CN104016898B - 3,4-disubstituted pyrroles compounds and its preparation method and application - Google Patents
3,4-disubstituted pyrroles compounds and its preparation method and application Download PDFInfo
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- CN104016898B CN104016898B CN201410246968.2A CN201410246968A CN104016898B CN 104016898 B CN104016898 B CN 104016898B CN 201410246968 A CN201410246968 A CN 201410246968A CN 104016898 B CN104016898 B CN 104016898B
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- pyrroles
- dmso
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- benzoyl
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- -1 3,4-disubstituted pyrroles compounds Chemical class 0.000 title claims abstract description 110
- 238000002360 preparation method Methods 0.000 title abstract description 110
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- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 4
- 229940041181 antineoplastic drug Drugs 0.000 claims abstract description 4
- 210000004027 cell Anatomy 0.000 claims description 74
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 7
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 6
- 208000029742 colonic neoplasm Diseases 0.000 claims description 6
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- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
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- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 2
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims 1
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 1
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- RMMZGPSYPUIIRO-UHFFFAOYSA-N di(thiophen-3-yl)methanone Chemical compound C1=CSC=C1C(=O)C=1C=CSC=1 RMMZGPSYPUIIRO-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- XFCTVNAJVQUGEP-UHFFFAOYSA-N ethyl 4-(3,4,5-trimethoxyphenyl)-1H-pyrrole-3-carboxylate Chemical class CCOC(=O)C1=CNC=C1C1=CC(OC)=C(OC)C(OC)=C1 XFCTVNAJVQUGEP-UHFFFAOYSA-N 0.000 description 1
- VWDOVYBPDRRKER-UHFFFAOYSA-N ethyl 4-(4-acetamidophenyl)-1H-pyrrole-3-carboxylate Chemical class CCOC(=O)C1=CNC=C1C1=CC=C(NC(C)=O)C=C1 VWDOVYBPDRRKER-UHFFFAOYSA-N 0.000 description 1
- VEUUMBGHMNQHGO-UHFFFAOYSA-N ethyl chloroacetate Chemical compound CCOC(=O)CCl VEUUMBGHMNQHGO-UHFFFAOYSA-N 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- BWLIIZFNXSJVLW-UHFFFAOYSA-N n-[4-(2-nitroethenyl)phenyl]acetamide Chemical group CC(=O)NC1=CC=C(C=C[N+]([O-])=O)C=C1 BWLIIZFNXSJVLW-UHFFFAOYSA-N 0.000 description 1
- AMXOFEWEPYFRPN-UHFFFAOYSA-N n-[4-(3-oxobut-1-enyl)phenyl]acetamide Chemical compound CC(=O)NC1=CC=C(C=CC(C)=O)C=C1 AMXOFEWEPYFRPN-UHFFFAOYSA-N 0.000 description 1
- 210000004287 null lymphocyte Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 238000006175 van Leusen reaction Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/333—Radicals substituted by oxygen or sulfur atoms
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/335—Radicals substituted by nitrogen atoms not forming part of a nitro radical
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D207/42—Nitro radicals
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- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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- 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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- 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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- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- Chemical & Material Sciences (AREA)
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- Pyrrole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A kind of 3,4-disubstituted pyrroles compounds, this compound has the structure shown in below formula:The preparation method of above-mentioned 3,4-disubstituted pyrroles compounds is to occur Michael addition, cyclization and elimination to react and obtain by disubstituted olefin with to Methyl benzenesulfonyl methyl isocyanide.Compared with prior art, a series of 3 the present invention relates to, 4-disubstituted pyrroles compounds has stronger anti tumor activity in vitro, Normocellular proliferation inhibition activity is suppressed very weak simultaneously, showing excellent tumor cells selectivity, future can as a class safely and effectively antitumor drug.The preparation method of the present invention is easy and simple to handle, and reaction time is short, and yield is higher.
Description
Technical field
The present invention relates to organic compound, particularly relate to a kind of 3,4-disubstituted pyrroles compounds and its preparation method and application.
Background technology
Tumor be body under various carcinogenic factor effects, the cell of local organization loses the normal regulation to its growth on gene level, causes its clonal abnormality hypertrophy and the abnormality that formed.According to " 2012 China tumors registration annual report " display, annual new tumor cases about 3,120,000 example of sending out in the whole nation, average every day 8550 people's new cancer, cancer morbidity is up to 2855.91/10 ten thousand.Although various countries' research worker processes in tumor research and treatment and obtains remarkable progress, but tumor remains the one of the main reasons of human death at present.In current medical system, oncotherapy often adopt chemotherapy individually or with the method for operative treatment and radiotherapy combined, the huge market demand promotes have the antitumoral compounds in a large number with different structure feature and action character to be found in annual world wide, including the compound in a large number with pyrroles's mother nucleus structure, their anti-tumor activity has been confirmed and has generally acknowledged, the structure (JournalofChemistry, 2011,54:8394-8406 of part of compounds；Bioorganic&MedicinalChemistry, 2007,15:17-35；MolecularPharmacology, 2007,72 (1): 132-140；JournalofCellularPhysiology, 2009,218 (1): 13-21 etc.) as shown in Figure 1.
Due to the specific mechanism of action of antitumoral compounds, these compounds, while killing tumor cell, generally also severely impact proper splitting cell, bring toxicity in various degree.To the tolerance of antitumoral compounds and reduce toxic action for improving sufferer, find can single-minded blocking-up or killing off tumor cells and do not affect the Main way that the antitumoral compounds of normal cell growth differentiation is current cancer research.
Summary of the invention
The purpose of the present invention, it is simply that in order to solve the problems referred to above, it is provided that a kind of 3,4-disubstituted pyrroles compounds and its preparation method and application.
In order to achieve the above object, present invention employs techniques below scheme: a kind of 3,4-disubstituted pyrroles compounds, there is the structure shown in below formula:
Wherein, R1=3,4-F2During Ph, R2=2-FPhCO, 4-FPhCO, 2-ClPhCO, 4-ClPhCO, 3-BrPhCO, 4-BrPhCO, 3-CH3OPhCO、4-CH3OPhCO、3-PyridylCO、4-PyridylCO、2-ThienylCO、2-NO2PhCO, PhCO, 1-naphtholCO or 4-biphenylCO；
R1During=4-CH3CONHPh, R2=NO2、CN、COOEt、COCH3、2-FPhCO、4-FPhCO、2-ClPhCO、4-ClPhCO、3-BrPhCO、4-BrPhCO、4-CH3PhCO, 2,4-(CH3)2PhCO、3-CH3OPhCO、4-CH3OPhCO, 2-pyridylCO, 3-pyridylCO, 4-pyridylCO, 2-thienylCO, PhCO, 1-naphtholCO or 4-biphenylCO；
R1=3-CH3During OPh, R2=2-FPhCO, 4-FPhCO, 2-ClPhCO, 4-ClPhCO, 3-BrPhCO, 4-BrPhCO, 3-CH3OPhCO、4-CH3OPhCO、3-pyridylCO、4-pyridylCO、2-thienylCO、2-NO2PhCO, PhCO, 1-naphtholCO or 4-biphenylCO；
R1=3,4-(CH3O)2During Ph, R2=2-FPhCO, 4-FPhCO, 2-ClPhCO, 4-ClPhCO, 3-BrPhCO, 4-BrPhCO, 3-CH3OPhCO、4-CH3OPhCO、3-pyridylCO、4-pyridylCO、2-thienylCO、2-NO2PhCO, PhCO, 1-naphtholCO or 4-biphenylCO；
R1=3,4,5-(CH3O)3During Ph, R2=NO2、CN、COOEt、COCH3、2-FPhCO、4-FPhCO、2-ClPhCO、4-ClPhCO、3-BrPhCO、4-BrPhCO、4-CH3PhCO, 2,4-(CH3)2PhCO、3-CH3OPhCO、4-CH3OPhCO, 2-pyridylCO, 3-pyridylCO, 4-pyridylCO, 2-thienylCO, 1-naphtholCO or 4-biphenylCO；
R1During=2-naphthol, R2=2-FPhCO, 2-ClPhCO, 4-ClPhCO or 2,4-(CH3)2PhCO；
R1During=2-pyridyl, R2=CN, COOEt, 4-CH3PhCO, 2,4-(CH3)2PhCO, 2-thienylCO, PhCO or 1-naphtholCO.
The preparation method of above-mentioned 3,4-disubstituted pyrroles compounds, is occur Michael addition, cyclization and elimination to react and obtain by disubstituted olefin i with to Methyl benzenesulfonyl methyl isocyanide, and synthetic route is as follows:
In anhydrous response system, add the TosMIC of 1 equivalent disubstituted olefin i and 1.1～1.3 equivalent, add the potassium tert-butoxide of 1.2～1.4 equivalents as alkaline condensing agent, 3,4-disubstituted pyrroles compounds can be prepared at low ambient temperatures.
After adding potassium tert-butoxide in reaction system and being sufficiently stirred for dissolving, reaction can be warming up to room temperature and carry out.
The preparation method of above-mentioned 3,4-disubstituted pyrroles compounds specifically includes following two step:
(1) preparation of disubstituted olefin i
Wherein R1Group is that initiation material introduces by the benzaldehyde of various replacements.
The structural formula of the benzaldehyde of various replacements is as shown in Figure 2.
According to R2The difference of group, the preparation of i can be divided into following four situation.
One, R is worked as2=NO2Time, with ammonium acetate for condensing agent, being added in Nitrocarbol. (simultaneously as reaction dissolvent) by the benzaldehyde of various replacements (reaction initial concentration 0.1mol/L), be heated to reflux 4-8h and can prepare and replace nitroolefin accordingly, course of reaction is as follows:
But, work as R2=NO2, R1=4-CH3During CONHPh, reaction dissolvent is used the higher glacial acetic acid of boiling point instead and is more beneficial for the carrying out of reaction: add 4-acetyl-benzaldehyde (reaction initial concentration 0.1mol/L) in glacial acetic acid and appropriate Nitrocarbol. is heated to reflux, can prepare 1-nitro-2-(4-acetylamino phenyl) ethylene under the condensation of ammonium acetate.
Two, R is worked as2During=CN or COOEt, jointly it is heated to reflux straight without gas generation with NSC 5284 (reaction initial concentration 1.5mol/L) respectively with appropriate chloroacetonitrile and ethyl chloroacetate, after cooling, reaction system prepares cyano group and ethoxycarbonyl Horner-Wadsworth-Emmons (HWE) reagent of activation respectively through decompression distilation, next jointly it is dissolved in THF with the benzaldehyde of various replacements, preparing replacement cyano group alkene under appropriate sodium hydride or potassium tert-butoxide effect and replace ethoxycarbonyl alkene, course of reaction is as follows:
Three, R is worked as2=COCH3Time, a small amount of metallic sodium is joined and absolute methanol prepares containing catalytic amount Sodium ethylate (CH3ONa) methanol solution (or dripping the methanol solution of 10% sodium hydrate aqueous solution containing 2-6); the benzaldehyde of various replacements and proper amount of acetone are added wherein; the reaction initial concentration making the benzaldehyde of various replacement is 0.1mol/L, and room temperature reaction 2-8h can prepare corresponding replacement acetyl group alkene；
Four, R is worked as2During for substituted benzoyl, preparation method is similar with three, adopts the aldol reaction of base catalysis, joins by a small amount of metallic sodium and prepare in absolute methanol containing catalytic amount CH3The methanol solution (or dripping the methanol solution of 10% sodium hydrate aqueous solution containing 2-6) of ONa, the benzaldehyde of various replacements and proper amount of acetone are added wherein, the reaction initial concentration making the benzaldehyde of various replacement is 0.1mol/L, room temperature reaction 10min-48h can prepare corresponding disubstituted olefin, there is larger difference in its response time according to activity and the sterically hindered difference of reaction substrate, and course of reaction is as follows:
The structural formula of the substituted acetophenone compound that wherein the present invention relates to is as shown in Figure 3.
(2) preparation of pyrroles's parent nucleus
With dry THF or DMSO for solvent, the initial action concentration of disubstituted olefin i is 0.1mol/L.Under the catalytic action of appropriate potassium tert-butoxide, i and appropriate TosMIC occurs Michael addition, cyclization and three steps of elimination to form pyrrole ring, and course of reaction is as follows:
The application of 3,4-above-mentioned disubstituted pyrroles compounds, various tumor cell strains is had proliferation inhibition activity by described 3,4-disubstituted pyrroles compounds, has the ability of excellent selective killing tumor cell, can be used for preparing antitumor drug.
16 kinds of tumor cell lines are had proliferation inhibition activity by 3,4-disubstituted pyrroles compounds provided by the invention, especially so that MGC80-3, DU145, A375, MCF-7, Hela, CHO and CT-26 is comparatively sensitive.
16 kinds of tumor cell lines include human gastric adenocarcinoma (SGC-7901), gastric carcinoma cells (MGC80-3), National People's Congress's cell lung cancer cell (NCI-H460), Human Prostate Cancer Cells (DU145), human breast cancer cell (MCF-7), human cervical carcinoma cell (Hela), people's malignant melanoma cell (A375), people chronic marrow source leukemia (K562), human colon cancer cell (HCT-116), people's Colon and rectum adenocarcinoma cell (HCT-15), human liver cancer cell (HepG2), human osteosarcoma cell (MG-63), human lung carcinoma cell (A549), mouse leukemia cell (L1210), mouse colonic cell (CT-26) and Chinese hamster ovary cancerous cell (CHO)；Normal cell strain includes human umbilical vein endothelial cell (HUVEC) and mouse embryo cell (NIH/3T3).
It has also been found that 3,4-disubstituted pyrroles compounds to normal cell strain HUVEC and NIH/3T3 almost without inhibitory activity, it was shown that selectivity that this compounds is excellent and safety, to being used as safely and effectively antitumor drug.
nullDescribed 3，4-disubstituted pyrroles compound includes (4-(3，4-difluorophenyl)-1H-pyrroles's-3-base) (2-fluorophenyl) ketone、(4-(3，4-difluorophenyl)-1H-pyrroles's-3-base) (4-fluorophenyl) ketone、(4-(3，4-difluorophenyl)-1H-pyrroles's-3-base) (2-chlorphenyl) ketone、(4-(3，4-difluorophenyl)-1H-pyrroles's-3-base) (4-chlorphenyl) ketone、(4-(3，4-difluorophenyl)-1H-pyrroles's-3-base) (3-bromophenyl) ketone、(4-(3，4-difluorophenyl)-1H-pyrroles's-3-base) (4-bromophenyl) ketone、(4-(3，4-difluorophenyl)-1H-pyrroles's-3-base) (3-methoxyphenyl) ketone、(4-(3，4-difluorophenyl)-1H-pyrroles's-3-base) (4-methoxyphenyl) ketone、(4-(3，4-difluorophenyl)-1H-pyrroles's-3-base) (3-pyridine radicals) ketone、(4-(3，4-difluorophenyl)-1H-pyrroles's-3-base) (4-pyridine radicals) ketone、(4-(3，4-difluorophenyl)-1H-pyrroles's-3-base) (2-thienyl) ketone、(4-(3，4-difluorophenyl)-1H-pyrroles's-3-base) (2-nitrobenzophenone) ketone、(4-(3，4-difluorophenyl)-1H-pyrroles's-3-base) (phenyl) ketone、(4-(3，4-difluorophenyl)-1H-pyrroles's-3-base) (1-naphthyl) ketone、(4-(3，4-difluorophenyl)-1H-pyrroles's-3-base) (4-xenyl) ketone、3-nitro-4-(4-acetylamino phenyl)-1H-pyrroles、3-cyano group-4-(4-acetylamino phenyl)-1H-pyrroles、3-ethoxycarbonyl-4-(4-acetylamino phenyl)-1H-pyrroles、3-acetyl group-4-(4-acetylamino phenyl)-1H-pyrroles、(4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (2-fluorophenyl) ketone、(4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (4-fluorophenyl) ketone、(4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (2-chlorphenyl) ketone、(4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (4-chlorphenyl) ketone、(4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (3-bromophenyl) ketone、(4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (4-bromophenyl) ketone、(4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (4-aminomethyl phenyl) ketone、(4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (2，4-3,5-dimethylphenyl) ketone、(4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (3-methoxyphenyl) ketone、(4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (4-methoxyphenyl) ketone、(4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (2-pyridine radicals) ketone、(4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (3-pyridine radicals) ketone、(4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (4-pyridine radicals) ketone、(4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (4-thienyl) ketone、(4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (phenyl) ketone、(4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (1-naphthyl) ketone、(4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (4-xenyl) ketone、(4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (2-fluorophenyl) ketone、(4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (4-fluorophenyl) ketone、(4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (2-chlorphenyl) ketone、(4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (4-fluorophenyl) ketone、(4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (3-bromophenyl) ketone、(4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (4-bromophenyl) ketone、(4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (3-methoxyphenyl) ketone、(4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (4-methoxyphenyl) ketone、(4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (3-pyridine radicals) ketone、(4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (4-pyridine radicals) ketone、(4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (2-thienyl) ketone、(4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (2-nitrobenzophenone) ketone、(4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (phenyl) ketone、(4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (1-naphthyl) ketone、(4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (4-xenyl) ketone、(4-(3，4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (2-fluorophenyl) ketone、(4-(3，4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (4-fluorophenyl) ketone、(4-(3，4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (2-chlorphenyl) ketone、(4-(3，4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (4-chlorphenyl) ketone、(4-(3，4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (3-bromophenyl) ketone、(4-(3，4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (4-bromophenyl) ketone、(4-(3，4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (3-methoxyphenyl) ketone、(4-(3，4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (4-methoxyphenyl) ketone、(4-(3，4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (3-pyridine radicals) ketone、(4-(3，4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (4-pyridine radicals) ketone、(4-(3，4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (2-thienyl) ketone、(4-(3，4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (2-nitrobenzophenone) ketone、(4-(3，4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (phenyl) ketone、(4-(3，4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (1-naphthyl) ketone、(4-(3，4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (4-xenyl) ketone、3-nitro-4-(3，4，5-trimethoxyphenyl)-1H-pyrroles、3-cyano group-4-(3，4，5-trimethoxyphenyl)-1H-pyrroles、3-ethoxycarbonyl-4-(3，4，5-trimethoxyphenyl)-1H-pyrroles、3-acetyl group-4-(3，4，5-trimethoxyphenyl)-1H-pyrroles、(4-(3，4，5-trimethoxyphenyl)-1H-pyrroles's-3-base) (2-fluorophenyl) ketone、(4-(3，4，5-trimethoxyphenyl)-1H-pyrroles's-3-base) (4-fluorophenyl) ketone、(4-(3，4，5-trimethoxyphenyl)-1H-pyrroles's-3-base) (2-chlorphenyl) ketone、(4-(3，4，5-trimethoxyphenyl)-1H-pyrroles's-3-base) (4-chlorphenyl) ketone、(4-(3，4，5-trimethoxyphenyl)-1H-pyrroles's-3-base) (3-bromophenyl) ketone、(4-(3，4，5-trimethoxyphenyl)-1H-pyrroles's-3-base) (4-bromophenyl) ketone、(4-(3，4，5-trimethoxyphenyl)-1H-pyrroles's-3-base) (4-aminomethyl phenyl) ketone、(4-(3，4，5-trimethoxyphenyl)-1H-pyrroles's-3-base) (2，4-3,5-dimethylphenyl) ketone、(4-(3，4，5-trimethoxyphenyl)-1H-pyrroles's-3-base) (3-methoxyphenyl) ketone、(4-(3，4，5-trimethoxyphenyl)-1H-pyrroles's-3-base) (4-methoxyphenyl) ketone、(4-(3，4，5-trimethoxyphenyl)-1H-pyrroles's-3-base) (2-pyridine radicals) ketone、(4-(3，4，5-trimethoxyphenyl)-1H-pyrroles's-3-base) (3-pyridine radicals) ketone、(4-(3，4，5-trimethoxyphenyl)-1H-pyrroles's-3-base) (4-pyridine radicals) ketone、(4-(3，4，5-trimethoxyphenyl)-1H-pyrroles's-3-base) (2-thienyl) ketone、(4-(3，4，5-trimethoxyphenyl)-1H-pyrroles's-3-base) (1-naphthyl) ketone、(4-(3，4，5-trimethoxyphenyl)-1H-pyrroles's-3-base) (4-xenyl) ketone、(4-(2-naphthyl)-1H-pyrroles's-3-base) (2-fluorophenyl) ketone、(4-(2-naphthyl)-1H-pyrroles's-3-base) (2-chlorphenyl) ketone、(4-(2-naphthyl)-1H-pyrroles's-3-base) (4-chlorphenyl) ketone、(4-(2-naphthyl)-1H-pyrroles's-3-base) (2，4-3,5-dimethylphenyl) ketone、3-cyano group-4-(2-pyridine radicals)-1H-pyrroles、3-ethoxycarbonyl-4-(2-pyridine radicals)-1H-pyrroles、(4-(2-pyridine radicals)-1H-pyrroles's-3-base) (4-aminomethyl phenyl) ketone、(4-(2-pyridine radicals)-1H-pyrroles's-3-base) (2，4-3,5-dimethylphenyl) ketone、(4-(2-pyridine radicals)-1H-pyrroles's-3-base) (2-thienyl) ketone、(4-(2-pyridine radicals)-1H-pyrroles's-3-base) (phenyl) ketone and (4-(2-pyridine radicals)-1H-pyrroles's-3-base) (1-naphthyl) ketone.
The present invention compared with prior art, has the following advantages that and feature:
1, the kind of 3,4-bit substituent groups has been greatly enriched；
2, having expanded the kind of tested tumor cell, the antitumor pedigree for finding this 3,4-disubstituted pyrroles compound provides sufficient basis；
3, add a kind of normal subject cell NIH/3T3, confirm described compound further to normal cell without the conclusion affected；
4, adding positive control 5-fluorouracil, the antitumor fully to compare described compound is applied；
Most importantly, the proliferation inhibition activity of compound on tumor cell of the present invention is significantly stronger than the polysubstituted pyrrole compound disclosed in patent CN102516149A.
Accompanying drawing explanation
Fig. 1 is the structural formula of the known antitumoral compounds of part；
Fig. 2 is the structural formula of the benzaldehyde of the various replacements that the present invention adopts；
Fig. 3 is the structural formula of the various substituted acetophenone compounds that the present invention adopts.
Detailed description of the invention
The following is specific embodiments of the invention, technical scheme be further described, it is emphasized that, the present invention is not limited to these embodiments.In the present invention, abbreviation used and implication thereof are as shown in table 1:
Table 1
| Abbreviation | Chinese implication or full name |
| TosMIC | To Methyl benzenesulfonyl methyl isocyanide |
| THF | Oxolane |
| DMSO | Dimethyl sulfoxide |
| t-BuOK | Potassium tert-butoxide |
| h | Hour |
| eq. | Equivalent |
| rt | Room temperature |
| MTT | 3-(4,5-dimethylthiazole-2)-2,5-diphenyltetrazolium bromide bromine salt, tetrazolium bromide |
| IC50 | Half-inhibition concentration (μm ol/L) |
| OD | Absorbance (Optical Density) |
One, the synthesis of 3,4-disubstituted pyrroles compounds
Embodiment 1
The synthesis of (4-(3,4-difluorophenyl)-1H-pyrroles's-3-base) (2-fluorophenyl) ketone:
By 1-(2-fluorophenyl)-3-(3,4-difluorophenyl) propenone (0.26g, 1.0mmol) with TosMIC (0.21g, 1.1mmol) it is dissolved in THF or DMSO of 10mL dried, stirring cooling under ice bath, slowly or be dividedly in some parts t-BuOK (0.14g, 1.2mmol), can room temperature reaction after each reactant is sufficiently stirred for contact.Stopped reaction after 2h, with the t-BuOK that the saturated aqueous ammonium chloride cancellation of ice is excessive, reactant liquor, with extraction into ethyl acetate three times (75mL, 25mL × 3), merges organic layer, after saturated common salt water washing once, anhydrous sodium sulfate standing and drying.Decompression boils off solvent, silica gel column chromatography (petroleum ether: ethyl acetate=1: 2) obtains white (4-(3,4-difluorophenyl)-1H-pyrroles's-3-base) (phenyl) ketone solid (0.19g, 0.64mmol), yield 69.4%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO) δ (ppm): 11.82 (s, 1H, NH), 7.57-7.48 (m, 3H ,-CO-Ar-H), 7.39-7.31 (m, 2H ,-CO-Ar-H+Ar-H), 7.30-7.23 (m, 2H, Ar-H), 7.19 (s, 1H, pyrrole-H), 7.16 (s, 1H, pyrrole-H)；13CNMR (100MHz, DMSO-d6) δ (ppm): 186.50,159.99,157.53,149.97,149.84,149.26,149.14,147.55,147.43,146.84,146.71,132.46,131.98,131.90,130.31,129.74,129.71,129.43,129.27,125.19,124.16,124.13,122.95,121.36,121.02,117.45,117.28,116.56,116.39,115.98,115.76.
Embodiment 2
The synthesis of (4-(3,4-difluorophenyl)-1H-pyrroles's-3-base) (4-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-fluorophenyl)-3-(3,4-difluorophenyl) propenone and TosMIC.
Product is slightly yellow solid, yield 83.7%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO) δ (ppm): 11.77 (s, 1H, NH), 7.76 (dd, J1=6.0Hz, J2=8.4Hz, 2H,-CO-Ar-H), 7.48 (ddd, J1=1.6Hz, J2=8.0Hz, J3=12Hz, 1H, Ar-H), 7.36-7.26 (m, 4H, Ar-H+-CO-Ar-H+pyrrole-H), 7.25-7.20 (m, 1H, Ar-H), 7.19 (s, 1H, pyrrole-H)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.79,165.29,162.81,150.08,149.95,149.10,148.97,147.66,147.54,146.68,146.55,136.41,132.77,131.66,131.57,128.57,124.86,123.30,120.41,120.22,117.12,116.94,116.64,116.48,115.19,114.98.
Embodiment 3
The synthesis of (4-(3,4-difluorophenyl)-1H-pyrroles's-3-base) (2-chlorphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-chlorphenyl)-3-(3,4-difluorophenyl) propenone and TosMIC.
Product is slightly yellow solid, yield 76.2%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO) δ (ppm): 11.81 (s, 1H, NH), 7.59 (dd, J1=8.0Hz, J2=12.8Hz, 1H ,-CO-Ar-H), 7.53-7.44 (m, 3H ,-CO-Ar-H), 7.42 (d, J=6.8Hz, 1H, Ar-H), 7.39-7.33 (m, 2H, Ar-H), 7.16 (s, 1H, pyrrole-H), 7.02 (s, 1H, pyrrole-H)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.48,149.98,149.85,149.30,149.18,147.56,147.43,146.88,146.75,140.52,132.43,130.77,130.59,129.53,128.57,126.80,125.17,122.92,121.30,120.89,117.43,117.25,116.59,116.42.
Embodiment 4
The synthesis of (4-(3,4-difluorophenyl)-1H-pyrroles's-3-base) (4-chlorphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-chlorphenyl)-3-(3,4-difluorophenyl) propenone and TosMIC.
Product is faint yellow solid, yield 83.8%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO) δ (ppm): 11.79 (s, 1H, NH), 7.76 (d, J=8.0Hz, 2H ,-CO-Ar-H), 7.55 (d, J=8.0Hz, 2H ,-CO-Ar-H), 7.49 (dd, J1=8.0Hz, J2=12Hz, 1H, Ar-H), 7.37-7.27 (m, 2H, Ar-H+pyrrole-H), 7.26-7.20 (m, 1H, Ar-H), 7.19 (s, 1H, pyrrole-H)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.93,150.07,149.94,149.14,149.02,147.66,147.53,146.72,146.59,138.57,136.31,132.73,130.74,128.93,128.23,124.96,123.30,120.56,120.07,117.17,117.00,116.64,116.47.
Embodiment 5
The synthesis of (4-(3,4-difluorophenyl)-1H-pyrroles's-3-base) (3-bromophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-bromophenyl)-3-(3,4-difluorophenyl) propenone and TosMIC.
Product is white solid, yield 80.6%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO) δ (ppm): 11.80 (s, 1H, NH), 7.81 (s, 1H,-CO-Ar-H), 7.78 (d, J=8.0Hz, 1H ,-CO-Ar-H), 7.72 (d, J=8.0Hz, 1H ,-CO-Ar-H), 7.50-7.41 (m, 2H, Ar-H+-CO-Ar-H), 7.36-7.27 (m, 2H, Ar-H+pyrrole-H), 7.25-7.20 (m, 1H, Ar-H), 7.19 (s, 1H, pyrrole-H)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.52,150.08,149.95,149.16,149.03,147.66,147.53,146.73,146.61,142.04,134.06,132.68,131.29,130.39,129.13,127.82,124.94,123.35,121.44,120.62,120.00,117.24,117.06,116.64,116.47.
Embodiment 6
The synthesis of (4-(3,4-difluorophenyl)-1H-pyrroles's-3-base) (4-bromophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-bromophenyl)-3-(3,4-difluorophenyl) propenone and TosMIC.
Product is faint yellow solid, yield 92.1%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO) δ (ppm): 11.79 (s, 1H, NH), 7.70 (d, J=8.8Hz, 2H ,-CO-Ar-H), 7.67 (d, J=8.8Hz, 2H ,-CO-Ar-H), 7.49 (ddd, J1=2Hz, J2=8.0Hz, J3=12.4Hz, 1H, Ar-H), 7.36-7.28 (m, 2H, Ar-H+pyrrole-H), 7.25-7.20 (m, 1H, Ar-H), 7.18 (s, 1H, pyrrole-H)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.06,150.06,149.94,149.14,149.01,147.65,147.52,146.71,146.59,138.93,132.79,131.18,130.91,128.99,125.29,124.94,123.31,120.58,120.03,117.18,117.00,116.65,116.48.
Embodiment 7
The synthesis of (4-(3,4-difluorophenyl)-1H-pyrroles's-3-base) (3-methoxyphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-methoxyphenyl)-3-(3,4-difluorophenyl) propenone and TosMIC.
Product is faint yellow solid, yield 67.3%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO) δ (ppm): 11.79 (s，1H，NH)，7.49(ddd，J1=1.6Hz，J2=8.0Hz，J3=12.4Hz，1H，Ar-H)，7.41(t，J=8.0Hz，1H，-CO-Ar-H)，7.36-7.28(m，3H，-CO-Ar-H+Ar-H+pyrrole-H)，7.26-7.21(m，2H，Ar-H+-CO-Ar-H)，7.17(s，1H，pyrrole-H)，7.16(dd，J1=2Hz，J2=8.0Hz，1H，-CO-Ar-H)，3.79(s，3H，-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.85,158.91,150.05,149.93,149.09,148.97,147.64,147.51,146.67,146.54,141.30,132.88,129.25,128.71,124.86,123.31,121.36,120.40,120.31,117.50,117.14,116.97,116.61,116.44,113.60,55.16.
Embodiment 8
The synthesis of (4-(3,4-difluorophenyl)-1H-pyrroles's-3-base) (4-methoxyphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-methoxyphenyl)-3-(3,4-difluorophenyl) propenone and TosMIC.
Product is yellow solid, yield 82.1%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO) δ (ppm): 11.68 (s, 1H, NH), 7.77 (d, J=8.0Hz, 2H ,-CO-Ar-H), 7.46 (ddd, J1=2Hz, J2=8.0Hz, J3=12.4Hz, 1H, Ar-H), 7.32-7.23 (m, 2H, Ar-H+pyrrole-H), 7.22-7.16 (m, 2H, Ar-H+pyrrole-H), 7.03 (d, J=8.0Hz, 2H ,-CO-Ar-H), 3.83 (s, 3H ,-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.09,162.14,150.10,149.97,149.00,148.87,147.68,147.55,146.58,146.45,133.01,132.23,131.27,127.49,124.71,123.14,120.52,120.01,116.89,116.72,116.67,116.50,113.42,55.37.
Embodiment 9
The synthesis of (4-(3,4-difluorophenyl)-1H-pyrroles's-3-base) (3-pyridine radicals) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-pyridine radicals)-3-(3,4-difluorophenyl) propenone and TosMIC.
Product is yellow solid, yield 38.3%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO) δ (ppm): 11.89 (s, 1H, NH), 8.73 (d, J=4.8Hz, 2H ,-CO-Ar-H), 7.60 (d, J=4.8Hz, 2H ,-CO-Ar-H), 7.54 (ddd, J1=2Hz, J2=8.0Hz, J3=12.4Hz, 1H, Ar-H), 7.36-7.25 (m, 3H, Ar-H+pyrrole-H), 7.20 (s, 1H, pyrrole-H)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.76,150.46,150.38,149.93,149.37,149.27,147.61,147.48,146.84,146.73,132.53,130.31,125.11,123.33,122.27,121.11,119.58,117.43,117.26,116.62,116.46.
