CN107098902B - 一种吡咯并[1,2-a]喹啉衍生物的合成方法 - Google Patents
一种吡咯并[1,2-a]喹啉衍生物的合成方法 Download PDFInfo
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- CN107098902B CN107098902B CN201710435864.XA CN201710435864A CN107098902B CN 107098902 B CN107098902 B CN 107098902B CN 201710435864 A CN201710435864 A CN 201710435864A CN 107098902 B CN107098902 B CN 107098902B
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- pyrrolo
- quinoline
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- synthetic method
- amido
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- XLIQPEZVRBALDD-UHFFFAOYSA-N pyrrolo[1,2-a]quinoline Chemical compound C1=CC2=CC=CC=C2N2C1=CC=C2 XLIQPEZVRBALDD-UHFFFAOYSA-N 0.000 title claims abstract description 31
- 238000010189 synthetic method Methods 0.000 title claims abstract description 29
- 238000006243 chemical reaction Methods 0.000 claims abstract description 62
- 239000012074 organic phase Substances 0.000 claims abstract description 24
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims abstract description 21
- 238000004440 column chromatography Methods 0.000 claims abstract description 11
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 150000004820 halides Chemical class 0.000 claims abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000007858 starting material Substances 0.000 claims abstract description 4
- 238000005352 clarification Methods 0.000 claims abstract description 3
- 239000002274 desiccant Substances 0.000 claims abstract description 3
- 239000012071 phase Substances 0.000 claims abstract description 3
- 239000012266 salt solution Substances 0.000 claims abstract description 3
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 238000004809 thin layer chromatography Methods 0.000 claims description 14
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- -1 propiono Chemical group 0.000 claims description 12
- 239000000376 reactant Substances 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 8
- 239000013067 intermediate product Substances 0.000 claims description 7
- IHLVCKWPAMTVTG-UHFFFAOYSA-N lithium;carbanide Chemical compound [Li+].[CH3-] IHLVCKWPAMTVTG-UHFFFAOYSA-N 0.000 claims description 7
