CN112778186B - Synthetic method of pyrrole compound - Google Patents
Synthetic method of pyrrole compound Download PDFInfo
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- CN112778186B CN112778186B CN202110129957.6A CN202110129957A CN112778186B CN 112778186 B CN112778186 B CN 112778186B CN 202110129957 A CN202110129957 A CN 202110129957A CN 112778186 B CN112778186 B CN 112778186B
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- -1 pyrrole compound Chemical class 0.000 title claims abstract description 28
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 238000010189 synthetic method Methods 0.000 title claims abstract description 6
- 238000000034 method Methods 0.000 claims abstract description 39
- 238000006243 chemical reaction Methods 0.000 claims abstract description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 21
- 150000003233 pyrroles Chemical class 0.000 claims abstract description 9
- IANQTJSKSUMEQM-UHFFFAOYSA-N benzofuran Natural products C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims abstract description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 6
- 238000003818 flash chromatography Methods 0.000 claims abstract description 6
- 239000012074 organic phase Substances 0.000 claims abstract description 6
- 239000002904 solvent Substances 0.000 claims abstract description 6
- 229940125904 compound 1 Drugs 0.000 claims abstract description 5
- 229940125782 compound 2 Drugs 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 5
- 238000001816 cooling Methods 0.000 claims abstract description 5
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 230000001681 protective effect Effects 0.000 claims abstract description 5
- 238000002390 rotary evaporation Methods 0.000 claims abstract description 5
- 229940126214 compound 3 Drugs 0.000 claims abstract description 4
- 239000012043 crude product Substances 0.000 claims abstract description 3
- 238000012544 monitoring process Methods 0.000 claims abstract description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 5
- HTMBKOASYIITDH-UHFFFAOYSA-N 3h-1-benzofuran-2-imine Chemical class C1=CC=C2OC(=N)CC2=C1 HTMBKOASYIITDH-UHFFFAOYSA-N 0.000 claims description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 239000007789 gas Substances 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 3
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 229910052786 argon Inorganic materials 0.000 claims description 3
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 3
- 125000004185 ester group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 239000005749 Copper compound Substances 0.000 claims 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 claims 1
- 150000001880 copper compounds Chemical class 0.000 claims 1
- 238000003810 ethyl acetate extraction Methods 0.000 claims 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- 238000006664 bond formation reaction Methods 0.000 abstract description 2
- 238000001308 synthesis method Methods 0.000 abstract description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 92
- 239000000047 product Substances 0.000 description 29
- 238000005160 1H NMR spectroscopy Methods 0.000 description 25
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 24
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000000463 material Substances 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 3
- 239000011261 inert gas Substances 0.000 description 3
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 3
- 239000004810 polytetrafluoroethylene Substances 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 102000002254 Glycogen Synthase Kinase 3 Human genes 0.000 description 2
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 2
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000008204 material by function Substances 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 125000000168 pyrrolyl group Chemical group 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 1
- LLQRRQZTMPJPMZ-UHFFFAOYSA-N 1-[2,3,4,5,6-penta(pyrrol-1-yl)phenyl]pyrrole Chemical compound C1=CC=CN1C1=C(N2C=CC=C2)C(N2C=CC=C2)=C(N2C=CC=C2)C(N2C=CC=C2)=C1N1C=CC=C1 LLQRRQZTMPJPMZ-UHFFFAOYSA-N 0.000 description 1
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 1
- 102000016928 DNA-directed DNA polymerase Human genes 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 238000003445 Hantzsch reaction Methods 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 238000006945 Knorr synthesis reaction Methods 0.000 description 1
- 238000006086 Paal-Knorr synthesis reaction Methods 0.000 description 1
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 description 1
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 description 1
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 1
- 102000004079 Prolyl Hydroxylases Human genes 0.000 description 1
- 108010043005 Prolyl Hydroxylases Proteins 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000013537 high throughput screening Methods 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000006452 multicomponent reaction Methods 0.000 description 1
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000005693 optoelectronics Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920000128 polypyrrole Polymers 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 239000003909 protein kinase inhibitor Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 239000004065 semiconductor Substances 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 239000012855 volatile organic compound Substances 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
- C07D207/335—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F17/00—Metallocenes
- C07F17/02—Metallocenes of metals of Groups 8, 9 or 10 of the Periodic System
Abstract
The invention discloses a synthesis method of pyrrole compounds, which comprises the following steps: taking an oxime ester compound 1, a benzofuran imine compound 2 and a cuprous compound, adding an organic solvent under inert protective gas, reacting at 60-120 ℃, monitoring the reaction process by TLC, cooling to room temperature after the reaction is finished, extracting with saturated saline and ethyl acetate, combining organic phases, removing the solvent by rotary evaporation to obtain a crude product, and performing flash column chromatography to obtain a pyrrole compound 3. The method has a short synthetic method route, utilizes C-C and C-N bond formation, constructs the pyrrole compound in one step, has high atom economy and superior efficiency, has the reaction yield of 95 percent, and realizes breakthrough progress of chemical synthesis of the system.