Embodiment 10
The synthesis of (4-(3,4-difluorophenyl)-1H-pyrroles's-3-base) (4-pyridine radicals) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-pyridine radicals)-3-(3,4-difluorophenyl) propenone and TosMIC.
Product is yellow solid, yield 56.1%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO) δ (ppm): 11.86 (s, 1H, NH), 8.86 (s, 1H ,-CO-Ar-H), 8.75 (d, J=4Hz, 1H,-CO-Ar-H), 8.08 (d, J=8.0Hz, 1H ,-CO-Ar-H), 7.54-7.47 (m, 2H ,-CO-Ar-H+Ar-H), 7.37 (s, 1H, pyrrole-H), 7.35-7.23 (m, 2H, Ar-H), 7.20 (s, 1H, pyrrole-H)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.46,151.84,150.06,149.94,149.38,149.19,149.06,147.64,147.52,146.77,146.64,136.25,135.43,132.62,129.55,125.03,123.37,123.32,120.80,120.23,117.34,117.17,116.63,116.47.
Embodiment 11
The synthesis of (4-(3,4-difluorophenyl)-1H-pyrroles's-3-base) (2-thienyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-thienyl)-3-(3,4-difluorophenyl) propenone and TosMIC.
Product is faint yellow solid, yield 53.9%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO) δ (ppm): 11.77 (s, 1H, NH), 7.96 (d, J=4Hz, 1H ,-CO-Ar-H), 7.76 (d, J=4Hz, 1H ,-CO-Ar-H), 7.58 (s, 1H, pyrrole-H), 7.48 (ddd, J1=2Hz, J2=8.0Hz, J3=12.4Hz, 1H, Ar-H), 7.37 (dd, J1=8.0Hz, J2=18Hz, 1H, Ar-H), 7.24-7.18 (m, 3H ,-CO-Ar-H+Ar-H+pyrrole-H)；13CNMR (100MHz, DMSO-d6) δ (ppm): 181.67,150.13,150.00,149.10,148.97,147.71,147.58,146.67,146.55,145.33,133.41,133.06,132.76,128.24,127.21,124.76,122.93,120.35,120.06,116.91,116.74,116.58.
Embodiment 12
The synthesis of (4-(3,4-difluorophenyl)-1H-pyrroles's-3-base) (2-nitrobenzophenone) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-nitrobenzophenone)-3-(3,4-difluorophenyl) propenone and TosMIC.
Product is faint yellow solid, yield 75.9%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO) δ (ppm): 11.82 (s，1H，NH)，8.15(d，J=7.6Hz，1H，-CO-Ar-H)，7.85(t，J=7.6Hz，1H，-CO-Ar-H)，8.76(t，J=7.6Hz，1H，-CO-Ar-H)，7.65(d，J=7.6Hz，1H，-CO-Ar-H)，7.57(ddd，J1=2Hz，J2=8.0Hz，J3=12.4Hz，1H，Ar-H)，7.41-7.31(m，2H，Ar-H)，7.17(s，1H，pyrrole-H)，7.10(s，1H，pyrrole-H)；13CNMR (100MHz, DMSO-d6) δ (ppm): 187.05,150.02,149.90,149.32,149.19,147.60,147.48,146.89,146.76,146.71,136.79,134.01,132.31,130.61,129.77,129.15,124.96,124.27,122.90,121.31,120.53,117.22,117.05,116.68,116.51.
Embodiment 13
The synthesis of (4-(3,4-difluorophenyl)-1H-pyrroles's-3-base) (phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(phenyl)-3-(3,4-difluorophenyl) propenone and TosMIC.
Product is white solid, yield 70.8%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO) δ (ppm): 11.74 (s, 1H, NH), 7.75 (d, J=7.6Hz, 2H ,-CO-Ar-H), 7.60 (t, J=7.6Hz, 1H ,-CO-Ar-H), 7.52-7.42 (m, 3H,-CO-Ar-H+Ar-H), 7.35 (dd, J1=8.8Hz, J2=20.8Hz, 1H, Ar-H), 7.27-7.20 (m, 2H, pyrrole-H+Ar-H), 7.18 (s, 1H, pyrrole-H)；13CNMR (100MHz, DMSO-d6) δ (ppm): 190.99,147.90,147.37,139.02,133.15,130.11,129.81,129.70,128.50,127.39,126.63,126.13,125.80,125.30,125.14,124.59,122.14,120.03,112.91,119.57,111.42,55.53,55.27.
Embodiment 14
The synthesis of (4-(3,4-difluorophenyl)-1H-pyrroles's-3-base) (1-naphthyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(1-naphthyl)-3-(3,4-difluorophenyl) propenone and TosMIC.
Product is slightly yellow solid, yield 81.5%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO) δ (ppm): 11.83 (s, 1H, NH), 8.28 (m, 1H ,-CO-Ar-H), 8.18 (m, 1H ,-CO-Ar-H), 7.65-7.40 (m, 6H,-CO-Ar-H+Ar-H), 7.38-7.28 (m, 2H, Ar-H+pyrrole-H), 7.27-7.21 (m, 1H, Ar-H), 7.18 (s, 1H, pyrrole-H)；13CNMR (100MHz, DMSO-d6) δ (ppm): 191.05,150.03,149.90,149.31,149.19,147.61,147.48,146.88,146.76,138.82,133.04,132.31,130.11,129.97,129.50,128.11,126.63,126.12,125.98,125.23,125.16,124.96,124.57,122.02,119.75,117.22,117.05,116.68,116.52.
Embodiment 15
The synthesis of (4-(3,4-difluorophenyl)-1H-pyrroles's-3-base) (4-xenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-xenyl)-3-(3,4-difluorophenyl) propenone and TosMIC.
Product is white solid, yield 48.3%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO) δ (ppm): 11.76 (s, 1H, NH), 7.85 (d, J=8.0Hz, 2H ,-CO-Ar-H), 7.80 (d, J=8.0Hz, 2H ,-CO-Ar-H), 7.75 (d, J=8.0Hz, 2H,-CO-Ar-H), 7.54-7.40 (m, 4H,-CO-Ar-H+Ar-H), 7.37-7.29 (m, 2H, Ar-H+pyrrole-H), 7.28-7.22 (m, 1H, Ar-H), 7.20 (s, 1H, pyrrole-H)；13CNMR (100MHz, DMSO-d6) δ (ppm): 190.21,150.06,149.93,149.09,148.97,147.64,147.52,146.67,146.54,139.90,132.88,131.52,128.88,128.68,128.13,124.87,123.29,120.39,120.35,117.14,116.96,116.62,116.45.
Embodiment 16
The synthesis of 3-nitro-4-(4-acetylamino phenyl)-1H-pyrroles
Preparation method is with embodiment 1, and raw material is 1-acetylaminohydroxyphenylarsonic acid 4-(2-nitroethylene base) benzene and TosMIC.
Product is brown solid, yield 39.1%.
The experimental data of product is as follows:
1HNMR (300MHz, DMSO-d6) δ (ppm): 12.04 (s, 1H, pyrrole-NH), 9.96 (s, 1H, PhNH-), 7.93 (dd, J1=3.0Hz, J2=1.8Hz, 1H, pyrroleH), 7.56 (d, J=9.0Hz, 2H, ArH), 7.32 (d, J=9.0Hz, 2H, ArH), 6.93 (t, J=3.0Hz, 1H, pyrroleH), 2.04 (s, 3H ,-COCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 168.20,138.12,133.37,129.31 (2C), 127.26,122.72,119.84,119.29,118.40 (2C), 23.98.
Embodiment 17
The synthesis of 3-cyano group-4-(4-acetylamino phenyl)-1H-pyrroles
Preparation method is with embodiment 1, and raw material is 3-(4-acetylamino phenyl) acrylonitrile and TosMIC.
Product is white solid, yield 49.7%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.86 (s, 1H, pyrrole-NH), 9.98 (s, 1H, PhNH-), 7.67 (dd, J1=4.0Hz, J2=2.0Hz, 1H, pyrroleH), 7.62 (d, J=8.0Hz, 2H, ArH), 7.56 (d, J=8.0Hz, 2H, ArH), 7.24 (t, J=4.0Hz, 1H, pyrroleH), 2.06 (s, 3H ,-COCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 168.18,137.93,128.37,128.00,126.14 (2C), 124.93,119.27 (2C), 117.54,117.10,89.07,23.95.
Embodiment 18
The synthesis of 3-ethoxycarbonyl-4-(4-acetylamino phenyl)-1H-pyrroles
Preparation method is with embodiment 1, and raw material is 3-(4-acetamidophenyl) ethyl acrylate and TosMIC.
Product is white solid, yield 51.6%.
The experimental data of product is as follows:
1HNMR (300MHz, DMSO-d6) δ (ppm): 11.48 (s, 1H, pyrrole-NH), 9.87 (s, 1H, PhNH-), 7.50 (d, J=9.0Hz, 2H, ArH), 7.43 (t, J=3.0Hz, 1H, pyrroleH), 7.35 (d, J=9.0Hz, 2H, ArH), 6.83 (t, J=3.0Hz, 1H, pyrroleH), 4.08 (dd, J1=12.0Hz, J2=6.0Hz, 2H ,-COOCH2-), 1.17 (t, J=6.0Hz, 3H ,-CH3), 2.03 (s, 3H ,-COCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 168.03,164.13,137.27,129.83,128.98 (2C), 125.70,124.84,118.68,118.20 (2C), 111.88,58.67,23.96,14.25.
Embodiment 19
The synthesis of 3-acetyl group-4-(4-acetylamino phenyl)-1H-pyrroles
Preparation method is with embodiment 1, and raw material is 4-(4-acetylamino phenyl)-3-butene-2-one and TosMIC.
Product is white solid, yield 78.6%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.49 (s, 1H, pyrrole-NH), 9.86 (s, 1H, PhNH-), 7.66 (dd, J1=4.0Hz, J2=2.0Hz, 1H, pyrroleH), 7.48 (d, J=8.0Hz, 2H, ArH), 7.33 (d, J=8.0Hz, 2H, ArH), 6.87 (t, J=4.0Hz, 1H, pyrroleH), 2.31 (s, 3H ,-COCH3), 2.04 (s, 3H ,-NHCOCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 192.53,167.99,137.20,130.30,128.96 (2C), 127.36,124.11,121.89,119.41,118.24 (2C), 28.24,23.94.
Embodiment 20
The synthesis of (4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (2-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-fluorophenyl)-3-(4-acetylamino phenyl) propenone and TosMIC.
Product is white solid, yield 63.9%.
The experimental data of product is as follows:
1HNMR (300MHz, DMSO-d6) δ (ppm): 11.67 (s, 1H, pyrrole-NH), 9.90 (s, 1H, PhNH-), 7.56-7.52 (m, 1H, ArH), 7.50 (d, J=9.0Hz, 2H, ArH), 7.475-7.44 (m, 1H, ArH), 7.39 (d, J=9.0Hz, 2H, ArH), 7.25 (t, J=9.0Hz, 2H, ArH), 7.11 (t, J=3.0Hz, 1H, pyrroleH), 7.00 (t, J=3.0Hz, 1H, pyrroleH), 2.04 (s, 3H ,-COCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 186.44,168.04, (158.77 1C, JCF=247.4Hz), 137.36, (131.78 1C, JCF=8.3Hz), 129.88,129.69, (129.62 1C, JCF=8.9Hz), 129.53,128.79 (2C), 124.88,124.11 (1C, JCF=3.3Hz), 121.43,119.95,118.28 (2C), 115.85 (1C, JCF=21.8Hz), 23.97.
Embodiment 21
The synthesis of (4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (4-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-fluorophenyl)-3-(4-acetylamino phenyl) propenone and TosMIC.
Product is white solid, yield 90.6%.
The experimental data of product is as follows:
1HNMR (300MHz, DMSO-d6) δ (ppm): 11.62 (s, 1H, pyrrole-NH), 9.86 (s, 1H, PhNH-), 7.81-7.30 (m, 2H, ArH), 7.45 (d, J=9.0Hz, 2H, ArH), 7.30-7.18 (m, 5H), 7.03 (t, J=3.0Hz, 1H, pyrroleH), 2.01 (s, 3H ,-COCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.94,168.01,163.98 (1C, JCF=249.2Hz), 137.13,136.51 (1C, JCF=2.7Hz), (131.62 2C, JCF=9.0Hz), 129.91,128.47 (2C), 127.87,125.16,120.28,119.21,118.46 (2C), (115.03 2C, JCF=21.6Hz), 23.94.
Embodiment 22
The synthesis of (4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (2-chlorphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-chlorphenyl)-3-(4-acetylamino phenyl) propenone and TosMIC.
Product is white solid, yield 93.9%.
The experimental data of product is as follows:
1HNMR (300MHz, DMSO-d6) δ (ppm): 11.65 (s, 1H, pyrrole-NH), 9.90 (s, 1H, PhNH-), 7.53-7.36 (m, 8H), 6.99 (t, J=3.0Hz, 1H, pyrroleH), 6.93 (dd, J1=3.0Hz, J2=1.8Hz, 1H, pyrroleH), 2.03 (s, 3H ,-COCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.37,168.07,140.79,137.43,130.43,130.37,129.54 (2C), 129.51,128.81 (2C), 128.52,126.77,124.89,120.93,120.22,118.30 (2C), 23.98.
Embodiment 23
The synthesis of (4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (4-chlorphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-chlorphenyl)-3-(4-acetylamino phenyl) propenone and TosMIC.
Product is white solid, yield 90.0%.
The experimental data of product is as follows:
1HNMR (300MHz, DMSO-d6) δ (ppm): 11.64 (s, 1H, pyrrole-NH), 9.87 (s, 1H, PhNH-), 7.73 (d, J=9.0Hz, 2H, ArH), 7.51 (d, J=9.0Hz, 2H, ArH), 7.46 (d, J=9.0Hz, 2H, ArH), 7.28 (d, J=9.0Hz, 2H, ArH), 7.23 (t, J=3.0Hz, 1H, pyrroleH), 7.03 (t, J=3.0Hz, 1H, pyrroleH), 2.01 (s, 3H ,-COCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.04,168.01,138.69,137.18,136.20,130.75 (2C), 129.83,128.51 (2C), 128.25,128.19 (2C), 125.17,120.13,119.36,118.44 (2C), 23.95.
Embodiment 24
The synthesis of (4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (3-bromophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-bromophenyl)-3-(4-acetylamino phenyl) propenone and TosMIC.
Product is white solid, yield 77.8%.
The experimental data of product is as follows:
1HNMR (300MHz, DMSO-d6) δ (ppm): 11.67 (s, 1H, pyrrole-NH), 9.88 (s, 1H, PhNH-), 7.76 (m, 1H, ArH), 7.69 (m, 1H, ArH), 7.62 (m, 1H, ArH), 7.44 (d, J=9.0Hz, 2H, ArH), 7.40 (t, J=9.0Hz, 1H, ArH), 7.26 (d, J=9.0Hz, 2H, ArH), 7.25-7.21 (m, 1H, pyrroleH), 7.03 (t, J=3.0Hz, 1H, pyrroleH), 2.01 (s, 3H ,-COCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.61,168.00,142.16,137.22,134.00,131.28,130.36,129.75,128.54 (2C), 128.53,127.86,125.22,121.44,120.00,119.46,118.41 (2C), 23.96.
Embodiment 25
The synthesis of (4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (4-bromophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-bromophenyl)-3-(4-acetylamino phenyl) propenone and TosMIC.
Product is white solid, yield 89.7%.
The experimental data of product is as follows:
1HNMR (300MHz, DMSO-d6) δ (ppm): 11.64 (s, 1H, pyrrole-NH), 9.87 (s, 1H, PhNH-), 7.64 (s, 4H, ArH), 7.44 (d, J=9.0Hz, 2H, ArH), 7.27 (d, J=9.0Hz, 2H, ArH), 7,23 (t, J=3.0Hz, 1H, pyrroleH), 7.03 (t, J=3.0Hz, 1H, pyrroleH), 2.01 (s, 3H ,-COCH3)；13CNMR (100MHz, DMSO-d6) δ (PPm): 189.17,168.01,139.05,137.19,131.14 (2C), 130.92 (2C), 129.82,128.51 (2C), 128.31,125.20,125.17,120.08,119.38,118.43 (2C), 23.96.