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 claims description 6
- 239000000758 substrate Substances 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 150000002790 naphthalenes Chemical class 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 claims description 2
- 229910052786 argon Inorganic materials 0.000 claims description 2
- 238000005815 base catalysis Methods 0.000 claims description 2
- 229910001873 dinitrogen Inorganic materials 0.000 claims description 2
- 235000019441 ethanol Nutrition 0.000 claims description 2
- 239000007789 gas Substances 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims 3
- 238000001035 drying Methods 0.000 claims 1
- 238000000926 separation method Methods 0.000 abstract description 19
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 230000007246 mechanism Effects 0.000 abstract description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 abstract description 4
- 125000005842 heteroatom Chemical group 0.000 abstract description 3
- 230000035484 reaction time Effects 0.000 abstract description 3
- 238000005516 engineering process Methods 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 238000001308 synthesis method Methods 0.000 abstract description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 239000007787 solid Substances 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 14
- 239000007788 liquid Substances 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 230000006837 decompression Effects 0.000 description 9
- 150000003233 pyrroles Chemical class 0.000 description 9
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 239000003208 petroleum Substances 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- MOMFXATYAINJML-UHFFFAOYSA-N 2-Acetylthiazole Chemical group CC(=O)C1=NC=CS1 MOMFXATYAINJML-UHFFFAOYSA-N 0.000 description 5
- 239000007832 Na2SO4 Substances 0.000 description 4
- 238000006555 catalytic reaction Methods 0.000 description 4
- BDJAEZRIGNCQBZ-UHFFFAOYSA-N methyl-cyclobutane Natural products CC1CCC1 BDJAEZRIGNCQBZ-UHFFFAOYSA-N 0.000 description 4
