CN113683563A - 一种多取代3-磺酰胺喹啉化合物的合成方法 - Google Patents
一种多取代3-磺酰胺喹啉化合物的合成方法 Download PDFInfo
- Publication number
- CN113683563A CN113683563A CN202111008249.3A CN202111008249A CN113683563A CN 113683563 A CN113683563 A CN 113683563A CN 202111008249 A CN202111008249 A CN 202111008249A CN 113683563 A CN113683563 A CN 113683563A
- Authority
- CN
- China
- Prior art keywords
- nmr
- cdcl
- compound
- catalyst
- yield
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 229940124530 sulfonamide Drugs 0.000 title claims abstract description 14
- 238000001308 synthesis method Methods 0.000 title abstract description 5
- 239000000758 substrate Substances 0.000 claims abstract description 40
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims abstract description 15
- 229910052737 gold Inorganic materials 0.000 claims abstract description 15
- 239000010931 gold Substances 0.000 claims abstract description 15
- 238000013508 migration Methods 0.000 claims abstract description 9
- 230000005012 migration Effects 0.000 claims abstract description 9
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims description 44
- 238000006243 chemical reaction Methods 0.000 claims description 29
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 27
- 239000003054 catalyst Substances 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 11
- 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
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 230000015572 biosynthetic process Effects 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 229910003803 Gold(III) chloride Inorganic materials 0.000 claims description 8
- RJHLTVSLYWWTEF-UHFFFAOYSA-K gold trichloride Chemical compound Cl[Au](Cl)Cl RJHLTVSLYWWTEF-UHFFFAOYSA-K 0.000 claims description 8
- 238000003786 synthesis reaction Methods 0.000 claims description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- -1 methoxy, 3, 4-methylenedioxy Chemical group 0.000 claims description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 6
- UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 229910003771 Gold(I) chloride Inorganic materials 0.000 claims description 4
- FDWREHZXQUYJFJ-UHFFFAOYSA-M gold monochloride Chemical compound [Cl-].[Au+] FDWREHZXQUYJFJ-UHFFFAOYSA-M 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 3
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 3
- 229910019032 PtCl2 Inorganic materials 0.000 claims description 3
- UCYRAEIHXSVXPV-UHFFFAOYSA-K bis(trifluoromethylsulfonyloxy)indiganyl trifluoromethanesulfonate Chemical compound [In+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F UCYRAEIHXSVXPV-UHFFFAOYSA-K 0.000 claims description 3
- 239000010949 copper Substances 0.000 claims description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 3
- HSYLTRBDKXZSGS-UHFFFAOYSA-N silver;bis(trifluoromethylsulfonyl)azanide Chemical compound [Ag+].FC(F)(F)S(=O)(=O)[N-]S(=O)(=O)C(F)(F)F HSYLTRBDKXZSGS-UHFFFAOYSA-N 0.000 claims description 3
- 230000002194 synthesizing effect Effects 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 229910001544 silver hexafluoroantimonate(V) Inorganic materials 0.000 claims 1
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 abstract description 3
- 230000003197 catalytic effect Effects 0.000 abstract description 2
- 238000010189 synthetic method Methods 0.000 abstract description 2
- 125000000304 alkynyl group Chemical group 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 127
- 239000000047 product Substances 0.000 description 36
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 31
- 238000005160 1H NMR spectroscopy Methods 0.000 description 31
- 238000002360 preparation method Methods 0.000 description 31
- 150000001875 compounds Chemical class 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 238000004293 19F NMR spectroscopy Methods 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 238000006555 catalytic reaction Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- QKLXBIHSGMPUQS-FGZHOGPDSA-M (3r,5r)-7-[4-(4-fluorophenyl)-2,5-dimethyl-1-phenylpyrrol-3-yl]-3,5-dihydroxyheptanoate Chemical compound CC1=C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)C(C=2C=CC(F)=CC=2)=C(C)N1C1=CC=CC=C1 QKLXBIHSGMPUQS-FGZHOGPDSA-M 0.000 description 2