Embodiment 26
The synthesis of (4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (4-aminomethyl phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-aminomethyl phenyl)-3-(4-acetylamino phenyl) propenone and TosMIC.
Product is white solid, yield 79.7%.
The experimental data of product is as follows:
null1HNMR(300MHz，DMSO-d6) δ (ppm): 11.55 (s，1H，pyrrole-NH)，9.87(s，1H，PhNH-)，7.63(d，J=6.0Hz，2H，ArH)，7.44(d，J=6.0Hz，2H，ArH)，7.27(d，J=6.0Hz，2H，ArH)，7.23(d，J=6.0Hz，2H，ArH)，7.16(dd，J1=3.0Hz，J2=0.9Hz，1H，pyrroleH)，7.01(t，J=3.0Hz，1H，pyrroleH)，2.35(s，3H，-PhCH3)，2.01(s，3H，-COCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 190.05,168.00,141.55,137.31,137.07,130.08,129.14 (2C), 128.67 (2C), 128.39 (2C), 127.58,125.08,120.50,119.05,118.48 (2C), 23.94,21.02
Embodiment 27
The synthesis of (4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (2,4-3,5-dimethylphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2,4-3,5-dimethylphenyl)-3-(4-acetylamino phenyl) propenone and TosMIC.
Product is white solid, yield 80.8%.
The experimental data of product is as follows:
null1HNMR(300MHz，DMSO-d6) δ (ppm): 11.52 (s，1H，pyrrole-NH)，9.88(s，1H，PhNH-)，7.27(d，J=9.0Hz，2H，ArH)，7.36(d，J=9.0Hz，2H，ArH)，7.23(d，J=9.0Hz，1H，ArH)，7.05(s，1H，ArH)，7.00(d，J=9.0Hz，1H，ArH)，6.96(s，1H，pyrroleH)，6.88(t，J=3.0Hz，1H，pyrroleH)，2.29(s，3H，PhCH3)，2.20(s，3H，PhCH3)，2.02(s，3H，-COCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 192.19,168.01,138.65,138.50,137.22,135.21,131.10,129.93,129.30,128.68 (2C), 127.96,125.45,124.88,121.91,119.66,118.32 (2C), 23.96,20.80,19.36.
Embodiment 28
The synthesis of (4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (3-methoxyphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-methoxyphenyl)-3-(4-acetylamino phenyl) propenone and TosMIC.
Product is yellow solid, yield 62.0%.
The experimental data of product is as follows:
null1HNMR(300MHz，DMSO-d6) δ (ppm): 11.59 (s，1H，pyrrole-NH)，9.87(s，1H，PhNH-)，7.44(d，J=9.0Hz，2H，ArH)，7.35(t，J=9.0Hz，1H，ArH)，7.29(m，1H，ArH)，7.27(d，J=9.0Hz，2H，ArH)，7.21(m，1H，ArH)，7.19(t，J=3.0Hz，1H，pyrroleH)，7.10(m，1H，ArH)，7.01(t，J=3.0Hz，1H，pyrroleH)，3.75(s，3H，PhOCH3)，2.01(s，3H，-COCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.94,168.00,158.86,141.42,137.12,130.00,129.20,128.48 (2C), 128.06,125.16,121.40,120.36,119.23,118.42 (2C), 117.46,113.57,55.13,23.95.
Embodiment 29
The synthesis of (4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (4-methoxyphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-methoxyphenyl)-3-(4-acetylamino phenyl) propenone and TosMIC.
Product is yellow solid, yield 78.9%.
The experimental data of product is as follows:
null1HNMR(300MHz，DMSO-d6) δ (ppm): 11.52 (s，1H，pyrrole-NH)，9.86(s，1H，PhNH-)，7.72(d，J=9.0Hz，2H，ArH)，7.42(d，J=9.0Hz，2H，ArH)，7.24(d，J=9.0Hz，2H，ArH)，7.16(dd，J1=3.0Hz，J2=0.9Hz，1H，pyrroleH)，7.01(t，J=3.0Hz，1H，pyrroleH)，6.97(d，J=9.0Hz，2H，ArH)，3.80(s，3H，PhOCH3)，2.02(s，3H，-COCH3)；13CNMR (100MHz, DMSO-d6) δ (PPm): 189.28,167.99,162.03,137.00,132.36,131.27 (2C), 130.13,128.29 (2C), 126.80,124.98,120.60,118.80,118.51 (2C), 113.36 (2C), 55.34,23.94.
Embodiment 30
The synthesis of (4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (2-pyridine radicals) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-pyridine radicals)-3-(4-acetylamino phenyl) propenone and TosMIC.
Product is yellow solid, yield 50.9%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.60 (s，1H，pyrrole-NH)，9.88(s，1H，PhNH-)，8.65(m，1H，pyridineH)，7.95(td，J1=8.0Hz，J2=2.0Hz，1H，pyridineH)，7.83(dt，J1=8.0Hz，J2=2.0Hz，1H，pyridineH)，7.74(dd，J1=8.0Hz，J2=2.0Hz，1H，pyrroleH)，7.55(m，1H，pyridineH)，7.50(d，J=8.0Hz，2H，PhH)，7.35(d，J=8.0Hz，2H，PhH)，6.97(t，J=4.0Hz，1H，pyrroleH)，2.05(s，3H，-COCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 187.41,168.01,156.82,148.24,137.19,137.07,130.55,130.33,128.82 (2C), 125.76,125.67,122.99,119.05,118.98,118.32 (2C), 23.95.
Embodiment 31
The synthesis of (4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (3-pyridine radicals) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-pyridine radicals)-3-(4-acetylamino phenyl) propenone and TosMIC.
Product is yellow solid, yield 42.8%.
The experimental data of product is as follows:
null1HNMR(300MHz，DMSO-d6) δ (ppm): 11.71 (s，1H，pyrrole-NH)，9.87(s，1H，PhNH-)，8.83(d，J=3.0Hz，1H，pyridineH)，8.70(dd，J1=3.0Hz，J2=0.9Hz，1H，pyridineH)，8.05(dt，J1=6.0Hz，J2=3.0Hz，1H，pyridineH)，7.48(m，1H，pyridineH)，7.46(d，J=9.0Hz，2H，ArH)，7.31(d，J=9.0Hz，2H，ArH)，7.31-7.295(m，1H，pyrroleH)，7.06(t，J=3.0Hz，1H，pyrroleH)，2.03(s，3H，-COCH3).
Embodiment 32
The synthesis of (4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (4-pyridine radicals) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-pyridine radicals)-3-(4-acetylamino phenyl) propenone and TosMIC.
Product is brown solid, yield 66.7%.
The experimental data of product is as follows:
1HNMR (300MHz, DMSO-d6) δ (ppm): 11.75 (s, 1H, pyrrole-NH), 9.88 (s, 1H, PhNH-), 8.70 (d, J=6.0Hz, 2H, pyridineH), 7.57 (d, J=6.0Hz, 2H, pyridineH), 7.48 (d, J=6.0Hz, 2H, ArH), 7.34 (d, J=6.0Hz, 2H, ArH), 7.27 (dd, J1=3.0Hz, J2=0.9Hz, 1H, pyrroleH), 7.05 (t, J=3.0Hz, 1H, pyrroleH), 2.04 (s, 3H ,-COCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.83,168.06,149.89 (2C), 146.88,137.37,129.70,129.60,128.75 (2C), 122.29 (2C), 119.95,119.66,118.37 (2C), 23.96.
Embodiment 33
The synthesis of (4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (2-thienyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-thienyl)-3-(4-acetylamino phenyl) propenone and TosMIC.
Product is yellow solid, yield 71.1%.
The experimental data of product is as follows:
null1HNMR(300MHz，DMSO-d6) δ (ppm): 11.62 (s，1H，pyrrole-NH)，9.87(s，1H，PhNH-)，7.93(dd，J1=3.0Hz，J2=0.9Hz，1H，thiophenylH)，7.71(d，J=3.0Hz，1H，thiophenylH)，7.50(m，1H，thiophenylH)，7.47(d，J=6.0Hz，2H，ArH)，7.28(d，J=6.0Hz，2H，ArH)，7.20(dd，J1=3.0Hz，J2=0.9Hz，1H，pyrroleH)，7.04(t，J=3.0Hz，1H，pyrroleH)，2.03(s，3H，-COCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 181.87,168.03,145.63,137.14,133.19,132.93,129.89,128.31 (2C), 128.18,126.64,124.80,120.19,119.17,118.58 (2C), 23.95.
Embodiment 34
The synthesis of (4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(phenyl)-3-(4-acetylamino phenyl) propenone and TosMIC.
Product is white solid, yield 65.3%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.58 (s，1H，pyrrole-NH)，9.87(s，1H，PhNH-)，7.73(d，J=8.0Hz，2H，ArH)，7.56(t，d，J=8.0Hz，1H，ArH)，7.47(d，J=8.0Hz，2H，ArH)，7.45(d，J=8.0Hz，2H，ArH)，7.30(d，J=8.0Hz，2H，ArH)，7.19(t，J=4.0Hz，1H，pyrroleH)，7.04(t，J=4.0Hz，1H，pyrroleH)，2.04(s，3H，-COCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 190.33,167.99,140.07,137.13,131.41,130.02,128.88 (2C), 128.48 (2C), 128.08 (2C), 128.00,125.19,120.45,119.20,118.46 (2C), 23.94.
Embodiment 35
The synthesis of (4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (1-naphthyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(1-naphthyl)-3-(4-acetylamino phenyl) propenone and TosMIC.
Product is yellow solid, yield 36.8%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.58 (s, 1H, pyrrole-NH), 9.90 (s, 1H, PhNH-), 8/06-7.96 (m, 3H), 7.62 (dd, J1=8.0Hz, J2=4.0Hz, 1H), 7.57-7.43 (m, 7H), 7.02 (t, J=4.0Hz, 1H, pyrroleH), 9.69 (t, J=4.0Hz, 1H, pyrroleH), 2.05 (s, 3H ,-COCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 191.43,168.02,138.93,137.32,133.14,130.14,129.97,129.88,129.69,128.81 (2C), 128.21,126.63,126.10,126.00,125.33,125.17,124.66,122.29,119.88,118.31 (2C), 23.96.
Embodiment 36
The synthesis of (4-(4-acetylamino phenyl)-1H-pyrroles's-3-base) (4-xenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-xenyl)-3-(4-acetylamino phenyl) propenone and TosMIC.
Product is yellow solid, yield 64.2%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.60 (s，1H，pyrrole-NH)，9.87(s，1H，PhNH-)，7.83(d，J=8.0Hz，2H，ArH)，7.77(d，J=8.0Hz，2H，ArH)，7.74(d，J=8.0Hz，2H，ArH)，7.51(t，J=8.0Hz，2H，ArH)，7.46(t，J=8.0Hz，2H，ArH)，7.42(m，1H，ArH)，7.32(d，J=8.0Hz，2H，ArH)，7.27(t，J=4.0Hz，1H，pyrroleH)，7.06(t，J=4.0Hz，1H，pyrroleH)，2.03(s，3H，-COCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.84,167.99,142.98,139.19,138.85,137.15,130.04,129.69 (2C), 129.02 (2C), 128.49 (2C), 128.05,127.90,126.84 (2C), 126.35 (2C), 125.19,120.50,119.20,118.49 (2C), 23.94.
Embodiment 37
The synthesis of (4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (2-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-fluorophenyl)-3-(3-methoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 65.4%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.71 (s, 1H, NH), 7.51 (m, 2H ,-CO-Ar-H), 7.26-7.15 (m, 4H ,-CO-Ar-H+Ar-H), 7.08 (t, J=2Hz, 1H, Ar-H), 7.04-7.02 (m, 2H, pyrrole-H+Ar-H), 6.78 (m, 1H, pyrrole-H), 3.74 (s, 3H ,-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 186.49,160.04,158.66,157.58,136.13,131.88,131.79,129.80,129.73,129.69,129.65,129.50,128.51,124.98,124.11,124.08,121.62,121.01,120.40,115.95,115.73,114.25,111.50,54.83.
Embodiment 38
The synthesis of (4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (4-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-fluorophenyl)-3-(3-methoxyphenyl) propenone and TosMIC.
Product is white solid, yield 72.5%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.65 (s, 1H, NH), 7.80 (dd, J1=6.0Hz, J2=8.4Hz, 2H ,-CO-Ar-H), 7.28-7.23 (m, 3H ,-CO-Ar-H+Ar-H), 7.17 (t, J=8.0Hz, 1H, Ar-H), 7.11 (m, 1H, pyrrole-H), 6.91-6.90 (m, 2H, Ar-H+pyrrole-H), 6.74 (dd, J1=2Hz, J2=8.0Hz, 1H, Ar-H) 3.70 (s, 3H ,-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.69,158.77,142.06,141.88,136.32,134.02,132.93,131.34,131.13,130.32,130.06,128.65,128.43,128.35,127.83,127.48,125.31,121.42,120.81,120.25,119.87,113.97,111.39,54.83.
Embodiment 39
The synthesis of (4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (2-chlorphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-chlorphenyl)-3-(3-methoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 76.2%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.71 (s, 1H, NH), 7.51-7.36 (m, 4H ,-CO-Ar-H), 7.23 (t, J=8.0Hz, 1H, Ar-H), 7.11-7.08 (m, 3H, Ar-H+pyrrole-H), 6.99 (m, 1H, pyrrole-H), 6.80 (dd, J1=2.4Hz, J2=8.0Hz, 2H, Ar-H), 3.76 (s, 3H ,-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.38,158.67,140.75,136.08,130.47,130.34,129.57,129.51,128.53,128.51,126.77,124.97,121.10,120.99,120.72,114.31,111.53,54.84.
Embodiment 40
The synthesis of (4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (4-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-chlorphenyl)-3-(3-methoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 84.2%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.70 (s, 1H, NH), 7.74 (d, J=8.4Hz, 2H ,-CO-Ar-H), 7.51 (d, J=8.4Hz, 2H ,-CO-Ar-H), 7.28 (t, J=2.4Hz, 1H, Ar-H), 7.18 (t, J=8.0Hz, 1H, Ar-H), 7.12 (m, 1H, pyrrole-H), 6.94-6.90 (m, H, Ar-H+pyrrole-H), 6.76 (dd, J1=2.4Hz, J2=8.0Hz, 1H, Ar-H), 3.71 (s, 3H ,-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.09,158.77,138.61,136.38,136.26,130.76,128.65,128.18,128.14,125.24,120.79,120.35,119.82,113.98,111.23,54.83.
Embodiment 41
The synthesis of (4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (3-bromophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-bromophenyl)-3-(3-methoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 78.0%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.71 (s, 1H, NH), 7.80-7.60 (m, 3H ,-CO-Ar-H), 7.49 (m, 1H ,-CO-Ar-H), 7.30 (t, J=2.5Hz, 1H, pyrrole-H), 7.18 (t, J=7.6Hz, 1H, Ar-H), 7.12 (t, J=7.6Hz, 1H, Ar-H), 6.98-6.92 (m, 2H, Ar-H+pyrrole-H), 6.74 (dd, J1=2.5Hz, J2=8.0Hz, 1H, Ar-H), 3.71 (s, 3H ,-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.98,165.25,162.77,158.77,136.45,131.68,131.59,128.65,127.75,125.21,120.75,120.50,119.67,115.13,114.91,113.93,111.18,54.81.
Embodiment 42
The synthesis of (4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (4-bromophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-bromophenyl)-3-(3-methoxyphenyl) propenone and TosMIC.
Product is slightly yellow solid, yield 69.8%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.70 (s, 1H, NH), 7.70-7.60 (m, 4H,-CO-Ar-H), 7.30 (t, J=2.3Hz, 1H, pyrrole-H), 7.18 (t, J=8.0Hz, 1H, Ar-H), 7.12 (s, 1H, Ar-H), 6.94-6.93 (m, 2H, Ar-H+pyrrole-H), 6.74 (dd, J1=2.2Hz, J2=8.0Hz, 1H, Ar-H), 3.71 (s, 3H ,-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.22,158.77,138.96,136.37,131.13,130.93,128.66,128.20,125.26,125.24,120.79,120.30,119.84,113.99,111.23,54.83.