- 150000003248 quinolines Chemical class 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- MJBPUQUGJNAPAZ-UHFFFAOYSA-N Butine Natural products O1C2=CC(O)=CC=C2C(=O)CC1C1=CC=C(O)C(O)=C1 MJBPUQUGJNAPAZ-UHFFFAOYSA-N 0.000 description 3
- 229940126062 Compound A Drugs 0.000 description 3
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 125000003368 amide group Chemical group 0.000 description 3
- 239000001110 calcium chloride Substances 0.000 description 3
- 229910001628 calcium chloride Inorganic materials 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 2
- 229930013930 alkaloid Natural products 0.000 description 2
- 150000003797 alkaloid derivatives Chemical class 0.000 description 2
- 150000001345 alkine derivatives Chemical class 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 238000010719 annulation reaction Methods 0.000 description 2
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 2
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- QRDAPCMJAOQZSU-KQQUZDAGSA-N (e)-3-[4-[(e)-3-(3-fluorophenyl)-3-oxoprop-1-enyl]-1-methylpyrrol-2-yl]-n-hydroxyprop-2-enamide Chemical compound C1=C(\C=C\C(=O)NO)N(C)C=C1\C=C\C(=O)C1=CC=CC(F)=C1 QRDAPCMJAOQZSU-KQQUZDAGSA-N 0.000 description 1
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical class NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
- REDUQXCPUSNJOL-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(CN(C(C1=CC=C(C=C1)C(C)C)=O)CC1=CC=C(C=C1)C(NO)=O)=O Chemical compound C(C1=CC=CC=C1)NC(CN(C(C1=CC=C(C=C1)C(C)C)=O)CC1=CC=C(C=C1)C(NO)=O)=O REDUQXCPUSNJOL-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- CYSWUSAYJNCAKA-FYJFLYSWSA-N ClC1=C(C=CC=2N=C(SC=21)OCC)OC1=CC=C(C=N1)/C=C/[C@H](C)NC(C)=O Chemical compound ClC1=C(C=CC=2N=C(SC=21)OCC)OC1=CC=C(C=N1)/C=C/[C@H](C)NC(C)=O CYSWUSAYJNCAKA-FYJFLYSWSA-N 0.000 description 1
- QBXVXKRWOVBUDB-GRKNLSHJSA-N ClC=1C(=CC(=C(CN2[C@H](C[C@H](C2)O)C(=O)O)C1)OCC1=CC(=CC=C1)C#N)OCC1=C(C(=CC=C1)C1=CC2=C(OCCO2)C=C1)C Chemical compound ClC=1C(=CC(=C(CN2[C@H](C[C@H](C2)O)C(=O)O)C1)OCC1=CC(=CC=C1)C#N)OCC1=C(C(=CC=C1)C1=CC2=C(OCCO2)C=C1)C QBXVXKRWOVBUDB-GRKNLSHJSA-N 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 241000157865 Dendrobates Species 0.000 description 1