- 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 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 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 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 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 2
- 238000011160 research Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 150000003456 sulfonamides Chemical class 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- VPMIAOSOTOODMY-KJAPKAAFSA-N (4r)-6-[(e)-2-[6-tert-butyl-4-(4-fluorophenyl)-2-propan-2-ylpyridin-3-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C([C@H](O)C1)C(=O)OC1/C=C/C=1C(C(C)C)=NC(C(C)(C)C)=CC=1C1=CC=C(F)C=C1 VPMIAOSOTOODMY-KJAPKAAFSA-N 0.000 description 1
- UTOIEVWJKDLJGE-AQRBRUGDSA-N (4r,6s)-6-[(e)-2-[4-(4-fluorophenyl)-2,6-di(propan-2-yl)pyrimidin-5-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C=1C=C(F)C=CC=1C1=NC(C(C)C)=NC(C(C)C)=C1\C=C\[C@@H]1C[C@@H](O)CC(=O)O1 UTOIEVWJKDLJGE-AQRBRUGDSA-N 0.000 description 1
- 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
- AEUAEICGCMSYCQ-UHFFFAOYSA-N 4-n-(7-chloroquinolin-1-ium-4-yl)-1-n,1-n-diethylpentane-1,4-diamine;dihydrogen phosphate Chemical compound OP(O)(O)=O.ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 AEUAEICGCMSYCQ-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
- FHKPLLOSJHHKNU-INIZCTEOSA-N [(3S)-3-[8-(1-ethyl-5-methylpyrazol-4-yl)-9-methylpurin-6-yl]oxypyrrolidin-1-yl]-(oxan-4-yl)methanone Chemical compound C(C)N1N=CC(=C1C)C=1N(C2=NC=NC(=C2N=1)O[C@@H]1CN(CC1)C(=O)C1CCOCC1)C FHKPLLOSJHHKNU-INIZCTEOSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- KSCRVOKQPYZBHZ-IXPOFIJOSA-N benzyl n-[(2s)-1-[[(2s)-1-[[(2s)-1-(1,3-benzothiazol-2-yl)-1-oxo-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C[C@H]1C(NCC1)=O)C(=O)C=1SC2=CC=CC=C2N=1)C(C)C)C(=O)OCC1=CC=CC=C1 KSCRVOKQPYZBHZ-IXPOFIJOSA-N 0.000 description 1
- 229960001701 chloroform Drugs 0.000 description 1
- 229960002328 chloroquine phosphate Drugs 0.000 description 1
- IVHBBMHQKZBJEU-UHFFFAOYSA-N cinchocaine hydrochloride Chemical compound [Cl-].C1=CC=CC2=NC(OCCCC)=CC(C(=O)NCC[NH+](CC)CC)=C21 IVHBBMHQKZBJEU-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 229940045574 dibucaine hydrochloride Drugs 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003454 indenyl group Chemical class C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 150000004010 onium ions Chemical class 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000006049 ring expansion reaction Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/38—Nitrogen atoms
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/056—Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明公开了一种多取代3‑磺酰胺喹啉化合物的合成方法，通过金催化叠氮基团对炔基的进攻，形成α‑亚胺金卡宾中间体；在α‑亚胺中间体的作用下引发1,2‑N迁移，从而形成多取代3‑磺酰胺喹啉化合物。本发明的合成方法具有高效性以及对底物的普适性强等优点。
Description
技术领域
本发明属于有机化学领域，具体涉及一种多取代3-磺酰胺喹啉化合物的合成方法。
背景技术
均相的金催化具有催化活性高、反应条件温和、官能团相融性好等优点，且通过叠氮化物对炔的进攻和随后的N2的排出形成α-亚胺金卡宾中间体。而喹啉是一种重要的精细化工原料，主要用于合成医药、染料、农药等。由于喹啉环上的氮原子具有碱性，可以与强酸形成稳定的盐。例如盐酸地步卡因是一种很好的麻醉药，磷酸氯喹是一种很好的抗疟疾药。
Toste等人(Journal of the American Chemical Society,2005,127(32):11260-11261)最先报道α-亚胺金卡宾，他们首次报道了关于用金催化剂催化分子内氮烯烃的转移，合成多取代的吡咯化合物，合成路线如下：
由于1,2-N迁移很少有人报道，在2014年Davies等人(Chem.Eur.J.2014,20,7262-7266) 报道了第一个例子，1,2-N迁移到金碳烯上，高选择性地通过1,1-碳烷氧基化的炔酰胺合成多取代的茚。
在2015年Liu等人(Chem.Eur.J.2015,21,18571-18575)报道一种高效的金催化氧化扩环反应，其中包括1,2-N迁移。
上述现有技术尽管通过金催化然后通过1,2-N迁移形成最终产物，然而，由α-亚胺金卡宾中间体引发的1,2-N迁移尚未有人报道。因此金催化的新方法仍然具有很大的挑战，对构建多官能团化的结构需求很大。
发明内容
由于α-亚胺金卡宾引发的1,2-N迁移尚未有人报道，本发明的目的在于提供一种高效的和对底物有很好普适性的多取代3-磺酰胺喹啉的合成方法。
本发明多取代3-磺酰胺喹啉化合物的合成方法，反应底物在金催化剂的作用下形成α-亚胺金卡宾中间体，通过1.2-N迁移形成3-磺酰胺喹啉化合物。
反应路线如下所示：
上述通式中：R1选自苯基或取代苯基、烷基或3-噻吩基，其中取代苯基的取代基选自甲基、甲氧基、卤素、三氟甲基、叔丁基或-CO2Me；R2选自甲基、甲氧基、3,4-亚甲基二氧基或卤素；R3选自苯基、取代苯基或甲基，其中取代苯基的取代基选自甲基、甲氧基、卤素、三氟甲基、叔丁基或-CO2Me。
具体包括如下步骤：
将0.1mmol的反应底物和0.02mmol的催化剂加入到3mL的溶剂中，在30-90℃下反应 72小时，得到目标产物。
由于不同的催化剂对反应的产率影响很大，通过对AuCl、AuCl3、tBuXPhosAuNTf2、JohnPhosAuNTf2、tBuXPhosAuSbF6、JohnPhosAuSbF6、ZnI2、(CH3COO)2Cu·H2O、 AuCl3/AgsbF6、AuCl3/AgNTf2、PtCl2、三氟甲磺酸铟、六氟磷酸四乙腈铜、醋酸钯/三苯基膦催化剂的研究，本发明优选催化剂为tBuXPhosAuNTf2。
