CN105294536B - 一种制备3-亚氨基异吲哚啉酮类化合物的方法 - Google Patents
一种制备3-亚氨基异吲哚啉酮类化合物的方法 Download PDFInfo
- Publication number
- CN105294536B CN105294536B CN201410307064.6A CN201410307064A CN105294536B CN 105294536 B CN105294536 B CN 105294536B CN 201410307064 A CN201410307064 A CN 201410307064A CN 105294536 B CN105294536 B CN 105294536B
- Authority
- CN
- China
- Prior art keywords
- compound
- group
- formula
- radical
- cdcl
- 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.)
- Active
Links
- 238000000034 method Methods 0.000 title claims abstract description 103
- -1 3- iminoisoindolinone class compounds Chemical class 0.000 title claims abstract description 69
- 150000001875 compounds Chemical class 0.000 claims abstract description 56
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 35
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 14
- 239000003054 catalyst Substances 0.000 claims abstract description 12
- 239000007800 oxidant agent Substances 0.000 claims abstract description 10
- 230000001590 oxidative effect Effects 0.000 claims abstract description 10
- 239000000758 substrate Substances 0.000 claims abstract description 5
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 4
- 230000009471 action Effects 0.000 claims abstract description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 38
- 238000006243 chemical reaction Methods 0.000 claims description 31
- 125000001931 aliphatic group Chemical group 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000001624 naphthyl group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 6
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 239000012442 inert solvent Substances 0.000 claims description 5
- 125000005968 oxazolinyl group Chemical group 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 claims description 4
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 4
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 4
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 claims description 4
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 239000003638 chemical reducing agent Substances 0.000 claims description 3
- 125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 claims description 3
- 125000002636 imidazolinyl group Chemical group 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000004193 piperazinyl group Chemical group 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
- 125000005888 tetrahydroindolyl group Chemical group 0.000 claims description 3
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- 239000003570 air Substances 0.000 claims description 2
- TWKVUTXHANJYGH-UHFFFAOYSA-L allyl palladium chloride Chemical compound Cl[Pd]CC=C.Cl[Pd]CC=C TWKVUTXHANJYGH-UHFFFAOYSA-L 0.000 claims description 2
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 claims description 2
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 claims description 2
- 229910000365 copper sulfate Inorganic materials 0.000 claims description 2
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 claims description 2
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 claims description 2
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 2
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- PBDBXAQKXCXZCJ-UHFFFAOYSA-L palladium(2+);2,2,2-trifluoroacetate Chemical compound [Pd+2].[O-]C(=O)C(F)(F)F.[O-]C(=O)C(F)(F)F PBDBXAQKXCXZCJ-UHFFFAOYSA-L 0.000 claims description 2
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 claims description 2
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 claims description 2
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 229910001958 silver carbonate Inorganic materials 0.000 claims description 2
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 claims description 2
- 229910001961 silver nitrate Inorganic materials 0.000 claims description 2
- 229910001923 silver oxide Inorganic materials 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 2
- CSIFGMFVGDBOQC-UHFFFAOYSA-N 3-iminobutanenitrile Chemical compound CC(=N)CC#N CSIFGMFVGDBOQC-UHFFFAOYSA-N 0.000 claims 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 239000002904 solvent Substances 0.000 abstract description 7
- 230000004913 activation Effects 0.000 abstract description 4
- 238000001994 activation Methods 0.000 abstract description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 250
- 238000005160 1H NMR spectroscopy Methods 0.000 description 64
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 62
- 239000007858 starting material Substances 0.000 description 60
- 230000035484 reaction time Effects 0.000 description 57
- 229940125904 compound 1 Drugs 0.000 description 56
- 150000003254 radicals Chemical class 0.000 description 35
- VIESAWGOYVNHLV-UHFFFAOYSA-N 1,3-dihydropyrrol-2-one Chemical compound O=C1CC=CN1 VIESAWGOYVNHLV-UHFFFAOYSA-N 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 229910001868 water Inorganic materials 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical class C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- 0 *C(c(cc1)ccc1Br)=O Chemical compound *C(c(cc1)ccc1Br)=O 0.000 description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- BFJMHTOBRRZELQ-UHFFFAOYSA-N 3-iodo-2h-pyrazolo[3,4-c]pyridine Chemical compound N1=CC=C2C(I)=NNC2=C1 BFJMHTOBRRZELQ-UHFFFAOYSA-N 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 229910052783 alkali metal Inorganic materials 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical class C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 5
- MMBYJYAFFGKUDC-UHFFFAOYSA-N 3-aminoisoindol-1-one Chemical class C1=CC=C2C(N)=NC(=O)C2=C1 MMBYJYAFFGKUDC-UHFFFAOYSA-N 0.000 description 5
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical class C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 5
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical class N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 5
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical class C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 4
- DCTOHCCUXLBQMS-UHFFFAOYSA-N 1-undecene Chemical compound CCCCCCCCCC=C DCTOHCCUXLBQMS-UHFFFAOYSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical class C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 229940098779 methanesulfonic acid Drugs 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 229930195734 saturated hydrocarbon Natural products 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 4
- QFXVHWDLFOSOCA-UHFFFAOYSA-N 2-tert-butyl-3-methoxyiminoisoindol-1-one Chemical compound C(C)(C)(C)N1C(C2=CC=CC=C2C1=NOC)=O QFXVHWDLFOSOCA-UHFFFAOYSA-N 0.000 description 3
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical class C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 238000010499 C–H functionalization reaction Methods 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical class C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 3
- 241000207961 Sesamum Species 0.000 description 3
- 235000003434 Sesamum indicum Nutrition 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical class C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 3
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- PXZQEOJJUGGUIB-UHFFFAOYSA-N isoindolin-1-one Chemical compound C1=CC=C2C(=O)NCC2=C1 PXZQEOJJUGGUIB-UHFFFAOYSA-N 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical class COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- AGFHSNBWCCFYKZ-UHFFFAOYSA-N 2-tert-butyl-3h-isoindol-1-one Chemical compound C1=CC=C2C(=O)N(C(C)(C)C)CC2=C1 AGFHSNBWCCFYKZ-UHFFFAOYSA-N 0.000 description 2
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical class C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 229910000318 alkali metal phosphate Inorganic materials 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical group CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Chemical class CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Chemical class C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- USGIERNETOEMNR-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO.CCCO USGIERNETOEMNR-UHFFFAOYSA-N 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- FAGLEPBREOXSAC-UHFFFAOYSA-N tert-butyl isocyanide Chemical compound CC(C)(C)[N+]#[C-] FAGLEPBREOXSAC-UHFFFAOYSA-N 0.000 description 2
- 229930192474 thiophene Natural products 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 1
- 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 1
- KAFZOLYKKCWUBI-HPMAGDRPSA-N (2s)-2-[[(2s)-2-[[(2s)-1-[(2s)-3-amino-2-[[(2s)-2-[[(2s)-2-(3-cyclohexylpropanoylamino)-4-methylpentanoyl]amino]-5-methylhexanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]butanediamide Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CCC(C)C)C(=O)N[C@@H](CN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CC(N)=O)C(N)=O)C(=O)CCC1CCCCC1 KAFZOLYKKCWUBI-HPMAGDRPSA-N 0.000 description 1
- KRIWIRSMQRQYJG-DLBZAZTESA-N (2s,3s)-3-[[7-(benzylamino)-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-5-yl]amino]butane-1,2,4-triol Chemical compound C=1C(N[C@@H](CO)[C@H](O)CO)=NC2=C(C(C)C)C=NN2C=1NCC1=CC=CC=C1 KRIWIRSMQRQYJG-DLBZAZTESA-N 0.000 description 1
- PHDIJLFSKNMCMI-ITGJKDDRSA-N (3R,4S,5R,6R)-6-(hydroxymethyl)-4-(8-quinolin-6-yloxyoctoxy)oxane-2,3,5-triol Chemical compound OC[C@@H]1[C@H]([C@@H]([C@H](C(O1)O)O)OCCCCCCCCOC=1C=C2C=CC=NC2=CC=1)O PHDIJLFSKNMCMI-ITGJKDDRSA-N 0.000 description 1
- LPNRUMVKXCLEBE-JXVRESAISA-L (3r)-4-[[(e)-2-[5-ethyl-4-(4-fluorophenyl)-6-phenyl-2-propan-2-ylpyridin-3-yl]ethenyl]-oxidophosphoryl]-3-hydroxybutanoate Chemical compound CCC1=C(C=2C=CC=CC=2)N=C(C(C)C)C(\C=C\P([O-])(=O)C[C@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 LPNRUMVKXCLEBE-JXVRESAISA-L 0.000 description 1
- COXVPYKZDDKVRF-ULQDDVLXSA-N (4,4-difluorocyclohexyl)methyl N-[(2S)-4-methyl-1-oxo-1-[[(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]pentan-2-yl]carbamate Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](C[C@@H]1CCNC1=O)C=O)NC(=O)OCC2CCC(CC2)(F)F COXVPYKZDDKVRF-ULQDDVLXSA-N 0.000 description 1
- FOLCUFKJHSQMEL-BIXPGCQOSA-N (4-butylcyclohexyl) N-[(2S)-4-methyl-1-oxo-1-[[(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]pentan-2-yl]carbamate Chemical compound CCCCC1CCC(CC1)OC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C[C@@H]2CCNC2=O)C=O FOLCUFKJHSQMEL-BIXPGCQOSA-N 0.000 description 1
- PNHBRYIAJCYNDA-VQCQRNETSA-N (4r)-6-[2-[2-ethyl-4-(4-fluorophenyl)-6-phenylpyridin-3-yl]ethyl]-4-hydroxyoxan-2-one Chemical compound C([C@H](O)C1)C(=O)OC1CCC=1C(CC)=NC(C=2C=CC=CC=2)=CC=1C1=CC=C(F)C=C1 PNHBRYIAJCYNDA-VQCQRNETSA-N 0.000 description 1
- QVBVQHTXLPNXEY-ZMFCMNQTSA-N (4r)-6-[2-[4-(4-fluorophenyl)-6-phenyl-2-propan-2-ylpyridin-3-yl]ethyl]-4-hydroxyoxan-2-one Chemical compound C([C@H](O)C1)C(=O)OC1CCC=1C(C(C)C)=NC(C=2C=CC=CC=2)=CC=1C1=CC=C(F)C=C1 QVBVQHTXLPNXEY-ZMFCMNQTSA-N 0.000 description 1
- VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 1
- QOLHWXNSCZGWHK-BWBORTOCSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-(11-phenoxyundecylcarbamoyloxy)-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@@H]([C@@H](OC(=O)NCCCCCCCCCCCOC=3C=CC=CC=3)C(O1)(C(O)=O)C(O)(C(O2)C(O)=O)C(O)=O)O)C1=CC=CC=C1 QOLHWXNSCZGWHK-BWBORTOCSA-N 0.000 description 1
- UXKLQDCALAWFIU-VKNDCNMPSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-tetradecoxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@H](O)[C@H](C(O2)(C(O)=O)C(O)(C(O1)C(O)=O)C(O)=O)OCCCCCCCCCCCCCC)C1=CC=CC=C1 UXKLQDCALAWFIU-VKNDCNMPSA-N 0.000 description 1
- VGNCBRNRHXEODV-XXVHXNRLSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-6-dodecoxy-4,7-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@H](O)[C@H](C(O2)(C(O)=O)C(O)(C(O1)C(O)=O)C(O)=O)OCCCCCCCCCCCC)C1=CC=CC=C1 VGNCBRNRHXEODV-XXVHXNRLSA-N 0.000 description 1
- IGVKWAAPMVVTFX-BUHFOSPRSA-N (e)-octadec-5-en-7,9-diynoic acid Chemical compound CCCCCCCCC#CC#C\C=C\CCCC(O)=O IGVKWAAPMVVTFX-BUHFOSPRSA-N 0.000 description 1
- JNPGUXGVLNJQSQ-BGGMYYEUSA-M (e,3r,5s)-7-[4-(4-fluorophenyl)-1,2-di(propan-2-yl)pyrrol-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound CC(C)N1C(C(C)C)=C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)C(C=2C=CC(F)=CC=2)=C1 JNPGUXGVLNJQSQ-BGGMYYEUSA-M 0.000 description 1
- VAVHMEQFYYBAPR-ITWZMISCSA-N (e,3r,5s)-7-[4-(4-fluorophenyl)-1-phenyl-2-propan-2-ylpyrrol-3-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound CC(C)C1=C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)C(C=2C=CC(F)=CC=2)=CN1C1=CC=CC=C1 VAVHMEQFYYBAPR-ITWZMISCSA-N 0.000 description 1
- FZTLLUYFWAOGGB-UHFFFAOYSA-N 1,4-dioxane dioxane Chemical compound C1COCCO1.C1COCCO1 FZTLLUYFWAOGGB-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- BOOYHBPHFVNWNH-OAHLLOKOSA-N 1-tert-butyl-6-[[(1R)-1-(4-chlorophenyl)ethyl]amino]-5-[(4-fluorophenyl)methyl]pyrazolo[3,4-d]pyrimidin-4-one Chemical compound C[C@H](C1=CC=C(C=C1)Cl)NC2=NC3=C(C=NN3C(C)(C)C)C(=O)N2CC4=CC=C(C=C4)F BOOYHBPHFVNWNH-OAHLLOKOSA-N 0.000 description 1
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- XTBAPWCYTNCZTO-UHFFFAOYSA-N 1H-isoindolone Natural products C1=CC=C2C(=O)N=CC2=C1 XTBAPWCYTNCZTO-UHFFFAOYSA-N 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- FRUWMYWEARDNTC-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1h-indole Chemical compound C1C=CC=C2NCCC21 FRUWMYWEARDNTC-UHFFFAOYSA-N 0.000 description 1
- CLTMYNWFSDZKKI-UHFFFAOYSA-N 2-(aminomethyl)benzoic acid Chemical compound NCC1=CC=CC=C1C(O)=O CLTMYNWFSDZKKI-UHFFFAOYSA-N 0.000 description 1
- NOIXNOMHHWGUTG-UHFFFAOYSA-N 2-[[4-[4-pyridin-4-yl-1-(2,2,2-trifluoroethyl)pyrazol-3-yl]phenoxy]methyl]quinoline Chemical class C=1C=C(OCC=2N=C3C=CC=CC3=CC=2)C=CC=1C1=NN(CC(F)(F)F)C=C1C1=CC=NC=C1 NOIXNOMHHWGUTG-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000003229 2-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000003504 2-oxazolinyl group Chemical group O1C(=NCC1)* 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical class C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical class C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- YLLRPQWLASQXSI-UHFFFAOYSA-N 3-(4b,8a,9,9a-tetrahydro-4aH-pyrido[2,3-b]indol-4-ylamino)phenol Chemical compound Oc1cccc(NC2=CC=NC3NC4C=CC=CC4C23)c1 YLLRPQWLASQXSI-UHFFFAOYSA-N 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- LIDUGWDLSDKCLM-CSKARUKUSA-N 4-[[3-[[[(e)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]methyl-dimethylsilyl]benzonitrile Chemical compound CC(C)(C)C#C/C=C/CN(CC)CC1=CC=CC(OC[Si](C)(C)C=2C=CC(=CC=2)C#N)=C1 LIDUGWDLSDKCLM-CSKARUKUSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- MWVKLRSIDOXBSE-UHFFFAOYSA-N 5-(1-piperidin-4-ylpyrazol-4-yl)-3-(6-pyrrolidin-1-yl-1,3-benzoxazol-2-yl)pyridin-2-amine Chemical compound NC1=NC=C(C2=CN(N=C2)C2CCNCC2)C=C1C(OC1=C2)=NC1=CC=C2N1CCCC1 MWVKLRSIDOXBSE-UHFFFAOYSA-N 0.000 description 1
- OJKONCJPCULNOW-DYVFJYSZSA-N 5-chloro-2-fluoro-4-[(1s,2r)-2-(2-methylpyrazol-3-yl)cyclohexyl]oxy-n-pyrimidin-4-ylbenzenesulfonamide Chemical compound CN1N=CC=C1[C@@H]1[C@@H](OC=2C(=CC(=C(F)C=2)S(=O)(=O)NC=2N=CN=CC=2)Cl)CCCC1 OJKONCJPCULNOW-DYVFJYSZSA-N 0.000 description 1
- HIHOEGPXVVKJPP-JTQLQIEISA-N 5-fluoro-2-[[(1s)-1-(5-fluoropyridin-2-yl)ethyl]amino]-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyridine-3-carbonitrile Chemical compound N([C@@H](C)C=1N=CC(F)=CC=1)C(C(=CC=1F)C#N)=NC=1NC=1C=C(C)NN=1 HIHOEGPXVVKJPP-JTQLQIEISA-N 0.000 description 1
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
- CDUACMUYDHRMBX-UHFFFAOYSA-N 6-(oxomethylidene)cyclohexa-2,4-diene-1-carboxylic acid Chemical compound OC(=O)C1C=CC=CC1=C=O CDUACMUYDHRMBX-UHFFFAOYSA-N 0.000 description 1
- VCUKKMIXURRDKL-UHFFFAOYSA-N 9-(dimethylamino)-3-(4-ethylphenyl)pyrido[1,2]thieno[3,4-d]pyrimidin-4-one Chemical compound C1=CC(CC)=CC=C1N1C(=O)C(SC=2C3=C(N(C)C)C=CN=2)=C3N=C1 VCUKKMIXURRDKL-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- DGJMHKMYSDYOFP-MRXNPFEDSA-N C=CC(N(CCC1)C[C@@H]1N1N=C(C2=CN(CC(C3=CC=CC=C3)(F)F)N=N2)C2=C(N)N=CN=C12)=O Chemical compound C=CC(N(CCC1)C[C@@H]1N1N=C(C2=CN(CC(C3=CC=CC=C3)(F)F)N=N2)C2=C(N)N=CN=C12)=O DGJMHKMYSDYOFP-MRXNPFEDSA-N 0.000 description 1
- VMMPZJCXYKZHQQ-XFFZJAGNSA-O CCCCNC(C(/C=N\C)=C)=[NH2+] Chemical compound CCCCNC(C(/C=N\C)=C)=[NH2+] VMMPZJCXYKZHQQ-XFFZJAGNSA-O 0.000 description 1
- HJBAJJLUVYAAPU-NBVRZTHBSA-N CN(/C(/c1c2cc(-c(cc3)ccc3Cl)nc1)=N/OC)C2=O Chemical compound CN(/C(/c1c2cc(-c(cc3)ccc3Cl)nc1)=N/OC)C2=O HJBAJJLUVYAAPU-NBVRZTHBSA-N 0.000 description 1
- HPUMZWJWFGMMPH-UHFFFAOYSA-N CONC(c1ccnc(-c2ccccc2)c1)=O Chemical compound CONC(c1ccnc(-c2ccccc2)c1)=O HPUMZWJWFGMMPH-UHFFFAOYSA-N 0.000 description 1
- BNYNWZAYGHFSAD-UHFFFAOYSA-N CONC(c1cnccc1)=O Chemical compound CONC(c1cnccc1)=O BNYNWZAYGHFSAD-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229940126559 Compound 4e Drugs 0.000 description 1
- HSWVJQBEXRKOBZ-QGZVFWFLSA-N FC1=C(OC2CCN(CC2)C=2N=C3C(=NC=2N[C@H]2COCC2)CN(CC3)C(C)=O)C=CC(=C1)F Chemical compound FC1=C(OC2CCN(CC2)C=2N=C3C(=NC=2N[C@H]2COCC2)CN(CC3)C(C)=O)C=CC(=C1)F HSWVJQBEXRKOBZ-QGZVFWFLSA-N 0.000 description 1
- WHIRIGYMEQONRX-UHFFFAOYSA-N ON1C(C=2C(C1=O)=CC=CC2)=N Chemical class ON1C(C=2C(C1=O)=CC=CC2)=N WHIRIGYMEQONRX-UHFFFAOYSA-N 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical class C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical class C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 229940125907 SJ995973 Drugs 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- BEXZJJQVPWJPOA-VOTSOKGWSA-N [(e)-hept-2-enyl] 6-methyl-4-(4-nitrophenyl)-2-oxo-3,4-dihydro-1h-pyrimidine-5-carboxylate Chemical compound CCCC\C=C\COC(=O)C1=C(C)NC(=O)NC1C1=CC=C([N+]([O-])=O)C=C1 BEXZJJQVPWJPOA-VOTSOKGWSA-N 0.000 description 1
- HGDWHTASNMRJMP-UHFFFAOYSA-N [1-(hydroxyamino)-1-oxo-5-(3-phenoxyphenyl)pentan-2-yl]phosphonic acid Chemical compound ONC(=O)C(P(O)(O)=O)CCCC1=CC=CC(OC=2C=CC=CC=2)=C1 HGDWHTASNMRJMP-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
- 125000005422 alkyl sulfonamido group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 125000005421 aryl sulfonamido group Chemical group 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001716 carbazoles Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- YBFBENHWPRGUMU-UHFFFAOYSA-N chembl398496 Chemical compound OC(=O)C1=CC=CC=C1NC(=O)N1CCN(C=2N=C3C=CC(O)=CC3=NC=2)CC1 YBFBENHWPRGUMU-UHFFFAOYSA-N 0.000 description 1
- 229940125872 compound 4d Drugs 0.000 description 1
- 229940126115 compound 4f Drugs 0.000 description 1
- 229940125880 compound 4j Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 150000002240 furans Chemical group 0.000 description 1
- 125000004438 haloalkoxy group Chemical group 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 125000000268 heptanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006038 hexenyl group 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
- 125000005980 hexynyl group Chemical group 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 150000002518 isoindoles Chemical class 0.000 description 1
- 150000002527 isonitriles Chemical class 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002537 isoquinolines Chemical class 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- XZMHJYWMCRQSSI-UHFFFAOYSA-N n-[5-[2-(3-acetylanilino)-1,3-thiazol-4-yl]-4-methyl-1,3-thiazol-2-yl]benzamide Chemical compound CC(=O)C1=CC=CC(NC=2SC=C(N=2)C2=C(N=C(NC(=O)C=3C=CC=CC=3)S2)C)=C1 XZMHJYWMCRQSSI-UHFFFAOYSA-N 0.000 description 1
- PBQZQTQFQFYBNJ-UHFFFAOYSA-N n-methoxybenzamide Chemical compound CONC(=O)C1=CC=CC=C1 PBQZQTQFQFYBNJ-UHFFFAOYSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000002916 oxazoles Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000004880 oxines Chemical class 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 150000003216 pyrazines Chemical class 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical class C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 150000004892 pyridazines Chemical class 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- RWWYLEGWBNMMLJ-YSOARWBDSA-N remdesivir Chemical compound NC1=NC=NN2C1=CC=C2[C@]1([C@@H]([C@@H]([C@H](O1)CO[P@](=O)(OC1=CC=CC=C1)N[C@H](C(=O)OCC(CC)CC)C)O)O)C#N RWWYLEGWBNMMLJ-YSOARWBDSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- 150000003577 thiophenes Chemical class 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
Landscapes
- Indole Compounds (AREA)
Abstract
本发明涉及一种制备3‑亚氨基异吲哚啉酮类化合物的方法。具体地,本发明公开了一种通过钯催化C–H键活化方式来制备式I所示的3‑亚氨基异吲哚啉酮类化合物的方法,包括步骤:在惰性溶剂的存在下,在钯催化剂的催化下,在氧化剂的作用下,将式II化合物(N‑烷氧基酰胺类化合物)与式III化合物(异腈类化合物)进行反应,得到式I化合物。其中,式I、式II、式II化合物结构详见说明书。该方法效率高、选择性好、经济环保,同时该方法步骤少、操作简便,而且对底物的适用范围非常地广,具有非常良好的原子经济性。本发明还提供了式I化合物的进一步转化的方法。
Description
技术领域
本发明属于有机合成领域。具体地,本发明涉及一种制备3-亚氨基异吲哚啉酮类化合物的方法,更具体地,涉及一种利用钯催化碳氢键插入的方式制备3-亚氨基异吲哚啉酮类化合物的方法。
背景技术
含氮杂环是有机化学中一类常见的化合物,广泛存在于天然产物以及具有生物活性的分子中。作为一类重要的含氮杂环,3-亚氨基氧化异吲哚啉酮类化合物由于其重要的生物活性,比如降血脂,消炎镇痛以及抗肿瘤等作用[L.Butner等,Biomed&Pharmacother.1996,50,290-296;A.R.K.Murthy等,Pharm.Res.1987,4,21-27;I.H.Hall等,Anti-Cancer Drugs,1994,5,207-212],因而受到人们的广泛关注。
目前,对于该类化合物的合成方法已有相关报道,但这些方法有多不足,如反应温度较高,收率较低,底物适用范围较窄等,这使得它们在工业应用方面受到了很大限制[T.Miura等,Org.Lett.2011,13,1429–1431;B.Liu等,Adv.Synth.Catal.2012,354,2288–2300]因此发展一种简单高效的合成方法,成为有机化学以及药物化学家的重要课题。
近年来,过渡金属催化的C–H键活化得到迅猛发展。基于过渡金属催化的碳氢键活化及官能团化反应,可以缩短反应流程,提高原子经济性,实现常规方法难以制备的目标产物,极大的推动了药物分子和天然产物的合成方法学的发展。最近,基于Rh,Re催化的碳氢键活化策略制备3-亚氨基氧化异吲哚啉酮类化合物已有相关报道。2011年,Zhu等人以[RhCl2Cp*]2为催化剂,Ts取代芳基酰胺通过C–H键活化与异腈发生环化反应,实现了3-亚氨基氧化异吲哚啉酮类化合物的合成。然而该方法的反应条件比较苛刻(130℃,20h),而且反应需要外加2当量铜盐作氧化剂,因此这一催化体系显然还不具备实用性和经济价值[C.Zhu等,Chem.Eur.J.2011,17,12591–12595]。2013年,Kuninobu等人以[Re2(CO)10]为催化剂,芳基亚胺酯通过C–H键活化与异氰酸酯发生环化反应,实现了该化合物的合成。同样该反应由于需要较高温度及较长反应时间(150℃,24h),限制了该方法的进一步应用[Y.Kuninobu等,Angew.Chem.Int.Ed.2013,52,11879–11883]。
所以,本领域急需发展一种具有工业应用价值的、经济环保、能在温和条件下简便高效的合成3-亚氨基氧化异吲哚啉酮类化合物的方法。
发明内容
本发明的目的是提供一种通过碳氢键活化来快速制备一系列3-亚氨基氧化异吲哚啉酮类化合物的方法。
本发明的另一目的是提供对上述方法制备的一系列3-亚氨基异吲哚啉酮类化合物的进一步转化的方法。
本发明的第一方面中,提供了一种式I化合物的制备方法,在惰性溶剂的存在下,在钯催化剂的催化下,在氧化剂的作用下,将式II化合物(N-烷氧基酰胺类化合物)与式III化合物(异腈类化合物)进行反应,得到式I化合物;
其中,表示C6~C14芳基或C2~C9杂芳基;
R1、R2、R3、R4各自独立地选自氢、C1~C40饱和或不饱和的脂肪族烃基(包括C1~C40烷基、C2~C40烯基、C2~C40炔基)、C1~C40烷氧基(C1~C40烷基-O-)、C1~C40烷硫基(C1~C40烷基-S-)、亚甲二氧基(-O-CH2-O-)、卤代的C1~C40饱和或不饱和脂肪族烃基、卤代的C1~C40烷氧基、卤素、硝基、氰基、-CO2R7、-OC(O)R8、-P(O)(R9)(R10)、-P(O)(OR9)(OR10)、-SO2NR11R12、-NR13R14、-C(O)NR15R16、C6~C14芳基、C6~C14芳氧基(C6~C14芳基-氧基)、C6~C14芳基-C1~C10烷氧基、C2-C9杂芳基、C2~C9杂环基;或R1、R2、R3、R4中相邻的两个基团和与这两个基团连接的碳原子共同构成C3~C6环烷基或C2~C9杂环基;
R5为C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C2~C9杂芳基、C2~C9杂环基;
R6为C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C2~C9杂芳基、C2~C9杂环基;
其中,R7为氢、C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C2~C9杂芳基、C2~C9杂环基;
R8为氢、C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C2~C9杂芳基、C2~C9杂环基;
R9为氢、C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C2~C9杂芳基、C2~C9杂环基;
R10为氢、C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C2~C9杂芳基、C2~C9杂环基;
R11为氢、C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C2~C9杂芳基、C2~C9杂环基;
R12为氢、C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C2~C9杂芳基、 C2~C9杂环基;
R13为氢、C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C6~C14芳基磺酰基、C1~C10烷基磺酰基、C1~C10酰基、C2~C9杂芳基、C2~C9杂环基;
R14为氢、C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C6~C14芳基磺酰基、C1~C10烷基磺酰基、C1~C10酰基、C2~C9杂芳基、C2~C9杂环基;
R15为氢、C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C2~C9杂芳基、C2~C9杂环基;
R16为氢、C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C2~C9杂芳基、C2~C9杂环基;
上述各基团中,所述芳基、杂芳基、杂环基任选被选自下组的一个或多个取代基所取代:卤素、C1~C40烷基、C1~C10酰基、C1~C40烷氧基。
在另一优选例中,R5为C1~C40饱和或不饱和的烃基、苯基、萘基或C2~C9杂环基;更优选为C1~C10饱和或不饱和的烃基;更优选为甲基或苄基。
在另一优选例中,R6为饱和或不饱和的烃基、苯基、萘基或C2~C9杂环基;更优选为C1~C10饱和或不饱和的烃基;更优选为叔丁基。
在另一优选例中,所述的C6~C14芳基包括苯基、萘基;所述芳基任选被选自下组的一个或多个取代基所取代:卤素、C1~C40烷基、C1~C10酰基、C1~C40烷氧基。
在另一优选例中,所述的C6~C14芳基为苯基或被选自下组的一个或多个取代基所取代的苯基:甲基、甲氧基、三氟甲基、C6~C14芳基、C2~C9杂芳基、取代胺基(-NR13R14)、酯基(-CO2R7)、氰基、卤素、膦酰基(如-P(O)(R9)(R10)、-P(O)(OR9)(OR10));或萘基或被选自下组的一个或多个取代基所取代的萘基:甲基、甲氧基、三氟甲基、C6~C14芳基、C2~C9杂芳基、取代胺基(-NR13R14)、酯基(-CO2R7)、氰基、卤素、膦酰基(-P(O)(R9)(R10)或-P(O)(OR9)(OR10))。
在另一优选例中,所述的C6~C14芳基为苯基、邻甲苯基、邻甲氧苯基、邻三氟甲基苯基、邻芳基苯基、邻杂芳基苯基、邻取代胺基苯基、邻酯基苯基、邻氰基苯基、邻卤苯基、间甲苯基、间甲氧基苯基、间取代胺基苯基、间三氟甲基苯基、间卤苯基、间芳基苯基、间杂芳基苯基、间酯基苯基、间氰基苯基、对甲苯基、对甲氧基苯基、对取代胺基苯基、对三氟甲基苯基、对卤苯基、对酯基苯基、对氰基苯基、对芳基苯基和对杂芳基苯基、2,3-双甲氧基苯基、1-萘基、2-萘基、膦酰基苯基。
在另一优选例中,所述的C2~C9杂芳基包括呋喃基、苯并呋喃基、噻吩基、苯并噻吩基、吲哚基、异吲哚基、吡咯基、噻唑基、噁唑基、吡唑基、咪唑基、吡喃基、哒嗪基、吡嗪基、嘧啶基、吡啶基、喹啉基、异喹啉基、咔唑基;所述杂芳基任选被选自下组的一个或多个取代基所取代:卤素、C1~C40烷基、C1~C10酰基、C1~C40烷氧基。
在另一优选例中,所述的C2~C9杂芳基为2-呋喃基、3-呋喃基、2-苯并呋喃 基、3-苯并呋喃基、2-噻吩基、3-噻吩基、2-苯并噻吩基、3-苯并噻吩基、2-吲哚基、3-吲哚基、2-吡咯基、3-吡咯基、5-噻唑基、4-吡唑基、3-吡啶基、4-吡啶基、6-喹啉基、5-异喹啉基、2-吡啶基、2-喹啉基、2-吡嗪基、2-嘧啶基、1-吡唑基、2-噻唑基。
在另一优选例中,所述C2~C9杂环基包括:四氢喹啉基、四氢吲哚基、噁唑啉基、二氢吡咯基、四氢吡啶基、四氢呋喃基、吗啉基、哌嗪基、哌啶基、吡咯啉基、咪唑啉基。
在另一优选例中,所述的C2~C9杂环基为6-四氢喹啉基、N-酰基四氢喹啉基、5-四氢吲哚基、N-酰基四氢吲哚基、噁唑啉基、取代噁唑啉基、四氢喹啉基、四氢吲哚基、2-噁唑啉基。
在另一优选例中,所述的卤素包括氟、氯、溴、碘;更优选为氟、氯、溴;最优选为氟、氯。
在另一优选例中,所述的钯催化剂包括三(二亚苄基丙酮)二钯、四(三苯基膦钯)、醋酸钯、氯化钯、[1,1'-双(二苯基磷)二茂铁]二氯化钯、双乙腈氯化钯、三氟醋酸钯、三氟甲磺酸钯、氢氧化钯、烯丙基氯化钯;和/或
所述的氧化剂为空气、氧气、氧化银、碳酸银、硝酸银、醋酸铜、硫酸铜、氯化铜、溴化铜。
在另一优选例中,所述的钯催化剂为三(二亚苄基丙酮)二钯、四(三苯基膦)钯、醋酸钯;更优选为三(二亚苄基丙酮)二钯。
在另一优选例中,所述的氧化剂是压力为0.5-100大气压的空气或氧气;较佳地,所述的氧化剂为压力为0.8-10大气压的空气或氧气;更优选,所述的氧化剂为1-5大气压的空气或氧气。
在另一优选例中,所述的惰性溶剂为甲苯、乙苯、四氢呋喃、1,4-二氧六环、N,N’-二甲基甲酰胺、N,N’-二甲基乙酰胺、N-甲基吡咯烷酮、二甲亚砜、1,2-二氯乙烷、乙醚、乙二醇二甲醚、乙腈、乙酸乙酯、二氯甲烷、丙酮。
在另一优选例中,所述惰性溶剂为1,4-二氧六环、四氢呋喃、甲苯;更优选为1,4-二氧六环。
在另一优选例中,式II化合物与式III化合物的摩尔比为5:1~1:5;和/或所述钯催化剂的用量是式II化合物的用量的0.1~20mol%。
在另一优选例中,式II化合物与式III化合物的摩尔比为1:1~1:2;更优选为1:1.5。
在另一优选例中,所述钯催化剂的用量是式II化合物的用量的0.2~5mol%;更优选为0.5~2.5mol%。
在另一优选例中,所述反应在20~140℃下进行;和/或所述反应进行0.1~40小时。
在另一优选例中,所述反应在60~100℃下进行;更优选在80℃下进行。
在另一优选例中,所述反应进行0.2~20小时;最优选为0.5~10小时。
在本发明第二方面中,提供了一种苯甲酸类化合物的制备方法,
(a)所述方法包括步骤:
(1)在还原剂的存在下,将式I化合物进行反应,从而得到式I-1化合物;
(2)在酸的存在下,将式I-1化合物进行反应,从而得到式I-2化合物;
(3)在酸的存在下,将式I-2化合物进行反应,从而得到式I-3化合物;
或(b)所述方法包括步骤:
(1)在碱的存在下,将式I化合物进行反应,从而得到式I-4化合物;
(2)在酸的存在下,将式I-4化合物进行反应,从而得到式I-5化合物;
(3)在碱的存在下,将式I-5化合物进行反应,从而得到式I-6化合物;
或(c)所述方法包括步骤:
(1)在酸的存在下,将式I化合物进行反应,从而得到式I-7化合物;
上述各式中,R1、R2、R3、R4、R5、R6定义如本发明第一方面中定义。
在另一优选例中,所述方法(a)中,在步骤(1)中,所述还原剂为钯/碳-氢气、钯/碳-甲酸铵、硼氢化钠、氰基硼氢化钠、醋酸硼氢化钠。
在另一优选例中,所述方法(a)中,在步骤(2)中,所述酸为三氟醋酸、三氟甲磺酸、甲磺酸、HCl、硫酸、硝酸。
在另一优选例中,所述方法(a)中,在步骤(3)中,所述酸为三氟醋酸、三氟甲磺酸、甲磺酸、HCl、硫酸、硝酸。
在另一优选例中,所述方法(b)中,在步骤(1)中,所述碱为碱金属的碳酸盐、碱金属的氢氧化物、碱金属的磷酸盐、碱金属的甲醇盐、碱金属的乙醇盐、碱金属的叔丁醇盐、1,8-二氮杂环[5,4,0]十一烯。
在另一优选例中,所述方法(b)中,在步骤(2)中,所述酸为三氟醋酸、三氟甲磺酸、甲磺酸、HCl、硫酸、硝酸。
在另一优选例中,所述方法(b)中,在步骤(3)中,所述碱为碱金属的碳酸盐、 碱金属的氢氧化物、碱金属的磷酸盐、碱金属的甲醇盐、碱金属的乙醇盐、碱金属的叔丁醇盐、1,8-二氮杂环[5,4,0]十一烯。
在另一优选例中,所述方法(c)中,在步骤(1)中,所述酸为三氟醋酸、三氟甲磺酸、甲磺酸、HCl、硫酸。
在本发明第三方面中,提供了结构如式I所示的化合物,
式中,R1、R2、R3、R4、R5、R6定义同本发明第一方面中所定义。
应理解,在本发明范围内中,本发明的上述各技术特征和在下文(如实施例)中具体描述的各技术特征之间都可以互相组合,从而构成新的或优选的技术方案。限于篇幅,在此不再一一累述。
具体实施方法
发明人通过深入的研究,意外地发现了一种利用碳氢键活化来快速制备式I所示的3-亚氨基氧化异吲哚啉酮类化合物的方法。该方法不仅效率高、选择性高、经济环保,同时步骤少、操作简便,而且对底物的适用范围非常地广,具有非常良好的原子经济性。在此基础上,完成了本发明。
基团定义
术语“C1~C40饱和或不饱和脂肪族烃基”表示直链或支链的含有1-40个碳原子的饱和脂肪族烃基或不饱和脂肪族烃基,包括烷基、烃基、炔基等。
术语“C1~C40烷基”表示直链或支链的含有1-40个碳原子的烷基。例如,包含但不限于甲基、乙基、丙基、异丙基、丁基、异丁基、叔丁基、戊基、异戊基、新戊基、己基、叔己基、庚基、异庚基、辛基及异辛基等。
术语“C2~C40烯基”表示直链或支链的含有2-40个碳原子的烯基。例如,包含但不限于乙烯基、丙烯基、丁烯基、戊烯基、己烯基等。
术语“C2~C40炔基”表示直链或支链的含有2-40个碳原子的炔基。例如,包含但不限于乙炔基、丙炔基、丁炔基、戊炔基、己炔基等。
术语“芳基”表示具有芳香环结构性质的取代基,优选为“C6~C10芳基”,其表示具有6-10个碳原子的芳基。例如,包含但不限于苯基、取代的苯基、萘基、取代的萘基、蒽基等。
术语“杂芳基”是指具有5-14个环原子的单环或多环基团,每个环含有4-6个原子,其中有一个或多个选自N、O或S的杂原子,其余为碳。“杂芳基”具有一定的芳香性。本文优选杂芳基为“C2~C9杂芳基”,其表示具有2-9个碳原子的杂芳基,例如包括但不限于,呋喃、取代的呋喃、苯并呋喃、取代的苯并呋喃、噻吩、取代的噻吩、苯并噻吩、取代的苯并噻吩、吲哚、取代的吲哚、异吲哚、取代的 异吲哚、吡咯、取代的吡咯、噻唑、取代的噻唑、噁唑、取代的噁唑、吡唑、取代的吡唑、咪唑、取代的咪唑、吡喃、取代的吡喃、哒嗪、取代的哒嗪、吡嗪、取代的吡嗪、嘧啶、取代的嘧啶、吡啶、取代的吡啶、喹啉、取代的喹啉、异喹啉、取代的异喹啉、咔唑、取代的咔唑等。
术语“杂环基”代表饱和的或部分饱和的环基,由一或多个环(优选1-2个)构成,每个环有5-7个原子,其中包括一或多个(优选1-2个)选自N、O或S的杂原子。本文“杂环基”优选为“C2~C9杂环基”,例如包含但不限于,四氢喹啉、四氢吲哚、噁唑啉基、二氢吡咯基、四氢吡啶基、四氢呋喃基、吗啉基、吡咯啉基、哌嗪基、哌啶基、咪唑啉基。
术语“C1~C10酰基”表示具有1-10个碳原子的酰基,例如,包括但不限于,甲酰基、乙酰基、丙酰基、异丙酰基、丁酰基、异丁酰基、叔丁酰基、戊酰基、异戊酰基、新戊酰基、己酰基、叔己酰基、庚酰基、异庚酰基、辛酰基及异辛酰基等
上述各个基团(包括烷基、烯基、炔基、芳基、杂芳基、杂环基)可以任选被一个或多个(优选1个或2个)独立选自下列基团的取代基取代:氰基、烷基、烷氧基、卤代烷基、卤代烷氧基、烷硫基、卤素、硝基、烷氧基羰基、烷基胺基、二烷基胺基、烷基磺酰基、烷基亚磺酰基、芳基磺酰基、烷基磺酰胺基、芳基磺酰胺基、杂环基、杂芳基。
术语“卤素”包括氟、氯、溴、碘;“卤代的”可以为氟代的、氯代的、溴代的、或碘代的。
本发明的主要优点:
1.本发明提供了一种制备式I所示的3-亚氨基异吲哚啉酮类化合物的方法。
该方法可使用空气作为氧化剂,无需任何的添加剂,催化剂的含量可降到0.5mol%,反应速度可快至半小时,反应体系干净,而且反应的副产物仅为一分子H2O,所以该方法非常的原子经济,符合经济环保的可持续发展技术要求。且该方法操作简便,能在温和条件下实施,成本低廉。
2.还提供了对这一系列3-亚氨基异吲哚啉酮类化合物的进一步转化的方法,上述方法制得的式I所示的3-亚氨基异吲哚啉酮类化合物可以转化为多种非常有用的中间体。
下面结合具体实施例,进一步阐述本发明。应理解,这些实施例仅用于说明本发明而不用于限制本发明的范围。下列实施例中未注明具体条件的实验方法,通常按照常规条件,或按照制造厂商所建议的条件。除非另外说明,否则百分比和份数按重量计算。
所用溶剂均市售可得,且可按照标准的溶剂处理方法纯化。所用试剂均从试剂公司直接购买,无需纯化。
Pd2(dba)3为三(二亚苄基丙酮)二钯,Pd(PPh3)4为四(三苯基膦)钯、Pd(OAc)2为醋酸钯。原料1a-1t、4a-4s、6a-6p的合成方法参见于文献[L.E.Fisher等,J.Org.Chem.1993,58,3643-3647]。
1.制备例
实施例1 反-2-叔丁基-3-甲氧基亚氨基异吲哚啉酮(3a)
在空气(air)(1atm)下,在15mL反应管中加入酰胺化合物1a15.1mg(0.10mmol),叔丁基异腈18μL,(0.15mmol),Pd2(dba)32.3mg(0.0025mmol),1,4-二氧六环(dioxane)1mL,混匀,80℃中反应0.5小时。反应结束后冷却至室温,浓缩,得粗产物。粗产物用制备板分离(石油醚与乙酸乙酯的体积比为20:1),得到产物反-2-叔丁基-3-甲氧基亚氨基氧化异吲哚啉酮21.7mg(94%);1HNMR(400MHz,CDCl3)δ8.26–8.24(m,1H),7.77–7.75(m,1H),7.58–7.50(m,2H),4.06(s,3H),1.76(s,9H);13C NMR(100MHz,CDCl3)δ167.33,149.98,132.78,131.74,131.10,128.53,127.73,122.65,63.24,58.65,29.60;HRMS(ESI-TOF)m/z Calcdfor C13H17N2O2(M+H)+:233.1285,found:233.1276.
实施例2 反-7-甲基-2-叔丁基-3-甲氧基亚氨基异吲哚啉酮(3b)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物1b代替化合物1a。反应时间10小时,产率67%;1H NMR(400MHz,CDCl3)δ8.13(d,J=7.6Hz,1H),7.43(t,J=7.6Hz,1H),7.28(d,J=7.6Hz,1H),4.05(s,3H),2.67(s,3H),1.75(s,9H);13C NMR(100MHz,CDCl3)δ168.37,149.80,137.14,133.71,132.35,129.10,128.40,125.51,63.30,58.58,29.73,17.90;HRMS(ESI-TOF)m/zCalcd for C14H19N2O2(M+H)+:247.1441,found:247.1451.
实施例3 反-6-甲基-2-叔丁基-3-甲氧基亚氨基异吲哚啉酮(3c)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物1c代替化合 物1a。反应时间0.5小时,产率90%;1H NMR(400MHz,CDCl3)δ8.11(d,J=7.6Hz,1H),7.55(s,1H),7.36(dd,J=8.0,0.8Hz,1H),4.05(s,3H),2.44(s,3H),1.75(s,9H);13C NMR(100MHz,CDCl3)δ167.63,150.25,141.86,133.63,132.12,127.58,126.18,123.09,63.23,58.66,29.70,21.81;HRMS(ESI-TOF)m/z Calcd for C14H19N2O2(M+H)+:247.1441,found:247.1452.
实施例4 反-5-甲基-2-叔丁基-3-甲氧基亚氨基异吲哚啉酮(3d)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物1d代替化合物1a。反应时间0.5小时,产率93%;1H NMR(400MHz,CDCl3)δ8.07(s,1H),7.64(d,J=7.6Hz,1H),7.34(d,J=7.6Hz,1H),4.07(s,3H),2.46(s,3H),1.74(s,9H);13C NMR(100MHz,CDCl3)δ167.58,150.14,143.63,132.01,129.43,128.93,128.23,122.61,63.33,58.64,29.68,22.17;HRMS(ESI-TOF)m/z Calcd for C14H19N2O2(M+H)+:247.1441,found:247.1452.
实施例5 反-2-叔丁基-6-甲氧基-3-甲氧基亚氨基异吲哚啉酮(3e)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物1e代替化合物1a。反应时间0.5小时,产率91%;1H NMR(400MHz,CDCl3)δ8.14(d,J=8.4Hz,1H),7.24(d,J=2.8Hz,1H),7.07(dd,J=8.8,2.8Hz,1H),4.04(s,3H),3.88(s,3H),1.75(s,9H);13C NMR(100MHz,CDCl3)δ167.38,162.17,150.03,134.01,129.18,121.39,119.99,106.15,63.22,58.80,55.85,HRMS(ESI-TOF)m/z Calcd for C14H19N2O3(M+H)+:263.1390,found:263.1391.
实施例6 反-2-叔丁基-5-甲氧基-3-甲氧基亚氨基异吲哚啉酮(3f)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物1f代替化合物1a。反应时间0.5小时,产率92%;1H NMR(600MHz,CDCl3)δ7.79(d,J=2.4Hz,1H),7.67(d,J=8.4Hz,1H),7.04(dd,J=8.4,2.4Hz,1H),4.06(s,3H),3.88(s,3H),1.74(s,9H);13C NMR(100MHz,CDCl3)δ167.39,163.61,149.87, 130.41,124.19,117.20,112.93,63.41,58.63,55.93,29.66;HRMS(ESI-TOF)m/z Calcd for C14H19N2O3(M+H)+:263.1390,found:263.1398.
实施例7 反-2-叔丁基-5-乙酰氨基-3-甲氧基亚氨基异吲哚啉酮(3g)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物1g代替化合物1a。反应时间2小时,产率91%;1H NMR(400MHz,CDCl3)δ8.42(d,J=1.2Hz,1H),8.18(br,1H),7.80(dd,J=8.4,1.2Hz,1H),7.67(d,J=8.4Hz,1H),4.02(s,3H),2.22(s,3H),1.74(s,9H);13C NMR(100MHz,CDCl3)δ168.97,167.17,149.57,142.47,129.45,127.15,123.60,122.23,118.73,3.43,58.84,29.64,24.78;HRMS(ESI-TOF)m/z Calcd for C15H20N3O3(M+H)+:290.1499,found:290.1503.
实施例8 反-2-叔丁基-3-甲氧基亚氨基-7-氟异吲哚啉酮(3h)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物1h代替化合物1a。反应时间10小时,产率80%;1H NMR(400MHz,CDCl3)δ8.09(d,J=7.6Hz,1H),7.58–7.30(m,1H),7.21–7.17(m,1H),4.07(s,3H),1.74(s,9H); 13C NMR(100MHz,CDCl3)δ164.32(d,J=2.3Hz),158.06(d,J=260.5Hz),149.03(d,J=1.9Hz),134.91(d,J=7.4Hz),130.67(d,J=2.4Hz),124.05(d,J=4.1Hz),119.01(d,J=19.2Hz),118.10(d,J=11.4Hz),63.52,59.13,29.58;19FNMR(376MHz,CDCl3)δ-118.23(dd,J=9.4,4.9Hz);HRMS(ESI-TOF)m/zCalcd for C13H16FN2O2(M+H)+:251.1190,found:251.1199.
实施例9 反-2-叔丁基-3-甲氧基亚氨基-5-氟异吲哚啉酮(3i)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物1i代替化合物1a。反应时间1小时,产率96%;1H NMR(400MHz,CDCl3)δ7.96(dd,J=8.8,2.4Hz,1H),7.74(dd,J=8.4,4.8Hz,1H),7.23(td,J=8.4,2.4Hz,1H),4.07(s, 3H),1.74(s,9H);13C NMR(100MHz,CDCl3)δ166.88,165.42(d,J=207.2Hz),149.08(d,J=3.0Hz),130.24(d,J=11.3Hz),127.72(d,J=2.2Hz),124.74(d,J=9.6Hz),118.59(d,J=23.5Hz),115.24(d,J=26.3Hz),63.51,59.01,29.58;HRMS(ESI-TOF)m/z Calcd for C13H16FN2O2(M+H)+:251.1190,found:251.1196.
实施例10 反-2-叔丁基-3-甲氧基亚氨基-5-氯异吲哚啉酮(3j)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物1j代替化合物1a。反应时间1小时,产率86%;1H NMR(400MHz,CDCl3)δ8.26(dd,J=1.6,0.4Hz,1H),7.69(dd,J=8.0,0.4Hz,1H),7.51(dd,J=8.0,2.0Hz,1H),4.08(s,3H),1.74(s,9H);13C NMR(100MHz,CDCl3)δ166.44,148.93,139.01,131.45,130.05,129.69,127.96,123.94,63.56,59.08,29.58;HRMS(ESI-TOF)m/z Calcd for C13H16ClN2O2(M+H)+:267.0895,found:267.0894.
实施例11 反-2-叔丁基-3-甲氧基亚氨基-6-氯异吲哚啉酮(3k)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物1k代替化合物1a。反应时间6小时,产率78%;1H NMR(400MHz,CDCl3)δ8.18(d,J=8.4Hz,1H),7.71(d,J=2.0Hz,1H),7.52(dd,J=8.4,2.0Hz,1H),4.07(s,3H),1.74(s,9H);13C NMR(100MHz,CDCl3)δ166.05,149.24,137.45,133.47,132.90,128.99,126.66,123.03,63.48,59.12,29.61;HRMS(ESI-TOF)m/z Calcd for C13H16ClN2O2(M+H)+:267.0895,found:267.0894.
实施例12 反-2-叔丁基-3-甲氧基亚氨基-5-溴异吲哚啉酮(3l)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物1l代替化合物1a。反应时间6小时,产率80%;1H NMR(400MHz,CDCl3)δ8.42(d,J=1.2Hz,1H),7.68(dd,J=8.0,1.6Hz,1H),7.62(d,J=8.0Hz,1H),4.08(s,3H),1.74(s,9H);13C NMR(100MHz,CDCl3)δ166.54,148.83,134.34,130.79,130.50, 129.87,127.40,124.15,63.58,9.09,29.58;HRMS(ESI-TOF)m/z Calcd for C13H16BrN2O2(M+H)+:311.0390,found:311.0401.
实施例13 反-2-叔丁基-3-甲氧基亚氨基-6-溴异吲哚啉酮(3m)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物3m代替化合物1a。反应时间6小时,产率76%;1H NMR(400MHz,CDCl3)δ8.12(d,J=8.4Hz,1H),7.88(d,J=2.0Hz,1H),7.69(dd,J=8.0,1.6Hz,1H),4.07(s,3H),1.74(s,9H);13C NMR(100MHz,CDCl3)δ165.97,149.35,135.82,133.56,129.19,127.11,126.08,125.62,63.52,59.14,29.63;HRMS(ESI-TOF)m/z Calcd for C13H16BrN2O2(M+H)+:311.0390,found:311.0399.
实施例14 反-2-叔丁基-6-三氟甲基-3-甲氧基亚胺基异吲哚啉酮(3n)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物1n代替化合物1a。反应时间10小时,产率72%;1H NMR(400MHz,CDCl3)δ8.39(d,J=8.0Hz,1H),8.03(s,1H),7.83(d,J=8.0Hz,1H),4.10(s,3H),1.76(s,9H);13CNMR(100MHz,CDCl3)δ165.99,149.01,133.22(q,J=32.9Hz),132.40,131.09,129.74(q,J=3.7Hz),128.35,123.57(q,J=271.2Hz),120.05(q,J=3.9Hz,9H),63.69,59.34,29.58;19F NMR(376MHz,CDCl3)δ-63.23;HRMS(ESI-TOF)m/z Calcd for C14H16F3N2O2(M+H)+:301.1158,found:301.1159.
实施例15 反-2-叔丁基-5-三氟甲基-3-甲氧基亚氨基异吲哚啉酮(3o)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物1o代替化合物1a。反应时间6小时,产率78%;1H NMR(400MHz,CDCl3)δ8.52(s,1H),7.88(d,J=8Hz,1H),7.81(d,J=8Hz,1H),4.13(s,3H),1.78(s,9H);13C NMR(100MHz,CDCl3)δ165.81,148.72,134.61(q,J=32.2Hz,134.46,128.62,128.12(q,J=3.5Hz),125.01,124.93(q,J=3.9Hz),123.65(q,J=271.5Hz),123.19,63.55,63.55,59.24,59.24,29.43;HRMS(ESI-TOF)m/zCalcd for C14H16F3N2O2(M+H)+:301.1158,found:301.1168.
实施例16 反-2-叔丁基-5-甲氧羰基-3-甲氧基亚氨基异吲哚啉酮(3p)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物1p代替化合物1a。反应时间3小时,产率87%;1H NMR(400MHz,CDCl3)δ8.87(t,J=0.8Hz,1H),8.23(dd,J=8.0,0.8Hz,1H),7.83(d,J=8.0Hz,1H),4.11(s,3H),3.97(s,3H),1.76(s,9H);13C NMR(100MHz,CDCl3)δ166.41,166.30,149.17,135.24,134.37,132.58,129.09,128.50,122.77,63.65,59.26,52.73,29.63;HRMS(ESI-TOF)m/z Calcd for C15H19N2O4(M+H)+:291.1339,found:291.1337.
实施例17 反-2-叔丁基-5-氰基-3-甲氧基亚氨基异吲哚啉酮(3q)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物1q代替化合物1a。反应时间6小时,产率79%;1H NMR(400MHz,CDCl3)δ8.60(s,1H),7.88(d,J=8.0Hz,1H),7.84(d,J=8.0Hz,1H),4.12(s,3H),1.76(s,9H);13CNMR(100MHz,CDCl3)δ165.47,148.30,134.78,134.76,131.69,128.61,123.55,118.08,116.40,63.76,59.55,29.48;HRMS(ESI-TOF)m/z Calcd for C14H16N3O2(M+H)+:258.1237,found:258.1240.
实施例18 反-2-叔丁基-5-苯基-3-甲氧基亚氨基异吲哚啉酮(3r)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物1r代替化合物1a。反应时间0.5小时,产率76%;1H NMR(400MHz,CDCl3)δ8.48(dd,J=1.6,0.8Hz,1H),7.82(dd,J=8.0,0.8Hz,1H),7.74(dd,J=8.0,1.6Hz,1H),7.62–7.60(m,2H),7.43–7.39(m,1H),4.08(s,3H),1.77(s,9H);13C NMR(100MHz,CDCl3)δ167.37,149.95,146.37,140.51,130.59,130.33,129.30,129.07,128.26,127.68,126.68,123.14,63.49,58.87,29.69;HRMS(ESI-TOF)m/z Calcd for C19H21N2O2(M+H)+:309.1598,found:309.1611.
实施例19 反-2-叔丁基-6,7-二甲氧基-3-甲氧基亚氨基异吲哚啉酮(3s)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物1s代替化合物1a。反应时间12小时,产率56%;1H NMR(400MHz,CDCl3)δ8.00(d,J=8.4Hz,1H),7.05(d,J=8.4Hz,1H),4.03(s,3H),4.02(s,3H),3.92(s,3H),1.74(s,9H);13C NMR(100MHz,CDCl3)δ165.51,155.36,149.31,146.43,124.25,123.54,122.17,116.03,63.19,62.24,58.77,56.53,29.71;HRMS(ESI-TOF)m/z Calcd for C15H21N2O4(M+H)+:293.1496,found:293.1484.
实施例20 反-2-叔丁基-3-甲氧基亚氨基苯并异吲哚啉酮(3t)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物1t代替化合物1a。反应时间2小时,产率80%;1H NMR(400MHz,CDCl3)δ8.76(s,1H),8.24(s,1H),7.99–7.96(m,2H),7.62–7.56(m,2H),4.13(s,3H),1.81(s,9H);13CNMR(100MHz,CDCl3)δ167.39,149.95,135.89,134.14,129.81,129.67,128.86,128.64,128.07,127.97,124.43,123.31,63.41,59.09,29.61;HRMS(ESI-TOF)m/z Calcd for C17H19N2O2(M+H)+:283.1441,found:283.1442.
实施例21 反-5-叔丁基-6-甲氧亚氨基呋喃并[2,3-c]二氢吡咯酮(5a)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4a代替化合物1a。反应时间0.5小时,产率73%;1H NMR(400MHz,CDCl3)δ7.60(d,J=1.6Hz,1H),6.59(d,J=2.0Hz,1H),4.06(s,3H),1.68(s,9H);13C NMR(100MHz,CDCl3)δ162.24,152.17,143.60,125.37,106.00,63.63,59.11,29.94;HRMS(ESI-TOF)m/z Calcd for C11H15N2O3(M+H)+:223.1077,found:223.1076.
实施例22 反-5-叔丁基-4-甲氧亚氨基呋喃并[2,3-c]二氢吡咯酮(5b)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4b代替化合物1a。反应时间1小时,产率97%;1H NMR(400MHz,CDCl3)δ7.60(d,J=2.0Hz,1H),6.70(d,J=1.6Hz,1H),4.01(s,3H),1.69(s,9H);13C NMR(100MHz,CDCl3)δ157.64,152.09,150.30,146.32,124.00,109.02,63.15,59.29,29.95;HRMS(ESI-TOF)m/z Calcd for C11H15N2O3(M+H)+:223.1077,found:223.1079.
实施例23 反-2-叔丁基-1-甲氧亚氨基苯并呋喃并[2,3-c]二氢吡咯酮(5c)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4c代替化合物1a。反应时间45分钟,产率97%;1H NMR(400MHz,CDCl3)δ7.82–7.0(m,1H),7.60(d,J=8.4Hz,1H),7.47–7.42(m,1H),7.39–7.35(m,1H),4.17(s,3H),1.75(s,9H);13CNMR(100MHz,CDCl3)δ160.94,158.47,153.57,146.84,127.58,124.62,123.88,121.92,119.88,113.16,63.22,59.74,HRMS(ESI-TOF)m/z Calcd for C15H17N2O3(M+H)+:273.1234,found:273.1235.
实施例24 反-5-叔丁基-4-甲氧亚氨基噻吩并[2,3-c]二氢吡咯酮(5d)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4d代替化合物1a。反应时间0.5h,产率93%;1H NMR(400MHz,CDCl3)δ7.59(d,J=4.8Hz,1H),7.43(d,J=4.8Hz,1H),4.03(s,3H),1.72(s,9H);13C NMR(100MHz,CDCl3)δ162.67,148.29,138.62,138.26,134.83,124.74,63.17,59.22,29.84;HRMS(ESI-TOF)m/z Calcd for C11H15N2O2S(M+H)+:239.0849,found:239.0860.
实施例25 反-2-叔丁基-1-甲氧亚氨基苯并噻吩并[2,3-c]二氢吡咯酮(5e)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4e代替化合 物1a。反应时间0.5h,产率96%;1H NMR(400MHz,CDCl3)δ8.43–8.41(m,1H),7.88–7.86(m,1H),7.48–7.42(m,2H),4.18(s,3H),1.78(s,9H);13C NMR(100MHz,CDCl3)δ163.07,147.97,145.91,140.78,133.88,132.17,127.04,126.67,125.58,123.86,63.08,59.69,30.04;HRMS(ESI-TOF)m/z Calcd for C15H17N2O2S(M+H)+:289.1005,found:289.1003.
实施例26 反-2-叔丁基-1-甲氧基亚氨基-4-甲基二氢吡咯酮并[3,4-b]吲哚(5f)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4f代替化合物1a。反应时间0.5h,产率90%;1H NMR(400MHz,CDCl3)δ8.02(d,J=8.0Hz,1H),7.48-7.33(m,3H),4.05(s,3H),4.03(s,3H),1.65(s,9H);13C NMR(100MHz,CDCl3)δ157.98,143.16,142.34,134.95,124.72,122.85,122.78,121.75,111.54,107.97,64.99,54.34,31.13,HRMS (ESI-TOF) m/z Calcd for C16H20N3O2(M+H)+:286.1550,found:286.1538.
实施例27 反-5-叔丁基-4-甲氧基亚氨基-1-甲基二氢吡咯酮并[3,4-b]吡咯(5g)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4g代替化合物1a。反应时间0.5h,产率88%;1H NMR(400MHz,CDCl3)δ6.87(d,J=2.4Hz,1H),6.32(d,J=2.4Hz,1H),3.96(s,3H),3.87(s,3H),1.47(s,9H);13CNMR(100MHz,CDCl3)δ157.72,143.73,130.35,127.89,118.45,108.02,64.77,54.50,34.69,HRMS(ESI-TOF)m/z Calcdfor C12H18N3O2(M+H)+:236.1394,found:236.1396.
实施例28 反-5-叔丁基-4-甲氧基亚氨基二氢吡咯酮并[3,4-b]噻唑(5h)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4h代替化 合物1a。反应时间8h,产率85%;1H NMR(400MHz,CDCl3)δ9.12(s,1H),4.15(s,3H),1.74(s,9H);13C NMR(100MHz,CDCl3)δ162.01,160.30,154.59,145.26,133.06,64.22,60.09,29.90;HRMS(ESI-TOF)m/z Calcd for C10H14N3O2S(M+H)+:240.0801,found:240.0808.
实施例29 反-5-叔丁基-6-甲氧基亚氨基-1-甲基二氢吡咯酮并[3,4-c]吡唑(5i)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4i代替化合物1a。反应时间0.5h,产率77%;1H NMR(400MHz,CDCl3)δ7.54(s,1H),4.16(s,3H),4.02(s,3H),1.68(s,9H);13C NMR(100MHz,CDCl3)δ161.47,142.74,140.02,131.98,122.50,109.87,62.57,58.83,41.46,29.48;HRMS(ESI-TOF)m/zCalcd for C11H17N4O2(M+H)+:237.1346,found:237.1351.
实施例30 反-5-叔丁基-4-甲氧基亚氨基-1-甲基二氢吡咯酮并[3,4-c]吡唑(5j)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4j代替化合物1a。反应时间0.5h,产率87%;1H NMR(400MHz,CDCl3)δ7.62(s,1H),4.09(s,3H),3.83(s,3H),1.70(s,9H);13C NMR(100MHz,CDCl3)δ158.90,145.60,145.50,142.38,130.01,63.76,59.24,32.55,30.04;HRMS(ESI-TOF)m/z Calcd for C11H17N4O2(M+H)+:237.1346,found:237.1349.
实施例31 反-5-叔丁基-6-甲氧基亚氨基-3-甲基二氢吡咯酮并[3,4-d]咪唑(5k)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4k代替化合物1a。反应时间10h,产率74%;1H NMR(400MHz,CDCl3)δ7.62(s,1H),4.09(s,3H),3.83(s,3H),1.70(s,9H);13C NMR(100MHz,CDCl3)δ158.90,145.60,145.50,142.38,130.01,63.76,59.24,32.55,30.04;HRMS(ESI-TOF)m/z Calcd for C11H17N4O2(M+H)+:237.1346,found:237.1348.
实施例32 反-2-叔丁基-1-甲氧基亚氨基二氢吡咯酮并[3,4-c]吡啶(5l)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4l代替化合物1a。反应时间11h,产率45%;1H NMR(400MHz,CDCl3)δ9.05(d,J=1.2Hz,1H),8.86(d,J=5.2Hz,1H),8.09(dd,J=5.2,1.2Hz,1H),4.10(s,3H),1.74(s,9H);13C NMR(100MHz,CDCl3)δ166.10,154.00,148.86,145.15,134.92,125.89,121.33,63.80,59.34,29.44;HRMS(ESI-TOF)m/z Calcd for C12H16N3O2(M+H)+:234.1237,found:234.1233.
实施例33 反-6-叔丁基-7-甲氧基亚氨基二氢吡咯酮并[3,4-b]吡啶(5l’)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4l代替化合物1a。反应时间10h,产率20%;1H NMR(400MHz,CDCl3)δ8.95(dd,J=4.8,1.6Hz,1H),8.08(dd,J=7.6,1.6Hz,1H),7.46(dd,J=7.6,4.8Hz,1H),4.19(s,3H),1.78(s,9H;13C NMR(100MHz,CDCl3)δ174.57,164.92,158.89,154.34,151.24,150.87,148.69,147.35,136.25,131.04,126.62,125.22,122.99,64.74,59.55,30.04,HRMS(ESI-TOF)m/z Calcd for HRMS(ESI-TOF)m/z Calcd for C12H16N3O2(M+H)+:234.1237,found:234.1233.
实施例34 反-2-叔丁基-3-甲氧基亚氨基二氢吡咯酮并[3,4-c]吡啶(5m)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4m代替化合物1a。反应时间10h,产率92%;1H NMR(400MHz,CDCl3)δ9.50(s,1H),8.85(d,J=4.8Hz,1H),7.68–7.67(m,1H),4.13(s,3H),1.76(s,9H);13C NMR(100MHz,CDCl3)δ165.77,152.02,148.79,138.50,123.89,116.54,63.66,59.52,29.52;HRMS(ESI-TOF)m/z Calcd for C12H16N3O2(M+H)+:234.1237,found:234.1233.
实施例35 反-2-叔丁基-6-甲氧基-3-甲氧基亚氨基二氢吡咯酮并[3,4-c]吡啶(5n)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4n代替化合物1a。反应时间6h,产率80%;1H NMR(400MHz,CDCl3)δ9.03(s,1H),7.05(s,1H),4.07(s,3H),4.01(s,3H),1.74(s,9H);13C NMR(100MHz,CDCl3)δ165.57,165.48,149.03,146.95,141.95,117.77,104.18,63.34,59.45,54.56,29.53;HRMS(ESI-TOF)m/z Calcd for C13H18N3O3(M+H)+:264.1343,found:263.1345.
实施例36反-2-叔丁基-6-吗啡啉-3-甲氧基亚氨基二氢吡咯酮并[3,4-c]吡啶(5o)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4o代替化合物1a。反应时间6h,产率80%;1H NMR(400MHz,CDCl3)δ8.99(s,1H),6.90(s,1H),4.04(s,3H),3.82(t,J=4.0Hz,4H),3.66(t,J=4.0Hz,4H),1.74(s,9H); 13C NMR(100MHz,CDCl3)δ166.40,160.08,149.65,147.82,140.96,113.79,98.66,66.64,63.15,59.17,45.39,HRMS(ESI-TOF)m/z Calcd for C16H23N4O3(M+H)+:319.1765,found:319.1760.
实施例37 反-7-叔丁基-8-甲氧基亚氨基二氢吡咯酮并[3,4-g]喹啉(5p)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4p代替化合物1a。反应时间2h,产率85%;1H NMR(400MHz,CDCl3)δ9.07(s,1H),9.03(dd,J=4.0,1.6Hz,1H),8.32(d,J=7.6Hz,1H),8.25(s,1H),7.52(dd,J=8.4,4.0Hz,1H),4.14(s,3H),1.81(s,9H);13C NMR(100MHz,CDCl3)δ166.69,152.35,150.62,149.40,137.61,130.07,129.42,129.37,127.54,123.18,122.65,63.52,59.40,29.55;HRMS(ESI-TOF)m/z Calcd forC16H18N3O2(M+H)+:284.1394,found:284.1397.
实施例38 反-2-叔丁基-3-甲氧基亚氨基二氢吡咯酮并[3,4-g]异喹啉(5q)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4q代替化合物1a。反应时间2h,产率65%;1H NMR(400MHz,CDCl3)δ9.42(s,1H),8.92(s,1H),8.65(d,J=5.6Hz,1H),8.24(s,1H),7.81(d,J=6.0Hz,1H),4.17(s,3H),1.81(s,9H);13C NMR(100MHz,CDCl3)δ166.37,154.16,149.16,144.92,136.79,133.49,132.63,130.64,128.56,125.46,121.86,63.66,59.57,29.54;HRMS(ESI-TOF)m/z Calcd for C16H18N3O2(M+H)+:284.1394,found:284.1396.
实施例39 (E)-1-乙酰基-7-叔丁基-8-甲氧基亚氨基二氢吡咯酮并[3,4-g]四氢喹啉(5r)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4r代替化合物1a。反应时间2h,产率93%;1H NMR(400MHz,CDCl3)δ8.18(s,1H),7.54(s,1H),4.05(s,3H),3.80(t,J=6.8Hz,2H),2.80(t,J=6.8Hz,2H),2.28(s,3H),1.98(p,J=6.8Hz,2H),1.74(s,9H);13C NMR(100MHz,CDCl3)δ170.30,167.01,149.72,143.10,128.27,126.89,123.98,122.54,63.44,58.82,43.85,29.61,27.71,23.95,23.63;HRMS(ESI-TOF)m/z Calcd forC18H24N3O3(M+H)+:330.1812,found:330.1814.
实施例40 反-1-乙酰基-6-叔丁基-7-甲氧基亚氨基二氢吡咯酮并[3,4-f]二氢吲哚(5s)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4s代替化合物1a。反应时间2h,产率62%;1H NMR(400MHz,CDCl3)δ9.02(s,1H),7.50(s,1H),4.15(t,J=8.4Hz,2H),4.07(s,3H),3.25(t,J=8.4Hz,2H),2.26(s,3H),1.74(s,9H);13C NMR(100MHz,CDCl3)δ169.23,167.15,149.74,147.03,134.85,128.86,127.57,118.82,115.81,63.44,58.68,49.42,29.69,27.88,24.51;HRMS(ESI-TOF)m/z Calcd for C17H22N3O3(M+H)+:316.1656,found:316.1664.
实施例41 反-2-叔丁基-3-甲氧基亚胺基-5-二苯氧膦异吲哚啉酮(5t)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物4t代替化合物1a。反应时间2h,产率91%;1H NMR(400MHz,CDCl3)δ8.63(d,J=12.0Hz,1H),7.86–7.47(m,12H),3.96(s,3H),1.74(s,9H);13C NMR(100MHz,CDCl3)δ166.32,149.11(d,J=1.7Hz),138.04(d,J=99.9Hz),134.75(d,J=10.9Hz,6H),134.47(d,J=2.5Hz),132.40(d,J=2.8Hz),132.15(d,J=9.9Hz),131.96(d,J=72.1Hz),128.76(d,J=12.3Hz),128.38(d,J=14.5Hz),122.72(d,J=12.6Hz),63.44,59.20,29.55;HRMS(ESI-TOF)m/z Calcd forC25H26N2O3P(M+H)+:433.1676,found:433.1667.
实施例42 反-2-叔丁基-5-(2-吡啶基)3-甲氧基亚氨基异吲哚啉酮((7a)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物6a代替化合物1a。反应时间1h,产率97%;1H NMR(400MHz,CDCl3)δ8.83–8.82(m,1H),8.73(d,J=4.8Hz,1H),8.22–8.17(m,1H),7.86(d,J=8.0Hz,1H),7.82–7.76(m,2H),7.31–7.28(m,1H),4.11(s,3H),1.78(s,9H);13C NMR(100MHz,CDCl3)δ167.18,156.49,149.98,149.74,144.23,137.05,131.91,130.16,129.14,126.33,123.09,122.97,121.32,63.53,58.90,29.66;HRMS(ESI-TOF)m/z Calcd for C18H20N3O2(M+H)+:310.1550,found:310.1540.
实施例43 反-2-叔丁基-5-(2-喹啉基)-3-甲氧基亚氨基异吲哚啉酮(7b)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物6b代替化合物1a。反应时间2h,产率93%;1H NMR(400MHz,CDCl3)δ8.97(d,J=0.8Hz,1H),8.40(d,J=8.0Hz,1H),8.26(d,J=8.8Hz,1H),8.20(d,J=8.6Hz,1H),7.90(dd,J=8.0,2.2Hz,1H),7.85(d,J=8.0Hz,1H),7.76(t,J=7.6Hz,1H),7.56(t,J=7.6Hz,1H),4.13(s,3H),1.79(s,9H);13CNMR(100MHz,CDCl3)δ167.21,156.29,149.82148.35,144.47,137.21,132.20,130.08,129.21,127.62, 126.95,126.92,123.21,119.27,63.58,58.99,29.70;HRMS(ESI-TOF)m/zCalcd for C22H22N3O2(M+H)+:360.1707,found:360.1715.
实施例44 反-2-叔丁基5-(2-吡嗪基)-3-甲氧基亚氨基异吲哚啉酮(7c)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物6c代替化合物1a。反应时间2h,产率90%;1H NMR(400MHz,CDCl3)δ9.08(d,J=0.8Hz,1H),8.88(s,1H),8.69(d,J=1.6Hz,1H),8.59(d,J=2.4Hz,1H),8.22(dd,J=8.0,1.6Hz,1H),7.90(d,J=7.6Hz,1H),4.13(s,3H),1.78(s,9H);13C NMR(100MHz,CDCl3)δ166.84,151.96,149.50,144.46,143.83,142.68,141.00,132.70,130.08,129.29,126.33,123.42,63.62,59.07,29.63;HRMS(ESI-TOF)m/z Calcd for C17H19N4O2(M+H)+:311.1503,found:311.1513.
实施例45 反-2-叔丁基-5-(2-嘧啶基)-3-甲氧基亚氨基异吲哚啉酮(7d)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物6d代替化合物1a。反应时间2h,产率91%;1H NMR(400MHz,CDCl3)δ9.27(s,1H),8.85(d,J=4.8Hz,2H),8.66(d,J=8.0Hz,1H),7.87(d,J=8.0Hz,1H),7.25(t,J=4.8Hz,1H),4.14(s,3H),1.78(s,9H);13C NMR(100MHz,CDCl3)δ167.06,163.82,157.44,149.63,142.20,133.39,131.23,128.88,127.60,122.85,119.82,63.58,58.95,29.66;HRMS(ESI-TOF)m/z Calcd forC17H19N4O2(M+H)+:311.1503,found:311.1509.
实施例46 反-2-叔丁基-5-(4,4-二甲基-4,5-二氢噁唑啉基)-3-甲氧基亚氨基异吲哚啉酮(7e)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物6e代替化合物1a。反应时间2h,产率91%;1H NMR(400MHz,CDCl3)δ8.74–8.73(m,1H),8.16(dd,J=7.6,1.2Hz,1H),7.79(dd,J=8.0,0.8Hz,1H),4.15(s,2H),4.10(s, 3H),1.76(s,9H),1.41(s,6H);13CNMR(100MHz,CDCl3)δ166.74,161.39,149.30,133.81,132.61,131.40,128.47,127.48,122.67,79.49,68.11,63.65,59.10,29.65,28.51;HRMS(ESI-TOF)m/z Calcd forC18H24N3O3(M+H)+:330.1812,found:330.1818.
实施例47 反-2-叔丁基-6-(4,4-二甲基-4,5-二氢噁唑啉基)-3-甲氧基亚氨基异吲哚啉酮(7f)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物6f代替化合物1a。反应时间2h,产率76%;1H NMR(400MHz,CDCl3)δ8.29(dd,J=1.6,0.8Hz,1H),8.26(dd,J=8.0,0.8Hz,1H),8.19(dd,J=8.0,1.6Hz,1H),4.15(s,2H),4.09(s,3H),1.75(s,9H),1.40(s,6H);13C NMR(100MHz,CDCl3)δ166.58,161.14,149.57,132.77,132.00,130.91,130.34,127.59,122.67,79.47,68.06,63.49,58.96,29.61,28.47;HRMS(ESI-TOF)m/z Calcd forC18H24N3O3(M+H)+:330.1812,found:330.1820.
实施例48 反-2-叔丁基-5-吡唑基-3-甲氧基亚氨基异吲哚啉酮(7g)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物6g代替化合物1a。反应时间2h,产率98%;1H NMR(400MHz,CDCl3)δ8.58(dd,J=2.0,0.4Hz,1H),8.00(dd,J=2.0,0.4Hz,1H),7.91(dd,J=8.4,2.0Hz,1H),7.83(dd,J=8.4,0.4Hz,1H),7.77(d,J=1.6,1H),6.52(dd,J=2.8,2.0Hz,1H),4.10(s,3H),1.76(s,9H);13C NMR(100MHz,CDCl3)δ166.60,149.20,143.67,142.00,129.74,129.31,127.26,123.96,121.81,118.09,108.55,63.58,58.95,29.57;HRMS(ESI-TOF)m/z Calcd for C16H19N4O2(M+H)+:299.1503,found:299.1507.
实施例49 反-2-叔丁基-5-(2-噻唑基)-3-甲氧基亚氨基异吲哚啉酮(7h)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物6h代替化 合物1a。反应时间2h,产率85%;1H NMR(400MHz,CDCl3)δ8.84(s,1H),8.15(dd,J=8.0,1.6Hz,1H),7.94(d,J=3.2Hz,1H),7.83(d,J=8.0Hz,1H),7.42(d,J=3.2Hz,1H),4.12(s,3H),1.77(s,9H);13C NMR(100MHz,CDCl3)δ167.16,166.79,149.38,144.33,137.92,132.67,129.54,129.29,125.88,123.43,120.14,63.67,59.10,29.65;HRMS(ESI-TOF)m/z Calcdfor C16H18N3O2S(M+H)+:316.1114,found:366.1122.
实施例50 反-2-叔丁基-6-苯基-3-甲氧基亚氨基二氢吡咯酮并[3,4-c]吡啶(7i)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物6i代替化合物1a。反应时间2h,产率90%;1H NMR(400MHz,CDCl3)δ9.52(d,J=1.2Hz,1H),8.10-8.09(m,3H),7.53–7.47(m,3H),4.13(s,3H),1.78(s,9H);13C NMR(100MHz,CDCl3)δ166.00,159.82,149.17,148.53,139.77,138.37,130.13,129.10,127.42,122.24,112.99,63.62,59.55,29.58;HRMS(ESI-TOF)m/z Calcd for C18H20N3O2(M+H)+:310.1550,found:310.1541.
实施例51 反-2-叔丁基-6-(3-甲基苯基)-3-甲氧基亚氨基二氢吡咯酮并[3,4-c]吡啶(7j)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物6j代替化合物1a。反应时间2h,产率85%;1H NMR(400MHz,CDCl3)δ9.51(d,J=1.2Hz,1H),8.07(d,J=1.2Hz,1H),7.92(s,1H),7.86(d,J=8.0Hz,1H),7.39(t,J=8.0Hz,1H),7.28(d,J=7.6Hz,1H),4.13(s,3H),2.45(s,3H),1.78(s,9H);13CNMR(100MHz,CDCl3)δ166.00,159.97,149.17,148.43,139.69,138.80,138.29,130.89,128.99,128.10,124.51,122.13,113.02,63.59,59.51,29.56,21.65;HRMS(ESI-TOF)m/z Calcd for C19H22N3O2(M+H)+:324.1707,found:324.1703.
实施例52 反-2-叔丁基-6-(3-甲氧基苯基)-3-甲氧基亚氨基二氢吡咯酮并[3,4-c]吡啶(7k)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物6k代替化合物1a。反应时间2h,产率81%;1H NMR(400MHz,CDCl3)δ9.46(d,J=1.2Hz,1H),δ9.51(d,J=1.2Hz,1H),8.08(d,J=1.2Hz,1H),7.68–7.63(m,2H),7.41(t,J=8.0Hz,1H),7.02(ddd,J=8.0,2.4,0.8Hz,1H),4.13(s,3H),3.90(s,3H),1.78(s,9H);13C NMR(100MHz,CDCl3)δ165.97,160.29,159.54,149.14,148.43,139.75,139.72,130.09,122.32,119.78,116.41,113.11,112.28,63.61,59.55,55.53,29.57;HRMS(ESI-TOF)m/z Calcd for C19H22N3O3(M+H)+:340.1656,found:340.1663.
实施例53 反-2-叔丁基-6-(3-氯苯基)-3-甲氧基亚氨基二氢吡咯酮并[3,4-c]吡啶(7l)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物6l代替化合物1a。反应时间2h,产率74%;1H NMR(400MHz,CDCl3)δ9.51(d,J=1.2Hz,1H),8.12(dd,J=2.4,1.2Hz,1H),8.06(d,J=1.2Hz,1H),7.95–7.92(m,1H),7.44–7.43(m,2H),4.14(s,3H),1.78(s,9H);13C NMR(100MHz,CDCl3)δ165.74,158.20,148.98,148.60,140.08,139.90,135.29,130.31,130.07,127.65,125.38,122.71,113.09,63.70,59.65,29.57;HRMS(ESI-TOF)m/zCalcd for C18H19ClN3O2(M+H)+:344.1160,found:344.1165.
实施例54 反-2-叔丁基-6-(4-甲基苯基)-3-甲氧基亚氨基二氢吡咯酮并[3,4-c]吡啶(7m)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物6m代替化合物1a。反应时间2h,产率88%;1H NMR(400MHz,CDCl3)δ9.48(d,J=1.2Hz,1H),8.05(d,J=1.2Hz,1H),7.98(d,J=8.0Hz,2H),7.30(d,J=8.0Hz,2H),4.11(s,3H),2.41(s,3H),1.77(s,9H);13C NMR(100MHz,CDCl3)δ166.02, 159.75,149.18,148.40,140.33,139.63,135.54,129.78,127.25,121.86,112.54,63.53,59.44,29.54,21.45;HRMS(ESI-TOF)m/z Calcdfor C19H22N3O2(M+H)+:327.1707,found:327.1712.
实施例55 反-2-叔丁基-6-(4-甲氧基苯基)-3-甲氧基亚氨基二氢吡咯酮并[3,4-c]吡啶(7n)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物6n代替化合物1a。反应时间2h,产率87%;1H NMR(400MHz,CDCl3)δ9.46(d,J=1.2Hz,1H),8.06(d,J=8.8Hz,2H),8.01(d,J=1.2Hz,1H),7.02(d,J=9.2Hz,2H),4.12(s,3H),3.88(s,3H),1.77(s,9H);13C NMR(100MHz,CDCl3)δ166.13,161.41,159.43,149.27,148.42,139.67,130.97,128.84,121.47,114.46,112.05,63.56,59.48,55.54,29.58;HRMS(ESI-TOF)m/z Calcdfor C19H22N3O3(M+H)+:340.1656,found:340.1663.
实施例56 反-2-叔丁基-6-(4-氯苯基)-3-甲氧基亚氨基二氢吡咯酮并[3,4-c]吡啶(7o)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物6o代替化合物1a。反应时间2h,产率86%;1H NMR(400MHz,CDCl3)δ9.49(s,1H),8.04(s,1H),8.03(d,J=8.4Hz,2H),7.47(d,J=8.4Hz,2H),4.13(s,3H),1.77(s,9H); 13C NMR(100MHz,CDCl3)δ165.59,158.23,148.81,148.35,139.63,136.52,136.16,129.08,128.43,122.18,112.52,63.45,59.39,29.35;HRMS(ESI-TOF)m/z Calcd for C18H19ClN3O2(M+H)+:344.1160,found:344.1167.
实施例57 反-2-叔丁基-6-(2-萘基)-3-甲氧基亚氨基二氢吡咯酮并[3,4-c]吡啶(7p)
采用与实施例1相似的步骤,不同点在于采用相应的原料化合物6p代替化合物1a。反应时间10h,产率74%;1H NMR(400MHz,CDCl3)δ9.56(d,J=1.2Hz,1H),8.59(d,J=1.2Hz,1H),8.23–8.20(m,2H),7.98–7.96(m,2H),7.89–7.87(m,1H),7.55–7.52(m,2H),4.14(s,3H),1.79(s,9H);13C NMR(100MHz,CDCl3)δ166.01,159.69,149.19,148.61,139.81,135.61,134.21,133.51,129.11,128.88,127.83,127.41,127.27,126.70,124.51,122.21,113.22,63.66,59.58,29.60;HRMS(ESI-TOF)m/z Calcd for C22H22N3O2(M+H)+:360.1707,found:360.1718.
按照实施例1的方法制备化合物3a,不同点在于采用表1相应的条件。
表1
2.放大实验
在空气下,250mL干燥的圆底烧饼中加入N-甲氧基苯甲酰胺(7.5mmol,1.13g),叔丁基异腈(11.25mmol)和Pd2(dba)3(34.3mg,0.0375mmol),75mL1,4-二氧六环(dioxane),装上回流冷凝管放入预先加热到80℃油浴中,当TLC监测反应完成后,除去溶剂,粗产物用正己烷和乙酸乙酯柱层析分离得到1.55克产物即为2-叔丁基-3-甲氧基亚氨基异吲哚啉酮。
3产物转化
在空气下,25mL干燥的圆底烧饼中加入2-叔丁基-3-甲氧基亚氨基异吲哚啉酮(0.2mmol,46.4mg),钯碳(0.02mmol,22.4mg),4mL甲醇,抽换氢气三次,室温(r.t.)下反应6小时,原料消失。反应结束后,用硅藻土过滤,乙酸乙酯冲洗三次,滤液旋干得纯的产物2-叔丁基异吲哚啉酮38mg,定量的收率。1H NMR(400MHz,CDCl3)δ7.78(d,J=7.2Hz,1H),7.49(t,J=7.2Hz,1H),7.44–7.40(m,2H),4.45(s,2H),1.57(s,9H);13C NMR(100MHz,CDCl3)δ168.92,140.73,134.46,130.92,127.85,123.13,122.39,54.38,48.55,28.08.
在空气下,15mL干燥的圆底烧饼中加入2-叔丁基异吲哚啉酮(0.1mmol,18.9mg),3mL三氟甲磺酸,室温下搅拌0.5小时。反应结束后,在冰水下缓慢滴加5mL水,加入10mL饱和碳酸钠调至碱性。水相用乙酸乙酯萃取,合并有机相,无水硫酸钠干燥,旋干得到纯的产物异吲哚啉酮(13.3mg,100%).1H NMR(400MHz,CDCl3)δ7.93(br,1H),7.88(d,J=8.0Hz,1H),7.58(t,J=8.0,1H),7.51–7.47(m,2H),4.48(s,2H);13C NMR(100MHz,CDCl3)δ172.41,143.80,132.24,131.87,128.12,123.82,123.29,45.93.
在空气下,15mL干燥的封管中加入异吲哚啉酮(0.1mmol,13.3mg),3mL6N盐酸溶液,加热回流(reflux)过夜。反应结束后,冷却至室温,水相用二氯甲烷洗三次。水相中将水除去得到产物2-氨甲基苯甲酸盐酸盐(15.5g,83%)。1H NMR (400MHz,D2O)δ8.05(d,J=8.0Hz,1H),7.63(t,J=7.6Hz,1H),7.55(t,J=7.6Hz,1H),7.49(d,J=8.0Hz,1H),4.34(s,2H).
在空气下,15mL干燥的封管中加入2-叔丁基-3-甲氧基亚胺基异吲哚啉酮(0.2mmol,46.4mg),3mL乙醇饱和氯化氢溶液,将反应管放到油浴加热到110℃反应12小时。反应结束后,冷却到室温条件下,加入10mL水稀释,用乙酸乙酯萃取三次,合并有机相,饱和氯化钠溶液洗两次,无水硫酸钠干燥。粗产物用柱层析进行分离得出产物邻苯二甲酸乙酯(36.4mg,82%)。1H NMR(400MHz,CDCl3)δ7.73(dd,J=6.0,3.6Hz,2H),7.53(dd,J=6.0,3.6Hz,2H),4.37(q,J=7.2Hz,4H),1.37(t,J=7.2Hz,6H).
在空气下,15mL干燥的封管中加入2-叔丁基-3-甲氧基亚胺基异吲哚啉酮(0.1mmol,23.2mg),氢氧化钠(16mg,0.4mmol),1mL水和0.25mL正丙醇(n-propanol),加热到100℃反应,直到原料消失。反应结束后,反应管冷却至室温,除去溶剂,粗产物用厚制备板分离得到产物N-叔丁基,N-甲氧基邻苯二甲酸胺(17.5mg,70%)。1H NMR(400MHz,CDCl3)δ8.05(d,J=7.2Hz,1H),7.57-7.51(m,3H),3.87(s,3H),1.09(s,9H);13C NMR(150MHz,CDCl3)δ169.15,155.02,132.54,131.71,131.67,130.27,129.95,128.56,61.45,53.07,31.40;HRMS(ESI-TOF)m/z Calcd for C13H19N2O3(M+H)+:251.1390,found:251.1395.
在空气下,15mL干燥的封管中加入N-叔丁基-N-甲氧基邻苯二甲酸胺(0.05mmol,12.5mg),9mL1,4-二氧六环(dioxane)和0.5mL饱和氯化氢甲醇溶液,50℃下反应3小时。反应结束后,冷却到室温,滴加5mL饱和碳酸氢钠溶液。乙酸乙酯萃取三次,合并有机相,无水硫酸钠干燥。除去溶剂后,粗产物用厚制备板分离得到产物2-叔丁胺羰基苯甲酸甲酯(9.6mg,83%).1H NMR(400MHz,CDCl3)δ7.88–7.86(m,1H),7.53–7.49(m,1H),7.47–7.42(m,2H),5.60(br,1H),3.89(s,3H),1.47(s,9H);13C NMR(100MHz,CDCl3)δ168.80,167.43,139.47,132.01,130.25,129.38,129.00,127.58,52.52,52.04,28.85;HRMS(ESI-TOF)m/zCalcd for C13H18NO3(M+H)+:236.1281,found:236.1285.
在空气下,15mL干燥的封管中加入2-叔丁胺羰基苯甲酸甲酯(0.1mmol,23.5mg),氢氧化钾(40mg,0.6mmol),2mL水和0.5mL正丙醇(n-propanol),加热到50℃反应,直到原料消失。反应结束后,反应管冷却至室温,加入二氯甲烷将水相洗三次。水相用2N盐酸溶液pH调至2,二氯甲烷萃取三次,合并有机相,无水硫酸钠干燥。除去溶剂得到纯的产物2-叔丁胺羰基苯甲酸(19.6mg,85%).1H NMR(400MHz,CD3OD)δ7.94(d,J=8.0Hz,1H),7.91(br,1H),7.58(td,J=7.6,1.2Hz,1H),7.49(td,J=7.6,1.2Hz,1H),7.38(dd,J=7.6,0.8Hz,1H),1.43(s,9H);13C NMR(100MHz,CD3OD)δ172.39,169.35,141.09,133.02,131.25,130.34,130.03,128.85,52.59,28.77;HRMS(ESI-TOF)m/z Calcd for C12H16NO3(M+H)+:222.1125,found:222.1127.
在本发明提及的所有文献都在本申请中引用作为参考,就如同每一篇文献被单独引用作为参考那样。此外应理解,在阅读了本发明的上述讲授内容之后,本领域技术人员可以对本发明作各种改动或修改,这些等价形式同样落于本申请所附权利要求书所限定的范围。
Claims (9)
1.一种式I化合物的制备方法,其特征在于,在惰性溶剂的存在下,在钯催化剂的催化下,在氧化剂的作用下,将式II化合物与式III化合物进行反应,得到式I化合物;其中,所述的氧化剂为空气、氧气、氧化银、碳酸银、硝酸银、醋酸铜、硫酸铜、氯化铜、溴化铜;
其中,
表示C6~C14芳基或C2~C9杂芳基;
R1、R2、R3、R4各自独立地选自氢、C1~C40饱和或不饱和的脂肪族烃基、C1~C40烷氧基、C1~C40烷硫基、亚甲二氧基、卤代的C1~C40饱和或不饱和脂肪族烃基、卤代的C1~C40烷氧基、卤素、硝基、氰基、-CO2R7、-OC(O)R8、-P(O)(R9)(R10)、-P(O)(OR9)(OR10)、-SO2NR11R12、-NR13R14、-C(O)NR15R16、C6~C14芳基、C6~C14芳氧基、C6~C14芳基-C1~C10烷氧基、C2-C9杂芳基、C2~C9杂环基;或R1、R2、R3、R4中相邻的两个基团和与这两个基团连接的碳原子共同构成C3~C6环烷基或C2~C9杂环基;
R5为C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C2~C9杂芳基、C2~C9杂环基;
R6为C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C2~C9杂芳基、C2~C9杂环基;
其中,R7为氢、C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C2~C9杂芳基、C2~C9杂环基;
R8为氢、C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C2~C9杂芳基、C2~C9杂环基;
R9为氢、C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C2~C9杂芳基、C2~C9杂环基;
R10为氢、C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C2~C9杂芳基、C2~C9杂环基;
R11为氢、C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C2~C9杂芳基、C2~C9杂环基;
R12为氢、C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C2~C9杂芳基、C2~C9杂环基;
R13为氢、C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C6~C14芳基磺酰基、C1~C10烷基磺酰基、C1~C10酰基、C2~C9杂芳基、C2~C9杂环基;
R14为氢、C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C6~C14芳基磺酰基、C1~C10烷基磺酰基、C1~C10酰基、C2~C9杂芳基、C2~C9杂环基;
R15为氢、C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C2~C9杂芳基、C2~C9杂环基;
R16为氢、C1~C40饱和或不饱和的脂肪族烃基、C6~C14芳基、C2~C9杂芳基、C2~C9杂环基;
上述各基团中,所述芳基、杂芳基、杂环基任选被选自下组的一个或多个取代基所取代:卤素、C1~C40烷基、C1~C10酰基、C1~C40烷氧基。
2.如权利要求1所述的制备方法,其特征在于,所述的C6~C14芳基选自下组:苯基、萘基;所述芳基任选被选自下组的一个或多个取代基所取代:卤素、C1~C40烷基、C1~C10酰基、C1~C40烷氧基。
3.如权利要求1所述的制备方法,其特征在于,所述的C2~C9杂芳基选自下组:呋喃基、苯并呋喃基、噻吩基、苯并噻吩基、吲哚基、异吲哚基、吡咯基、噻唑基、噁唑基、吡唑基、咪唑基、吡喃基、哒嗪基、吡嗪基、嘧啶基、吡啶基、喹啉基、异喹啉基、咔唑基;所述杂芳基任选被选自下组的一个或多个取代基所取代:卤素、C1~C40烷基、C1~C10酰基、C1~C40烷氧基。
4.如权利要求1所述的制备方法,其特征在于,所述C2~C9杂环基选自下组:四氢喹啉基、四氢吲哚基、噁唑啉基、二氢吡咯基、四氢吡啶基、四氢呋喃基、吗啉基、哌嗪基、哌啶基、吡咯啉基、咪唑啉基。
5.如权利要求1所述的制备方法,其特征在于,
所述的钯催化剂选自下组:三(二亚苄基丙酮)二钯、四(三苯基膦钯)、醋酸钯、氯化钯、[1,1'-双(二苯基磷)二茂铁]二氯化钯、双乙腈氯化钯、三氟醋酸钯、三氟甲磺酸钯、氢氧化钯、烯丙基氯化钯。
6.如权利要求1所述的制备方法,其特征在于,所述的惰性溶剂为甲苯、乙苯、四氢呋喃、1,4-二氧六环、N,N’-二甲基甲酰胺、N,N’-二甲基乙酰胺、N-甲基吡咯烷酮、二甲亚砜、1,2-二氯乙烷、乙醚、乙二醇二甲醚、乙腈、乙酸乙酯、二氯甲烷、丙酮。
7.如权利要求1所述的制备方法,其特征在于,式II化合物与式III化合物的摩尔比为5:1~1:5;和/或所述钯催化剂的用量是式II化合物的用量的0.1~20mol%。
8.如权利要求1所述的制备方法,其特征在于,所述反应在20~140℃下进行;和/或所述反应进行0.1~40小时。
9.一种式1-3、式1-6和式1-7所示的苯甲酸衍生物的制备方法,其特征在于,
(a)所述方法包括步骤:
(1)在还原剂的存在下,将式I化合物进行反应,从而得到式I-1化合物;
(2)在酸的存在下,将式I-1化合物进行反应,从而得到式I-2化合物;
(3)在酸的存在下,将式I-2化合物进行反应,从而得到式I-3化合物或其与所述的酸形成的盐;
或(b)所述方法包括步骤:
(1)在碱的存在下,将式I化合物进行反应,从而得到式I-4化合物;
(2)在酸的存在下,将式I-4化合物进行反应,从而得到式I-5化合物;
(3)在碱的存在下,将式I-5化合物进行反应,从而得到式I-6化合物;
或(c)所述方法包括步骤:
(1)在酸的存在下,将式I化合物进行反应,从而得到式I-7化合物;
上述各式中,R1、R2、R3、R4、R5、R6定义如权利要求1中定义。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410307064.6A CN105294536B (zh) | 2014-06-30 | 2014-06-30 | 一种制备3-亚氨基异吲哚啉酮类化合物的方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410307064.6A CN105294536B (zh) | 2014-06-30 | 2014-06-30 | 一种制备3-亚氨基异吲哚啉酮类化合物的方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105294536A CN105294536A (zh) | 2016-02-03 |
CN105294536B true CN105294536B (zh) | 2018-06-29 |
Family
ID=55192458
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201410307064.6A Active CN105294536B (zh) | 2014-06-30 | 2014-06-30 | 一种制备3-亚氨基异吲哚啉酮类化合物的方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN105294536B (zh) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108017571A (zh) * | 2016-10-29 | 2018-05-11 | 浙江九洲药物科技有限公司 | 一种取代异吲哚啉化合物的制备方法 |
EP3559005A1 (en) | 2016-12-21 | 2019-10-30 | Biotheryx Inc. | Thienopyrrole derivatives for use in targeting proteins, compositions, methods, and uses thereof |
CN109369504B (zh) * | 2018-12-06 | 2020-05-12 | 温州大学 | 含硫3-亚甲基异吲哚啉-1-酮衍生物的制备方法 |
CN110437129B (zh) * | 2019-08-17 | 2022-08-09 | 齐鲁工业大学 | 一种合成3-醚基异吲哚啉酮类化合物的简单方法 |
CN111732592A (zh) * | 2020-07-02 | 2020-10-02 | 湖北文理学院 | 一种含吲哚骨架的稠环化合物及其制备方法 |
CN111732546A (zh) * | 2020-07-02 | 2020-10-02 | 湖北文理学院 | 一种含咪唑骨架的稠环化合物及其制备方法 |
CN115340486B (zh) * | 2022-09-21 | 2023-11-28 | 中国科学技术大学 | 异吲哚啉化合物及其制备方法和应用 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3118126A1 (de) * | 1981-05-07 | 1982-12-02 | Bayer Ag, 5090 Leverkusen | Sulfenamide zur verwendung in arzneimitteln |
CN102911109A (zh) * | 2012-10-29 | 2013-02-06 | 山西医科大学 | 一种6-氨基-5-氟-1-异吲哚啉酮的制备方法 |
-
2014
- 2014-06-30 CN CN201410307064.6A patent/CN105294536B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3118126A1 (de) * | 1981-05-07 | 1982-12-02 | Bayer Ag, 5090 Leverkusen | Sulfenamide zur verwendung in arzneimitteln |
CN102911109A (zh) * | 2012-10-29 | 2013-02-06 | 山西医科大学 | 一种6-氨基-5-氟-1-异吲哚啉酮的制备方法 |
Non-Patent Citations (5)
Title |
---|
Lewis酸催化合成3-取代异吲哚啉酮;刘明星,等;《中国化学会·第八届有机化学学术会议暨首届重庆有机化学国际研讨会》;20131017;第348页 * |
Reaction of bis(nitromethyl)prehnitene with aqueous ammonia;Koji Chiba,等;《Chemistry Letters》;19741231(第6期);第569-570页尤其是第570页第1-2行化合物5 * |
Rhenium-Catalyzed Synthesis of 3-Imino-1-isoindolinones by C-H Bond Activation: Application to the Synthesis of Polyimide Derivatives;Shunsuke Sueki,等;《Angewandte Chemie International Edition》;20130913;第52卷(第45期);第11879-11883页 * |
Rhodium-Catalyzed Annulation of N-Benzoylsulfonamide with Isocyanide through C-H Activation;Chen Zhu,等;《Chemistry A European Journal》;20111004;第17卷(第45期);第12591-12595页 * |
Studies on the oxidation of hexamethylbenzene. III. The preparation of tetramethylphthalic anhydride;Koji Chiba,等;《Bulletin of the Chemical Society of Japan》;19760930;第49卷(第9期);第2614-2616页尤其是第2616页左栏第1-2行化合物9 * |
Also Published As
Publication number | Publication date |
---|---|
CN105294536A (zh) | 2016-02-03 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105294536B (zh) | 一种制备3-亚氨基异吲哚啉酮类化合物的方法 | |
CN110204486B (zh) | 一种喹啉衍生物的合成方法 | |
CN113336689B (zh) | 3-(α-氟乙烯基/羰基)吲哚类化合物的合成方法及抗癌活性 | |
KR20100041772A (ko) | 알리스키렌과 같은 레닌 억제제의 중간체의 합성 방법 | |
CN102659662A (zh) | 3-r-3-羟基-2-氧化吲哚类化合物的合成方法 | |
Wang et al. | An efficient route to quinoline-2-carboxylates via a rhodium-catalyzed oxidative [5+ 1] annulation of 2-vinylanilines with α-diazocarbonyl compounds | |
Yasui et al. | Toward general access to the aspidosperma-type terpenoid indole alkaloids: synthesis of the key 3, 3-disubstituted piperidones through enantioselective intramolecular heck-type reaction of chloroformamides | |
CN115215796B (zh) | 一种3-酰基喹啉类化合物的合成方法 | |
CN116178243A (zh) | 一种(杂)芳基稠和咔唑类化合物的制备方法及其应用 | |
CN102838597B (zh) | 杂芳环咪唑并[1,2-a]吡啶化合物的制备方法 | |
CN111484436A (zh) | 一种在吲哚c3位引入异戊烯基的方法 | |
CN113912609B (zh) | 一种天然生物碱色胺酮及其衍生物的制备方法 | |
CN115215814A (zh) | 异恶唑烷类化合物的合成方法 | |
CN109988113B (zh) | 一种[60]富勒烯四氢喹啉衍生物的合成方法 | |
CN115054599A (zh) | 2-氨基吲哚类化合物在抗肿瘤药物中的应用 | |
CN111004164B (zh) | 一种多取代2-芳基吲哚衍生物的制备方法 | |
CN113979918A (zh) | 一种含有全碳四取代烯烃结构的c-3位五元螺环吲哚酮衍生物及其制备和应用 | |
CN109369647B (zh) | 一种稠环[1,2-a]吲哚类化合物和2,3-二取代吲哚类化合物的合成方法 | |
Dimitrijević et al. | Rapid access to pyrrolo [3, 4-c] quinoline-1, 3-diones: An improved synthetic protocol using a precursor prepared by Pfitzinger reaction | |
CN111662202A (zh) | 一种α-酮酰胺类化合物的合成方法 | |
CN106831522B (zh) | 内酰胺类化合物及其制备方法 | |
CN106866348B (zh) | 一种多环芳烃化合物、合成方法及用途 | |
CN111808072B (zh) | 一种3-甲酰基吲哚衍生物的合成方法 | |
CN114349684B (zh) | 一种苯并[c,d]吲哚亚胺衍生物的合成方法 | |
CN113754544B (zh) | 一种多取代(e)-三氟甲基烯烃的制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |