CN104974095A - 2,4,5-polysubstituted imidazole compound and preparation method thereof - Google Patents

2,4,5-polysubstituted imidazole compound and preparation method thereof Download PDF

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CN104974095A
CN104974095A CN201510371663.9A CN201510371663A CN104974095A CN 104974095 A CN104974095 A CN 104974095A CN 201510371663 A CN201510371663 A CN 201510371663A CN 104974095 A CN104974095 A CN 104974095A
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phenyl
imidazoles
polysubstituted
ethyl formate
replacement
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CN104974095B (en
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邵加安
刘星雨
舒可
陈斌辉
陈文腾
俞永平
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Zhejiang University ZJU
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • 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
    • C07D405/04—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 directly linked by a ring-member-to-ring-member bond

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  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The invention provides a 2,4,5-polysubstituted imidazole compound. The functionalized imidazole compound is synthesized by selective reactions between olefin nitrine and substituted hydrazino-formate under a heating condition. The provided preparation method has the advantages that the operation is simple, the raw materials are easily available, multiple substitutes can be introduced at the same time, and the product is easy to separate. The prepared 2,4,5-polysubstituted imidazole compound has a certain in-vitro anti-tumor activity and thus can be used as an anti-tumor lead compound. The structural formula of the compound is represented in the description.

