferred saturated aqueous common salt described in step (3) to wash, described drying preferably uses anhydrous magnesium sulfate drying, described suction filtration is preferably with short silicagel column suction filtration, and described chromatography refers to that described organic solvent is preferably petrol ether/ethyl acetate mixed solvent with silica gel column chromatography.
Above-mentioned imidazoheterocycles carbamate derivatives has solid state fluorescence luminescent properties, can be applicable to bio-imaging field.
The preparation principle of imidazoheterocycles carbamate derivatives of the present invention is shown below:
Compared with prior art, the present invention has the following advantages and beneficial effect:
The syntheti c route of imidazoheterocycles carbamate of the present invention a kind ofly has that technical process is simple, cost is low, the technical process of advantages of environment protection.The present invention adopts cheap molysite to make catalyzer, can complete under normal pressure; Obtain carbamate technical elements and do not relate to phosgene, meet the requirement of our times development green chemical industry.
The imidazoheterocycles carbamate derivatives of the present invention's synthesis has excellent fluorescence property.
Embodiment
Below in conjunction with embodiment, the present invention is described in further detail, but embodiments of the present invention are not limited thereto.
Embodiment 1
(1) synthesis of Imidazoheterocyclic compounds substrate:
By compound 1 and compound 2 with mol ratio 1:1, the molar percentage of DABCO is 10% (in compound 1 for benchmark), and wherein the amount of compound 1 is 5mmol, and solvent is 15mL water, add successively in round-bottomed flask, stirring reaction 4 hours at 60 DEG C.Reaction terminates rear cooling, and mixed solution AcOEt dilutes, and then uses saturated aqueous common salt (3 × 10mL) to wash, extraction, the organic phase anhydrous magnesium sulfate drying obtained, with short silicagel column suction filtration, filtrate is revolved and is steamed except desolventizing, residuum silica gel column chromatography, the drip washing of petrol ether/ethyl acetate mixed solvent, TLC detects, and merges the effluent liquid containing product, Rotary Evaporators distillation desolventizing, vacuum-drying obtains target product compound 3.
The reaction formula of step (1) is as follows:
(2) aminating reaction of Imidazoheterocyclic compounds and DEAD:
By compound 3 and compound 4 with mol ratio 1:1.5, FeCl 3molar percentage be 10% (in compound 3 for benchmark), wherein the amount of compound 3 is 2mmol, solvent C H 3cN is 15ml, joins successively in the reaction tubes of 50mL, stirring reaction 12 hours at 80 DEG C.Reaction terminates rear cooling, and mixed solution AcOEt dilutes, and then uses saturated sodium thiosulfate solution (3 × 10mL) to wash, extraction, the organic phase anhydrous magnesium sulfate drying obtained, with short silicagel column suction filtration, filtrate is revolved and is steamed except desolventizing, residuum silica gel column chromatography, the drip washing of petrol ether/ethyl acetate mixed solvent, TLC detects, merge the effluent liquid containing product, Rotary Evaporators distillation desolventizing, vacuum-drying obtains target product compound 5, and productive rate is 65%.Compound 5 under 365nm, solid-state jaundice green fluorescence, maximum emission wavelength 533nm.
In step (2), reaction significant temp is 40 DEG C-120 DEG C, is preferably 80 DEG C.As the mol ratio 1:1.5 of compound 3 and compound 4, solvent C H 3cN, temperature of reaction 40 DEG C, reacts 12 hours, and the productive rate of compound 5 is 18%.As the mol ratio 1:1.5 of compound 3 and compound 4, solvent C H 3cN, temperature of reaction 120 DEG C, reacts 12 hours, and the productive rate of compound 5 is 45%.
The reaction formula of step (2) is as follows:
(3) preparation of imidazoheterocycles carbamate compounds:
In the reaction tubes of 50mL, by the compound 5 of 2mmol, the Cs of 2eq 2cO 3, the ethyl bromoacetate of 1eq and the solvent C H of 15ml 3cN adds successively, stirring reaction 3 hours at 80 DEG C.Reaction terminates rear cooling, the saturated NH of mixed solution 4the quencher of Cl solution, then dilute with AcOEt, then saturated aqueous common salt (3 × 10mL) is used to wash, extraction, the organic phase anhydrous sodium sulfate drying obtained, with short silicagel column suction filtration, filtrate is revolved and is steamed except desolventizing, residuum silica gel column chromatography, the drip washing of petrol ether/ethyl acetate mixed solvent, TLC detects, and merges the effluent liquid containing product, Rotary Evaporators distillation desolventizing, vacuum-drying obtains target product and compound 6, productive rate is 51%, and target product solid matter is Yellow light-emitting low temperature under 365nm, maximum emission wavelength 527nm.