进一步，通过对1,2-二氯乙烷、二氯甲烷、三氯甲烷、乙腈、1,4-二氧六环、苯、甲苯、丙酮、四氢呋喃、DMF有机溶剂的研究，本发明优选丙酮作为反应溶剂。
进一步，由于温度对反应产率有很大的影响，通过对30-90℃的筛选，本发明优选75℃为最佳的反应温度。
本发明为了验证底物的普适性，在上述最优的条件下进一步提供炔基不同取代基1a-1q 在金催化下的反应，反应路线和对应产物如下所示：
反应过程将0.1mmol的1a-1q和0.02mmol的催化剂加入到3mL的有机溶剂中，在75℃下反应72小时。在该反应中，具有不同取代基团基的底物1a-1q都适用于该反应，得到相应多取代的3-磺酰胺喹啉化合物。在苯基部分引入给电子取代基(1a-f)，产率相对较高；而苯环上带有吸电子基(1g-m)，产率中等及以上；含有杂原子的噻吩，长链己基、叔丁基和环己基 (1n-1q)也能得到反应。
另外，本发明还验证当底物叠氮取代基的苯基上取代基的变化，本发明的方法也具有良好的适用性。
反应过程将0.1mmol的1r-1y和0.02mmol的催化剂加入到3mL的有机溶剂中，在75℃下反应72小时。
可以看出无论取代基的位置及电子性质如何变化，本发明的反应在最优的条件下都能够顺利进行，且都能得到中等至良好的产率，得到相应多取代的3-磺酰胺喹啉化合物。
为了深入验证本发明合成方法对各种底物具有广泛的应用性，本实验还研究与磺酰胺相连的基团对反应的影响。
反应过程将0.1mmol的1z-1e'和0.02mmol的催化剂加入到3mL的有机溶剂中，在75℃下反应72小时。
可以看出无论与磺酰胺相连的苯环上取代基电子性质如何变化，本发明的反应在最优的条件下都能够顺利进行，且都能得到中等至良好的产率。当与磺酰胺相连的基团为甲基也能得到很好的反应，都能得到相应多取代的3-磺酰胺喹啉化合物。
具体实施方式
以下通过具体的实施方式，对本发明的上述内容做进一步的详细说明，但不应该将此理解为对本发明保护主体的任何限制。凡基于本发明上述内容所实现的技术方案均属于本发明的范围。本发明对试验中所使用到的材料以及试验方法进行一般性和/或具体的描述。
首先对催化剂的筛选，在Schlenk管中分别加入0.02mmolAuCl、AuCl3、tBuXPhosAuNTf2、 JohnPhosAuNTf2、tBuXPhosAuSbF6、JohnPhosAuSbF6、ZnI2、(CH3COO)2Cu·H2O、 AuCl3/AgsbF6、AuCl3/AgNTf2、PtCl2、三氟甲磺酸铟、六氟磷酸四乙腈铜、醋酸钯/三苯基膦催化剂。抽真空并充入氮气，使用注射器在室温下将溶于3mL 1,2-二氯乙烷的1a40.2mg加入到Schlenk管中，将管密封，混合物加热到75℃反应72小时。减压蒸发溶剂，残留物通过硅胶柱色谱纯化，石油醚/乙酸乙酯＝10/1～30/1，得到白色产物2a，产率分别为18％、30％、 64％、56％、60％、55％、15％、23％、28％、36％、15％、0、0、0。可以看出tBuXPhosAuNTf2是最优的催化剂。
在最优的催化剂tBuXPhosAuNTf2条件下，对反应溶剂进行筛选。将tBuXPhosAuNTf218 mg加入到烘箱烘干的Schlenk管中；抽真空并充入氮气，使用注射器在室温下将1a40.2mg 分别溶于3mL二氯甲烷、乙腈、1,4-二氧六环、苯、甲苯、丙酮、四氢呋喃、DMF加入到Schlenk管中，将管密封，混合物加热到75℃反应72小时。减压蒸发溶剂，残留物通过硅胶柱色谱纯化，石油醚/乙酸乙酯＝10/1～30/1，得到白色产物2a，产率分别为51％、42％、51％、40％、50％、80％、66％、45％。可以看出丙酮是最优的溶剂。
在最优的催化剂和溶剂的条件下对反应温度进行筛选。将tBuXPhosAuNTf2 18mg加入到烘箱烘干的Schlenk管中；抽真空并充入氮气，使用注射器在室温下将被3mL丙酮溶解的1a 40.2mg加入到Schlenk管中，将管密封，混合物分别加热到60℃、75℃、90℃反应72小时。减压蒸发溶剂，残留物通过硅胶柱色谱纯化，石油醚/乙酸乙酯＝10/1～30/1，得到白色产物2a，产率80％。产率分别为46％、80％、64％。可以看出最佳的反应温度为75℃。
综上所述，可以得出在tBuXPhosAuNTf2作为催化剂，丙酮为溶剂，反应温度为75℃时，反应效果是最好的。
实施例1：化合物2a的制备
将tBuXPhosAuNTf2 18mg加入到烘箱烘干的Schlenk管中。抽真空并充入氮气，使用注射器在室温下将被3mL丙酮溶解的1a 40.2mg加入到Schlenk管中，将管密封，混合物加热到75℃反应72小时。减压蒸发溶剂，残留物通过硅胶柱色谱纯化，石油醚/乙酸乙酯＝10/1～ 30/1，得到白色产物2a，产率80％。
1H NMR(400MHz,CDCl3)δ8.47(s,1H),8.03(d,J＝8.3Hz,1H),7.86(dd,J＝8.2,1.4Hz, 1H),7.66(ddd,J＝8.5,6.9,1.5Hz,1H),7.60–7.54(m,1H),7.50(d,J＝8.3Hz,2H),7.47–7.40 (m,3H),7.18(d,J＝8.1Hz,2H),7.14–7.10(m,2H),6.80(s,1H),2.38(s,3H).13CNMR(101 MHz,CDCl3)δ152.17,144.05,143.40,135.53,134.73,128.81,128.38,128.30,128.16,128.13, 127.36,126.67,126.47,126.34,126.09,125.23,20.53.HRMS(ESI)m/z(M+H)+calculated for C22H19N2O2S:375.1167,observed:375.1174.
实施例2：化合物2b的制备
用底物1b代替1a，通过实施例1的方法，制备得到白色产物2b，产率84％。
1H NMR(600MHz,CDCl3)δ8.49(s,1H),8.01(d,J＝8.8Hz,1H),7.87(d,J＝8.1Hz,1H), 7.68–7.62(m,1H),7.59–7.53(m,3H),7.38(td,J＝7.6,1.4Hz,1H),7.31(d,J＝7.6Hz,1H), 7.20(t,J＝7.8Hz,3H),6.75(d,J＝7.3Hz,1H),6.48(s,1H),2.37(s,3H),1.89(s,3H).13C NMR (101MHz,CDCl3)δ152.99,144.83,144.54,136.65,135.78,135.26,131.26,129.85,129.73, 129.14,128.91,128.42,127.72,127.51,127.39,127.25,126.67,124.37,21.58,19.14.HRMS(ESI) m/z(M+H)+calculated for C23H21N2O2S:389.1324,observed:389.1332.
实施例3：化合物2c的制备
用底物1c代替1a，通过实施例1的方法，制备得到白色产物2c，产率53％。
1H NMR(600MHz,CDCl3)δ8.48(s,1H),8.03(d,J＝8.4Hz,1H),7.86(d,J＝7.6Hz,1H), 7.66(t,J＝7.5Hz,1H),7.56(ddd,J＝8.1,6.9,1.2Hz,1H),7.48(d,J＝8.1Hz,2H),7.31(t,J＝ 7.6Hz,1H),7.25(d,J＝7.0Hz,1H),7.18(d,J＝8.1Hz,2H),6.90(d,J＝7.4Hz,1H),6.84(s, 1H),6.81(s,1H),2.37(s,3H),2.34(s,3H).13C NMR(101MHz,CDCl3)δ153.56,145.09,144.34, 139.22,136.44,135.82,130.19,129.82,129.19,129.17,129.15,128.98,128.41,127.70,127.52, 127.32,127.13,126.36,125.22,21.59,21.48.RMS(ESI)m/z(M+H)+calculated for C23H21N2O2S: 389.1324,observed:389.1332.
实施例4：化合物2d的制备
用底物1d代替1a，通过实施例1的方法，制备得到白色产物2d，产率91％。
1H NMR(400MHz,CDCl3)δ8.44(s,1H),8.02(d,J＝8.2Hz,1H),7.85(d,J＝7.8Hz,1H), 7.65(ddd,J＝8.4,6.9,1.5Hz,1H),7.58–7.52(m,3H),7.26–7.21(m,2H),7.19(d,J＝8.1Hz, 2H),7.03(d,J＝8.1Hz,2H),6.83(s,1H),2.43(s,3H),2.38(s,3H).13C NMR(101MHz,CDCl3) δ153.18,145.04,144.44,139.51,135.77,133.57,130.01,129.82,129.17,129.01,128.52,128.31, 127.64,127.45,127.25,127.17,125.61,21.59,21.38.HRMS(ESI)m/z(M+H)+calculated for C23H21N2O2S:389.1324,observed:389.1332.