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 1
- 229910003767 Gold(III) bromide Inorganic materials 0.000 description 1
- 229910003803 Gold(III) chloride Inorganic materials 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 1
- 238000010958 [3+2] cycloaddition reaction Methods 0.000 description 1
- 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 1
- 230000004913 activation Effects 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- SRVFFFJZQVENJC-IHRRRGAJSA-N aloxistatin Chemical compound CCOC(=O)[C@H]1O[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)NCCC(C)C SRVFFFJZQVENJC-IHRRRGAJSA-N 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- QTCBDUJYMXZGJB-UHFFFAOYSA-N fluorobenzene formaldehyde Chemical compound C=O.FC1=CC=CC=C1 QTCBDUJYMXZGJB-UHFFFAOYSA-N 0.000 description 1
- 150000002240 furans Chemical class 0.000 description 1
- IQTIQAXNJBRKRG-IZDLKJCPSA-N gephyrotoxin Chemical compound C#C\C=C/C[C@H]1CCC[C@@H]2N3[C@@H](CCO)CC[C@H]3CC[C@@H]21 IQTIQAXNJBRKRG-IZDLKJCPSA-N 0.000 description 1
- IQTIQAXNJBRKRG-UHFFFAOYSA-N gephyrotoxin 287 C Natural products C#CC=CCC1CCCC2N3C(CCO)CCC3CCC21 IQTIQAXNJBRKRG-UHFFFAOYSA-N 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- OVWPJGBVJCTEBJ-UHFFFAOYSA-K gold tribromide Chemical compound Br[Au](Br)Br OVWPJGBVJCTEBJ-UHFFFAOYSA-K 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- QAPTWHXHEYAIKG-RCOXNQKVSA-N n-[(1r,2s,5r)-5-(tert-butylamino)-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](NC(C)(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 QAPTWHXHEYAIKG-RCOXNQKVSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 238000006772 olefination reaction Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000010970 precious metal Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229910001544 silver hexafluoroantimonate(V) Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
本发明公开一种吡咯并[1,2‑a]喹啉衍生物的合成方法,其以3‑胺基环丁烯酮类化合物和α卤代炔作为起始原料,溶于有机溶剂中,在碱性催化剂存在下反应,TLC监测反应进程;反应结束后,冷却至室温,向反应体系中加入饱和食盐水,再用萃取剂萃取,至水相澄清为止,合并有机相;有机相用干燥剂干燥,过滤,浓缩,柱层析,即获得吡咯并[l,2‑a]喹啉衍生物。本发明不需要经过中间体的分离,一步法合成高复杂结构的多元含氮稠杂环吡咯并[l,2‑a]喹啉衍生物,反应原料易得,便于操作,产品产率高,合成工艺更加简便,缩短了反应历程,降低了反应时间。