In step (3), working lipe, scope was 1-3 hour, 3 hours preferred time.When solvent is CH 3cN, temperature of reaction 50 DEG C, reacts 3 hours, and the productive rate of compound 6 is 23%.When solvent is CH 3cN, temperature of reaction 100 DEG C, reacts 3 hours, and the productive rate of compound 6 is 38%.
The reaction formula of step (3) is as follows:
The proton nmr spectra of the imidazoheterocycles carbamate derivatives that the present embodiment obtains, the detection data of mass spectrum and infrared spectra are as follows:
1HNMR(500MHz,Chloroform-d)δ9.00(s,1H),8.58(d,J＝6.9Hz,1H),7.94(d,J＝7.6Hz,1H),7.61(d,J＝9.1Hz,1H),7.32(t,J＝7.8Hz,1H),7.26(t,J＝8.0Hz,1H),7.14(t,J＝7.5Hz,1H),6.88(t,J＝6.9Hz,1H),6.79(d,J＝8.4Hz,1H),4.34(q,J＝7.3Hz,2H),1.33(t,J＝7.1Hz,3H). 13CNMR(126MHz,CDCl 3)δ169.8,157.4,155.2,154.1,142.7,132.6,129.6,125.4,124.5,122.7,122.3,117.2,112.4,111.2,61.9,14.4.
IR(ATR,cm-1):3256,2968,1746,1743,1539,1237,1043,745,673.HRMS(ESI)forC 16H 16N 3O 3 +(M+H) +:calcd298.1186,found298.1178.
Embodiment 2
The difference of the present embodiment and embodiment 1 is: compound 1 is PA, and compound 2 is the bromo-1-of 2-(the chloro-phenyl of 4-) ethyl ketone, and the productive rate of obtained target product imidazoheterocycles carbamate derivatives is 77%, and structural formula is as follows:
ethyl(2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)carbamate.Yellowsolid.77％yield.M.P.:165–166℃.
The proton nmr spectra of the imidazoheterocycles carbamate derivatives that the present embodiment obtains, the detection data of mass spectrum and infrared spectra are as follows:
1HNMR(500MHz,CDCl 3)δ7.85(s,1H),7.74–7.65(m,3H),7.49(d,J＝7.5Hz,1H),7.16(d,J＝6.5Hz,3H),6.77(t,J＝6.0Hz,1H),4.23(s,2H),1.43–1.10(m,3H). 13CNMR(125MHz,CDCl 3)δ155.2,142.6,138.0,133.7,131.3,128.,128.2,125.4,122.5,117.3,114.5,112.6,62.3,14.5.
IR(ATR,cm-1):2973,1633,1513,1334,1235,1053,838,758.HRMS(ESI)forC 16H 15N 3O 2Cl(M+H) +:calcd316.0847,found316.0848.
Embodiment 3
The difference of the present embodiment and embodiment 1 is: compound 1 is 2-aminopyrimidine, and compound 2 is 2-bromo Phenyl ethyl ketone, and the productive rate of obtained target product imidazoheterocycles carbamate derivatives is 41%, and structural formula is as follows:
ethyl(2-phenylimidazo[1,2-a]pyrimidin-3-yl)carbamate.Yellowsolid.41％yield.M.P.:157–158℃.
The proton nmr spectra of the imidazoheterocycles carbamate derivatives that the present embodiment obtains, the detection data of mass spectrum and infrared spectra are as follows:
1HNMR(500MHz,CDCl 3)δ8.43(s,1H),8.18(s,1H),7.92(s,2H),7.35–7.30(m,3H),6.82(s,1H),4.25(s,2H),1.33–1.26(m,3H). 13CNMR(125MHz,CDCl 3)δ154.9,150.4,145.3,140.0,132.0,128.6,128.5127.5,113.0,108.7,62.5,14.5.
IR(ATR,cm-1):2983,1718,1556,1453,1239,956,869,766.HRMS(ESI)forC 15H 15N 4O 2(M+H) +:calcd283.1190,found283.1199.
Embodiment 4
The difference of the present embodiment and embodiment 1 is: compound 1 is thiazolamine, and compound 2 is 2-bromo Phenyl ethyl ketone, and the productive rate of obtained target product imidazoheterocycles carbamate derivatives is 79%, and structural formula is as follows:
ethyl(6-phenylimidazo[2,1-b]thiazol-5-yl)carbamate.Yellowsolid.79％yield.M.P.:145–146℃.