实施例5：化合物2e的制备
用底物1e代替1a，通过实施例1的方法，制备得到白色产物2e，产率85％。
1H NMR(600MHz,CDCl3)δ8.43(s,1H),8.02(d,J＝8.4Hz,1H),7.84(d,J＝8.1Hz,1H), 7.64(t,J＝7.5Hz,1H),7.55(t,J＝7.9Hz,3H),7.45(d,J＝8.0Hz,2H),7.19(d,J＝8.0Hz,2H), 7.11(d,J＝8.0Hz,2H),6.92(s,1H),2.38(s,3H),1.37(s,9H).13C NMR(151MHz,CDCl3)δ 153.12,152.55,145.05,144.38,135.72,133.56,129.82,129.16,128.99,128.45,128.07,127.60, 127.42,127.23,127.13,126.34,125.61,34.80,31.25,21.59.HRMS(ESI)m/z(M+H)+calculated for C26H27N2O2S:431.1793,observed:431.1788.
实施例6：化合物2f的制备
用底物1f代替1a，通过实施例1的方法，制备得到白色产物2f，产率91％。
1H NMR(600MHz,CDCl3)δ8.42(s,1H),8.01(d,J＝8.4Hz,1H),7.84(d,J＝8.1Hz,1H), 7.64(t,J＝7.7Hz,1H),7.54(d,J＝7.8Hz,3H),7.19(d,J＝8.0Hz,2H),7.10(d,J＝8.3Hz,2H), 6.95(d,J＝8.7Hz,2H),6.85(s,1H),3.87(s,3H),2.37(s,3H).13C NMR(101MHz,CDCl3)δ 159.40,151.82,144.01,143.37,134.78,128.82,128.79,128.07,127.96,127.74,127.51,126.52, 126.38,126.14,126.10,124.61,113.71,54.45,20.54.HRMS(ESI)m/z(M+H)+calculated for C23H21N2O3S:405.1273,observed:405.1269.
实施例7：化合物2g的制备
用底物1g代替1a，通过实施例1的方法，制备得到白色产物2g，产率83％。
1H NMR(600MHz,CDCl3)δ8.45(s,1H),8.02(d,J＝8.4Hz,1H),7.87(d,J＝7.5Hz,1H), 7.68(t,J＝7.6Hz,1H),7.58(t,J＝7.8Hz,1H),7.52(d,J＝8.3Hz,2H),7.20(d,J＝8.1Hz,2H), 7.15–7.09(m,4H),6.68(s,1H),2.39(s,3H).13C NMR(151MHz,Chloroform-d)δ163.24(d,J＝ 250.2Hz),152.26,145.12,144.54,135.82,132.68(d,J＝3.5Hz),130.52,130.47,129.87,129.34, 129.11,128.26,127.69,127.51,127.07,126.88,116.33(d,J＝21.9Hz),21.58.19F NMR(564MHz, CDCl3)δ-111.16.RMS(ESI)m/z(M+H)+calculated forC22H18FN2O2S:393.1076,observed: 393.1079.
实施例8：化合物2h的制备
用底物1h代替1a，通过实施例1的方法，制备得到白色产物2h，产率62％。
1H NMR(400MHz,CDCl3)δ8.49(s,1H),8.03(d,J＝8.4Hz,1H),7.89(d,J＝9.5Hz,1H),7.72 –7.65(m,1H),7.62–7.55(m,1H),7.45(d,J＝8.3Hz,2H),7.42–7.37(m,1H),7.18(d,J＝8.1 Hz,2H),7.16–7.11(m,1H),6.96(d,J＝6.3Hz,1H),6.68–6.63(m,1H),2.39(s,3H).13C NMR (101MHz,CDCl3)δ163.03(d,J＝249.0Hz),152.22,145.26,144.67,138.78(d,J＝7.4Hz), 135.68,130.90(d,J＝8.3Hz),129.95,129.56,129.22,128.07,128.00,127.83,127.65(d,J＝5.1 Hz),127.02,123.85,116.41(d,J＝21.2Hz),115.97(d,J＝22.4Hz),21.55.19F NMR(564MHz, CDCl3)δ-110.69.RMS(ESI)m/z(M+H)+calculated forC22H18FN2O2S:393.1076,observed: 393.1079.
实施例9：化合物2i的制备
用底物1i代替1a，通过实施例1的方法，制备得到白色产物2i，产率67％。
1H NMR(600MHz,DMSO-d6)δ10.11(s,1H),8.16(s,1H),8.02–7.97(t,2H),7.77(t,J＝ 7.8Hz,1H),7.66–7.60(t,1H),7.38(d,J＝8.1Hz,2H),7.28(t,J＝9.1Hz,1H),7.23(d,J＝7.9 Hz,2H),7.14(d,J＝8.1Hz,2H),2.34(s,3H).13C NMR(101MHz,DMSO-d6)δ161.83(dd,J＝ 245.5,13.4Hz),154.28,145.32,143.09,141.55(t,J＝9.9Hz),137.13,134.53,130.14,129.60, 128.73,128.26,127.68,127.65,127.39,126.42,112.52(dd,J＝19.1,8.2Hz),103.75(t,J＝25.5 Hz),20.93.19F NMR(377MHz,CDCl3)δ-105.76.RMS(ESI)m/z(M+H)+calculated for C22H18F2N2O2S:411.0979,observed:411.0984.
实施例10：化合物2j的制备
用底物1j代替1a，通过实施例1的方法，制备得到白色产物2j，产率63％。
1H NMR(400MHz,CDCl3)δ8.46(s,1H),8.02(d,J＝8.2Hz,1H),7.87(d,J＝8.7Hz,1H),7.68 (ddd,J＝8.4,6.9,1.5Hz,1H),7.62–7.57(m,1H),7.52(d,J＝8.3Hz,2H),7.42–7.37(m,2H), 7.20(d,J＝8.1Hz,2H),7.10–7.05(m,2H),6.65(s,1H),2.39(s,3H).13C NMR(101MHz, CDCl3)δ152.16,145.24,144.61,135.85,135.69,135.10,129.94,129.92,129.46,129.19,128.20, 127.77,127.62,127.57,127.17,127.11,21.61.HRMS(ESI)m/z(M+H)+calculated for C22H18ClN2O2S:409.0778,observed:409.0786.