Description
Technical Field
The invention belongs to the field of organic compound synthesis, and particularly relates to a synthesis method of a pyrrole compound.
Background
The pyrrole structure is one of the most common five-membered heterocycles and is present in a large number of natural products, drugs and functional materials. Azoles have remarkable biological and pharmacological properties, such as antibacterial, antifungal, anti-inflammatory, antioxidant, antitumor and ionic. It also acts as a retroviral reverse transcriptase [ i.e., human immunodeficiency virus type 1 (HIV-1) ], poly (ADP-ribose) polymerase, prolyl-4-hydroxylase, cellular DNA polymerase, glycogen synthase kinase 3(GSK-3) and protein kinase inhibitor. In functional material research, pyrrole and its derivatives have been the focus of attention of material scientists because of their potential as optoelectronic materials, such as Polymer Light Emitting Diodes (PLED), Organic Light Emitting Diodes (OLED), thin film transistors, nonlinear optical polymers, high performance semiconductors derived from hexa (N-pyrrolyl) benzene, and glucose sensors for detecting and identifying volatile organic compounds based on polypyrrole-latex materials and polypyrrole materials. Therefore, many synthetic strategies have been developed to obtain this important class of compounds. The conventional methods include Knorr, Hantzsch and Paal-Knorr reactions, the construction of polysubstituted pyrroles by condensation of carbonyl compounds and amines. However, these methods generally require the use of strong acids at higher reaction temperatures to promote condensation, which also results in limited substrate range and functional groups. In recent years, methods have also been developed which allow the synthesis of pyrroles with better regioselectivity under relatively mild conditions, such as: multicomponent reactions and transition metal catalyzed couplings. However, these methods generally require highly functionalized starting materials (e.g. iminoallene, alkynylaziridine or azide) and thus limit the range of products. Furthermore, many of the existing strategies require the use of substrates with protected nitrogen and therefore require removal or replacement of the protecting group after synthesis of the pyrrole ring, which greatly reduces the efficiency of the process.
Therefore, the development of a simple, efficient and practical method for catalytically synthesizing the pyrrole compounds can provide a practical and reliable new method for drug research and development, high-throughput screening of small molecule drugs and synthesis of functional materials, and has very important research significance and application prospect.
Disclosure of Invention
The invention aims to provide a synthetic method of pyrrole compounds, which has a short synthetic route, utilizes C-C and C-N bond formation, constructs the pyrrole compounds in one step, has high atom economy and superior efficiency, has a reaction yield of up to 95 percent, and realizes breakthrough progress of chemical synthesis of the system.
The method takes oxime ester compounds and benzofuran imine compounds as raw materials to react under the catalysis of Cu compounds to obtain pyrrole compounds under the protection of argon, and the specific scheme is as follows:
a synthetic method of pyrrole compounds comprises the following steps:
taking an oxime ester compound 1, a benzofuran imine compound 2 and a cuprous compound, adding an organic solvent under inert protective gas, reacting at 60-120 ℃, monitoring the reaction process by TLC, cooling to room temperature after the reaction is finished, extracting with ethyl acetate, washing with saturated saline solution, combining organic phases, removing the solvent by rotation to obtain a crude product, and performing flash column chromatography to obtain a pyrrole compound 3;
the reaction formula is as follows:
r in the oxime ester compound 11Is aryl, alkyl or ester group; r is2Is phenyl or alkyl.
R in the benzofuran compound 23Is H or methoxy; r4Is aryl; r5Cyano, halogen, alkyl or alkoxy.
R in the pyrrole compound 31Is aryl, alkyl or ester group; r2Is phenyl or alkyl; r3Is H or methoxy; r is4Is aryl; r is5Cyano, halogen, alkyl or alkoxy.
The mmol ratio of the oxime ester compound 1 to the benzofuran imine compound 2 is 0.1-5: 0.12-6.
The reaction time was 16 hours.
The ethyl acetate in the extraction was extracted 3 times.
The catalyst is CuCl, CuBr, CuI, CuOAc and CuCl2、CuBr2、CuI2Or Cu (OAc)2。
The organic solvent is DMSO, THF, 1,4-dioxane, Toluene, DMF, DCE and DCM.
The inert protective gas is argon.
According to the invention, the rapid construction of the C-C, C-N bond is realized by utilizing the transition metal to catalyze and break the N-O bond of the oxime ester compound to generate the free radical, and the Cu metal is used to catalyze the N-O bond to break because the synthesis strategy has the advantages of environmental friendliness, high efficiency, high selectivity and atom economy, so that the reaction of the oxime ester compound and the benzofuran imine compound is completed to construct the pyrrole compound in one step. The reaction raw materials are cheap and easy to obtain, the steps are short, and the method has high atom economy.