The proton nmr spectra of the imidazoheterocycles carbamate derivatives that the present embodiment obtains, the detection data of mass spectrum and infrared spectra are as follows:
1HNMR(500MHz,CDCl 3)δ7.79–7.64(m,3H),7.18–7.01(m,4H),6.59(s,1H),4.12(s,2H),1.20(s,3H). 13CNMR(126MHz,CDCl 3)δ155.2,146.9,139.6,133.2,128.4,128.3,127.3,126.4,116.3,112.4,62.2,14.5.
IR(ATR,cm-1):2978,1564,1461,1239,1093,979,860.HRMS(ESI)forC 14H 14N 3O 2S(M+H) +:calcd288.0801,found288.0807.
Embodiment 5
The difference of the present embodiment and embodiment 1 is: compound 1 is thiazolamine, compound 2 is 2-bromo-1-(4-p-methoxy-phenyl) ethyl ketone, the productive rate of obtained target product imidazoheterocycles carbamate derivatives is 61%, and structural formula is as follows:
ethyl(6-(4-methoxyphenyl)imidazo[2,1-b]thiazol-5-yl)carbamate.Whitesolid.61％yield.M.P.:114–115℃.
The proton nmr spectra of the imidazoheterocycles carbamate derivatives that the present embodiment obtains, the detection data of mass spectrum and infrared spectra are as follows:
1HNMR(500MHz,CDCl 3)δ7.66(s,2H),7.12(s,1H),6.81–6.68(s,3H),4.22(s,2H),3.77(s,3H),1.30–1.12(m,3H). 13CNMR(125MHz,CDCl 3)δ158.9,155.3,146.7,139.7,127.7,126.0,117.3,115.4,113.8,112.0,77.4,77.1,76.9,62.2,55.2,14.5.
IR(ATR,cm-1):2971,1703,1539,1452,1256,958,887.HRMS(ESI)forC 15H 16N 3O 3S(M+H) +:calcd318.0907,found318.0912.
Embodiment 6
The difference of the present embodiment and embodiment 1 is: compound 1 is thiazolamine, and compound 2 is the bromo-1-of 2-(4-chloro-phenyl-) ethyl ketone, and the productive rate of obtained target product imidazoheterocycles carbamate derivatives is 61%, and structural formula is as follows:
ethyl(6-(4-chlorophenyl)imidazo[2,1-b]thiazol-5-yl)carbamate.Yellowsolid61％yield.M.P.:179–180℃.
The proton nmr spectra of the imidazoheterocycles carbamate derivatives that the present embodiment obtains, the detection data of mass spectrum and infrared spectra are as follows:
1HNMR(500MHz,CDCl 3)δ7.69(s,1H),7.31–7.23(m,2H),7.23(s,1H),6.99(s,1H),6.81(s,1H),4.24(s,2H),1.26(s,3H). 13CNMR(125MHz,CDCl 3)δ154.9,147.2,138.9,133.2,131.8,128.7,127.6,117.2,116.0,112.8,62.5,14.5.IR(ATR,cm-1):2974,1626,1470,1242,965,851.HRMS(ESI)forC 14H 13N 3O 2SCl(M+H) +:calcd322.0412,found322.0417.
Embodiment 7
The difference of the present embodiment and embodiment 1 is: compound 1 is 2-aminobenzothiazole, and compound 2 is the bromo-methyl phenyl ketone of 2-, and the productive rate of obtained target product imidazoheterocycles carbamate derivatives is 89%, and structural formula is as follows:
ethyl(2-phenylbenzo[d]imidazo[2,1-b]thiazol-3-yl)carbamate.Yellowsolid.89％yield.M.P.:151–152℃.
The proton nmr spectra of the imidazoheterocycles carbamate derivatives that the present embodiment obtains, the detection data of mass spectrum and infrared spectra are as follows:
1HNMR(500MHz,CDCl 3)δ7.81(s,2H),7.67(s,2H),7.39(m,4H),7.26(s,1H),4.34–4.09(m,2H),1.40–1.24(m,3H). 13CNMR(125MHz,CDCl 3)δ155.5,145.7,132.9,132.43,130.2,129.1,128.4,127.5,126.4,126.1,124.7,124.0,117.8,112.9,62.5,14.6.IR(ATR,cm-1):2973,1533,1414,1382,1245,1053,885,738.HRMS(ESI)forC18H16N3O2S(M+H)+:calcd338.0958,found338.0962.
Above-described embodiment is the present invention's preferably embodiment; but embodiments of the present invention are not restricted to the described embodiments; change, the modification done under other any does not deviate from spirit of the present invention and principle, substitute, combine, simplify; all should be the substitute mode of equivalence, be included within protection scope of the present invention.

Claims (10)

1. an imidazoheterocycles carbamate derivatives, is characterized in that, its structural formula is such as formula shown in (1):
wherein, R is alkyl, CH 3o, F, Cl, Br or CN; Het is thiazole, benzothiazole, pyridine or pyrimidine.