实施例11：化合物2k的制备
用底物1j代替1a，通过实施例1的方法，制备得到白色产物2j，产率65％。
1H NMR(600MHz,CDCl3)δ8.46(s,1H),8.01(d,J＝8.4Hz,1H),7.87(d,J＝8.1Hz,1H),7.68 (t,J＝7.6Hz,1H),7.57(dd,J＝21.4,8.0Hz,3H),7.52(d,J＝8.1Hz,2H),7.20(d,J＝8.1Hz, 2H),7.01(d,J＝8.2Hz,2H),6.63(s,1H),2.39(s,3H).13C NMR(101MHz,CDCl3)δ152.17, 145.24,144.59,135.83,135.55,132.39,130.16,129.90,129.44,129.18,128.12,127.75,127.61, 127.55,127.20,127.08,123.89,21.59.HRMS(ESI)m/z(M+H)+calculated for C22H18BrN2O2S: 453.0254,observed:453.0275.
实施例12：化合物2l的制备
用底物1l代替1a，通过实施例1的方法，制备得到白色产物2l，产率51％。
1H NMR(600MHz,CDCl3)δ8.48(s,1H),8.03(d,J＝8.4Hz,1H),7.89(d,J＝8.2Hz,1H),7.71 (t,J＝7.7Hz,1H),7.66(d,J＝7.9Hz,2H),7.61(t,J＝7.6Hz,1H),7.49(d,J＝8.0Hz,2H),7.27 (d,J＝9.2Hz,2H),7.19(d,J＝7.9Hz,2H),6.62(s,1H),2.40(s,3H).13CNMR(101MHz,CDCl3) δ152.13,145.39,144.65,140.41,135.85,131.53,131.20,129.95,129.70,129.25,129.10,128.25, 128.18(q,J＝203.2Hz),128.00,127.87,127.84,127.63,127.06,126.07(q,J＝3.6Hz),21.59.19F NMR(377MHz,CDCl3)δ-62.80.RMS(ESI)m/z(M+H)+calculated for C23H18F3N2O2S: 443.1041,observed:443.1046.
实施例13：化合物2m的制备
用底物1m代替1a，通过实施例1的方法，制备得到白色产物2m，产率37％。
1H NMR(600MHz,DMSO-d6)δ8.50(s,1H),8.09(d,J＝7.9Hz,2H),8.04(d,J＝8.5Hz,1H), 7.89(d,J＝8.2Hz,1H),7.70(t,J＝7.7Hz,1H),7.60(t,J＝7.5Hz,1H),7.48(d,J＝8.1Hz,2H), 7.20(dd,J＝8.2,3.9Hz,4H),3.99(s,3H),2.40(s,3H).13C NMR(101MHz,CDCl3)δ168.81, 166.37,152.35,144.63,141.07,135.74,130.87,130.38,129.93,129.52,129.23,128.64,128.11, 127.83,127.72,127.60,127.50,127.05,52.46,21.59.RMS(ESI)m/z(M+H)+calculated for C24H21N2O2S:401.1324,observed:401.1328.
实施例14：化合物2n的制备
用底物1n代替1a，通过实施例1的方法，制备得到白色产物2n，产率40％。
1H NMR(600MHz,CDCl3)δ8.40(s,1H),8.01(d,J＝8.4Hz,1H),7.83(d,J＝8.1Hz,1H), 7.65(t,J＝7.2Hz,1H),7.58(d,J＝8.1Hz,2H),7.57–7.53(m,1H),7.47(dd,J＝4.9,2.9Hz,1H), 7.28(d,J＝1.7Hz,1H),7.20(d,J＝8.0Hz,2H),7.07(d,J＝4.4Hz,1H),6.92(s,1H),2.37(s, 3H).13C NMR(151MHz,CDCl3)δ148.50,145.12,144.48,137.59,135.87,129.89,129.13, 129.09,128.54,127.71,127.67,127.57,127.42,127.36,127.06,126.03,125.67,21.56.RMS(ESI) m/z(M+H)+calculated for C20H17N2O2S2:381.0731,observed:381.0736.
实施例15：化合物2o的制备
用底物1o代替1a，通过实施例1的方法，制备得到白色产物2o，产率47％。
1H NMR(600MHz,CDCl3)δ8.21(s,1H),7.95(d,J＝8.4Hz,1H),7.76(d,J＝8.2Hz,1H), 7.63(dd,J＝14.8,8.0Hz,3H),7.48(t,J＝7.4Hz,1H),7.21(d,J＝8.0Hz,2H),6.86(s,1H),2.66 –2.58(m,2H),2.36(s,3H),1.52(p,J＝7.8Hz,2H),1.28(dt,J＝14.8,7.4Hz,3H),1.24–1.18 (m,3H),0.86(t,J＝7.1Hz,3H).13C NMR(151MHz,cdcl3)δ156.25,145.57,144.35,136.16, 129.87,129.04,128.53,128.51,128.41,127.45,127.10,127.06,126.46,34.12,31.64,29.25,28.27, 22.53,21.52,14.06.HRMS(ESI)m/z(M+H)+calculated for C22H27N2O2S:383.1793,observed: 383.1798.
实施例16：化合物2p的制备
用底物1p代替1a，通过实施例1的方法，制备得到白色产物2p，产率40％。
1H NMR(600MHz,CDCl3)δ8.22(s,1H),7.96(d,J＝8.4Hz,1H),7.77(d,J＝8.2Hz,1H), 7.63(t,J＝7.6Hz,1H),7.60(d,J＝8.1Hz,2H),7.51–7.45(m,1H),7.22(d,J＝8.0Hz,2H),6.80 (s,1H),2.46(tt,J＝11.7,3.4Hz,1H),2.36(s,3H),1.76(d,J＝12.6Hz,2H),1.69(d,J＝11.8Hz, 1H),1.62(q,J＝12.4Hz,2H),1.32(d,J＝13.3Hz,2H),1.30–1.22(m,1H),1.24–1.16(m, 1H).13C NMR(101MHz,CDCl3)δ160.56,146.21,144.29,136.17,130.85,129.86,129.11,128.86, 127.54,127.38,127.16,126.79,126.36,40.48,31.78,26.44,25.77,21.52.RMS(ESI)m/z(M+H)+ calculated for C22H25N2O2S:381.1637,observed:381.1641.
实施例17：化合物2q的制备
用底物1q代替1a，通过实施例1的方法，制备得到白色产物2q，产率47％。
1H NMR(600MHz,CDCl3)δ8.28(s,1H),7.93(d,J＝8.4Hz,1H),7.71(d,J＝8.2Hz,3H),7.62 –7.57(m,1H),7.48(d,J＝7.4Hz,1H),7.21(d,J＝8.0Hz,2H),6.87(s,1H),2.35(s,3H),1.41(s, 9H).13C NMR(101MHz,CDCl3)δ158.84,144.46,144.02,136.19,129.80,129.18,129.15,128.48, 127.43,126.83,126.73,125.99,38.21,29.86,21.56.RMS(ESI)m/z(M+H)+calculated for C20H23N2O2S:355.1480,observed:355.1485.