The invention has the advantages that the used raw materials are simple and easily obtained, are all industrialized commodities, have wide sources, low price, stable properties and non-harsh storage conditions; secondly, the synthetic route of the invention is short, the pyrrole compound is constructed in one step by utilizing the formation of C-C and C-N bonds, the atom economy is high, the efficiency is excellent, the reaction yield is up to 95 percent, the breakthrough progress of the chemical synthesis of the system is realized, and the deep extension of the related pharmaceutical chemistry research of the system is promoted.
Detailed Description
The data given in the examples below include specific operating and reaction conditions and products, all of which are characterized by nuclear magnetism.
The reagents of the invention are all commercial analytical pure reagents.
Example 1
A10 mL reaction tube was filled with weighed oxime ester compound 1a (0.2mmol), benzofuranimine compound 2a (0.24mmol), and CuCl (0.02mmol), and then DMSO (2mL) was added under inert gas protection, and the reaction tube was sealed with a polytetrafluoroethylene stopper. Placing the reaction tube in an oil bath kettle at 80 ℃ and stirring for 16 hours, cooling to room temperature after the reaction is finished, extracting with (20mL multiplied by 3) ethyl acetate for three times, washing with 40mL saturated saline solution, combining organic phases, removing the solvent by rotary evaporation to obtain a mixture containing 3aa, and then carrying out flash column chromatography to obtain a product 3aa with the yield of 95%.
1H NMR(600MHz,CDCl3)δ11.01(s,1H),10.78(s,1H),7.82(d,J＝7.8Hz,2H),7.64(d,J＝7.8Hz,2H),7.30(d,J＝7.8Hz,2H),7.25(m,2H),7.04(d,J＝7.8Hz,1H),7.00-7.07(m,4H),6.93(d,J＝6.6Hz,2H),6.72-6.75(m,2H),2.42(s,3H),2.36(s,3H).13C NMR(151MHz,CDCl3) δ 168.3,160.5,144.0,139.1,139.0,138.4,137.5,135.0,134.5,130.0,129.6,128.8,127.9,127.5,127.0,126.7,125.0,122.3,119.5,118.9,117.4,109.7,21.5, 21.3.; (ESI) calculation of value C31H26N2O3S,[M+H]+507.1734, actual value 507.1737.
Example 2
(1)
The weighed oxime ester compound 1b (0.12mmol), benzofuranimine compound 2a (0.1mmol) and CuBr (0.01mmol) were added to a 10mL reaction tube, and then DMSO (1mL) was added thereto under an inert gas atmosphere, and the reaction tube was sealed with a polytetrafluoroethylene stopper. The reaction tube is placed in an oil bath kettle at 80 ℃ and stirred for 10 hours, after the reaction is finished, the temperature is reduced to room temperature, the mixture is extracted three times by ethyl acetate (20mL multiplied by 3), 40mL saturated saline solution is used for washing, organic phases are combined, solvent is removed by rotary evaporation to obtain a mixture containing 3ba, and then the mixture is subjected to flash column chromatography to obtain a product 3ba, wherein the yield is 52%.
1H NMR(600MHz,CDCl3)δ11.08(s,1H),10.79(s,1H),7.84(d,J＝7.2Hz,2H),7.76(d,J＝7.0Hz,2H),7.50(t,J＝6.8Hz,2H),7.40(t,J＝7.0Hz,1H),7.27(s,1H),7.11(d,J＝6.7Hz,1H),7.08–6.99(m,4H),6.95(d,J＝6.5Hz,2H),6.81–6.72(m,2H),6.27(t,J＝7.0Hz,1H),2.37(s,3H).13C NMR(151MHz,CDCl3) δ 168.6,160.7,144.1,138.7,138.0,137.4,135.1,134.5,134.4,130.3,129.6,129.3,128.7,128.0,127.0,126.8,125.1,122.4,119.3,119.0,117.5,109.9,21.5 HRMS (ESI) calculated value C30H24N2O3S[M+H]+493.1579, actual value 493.1580.
(2)
The procedure is as in example 1 to give the product 3ba in 90% yield.
Example 3
The procedure is as in example 1 to give the product 3da in 82% yield.
1H NMR(600MHz,CDCl3)δ11.03(s,1H),10.79(s,1H),7.82(d,J＝8.1Hz,2H),7.69(d,J＝8.3Hz,2H),7.52(d,J＝8.3Hz,2H),7.27–7.23(m,2H),7.11–6.98(m,5H),6.93(d,J＝6.8Hz,2H),6.71–6.76(m,2H),6.25(t,J＝7.6Hz,1H),2.36(s,3H),1.37(s,9H).13C NMR(151MHz,CDCl3) δ 168.4,160.6,152.2,144.0,139.1,138.4,137.5,135.0,134.5,129.6,128.8,127.9,127.4,127.0,126.7,126.3,124.9,122.3,119.5,118.9,117.4,109.8,34.8,31.2, 21.5; (ESI) calculation of value C34H32N2O3S,[M+H]+549.2205, actual value 549.2206.