2. imidazoheterocycles carbamate derivatives according to claim 1, is characterized in that, described alkyl is C1-C6 alkyl.
3. the preparation method of the imidazoheterocycles carbamate derivatives described in claim 1 or 2, is characterized in that, comprise the following steps:
(1) by compound 1 and compound 2 with mol ratio 1:1 under catalyzer and water condition, stirring reaction 4 hours at 60 DEG C; Reaction terminates rear cooling, and mixed solution AcOEt dilutes, washing, extraction, suction filtration after organic phase drying, and filtrate revolves steaming, residuum chromatography, organic solvent drip washing, and TLC detects, and merge the effluent liquid containing product and revolve steaming, vacuum-drying obtains compound 3; The structural formula of described compound 1 is het is thiazole, benzothiazole, pyridine or pyrimidine; The structural formula of described compound 2 is
(2) by compound 3 and DEAD with mol ratio 1:1-2 under catalysts and solvents condition, stirring reaction 12 hours at 40-120 DEG C; Reaction terminates rear cooling, and mixed solution AcOEt dilutes, washing, extraction, suction filtration after organic phase drying, and filtrate revolves steaming, residuum chromatography, organic solvent drip washing, and TLC detects, and merge the effluent liquid containing product and revolve steaming, vacuum-drying obtains compound 5;
(3) by compound 5, alkali and ethyl bromoacetate 2:2:1 in molar ratio, in a solvent with stirring reaction 1-3 hour at 50-120 DEG C; Reaction terminates rear cooling, the saturated NH of mixed solution 4the quencher of Cl solution, mixed solution AcOEt dilutes, washing, extraction, suction filtration after organic phase drying, filtrate revolves steaming, residuum chromatography, organic solvent drip washing, TLC detects, and merge the effluent liquid containing product and revolve steaming, vacuum-drying obtains target product and described imidazoheterocycles carbamate derivatives.
4. the preparation method of imidazoheterocycles carbamate derivatives according to claim 3, is characterized in that, step (1) described catalyzer is DABCO, and its add-on is the 10mol% of compound 1 molar weight;
Step (2) described catalyzer is FeCl 3, its add-on is the 10mol% of compound 3 molar weight;
Step (3) described alkali is Cs 2cO 3, Na 2cO 3or K 2cO 3.
5. the preparation method of imidazoheterocycles carbamate derivatives according to claim 3, is characterized in that, step (2) described temperature of reaction is 80 DEG C; Step (3) described temperature of reaction is 50 DEG C-100 DEG C.
6. the preparation method of imidazoheterocycles carbamate derivatives according to claim 3, is characterized in that, step (3) described temperature of reaction is 80 DEG C, and described alkali is Cs 2cO 3.
7. the preparation method of imidazoheterocycles carbamate derivatives according to claim 3, is characterized in that, step (2) and (3) described solvent include DMSO, CH 3cN, DCE, DMA, NMP, EtOH, PhMe or DMF.
8. the preparation method of imidazoheterocycles carbamate derivatives according to claim 3, is characterized in that, step (2) and (3) described solvent are CH 3cN.
9. the preparation method of imidazoheterocycles carbamate derivatives according to claim 3, is characterized in that,
Wash as washing with saturated aqueous common salt described in step (1) and (3), washing described in step (2) is for using the washing of saturated sodium thiosulfate solution;
In step (1), (2) and (3): described drying is for using anhydrous magnesium sulfate drying, described suction filtration is with short silicagel column suction filtration, described chromatography refers to that described organic solvent is petrol ether/ethyl acetate mixed solvent with silica gel column chromatography.
10. the application of imidazoheterocycles carbamate derivatives in bio-imaging field described in claim 1 or 2.
CN201610046408.1A 2016-01-22 2016-01-22 Imidazo heterocycle carbamic acid ester derivate and preparation method and application thereof Pending CN105503868A (en)

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CN106279158A (en) * 2016-08-11 2017-01-04 华南农业大学 A kind of imidazoheterocycles amino acid ester compound and its preparation method and application
CN108503635A (en) * 2018-05-02 2018-09-07 泰山医学院 A kind of substituted imidazole simultaneously [1,2-a] pyridines pH fluorescence probes and its application

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CN106279158B (en) * 2016-08-11 2019-02-19 华南农业大学 A kind of imidazoheterocycles amino acid ester compound and its preparation method and application
CN108503635A (en) * 2018-05-02 2018-09-07 泰山医学院 A kind of substituted imidazole simultaneously [1,2-a] pyridines pH fluorescence probes and its application

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