Embodiment 43
The synthesis of (4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (3-methoxyphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-methoxyphenyl)-3-(3-methoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 79.4%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.62 (s，1H，NH)，7.38(t，J=8.0Hz，1H，-CO-Ar-H)，7.31(d，J=8.0Hz，1H，-CO-Ar-H)，7.25(m，1H，-CO-Ar-H)，7.21(s，1H，-CO-Ar-H)，7.17-7.10(m，3H，pyrrole-H+Ar-H)，6.98-6.90(m，2H，Ar-H+pyrrole-H)，6.74(dd，J1=2.4Hz，J2=8.0Hz，1H，Ar-H)，3.76(s，3H，-OCH3)，3.70(s，3H，-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.99,158.87,158.75,141.33,136.54,129.20,128.62,127.94,125.23,121.42,120.74,120.60,119.67,117.55,113.95,113.60,111.20,55.12,54.81.
Embodiment 44
The synthesis of (4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (4-methoxyphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-methoxyphenyl)-3-(3-methoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 86.7%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.59 (s，1H，NH)，7.77(d，J=8.8Hz，2H，-CO-Ar-H)，7.20(d，J=1.6Hz，1H，pyrrole-H)，7.18(t，J=8.0Hz，1H，Ar-H)，7.11(d，J=1.6Hz，1H，pyrrole-H)，6.99(d，J=8.8Hz，2H，-CO-Ar-H)，6.93-6.90(m，2H，Ar-H)，6.74(dd，J1=1.6Hz，J2=8.0Hz，1H，Ar-H)，3.82(s，3H，-OCH3)，3.69(s，3H，-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.34,162.09,158.80,136.64,132.30,131.28,128.68,126.66,125.01,120.82,120.57,119.26,113.77,113.37,110.98,55.36,54.79.
Embodiment 45
The synthesis of (4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (3-pyridine radicals) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-pyridine radicals)-3-(3-methoxyphenyl) propenone and TosMIC.
Product is yellowish solid, yield 90.8%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.80 (s, 1H, NH), 8.70 (d, J=5.2Hz, 2H ,-CO-Ar-H), 7.59 (d, J=5.2Hz, 2H ,-CO-Ar-H), 7.33 (s, 1H, pyrrole-H), 7.25 (t, J=8.0Hz, 1H, Ar-H), 7.12-7.09 (m, 3H, Ar-H+pyrrole-H), 6.83 (dd, J1=2Hz, J2=8.0Hz, 1H, Ar-H), 3.70 (s, 3H ,-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.83,158.78,147.63,146.86,136.13,129.94,127.74,125.27,122.27,119.98,119.05,118.94,113.84,111.07,54.51.
Embodiment 46
The synthesis of (4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (4-pyridine radicals) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-pyridine radicals)-3-(3-methoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 86.5%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.77 (s，1H，NH)，8.81(d，J=1.2Hz，1H，-CO-Ar-H)，8.72(dd，J1=1.2Hz，J2=4Hz，1H，-CO-Ar-H)，8.06(d，J=8.0Hz，1H，-CO-Ar-H)，7.49(dd，J1=4Hz，J2=8.0Hz，1H，-CO-Ar-H)，7.33(t，J=2Hz，1H，pyrrole-H)，7.26(t，J=8.0Hz，1H，Ar-H)，7.11-7.08(m，3H，Ar-H+pyrrole-H)，6.85(dd，J1=2.4Hz，J2=8.0Hz，1H，Ar-H)，3.71(s，3H，-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.83,158.85,151.71,147.13,136.23,136.17,135.54,128.94,127.96,125.16,123.17,119.98,119.67,119.05,113.94,111.37,54.81.
Embodiment 47
The synthesis of (4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (2-thienyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-thienyl)-3-(3-methoxyphenyl) propenone and TosMIC.
Product is white solid, yield 70.8%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.66 (s, 1H, NH), 7.92 (d, J=4Hz, 1H ,-CO-Ar-H), 7.71 (d, J=4Hz, 1H ,-CO-Ar-H), 7.51 (t, J=4Hz, 1H,-CO-Ar-H), 7.20-7.15 (m, 2H, Ar-H), 7.13 (s, 1H, pyrrole-H), 6.96-6.92 (m, 2H, pyrrole-H+Ar-H), 6.77 (dd, J1=2.4Hz, J2=8.0Hz, 1H, Ar-H), 3.72 (s, 3H ,-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 181.96,158.84,145.59,136.42,133.30,133.03,128.76,128.19,126.54,124.81,120.59,120.37,119.64,113.83,111.05,54.83.
Embodiment 48
The synthesis of (4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (2-nitrobenzophenone) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-nitrobenzophenone)-3-(3-methoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 66.9%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.72 (s，1H，NH)，8.12(d，J=7.6Hz，1H，-CO-Ar-H)，7.82(t，J=7.6Hz，1H，-CO-Ar-H)，7.73(t，J=7.6Hz，1H，-CO-Ar-H)，7.62(d，J=7.6Hz，1H，-CO-Ar-H)，7.26(m，1H，Ar-H)，7.20(t，J=8.0Hz，1H，Ar-H)，7.13(m，1H，pyrrole-H)，6.94-6.92(m，2H，Ar-H+pyrrole-H)，6.80(dd，J1=2Hz，J2=8.0Hz，1H，Ar-H)，3.73(s，3H，-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.13,158.77,146.79,137.14,136.43,133.96,130.51,129.08,129.01,127.84,125.16,124.07,120.60,120.48,119.65,113.94,111.16,54.79.
Embodiment 49
The synthesis of (4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(phenyl)-3-(3-methoxyphenyl) propenone and TosMIC.
Product is slightly yellow solid, yield 66.4%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 8.61 (s，1H，NH)，7.84(dt，J1=0.8Hz，J2=7.2Hz，2H，-CO-Ar-H)，7.51(tt，J1=0.8Hz，J2=7.2Hz，1H，-CO-Ar-H)，7.40(t，J=7.2Hz，2H，-CO-Ar-H)，7.26(t，J=2.8Hz，1H，pyrrole-H)，7.22(t，J=7.6Hz，1H，Ar-H)，7.02(m，1H，Ar-H)，6.97(t，J=2Hz，1H，Ar-H)，6.96(t，J=2.8Hz，1H，pyrrole-H)，6.74(dd，J1=2.4Hz，J2=8.0Hz，1H，Ar-H)，3.77(s，3H，-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 190.36,158.75,139.95,136.53,131.49,128.92,128.62,128.09,127.94,125.24,120.75,120.62,119.68,113.95,111.17,54.81.
Embodiment 50
The synthesis of (4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (1-naphthyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(1-naphthyl)-3-(3-methoxyphenyl) propenone and TosMIC.
Product is white solid, yield 75.6%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.67 (s, 1H, NH), 8.18 (m, 1H ,-CO-Ar-H), 7.99 (m, 1H ,-CO-Ar-H), 7.66-7.46 (m, 5H ,-CO-Ar-H), 7.28 (m, 1H, pyrrole-H), 7.19 (m, 1H, Ar-H), 7.12 (m, 1H, pyrrole-H), 6.97 (m, 2H, Ar-H), 6.75 (m, 1H, Ar-H), 3.73 (s, 3H ,-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 191.13,158.65,139.03,136.51,133.14,130.13,129.99,129.66,128.21,127.94,126.63,126.10,125.89,125.33,125.17,124.66,122.27,119.88,119.28,113.95,111.17,54.82.
Embodiment 51
The synthesis of (4-(3-methoxyphenyl)-1H-pyrroles's-3-base) (4-xenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-xenyl)-3-(3-methoxyphenyl) propenone and TosMIC.
Product is yellowish solid, yield 83.4%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.66 (s，1H，NH)，7.85(d，J=8.0Hz，2H，-CO-Ar-H)，7.77(d，J=8.0Hz，2H，-CO-Ar-H)，7.743(d，J=7.6Hz，2H，-CO-Ar-H)，7.53(t，J=7.6Hz，2H，-CO-Ar-H)，7.43(t，J=7.6Hz，1H，-CO-Ar-H)，7.29(m，1H，pyrrole-H)，7.20(m，1H，Ar-H)，7.13(m，1H，pyrrole-H)，6.98(m，2H，Ar-H)，6.76(m，1H，Ar-H)，3.72(s，3H，-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.87,158.79,143.04,139.17,138.75,136.56,129.73,129.03,128.66,128.07,127.89,126.84,126.36,125.23,120.75,120.66,119.73,113.97,111.15,54.82.
Embodiment 52
The synthesis of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (2-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-fluorophenyl)-3-(3,4-Dimethoxyphenyl) propenone and TosMIC.
Product is white solid, yield 53.5%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.66 (s, 1H, NH), 7.52 (m, 2H,-CO-Ar-H), 7.25 (m, 2H,-CO-Ar-H), 7.13 (s, 1H, pyrrole-H), 7.08 (d, J=1.6Hz, 1H, Ar-H), 7.03-6.99 (m, 2H, pyrrole-H+Ar-H), 6.85 (d, J=8.0Hz, 1H, Ar-H), 3.75 (s, 3H ,-OCH3), 3.73 (s, 3H ,-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 186.52,159.98,157.52,147.85,147.32,131.77,131.69,129.80,129.69,127.55,125.10,124.09,121.53,120.74,119.80,115.92,115.70,113.08,111.39,55.52,55.31.
Embodiment 53
The synthesis of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (4-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-fluorophenyl)-3-(3,4-Dimethoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 69.3%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.62 (s, 1H, NH), 7.80 (dd, J1=6.0Hz, J2=8.4Hz, 2H,-CO-Ar-H), 7.28-7.21 (m, 3H ,-CO-Ar-H+pyrrole-H), 7.06 (s, 1H, pyrrole-H), 6.96 (d, J=1.6Hz, 1H, Ar-H), 6.92 (dd, J1=1.6Hz, J2=8.0Hz, 1H, Ar-H), 6.85 (d, J=8.0Hz, 1H, Ar-H), 3.73 (s, 3H ,-OCH3), 3.68 (s, 3H ,-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.08,165.16,162.69,147.99,147.13,136.60,131.64,131.55,127.92,127.69,125.29,120.45,120.41,119.06,115.07,114.85,112.82,111.53,55.50,55.32.
Embodiment 54
The synthesis of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (2-chlorphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-chlorphenyl)-3-(3,4-Dimethoxyphenyl) propenone and TosMIC.
Product is yellow solid, yield 52.8%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.65 (s, 1H, NH), 7.52-7.42 (m, 3H ,-CO-Ar-H), 7.39 (t, J=7.2Hz, 1H ,-CO-Ar-H), 7.15 (d, J=1.6Hz, 1H, Ar-H), 7.08 (dd, J1=1.6Hz, J2=8.0Hz, 1H, Ar-H), 7.03 (t, J=2.4Hz, 1H, pyrrole-H), 6.98 (t, J=2.4Hz, 1H, pyrrole-H), 6.90 (d, J=8.0Hz, 1H, Ar-H), 3.76 (s, 6H ,-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.41,147.87,147.37,140.86,130.40,130.19,129.53,129.49,128.50,127.50,126.74,125.10,121.00,120.72,120.07,113.09,111.39,55.54,55.32.
Embodiment 55
The synthesis of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (4-chlorphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-chlorphenyl)-3-(3,4-Dimethoxyphenyl) propenone and TosMIC.
Product is yellow solid, yield 77.0%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.66 (s，1H，NH)，7.72(d，J=8.0Hz，2H，-CO-Ar-H)，7.50(d，J=8.0Hz，2H，-CO-Ar-H)，7.25(s，1H，pyrrole-H)，7.06(s，1H，pyrrole-H)，6.98(d，J=1.6Hz，1H，Ar-H)，6.92(dd，J1=1.6Hz，J2=8.0Hz，1H，Ar-H)，6.85(d，J=8.0Hz，1H，Ar-H)，3.73(s，3H，-OCH3)，3.69(s，3H，-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.19,147.99,147.18,138.80,136.11,130.73,128.13,128.06,127.85,125.32,120.51,120.26,119.21,112.87,111.54,55.53,55.34.
Embodiment 56
The synthesis of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (3-bromophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-bromophenyl)-3-(3,4-Dimethoxyphenyl) propenone and TosMIC.
Product is yellow solid, yield 73.7%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.67 (s，1H，NH)，7.77(s，1H，-CO-Ar-H)，7.73(d，J=8.0Hz，1H，-CO-Ar-H)，7.69(d，J=8.0Hz，1H，-CO-Ar-H)，7.40(t，J=8.0Hz，1H，-CO-Ar-H)，7.29(t，J=2.4Hz，1H，pyrrole-H)，7.06(t，J=2.4Hz，1H，pyrrole-H)，6.95(d，J=1.6Hz，1H，Ar-H)，6.92(dd，J1=1.6Hz，J2=8.0Hz，1H，Ar-H)，6.85(d，J=8.0Hz，1H，Ar-H)，3.73(s，3H，-OCH3)，3.68(s，3H，-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.79,147.99,147.19,142.23,133.89,131.34,130.27,128.23,127.79,125.39,121.37,120.51,120.19,119.26,112.90,111.55,55.52,55.31.
Embodiment 57
The synthesis of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (4-bromophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-bromophenyl)-3-(3,4-Dimethoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 62.8%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.64 (s, 1H, NH), 7.72 (s, 4H ,-CO-Ar-H), 7.25 (t, J=2.4Hz, 1H, pyrrole-H), 7.06 (t, J=2.4Hz, 1H, pyrrole-H), 6.98 (d, J=1.6Hz, 1H, Ar-H), 6.94 (dd, J1=1.6Hz, J2=8.0Hz, 1H, Ar-H), 6.85 (d, J=8.0Hz, 1H, Ar-H), 3.73 (s, 3H ,-OCH3), 3.69 (s, 3H ,-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.31,147.99,147.19,139.15,131.07,130.91,128.12,127.84,125.32,125.10,120.52,120.21,119.22,112.87,111.54,55.54,55.35.
Embodiment 58
The synthesis of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (3-methoxyphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-methoxyphenyl)-3-(3,4-Dimethoxyphenyl) propenone and TosMIC.
Product is yellow solid, yield 64.8%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.59 (s，1H，NH)，7.37(t，J=8.0Hz，1H，-CO-Ar-H)，7.30(d，J=8.0Hz，1H，-CO-Ar-H)，7.24(t，J=2.4Hz，1H，pyrrole-H)，7.20(s，1H，-CO-Ar-H)，7.11(d，J=8.0Hz，1H，-CO-Ar-H)，7.05(t，J=2.4Hz，1H，pyrrole-H)，6.97(d，J=1.6Hz，1H，Ar-H)，6.94(dd，J1=1.6Hz，J2=8.0Hz，1H，Ar-H)，6.85(d，J=8.0Hz，1H，Ar-H)，3.76(s，3H，-OCH3)，3.73(s，3H，-OCH3)，3.68(s，3H，-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 190.10,158.82,147.95,147.12,141.52,129.14,128.03,127.89,125.30,121.37,120.50,120.41,119.06,117.41,113.62,112.88,111.50,55.51,55.31,55.12.
Embodiment 59
The synthesis of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (4-methoxyphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-methoxyphenyl)-3-(3,4-Dimethoxyphenyl) propenone and TosMIC.
Product is yellow solid, yield 81.1%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.55 (s，1H，NH)，7.75(d，J=8.4Hz，2H，-CO-Ar-H)，7.19(t，J-1.2Hz，1H，pyrrole-H)，7.05(t，J=1.2Hz，1H，pyrrole-H)，6.99-6.95(m，3H，-CO-Ar-H+Ar-H)，6.91(dd，J1=1.6Hz，J2=8.0Hz，1H，Ar-H)，6.84(d，J=8.0Hz，1H，Ar-H)，3.81(s，3H，-OCH3)，3.72(s，3H，-OCH3)，3.68(s，3H，-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.45,161.99,148.00,147.02,132.47,131.25,128.16,126.60,125.07,120.72,120.26,118.63,113.31,112.68,111.58,55.50,55.34,55.30.
Embodiment 60
The synthesis of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (3-pyridine radicals) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-pyridine radicals)-3-(3,4-Dimethoxyphenyl) propenone and TosMIC.