Description
技术领域
本发明属于化合物合成技术领域,尤其是涉及一种吡咯并[1,2-a]喹啉衍生物的合成方法。
背景技术
含氮稠杂环化合物通常具有独特的生物活性、毒性低和高内吸性,经常用作医药活性分子和农药的结构单元,此外,在染料、天然产物全合成以及高分子材料等领域也有着重要的应用。在含氮稠杂环中,取代的吡咯[l,2-a]喹啉及其氧化或还原形式的化合物为许多天然产物或生物活性化合物的母体结构,存在于具有生物活性的天然生物碱gephyrotoxin中,它是Daly于1977年从一种蛙类动物Dendrobates histrionics的分泌物中提取出来的生物碱(Helv.Chim.Acta 1974,57,2597)。研究表明它是一种毒蕈碱受体措抗药,表现出一系列神经生物活性,具有抗肿瘤、抗菌、抗真菌活性,因此它吸引了许多化学家的兴趣去开发各种合成方法。
1992年,Reinhoudt等报道了2-氟代苯甲醛、含有手性碳的吡咯以及丙二腈经由分子间取代,加成以及分子内成环反应合成了一系列具有光学活性的吡咯[l,2-a]喹啉类衍生物。2008年,Chen课题组开发了一价金催化的1,4-胺基炔和芳基炔参与的串联环化反应,构建了多取代的吡咯[l,2-a]喹啉衍生物(Angew.Chem.Int.Ed.,2008,47,3805.)。2009年,Lautens等报道了一类Pd催化的Suzuki-Miyaura偶联反应,利用二溴代烯烃分子直接芳基化反应合成了多取代的吡咯[l,2-a]喹啉化合物(J.Org.Chem.,2009,74,3054)。同年,Zhou等人采用AuBr3/AgSbF6催化含炔基的苯胺类化合物与炔的多级串连反应合成了多取代的吡咯[l,2-a]喹啉类衍生物(J.Org.Chem.2009,74,7344)。2013年,Umasish采用Fe(III)催化硝基烯烃、1,3-二羰基化合物、2-炔基苯胺衍生物的三组分偶联反应合成1-[2-(苯乙炔基)苯基]吡咯中间产物,再进一步通过AuCl3催化中间产物分子内炔基的芳基化反应合成了多官能化的吡咯[l,2-a]喹啉类化合物(Eur.J.Org.Chem.,2013,6055)。
近年来,研究人员也开发了氮叶立德杂环与缺电子的烯烃或炔烃的[3+2]环加成反应,多组分偶联反应,重排反应,以及分子间或分子内的烯基化反应等构建吡咯[l,2-a|喹啉衍生物。虽然在吡咯并[l,2-a]喹啉衍生物的合成方面人们已取得巨大的成就,但是很多的合成方法仍存在着不足之处,如:采用贵重金属催化剂、昂贵的配体、结构复杂且难得的化合物作为起始原料,反应物的普适性受限,合成步骤繁琐,并且需要微波或高温等苛刻反应条件,反应时间长,收率低等。
发明内容
为解决上述问题,本发明的目的是提供一种简洁高效、底物易得且具有多样化的取代基、反应条件温和的吡咯并[1,2-a]喹啉衍生物的合成方法。
为实现上述发明目的,本发明采用如下技术方案:
一种吡咯并[1,2-a]喹啉衍生物的合成方法,其包括以下步骤:
步骤1、将3-胺基环丁烯酮类化合物A和α卤代炔作为起始原料,两反应物按照摩尔比1∶(1~1.5)溶于有机溶剂中,在碱性催化剂存在下,在50~110℃的温度条件下搅拌2~4小时反应;用薄层层析TLC跟踪反应进程;至化合物A完全反应,并转化为中间产物M,由于中间产物M的极性与化合物A相近,在薄层层析时,用显色剂(香兰素(3g)/甲醇(50mL)+浓硫酸(0.5mL))区分化合物A与中间产物M;上述碱性催化剂与3-胺基环丁烯酮类化合物A的摩尔比为(1~2)∶1;
步骤2、继续反应4~6小时,50~110℃的温度下搅拌反应至所述中间产物M反应完全;反应结束后,冷却至室温,向反应体系中加入饱和食盐水以停止反应,再用萃取剂萃取,至水相澄清为止,合并有机相;有机相用干燥剂干燥,过滤,浓缩,柱层析,即获得吡咯并[l,2-a]喹啉衍生物B,吡咯并[l,2-a]喹啉衍生物B的极性比3-胺基环丁烯酮类化合物A的极性小。
上述的吡咯并[1,2-a]喹啉衍生物的合成方法中,所合成的吡咯并[1,2-a]喹啉衍生物具有如式(Ⅰ)所示的化学结构通式:
其中,R1为乙酰基、丙酰基、乙酯基、甲酯基或苯基;R2为C1-5烷基或苯基;R’为氢、C1-2烷基或卤素;R5为氢、苯基或三甲基硅基。
上述的吡咯并[1,2-a]喹啉衍生物的合成方法中,3-胺基环丁烯酮类化合物A具有如式(Ⅱ)所示的化学结构通式:
其中,R1为乙酰基、丙酰基、乙酯基、甲酯基、或苯基;R2为C1-5烷基或苯基;R3为苯基、C1-5烷基取代苯基、卤代苯基、萘基、C1-2取代萘基或卤代萘基;R4为氢。
上述的吡咯并[1,2-a]喹啉衍生物的合成方法中,α卤代炔为3-溴丙炔、3-氯丙炔、1-溴-2-丁炔或3-溴-1-三甲基硅基-1-丙炔。
上述的吡咯并[1,2-a]喹啉衍生物的合成方法中,有机溶剂为乙腈、二甲苯、四氢呋喃、N,N-二甲基甲酰胺、乙醇、甲醇、1,4-二氧六环、苯中的一种。