Description

The polysubstituted glyoxaline compound of 2,4,5-and preparation method
Technical field
The invention belongs to the synthetic method of compound, relate generally to polysubstituted glyoxaline compound of 2,4,5-and preparation method thereof.
Background technology
The polysubstituted glyoxaline compound of 2,4,5-has biological activity (Nature widely 1994, 72,739; J. Med. Chem. 2002, 45,1697; Bioorganic Medicinal Chemistry 201018,292), cause the interest of pharmaceutical chemists, current 2, the synthetic method of the polysubstituted glyoxaline compound of 4,5-mainly builds imidazole ring skeleton based on transition metal, lewis acid or base catalysis, but the bibliographical information synthesizing polysubstituted glyoxaline compound simply, fast, efficiently compares limitation.
Summary of the invention
The object of this invention is to provide the polysubstituted glyoxaline compound of a kind of 2,4,5-, its structural formula is:
Wherein: R 1for electrophilic with to the phenyl of electronics replacement or furans, R 2for ester group, Ar is contraposition methyl substituted and the phenyl without replacement.
2,4,5-polysubstituted glyoxaline compounds provided by the invention be selected from following any one:
5-(4-ethoxyl phenenyl)-2-(4-aminomethyl phenyl)-1 h-imidazoles 4-ethyl formate (embodiment 1),
5-(4-aminomethyl phenyl)-2-(4-aminomethyl phenyl)-1 h-imidazoles 4-ethyl formate (embodiment 2),
5-(4-bromophenyl)-2-(4-aminomethyl phenyl)-1 h-imidazoles 4-ethyl formate (embodiment 3),
5-(4-aminomethyl phenyl)-2-phenyl-1 h-imidazoles 4-ethyl formate (embodiment 4),
5-(3-p-methoxy-phenyl)-2-phenyl-1 h-imidazoles 4-ethyl formate (embodiment 5),
5-(4-chloro-phenyl-)-2-phenyl-1 h-imidazoles 4-ethyl formate (embodiment 6),
5-(2-furyl)-2-phenyl-1 h-imidazoles 4-ethyl formate (embodiment 7),
5-(2-furyl)-2-(4-aminomethyl phenyl)-1 h-imidazoles 4-ethyl formate (embodiment 8).
Another object of the present invention is to provide the preparation method of above-mentioned 2,4,5-polysubstituted glyoxaline compounds, is realized by following steps:
(1) by the carbazates of alkene azide compounds, replacement in organic solvent in 130 oc reacts, and the reaction times is 8-10 hour, and the mol ratio of the carbazates of alkene azide compounds and replacement is 1:1.1.
The structural formula of described alkene azide compounds is:
The carbazates structural formula of described replacement is:
Wherein R 3for methyl substituted aryl (-CH2Ar) or benzyl, LG is tert.-butoxy;
(2) after reaction solution step (1) obtained is concentrated, with water and extraction into ethyl acetate, obtain residue after the organic phase drying obtained is concentrated, residue is carried out silica gel column chromatography, obtains the polysubstituted glyoxaline compound of 2,4,5-;
Reaction formula is:
R 1for electrophilic with to the phenyl of electronics replacement or furans, R 2for ester group, Ar is contraposition methyl substituted and the phenyl without replacement.
Organic solvent of the present invention is acetonitrile, Isosorbide-5-Nitrae-dioxane, DMF or toluene.
Another object of the present invention is to provide the application of described compound in preparation tumor.
Contriver reacts 8 hours under 130 degree of conditions by being dissolved in acetonitrile with replacement carbazates by alkene azide compounds, obtains 2,4,5-polysubstituted glyoxaline compounds (as shown in Equation 1) of novel structure.This synthetic method yield is high, convenient post-treatment, and without the need to using any additive or metal catalyst, reaction raw materials used is easy to get, and provides a kind of simple method for efficiently synthesizing the polysubstituted glyoxaline compound of 2,4,5-.In addition, of the present invention described 2,4, the polysubstituted glyoxaline compound of 5-has no bibliographical information, and the synthetic method described in it also has no bibliographical information, prepares 2 of gained, it is active that the polysubstituted glyoxaline compound of 4,5-has certain extracorporeal suppression tumor cell, can be used as antitumor lead compound.
The preparation method of the compounds of this invention has following characteristics: (1) the present invention is without the need to by any additive or metal catalyst; (2) reaction yield is high, and the separation yield of most of product is more than 75%; (3) reaction raw materials is easy is easy to get, and multiple substrate structure all can tolerate this reaction conditions, applied widely.
Embodiment
Below will the invention will be further described by embodiment.
Embodiment 1 5-(4-ethoxyl phenenyl)-2-(4-aminomethyl phenyl)-1 h-imidazoles 4-ethyl formate
Will ( z)-2-nitrine-3-(4-ethoxyl phenenyl) ethyl propenoate (1 mmol), 2-(4-methyl-benzyl) hydrazine-1-tert-butyl methyl ether (1.1 mmol) adds in the glass tube sealing of high pressure resistant high temperature, after add the anhydrous acetonitrile of 2.0 mL, after reinforced, 130 oreact in C oil bath, TLC detection reaction (ethyl acetate: sherwood oil=1:3), after 8 hours, reaction terminates.Reaction solution vacuum concentration, concentrated solution is extracted with ethyl acetate (20 mL × 3), organic phase washes 2 times with water after merging, saturated common salt washes 1 time, anhydrous sodium sulfate drying, filters, be spin-dried for and obtain residue, carry out column chromatography for separation (elutriant is ethyl acetate: sherwood oil=1:3), obtain white solid, yield is 87%.