Product is yellow solid, yield 81.9%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.75 (s，1H，NH)，8.69(d，J=5.2Hz，2H，-CO-Ar-H)，7.57(d，J=5.2Hz，2H，-CO-Ar-H)，7.29(t，J=2.2Hz，1H，pyrrole-H)，7.08(t，J=2.2Hz，1H，pyrrole-H)，7.05(d，J=1.6Hz，1H，Ar-H)，6.98(dd，J1=1.6Hz，J2=8.0Hz，1H，Ar-H)，6.87(d，J=8.0Hz，1H，Ar-H)，3.74(s，3H，-OCH3)，3.71(s，3H，-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.92,149.84,147.93,147.34,146.99,129.57,127.59,125.42,122.28,120.70,119.82,119.75,113.05,111.43,55.50,55.37.
Embodiment 61
The synthesis of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (4-pyridine radicals) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-pyridine radicals)-3-(3,4-Dimethoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 87.3%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.72 (s，1H，NH)，8.82(d，J=1.2Hz，1H，-CO-Ar-H)，8.69(dd，J1=1.2Hz，J2=4.8Hz，1H，-CO-Ar-H)，8.04(d，J=8.0Hz，1H，-CO-Ar-H)，8.04(dd，J1=4.8Hz，J2=8.0Hz，1H，-CO-Ar-H)，7.32(t，J=2.2Hz，1H，pyrrole-H)，7.08(t，J=2.2Hz，1H，pyrrole-H)，6.99(d，J=1.6Hz，1H，Ar-H)，6.95(dd，J1=1.6Hz，J2=8.0Hz，1H，Ar-H)，6.85(d，J=8.0Hz，1H，Ar-H)，3.73(s，3H，-OCH3)，3.69(s，3H，-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.71,151.67,149.39,147.97,147.22,136.19,135.60,128.65,127.69,125.35,123.27,120.63,120.42,119.46,112.98,111.48,55.49,55.34.
Embodiment 62
The synthesis of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (2-thienyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-thienyl)-3-(3,4-Dimethoxyphenyl) propenone and TosMIC.
Product is yellow solid, yield 78.9%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.61 (s，1H，NH)，7.91(d，J=4.8Hz，1H，-CO-Ar-H)，7.68(d，J=4Hz，1H，-CO-Ar-H)，7.49(t，J=2.4Hz，1H，pyrrole-H)，7.19(dd，J1=4Hz，J2=4.8Hz1H，-CO-Ar-H)，7.05(t，J=2.4Hz，1H，pyrrole-H)，7.00(d，J=1.2Hz，1H，Ar-H)，6.92(dd，J1=1.2Hz，J2=8.0Hz，1H，Ar-H)，6.87(d，J=8.0Hz，1H，Ar-H)，3.74(s，3H，-OCH3)，3.71(s，3H，-OCH3)；13CNMR (100MHz, DMSO-d6) δ (PPm): 182.02,148.06,147.15,145.71,133.11,132.92,128.14,127.90,126.41,124.93,120.37,120.28,119.02,112.64,111.60,55.50,55.36.
Embodiment 63
The synthesis of (4-(3,4-methoxyphenyl)-1H-pyrroles's-3-base) (2-nitrobenzophenone) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-nitrobenzophenone)-3-(3,4-Dimethoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 76.0%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.67 (s，1H，NH)，8.10(d，J=7.6Hz，1H，-CO-Ar-H)，7.80(t，J=7.6Hz，1H，-CO-Ar-H)，7.72(t，J=7.6Hz，1H，-CO-Ar-H)，7.60(d，J=7.6Hz，1H，-CO-Ar-H)，7.12(d，J=1.6Hz，1H，Ar-H)，7.07(t，J=2.4Hz，1H，pyrrole-H)，7.05-7.00(m，2H，pyrrole-H+Ar-H)，6.88(d，J=8.0Hz，1H，Ar-H)，3.75(s，3H，-OCH3)，3.73(s，3H，-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 186.99,147.90,147.37,146.78,137.12,133.85,130.41,129.13,129.10,127.39,125.13,124.16,120.66,120.55,120.03,112.91,111.42,55.53,55.27.
Embodiment 64
The synthesis of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(phenyl)-3-(3,4-Dimethoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 75.7%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.59 (s，1H，NH)，7.72(d，J=7.2Hz，2H，-CO-Ar-H)，7.56(t，J=7.2Hz，1H，-CO-Ar-H)，7.46(t，J=7.2Hz，2H，-CO-Ar-H)，7.20(t，J=2.4Hz，1H，pyrrole-H)，7.05(t，J=2.4Hz，1H，pyrrole-H)，6.99(d，J=1.6Hz，1H，Ar-H)，6.94(dd，J1=1.6Hz，J2=8.0Hz，1H，Ar-H)，6.85(d，J=8.0Hz，1H，Ar-H)，3.73(s，3H，-OCH3)，3.68(s，3H，-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 190.46,147.96,147.11,140.14,131.35,128.89,128.03,128.01,127.89,125.30,120.52,120.43,119.07,112.87,111.50,55.50,55.32.
Embodiment 65
The synthesis of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (1-naphthyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(1-naphthyl)-3-(3,4-Dimethoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 52.3%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.63 (s，1H，NH)，8.10(m，1H，-CO-Ar-H)，7.93(m，1H，-CO-Ar-H)，7.61-7.40(m，5H，-CO-Ar-H)，7.27(s，1H，pyrrole-H)，7.07(s，1H，pyrrole-H)，7.02(d，J=2Hz，1H，Ar-H)，6.97(dd，J1=2Hz，J2=8.0Hz，1H，Ar-H)，6.89(d，J=8.0Hz，1H，Ar-H)，3.73(s，3H，-OCH3)，3.70(s，3H，-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 190.99,147.90,147.37,139.02,133.15,130.11,129.81,129.70,128.50,127.39,126.63,126.13,125.80,125.30,125.14,124.59,122.14,120.03,112.91,119.57,111.42,55.53,55.27.
Embodiment 66
The synthesis of (4-(3,4-Dimethoxyphenyl)-1H-pyrroles's-3-base) (4-xenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-xenyl)-3-(3,4-Dimethoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 64.6%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.61 (s，1H，NH)，7.83(d，J=8.0Hz，2H，-CO-Ar-H)，7.76(t，J=8.0Hz，4H，-CO-Ar-H)，7.53(t，J=7.2Hz，2H，-CO-Ar-H)，7.44(t，J=7.2Hz，1H，-CO-Ar-H)，7.28(t，J=1.6Hz，1H，pyrrole-H)，7.08(t，J=1.6Hz，1H，pyrrole-H)，7.02(d，J=2Hz，1H，Ar-H)，6.96(dd，J1=2Hz，J2=8.0Hz，1H，Ar-H)，6.87(d，J=8.0Hz，1H，Ar-H)，3.73(s，3H，-OCH3)，3.70(s，3H，-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.97,148.00,147.15,142.92,139.20,138.94,129.69,129.03,128.03,127.81,126.83,126.31,125.31,120.56,120.46,119.08,112.87,111.55,55.51,55.34.
Embodiment 67
The synthesis of 3-nitro-4-(3,4,5-trimethoxyphenyl)-1H-pyrroles
Preparation method is with embodiment 1, and raw material is 1,2,3-trimethoxy-5-(2-nitroethylene base) benzene and TosMIC.
Product is brown solid, yield 48.6%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 12.08 (s, 1H, pyrrole-NH), 7.95 (t, J=2.0Hz, 1H, pyrroleH), 7.01 (t, J=2.0Hz, 1H, pyrroleH), 6.70 (s, 2H, PhH), 3.77 (s, 6H, 3 ', 5 '-OCH3), 3.69 (s, 3H, 4 '-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 152.27 (2C), 136.67,133.47,128.15,122.72,120.13,119.67,106.75 (2C), 59.99,55.87 (2C).
Embodiment 68
The synthesis of 3-cyano group-4-(3,4,5-trimethoxyphenyl)-1H-pyrroles
Preparation method is with embodiment 1, and raw material is 3-(3,4,5-trimethoxyphenyl) acrylonitrile and TosMIC.
Product is yellow solid, yield 52.3%.
The experimental data of product is as follows:
1HNMR (400MHz, CDCl3) δ (ppm): 8.94 (s, 1H, pyrrole-NH), 7.38 (dd, J1=2.8Hz, J2=2.0Hz, 1H, pyridineH), 7.00 (t, J=2.8Hz, 1H, pyrroleH), 6.88 (s, 2H, PhH), 3.94 (s, 6H, 3 ', 5 '-OCH3), 3.90 (s, 3H, 4 '-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 153.03 (2C), 136.38,128.81,128.35,125.29,117.63,117.58,103.45 (2C), 89.26,60.04,55.81 (2C).
Embodiment 69
The synthesis of 3-ethoxycarbonyl-4-(3,4,5-trimethoxyphenyl)-1H-pyrroles
Preparation method is with embodiment 1, and raw material is 3-(3,4,5-trimethoxyphenyl) ethyl acrylate and TosMIC.
Product is white solid, yield 61.3%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.54 (s, 1H, pyrrole-NH), 7.46 (t, J=4.0Hz, 1H, pyrroleH), 6.98 (t, J=4.0Hz, 1H, pyrroleH), 6.77 (s, 2H, PhH), 4.14 (dd, J1=12.0Hz, J2=8.0Hz, 2H,-COOCH2-), 3.78 (s, 6H, 3 ', 5 '-OCH3), 3.67 (s, 3H, 4'-OCH3), 1.20 (t, J=8.0Hz, 3H ,-CH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 164.16,152.02 (2C), 136.00,130.61,125.81,125.12,119.07,112.02,106.38 (2C), 59.97,58.72,55.73 (2C), 14.28.
Embodiment 70
The synthesis of 3-acetyl group-4-(3,4,5-trimethoxyphenyl)-1H-pyrroles
Preparation method is with embodiment 1, and raw material is 4-(3,4,5-trimethoxyphenyl)-3-butene-2-one and TosMIC.
Product is yellow solid, yield 87.7%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.53 (s, 1H, pyrrole-NH), 7.67 (dd, J1=2.8Hz, J2=2.0Hz, 1H, pyridineH), 6.98 (t, J=2.8Hz, 1H, pyrroleH), 6.76 (s, 2H, PhH), 3.76 (s, 6H, 3 ', 5'-OCH3), 3.67 (s, 3H, 4'-OCH3), 2.33 (s, 3H ,-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 192.61,151.98 (2C), 135.98,131.00,127.54,124.44,121.94,119.82,106.53 (2C), 59.95,55.74 (2C), 28.37.
Embodiment 71
The synthesis of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles's-3-base) (2-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-fluorophenyl)-3-(3,4,5-trimethoxyphenyl) propenone and TosMIC.
Product is white solid, yield 87.5%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.70 (s, 1H, pyrrole-NH), 7.46 (d, J=8.0Hz, 1H, ArH), 7.22 (t, J=8.0Hz, 2H, ArH), 7.17 (t, J=4.0Hz, 1H, pyrroleH), 7.08 (dd, J1=4.0Hz, J2=2.0Hz, 1H, pyrroleH), 6.75 (s, 2H, ArH), 3.74 (s, 6H, 3 ', 5'-OCH3), 3.64 (s, 3H, 4'-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 186.61,158.77 (1C, JCF=247.5Hz), 152.05 (2C), 136.05, (131.80 1C, JCF=8.2Hz), 130.31,129.72, (129.66 1C, JCF=3.9Hz), 129.53,125.26, (124.03 1C, JCF=3.4Hz), 121.70,120.14, (115.77 1C, JCF=21.9Hz), 106.39 (2C), 59.92,55.70 (2C).
Embodiment 72
The synthesis of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles's-3-base) (4-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-fluorophenyl)-3-(3,4,5-trimethoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 81.0%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.66 (s, 1H, pyrrole-NH), 7.76 (d, J=4.0Hz, 1H, ArH), 7.74 (d, J=4.0Hz, 1H, ArH), 7.27 (t, J=4.0Hz, 2H, pyrroleH), 7.22 (t, J=8.0Hz, 1H, ArH), 7.12 (t, J=4.0Hz, 1H, pyrroleH), 6.63 (s, 2H, ArH), 3.69 (s, 6H, 3 ', 5'-OCH3), 3.62 (s, 3H, 4'-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.18,163.91 (1C, JCF=249.1Hz), 152.18 (2C), 136.59 (1C, JCF=2.9Hz), 135.89, (131.58 2C, JCF=9.0Hz), 130.70,127.67,125.41,120.62,119.42,114.89 (2C, JCF=21.7Hz), 106.15 (2C), 59.95,55.70 (2C).
Embodiment 73
The synthesis of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles's-3-base) (2-chlorphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-chlorphenyl)-3-(3,4,5-trimethoxyphenyl) propenone and TosMIC.
Product is white solid, yield 89.9%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.70 (s, 1H, pyrrole-NH), 7.50 (d, J=8.0Hz, 1H, ArH), 7.44 (t, J=8.0Hz, 2H, ArH), 7.37 (m, 1H, ArH), 7.10 (t, J=4.0Hz, 1H, pyrroleH), 7.03 (dd, J1=4.0Hz, J2=2.0Hz, 1H, pyrroleH), 6.82 (s, 2H, ArH), 3.78 (s, 6H, 3 ', 5 ' OCH3), 3.67 (s, 3H, 4'-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 184.50,152.06 (2C), 140.76,136.10,130.43,130.24,130.09,129.55,129.47,128.56,126.70,125.25,121.16,120.45,106.37 (2C), 59.94,55.71 (2C).
Embodiment 74
The synthesis of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles's-3-base) (4-chlorphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-chlorphenyl)-3-(3,4,5-trimethoxyphenyl) propenone and TosMIC.
Product is white solid, yield 77.4%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.69 (s, 1H, pyrrole-NH), 7.69 (d, J=8.0Hz, 1H, ArH), 7.48 (t, J=8.0Hz, 2H, ArH), 7.29 (t, J=4.0Hz, 1H, pyrroleH), 7.12 (t, J=4.0Hz, 1H, pyrroleH), 6.64 (s, 2H, ArH), 3.70 (s, 6H, 3 ', 5 ' OCH3), 3.63 (s, 3H, 4'-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.31,152.17 (2C), 138.76,136.09,135.95,130.71 (2C), 130.63,128.04 (2C), 127.97,125.45,120.50,119.53,106.21 (2C), 59.98,55.71 (2C).
Embodiment 75
The synthesis of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles's-3-base) (3-bromophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-bromophenyl)-3-(3,4,5-trimethoxyphenyl) propenone and TosMIC.
Product is yellow solid, yield 71.5%.
The experimental data of product is as follows:
1HNMR (300MHz, DMSO-d6) δ (ppm): 11.71 (s, 1H, pyrrole-NH), 7.69 (s, 1H, ArH), 7.65 (d, J=9.0Hz, 1H, ArH), 7.57 (d, J=9.0Hz, 1H, ArH), 7.42 (m, 1H, ArH0,7.32 (dd, J1=3.0Hz, J2=1.5Hz, 1H, pyrroleH), 7.10 (t, J=3.0Hz, 1H, pyrroleH), 6.60 (s, 2H, ArH), 3.68 (s, 6H, 3 ', 5 '-OCH3), 3.61 (s, 3H, 4'-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.93,152.18 (2C), 142.09,135.88,133.85,131.46,130.59,130.19,127.98,127.65,125.53,121.25,120.48,119.48,106.23 (2C), 59.86,55.68 (2C).
Embodiment 76
The synthesis of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles's-3-base) (4-bromophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-bromophenyl)-3-(3,4,5-trimethoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 70.3%.
The experimental data of product is as follows:
1HNMR (300MHz, DMSO-d6) δ (ppm): 11.69 (s, 1H, pyrrole-NH), 7.59 (s, 4H, ArH), 7.28 (dd, J1=3.0Hz, J2=1.5Hz, 1H, pyrroleH), 7.11 (t, J=3.0Hz, 1H, pyrroleH), 6.63 (s, 2H, ArH), 3.69 (s, 6H, 3 ', 5'-OCH3), 3.62 (s, 3H, 4 '-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.44,152.17 (2C), 139.10,135.94,130.98 (2C), 130.89 (2C), 130.62,125.45,125.06,120.43,119.55,106.21 (2C), 60.00,55.71 (2C).
Embodiment 77
The synthesis of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles's-3-base) (4-aminomethyl phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-aminomethyl phenyl)-3-(3,4,5-trimethoxyphenyl) propenone and TosMIC.
Product is white solid, yield 76.0%.