进一步地,上述的3-胺基环丁烯酮类化合物与有机溶剂的比例为1mmol/10~15ML。
上述的吡咯并[1,2-a]喹啉衍生物的合成方法中,碱性催化剂为氢氧化钠、氢氧化钾、叔丁醇钾、甲基锂、叔丁基锂、二异丙基氨基锂中的一种。
上述的吡咯并[1,2-a]喹啉衍生物的合成方法中,步骤2中采用的萃取剂为二氯甲烷、乙酸乙酯、正丁醇或氯仿。
上述的吡咯并[1,2-a]喹啉衍生物的合成方法中,碱性催化剂为甲基锂、叔丁基锂或二异丙基氨基锂时,反应体系必须是无水无氧,步骤1中采用的有机溶剂为干燥的二甲苯或四氢呋喃。
上述的吡咯并[1,2-a]喹啉衍生物的合成方法中,碱性催化剂为甲基锂、叔丁基锂或二异丙基氨基锂时,反应体系处于惰性气体氮气或氩气保护下。
上述的吡咯并[1,2-a]喹啉衍生物的合成方法中,吡咯并[1,2-a]喹啉衍生物为以下化合物之一:
上述的吡咯并[1,2-a]喹啉衍生物的合成方法中,3-胺基环丁烯酮类化合物为以下化合物之一:
本发明吡咯并[1,2-a]喹啉衍生物的合成方法,其反应式如下:
第一步:
第二步:
总反应过程:
由于采用如上所述的技术方案,本发明具有如下优越性:
本发明吡咯并[1,2-a]喹啉衍生物的合成方法,其反应原料易得,成本低廉,便于操作,产品产率高,合成工艺更加简便,缩短了反应历程,降低了反应时间。
本发明吡咯并[1,2-a]喹啉衍生物的合成方法,其采用的碱性催化剂均为无机碱,成本低廉,而且水溶性较好,后处理工序比较简单,避免了向反应中加入过渡金属催化剂,在一定程度上降低了重金属对环境的危害。
本发明吡咯并[1,2-a]喹啉衍生物的合成方法,其利用3-胺基环丁烯酮类化合物与α卤代炔在碱性催化体系中经由[3+2]成环反应/分子内电开环/再环合多米诺反应,不需要经过中间体的分离,一步法合成高复杂结构的多元含氮稠杂环吡咯并[l,2-a]喹啉衍生物。
具体实施方式
参照以下实施例可以对本发明作进一步详细说明;但是,以下实施例仅仅是例证,本发明并不局限于这些实施例。
实施例1
称取1.0mmol、229mg的2-丙酰基-3-苯胺基-4-甲基环丁烯酮1a、1mmol、0.08mL的3-溴丙炔、2.0mmol、80mg氢氧化钠置于25mL圆底烧瓶中,随后加入10mL乙腈,80℃搅拌8小时,TLC监测反应进程,直到反应物消失;反应结束后将反应液倒入20mL的饱和氯化钠溶液中,用二氯甲烷萃取三次(3×20mL),分液,合并有机相;有机相用无水Na2SO4干燥,减压蒸去溶剂,最后用石油醚和丙酮为展开剂,柱层析分离,得到白色固体目标化合物2a 254mg,产率为95%。
具体反应式为:
White solid(95%yield);1H NMR(400MHz,CDCI3)δ:1.50(t,J=8.0Hz,3H),3.31(q,J=6.5Hz,2H),2.58(s,3H),2.62(s,3H),6.57(s,1H),7.29(d,J=8.0Hz,1H),7.98(m,J=7.5Hz,1H),8.34(m,J=7.5Hz,1H),8.73(d,J=8.0Hz,1H),11.34(s,1H)。
实施例2
称取1.0mmol、231mg的2-甲酯基-3-苯胺基-4-甲基环丁烯酮1b、1mmol、0.08mL的3-溴丙炔、2mmol、0.224mg的叔丁醇钾置于25mL圆底烧瓶中,随后加入10mL N,N-二甲基甲酰胺,70℃搅拌7小时,TLC监测反应进程,直到反应物消失;反应结束后将反应液倒入30mL饱和氯化钠溶液中,用二氯甲烷萃取三次(3×20mL),分液,有机相用蒸馏水(20×2mL)反萃两次,合并有机相;有机相用无水MgSO4干燥,减压蒸去溶剂,柱层析分离,得到白色固体目标化合物2b 261mg,产率为97%。
具体反应式为:
White solid(97%yield);1H NMR(400MHz,CDCI3)δ:2.68(s,3H),2.74(s,3H),4.06(s,3H),7.08(s,1H),7.21(d,J=7.5Hz,1H),6.97(m,J=7.0Hz,1H),7.34(m,J=7.5Hz,1H),7.65(d,J=8.0Hz,1H),10.89(s,1H)。
实施例3
称取1.0mmol、215mg的2-乙酰基-3-苯胺基-4-甲基环丁烯酮1c,1mmol、0.08mL的3-氯丙炔、2.0mmol、48mg的氢化钠置于25mL圆底烧瓶中,随后加入10mL四氢呋喃,60℃搅拌8小时,TLC监测反应进程,直到反应物消失;反应结束后将反应液倒入25mL的饱和氯化钠溶液中,用二氯甲烷萃取三次(3×20mL),分液,合并有机相;有机相用无水Na2SO4干燥,减压蒸去溶剂,最后用石油醚和丙酮为展开剂,柱层析分离,得到白色固体目标化合物2c 238mg,产率为94%。
具体反应式为:
White solid(94%yield);1H NMR(400MHz,CDCI3)δ:2.43(s,3H),2.47(s,3H),2.56(s,3H),7.11(d,J=7.5Hz,1H),7.15(s,1H),6.89(m,J=7.0Hz,1H),6.94(m,J=7.0Hz,1H),7.39(d,J=8.0Hz,1H),11.01(s,1H)。