Example 4
The procedure is as in example 1 to give product 3ea in 65% yield.
1H NMR(600MHz,CDCl3)δ10.92(s,1H),10.79(s,1H),7.83(d,J＝7.6Hz,2H),7.71(d,J＝8.2Hz,2H),7.27(s,1H),7.11–7.00(m,7H),6.95(d,J＝6.7Hz,2H),6.75(d,J＝8.1Hz,1H),6.68(s,1H),6.25(t,J＝7.2Hz,1H),3.88(s,3H),2.37(s,3H).13C NMR(151MHz,CDCl3) δ 167.9,160.3,143.9,143.5,139.3,138.9,137.6,134.8,134.5,134.5,129.6,129.6,128.8,127.9,127.0,126.7,126.6,126.4,123.0,122.3,119.6,118.9,117.4,114.8,109.6,55.4,21.5.(ESI) calculated value C31H26N2O4S,[M+H]+523.1684, actual value 523.1686.
Example 5
The procedure is as in example 1 to provide product 3fa in 43% yield.
1H NMR(600MHz,DMSO) δ 11.76(s,1H),9.44(s,1H),7.93(d, J ═ 6.9Hz,2H), 7.41-7.59 (m,4H),7.22(d, J ═ 7.9Hz,2H), 6.85-7.04 (m,7H),6.73(s,1H),6.49(s,1H),6.33(s,1H),2.33(s,3H). (ESI) calculated value C30H23ClN2O3S,[M+H]+527.1189, actual value 527.1191.
Example 6
The procedure is as in example 1 to give product 3ga in 91% yield.
1H NMR(600MHz,CDCl3)δ11.09(s,1H),10.74(s,1H),7.87–7.78(m,4H),7.47(d,J＝7.8Hz,2H),7.28(d,J＝7.6Hz,2H),7.15–7.00(m,5H),6.96(d,J＝6.9Hz,2H),6.75(d,J＝10.7Hz,2H),6.27(t,J＝7.4Hz,1H),2.38(s,3H).13C NMR (151MHz, DMSO) delta 164.0,139.4,133.7,132.7,132.6,130.5,129.7,129.4,125.1,124.9,123.9,123.3,122.2,122.1,121.8,114.2,112.7,105.2,89.4,16.8.(ESI) calculated C30H23IN2O3S,[M+H]+619.0548, actual value 619.0547.
Example 7
The procedure is as in example 1 to give the product 3ha in 79% yield.
1H NMR(600MHz,CDCl3)δ10.97(s,1H),10.76(s,1H),7.80(d,J＝7.8Hz,2H),7.63(d,J＝8.1Hz,2H),7.32(d,J＝7.9Hz,2H),7.23(d,J＝8.1Hz,3H),7.09–6.96(m,5H),6.91(d,J＝7.5Hz,2H),6.75–6.68(m,2H),6.22(t,J＝7.6Hz,1H),2.51(s,3H),2.34(s,3H).13C NMR(151MHz,CDCl3) δ 168.2,160.5,144.0,139.9,138.5,138.4,137.5,135.0,134.5,134.4,129.6,128.7,128.0,127.0,126.9,126.8,125.4,122.4,119.4,118.9,117.4,109.8,21.5,15.5.(ESI) calculated value C31H26N2O3S2,[M+H]+539.1457, actual value 539.1458.
Example 8
The procedure is as in example 1 to give the product 3ia in 86% yield.
1H NMR(600MHz,CDCl3)δ10.98(s,1H),10.75(s,1H),7.81(d,J＝7.4Hz,2H),7.53–7.46(m,2H),7.24(m,3H),7.10–6.98(m,5H),6.92(d,J＝6.9Hz,2H),6.77–6.69(m,2H),6.24(t,J＝7.4Hz,1H),2.34–2.38(m,6H),2.33(s,3H).13C NMR(151MHz,CDCl3) Delta 168.3,160.5,139.4,138.5,137.8,137.6,137.5,134.9,134.5,134.5,130.5,129.6,128.7,127.9,127.8,127.0,126.7,126.3,122.6,122.3,119.6,118.9,117.4,109.8,21.5,19.9,19.7.(ESI) calculated value C32H28N2O3S,[M+H]+521.1892, actual value 521.1893.
Example 9
The procedure is as in example 1 to give product 3ja in 71% yield.
1H NMR(600MHz,CDCl3)δ10.94(s,1H),10.71(s,1H),7.82(d,J＝7.3Hz,2H),7.65(s,1H),7.46(s,2H),7.27(d,J＝8.2Hz,2H),7.00–7.10(m,5H),6.94(d,J＝6.6Hz,2H),6.75(d,J＝8.2Hz,1H),6.65(s,1H),6.25(t,J＝7.4Hz,1H),2.37(s,3H).13C NMR(151MHz,CDCl3) δ 168.3,160.5,144.0,138.2,137.6,137.5,135.0,134.9,134.4,132.1,129.6,128.7,127.9,127.2,127.0,126.8,125.1,121.3,119.4,119.0,117.4,110.1,21.5.(ESI) calculated value C28H22N2O3S2,[M+H]+499.1144, actual value 499.1145.
Example 10
The procedure is as in example 1 to give product 3ka in 60% yield.
1H NMR(600MHz,CDCl3)δ10.82(s,1H),10.45(s,1H),7.85(d,J＝8.2Hz,2H),7.29(d,J＝8.2Hz,2H),7.09(d,J＝7.9Hz,1H),7.06–6.99(m,4H),6.98–6.94(m,2H),6.80–6.78(m,1H),6.73(d,J＝8.1Hz,1H),6.66(dd,J＝3.7,1.6Hz,1H),6.53(d,J＝2.7Hz,1H),6.29–6.22(m,2H),3.91(s,3H),2.39(s,3H).13C NMR(151MHz,CDCl3) Delta 167.4,165.3,160.2,143.9,138.4,137.8,134.7,134.5,134.4,132.4,129.6,128.8,127.9,127.0,126.7,125.8,124.5,122.0,119.7,118.9,117.4,110.9,110.5,108.8,35.9,21.5.(ESI) calcd for C29H25N3O3S,[M+H]+496.1690, actual value 496.1689.
Example 11
The procedure is as in example 1 to give product 3la in 58% yield.
1H NMR(600MHz,CDCl3)δ10.86(s,1H),10.64(s,1H),7.93(d,J＝8.0Hz,2H),7.34(d,J＝8.0Hz,2H),7.08(d,J＝7.8Hz,1H),6.99–7.06(m,6H),6.72(d,J＝8.2Hz,1H),6.50(d,J＝2.4Hz,1H),6.22(t,J＝7.5Hz,1H),4.74(s,2H),4.43(s,2H),4.23(s,5H),2.42(s,3H).13C NMR(151MHz,CDCl3) δ 166.7,160.3,143.9,140.7,139.0,138.3,134.7,134.6,134.6,129.7,128.9,127.9,126.9,126.7,121.9,119.6,118.8,117.2,110.1,74.6,70.2,69.8,66.2,21.5.(ESI) calculated value C34H28FeN2O3S,[M+H]+601.1242, actual value 601.1243.
Example 12
The procedure is as in example 1 to give the product 3ma in 66% yield.
1H NMR(600MHz,CDCl3)δ11.15(s,1H),10.75(s,1H),9.03(s,1H),8.61(d,J＝4.1Hz,1H),8.01(d,J＝7.8Hz,1H),7.85(d,J＝7.8Hz,2H),7.42(dd,J＝7.7,4.9Hz,1H),7.30(d,J＝7.9Hz,2H),7.17–6.98(m,7H),6.84(s,1H),6.75(d,J＝8.3Hz,1H),6.31(t,J＝7.6Hz,1H),2.39(s,3H).13C NMR(151MHz,CDCl3) Delta 169.1,149.2,146.6,144.3,137.4,135.4,134.8,134.0,131.8,129.7,128.6,128.1,127.0,126.9,126.7,123.9,119.0,117.5,110.1,21.5.(ESI) calculated value C29H23N3O3S,[M+H]+494.1532, actual value 494.1533.
Example 13
The procedure is as in example 1 to give the product 3na in 76% yield.
1H NMR(600MHz,CDCl3)δ10.91(s,1H),10.44(s,1H),7.84(d,J＝8.1Hz,2H),7.29(d,J＝8.1Hz,2H),7.08(d,J＝7.8Hz,1H),6.96–7.04(m,4H),6.93–6.89(m,2H),6.72(d,J＝8.2Hz,1H),6.28(d,J＝2.8Hz,1H),6.23(t,J＝7.6Hz,1H),2.39(s,3H),1.47(s,9H).13C NMR(151MHz,CDCl3) δ 167.3,159.4,149.9,142.9,136.9,136.9,133.9,133.7,133.7,128.6,127.9,126.8,125.9,125.4,119.6,118.6,117.8,116.2,107.8,31.2,29.0,20.5.(ESI) calculated value C28H28N2O3S,[M+H]+473.1904, actual value 473.1899.
Example 14
The procedure is as in example 1 to give the product 3oa in 50% yield.
1H NMR(600MHz,CDCl3)δ11.79(s,1H),10.37(s,1H),7.77(d,J＝6.7Hz,2H),7.22(s,2H),7.15–7.00(m,7H),6.83(d,J＝7.7Hz,1H),6.46(t,J＝7.4Hz,1H),4.38(q,J＝6.9Hz,2H),2.37(s,3H),1.40(t,J＝6.9Hz,3H).13C NMR(151MHz,CDCl3) Delta 171.3,162.3,160.2,144.6,136.7,134.0,133.3,129.7,128.3,127.8,127.3,126.9,126.1,122.8,119.4,118.0,114.4,61.2,21.5,14.3.(ESI) calculated value C27H24N2O5S,[M+H]+489.1483, actual value 489.1479.
