CN112010886A - 一种吡咯并噁嗪环类化合物及其制备方法 - Google Patents
一种吡咯并噁嗪环类化合物及其制备方法 Download PDFInfo
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- CN112010886A CN112010886A CN201910475356.3A CN201910475356A CN112010886A CN 112010886 A CN112010886 A CN 112010886A CN 201910475356 A CN201910475356 A CN 201910475356A CN 112010886 A CN112010886 A CN 112010886A
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- Prior art keywords
- silver
- gold
- compound
- room temperature
- sodium
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- 150000001875 compounds Chemical class 0.000 title claims description 16
- 238000002360 preparation method Methods 0.000 title abstract description 7
- -1 pyrrolooxazine ring compound Chemical class 0.000 claims abstract description 76
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 55
- 239000000243 solution Substances 0.000 claims description 43
- 229940125904 compound 1 Drugs 0.000 claims description 31
- 238000006243 chemical reaction Methods 0.000 claims description 28
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 20
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 10
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052737 gold Inorganic materials 0.000 claims description 8
- 239000010931 gold Substances 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 125000002971 oxazolyl group Chemical group 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 5
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- 229910052709 silver Inorganic materials 0.000 claims description 4
- 239000004332 silver Substances 0.000 claims description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 3
- 239000005708 Sodium hypochlorite Substances 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- CZKMPDNXOGQMFW-UHFFFAOYSA-N chloro(triethyl)germane Chemical compound CC[Ge](Cl)(CC)CC CZKMPDNXOGQMFW-UHFFFAOYSA-N 0.000 claims description 3
- KENFWULSTODHHA-UHFFFAOYSA-N cyclohexyl butanoate;silver Chemical compound [Ag].CCCC(=O)OC1CCCCC1 KENFWULSTODHHA-UHFFFAOYSA-N 0.000 claims description 3
- WRZZIMVMWOQUES-UHFFFAOYSA-N gold(1+);triphenylphosphane Chemical compound [Au+].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 WRZZIMVMWOQUES-UHFFFAOYSA-N 0.000 claims description 3
- IFPWCRBNZXUWGC-UHFFFAOYSA-M gold(1+);triphenylphosphane;chloride Chemical compound [Cl-].[Au+].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 IFPWCRBNZXUWGC-UHFFFAOYSA-M 0.000 claims description 3
- GCWCLHMEYZKZRO-UHFFFAOYSA-M gold(1+);tris(2,4-ditert-butylphenyl) phosphite;chloride Chemical compound [Au]Cl.CC(C)(C)C1=CC(C(C)(C)C)=CC=C1OP(OC=1C(=CC(=CC=1)C(C)(C)C)C(C)(C)C)OC1=CC=C(C(C)(C)C)C=C1C(C)(C)C GCWCLHMEYZKZRO-UHFFFAOYSA-M 0.000 claims description 3
- 150000002466 imines Chemical class 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 239000011736 potassium bicarbonate Substances 0.000 claims description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 3
- IWOLVLSIZCEOHM-UHFFFAOYSA-M silver;dibenzyl phosphate Chemical compound [Ag+].C=1C=CC=CC=1COP(=O)([O-])OCC1=CC=CC=C1 IWOLVLSIZCEOHM-UHFFFAOYSA-M 0.000 claims description 3
- 239000001632 sodium acetate Substances 0.000 claims description 3
- 235000017281 sodium acetate Nutrition 0.000 claims description 3
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 claims description 3
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims description 3
- 239000001488 sodium phosphate Substances 0.000 claims description 3
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 3
- 229910052979 sodium sulfide Inorganic materials 0.000 claims description 3
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 claims description 3
- GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 3
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
- 229930029653 phosphoenolpyruvate Natural products 0.000 claims description 2
- DTBNBXWJWCWCIK-UHFFFAOYSA-N phosphoenolpyruvic acid Chemical compound OC(=O)C(=C)OP(O)(O)=O DTBNBXWJWCWCIK-UHFFFAOYSA-N 0.000 claims description 2
- 238000000746 purification Methods 0.000 claims description 2
- 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 2
- LWGRABKSXOHZKA-UHFFFAOYSA-M silver;diphenyl phosphate Chemical compound [Ag+].C=1C=CC=CC=1OP(=O)([O-])OC1=CC=CC=C1 LWGRABKSXOHZKA-UHFFFAOYSA-M 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims 2
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims 2
- 235000011181 potassium carbonates Nutrition 0.000 claims 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 2
- 229910019142 PO4 Inorganic materials 0.000 claims 1
- 239000002585 base Substances 0.000 claims 1
- ASMQGLCHMVWBQR-UHFFFAOYSA-M diphenyl phosphate Chemical compound C=1C=CC=CC=1OP(=O)([O-])OC1=CC=CC=C1 ASMQGLCHMVWBQR-UHFFFAOYSA-M 0.000 claims 1
- 238000000605 extraction Methods 0.000 claims 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 1
- 239000010452 phosphate Substances 0.000 claims 1
- HCJTYESURSHXNB-UHFFFAOYSA-N propynamide Chemical compound NC(=O)C#C HCJTYESURSHXNB-UHFFFAOYSA-N 0.000 claims 1
- 238000010791 quenching Methods 0.000 claims 1
- 230000000171 quenching effect Effects 0.000 claims 1
- 235000017550 sodium carbonate Nutrition 0.000 claims 1
- 235000011008 sodium phosphates Nutrition 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 38
- 230000015572 biosynthetic process Effects 0.000 abstract description 35
- 230000001766 physiological effect Effects 0.000 abstract description 3
- 229930014626 natural product Natural products 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 84
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 58
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 48
- 229910052757 nitrogen Inorganic materials 0.000 description 30
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- 239000000741 silica gel Substances 0.000 description 28
- 229910002027 silica gel Inorganic materials 0.000 description 28
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
- 239000007787 solid Substances 0.000 description 28
- 238000005160 1H NMR spectroscopy Methods 0.000 description 24
- FOAVQZHGNGLPNA-UHFFFAOYSA-N CC1=CC=C(C=C1)S(=O)(=O)N(C#CC1=CC=CC=C1)C Chemical compound CC1=CC=C(C=C1)S(=O)(=O)N(C#CC1=CC=CC=C1)C FOAVQZHGNGLPNA-UHFFFAOYSA-N 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 238000007363 ring formation reaction Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 4
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 3
- 150000001335 aliphatic alkanes Chemical class 0.000 description 3
- OSVHLUXLWQLPIY-KBAYOESNSA-N butyl 2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-3-yl]-2-methylpropanoate Chemical compound C(CCC)OC(C(C)(C)C1=CC(=C2[C@H]3[C@H](C(OC2=C1)(C)C)CC[C@H](C3)CO)O)=O OSVHLUXLWQLPIY-KBAYOESNSA-N 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 239000000575 pesticide Substances 0.000 description 3
- 230000002194 synthesizing effect Effects 0.000 description 3
- BKBSMMUEEAWFRX-NBVRZTHBSA-N (E)-flumorph Chemical compound C1=C(OC)C(OC)=CC=C1C(\C=1C=CC(F)=CC=1)=C\C(=O)N1CCOCC1 BKBSMMUEEAWFRX-NBVRZTHBSA-N 0.000 description 2
- NRTLIYOWLVMQBO-UHFFFAOYSA-N 5-chloro-1,3-dimethyl-N-(1,1,3-trimethyl-1,3-dihydro-2-benzofuran-4-yl)pyrazole-4-carboxamide Chemical compound C=12C(C)OC(C)(C)C2=CC=CC=1NC(=O)C=1C(C)=NN(C)C=1Cl NRTLIYOWLVMQBO-UHFFFAOYSA-N 0.000 description 2
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- 230000000202 analgesic effect Effects 0.000 description 2
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- 230000004071 biological effect Effects 0.000 description 2
- WYEMLYFITZORAB-UHFFFAOYSA-N boscalid Chemical compound C1=CC(Cl)=CC=C1C1=CC=CC=C1NC(=O)C1=CC=CN=C1Cl WYEMLYFITZORAB-UHFFFAOYSA-N 0.000 description 2
- 229940118790 boscalid Drugs 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000000417 fungicide Substances 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- QMGHHBHPDDAGGO-IIWOMYBWSA-N (2S,4R)-1-[(2S)-2-[[2-[3-[4-[3-[4-[[5-bromo-4-[3-[cyclobutanecarbonyl(methyl)amino]propylamino]pyrimidin-2-yl]amino]phenoxy]propoxy]butoxy]propoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide Chemical compound CN(CCCNC1=NC(NC2=CC=C(OCCCOCCCCOCCCOCC(=O)N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)NCC3=CC=C(C=C3)C3=C(C)N=CS3)C(C)(C)C)C=C2)=NC=C1Br)C(=O)C1CCC1 QMGHHBHPDDAGGO-IIWOMYBWSA-N 0.000 description 1
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 1
- RTTUBUXMNUJHRR-DXRVJIQQSA-N (3s)-4-[[(e)-2-[1-(4-fluorophenyl)-3-propan-2-ylindol-2-yl]ethenyl]-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound C12=CC=CC=C2C(C(C)C)=C(\C=C\P(O)(=O)C[C@@H](O)CC(O)=O)N1C1=CC=C(F)C=C1 RTTUBUXMNUJHRR-DXRVJIQQSA-N 0.000 description 1
- AOSODOHQJJPEAM-VUVZNRFTSA-N (3s)-4-[[(e)-2-[3'-(4-fluorophenyl)spiro[cyclopentane-1,1'-indene]-2'-yl]ethenyl]-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound OC(=O)C[C@H](O)CP(O)(=O)\C=C\C1=C(C=2C=CC(F)=CC=2)C2=CC=CC=C2C11CCCC1 AOSODOHQJJPEAM-VUVZNRFTSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
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- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
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- 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
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
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- 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
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- C07F7/1872—Preparation; Treatments not provided for in C07F7/20
- C07F7/1892—Preparation; Treatments not provided for in C07F7/20 by reactions not provided for in C07F7/1876 - C07F7/1888
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
本发明属于化学合成领域,涉及一种吡咯并噁嗪环类化合物及其制备方法。本发明基于含氮杂环类化合物是一类重要的杂环化合物,广泛存在于若干具有生物活性的天然产物中以及具有药物活性的化合物中,该类化合物在医药、农药、染料等领域具有极其广泛的应用,提供了一种操作简单,路线简洁,收率高的制备吡咯并噁嗪环类化合物的技术路线,所得目标产物可用于多个具有重要生理活性天然产物的多样性合成研究。
Description
技术领域
本发明属于化学合成领域,涉及一种吡咯并噁嗪环类化合物及其制备方法。
背景技术
现有技术公开了含氮杂环化合物广泛存在于自然界中,由于含氮杂环化合物具有独特的生理活性和药理活性,因此在医药和农药行业得到广泛应用。研究显示,植物中的有效成分生物碱类,如:抗癌的喜树碱、治高血压的利血平和镇痛的吗啡均为含氮杂环化合物;在动物体内起着重要生理作用的维生素、血红素、核酸、氨基酸、叶绿素均为含有生物活性的氮杂环化合物;青霉素救治若干病人的生命,并且具有划时代的意义,其依然是含氮杂环化合物【1】。在农用化学品中,酰胺或内酰胺类化合物作为杀菌剂已经有几十年的历史,由于其具有活性高效、对作物安全和对环境污染少等优点,一直受到农药和药物工作者的极大重视,其合成和生物活性研究一直是农药化学研究的热点。据报道,本领域数十年相继开发了数十种高效低毒的农业用杀菌剂,如下列出常见几种酰胺类杀菌剂:BayerLeverkusen公司开发甲呋酰胺4(fenfuram),德国巴斯夫公司开发的啶酰菌胺5(boscalid),日本住友化学工业公司开发呋吡菌胺6(furametpyr)和沈阳化工研究院开发的氟吗啉7(flumorph)等【2】。
因此,含氮杂环合成方法学的研究具有及其重要的意义。研究显示,在杂环的合成方法中,过渡金属催化的环化反应是最有效和广泛使用的方法之一,因其能够在较温和的条件下,从简单易得的底物出发直接获得结构复杂的杂环分子【3】。传统构筑C-N键的方法除了Ullmann和Goldberg报道的铜催化卤代烃和胺的交叉偶联方外,Buchwald和Hartwig发展的钯催化胺基化反应也是一种有效构建C-N键的策略;实践显示,这些反应存在诸多问题,如:底物需要预官能团化、苛刻的反应条件、生成大量副产物卤代盐等【4】。崔秀灵小组发展了一种过渡金属铱催化,酸促进的C-H键胺基化和分子内环化的串联反应,合成了一系列N-磺酰基多取代苯并咪唑类化合物,还建立了一种铑催化N-Ts-2-苯基苯并咪唑与1,4-二氧噁唑酮反应生成苯并咪唑并喹唑啉稠杂环化合物【4】。近几十年来,金已成为有机合成的有力工具,已成为催化研究的主要课题之一。金(I)催化因其高选择性、高原子经济性和温和的条件而被广泛应用【5】。Ye,Hashmi和Rai-Shung Liu研究小组已经深入地研究了含蒽醌或异噁唑的炔酰胺或丙酸酯的金催化的环化反应【6】。初步药理试验结果表明,母体化合物吡咯并噁嗪酮具有较强的镇痛作用【7】。
基于现有技术的基础与现状,本申请的发明人拟提供一种吡咯并噁嗪环类化合物及其制备方法,尤其是一种金催化合成吡咯并噁嗪环类化合物的方法。
与本发明相关的参考文献有:
[1]吴和义.几类含氮杂环化合物的合成与表征[D].江西:江西师范大学,2018.
[2]李阳.氮杂环类化合物的合成及农业杀菌活性的研究进展[J].化学与黏合,2019,41,133.
[3]冯承涛.金属催化的环化反应在含氮稠杂环合成中的应用[D].中国科学技术大学,2014.
[4]徐林华.过渡金属催化合成苯并氮杂环的研究[D].华侨大学,2018.
[5]Maria Camila Blanco Jaimes,Vanessa Weingand,Frank Rominger,andA.Stephen K.Hashmi.From Ynamides to Highly Substituted Benzo furans:Gold(I)-Catalyzed5-endo-dig-Cyclization/Rearrangement of Alkylic OxoniumIntermediates.Chem.Eur.J.2013,19,12504.
[6]Prakash D.Jadhav,Xin Lu,and Rai-ShunLiu.ACS.Catal.2018,8,9697.
[7]傅德才,孙光,楼扬通等.二氢吡咯并噁酮衍生物的合成和抗炎镇痛作用[J].中国药物化学杂志,2002,12,329.
发明内容
本发明的目的在于基于现有技术的基础与现状,提供一种吡咯并噁嗪环类化合物及其制备方法,尤其是一种金催化合成吡咯并噁嗪环类化合物的方法。本发明的制备方法中的路线的特点是:反应条件简单,选择性高。
本发明合成的吡咯并噁嗪环类化合物具有式(I)的化学结构:
其中,取代基R,R1,R2和R3代表烷基,芳香基或噁唑环。
进一步地,所述取代基R代表苯基、2-甲基苯基、4-甲基苯基、4-甲氧基苯基和正戊基,R1代表苯基、2-氯苯基、4-氯苯基、4-溴苯基,R2代表对甲苯磺酰基或噁唑环,R3代表甲基、苄基、苯基或噁唑环。本发明提供了下述24种吡咯并噁嗪环类化合物的具体化学结构,具体编号依次为3a、3b、3c、3d、3e、3f、3g、3h、3i、3j、3k、3l、3m、3n、3o、3p、3q、3r、3s、3t、3u、3v、3w和3x。
为了详实的描述式(I)化合物的结构,本发明定义上下文中的术语。
术语“烷基”应指从烷烃的任一碳原子上除去氢原子而衍生的一价基团,“烷基”的碳原子形成直链或支链的骨架,因此,“烷基”可分为“直链烷基”和“支链烷基”。该术语包括伯、仲、叔烷基子类,如甲基、乙基、正丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、正己基、异己基。特别地,术语“烷烃”是指仅仅含有碳、氢的饱和烃化合物。
术语“芳香基”又可以称为“芳基”,应包括碳环芳环基团,碳原子数为C6-C10芳环基团,比如苯基(C6)、萘基(C10)和C8芳环基团。
为了合成具有式(I)结构的吡咯并噁嗪环类化合物,本发明的具体技术路线如下,其中化合物1【8】和2【9】是根据文献方法制备,具体见文献([8]Si C.-M.;Huang W.;Du Z.-T.;Wei B.-G.;Lin G.-Q.Org.Lett.2014,16,4328;[9]Yao B.-B.;Liang Z.-J.;Niu T.-M.;Zhang Y.-H.J.Org.Chem.2009,74,4630)。
上述合成路线包括以下合成步骤:
步骤1:室温氮气保护下将一种金催化剂和一种银盐,在溶剂中于室温下反应0.5-1.0小时,之后将化合物1和炔酰胺的溶液滴入,室温下反应1-24小时后加入一种碱,室温反应5-10分钟,经萃取、浓缩、纯化得化合物3a-3x。所说的一种金催化剂是指三苯基膦氯化金、SIPrAuCl、9,10-双二苯基膦基乙基蒽乙腈氯化金、三苯基膦金(I)二(三氟甲基)亚胺、氯[三(2,4-二叔丁基苯基)亚磷酸]金、氯[三(对甲苯基)膦]金(I)或[二苯基(邻甲苯基)膦]氯化金(I);所说的一种银盐是指双三氟甲烷磺酰亚胺银盐、六氟锑酸银、三氟甲烷磺酸银、磷酸烯醇丙酮酸银盐、磷酸二苯酯银盐、二苄基磷酸银盐或环己基丁酸银;所说的一种碱是指碳酸钠水溶液、碳酸氢钠水溶液、乙酸钠水溶液、磷酸钠水溶液、次氯酸钠水溶液、硫化钠水溶液、硫氢化钠水溶液、碳酸钾水溶液或碳酸氢钾水溶液。
本发明所述制备吡咯并噁嗪环类化合物的技术路线,操作简单,路线简洁,收率高,所得目标产物可用于多个具有重要生理活性天然产物的多样性合成研究。
具体实施方式
实施例1
合成化合物3a
N-Benzyl-N-((6S,7R)-6-((tert-butyldimethylsilyl)oxy)-1-oxo-4,7-diphenyl-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-3-yl)-4-methylbenzenesulfonamide(3a)
室温氮气保护下,将SIPrAuCl(15.8mg,0.0254mmol,0.1eq)和六氟锑酸银(8.7mg,0.0254mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.254mmol,1eq)和N-苄基-4-甲基-N-(苯乙炔基)苯磺酰胺(110mg,0.305mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3a(157mg,91%)。1HNMR(400MHz,CDCl3)δ7.90-7.67(m,2H),7.38-7.33(m,2H),7.33-7.21(m,10H),7.20-7.10(m,2H),6.96-6.87(m,3H),4.86-4.80(m,1H),4.79-4.71(m,1H),4.23-4.10(m,3H),2.40(s,3H),2.00-1.90(m,1H),1.80-1.64(m,1H),0.79(s,9H),-0.14--0.27(m,6H)ppm.
合成化合物3b
N-((6S,7R)-6-((tert-butyldimethylsilyl)oxy)-1-oxo-4,7-diphenyl-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-3-yl)-N,4-dimethylbenzenesulfonamide(3b)
室温氮气保护下,将SIPrAuCl(15.8mg,0.0254mmol,0.1eq)和六氟锑酸银(8.7mg,0.0254mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.254mmol,1eq)和N,4-二甲基-N-(苯乙炔基)苯磺酰胺(87mg,0.305mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3b(115mg,75%)。1H NMR(400MHz,CDCl3)δ7.72-7.66(m,2H),7.43-7.34(m,7H),7.33-7.28(m,3H),7.26-7.20(m,2H),5.06-4.98(m,1H),4.92-4.88(m,1H),4.31-4.24(m,1H),2.82(s,3H),2.38(s,3H),2.16-2.07(m,1H),1.91-1.82(m,1H),0.82(s,9H),-0.10--0.21(m,6H)ppm.
合成化合物3c
N-Benzyl-N-((6S,7R)-6-((tert-butyldimethylsilyl)oxy)-4-(2-chlorophenyl)-1-oxo-7-phenyl-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-3-yl)-4-methylbenzenesulfonamide(3c)
室温氮气保护下,将SIPrAuCl(15.8mg,0.0254mmol,0.1eq)和六氟锑酸银(8.7mg,0.0254mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.254mmol,1eq)和N-苄基-N-((2-氯苯基)乙炔基)-4-甲基苯磺酰胺(120mg,0.305mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3c(151mg,83%)。1H NMR(400MHz,CDCl3)δ7.83-7.77(m,2H),7.41-7.32(m,3H),7.29-7.18(m,9H),7.17-7.11(m,2H),7.00-6.92(m,2H),5.20-5.12(m,1H),4.85-4.80(m,1H),4.25-4.15(m,3H),2.41-2.37(s,3H),2.01-1.94(m,1H),1.69-1.63(m,1H),0.78(s,9H),-0.11--0.29(m,6H)ppm.
合成化合物3d
N-Benzyl-N-((6S,7R)-4-(4-bromophenyl)-6-((tert-butyldimethylsilyl)oxy)-1-oxo-7-phenyl-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-3-yl)-4-methylbenzenesulfonamide(3d)
室温氮气保护下,将SIPrAuCl(15.8mg,0.0254mmol,0.1eq)和六氟锑酸银(8.7mg,0.0254mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.254mmol,1eq)和N-苄基-N-((4-溴苯基)乙炔基)-4-甲基苯磺酰胺(134mg,0.305mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3d(143mg,74%)。1H NMR(400MHz,CDCl3)δ7.96-7.67(m,2H),7.41-7.26(m,10H),7.22-7.12(m,2H),7.04-6.88(m,2H),6.84-6.44(m,2H),4.86-4.79(m,1H),4.77-4.65(m,1H),4.30-4.17(m,2H),4.15-3.90(m,1H),2.41(s,3H),1.97-1.90(m,1H),1.77-1.64(m,1H),0.80(s,9H),-0.13--0.24(m,6H)ppm.
合成化合物3e
N-Benzyl-N-((6S,7R)-6-((tert-butyldimethylsilyl)oxy)-4-(4-chlorophenyl)-1-oxo-7-phenyl-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-3-yl)-4-methylbenzenesulfonamide(3e)
室温氮气保护下,将SIPrAuCl(15.8mg,0.0254mmol,0.1eq)和六氟锑酸银(8.7mg,0.0254mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.254mmol,1eq)和N-苄基-N-((4-氯苯基)乙炔基)-4-甲基苯磺酰胺(120mg,0.305mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3e(129mg,71%)。1H NMR(400MHz,CDCl3)δ7.93-7.68(m,2H),7.38-7.15(m,12H),7.05-6.92(m,2H),6.90-6.60(m,2H),4.87-4.79(m,1H),4.77-4.65(m,1H),4.29-4.17(m,2H),4.15-3.93(m,1H),2.41(s,3H),1.98-1.86(m,1H),1.78-1.62(m,1H),0.80(s,9H),-0.13--0.27(m,6H)ppm.
合成化合物3f
(6S,7R)-6-((tert-butyldimethylsilyl)oxy)-3-(2-oxooxazolidin-3-yl)-4,7-diphenyl-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-1-one(3f)
室温氮气保护下,将SIPrAuCl(15.8mg,0.0254mmol,0.1eq)和六氟锑酸银(8.7mg,0.0254mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.254mmol,1eq)和3-(苯乙基)恶唑啉-2-酮(62mg,0.305mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3f(86mg,67%)。1H NMR(400MHz,CDCl3)δ7.42-7.29(m,9H),7.25-7.23(m,1H),5.06-4.99(m,1H),4.94-4.89(m,1H),4.32-4.26(m,3H),3.94-3.86(m,1H),3.71-3.64(m,1H),2.14-2.06(m,1H),1.91-1.81(m,1H),0.83(s,9H),-0.09--0.20(m,6H)ppm.
合成化合物3g
(6S,7R)-6-((tert-butyldimethylsilyl)oxy)-3-((R)-4-isopropyl-2-oxooxazolidin-3-yl)-4,7-diphenyl-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-1-one(3g)
室温氮气保护下,将SIPrAuCl(15.8mg,0.0254mmol,0.1eq)和六氟锑酸银(8.7mg,0.0254mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.254mmol,1eq)和(R)-4-异丙基-3-(苯乙炔基)恶唑啉-2-酮(70mg,0.305mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3g(70mg,50%)。1HNMR(400MHz,CDCl3)δ7.43-7.29(m,10H),5.02-4.90(m,2H),4.31-4.23(m,1H),4.22-4.15(m,1H),3.99-3.93(m,1H),3.88-3.72(m,1H),2.13-2.03(m,1H),1.97-1.88(m,2H),0.99-0.92(m,3H),0.84(s,9H),0.77-0.68(m,3H),-0.07--0.17(m,6H)ppm.
合成化合物3h
(6S,7R)-6-((tert-butyldimethylsilyl)oxy)-3-((R)-2-oxo-4-phenyloxazolidin-3-yl)-4,7-diphenyl-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-1-one(3h)
室温氮气保护下,将SIPrAuCl(15.8mg,0.0254mmol,0.1eq)和六氟锑酸银(8.7mg,0.0254mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.254mmol,1eq)和(R)-4-苯基-3-(苯乙炔基)恶唑啉-2-酮(80mg,0.305mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3h(71mg,48%)。1HNMR(400MHz,CDCl3)δ7.48-7.30(m,9H),7.26-7.23(m,2H),7.21-7.16(m,2H),7.00-6.94(m,2H),5.06-4.90(m,1H),4.85-4.77(m,2H),4.59-4.51(m,1H),4.19-4.13(m,2H),1.97-1.87(m,1H),1.74-1.67(m,1H),0.77(s,9H),-0.17--0.27(m,6H)ppm.
合成化合物3i
(5R,6S)-5-((tert-Butyldimethylsilyl)oxy)-6-(2-(2-chlorophenyl)-2-oxoethyl)piperidin-2-one(3i)
室温氮气保护下,将SIPrAuCl(15.8mg,0.0254mmol,0.1eq)和六氟锑酸银(8.7mg,0.0254mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.254mmol,1eq)和(R)-4-苄基-3-(苯乙炔基)恶唑啉-2-酮(85mg,0.305mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3i(74mg,49%)。1HNMR(400MHz,CDCl3)δ7.45-7.27(m,11H),7.24-7.14(m,4H),4.92-4.80(m,1H),4.77.-4.64(m,1H),4.26-4.16(m,2H),3.97-3.89(m,1H),3.19-3.08(m,1H),2.77-2.65(m,1H),2.08-1.94(m,1H),1.79-1.73(m,1H),0.82(s,9H),-0.09-0.22(m,6H)ppm.
合成化合物3j
(6S,7R)-6-((tert-butyldimethylsilyl)oxy)-3-((4S,5S)-4-methyl-2-oxo-5-phenyloxazolidin-3-yl)-4,7-diphenyl-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-1-one(3j)
室温氮气保护下,将SIPrAuCl(15.8mg,0.0254mmol,0.1eq)和六氟锑酸银(8.7mg,0.0254mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.254mmol,1eq)和(4S,5S)-4-甲基-5-苯基-3-(苯乙炔基)恶唑啉-2-酮(84mg,0.305mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3j(105mg,69%)。1H NMR(400MHz,CDCl3)δ7.51-7.28(m,11H),7.22-7.16(m,2H),6.89-6.81(m,2H),5.46-5.40(m,1H),4.94-4.83(m,2H),4.49-4.36(m,1H),4.32-4.25(m,1H),2.12-2.02(m,2H),0.844(s,9H),0.75-0.54(m,3H),-0.08--0.20(m,6H)ppm.
合成化合物3k
N-((6S,7R)-6-((tert-butyldimethylsilyl)oxy)-7-(4-methoxyphenyl)-1-oxo-4-phenyl-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-3-yl)-4-methyl-N-phenylbenzenesulfonamide(3k)
室温氮气保护下,将SIPrAuCl(14.7mg,0.0236mmol,0.1eq)和六氟锑酸银(8.1mg,0.0236mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.236mmol,1eq)和4-甲基-N-苯基-N-(苯乙炔基)苯磺酰胺(98mg,0.283mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3k(143mg,87%)。1HNMR(400MHz,CDCl3)δ7.61-7.52(m,2H),7.43-7.36(m,3H),7.35-7.30(m,2H),7.25-7.21(m,2H),7.21-7.14(m,3H),7.13-7.07(m,2H),6.94-6.85(m,2H),6.85-6.72(m,2H),4.91-4.78(m,2H),4.31-4.20(m,1H),3.81(s,3H),2.35(s,3H),2.11-1.97(m,1H),1.95-1.84(m,1H),0.80(s,9H),-0.12--0.24(m,6H)ppm.
合成化合物3l
N-((6S,7R)-6-((tert-butyldimethylsilyl)oxy)-1-oxo-4-phenyl-7-(p-tolyl)-4a,5,6,7-tetrahydto-1H-pyrrolo[1,2-c][1,3]oxazin-3-yl)-4-methyl-N-phenylbenzenesulfonamide(3l)
室温氮气保护下,将SIPrAuCl(15.3mg,0.0246mmol,0.1eq)和六氟锑酸银(8.4mg,0.0246mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.246mmol,1eq)和4-甲基-N-苯基-N-(苯乙炔基)苯磺酰胺(102mg,0.295mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3l(131mg,78%)。1HNMR(400MHz,CDCl3)δ7.39-7.7.22(m,2H),7.18-7.02(m,5H),6.97-6.79(m,9H),6.61-6.44(m,2H),4.69-4.49(m,2H),4.06-3.39(m,1H),2.13-2.02(m,6H),1.82-1.74(m,1H),1.67-1.56(m,1H),0.53(s,9H),-0.35--0.48(m,6H)ppm.
合成化合物3m
N-((6S,7R)-6-((tert-butyldimethylsilyl)oxy)-1-oxo-4-phenyl-7-(o-tolyl)-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-3-yl)-4-methyl-N-phenylbenzenesulfonamide(3m)
室温氮气保护下,将SIPrAuCl(15.3mg,0.0246mmol,0.1eq)和六氟锑酸银(8.4mg,0.0246mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.246mmol,1eq)和4-甲基-N-苯基-N-(苯乙炔基)苯磺酰胺(102mg,0.305mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3m(149mg,89%)。1HNMR(400MHz,CDCl3)δ7.62-7.54(m,2H),7.43-7.32(m,5H),7.21-7.07(m,9H),6.90-6.69(m,2H),5.21-5.09(m,1H),5.04-4.93(m,1H),4.32-4.24(m,1H),2.50(s,3H),2.33(s,3H),2.12-2.04(m,1H),1.99-1.88(m,1H),0.77(s,9H),-0.15-0.33(m,6H)ppm.
合成化合物3n
N-((6S,7R)-6-((tert-butyldimethylsilyl)oxy)-1-oxo-4,7-diphenyl-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-3-yl)-4-methyl-N-phenylbenzenesulfonamide(3n)
室温氮气保护下,将SIPrAuCl(15.8mg,0.0254mmol,0.1eq)和六氟锑酸银(8.7mg,0.0254mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.254mmol,1eq)和4-甲基-N-苯基-N-(苯乙炔基)苯磺酰胺(106mg,0.305mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3n(134mg,79%)。1HNMR(400MHz,CDCl3)δ7.64-7.52(m,2H),7.45-7.27(m,10H),7.22-7.15(m,3H),7.14-7.07(m,2H),6.88-6.69(m,2H),4.93-4.82(m,2H),4.30-4.23(m,1H),2.35(s,3H),2.10-2.01(m,1H),1.97-1.87(m,1H),0.80(s,9H),-0.12-0.0.24(m,6H)ppm.
合成化合物3o
N-((6S,7R)-6-((tert-butyldimethylsilyl)oxy)-1-oxo-7-pentyl-4-phenyl-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-3-yl)-4-methyl-N-phenylbenzenesulfonamide(3o)
室温氮气保护下,将SIPrAuCl(16.1mg,0.0258mmol,0.1eq)和六氟锑酸银(8.9mg,0.0258mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.258mmol,1eq)和4-甲基-N-苯基-N-(苯乙炔基)苯磺酰胺(108mg,0.310mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3o(104mg,61%)。1HNMR(400MHz,CDCl3)δ7.49-7.43(m,2H),7.30-7.27(m,1H),7.24-7.13(m,4H),7.12-7.06(m,3H),7.02-6.97(m,2H),6.76-6.63(m,2H),4.46-4.40(m,1H),3.97-3.88(m,2H),2.27(s,3H),1.96-1.91(m,1H),1.69-1.61(m,1H),1.60-1.50(m,2H),1.35-1.26(m,2H),1.25-1.19(m,4H),0.81-0.76(m,3H),0.73(s,9H),-0.08(s,3H),-0.15(s,3H)ppm.
合成化合物3p
N-Benzyl-N-((6S,7R)-6-((tert-butyldimethylsilyl)oxy)-7-(4-methoxyphenyl)-1-oxo-4-phenyl-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-3-yl)-4-methylbenzenesulfonamide(3p)
室温氮气保护下,将SIPrAuCl(14.7mg,0.0236mmol,0.1eq)和六氟锑酸银(8.1mg,0.0236mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.236mmol,1eq)和N-苄基-4-甲基-N-(苯乙炔基)苯磺酰胺(102mg,0.283mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3p(136mg,81%)。1HNMR(400MHz,CDCl3)δ7.89-7.61(m,2H),7.32-7.13(m,11H),6.95-6.86(m,5H),4.81-4.70(m,2H),4.22-4.10(m,3H),3.80(m,3H),2.40(s,3H),1.99-1.90(m,1H),1.77-1.64(m,1H),0.79(s,9H),-0.11--0.25(m,6H)ppm.
合成化合物3q
N-((6S,7R)-6-((tert-butyldimethylsilyl)oxy)-1-oxo-4-phenyl-7-(o-tolyl)-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-3-yl)-N,4-dimethylbenzenesulfonamide(3q)
室温氮气保护下,将SIPrAuCl(15.3mg,0.0246mmol,0.1eq)和六氟锑酸银(8.4mg,0.0246mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.246mmol,1eq)和N,4-二甲基-N-(苯乙炔基)苯磺酰胺(91mg,0.305mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3q(102mg,67%)。1H NMR(400MHz,CDCl3)δ7.73-7.67(m,2H),7.50-7.33(m,6H),7.23-7.11(m,5H),5.16-5.09(m,2H),4.33-4.24(m,1H),2.80(s,3H),2.48(s,3H),2.37(s,3H),2.17-2.10(m,1H),1.93-1.83(s,1H),0.79(s,9H),-0.14--0.31(m,6H)ppm.
合成化合物3r
N-((6S,7R)-6-((tert-butyldimethylsilyl)oxy)-7-(4-methoxyphenyl)-1-oxo-4-phenyl-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-3-yl)-N,4-dimethylbenzenesulfonamide(3r)
室温氮气保护下,将SIPrAuCl(14.7mg,0.0236mmol,0.1eq)和六氟锑酸银(8.1mg,0.0236mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.236mmol,1eq)和N,4-二甲基-N-(苯乙炔基)苯磺酰胺(88mg,0.283mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3r(118mg,79%)。1H NMR(400MHz,CDCl3)δ7.73-7.64(m,2H),7.44-7.34(m,5H),7.31-7.18(m,5H),6.94-6.86(m,2H),5.05-4.95(m,1H),4.88-4.80(m,1H),4.31-4.22(m,1H),3.83-3.78(m,3H),2.81(s,3H),2.38(s,3H),2.15-2.07(m,1H),1.90-1.80(m,1H),0.81(s,9H),-0.09--0.20(m,6H)ppm.
合成化合物3s
N-((6S,7R)-6-((tert-butyldimethylsilyl)oxy)-1-oxo-4-phenyl-7-(p-tolyl)-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-3-yl)-N,4-dimethylbenzenesulfonamide(3s)
室温氮气保护下,将SIPrAuCl(15.3mg,0.0246mmol,0.1eq)和六氟锑酸银(8.4mg,0.0246mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.246mmol,1eq)和N,4-二甲基-N-(苯乙炔基)苯磺酰胺(91mg,0.295mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3s(111mg,73%)。1H NMR(400MHz,CDCl3)δ7.74-7.65(m,2H),7.45-7.34(m,5H),7.26-7.22(m,2H),7.21-7.14(m,4H),5.06-4.94(m,1H),4.90-4.84(m,1H),4.32-4.24(m,1H),2.82(s,3H),2.38(s,3H),2.34(s,3H),0.82(s,9H),-0.09--0.19(m,6H)ppm.
合成化合物3t
(6S,7R)-6-((tert-butyldimethylsilyl)oxy)-3-(2-oxooxazolidin-3-yl)-4-phenyl-7-(o-tolyl)-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-1-one(3t)
室温氮气保护下,将SIPrAuCl(15.3mg,0.0246mmol,0.1eq)和六氟锑酸银(8.4mg,0.0246mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.246mmol,1eq)和3-(苯乙炔基)恶唑啉-2-酮(55mg,0.305mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3t(114mg,89%)。1H NMR(400MHz,CDCl3)δ7.39-7.30(m,3H),7.23-7.12(m,6H),5.14-5.04(m,2H),4.28-4.21(m,3H),3.89-3.81(m,1H),3.66-3.58(m,1H),2.43(m,3H),2.13-2.03(m,1H),1.89-1.79(m,1H),0.75(s,9H),-0.19--0.33(m,6H)ppm.
合成化合物3u
(6S,7R)-6-((tert-butyldimethylsilyl)oxy)-7-(4-methoxyphenyl)-3-(2-oxooxazolidin-3-yl)-4-phenyl-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-1-one(3u)
室温氮气保护下,将SIPrAuCl(14.7mg,0.0236mmol,0.1eq)和六氟锑酸银(8.1mg,0.0236mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.236mmol,1eq)和3-(苯乙基)恶唑啉-2-酮(57mg,0.283mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3u(95mg,75%)。1H NMR(400MHz,CDCl3)δ7.42-7.33(m,3H),7.27-7.21(m,4H),6.95-6.88(m,2H),5.07-4.90(m,1H),4.90-4.82(m,1H),4.32-4.23(m,3H),3.98-3.85(m,1H),3.81(s,3H),3.71-3.64(m,1H),2.15-2.03(m,1H),1.89-1.80(m,1H),0.82(s,9H),-0.10--0.20(m,6H)ppm.
合成化合物3v
(6S,7R)-6-((tert-butyldimethylsilyl)oxy)-3-(2-oxooxazolidin-3-yl)-4-phenyl-7-(p-tolyl)-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-1-one(3v)
室温氮气保护下,将SIPrAuCl(15.3mg,0.0246mmol,0.1eq)和六氟锑酸银(8.4mg,0.0246mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.246mmol,1eq)和3-(苯乙炔基)恶唑啉-2-酮(60mg,0.295mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3v(119mg,93%)。1H NMR(400MHz,CDCl3)δ7.26-7.20(m,2H),7.19-6.95(m,7H),4.97-4.84(m,1H),4.83-4.73(m,1H),4.21-4.12(m,3H),3.83-3.73(m,1H),3.61-3.51(m,1H),2.23(s,3H),2.04-1.93(m,1H),1.78-1.69(m,1H),0.71(s,9H),-0.16--0.32(m,6H)ppm.
合成化合物3w
(6S,7R)-6-((tert-butyldimethylsilyl)oxy)-3-((R)-4-isopropyl-2-oxooxazolidin-3-yl)-4-phenyl-7-(p-tolyl)-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-1-one(3w)
室温氮气保护下,将SIPrAuCl(15.3mg,0.0246mmol,0.1eq)和六氟锑酸银(8.4mg,0.0246mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.246mmol,1eq)和(R)-4-异丙基-3-(苯乙炔基)恶唑啉-2-酮(68mg,0.295mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3w(93mg,67%)。1HNMR(400MHz,CDCl3)δ7.40-7.25(m,5H),7.24-7.05(m,4H),5.00-4.82(m,2H),4.31-4.23(m,1H),4.23-4.14(m,1H),4.00-3.91(m,1H),3.90-3.69(m,1H),2.34(s,3H),2.11-2.04(m,1H),1.97-1.84(m,2H),1.00-0.90(m,3H),0.84(s,9H),0.76-0.61(m,3H),-0.04--0.18(m,6H)ppm.
合成化合物3x
(6S,7R)-6-((tert-butyldimethylsilyl)oxy)-3-((R)-2-oxo-4-phenyloxazolidin-3-yl)-4-phenyl-7-(p-tolyl)-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-1-one(3x)
室温氮气保护下,将SIPrAuCl(15.3mg,0.0246mmol,0.1eq)和六氟锑酸银(8.4mg,0.0246mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.246mmol,1eq)和(R)-4-苯基-3-(苯乙炔基)恶唑啉-2-酮(78mg,0.295mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3x(81mg,55%)。1HNMR(400MHz,CDCl3)δ7.45-7.31(m,7H),7.18-7.10(m,5H),6.99-6.93(m,2H),5.08-4.88(m,1H),4.84-4.75(m,2H),4.59-4.52(m,1H),4.20-4.14(m,2H),2.33(s,3H),1.96-1.88(m,1H),1.68-1.59(m,1H),0.77(s,9H),-0.12--0.29(m,6H)ppm.
实施例2
合成化合物3a
N-Benzyl-N-((6S,7R)-6-((tert-butyldimethylsilyl)oxy)-1-oxo-4,7-diphenyl-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-3-yl)-4-methylbenzenesulfonamide(3a)
室温氮气保护下,将SIPrAuCl(15.8mg,0.0254mmol,0.1eq)和六氟锑酸银(8.7mg,0.0254mmol,0.1eq)溶于二氯甲烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.254mmol,1eq)和N-苄基-4-甲基-N-(苯乙炔基)苯磺酰胺(110mg,0.305mmol,1.2eq)的二氯甲烷(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3a(121mg,70%)。
实施例3
合成化合物3a
N-Benzyl-N-((6S,7R)-6-((tert-butyldimethylsilyl)oxy)-1-oxo-4,7-diphenyl-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-3-yl)-4-methylbenzenesulfonamide(3a)
室温氮气保护下,将六氟锑酸银(8.7mg,0.0254mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,滴加入化合物1(100mg,0.254mmol,1eq)和N-苄基-4-甲基-N-(苯乙炔基)苯磺酰胺(110mg,0.305mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3a(56mg,32%)。
实施例4
合成化合物3b
N-((6S,7R)-6-((tert-butyldimethylsilyl)oxy)-1-oxo-4,7-diphenyl-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-3-yl)-N,4-dimethylbenzenesulfonamide(3b)
室温氮气保护下,将SIPrAuCl(7.9mg,0.0127mmol,0.05eq)和六氟锑酸银(4.4mg,0.0127mmol,0.05eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.254mmol,1eq)和N,4-二甲基-N-(苯乙炔基)苯磺酰胺(87mg,0.305mmol,1.2eq)的1,2-二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3b(52mg,34%)。
实施例5
合成化合物3b
N-((6S,7R)-6-((tert-butyldimethylsilyl)oxy)-1-oxo-4,7-diphenyl-4a,5,6,7-tetrahydro-1H-pyrrolo[1,2-c][1,3]oxazin-3-yl)-N,4-dimethylbenzenesulfonamide(3b)
室温氮气保护下,将SIPrAuCl(15.8mg,0.0254mmol,0.1eq)和AgNTf2(9.8mg,0.0254mmol,0.1eq)溶于1,2-二氯乙烷(1mL)中,室温反应15分钟,之后滴加入化合物1(100mg,0.254mmol,1eq)和N,4-二甲基-N-(苯乙炔基)苯磺酰胺(87mg,0.305mmol,1.2eq)的1,2-一二氯乙烷溶液(1mL),反应12小时后用碳酸氢钠水溶液淬灭,乙酸乙酯萃取,饱和食盐水洗涤,无水硫酸镁干燥,过滤,浓缩,硅胶柱纯化得白色固体3b(98mg,64%)。
Claims (7)
2.根据权利要求1所述的吡咯并噁嗪环类化合物,其特征在于,所述取代基R代表苯基、2-甲基苯基、4-甲基苯基、4-甲氧基苯基和正戊基,R1代表苯基、2-氯苯基、4-氯苯基、4-溴苯基,R2代表对甲苯磺酰基或噁唑环,R3代表甲基、苄基、苯基或噁唑环。
4.权利要求1所述的式(I)结构的吡咯并噁嗪环类化合物的制备方法,其特征在于,采用下述反应路线制备:
其中,取代基R,R1,R2和R3代表烷基,芳香基或噁唑环;
按下述步骤:
步骤1):室温氮气保护下将一种金催化剂三苯基膦氯化金、SIPrAuCl、9,10-双二苯基膦基乙基蒽乙腈氯化金、三苯基膦金(I)二(三氟甲基)亚胺、氯[三(2,4-二叔丁基苯基)亚磷酸]金、氯[三(对甲苯基)膦]金(I)或[二苯基(邻甲苯基)膦]氯化金(I)和一种银盐双三氟甲烷磺酰亚胺银盐、六氟锑酸银、三氟甲烷磺酸银、磷酸烯醇丙酮酸银盐、磷酸二苯酯银盐、二苄基磷酸银盐或环己基丁酸银,在溶剂乙醚、1,2-二氯乙烷、二氯甲烷、异丙醚、四氢呋喃、2-甲基四氢呋喃或二氧六环中于室温下反应0.5-1.0小时,之后将化合物1和炔酰胺的乙醚、1,2-二氯乙烷、二氯甲烷、异丙醚、四氢呋喃、2-甲基四氢呋喃或二氧六环溶液滴入,室温下反应1-24小时后加入一种碱碳酸钠水溶液、碳酸氢钠水溶液、乙酸钠水溶液、磷酸钠水溶液、次氯酸钠水溶液、硫化钠水溶液、硫氢化钠水溶液、碳酸钾水溶液或碳酸氢钾水溶液淬灭,室温反应5-10分钟,经萃取、浓缩、纯化得化合物3a-3x。
5.按权利要求4所述的制备方法,其特征在于,所述步骤1)中的一种金催化剂是三苯基膦氯化金、SIPrAuCl、9,10-双二苯基膦基乙基蒽乙腈氯化金、三苯基膦金(I)二(三氟甲基)亚胺、氯[三(2,4-二叔丁基苯基)亚磷酸]金或氯[三(对甲苯基)膦]金(I),特别是指SIPrAuCl。
6.按权利要求4所述的制备方法,其特征在于,所述步骤1)中的一种银盐是双三氟甲烷磺酰亚胺银盐、六氟锑酸银、三氟甲烷磺酸银、磷酸烯醇丙酮酸银盐、磷酸二苯酯银盐、二苄基磷酸银盐或环己基丁酸银,特别是指六氟锑酸银。
7.按权利要求4所述的制备方法,其特征在于,所述步骤1)中的一种碱是碳酸钠水溶液、碳酸氢钠水溶液、乙酸钠水溶液、磷酸钠水溶液、次氯酸钠水溶液、硫化钠水溶液、硫氢化钠水溶液、碳酸钾水溶液或碳酸氢钾水溶液。
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