实施例4
称取1.0mmol、307mg的2-乙酰基-3-对溴甲苯胺基-4-甲基环丁烯酮1d、1mmol、0.08mL的3-溴丙炔、2.0mmol、48mg的氢化钠置于25mL圆底烧瓶中,随后加入10mL二甲苯,90℃搅拌6小时,TLC监测反应进程,直到反应物消失;反应结束后将反应液倒入20mL的饱和氯化钠溶液中,用乙酸乙酯萃取三次(3×20mL),分液,合并有机相;有机相用无水CaCl2干燥,减压蒸去溶剂,最后用石油醚和丙酮为展开剂,柱层析分离,得到白色固体目标化合物2d307mg,产率为89%。
具体反应式为:
White solid(89%yield);1H NMR(400MHz,CDCI3)δ:1.47(t,J=8.0Hz,3H),2.67(s,3H),2.71(s,3H),3.13(q,J=7.0Hz,2H),6.72(s,1H),7.31(d,J=8.0Hz,1H),7.71(s,1H),7.74(d,J=7.0Hz,1H),10.21(s,1H)。
实施例5
称取1.0mmol、279mg的2-乙酰基-3-奈胺基-4-甲基环丁烯酮1e、1mmol、0.08mL的3-溴代丙炔、2.0mmol、0.25mL的二异丙基氨基锂置于25mL圆底烧瓶中,随后加入10mL干燥二甲苯,氮气保护,60℃搅拌6h,TLC监测反应进程,直到反应物消失;反应结束后将反应液倒入20mL的饱和氯化钠溶液中,用正丁醇萃取三次(3×20mL),分液,合并有机相,有机相用无水CaCl2干燥,减压蒸去溶剂,最后用石油醚和丙酮为展开剂,柱层析分离,得到白色固体目标化合物2e 263mg,产率为83%。
具体反应式为:
White solid(83%yield);1H NMR(400MHz,CDCI3)δ:1.45(t,J=8.0Hz,3H),2.67(s,3H),2.71(s,3H),3.34(q,J=6.5Hz,2H),6.63(s,1H),7.13(d,J=7.5Hz,1H),7.43(d,J=7.0Hz,1H),7.98(d,J=7.0Hz,1H),8.03(m,J=8.0Hz,1H),8.05(m,J=7.5Hz,1H),8.12(d,J=7.5Hz,1H),11.51(s,1H)。
实施例6
称取1.0mmol、229mg的2-丙酰基-3-苯胺基-4-甲基环丁烯酮1f、1mmol、0.1mL的1-溴-2-丁炔、2.0mmol、80mg的氢氧化钠置于25mL圆底烧瓶中,随后加入15mL N,N-二甲基甲酰胺,70℃搅拌10小时,TLC监测反应进程,直到反应物消失;反应结束后将反应液倒入20mL的饱和氯化钠溶液中,用正丁醇萃取三次(3×20mL),分液,合并有机相,有机相用无水Na2SO4干燥,减压蒸去溶剂,最后用石油醚和丙酮为展开剂,柱层析分离,得到白色固体目标化合物2f 239mg,产率为85%。
具体反应式为:
White solid(85%yield);1H NMR(400MHz,CDCI3)δ:1.34(t,J=7.5Hz,3H),1.53(t,J=8.0Hz,3H),2.59(s,3H),2.61(q,J=7.0Hz,2H),2.74(q,J=7.5Hz,2H),2.71(s,3H),6.49(s,1H),6.89(d,J=7.5Hz,1H),7.01(m,J=7.0Hz,1H),7.37(m,J=7.0Hz,1H),7.98(d,J=7.5Hz,1H),11.42(s,1H)。
实施例7
称取1.0mmol、229mg的2-丙酰基-3-苯胺基-4-甲基环丁烯酮1g、1mmol、0.16mL的3-溴-1-三甲基硅基-1-丙炔、2.0mmol、48mg的氢化钠置于25mL圆底烧瓶中,随后加入15mL1,4-二氧六环,80℃搅拌8小时,TLC监测反应进程,直到反应物消失;反应结束后将反应液倒入20mL的饱和氯化钠溶液中,用氯仿萃取三次(3×20mL),分液,合并有机相,有机相用无水Na2SO4干燥,减压蒸去溶剂,最后用石油醚和丙酮为展开剂,柱层析分离,得到目标化合物2g 268mg,产率为79%。
具体反应式为:
White solid(79%yield);1H NMR(400MHz,CDCI3)δ:1.49(t,J=7.5Hz,3H),2.01(s,2H),261(s,3H),2.64(q,J=7.5Hz,2H),6.62(s,1H),7.56(m,J=7.5Hz,1H),7.77(m,J=7.0Hz,1H),8.14(d,J=7.5Hz,1H),8.26(d,J=7.5Hz,1H),11.17(s,1H)。
实施例8
称取1.0mmol、293mg的2-乙酰基-3-(6-甲基)奈胺基-4-甲基环丁烯酮1h、1mmol、0.08mL的3-溴丙炔、2.0mmol、224mg的叔丁醇钾置于25mL圆底烧瓶中,随后加入10mL N,N-二甲基甲酰胺;60℃搅拌9h,TLC监测反应进程,直到反应物消失;反应结束后将反应液倒入20mL的饱和氯化钠溶液中,用氯仿萃取三次(3×20mL),分液,有机相用蒸馏水(20×2mL)反萃两次,合并有机相,用无水CaCl2干燥,减压蒸去溶剂,最后用石油醚和丙酮为展开剂,柱层析分离,得到目标化合物2h 265mg,产率为80%。