实施例18：化合物2r的制备
用底物1r代替1a，通过实施例1的方法，制备得到白色产物2r，产率71％。
1H NMR(600MHz,CDCl3)δ8.58(s,1H),7.88(d,J＝8.4Hz,1H),7.57–7.53(m,1H),7.51 (d,J＝8.1Hz,2H),7.44(dt,J＝14.0,6.9Hz,3H),7.39(d,J＝7.0Hz,1H),7.19(d,J＝8.0Hz, 2H),7.15(d,J＝6.5Hz,2H),6.82(s,1H),2.72(s,3H),2.38(s,3H).13C NMR(151MHz,CDCl3) δ152.56,145.34,144.43,136.57,135.66,134.41,129.81,129.35,129.30,128.84,128.40,127.99, 127.68,127.37,127.21,127.10,123.16,21.57,18.82.RMS(ESI)m/z(M+H)+calculated for C23H21N2O2S:389.1324,observed:389.1329.
实施例19：化合物2s的制备
用底物1s代替1a，通过实施例1的方法，制备得到白色产物2s，产率54％。
1H NMR(600MHz,CDCl3)δ8.38(s,1H),7.92(d,J＝8.5Hz,1H),7.62(s,1H),7.49(d,J＝ 8.2Hz,3H),7.43(dt,J＝14.2,7.0Hz,3H),7.18(d,J＝8.0Hz,2H),7.11(d,J＝6.6Hz,2H),6.76 (s,1H),2.55(s,3H),2.38(s,3H).13C NMR(151MHz,CDCl3)δ152.24,144.33,143.73,137.38, 136.67,135.78,131.49,129.78,129.26,128.83,128.40,128.32,127.74,127.10,126.27,125.69, 21.66,21.55.RMS(ESI)m/z(M+H)+calculated forC23H21N2O2S:389.1324,observed:389.1329.
实施例20：化合物2t的制备
用底物1t代替1a，通过实施例1的方法，制备得到白色产物2t，产率79％。
1H NMR(600MHz,CDCl3)δ8.42(s,1H),7.69(d,J＝8.1Hz,1H),7.51(t,J＝7.6Hz,3H), 7.48–7.43(m,4H),7.21(d,J＝6.7Hz,2H),7.17(d,J＝8.0Hz,2H),6.85(s,1H),2.72(s,3H), 2.37(s,3H).13C NMR(151MHz,CDCl3)δ151.52,144.30,144.27,137.33,137.15,135.80, 129.80,129.17,129.13,129.12,128.69,128.01,127.62,127.14,127.10,126.37,125.43,21.56, 17.82.RMS(ESI)m/z(M+H)+calculated for C23H21N2O2S:389.1324,observed:389.1329.
实施例21：化合物2u的制备
用底物1u代替1a，通过实施例1的方法，制备得到白色产物2u，产率59％。
1H NMR(400MHz,CDCl3)δ8.38(s,1H),7.91(d,J＝9.2Hz,1H),7.49(d,J＝8.2Hz,2H), 7.46–7.38(m,3H),7.30(dd,J＝9.2,2.8Hz,1H),7.18(d,J＝8.0Hz,2H),7.12–7.07(m,3H), 6.77(s,1H),3.96(s,3H),2.38(s,3H).13C NMR(101MHz,CDCl3)δ158.48,150.56,144.41, 141.29,136.67,135.82,130.63,129.85,129.30,129.23,128.93,128.70,128.48,127.10,125.21, 122.16,104.74,55.67,21.60.RMS(ESI)m/z(M+H)+calculatedfor C23H21N2O3S:405.1273, observed:405.1278.
实施例22：化合物2v的制备
用底物1v代替1a，通过实施例1的方法，制备得到白色产物2v，产率52％。
1H NMR(400MHz,CDCl3)δ8.42(s,1H),7.76(d,J＝9.0Hz,1H),7.47–7.35(m,6H),7.24 (dd,J＝9.0,2.6Hz,1H),7.16(d,J＝8.0Hz,2H),7.05(d,J＝6.9Hz,2H),6.69(s,1H),3.91(s, 3H),2.38(s,3H).13C NMR(101MHz,CDCl3)δ160.76,153.75,146.99,144.26,136.84,135.80, 129.79,129.22,128.56,128.30,127.83,127.11,126.46,122.88,120.79,107.09,55.59,21.58.RMS (ESI)m/z(M+H)+calculated for C23H21N2O3S:405.1273,observed:405.1278.
实施例23：化合物2w的制备
用底物1w代替1a，通过实施例1的方法，制备得到白色产物2w，产率76％。
1H NMR(600MHz,CDCl3)δ8.31(s,1H),7.40(dt,J＝24.1,7.6Hz,5H),7.30(s,1H),7.16 (d,J＝8.0Hz,2H),7.10(s,1H),7.04(d,J＝7.3Hz,2H),6.67(s,1H),6.11(s,2H),2.38(s,3H). 13C NMR(151MHz,CDCl3)δ150.87,150.71,148.56,144.23,143.49,136.72,135.75,129.74, 129.17,129.07,128.37,127.06,127.01,126.74,124.88,105.60,102.44,101.86,21.55.RMS(ESI) m/z(M+H)+calculated for C23H19N2O4S:419.1066,observed:419.1071.
实施例24：化合物2x的制备
用底物1x代替1a，通过实施例1的方法，制备得到白色产物2x，产率52％。
1H NMR(600MHz,CDCl3)δ8.38(s,1H),8.01(dd,J＝9.2,5.3Hz,1H),7.54(d,J＝8.1Hz, 2H),7.51–7.39(m,5H),7.21(d,J＝8.0Hz,2H),7.16(d,J＝7.6Hz,2H),6.81(s,1H),2.39(s, 3H).13C NMR(151MHz,CDCl3)δ161.03(d,J＝249.5Hz),152.19,144.59,142.02,136.23, 135.68,131.72(d,J＝9.5Hz),129.89,129.55,129.41,129.22,128.47(d,J＝10.6Hz),128.37, 127.12,124.60(d,J＝5.6Hz),119.27(d,J＝25.9Hz),110.41(d,J＝22.3Hz),21.58.19F NMR (564MHz,CDCl3)δ-112.09.RMS(ESI)m/z(M+H)+calculatedfor C22H18FN2O2S:393.1073, observed:393.1078.