White solid, m.p. 148.3-149.2 oC, 1H NMR (500 MHz, CDCl 3) δ 7.86 (d, J= 8.0 Hz, 4H), 7.24 (d, J= 8.0 Hz, 2H), 6.92 (d, J= 8.8 Hz, 2H), 4.38-4.29 (m, 2H), 4.16-4.01 (m, 2H), 2.39 (s, 3H), 1.43 (t, J= 7.0 Hz, 3H), 1.32 (t, J= 7.0 Hz, 3H).HRMS (ESI): m/z calcd for (C 21H 22N 2O 3+H) +: 351.1703; found: 351.1709。
Embodiment 2 5-(4-aminomethyl phenyl)-2-(4-aminomethyl phenyl)-1 h-imidazoles 4-ethyl formate
Synthesis step with embodiment 1, just (Z)-2-nitrine-3-(4-ethoxyl phenenyl) ethyl propenoate is changed into ( z)-2-nitrine-3-(4-aminomethyl phenyl) ethyl propenoate, obtain white solid, yield is 89%.
White solid, m.p. 229.1-229.8 oC, 1H NMR (500 MHz, CDCl 3) δ 9.97 (s, 1H), 7.85-7.84 (m, 3H), 7.28-7.24 (m, 5H), 4.35 (q, J= 7.0 Hz, 2H), 1.34 (t, J= 7.0 Hz, 3H). 13C NMR (125 MHz, DMSO) δ 161.2, 147.6, 140.2, 138.7, 129.8, 129.4, 128.7, 126.1, 61.1, 21.6, 21.5, 14.4. HRMS (ESI): m/z calcd for (C 20H 20N 2O 2+H) +: 321.1598; found: 321.1607。
Embodiment 3 5-(4-bromophenyl)-2-(4-aminomethyl phenyl)-1 h-imidazoles 4-ethyl formate
Synthesis step with embodiment 1, just (Z)-2-nitrine-3-(4-ethoxyl phenenyl) ethyl propenoate is changed into ( z)-2-nitrine-3-(4-bromophenyl) ethyl propenoate, obtain light yellow solid, yield is 85%.
Light yellow solid, m.p. 181.9-182.8 oC, 1H NMR (500 MHz, CDCl 3) δ 10.09 (s, 1H), 7.88-7.84 (m, 4H), 7.54 (d, J= 8.5 Hz, 2H), 7.28 (d, J= 8.0 Hz, 2H), 4.35 (q, J= 7.0 Hz, 2H), 2.41 (s, 3H), 1.34 (t, J= 7.0 Hz, 3H). 13C NMR (125 MHz, DMSO) δ 160.4, 148.2, 147.1, 140.5, 131.2, 131.1, 129.9, 126.1, 126.0, 122.9, 61.3, 21.6, 14.4. HRMS (ESI): m/z calcd for (C 19H 17BrN 2O 2+H) +:385.0546; found: 385.0553。
Embodiment 4 5-(4-aminomethyl phenyl)-2-phenyl-1 h-imidazoles 4-ethyl formate
Synthesis step is with embodiment 2, and just change 2-(4-methyl-benzyl) hydrazine-1-tert-butyl methyl ether into 2-benzyl hydrazine-1-tert-butyl methyl ether, obtain white solid, yield is 90%.
White solid, m.p. 229.2-230.4 oC, 1H NMR (500 MHz, DMSO) δ 8.12 (d, J= 7.5 Hz, 2H), 7.70 (d, J= 8.0 Hz, 2H), 7.50-7.46 (m, 2H), 7.43-7.40 (m, 1H), 7.25 (d, J= 8.0 Hz, 2H), 4.23 (q, J = 7.0 Hz, 2H), 2.36 (s, 3H), 1.24 (t, J= 7.0 Hz, 3H). 13C NMR (125 MHz, DMSO) δ 161.7, 146.9, 137.6, 129.9, 129.3, 128.9, 128.7, 128.3, 125.9, 59.7, 20.9, 14.2.HRMS (ESI): m/z calcd for (C 19H 18N 2O 2+H) +:307.1441; found: 307.1447。
Embodiment 5 5-(3-p-methoxy-phenyl)-2-phenyl-1 h-imidazoles 4-ethyl formate
Synthesis step is with embodiment 4, just change (Z)-2-nitrine-3-(4-aminomethyl phenyl) ethyl propenoate into (Z)-2-nitrine-3-(3-p-methoxy-phenyl) ethyl propenoate, obtain white solid, yield is 80%.
White solid, m.p. 127.4-129.1 oC, 1H NMR (500 MHz, CDCl 3) δ 10.60 (s, 1H), 7.96 (m, 2H), 7.59-7.38 (m, 5H), 7.30 (d, J= 7.5 Hz, 1H), 6.91 (d, J= 7.0 Hz, 1H), 4.31 (q, J= 7.0 Hz, 2H), 3.82 (s, 3H), 1.37-1.23 (m, 3H).HRMS (ESI): m/z calcd for (C 19H 18N 2O 3+H) +:323.1390; found: 323.1394。
Embodiment 6 5-(4-chloro-phenyl-)-2-phenyl-1 h-imidazoles 4-ethyl formate
Synthesis step is with embodiment 4, and just change (Z)-2-nitrine-3-(4-aminomethyl phenyl) ethyl propenoate into (Z)-2-nitrine-3-(4-chloro-phenyl-) ethyl propenoate, obtain yellow solid, yield is 84%.
Yellow solid, m.p.: 209.6-210.1 oC 1H NMR (500 MHz, CDCl 3) δ 10.16 (s, 1H), 8.01-7.93 (m, 3H), 7.53-7.46 (m, 3H), 7.44-7.40 (m, 2H), 4.39 (q, J= 7.0 Hz, 2H), 1.38 (t, J= 7.0 Hz, 3H). 13C NMR (125 MHz, DMSO) δ 159.7, 134.6, 130.9, 130.2, 129.2, 128.9, 128.2, 128.3, 126.1, 61.4, 14.4. HRMS (ESI): m/z calcd for (C 18H 15ClN 2O 3+H) +:327.0895; found: 327.0899。
Embodiment 7 5-(2-furyl)-2-phenyl-1 h-imidazoles 4-ethyl formate
Synthesis step is with embodiment 4, and just change (Z)-2-nitrine-3-(4-aminomethyl phenyl) ethyl propenoate into (Z)-2-nitrine-3-(2-furyl) ethyl propenoate, obtain brown solid, yield is 75%.
Brown solid, m.p.: 222.6-223.7 oC. 1H NMR (500 MHz, CDCl 3) δ 7.97 (d, J= 6.5 Hz, 2H), 7.55 (s, 1H), 7.52-7.41 (m, 4H), 6.56 (dd, J= 3.5, 2.0 Hz, 1H), 4.45 (q, J= 7.0 Hz, 2H), 1.45 (t, J= 7.0 Hz, 3H). 13C NMR (125 MHz, DMSO) δ 142.9, 130.1, 129.1, 128.8, 126.2, 112.6, 112.3, 61.2, 14.6. HRMS (ESI): m/z calcd for (C 16H 14N 2O 3+H) +:283.1077; found: 283.1081。
Embodiment 8 5-(2-furyl)-2-(4-aminomethyl phenyl)-1 h-imidazoles 4-ethyl formate
Synthesis step is with embodiment 7, and just change 2-benzyl hydrazine-1-tert-butyl methyl ether into 2-(4-methyl-benzyl) hydrazine-1-tert-butyl methyl ether, obtain brown solid, yield is 76%.
Brown solid, m.p.: 229.2-230.4 oC. 1H NMR (500 MHz, CDCl 3) δ 10.26 (s, 1H), 7.88 (s, 2H), 7.47 (m, 2H), 7.24 (d, J= 7.0 Hz, 2H), 6.54 (s, 1H), 4.42 (q, J= 7.0 Hz, 2H), 2.38 (s, 3H), 1.40 (t, J= 7.0 Hz, 3H).HRMS (ESI): m/z calcd for (C 17H 16N 2O 3+H) +:297.1234; found: 297.1243。
Embodiment 9 anti-tumor activity is tested
With A431(people's epidermal carcinoma cell) be test cell strain, mtt assay is adopted to carry out the evaluation of extracorporeal anti-tumor cytoactive to synthetic compound, testing compound is made into certain concentration and A431 cell strain hatches 72 hours altogether, measures its inhibiting rate to cancer cells, in table 1.
Detection method is specific as follows:
1. collect the A431 cell of logarithmic phase, regulate concentration of cell suspension to be 3500/hole;
2. adding testing compound makes its final concentration reaching every hole be 20 μm of mol/L;
3. 37 oc, 5% CO 272 hours are hatched under condition;
4. every hole adds the MTT solution of 20 μ L, continues cultivation 4 hours;
5. remove supernatant liquor, every hole adds the DMSO of 150 μ L, mixes 5 minutes, detects its absorbance under microplate reader 570nm wavelength;
6. the calculation formula of inhibiting rate is: cell inhibitory rate=1-(dosing group OD/ control group OD).
。