具体反应式为:
White solid(80%yield);1H NMR(400MHz,CDCI3)δ:1.35(t,J=7.5Hz,3H),2.01(s,2H),2.23(s,3H),2.42(s,3H),2.78(q,J=7.5Hz,2H),6.73(s,1H),7.21(d,J=7.5Hz,1H),7.47(d,J=7.0Hz,1H),7.69(d,J=7.0Hz,1H),7.91(d,J=7.0Hz,1H),8.24(s,1H),10.93(s,1H)。
实施例9
称取1.0mmol、357mg的2-乙酰基-3-(6-溴)奈胺基-4-甲基环丁烯酮1i、1mmol、0.1mL的1-溴-2-丁炔置于25mL圆底烧瓶中,随后加入10mL干燥四氢呋喃,2.0mmol、0.05mL的甲基锂,氮气保护,60℃搅拌6h,TLC监测反应进程,直到反应物消失;反应结束后将反应液倒入20mL的饱和氯化钠溶液中,用二氯甲烷萃取三次(3×20mL),分液,合并有机相,用无水CaCl2干燥,减压蒸去溶剂,最后用石油醚和丙酮为展开剂,柱层析分离,得到目标化合物2i319mg,产率为78%。
具体反应式为:
White solid(78%yield);1H NMR(400MHz,CDCI3)δ:1.21(t,J=7.5Hz,3H),1.26(t,J=7.0Hz,3H),2.21(s,2H),2.42(q,J=7.5Hz,2H),2.47(q,J=7.0Hz,2H),6.69(s,1H),7.43(d,J=7.0Hz,1H),7.55(d,J=6.5Hz,1H),7.83(d,J=7.0Hz,1H),8.20(s,1H),8.44(d,J=6.5Hz,1H),9.92(s,1H)。
以上所述仅为本发明的较佳实施例而已,并不用以限制本发明,凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等,均应包含在本发明的保护范围之内。
Claims (7)
1.一种吡咯并[1,2-a]喹啉衍生物的合成方法,其特征是:其包括以下步骤:
步骤1、将3-胺基环丁烯酮类化合物和α卤代炔作为起始原料,两反应物按照摩尔比1∶(1~1.5)溶于有机溶剂中,在碱性催化剂存在下,在50~110℃的温度条件下搅拌2~4小时反应;用薄层层析TLC跟踪反应进程;至化合物完全反应,并转化为中间产物;上述碱性催化剂与3-胺基环丁烯酮类化合物的摩尔比为(1~2)∶1;
上述的3-胺基环丁烯酮类化合物具有如式(Ⅱ)所示的化学结构通式:
其中,R1为乙酰基、丙酰基、乙酯基、甲酯基、或苯基;R2为C1-5烷基或苯基;R3为苯基、C1-2烷基取代苯基、卤代苯基、萘基、C1-2烷基取代萘基或卤代萘基;R4为氢;
上述的α卤代炔为3-溴丙炔、3-氯丙炔或3-溴-1-三甲基硅基-1-丙炔;
步骤2、继续反应4~6小时,50~110℃的温度下搅拌反应至所述中间产物反应完全;反应结束后,冷却至室温,向反应体系中加入饱和食盐水,再用萃取剂萃取,至水相澄清为止,合并有机相;有机相用干燥剂干燥,过滤,浓缩,柱层析,即获得吡咯并[l,2-a]喹啉衍生物;当3-胺基环丁烯酮类化合物(Ⅱ)中的R3为苯基、C1-2烷基取代苯基、卤代苯基时,所合成的吡咯并[1,2-a]喹啉衍生物具有的化学结构通式为(Ⅰ);当3-胺基环丁烯酮类化合物中的R3为萘基、C1-2烷基取代萘基或卤代萘基时,所合成的吡咯并[1,2-a]喹啉衍生物具有的化学结构通式为(Ⅰ’):
其中,R1为乙酰基、丙酰基、乙酯基、甲酯基或苯基;R2为C1-5烷基或苯基;R’为氢、C1-2烷基或卤素;R5为氢或三甲基硅基。
2.根据权利要求1所述的吡咯并[1,2-a]喹啉衍生物的合成方法,其特征是:其有机溶剂为乙腈、二甲苯、四氢呋喃、N,N-二甲基甲酰胺、乙醇、甲醇、1,4-二氧六环、苯中的一种。
3.根据权利要求1所述的吡咯并[1,2-a]喹啉衍生物的合成方法,其特征是:其碱性催化剂为氢氧化钠、氢氧化钾、叔丁醇钾、甲基锂、叔丁基锂、二异丙基氨基锂中的一种。
4.根据权利要求3所述的吡咯并[1,2-a]喹啉衍生物的合成方法,其特征是:其碱性催化剂为甲基锂、叔丁基锂或二异丙基氨基锂时,步骤1中采用的有机溶剂为干燥的二甲苯或四氢呋喃。
5.根据权利要求3所述的吡咯并[1,2-a]喹啉衍生物的合成方法,其特征是:其碱性催化剂为甲基锂、叔丁基锂或二异丙基氨基锂时,反应体系处于惰性气体氮气或氩气保护下。
6.根据权利要求1所述的吡咯并[1,2-a]喹啉衍生物的合成方法,其特征是:其吡咯并[1,2-a]喹啉衍生物为以下化合物之一:
7.根据权利要求1所述的吡咯并[1,2-a]喹啉衍生物的合成方法,其特征是:其3-胺基环丁烯酮类化合物为以下化合物之一:
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