The experimental data of product is as follows:
1HNMR (300MHz, DMSO-d6) δ (ppm): 11.59 (s, 1H, pyrrole-NH), 7.61 (d, J=6.0Hz, 2H, ArH), 7.23 (d, J=6.0Hz, 2H, ArH), 7.20-7.18 (m, 1H, pyrroleH), 7.11 (t, J=3.0Hz, 1H, pyrroleH), 6.65 (s, 2H, ArH), 3.68 (s, 6H, 3 ', 5 '-OCH3), 3.62 (s, 3H, 4 '-OCH3), 2.33 (s, 3H, PhCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 190.31,152.17 (2C), 141.46,137.38,135.85,130.85,129.12 (2C), 128.54 (2C), 127.38,125.31,120.83,119.27,106.06 (2C), 59.96,55.69 (2C), 20.97.
Embodiment 78
The synthesis of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles's-3-base) (2,4-3,5-dimethylphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2,4-3,5-dimethylphenyl)-3-(3,4,5-trimethoxyphenyl) propenone and TosMIC.
Product is white solid, yield 69.1%.
The experimental data of product is as follows:
1HNMR (300MHz, DMSO-d6) δ (ppm): 11.57 (s, 1H, pyrrole-NH), 7.22 (d, J=6.0Hz, 1H, ArH), 7.06 (t, J=3.0Hz, 1H, pyrroleH), 7.03 (s, 1H, ArH), 6.97 (t, J=3.0Hz, 1H, pyrroleH), 6.99-6.94 (m, 1H, ArH), 6.75 (s, 2H, ArH), 3.73 (s, 6H, 3 ', 5'-OCH3), 3.64 (s, 3H, 4 '-OCH3), 2.27 (s, 3H, PhCH3), 2.22 (s, 3H, PhCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 192.25,152.06 (2C), 138.62,138.49,135.97,135.17,131.03,130.66,129.09,128.02,125.39,125.22,122.15,119.93,106.27 (2C), 59.96,55.69 (2C), 20.77,19.36.
Embodiment 79
The synthesis of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles's-3-base) (3-methoxyphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl) propenone and TosMIC.
Product is white solid, yield 79.1%.
The experimental data of product is as follows:
null1HNMR(300MHz，DMSO-d6) δ (ppm): 11.64 (s，1H，pyrrole-NH)，7.32(t，J=9.0Hz，1H，ArH)，7.28-7.22(m，2H，ArH)，7.15(dd，J1=3.0Hz，J2=1.5Hz，1H，pyrroleH)，7.10(t，J=3.0Hz，1H，pyrroleH)，7.09-7.04(m，1H，ArH)，6.63(s，2H，ArH)，3.72(s，3H，-COPhOCH3)，3.68(s，6H，3’，5'-OCH3)，3.61(s，3H，4’-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 190.22,158.79,152.15 (2C), 141.47,135.86,130.80,129.09,127.85,125.41,121.33,120.73,119.42,117.45,113.63,106.15 (2C), 59.93,55.68 (2C), 55.09.
Embodiment 80
The synthesis of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles's-3-base) (4-methoxyphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl) propenone and TosMIC.
Product is white solid, yield 82.8%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.57 (s, 1H, pyrrole-NH), 7.72 (d, J=8.0Hz, 2H, ArH), 7.21 (t, J=4.0Hz, 1H, pyrroleH), 7.12 (t, J=4.0Hz, 1H, pyrroleH), 6.96 (d, J=8.0Hz, 2H, ArH), 6.64 (s, 2H, ArH), 3.80 (s, 3H ,-COPhOCH3), 3.68 (s, 6H, 3 ', 5 '-OCH3), 3.62 (s, 3H, 4 '-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.54,162.00,152.20 (2C), 135.79,132.46,131.24 (2C), 130.90,126.64,125.18,120.93,119.03,113.27 (2C), 105.96 (2C), 59.95,55.68 (2C), 55.34.
Embodiment 81
The synthesis of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles's-3-base) (2-pyridine radicals) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-pyridine radicals)-3-(3,4,5-trimethoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 68.3%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.65 (s，1H，pyrrole-NH)，8.62(m，1H，pyridineH)，7.95(td，J1=8.0Hz，J2=2.0Hz，1H，pyridineH)，7.80(td，J1=8.0Hz，J2=0.8Hz，1H，pyridineH)，7.70(dd，J1=4.0Hz，J2=2.0Hz，1H，pyrroleH)，7.54(m，1H，pyridineH)，7.06(t，J=4.0Hz，1H，pyrroleH)，6.72(s，2H，PhH)，3.75(s，6H，3’，5’OCH3)，3.67(s，3H，4’-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 187.75,156.93,152.04 (2C), 148.21,137.00,135.92,131.08,130.38,126.07,125.60,123.04,119.38,119.25,106.36 (2C), 59.95,55.73 (2C).
Embodiment 82
The synthesis of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles's-3-base) (3-pyridine radicals) ketone
Preparation method is with embodiment 1, and raw material is 1-(3-pyridine radicals)-3-(3,4,5-trimethoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 50.0%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.77 (s，1H，pyrrole-NH)，8.80(s，1H，pyridineH)，8.68(dd，J1=8.0Hz，J2=1.6Hz，1H，pyridineH)，8.01(dt，J1=8.0Hz，J2=2.0Hz，1H，pyridineH)，7.44(m，1H，pyridineH)，7.36(dd，J1=4.0Hz，J2=1.6Hz，1H，pyrroleH)，7.15(t，J=4.0Hz，1H，pyrroleH)，6.68(s，2H，PhH)，3.71(s，6H，3’，5’-OCH3)，3.64(s，3H，4’-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.78,152.18 (2C), 151.65,149.36,136.16,135.96,135.58,130.46,128.61,125.46,123.21,120.59,119.84,106.30 (2C), 59.94,55.73 (2C).
Embodiment 83
The synthesis of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles's-3-base) (4-pyridine radicals) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-pyridine radicals)-3-(3,4,5-trimethoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 36.7%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.80 (s, 1H, pyrrole-NH), 8.68 (d, J=8.0Hz, 2H, pyridineH), 7.56 (d, J=8.0Hz, 2H, pyridineH), 7.32 (t, J=4.0Hz, 1H, pyrroleH), 7.16 (t, J=4.0Hz, 1H, pyrroleH), 6.73 (s, 2H, PhH), 3.73 (s, 6H, 3 ', 5 '-OCH3), 3.65 (s, 3H, 4 '-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 189.00,152.14 (2C), 149.80 (2C), 146.93,136.10,130.37,129.56,125.54,122.28 (2C), 120.21,119.91,106.37 (2C), 59.96,55.76 (2C).
Embodiment 84
The synthesis of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles's-3-base) (2-thienyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-thienyl)-3-(3,4,5-trimethoxyphenyl) propenone and TosMIC.
Product is white solid, yield 79.0%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.66 (s，1H，pyrrole-NH)，7.92(dd，J1=4.0Hz，J2=1.2Hz，1H，thiopheneH)，7.65(dd，J1=4.0Hz，J2=1.2Hz，1H，thiopheneH)，7.50(dd，J1=4.0Hz，J2=2.0Hz，1H，pyrroleH)，7.18(dd，J1=4.0Hz，J2=1.2Hz，1H，thiopheneH)，7.14(t，J=4.0Hz，1H，pyrroleH)，6.70(s，2H，ArH)，3.73(s，6H，3’，5’-OCH3)，3.65(s，3H，4’-OCH3)；13CNMR (100MHz, DMSO-d6) δ (PPm): 182.09,152.25 (2C), 145.65,135.92,133.12,132.98,130.70,128.11,126.50,125.03,120.42,119.47,105.98 (2C), 59.97,55.73 (2C).
Embodiment 85
The synthesis of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles's-3-base) (1-naphthyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(1-naphthyl)-3-(3,4,5-trimethoxyphenyl) propenone and TosMIC.
Product is brown solid, yield 89.1%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.51 (s，1H，pyrrole-NH)，7.97(dd，J1=8.0Hz，J2=2.8Hz，1H，naphthaleneH)，7.91(d，J=8.0Hz，1H，naphthaleneH)，7.51-7.46(m，3H，naphthaleneH)，7.40(t，J=8.0Hz，1H，naphthaleneH)，7.14(t，J=4.0Hz，1H，pyrroleH)，7.03(t，J=4.0Hz，1H，pyrroleH)，6.57(s，2H，PhH)，3.68(s，6H，3’，5’-OCH3)，3.63(s，3H，4’-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 192.13,152.47 (2C), 139.19,136.38,133.60,131.11,130.64,130.26,129.81,128.70,127.14,126.82,126.52,126.09,125.80,125.05,123.14,120.46,106.83 (2C), 60.36,56.05 (2C).
Embodiment 86
The synthesis of (4-(3,4,5-trimethoxyphenyl)-1H-pyrroles's-3-base) (4-xenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-xenyl)-3-(3,4,5-trimethoxyphenyl) propenone and TosMIC.
Product is faint yellow solid, yield 61.7%.
The experimental data of product is as follows:
null1HNMR(300MHz，DMSO-d6) δ (ppm): 11.66 (s，1H，pyrrole-NH)，7.79(d，J=6.0Hz，2H，ArH)，7.72(d，J=6.0Hz，2H，ArH)，7.70(d，J=6.0Hz，2H，ArH)，7.48(t，J=6.0Hz，2H，ArH)，7.40(t，J=6.0Hz，1H，ArH)，7.30(t，J=6.0Hz，1H，pyrroleH)，7.13(t，J=6.0Hz，1H，pyrroleH)，6.67(s，2H，ArH)，3.69(s，6H，3’，5’-OCH3)，3.59(s，3H，4’-OCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 190.06,152.19 (2C), 142.94,139.20,138.89,135.91,130.79,129.70 (2C), 129.01 (2C), 128.04,127.80,126.81 (2C), 126.25 (2C), 125.43,120.76,119.47,106.16 (2C), 59.94,55.72 (2C).
Embodiment 87
The synthesis of (4-(2-naphthyl)-1H-pyrroles's-3-base) (2-fluorophenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-fluorophenyl)-3-(2-naphthyl) propenone and TosMIC.
Product is brown solid, yield 61.6%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.81 (s，1H，pyrrole-NH)，7.89(dd，J1=8.0Hz，J2=2.0Hz，1H，naphthaleneH)，7.82(d，J=12.0Hz，2H，naphthaleneH)，7.45(t，J=8.0Hz，2H)，7.43-7.35(m，4H)，7.33(t，J=4.0Hz，1H，pyrroleH)，7.14(dd，J1=4.0Hz，J2=2.0Hz，1H)，7.12(d，J=8.0Hz，1H)，7.00(t，J=4.0Hz，1H，pyrroleH)；13CNMR (100MHz, DMSO-d6) δ (ppm): 186.04,158.67JCF=247.7Hz, 133.53,132.95,132.35,131.66JCF=8.1Hz, 129.42JCF=3.4Hz, 129.06JCF=15.9Hz, 128.22,127.78,127.20,126.68,125.96,125.44,125.27,125.08,123.86JCF=3.4Hz, 123.68,122.52,120.92,115.63JCF=21.7Hz.
Embodiment 88
The synthesis of (4-(2-naphthyl)-1H-pyrroles's-3-base) (2-chlorphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-chlorphenyl)-3-(2-naphthyl) propenone and TosMIC.
Product is yellow solid, yield 75.3%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.80 (s, 1H, pyrrole-NH), 7.90 (d, J=8.0Hz, 1H, naphthaleneH), 7.86 (d, J=8.0Hz, 1H, naphthaleneH), 7.82 (d, J=8.0Hz, 1H, naphthaleneH), 7.48-7.43 (m, 2H), 7.50-7.30 (m, 5H), 7.27 (m, 1H), 7.17 (dd, J1=4.0Hz, J2=2.0Hz, 1H, pyrroleH), 6.99 (t, J=4.0Hz, 1H, pyrroleH)；13CNMR (100MHz, DMSO-d6) δ (ppm): 187.82,140.22,133.51,132.93,132.38,130.37,129.48,129.37,128.82,128.43,127.74,127.19,126.74,126.55,126.30,125.40,125.31,125.06,123.12,122.49,121.25.
Embodiment 89
The synthesis of (4-(2-naphthyl)-1H-pyrroles's-3-base) (4-chlorphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-chlorphenyl)-3-(2-naphthyl) propenone and TosMIC.
Product is yellow solid, yield 58.1%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.81 (s，1H，pyrrole-NH)，7.88(dd，J1=8.0Hz，J2=2.0Hz，1H，naphthaleneH)，7.80(m，2H，naphthalerneH)，7.66(d，J=8.0Hz，2H，PhH)，7.46-7.42(m，2H，naphthaleneH)，7.43(d，J=8.0Hz，2H，PhH)，7.41(t，J=4.0Hz，1H，pyfroleH)，7.35(dd，J1=8.0Hz，J2=2.0Hz，2H，naphthaleneH)，7.04(t，J=4.0Hz，1H，pyrroleH)；13CNMR (100MHz, DMSO-d6) δ (ppm): 188.39,138.40,135.96,133.83,133.04,132.24,130.34 (2C), 128.03 (2C), 127.83,127.25,127.20,126.50,125.79,125.47,125.27,125.19,122.97,122.29,120.64.
Embodiment 90
The synthesis of (4-(2-naphthyl)-1H-pyrroles's-3-base) (2,4-3,5-dimethylphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2,4-3,5-dimethylphenyl)-3-(2-naphthyl) propenone and TosMIC.
Product is brown solid, yield 62.4%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.68 (s，1H，pyrrole-NH)，7.89(dd，J1=8.0Hz，J2=2.0Hz，1H，naphthaleneH)，7.82(d，J=8.0Hz，2H)，7.470-7.41(m，2H)，7.39-7.34(m，2H)，7.26(d，J=8.0Hz，2H)，7.12(dd，J1=4.0Hz，J2=2.0Hz，1H，pyrroleH)，6.99-6.93(m，3H，1pyrroleH+2ArH)，2.26(s，3H，phCH3)，2.15(s，3H，phCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 191.46,138.52,137.93,135.11,134.05,132.99,132.43,131.00,127.91,127.80,127.76,127.06,126.48,126.12,125.32,125.29,125.24,125.12,124.09,122.61,120.74,20.75,19.25.
Embodiment 91
The synthesis of 3-cyano group-4-(2-pyridine radicals)-1H-pyrroles
Preparation method is with embodiment 1, and raw material is 3-(2-pyridine radicals) acrylonitrile and TosMIC.
Product is brown solid, yield 74.4%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 12.01 (s, 1H, pyrrole-NH), 8.56 (s, 1H, pyridineH), 7.80 (t, J=8.0Hz, 1H, pyridineH), 7.75 (m, 2H, pyridineH), 7.60 (t, J=4.0Hz, 1H, pyrroleH), 7.22 (t, J=4.0Hz, 1H, pyrroleH)；13CNMR (100MHz, DMSO-d6) δ (ppm): 191.91,149.23,136.75,129.26,124.93,121.41,119.67,119.30,117.27,89.81.
Embodiment 92
The synthesis of 3-ethoxycarbonyl-4-(2-pyridine radicals)-1H-pyrroles
Preparation method is with embodiment 1, and raw material is 3-(2-pyridine radicals) ethyl acrylate and TosMIC.
Product is brown solid, yield 53.8%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.62 (s，1H，pyrrole-NH)，8.50(m，1H，pyridineH)，7.77(dt，J1=8.0Hz，J2=2.0Hz，1H，pyridineH)，7.70(dt，J1=8.0Hz，J2=2.0Hz，1H，pyridineH)，7.47(dd，J1=4.0Hz，J2=2.0Hz，1H，pyrroleH)，7.22(t，J=4.0Hz，1H，pyrroleH)，7.18(m，1H，pyridineH)，4.15(dd，J1=12.0Hz，J2=4.0Hz，2H，-COOCH2-)，1.20(t，J=8.0Hz，3H，-CH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 164.29,153.49,148.46,135.60,125.96,124.66,123.24,121.19,120.85,112.39,58.98,14.17.
Embodiment 93
The synthesis of (4-(2-pyridine radicals)-1H-pyrroles's-3-base) (4-aminomethyl phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(4-aminomethyl phenyl)-3-(2-pyridine radicals) propenone and TosMIC.
Product is faint yellow solid, yield 71.3%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.64 (s，1H，pyrrole-NH)，8.37(m，1H，pyridineH)，7.67(d，J=8.0Hz，2H，PhH)，7.63(td，J1=8.0Hz，J2=4.0Hz，1H，pyridineH)，7.52(dt，J1=8.0Hz，J2=0.8Hz，1H，pyridineH)，7.36(t，J=4.0Hz，1H，pyrroleH)，7.26(d，J=8.0Hz，2H，PhH)，7.20(dd，J1=4.0Hz，J2=2.0Hz，1H，pyrroleH)，7.09(ddd，J1=7.2Hz，J2=5.2Hz，J1=0.8Hz，1H，pyridineH)，2.36(s，3H，phCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 190.47,153.72,148.56,141.73,137.02,135.66,129.16 (2C), 128.63 (2C), 126.63,125.09,122.18,121.34,121.04,120.47,21.0l.
Embodiment 94
The synthesis of (4-(2-pyridine radicals)-1H-pyrroles's-3-base) (2,4-3,5-dimethylphenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2,4-3,5-dimethylphenyl)-3-(2-pyridine radicals) propenone and TosMIC.
Product is faint yellow solid, yield 55.9%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.64 (s，1H，pyrrole-NH)，8.43(dd，J1=4.0Hz，J2=1.6Hz，1H，pyridineH)，7.74(d，J=8.0Hz，1H)，7.66(td，J1=8.0Hz，J2=1.6Hz，1H，pyridineH)，7.32(t，J=4.0Hz，1H，pyrroleH)，7.26(d，J=8.0Hz，1H)，7.14dd，J1=8.0Hz，J2=4.0Hz，1H，pyrroleH)，7.07(s，1H，PhH)，7.02-6.97(m，2H)，2.30(s，3H，phCH3)，2.28(s，3H，phCH3)；13CNMR (100MHz, DMSO-d6) δ (ppm): 192.59,153.61,148.48,138.94,138.26,135.69,135.54,131.17,128.80,128.29,125.40,124.93,122.81,122.69,121.90,120.68,20.79,19.48
Embodiment 95
The synthesis of (4-(2-pyridine radicals)-1H-pyrroles's-3-base) (2-thienyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(2-thienyl)-3-(2-pyridine radicals) propenone and TosMIC.
Product is yellow solid, yield 62.4%.
The experimental data of product is as follows:
1HNMR (400MHz, DMSO-d6) δ (ppm): 11.71 (s, 1H, pyrrole-NH), 8.42 (m, 1H, pyridineH), 7.94 (dd, J1=4.0Hz, J2=2.0Hz, 1H), 7.70-7.62 (m, 2H), 7.52-7.46 (m, 2H), 7.36 (t, J=4.0Hz, 1H, pyrroleH), 7.18 (dd, J1=4.0Hz, J2=2.0Hz, 1H, pyrroleH), 7.12 (m, 1H)；13CNMR (100MHz, DMSO-d6) δ (ppm): 182.38,153.58,148.65,145.57,135.85,133.47,133.16,128.18,126.12,124.78,122.09,121.30,120.91,120.61.
Embodiment 96
The synthesis of (4-(2-pyridine radicals)-1H-pyrroles's-3-base) (phenyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(phenyl)-3-(2-pyridine radicals) propenone and TosMIC.
Product is faint yellow solid, yield 64.6%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.70 (s，1H，pyrrole-NH)，8.35(dd，J1=4.0Hz，J2=1.6Hz，1H，pyridineH)，7.75(d，J=8.0Hz，2H，PhH)，7.63(td，J1=8.0Hz，J2=1.6Hz，1H，pyridineH)，7.55(m，2H，PhH)，7.44(t，J=8.0Hz，2H，pyridineH)，7.37(t，J=4.0Hz，1H，pyrroleH)，7.23(t，J=4.0Hz，1H，pyrroleH)，7.09(ddd，J1=7.2Hz，J2=5.2Hz，J3=0.8Hz，1H，pyridineH)；13CNMR (100MHz, DMSO-d6) δ (ppm): 190.80,153.66,148.53,139.72,135.66,131.58,128.93 (2C), 128.05 (2C), 127.04,125.18,122.27,121.25,121.14,120.51.
Embodiment 97
The synthesis of (4-(2-pyridine radicals)-1H-pyrroles's-3-base) (1-naphthyl) ketone
Preparation method is with embodiment 1, and raw material is 1-(1-naphthyl)-3-(2-pyridine radicals) propenone and TosMIC.
Product is brown solid, yield 54.3%.
The experimental data of product is as follows:
null1HNMR(400MHz，DMSO-d6) δ (ppm): 11.70 (s，1H，pyrrole-NH)，8.36(dd，J1=4.0Hz，J2=1.6Hz，1H)，8.13(d，J=8.0Hz，1H)，8.03(d，J=8.0Hz，2H)，8.00-7.96(m，1H)，7.83(d，J=8.0Hz，1H)，7.67(dd，J1=8.0Hz，J2=4.0Hz，1H)，7.64(d，J=8.0Hz，1H)，7.57-7.48(m，3H)，7.36(t，J=4.0Hz，1H，pyrroleH)，7.12(dd，J1=8.0Hz，J2=4.0Hz，1H)，7.06(t，J=4.0Hz，1H，pyrroleH)；13CNMR (100MHz, DMSO-d6) δ (ppm): 191.97,153.56,148.45,138.71,135.59,133.15,130.25,130.01,129.49,128.18,126.70,126.43,126.10,125.46,125.21,124.55,123.04,122.89,122.06,120.77.
Two, the cell inhibitory effect activity of 3,4-disubstituted pyrroles compounds
1. reagent and material
nullCell strain totally 16 kinds of tumor cells used，Including human gastric adenocarcinoma (SGC-7901)、Gastric carcinoma cells (MGC80-3)、National People's Congress's cell lung cancer cell (NCI-H460)、Human Prostate Cancer Cells (DU145)、Human breast cancer cell (MCF-7)、Human cervical carcinoma cell (Hela)、People's malignant melanoma cell (A375)、People chronic marrow source leukemia (K562)、Human colon cancer cell (HCT-116)、People's Colon and rectum adenocarcinoma cell (HCT-15)、Human liver cancer cell (HepG2)、Human osteosarcoma cell (MG-63)、Human lung carcinoma cell (A549)、Mouse leukemia cell (L1210)、Mouse colonic cell (CT-26) and Chinese hamster ovary cancerous cell (CHO)，And two kinds of normal cells strain human umbilical vein endothelial cell (HUVEC) and mouse embryo cell (NIH/3T3).
nullAgents useful for same mainly includes RPMI-1640 culture medium (HyClone)、DMEM (high sugar) culture medium (HyClone)、Hyclone (HyClone，South America blood relationship)、Nonessential aminoacid (HyClone，Non-EssentialAminoAcidsSolution)、Pen .-Strep (dual anti-) solution (HyClone)、0.25%trypsin-EDTA trypsin solution (Gibco)、Tetrazolium bromide (Sigma)、Biology DMSO、PBS (HyClone)、Sodium lauryl sulphate (Chemical Reagent Co., Ltd., Sinopharm Group，SDS)、Isobutanol (Chemical Reagent Co., Ltd., Sinopharm Group)、Concentrated hydrochloric acid (Chemical Reagent Co., Ltd., Sinopharm Group)、Positive control Taxol (Sigma) and 5-fluorouracil (Sigma).
Consumptive material used mainly includes aseptic dropper, aseptic pin type filter (Millex), Tissue Culture Dish (Corning) and 96 orifice plates (Corning).
Instrument mainly includes sterile purification workbench (Shanghai new talent medical apparatus and instruments prepares company limited), CO2 gas incubator (ThermoFormaSeriesII), enzyme-linked immunosorbent assay instrument (ThermoMK3), inverted microscope (OlympusIX71, electronic balance (MetterToledoAL204) and centrifuge (flying pigeon TDL80-23).
2. the configuration of sample and reagent
By 3,4-disubstituted pyrroles compound and positive control (paclitaxel and 5-fluorouracil) are dissolved in biology DMSO, the stock solution being configured to 1.0mg/mL is stand-by, tests front serum-free medium and is diluted to the sample dope of concentration respectively 1000mg/mL, 500mg/mL, 200mg/mL, 100mg/mL, 10mg/mL and 1mg/mL；Negative control solution is the culture medium solution containing only equivalent DMSO.
The preparation of MTT solution: 0.5gMTT solid is dissolved in 100mLPBS solution, final concentration of 5mg/mL is stand-by after aseptic filtration, lucifuge-20 DEG C preservation.
The preparation of three liquid: 10gSDS, 5mL isobutanol and 0.1mL concentrated hydrochloric acid (36.5%) are dissolved in appropriate distilled water to be configured to three liquid of 100mL stand-by.
3. mtt assay measures IC50 value
By frozen cell recovery to be measured, carrying out cell cultivation with the culture medium containing the dual anti-solution of 10% hyclone and 1%, culture dish is placed in 37 DEG C of constant temperature, incubator containing 5% carbon dioxide, the cultivation of cell, changes liquid and going down to posterity and all carries out according to standard operation.
The cell that phase of taking the logarithm grows, after trypsinization, blowing and beating into individual cells, being configured to cell concentration is 5 × 104The cell suspension of individual/mL, it is inoculated in 96 orifice plates, every hole 90 μ L, 96 orifice plates are placed in cell culture incubator and cultivate after 24h, add containing variable concentrations 3, the sample solution of 4-disubstituted pyrroles compound, the sample solution containing variable concentrations positive control paclitaxel and each 10 μ L of negative control solution, make medicine and positive control concentration respectively 100mg/mL, 50mg/mL, 20mg/mL, 10mg/mL, 1mg/mL and 0.1mg/mL, each concentration arranges 4 multiple holes, continues to cultivate 24h in cell culture incubator.Terminate every hole after cultivating and add the MTT solution of 20 μ L, continue to cultivate 6h.
After terminating MTT cultivation, for attached cell post processing it is: abandon the supernatant in 96 orifice plates, add the DMSO of 100 μ L, after first a ceremonial jade-ladle, used in libation is fully dissolved, OD value under enzyme-linked immunosorbent assay instrument detection 570nm, make the standard curve of compound concentration and suppression ratio accordingly, use nonlinear regression analysis to calculate correspondingly IC50 value.For suspension cell post processing it is: in 96 orifice plates, directly add three liquid of 100 μ L, cultivate 12 hours, OD value under enzyme-linked immunosorbent assay instrument detection 570nm, makes the standard curve of compound concentration and suppression ratio accordingly, uses nonlinear regression analysis to calculate corresponding IC50 value.
Compound is as shown in table 2 to the IC50 value (μm ol/L) of normal cell and part relatively Sensitive Tumor Cells.
Table 2
Compound and the IC50 value thereof with other sensitive cells strains are as shown in table 3:
Table 3
Note: cell inhibitory effect activity experiment all repeats 3 times；
> 100: illustrate that compound is only small to this cell strain lethal effect；
----: illustrate compound to this cell strain without lethal effect.
In sum, the present invention adopts VanLeusen pyrroles's synthetic method, has synthesized 97 3,4-disubstituted pyrroles compounds, and reaction has that the time is short, productivity is high and the advantage such as side reaction is few.The data testing Compound cellular proliferation inhibition activity through mtt assay show, kinds of tumor cells is had the cytotoxicity of excellence by 3,4-disubstituted pyrroles compounds, and the activity of chemical compound lot is better than 5-fluorouracil, even can match in excellence or beauty with paclitaxel, or activity exceedes paclitaxel.Positive drug paclitaxel contrast better with activity, the advantage of the present invention is as follows:
Embodiment 4,38,40,51,53,55-59,62 and 75 product the cell inhibitory effect activity of MGC80-3 is in the same order of magnitude with paclitaxel, wherein the activity of embodiment 55,57 and 59 is more than paclitaxel；
The product of embodiment 55,57,59 and 62 is active in paclitaxel to the cell inhibitory effect of DU145；
The cell inhibitory effect activity of HepG2 is in the same order of magnitude with paclitaxel by the product of embodiment 13,15,53,55,56,57,59,62 and 64, and wherein the activity of embodiment 13,15,55,56,57,59,62 and 64 is more than paclitaxel；
The cell inhibitory effect activity of MCF-7 is in the same order of magnitude with paclitaxel by the product of embodiment 42；
Embodiment 2,38,42,49,51,55, the product of 57-59,62,64,66,75 and 76 the cell inhibitory effect activity of CHO is in the same order of magnitude with paclitaxel, wherein the activity of embodiment 57,58,59 and 66 is more than paclitaxel；
Embodiment 42,44,53, the product of 55-57,59,62,64 and 66 to the cell inhibitory effect activity of CT-26 more than paclitaxel.
Meanwhile, normal cell almost without impact, thus be may infer that 3,4-disubstituted pyrroles compounds are full of prospect in the future in antitumor utilization by these compounds.
Claims (4)
1. a disubstituted pyrroles compound, it is characterised in that this compound has the structure shown in below formula:
Wherein R1=3, during 4-difluorophenyl, R2=2-fluoro benzoyl; 4-fluoro benzoyl; 2-chlorobenzene formacyl, 4-chlorobenzene formacyl, 3-benzoyl bromide, 4-benzoyl bromide, 3-anisoyl, 4-anisoyl, 3-picolinoyl, 4-picolinoyl, 2-Thenoyl, 2-nitro benzoyl, benzoyl, 1-naphthyl formoxyl or 4-dibenzoyl base；
R1During=4-toluyl amido, R2=nitro, cyano group, group-4 ethyl formate, acetyl group, 2-fluoro benzoyl, 4-fluoro benzoyl, 2-chlorobenzene formacyl, 4-chlorobenzene formacyl, 3-benzoyl bromide, 4-benzoyl bromide, 4-methyl benzoyl, 2,4-dimethylbenzoyl, 3-anisoyl, 4-anisoyl, 2-picolinoyl, 3-picolinoyl, 4-picolinoyl, 2-Thenoyl, benzoyl, 1-naphthyl formoxyl or 4-dibenzoyl base；
R1During=3-methoxyphenyl, R2=2-fluoro benzoyl, 4-fluoro benzoyl, 2-chlorobenzene formacyl, 4-chlorobenzene formacyl, 3-benzoyl bromide, 4-benzoyl bromide, 4-anisoyl, 3-picolinoyl, 4-picolinoyl, 2-Thenoyl, 2-nitro benzoyl, 1-naphthyl formoxyl or 4-dibenzoyl base；
During R1=3,4-Dimethoxyphenyl, R2=2-fluoro benzoyl, 4-fluoro benzoyl, 2-chlorobenzene formacyl, 4-chlorobenzene formacyl, 3-benzoyl bromide, 4-benzoyl bromide, 3-anisoyl, 3-picolinoyl, 4-picolinoyl, 2-Thenoyl, 2-nitro benzoyl, 1-naphthyl formoxyl or 4-dibenzoyl base；
R1=3,4, during 5-trimethoxyphenyl, R2=nitro, acetyl group, 2-fluoro benzoyl, 4-fluoro benzoyl, 2-chlorobenzene formacyl, 4-chlorobenzene formacyl, 3-benzoyl bromide, 4-benzoyl bromide, 4-methyl benzoyl, 2,4-dimethylbenzoyl, 3-anisoyl, 4-anisoyl, 2-picolinoyl, 3-picolinoyl, 4-picolinoyl, 2-Thenoyl, 1-naphthyl formoxyl or 4-dibenzoyl base；
R1During=2-naphthyl, R2=2-fluoro benzoyl, 2-chlorobenzene formacyl, 4-chlorobenzene formacyl or 2,4-dimethylbenzoyl；
R1During=2-pyridine radicals, R2=4-methyl benzoyl, 2,4-dimethylbenzoyl, 2-Thenoyl, benzoyl or 1-naphthyl formoxyl.
2. 3 described in claim 1,4-disubstituted pyrroles compound application in preparing antitumor drug, it is characterised in that described 3, various tumor cell strains is had proliferation inhibition activity by 4-disubstituted pyrroles compound, has the ability of excellent selective killing tumor cell.
3. application according to claim 2, it is characterized in that, described various tumor cell strains includes gastric carcinoma cells, Human Prostate Cancer Cells, human cervical carcinoma cell, people's malignant melanoma cell, human breast cancer cell, Chinese hamster ovary cancerous cell, mouse colonic cell and human lung carcinoma cell.
4. application according to claim 2, it is characterized in that, described various tumor cell strains also includes human gastric adenocarcinoma, National People's Congress's cell lung cancer cell, people chronic marrow source leukemia, human colon cancer cell, people's Colon and rectum adenocarcinoma cell, human liver cancer cell, human osteosarcoma cell and mouse leukemia cell.
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