Claims (5)

1. a polysubstituted glyoxaline compound, is characterized in that, has following structural formula:
Wherein R 1for electrophilic with to the phenyl of electronics replacement or furans, R 2for ester group, Ar is contraposition methyl substituted and the phenyl without replacement.
2. according to claims 12,4,5-polysubstituted glyoxaline compounds, is characterized in that, are selected from following any one:
5-(4-ethoxyl phenenyl)-2-(4-aminomethyl phenyl)-1 h-imidazoles 4-ethyl formate
5-(4-aminomethyl phenyl)-2-(4-aminomethyl phenyl)-1 h-imidazoles 4-ethyl formate
5-(4-bromophenyl)-2-(4-aminomethyl phenyl)-1 h-imidazoles 4-ethyl formate
5-(4-aminomethyl phenyl)-2-phenyl-1 h-imidazoles 4-ethyl formate
5-(3-p-methoxy-phenyl)-2-phenyl-1 h-imidazoles 4-ethyl formate
5-(4-chloro-phenyl-)-2-phenyl-1 h-imidazoles 4-ethyl formate
5-(2-furyl)-2-phenyl-1 h-imidazoles 4-ethyl formate
5-(2-furyl)-2-(4-aminomethyl phenyl)-1 h-imidazoles 4-ethyl formate.
3. the preparation method of a kind of 2,4,5-polysubstituted glyoxaline compounds according to claim 1 and 2, be is characterized in that, realized by following steps:
(1) by the carbazates of alkene azide compounds, replacement in organic solvent in 130 oc reacts, and the reaction times is 8-10 hour, and the mol ratio of the carbazates of alkene azide compounds and replacement is 1:1.1,
The structural formula of described alkene azide compounds is:
Described replacement carbazates structural formula is:
Wherein R 3for methyl substituted aryl (-CH2Ar) or benzyl, LG is tert.-butoxy;
(2) after reaction solution step (1) obtained is concentrated, with water and extraction into ethyl acetate, obtain residue after the organic phase drying obtained is concentrated, residue is carried out silica gel column chromatography, obtains 2,4,5-polysubstituted glyoxaline compounds according to claim 1;
Reaction formula is:
Described R 1, R 2, Ar definition with claim 1.
4. the preparation method of 2,4,5-polysubstituted glyoxaline compounds according to claim 3, is characterized in that, described organic solvent is acetonitrile, Isosorbide-5-Nitrae-dioxane, DMF or toluene.
5. the application of 2,4,5-polysubstituted imidazoles according to claim 1 and 2 in preparation tumor.
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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105968053A (en) * 2016-07-06 2016-09-28 王建军 Synthesis method of pharmaceutical intermediate diarylimidazoles compound

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1153172A (en) * 1995-09-11 1997-07-02 日本农药株式会社 Azole derivatives, their use, production and usage
CN1265033A (en) * 1997-07-03 2000-08-30 纽罗杰有限公司 Certain diarylimidaozle derivatives, new class of NPY speific ligands
US20050148601A1 (en) * 2003-12-19 2005-07-07 Maynard George D. Neurokinin-3 receptor modulators: diaryl imidazole derivatives
CN101796038A (en) * 2007-05-10 2010-08-04 萨勒姆有限公司 Oxazole tyrosine kinase inhibitors
CN104387326A (en) * 2014-10-26 2015-03-04 浙江大学 Preparation method for 1,4,5-trisubstituted-2-amino imidazole compound
CN104529809A (en) * 2014-10-10 2015-04-22 浙江大学 Preparation method polysubstituted imidazole derivatives

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1153172A (en) * 1995-09-11 1997-07-02 日本农药株式会社 Azole derivatives, their use, production and usage
CN1265033A (en) * 1997-07-03 2000-08-30 纽罗杰有限公司 Certain diarylimidaozle derivatives, new class of NPY speific ligands
US20050148601A1 (en) * 2003-12-19 2005-07-07 Maynard George D. Neurokinin-3 receptor modulators: diaryl imidazole derivatives
CN101796038A (en) * 2007-05-10 2010-08-04 萨勒姆有限公司 Oxazole tyrosine kinase inhibitors
CN104529809A (en) * 2014-10-10 2015-04-22 浙江大学 Preparation method polysubstituted imidazole derivatives
CN104387326A (en) * 2014-10-26 2015-03-04 浙江大学 Preparation method for 1,4,5-trisubstituted-2-amino imidazole compound

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
KARLHEINZ BUNGE,等: "1.3-Dipolare Cycloadditionen, 64. Weitere Umsetzungen von Nitril-yliden mit Hetero-Mehrfachbindungen", 《CHEMISCHE BERICHTE》 *
MATTHEW R. SMITH，等: "Carbene Reactivity of 4-Diazo-4H-imidazoles toward Nucleophiles and Aromatic Compounds", 《J. ORG. CHEM.》 *
MEI-YUAN HSU,等: "Synthesis of di- and tri-substituted imidazole-4-carboxylates via PBu3-mediated [3+2] cycloaddition", 《SYNTHETIC COMMUNICATIONS》 *
NEUNHOEFFER, 等: "Zur Chemie der 1,2,4-Triazine, VIII. Struktur eines Reaktionsproduktes von 3-(p-Tolyl)-l,2,4-triazinen mit Acetylendicarbonsaure-dimethylester", 《LIEBIGS ANN. CHEM》 *
程云锋,等: "咪唑啉-2-酮衍生物的合成及其抗肿瘤活性", 《药学学报》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105968053A (en) * 2016-07-06 2016-09-28 王建军 Synthesis method of pharmaceutical intermediate diarylimidazoles compound

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