Example 15
The procedure is as in example 1 to give product 3pa in 66% yield.
1H NMR(600MHz,CDCl3)δ10.28(s,1H),9.93(s,1H),7.74(d,J＝7.8Hz,2H),7.16–7.26(m,3H),6.96(t,J＝7.3Hz,2H),6.91(dd,J＝11.6,7.2Hz,2H),6.86(d,J＝7.4Hz,1H),6.81(d,J＝7.2Hz,2H),6.59(d,J＝8.2Hz,1H),6.15(t,J＝7.3Hz,1H),2.74(q,J＝7.6Hz,2H),2.35(s,3H),1.92(s,3H),1.36(t,J＝7.6Hz,3H).13C NMR(151MHz,CDCl3) δ 167.0,143.5,141.7,138.2,137.8,134.2,133.7,130.0,129.5,127.6,126.9,126.3,122.3,119.0,118.7,117.3,21.5,19.9,12.4,9.5.(ESI) calcd for C27H26N2O3S,[M+H]+459.1740, actual value 459.1737.
Example 16
(1)
(2)
A10 mL reaction tube was taken, weighed oxime ester compound 1r (0.12mmol), benzofuranimine compound 2a (0.1mmol) and CuI (0.02mmol) were added, DMSO/1,4-Dioxane (1mL) was added under the protection of inert gas, and the reaction tube was sealed with a plug of polytetrafluoroethylene. Placing the reaction tube in an oil bath kettle at 80 ℃ and stirring for 10 hours, cooling to room temperature after the reaction is finished, extracting with (20mL multiplied by 3) ethyl acetate for three times, washing with 40mL saturated saline solution, combining organic phases, removing the solvent by rotary evaporation to obtain a mixture containing 3qa, and then performing flash column chromatography to obtain a product 3qa with the yield of 42/79%.
1H NMR(600MHz,CDCl3)δ10.27(s,1H),10.22(s,1H),7.76(d,J＝7.4Hz,2H),7.65(d,J＝7.6Hz,2H),7.44(t,J＝7.5Hz,2H),7.34(t,J＝7.3Hz,1H),7.20(d,J＝7.8Hz,2H),7.02–6.86(m,5H),6.83(d,J＝7.3Hz,2H),6.58(d,J＝8.2Hz,1H),6.22(t,J＝7.5Hz,1H),2.52(d,J＝7.0Hz,2H),2.31(s,3H),1.25(m,1.20–1.28,1H),0.42(d,J＝6.5Hz,6H).13C NMR (151MHz, DMSO). delta. 164.0,139.0,133.3,132.8,132.7,129.7,129.6,127.4,125.4,124.9,124.3,123.8,123.0,123.0,122.3,121.8,118.8,118.4,117.2,115.3,114.3,112.7,28.6,23.9,17.4,16.8.(ESI) calculated value C34H32N2O3S,[M+H]+549.2206, actual value 549.2208.
Example 17
The procedure is as in example 1 to give the product 3ab in 97% yield.
1H NMR(600MHz,CDCl3)δ11.00(s,1H),10.77(s,1H),7.81(d,J＝8.0Hz,2H),7.75(d,J＝7.6Hz,2H),7.49(t,J＝7.6Hz,2H),7.39(t,J＝7.3Hz,1H),7.26–7.23(m,2H),7.10(dd,J＝14.4,7.2Hz,2H),6.96(t,J＝7.9Hz,1H),6.79–6.74(m,2H),6.61–6.54(m,2H),6.42(s,1H),6.30(t,J＝7.6Hz,1H),3.63(s,3H),2.36(s,3H).13C NMR(151MHz,CDCl3) Delta 168.7,160.5,159.1,144.1,138.7,137.9,137.4,135.7,135.2,134.3,130.3,129.6,129.3,129.0,128.8,127.0,125.1,121.3,119.1,117.4,113.8,113.2,109.8,55.1,21.5.(ESI) calcd for C31H26N2O4S,[M+H]+523.1686, actual value 523.1686.
Example 18
The procedure is as in example 1 to give product 3ac in 93% yield.
1H NMR(600MHz,CDCl3)δ11.08(s,1H),10.73(s,1H),7.82(d,J＝8.0Hz,2H),7.74(d,J＝7.6Hz,2H),7.48(t,J＝7.6Hz,2H),7.38(t,J＝7.3Hz,1H),7.26–7.23(m,2H),7.11(d,J＝7.8Hz,1H),7.08(t,J＝7.6Hz,1H),6.79–6.88(m,4H),6.72–6.77(m,2H),6.27(t,J＝7.5Hz,1H),2.36(s,3H),2.18(s,3H).13C NMR(151MHz,CDCl3) δ 168.8,160.7,144.0,138.7,138.1,137.5,136.4,134.9,134.6,131.4,130.4,129.6,129.3,128.7,128.6,127.0,125.0,122.3,119.4,119.0,117.5,109.8,21.5,21.0.(ESI) calcd for C31H26N2O3S,[M+H]+507.1736, actual value 507.1737.
Example 19
The procedure is as in example 1 to give the product 3ad in 82% yield.
1H NMR(600MHz,CDCl3)δ10.35–11.00(m,2H),7.74(d,J＝7.7Hz,2H),7.66(d,J＝7.6Hz,2H),7.42(t,J＝7.5Hz,2H),7.32(t,J＝7.2Hz,1H),7.21–7.17(m,2H),7.09(d,J＝8.3Hz,2H),7.06(d,J＝7.4Hz,1H),6.98(d,J＝6.9Hz,1H),6.75(d,J＝8.1Hz,2H),6.70(d,J＝8.3Hz,1H),6.66(d,J＝2.0Hz,1H),6.25(t,J＝7.5Hz,1H),2.30(s,3H).13C NMR(151MHz,CDCl3) Delta 167.3,143.2,137.8,136.4,135.4,134.3,133.1,132.4,130.1,129.2,128.7,128.3,127.8,126.0,124.1,121.5,120.0,118.2,116.7,108.7,20.5.(ESI) calculated value C30H23BrN2O3S,[M+H]+571.0688, practiceValue 571.0686.
Example 20
The procedure is as in example 1 to give product 3ae in 83% yield.
1H NMR(600MHz,CDCl3)δ10.45–11.50(m,2H),7.83(d,J＝7.0Hz,2H),7.73(d,J＝7.7Hz,2H),7.50(t,J＝7.5Hz,2H),7.41(t,J＝7.1Hz,1H),7.33(d,J＝7.8Hz,2H),7.29(d,J＝7.7Hz,2H),7.14(t,J＝7.5Hz,1H),7.08(d,J＝7.8Hz,2H),7.03(s,1H),6.78(d,J＝8.4Hz,2H),6.31(t,J＝7.5Hz,1H),2.39(s,3H).13C NMR(151MHz,CDCl3) Delta 168.0,144.4,139.3,138.9,137.3,135.6,133.9,131.7,129.9,129.7,129.4,129.1,129.0,127.0,125.1,119.2,118.7,117.8,110.2,109.7,21.5.(ESI) calculated value C31H23N3O3S,[M+H]+518.1531, actual value 518.1533.
Example 21
The procedure is as in example 1 to give the product 3af in 89% yield.1H NMR(600MHz,CDCl3)δ10.92(s,1H),10.42(s,1H),7.84(d,J＝7.2Hz,2H),7.75(d,J＝7.5Hz,2H),7.49(t,J＝7.6Hz,2H),7.39(t,J＝7.4Hz,1H),7.29(d,J＝7.8Hz,2H),7.08(d,J＝5.9Hz,1H),7.01(t,J＝7.4Hz,1H),6.95–6.87(m,3H),6.84(d,J＝6.9Hz,1H),6.70(d,J＝2.2Hz,1H),6.66(d,J＝8.2Hz,1H),6.29(t,J＝7.3Hz,1H),2.41(s,3H),2.18(s,3H).13C NMR(151MHz,CDCl3) δ 167.8,143.9,139.1,138.1,137.9,135.7,134.5,134.2,130.6,130.2,129.8,129.7,129.3,128.8,127.2,127.0,125.3,125.2,124.4,119.8,118.7,117.4,111.8,21.5,20.0.(ESI) calcd for C31H26N2O3S,[M+H]+507.1732, actual value 507.1737.
Example 22
The procedure is as in example 1 to give the product 3ag in 87% yield.
1H NMR(600MHz,CDCl3)δ12.28(s,1H),10.57(s,1H),7.78(d,J＝8.0Hz,2H),7.74(d,J＝7.7Hz,2H),7.49(t,J＝7.5Hz,2H),7.38(t,J＝7.4Hz,1H),7.22(d,J＝7.9Hz,2H),7.10–7.01(m,4H),6.91(d,J＝7.6Hz,2H),6.74(s,1H),6.25(s,1H),5.85(d,J＝9.1Hz,1H),3.67(s,3H),2.32(s,3H).13C NMR(151MHz,CDCl3) Delta 168.3,166.1,164.7,143.9,137.5,137.5,136.7,135.9,134.4,130.6,129.5,129.3,129.0,128.4,128.0,127.0,126.6,124.8,121.5,112.3,108.8,107.7,100.7,55.4,21.5.(ESI) calcd for C31H26N2O4S,[M+H]+523.1682, actual value 523.1686.
Example 23
The procedure is as in example 1 to give the product 3ah in 92% yield.
1H NMR(600MHz,CDCl3)δ11.14(s,1H),10.75(s,1H),7.86(d,J＝8.8Hz,2H),7.75(d,J＝7.4Hz,2H),7.49(t,J＝7.7Hz,2H),7.39(t,J＝7.4Hz,1H),7.13–7.08(m,1H),7.08–6.99(m,4H),6.96–6.93(m,2H),6.91(d,J＝8.9Hz,2H),6.73–6.78(m,2H),6.27(t,J＝7.6Hz,1H),3.80(s,3H).13C NMR (151MHz, DMSO) delta 163.9,158.6,156.0,133.8,133.0,130.4,129.7,129.6,127.2,125.6,124.6,124.5,124.0,123.3,122.0,120.3,117.6,114.6,114.2,112.7,109.5,105.0,50.9.(ESI) calculated C30H24N2O4S,[M+H]+509.1527, actual value 509.1530.
Example 24
The procedure is as in example 1 to give the product 3ai in 59% yield.
1H NMR(600MHz,CDCl3)δ10.65(s,1H),10.25(s,1H),8.07(d,J＝8.0Hz,2H),7.69–7.79(m,4H),7.51(t,J＝7.7Hz,2H),7.42(t,J＝7.4Hz,1H),7.12–7.00(m,5H),6.97(d,J＝7.3Hz,2H),6.79(d,J＝2.6Hz,1H),6.74(d,J＝8.1Hz,1H),6.30(t,J＝7.4Hz,1H).13C NMR(151MHz,CDCl3)δ167.6,158.7,143.1,138.7,138.4,134.2,133.1,129.0,128.4,128.1,127.7,127.0,126.5,125.9,125.1,125.1,124.2,122.0,121.2,118.7,118.4,116.6,109.8.19F NMR(565MHz,CDCl3) Delta-63.19 (ESI) calculation C30H21F3N2O3S,[M+H]+547.1298, actual value 547.1298.
Example 25
The procedure is as in example 1 to give the product 3aj in 85% yield.
1H NMR(600MHz,CDCl3)δ11.07(s,1H),10.69(s,1H),7.94(d,J＝7.3Hz,1H),7.74(d,J＝7.6Hz,2H),7.49(t,J＝7.7Hz,2H),7.40(q,J＝7.8Hz,2H),7.32(d,J＝7.5Hz,1H),7.20(t,J＝7.3Hz,1H),7.14–7.10(m,1H),7.09–7.04(m,3H),7.02(d,J＝6.9Hz,1H),6.99(d,J＝7.0Hz,2H),6.77–6.72(m,2H),6.27(t,J＝7.6Hz,1H),2.80(s,3H).13C NMR(151MHz,CDCl3) Delta 168.9,138.5,138.4,137.4,135.1,134.4,133.2,132.5,130.3,129.3,128.7,128.7,128.5,128.0,126.8,126.1,125.0,119.0,117.6,109.9,20.7.(ESI) calculated value C30H24N2O3S,[M+H]+493.1580, actual value 493.1580.
Claims (7)
1. A synthetic method of pyrrole compounds is characterized by comprising the following steps:
taking oxime ester compounds 1, benzofuranimine compounds 2,Adding organic solvent under inert protective gas, 60-120% of cuprous compoundoC, reacting under TLC, monitoring the reaction process by TLC, cooling to room temperature after the reaction is finished, extracting by ethyl acetate, washing by saturated saline solution, combining organic phases, removing a solvent by rotary evaporation to obtain a crude product, and performing flash column chromatography to obtain a pyrrole compound 3;
the reaction formula is as follows:
wherein R is1Is aryl, alkyl or ester group; r2Is H or alkyl; r3Is H or methoxy; r4Is aryl; r5Cyano, halogen, alkyl or alkoxy.
2. The method of claim 1, wherein: the mol ratio of the oxime ester compound 1 to the benzofuran imine compound 2 is 1: 1.2.
3. The method of claim 1, wherein: the reaction time was 16 hours.
4. The method of claim 1, wherein: the extraction is ethyl acetate extraction for 3 times.
5. The method of claim 1, wherein: the monovalent copper compound is CuCl, CuBr, CuI or CuOAc.
6. The method of claim 1, wherein: the organic solvent is dimethyl sulfoxide, tetrahydrofuran, 1,4-dioxane, toluene, N-dimethyl amide, 1, 2-dichloroethane or dichloromethane.
7. The method of claim 1, wherein: the inert protective gas is argon.
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| CN101321726A (en) * | 2005-09-30 | 2008-12-10 | 大日本住友制药株式会社 | Novel fused pyrrole derivative |
| CN102241618A (en) * | 2010-05-14 | 2011-11-16 | 北京大学 | Method for preparing 1,3,4-trisubstituted or 3,4-disubstituted pyrrole ring compounds |
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| CN102241618A (en) * | 2010-05-14 | 2011-11-16 | 北京大学 | Method for preparing 1,3,4-trisubstituted or 3,4-disubstituted pyrrole ring compounds |
| CN113336702A (en) * | 2021-06-01 | 2021-09-03 | 西南大学 | Preparation method of 2-amino fused pyridine compound |
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