实施例25：化合物2y的制备
用底物1y代替1a，通过实施例1的方法，制备得到白色产物2y，产率91％。
1H NMR(600MHz,CDCl3)δ8.34(s,1H),7.95(d,J＝8.9Hz,1H),7.83(d,J＝2.3Hz,1H), 7.57(dd,J＝8.9,2.3Hz,1H),7.54(d,J＝8.2Hz,2H),7.47(dt,J＝14.3,7.1Hz,3H),7.22(d,J＝ 8.0Hz,2H),7.17(d,J＝6.7Hz,2H),6.83(s,1H),2.39(s,3H).13C NMR(151MHz,CDCl3)δ 153.07,144.62,143.24,136.15,135.64,133.20,130.76,129.93,129.91,129.64,129.43,129.30, 128.34,128.31,127.12,125.96,124.23,21.58.RMS(ESI)m/z(M+H)+calculated for C22H18ClN2O2S:409.0778,observed:409.0783.
实施例26：化合物2z的制备
用底物1z代替1a，通过实施例1的方法，制备得到白色产物2z，产率80％。
1H NMR(600MHz,CDCl3)δ8.50(s,1H),8.03(d,J＝8.4Hz,1H),7.88(d,J＝7.5Hz,1H), 7.68(t,J＝7.6Hz,1H),7.57(dt,J＝22.6,7.5Hz,4H),7.46(t,J＝7.3Hz,1H),7.44–7.38(m, 4H),7.08(d,J＝6.9Hz,2H),6.78(s,1H).13C NMR(101MHz,CDCl3)δ153.34,145.21,138.76, 136.54,133.43,129.43,129.38,129.31,129.28,129.24,128.33,128.19,127.70,127.55,127.44, 127.05,126.74.RMS(ESI)m/z(M+H)+calculated forC21H17N2O2S:361.1011,observed: 361.1016.
实施例27：化合物2a'的制备
用底物1a'代替1a，通过实施例1的方法，制备得到白色产物2a'，产率82％。
1H NMR(600MHz,CDCl3)δ8.46(s,1H),8.05(d,J＝8.4Hz,1H),7.88(d,J＝8.8Hz,1H), 7.69(t,J＝7.8Hz,1H),7.62–7.54(m,3H),7.45(dq,J＝14.1,7.2,6.8Hz,3H),7.15–7.10(m, 2H),7.04(t,J＝8.5Hz,2H),6.85(s,1H).13C NMR(101MHz,CDCl3)δ165.45(d,J＝256.4Hz), 153.53,145.36,136.67,134.86(d,J＝3.0Hz),129.85,129.76,129.48,129.47,129.40,129.30, 128.30,128.02,127.67,127.53,127.38,116.53(d,J＝22.7Hz),77.38,77.06,76.74.19F NMR(377 MHz,CDCl3)δ-103.63.RMS(ESI)m/z(M+H)+calculatedfor C21H16FN2O2S:379.0917, observed:379.0923.
实施例28：化合物2b'的制备
用底物1b'代替1a，通过实施例1的方法，制备得到白色产物2b'，产率86％。
1H NMR(600MHz,CDCl3)δ8.46(s,1H),8.05(d,J＝8.4Hz,1H),7.88(d,J＝8.2Hz,1H), 7.70(t,J＝7.6Hz,1H),7.59(t,J＝7.6Hz,1H),7.46(dq,J＝14.5,7.4,6.8Hz,5H),7.33(d,J＝ 8.5Hz,2H),7.13(d,J＝6.6Hz,2H),6.87(s,1H).13C NMR(101MHz,CDCl3)δ153.55,145.47, 140.04,137.18,136.58,129.59,129.54,129.48,129.41,129.31,128.42,128.27,127.78,127.72, 127.63,127.57.RMS(ESI)m/z(M+H)+calculated forC21H16ClN2O2S:395.0621,observed: 395.0626.
实施例29：化合物2c'的制备
用底物1c'代替1a，通过实施例1的方法，制备得到白色产物2c'，产率81％。
1H NMR(600MHz,CDCl3)δ8.46(s,1H),8.05(d,J＝8.4Hz,1H),7.88(d,J＝8.2Hz,1H), 7.70(t,J＝7.8Hz,1H),7.59(t,J＝7.5Hz,1H),7.51–7.42(m,5H),7.38(d,J＝8.3Hz,2H),7.12 (d,J＝7.8Hz,2H),6.87(s,1H).13C NMR(101MHz,CDCl3)δ153.56,145.47,137.69,136.55, 132.51,129.60,129.46,129.40,129.30,128.54,128.45,128.25,127.86,127.67,127.61,127.56. RMS(ESI)m/z(M+H)+calculated for C21H16BrN2O2S:439.0116,observed:439.0121.
实施例30：化合物2d'的制备
用底物1d'代替1a，通过实施例1的方法，制备得到白色产物2d'，产率80％。
1H NMR(600MHz,CDCl3)δ8.51(s,1H),8.04(d,J＝8.4Hz,1H),7.89(d,J＝8.1Hz,1H), 7.68(t,J＝7.9Hz,1H),7.58(t,J＝7.6Hz,1H),7.50(d,J＝8.4Hz,2H),7.44(d,J＝7.4Hz,1H), 7.40(d,J＝8.0Hz,4H),7.03(d,J＝6.8Hz,2H),6.76(s,1H),1.31(s,9H).13CNMR(101MHz, CDCl3)δ157.41,153.49,145.20,136.63,135.78,129.37,129.31,129.26,129.22,128.39,128.33, 127.78,127.62,127.40,126.99,126.90,126.29,35.24,31.05.RMS(ESI)m/z(M+H)+calculated for C25H25N2O2S:417.1637,observed:417.1642.
实施例31：化合物2e'的制备
用底物1e'代替1a，通过实施例1的方法，制备得到白色产物2e'，产率74％。
1H NMR(600MHz,CDCl3)δ8.37(s,1H),8.10(d,J＝8.4Hz,1H),7.85(d,J＝8.2Hz,1H), 7.69(t,J＝7.0Hz,1H),7.56(ddd,J＝23.5,15.9,6.8Hz,6H),6.78(s,1H),2.93(s,3H).13C NMR (151MHz,CDCl3)δ152.51,145.05,136.77,129.72,129.64,129.25,129.21,128.60,128.59, 128.55,127.69,127.60,127.34,124.62,39.79.RMS(ESI)m/z(M+H)+calculated for C16H15N2O2S: 299.0854,observed:299.0859。
Claims (7)
1.一种多取代3-磺酰胺喹啉化合物的合成方法，其特征在于：
反应底物在金催化剂的作用下形成α-亚胺金卡宾中间体，通过1.2-N迁移形成3-磺酰胺喹啉化合物；反应路线如下所示：
上述通式中：
上述通式中：R1选自苯基或取代苯基、烷基或3-噻吩基，其中取代苯基的取代基选自甲基、甲氧基、卤素、三氟甲基、叔丁基或-CO2Me；R2选自甲基、甲氧基、3,4-亚甲基二氧基或卤素；R3选自苯基、取代苯基或甲基，其中取代苯基的取代基选自甲基、甲氧基、卤素、三氟甲基、叔丁基或-CO2Me。
2.根据权利要求1所述的合成方法，其特征在于包括如下步骤：
将0.1mmol的反应底物和0.02mmol的催化剂加入溶剂中，在30-90℃下反应72小时，得到目标产物。
3.根据权利要求2所述的合成方法，其特征在于：
所述催化剂包括AuCl、AuCl3、tBuXPhosAuNTf2、JohnPhosAuNTf2、tBuXPhosAuSbF6、JohnPhosAuSbF6、ZnI2、(CH3COO)2Cu·H2O、AuCl3/AgSbF6、AuCl3/AgNTf2、PtCl2、三氟甲磺酸铟、六氟磷酸四乙腈铜或醋酸钯/三苯基膦催化剂。
4.根据权利要求3所述的合成方法，其特征在于：
所述催化剂为tBuXPhosAuNTf2。
5.根据权利要求2所述的合成方法，其特征在于：
所述溶剂包括1,2-二氯乙烷、二氯甲烷、三氯甲烷、乙腈、1,4-二氧六环、苯、甲苯、丙酮、四氢呋喃或DMF。
6.根据权利要求5所述的合成方法，其特征在于：
所述溶剂为丙酮。
7.根据权利要求2所述的合成方法，其特征在于：
反应温度为75℃。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111008249.3A CN113683563B (zh) | 2021-08-31 | 2021-08-31 | 一种多取代3-磺酰胺喹啉化合物的合成方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111008249.3A CN113683563B (zh) | 2021-08-31 | 2021-08-31 | 一种多取代3-磺酰胺喹啉化合物的合成方法 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113683563A true CN113683563A (zh) | 2021-11-23 |
| CN113683563B CN113683563B (zh) | 2024-01-30 |
Family
ID=78584244
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111008249.3A Active CN113683563B (zh) | 2021-08-31 | 2021-08-31 | 一种多取代3-磺酰胺喹啉化合物的合成方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113683563B (zh) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104334527A (zh) * | 2012-02-22 | 2015-02-04 | 桑福德-伯纳姆医学研究院 | 磺酰胺化合物及作为tnap抑制剂的用途 |
| KR20210088789A (ko) * | 2020-01-06 | 2021-07-15 | 성균관대학교산학협력단 | 아민화된 아진의 신규한 제조방법 |
-
2021
- 2021-08-31 CN CN202111008249.3A patent/CN113683563B/zh active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104334527A (zh) * | 2012-02-22 | 2015-02-04 | 桑福德-伯纳姆医学研究院 | 磺酰胺化合物及作为tnap抑制剂的用途 |
| KR20210088789A (ko) * | 2020-01-06 | 2021-07-15 | 성균관대학교산학협력단 | 아민화된 아진의 신규한 제조방법 |
Non-Patent Citations (3)
| Title |
|---|
| XIAN-FENG CAI等: "Chiral Phosphoric Acid-Catalyzed Asymmetric Transfer Hydrogenation of Quinolin-3-amines", 《ORG. LETT.》, vol. 16, pages 2680 - 2683 * |
| XIANG WU等: "Access to 3‑Sulfonamidoquinolines by Gold-Catalyzed Cyclization of 1‑(2′-Azidoaryl)propargylsulfonamides through 1, 2‑N Migration", 《J. ORG. CHEM.》, vol. 87, pages 801 - 812 * |
| 郑琅琅: "金催化叠氮芳基炔丙醇化合物合 成多取代4-喹诺酮的研究", 《中国优秀硕士学位论文全文数据库 工程科技I辑》, no. 2, pages 014 - 389 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113683563B (zh) | 2024-01-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5766717B2 (ja) | Ｒｏｍｐとｒｃｍ反応に対する高効率複分解触媒 | |
| Mojumdar et al. | [1] Benzofuro [3, 2-c] pyridine synthesis and coordination reactions | |
| Jin et al. | Assembly of functionalized π-extended indolizine polycycles through dearomative [3+ 2] cycloaddition/oxidative decarbonylation | |
| CN109369629B (zh) | β-内酰胺衍生物的制备方法 | |
| WO2008059771A1 (fr) | Procédé de production d'un dérivé du fullerène | |
| CN109438317B (zh) | 一种氮-烷基（氘代烷基）芳杂环和烷基（氘代烷基）芳基醚类化合物的制备方法 | |
| CN110330485B (zh) | 一类茚并异喹啉类化合物及其制备方法 | |
| EP2147923A1 (en) | Method for producing aromatic compound | |
| CN113683563A (zh) | 一种多取代3-磺酰胺喹啉化合物的合成方法 | |
| CN108164493B (zh) | 一种芳香聚酮类化合物及其制备方法 | |
| CN115785122A (zh) | 一种吲哚衍生哌啶类化合物及其合成方法 | |
| CN106883229B (zh) | 一种3-羟基咪唑并[1,2-a]吡啶衍生物的制备方法 | |
| CN113045496B (zh) | 选择性合成二氢菲啶或菲啶类化合物的方法 | |
| CN113004294B (zh) | 一种四氢呋喃并1,4-二氢喹啉类化合物及其制备方法和应用 | |
| CN108047128A (zh) | 一种合成(e)-2-甲基-4-苯基-6-苯乙烯基取代吡啶化合物的方法 | |
| CN110872295B (zh) | 一种合成咪唑并[1,2-a]吲哚类化合物的方法 | |
| CN110669006A (zh) | 茚并异喹啉类化合物及其制备方法 | |
| CN114773252B (zh) | 一种手性氨基吲哚啉衍生物及其制备方法和用途 | |
| CN112480049B (zh) | 一种茚酮并[1,2-c]呋喃类化合物的合成方法 | |
| CN110117246B (zh) | 一种3-位吲哚化环己烯酮化合物的制备方法 | |
| CN112239425B (zh) | 一种阿朴菲生物碱及其中间体的制备方法 | |
| KR102628273B1 (ko) | 아세트아미드 작용기를 포함하는 테트라하이드로퀴놀린 유도체 제조방법 및 이를 이용하여 제조된 테트라하이드로퀴놀린 유도체 | |
| CN108276266B (zh) | 一种蒽环类化合物及其制备方法 | |
| CN114349684B (zh) | 一种苯并[c,d]吲哚亚胺衍生物的合成方法 | |
| CN114478516B (zh) | 3,4-二氢-2h-喹嗪-2-酮类化合物及其制备方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |