CN105153032A - 6-h-菲啶类化合物的一锅法制备方法 - Google Patents
6-h-菲啶类化合物的一锅法制备方法 Download PDFInfo
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- CN105153032A CN105153032A CN201510668949.3A CN201510668949A CN105153032A CN 105153032 A CN105153032 A CN 105153032A CN 201510668949 A CN201510668949 A CN 201510668949A CN 105153032 A CN105153032 A CN 105153032A
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- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 238000005580 one pot reaction Methods 0.000 title claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 19
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000003446 ligand Substances 0.000 claims abstract description 8
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 7
- 239000003054 catalyst Substances 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims abstract description 5
- 239000003513 alkali Substances 0.000 claims abstract description 4
- 239000011261 inert gas Substances 0.000 claims abstract description 4
- 229910052751 metal Inorganic materials 0.000 claims abstract description 3
- 239000002184 metal Substances 0.000 claims abstract description 3
- -1 phenanthridine compound Chemical class 0.000 claims description 17
- RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthrridine Natural products C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 6
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 238000004587 chromatography analysis Methods 0.000 claims description 4
- 238000004440 column chromatography Methods 0.000 claims description 4
- 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 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 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 3
- 125000006239 protecting group Chemical group 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 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 2
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- PAGZTSLSNQZYEV-UHFFFAOYSA-L 2,2-dimethylpropanoate;palladium(2+) Chemical compound [Pd+2].CC(C)(C)C([O-])=O.CC(C)(C)C([O-])=O PAGZTSLSNQZYEV-UHFFFAOYSA-L 0.000 claims description 2
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 2
- 229910052786 argon Inorganic materials 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 claims description 2
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 claims description 2
- 238000000605 extraction Methods 0.000 claims description 2
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 claims description 2
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 claims description 2
- 229910052808 lithium carbonate Inorganic materials 0.000 claims description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- SJRDNQOIQZOVQD-UHFFFAOYSA-M sodium;2,2-dimethylpropanoate Chemical compound [Na+].CC(C)(C)C([O-])=O SJRDNQOIQZOVQD-UHFFFAOYSA-M 0.000 claims description 2
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 abstract description 14
- 150000004982 aromatic amines Chemical class 0.000 abstract description 6
- 239000002994 raw material Substances 0.000 abstract description 5
- 238000010438 heat treatment Methods 0.000 abstract description 2
- VCJZTATVUDMNLU-UHFFFAOYSA-N dibromomethylbenzene Chemical class BrC(Br)C1=CC=CC=C1 VCJZTATVUDMNLU-UHFFFAOYSA-N 0.000 abstract 2
- 238000010523 cascade reaction Methods 0.000 abstract 1
- 230000001681 protective effect Effects 0.000 abstract 1
- 239000000376 reactant Substances 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 76
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 19
- 238000005160 1H NMR spectroscopy Methods 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 5
- 150000005053 phenanthridines Chemical class 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 125000006280 2-bromobenzyl group Chemical group [H]C1=C([H])C(Br)=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- OJRUSAPKCPIVBY-KQYNXXCUSA-N C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N Chemical compound C1=NC2=C(N=C(N=C2N1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)I)N OJRUSAPKCPIVBY-KQYNXXCUSA-N 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- 238000010499 C–H functionalization reaction Methods 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 238000006929 Pictet-Spengler synthesis reaction Methods 0.000 description 1
- 239000004115 Sodium Silicate Substances 0.000 description 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
- 238000005899 aromatization reaction Methods 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940126543 compound 14 Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 239000008204 material by function Substances 0.000 description 1
- LBTPIFQNEKOAIM-UHFFFAOYSA-N n-phenylmethanesulfonamide Chemical compound CS(=O)(=O)NC1=CC=CC=C1 LBTPIFQNEKOAIM-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000001699 photocatalysis Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000007348 radical reaction Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229910052911 sodium silicate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/10—Aza-phenanthrenes
- C07D221/12—Phenanthridines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/18—Ring systems of four or more rings
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明公开了一种6-<i>H</i>-菲啶类化合物的制备方法,包括:在溶剂中加入反应物<i>N</i>-保护的芳胺和邻溴溴苄类化合物,再加入金属钯催化剂,配体和碱,在加热及惰性气体保护条件下进行化学反应,反应完成经后处理得到本发明化合物纯品。本发明的制备方法采用简单易得的<i>N</i>-保护的芳胺和商业易得的邻溴溴苄类化合物为原料,通过“一锅煮”三步串联反应获得6-<i>H</i>-菲啶类化合物,具有操作简便、后处理简单、产率较高等特点。
Description
技术领域
本发明属于杂环化合物技术领域,具体涉及到6-H-菲啶类化合物的制备方法。
背景技术
菲啶是一类重要的稠杂环化合物,其结构单元广泛存在于天然产物、药物活性分子和有机功能材料中,因此针对这类化合物的合成受到越来越多的关注。传统的方法是通过Pictet-Spengler反应来合成,近年来也发展了其它的新方法,如光催化的自由基反应、微波辐射的环化反应、5,6-二氢菲啶化合物的氧化反应等等。但是对于6-H-菲啶类化合物的合成报道较少,尤其是使用简单易得的原料通过“一锅煮”的方法来合成这类化合物还未见报道。本发明以易得的N-保护的芳胺和商业易得的邻溴溴苄类化合物为原料,采用“一锅煮”的方法,可以简便、高效的合成6-H-菲啶类化合物。
发明内容
本发明的目的在于提供一种以N-保护的芳胺和邻溴溴苄类化合物制备6-H-菲啶类化合物的方法。
本发明所涉及的6-H-菲啶类化合物化学结构通式为:
其中,取代基R1和R2为烷基、烷氧基、酰基、硝基、氰基、卤素中的任意一种。
其反应过程如下:
上述所述的催化剂为零价钯[如四(三苯基膦)钯、三(二亚苄基丙酮)二钯等]和二价钯催化剂[醋酸钯、三氟乙酸钯、特戊酸钯、氯化钯等]。
上述反应中,配体为膦配体[三苯基膦、三正丁基膦,1,3-双(二苯基膦)丙烷、4,5-双二苯基膦-9,9-二甲基氧杂蒽,2,2'-双-(二苯膦基)-1,1'-联萘,1,1'-双(二苯基膦)二茂铁等]和氮配体[吡啶、1,10-菲啰啉等]。
上述反应中,碱为无机碱,如氢氧化钠、氢氧化钾、碳酸锂、碳酸钠、碳酸钾、碳酸铯、特戊酸钠等。
上述反应中,溶剂可选用对反应底物和目标产物具有较好溶解性的溶剂,以利于反应的顺利进行,例如:N,N-二甲基甲酰胺,二甲基亚砜,甲苯,1,4-二氧六环,乙腈等。
上述反应中,惰性气体为氩气或者氮气。
上述反应的温度为120~160℃。
上述反应的时间为20-28小时。
所制得的6-H-菲啶类化合物可以采用色谱、结晶、层析、萃取等方法分离,优选用柱色谱方法进行分离。
本发明以N-保护的芳胺和邻溴溴苄类化合物为原料合成6-H-菲啶类化合物,具有以下优点:
1.合成的路线短(一步可得到目标化合物),收率较高;
2.原料易得,反应易于操作;
3.通过亲核取代/C-H活化/芳构化串联反应得到目标化合物。
附图说明
图1为本发明实施例制备的6-H-菲啶类化合物代表性图谱1。
图2为本发明实施例制备的6-H-菲啶类化合物代表性图谱2。
具体实施方式
下面结合附图和具体实施例对本发明的实施方式作进一步说明,但是本发明并不限于下述实施方式,在本领域普通技术人员所具备的知识范围内,还可能对其作出种种变化。
一种“一锅法”制备6-H-菲啶类化合物的方法,其反应过程如下:
其中,PG(ProtectedGroup)为保护基,包括-Ms(甲磺酰基)、-Ts(对甲基苯磺酰基)、-Ns(对硝基苯磺酰基)和-Ac(乙酰基);取代基R1和R2为烷基、烷氧基、酰基、硝基、氰基、卤素中的任意一种。
合成代表性化合物1的操作步骤:
将N-保护的芳胺、邻溴溴苄类化合物,金属钯催化剂,配体和碱加入到有机溶剂中,在加热及惰性气体保护条件下反应,反应完成经后处理得到本发明化合物纯品。
所述的N-保护的芳胺化合物的结构式如下:
,PG(ProtectedGroup)为保护基,包括-Ms(甲磺酰基)、Ts(对甲基苯磺酰基)、Ns(对硝基苯磺酰基)、Ac(乙酰基)等。
所述的邻溴溴苄类化合物的结构式如下:
所述的6-H-菲啶类化合物的结构式如下:
本发明制备6-H-菲啶化合物的制备方法中,采用柱色谱纯化的方法,使用的溶剂是:乙酸乙酯和石油醚(V:V=1:5)。
称取N-甲磺酰基苯胺(51.4mg,0.3mmol)和邻溴溴苄(75.0mg,0.3mmol)于干燥的反应瓶中,并加入碳酸铯(391.0mg,1.2mmol),三氟乙酸钯(5.0mg,0.015mmol),三苯基膦(15.7mg,0.06mmol)和2mL无水N,N-二甲基甲酰胺,氮气保护下,160°C反应24小时。反应完毕后将反应液倒入10mL饱和食盐水中,用乙酸乙酯萃取(5x10mL),合并有机相,无水Na2SO4干燥,过滤,浓缩得粗产物。经柱色谱分离得到目标化合物1(43.0mg,80%)。
在本实施例中,使用与制备化合物1相同的反应条件,还可得到化合物2-19:
化合物1-19的数据为:
化合物1:Whitesolid,mp106.8-108.2°C;1HNMR(400MHz,CDCl3)δ9.27(s,1H),8.60-8.53(m,2H),8.20(d,J=8.0Hz,1H),8.01(d,J=8.0Hz,1H),7.84-7.80(m,1H),7.77-7.71(m,1H),7.69-7.64(m,2H);13CNMR(100MHz,CDCl3)δ153.6,144.5,132.6,131.1,130.2,128.8,128.7,127.5,127.1,126.4,124.2,122.3,121.9;HRMS(ESI-TOF)Calcd.forC13H10N[M+H]+:180.0808;found:180.0803.
化合物2:Lightyellowsolid,mp93.1-94.6°C;1HNMR(400MHz,CDCl3)δ9.30(s,1H),8.56(d,J=8.0Hz,1H),8.41(d,J=8.0Hz,1H),8.02(d,J=8.0Hz,1H),7.83-7.79(m,1H),7.69-7.65(m,1H),7.61-7.53(m,2H),2.99(s,3H);13CNMR(100MHz,CDCl3)δ152.2,143.3,137.8,132.9,131.0,129.6,128.7,127.3,126.7,126.2,124.0,122.1,120.2,18.8;HRMS(ESI-TOF)Calcd.forC14H12N[M+H]+:194.0964;found:194.0958.
化合物3:Lightyellowoil;1HNMR(400MHz,CDCl3)δ9.31(s,1H),8.57(d,J=8.0Hz,1H),8.43-8.41(m,1H),8.02(d,J=8.0Hz,1H),7.82-7.78(m,1H),7.68-7.64(m,1H),7.63-7.59(m,2H),3.40(q,J=7.6Hz,2H),1.45(td,J=1.2Hz,7.6Hz,3H);13CNMR(100MHz,CDCl3)δ152.2,143.7,142.7,133.0,130.8,128.7,127.9,127.3,126.9,126.2,124.1,122.1,120.1,25.3,15.6;HRMS(ESI-TOF)Calcd.forC15H14N[M+H]+:208.1121;found:208.1120.
化合物4:Whitesolid,mp73.4-74.8°C;1HNMR(400MHz,DMSO-d 6+CDCl3)δ9.12(s,1H),8.39(d,J=8.4Hz,1H),7.95(d,J=8.4Hz,1H),7.86(d,J=8.0Hz,1H),7.67-7.63(m,1H),7.51(d,J=7.2Hz,1H),7.40(t,J=8.0Hz,1H),6.97(d,J=8.0Hz,1H),4.16(q,J=7.2Hz,2H),1.44(td,J=0.8Hz,7.0Hz,3H);13CNMR(100MHz,DMSO-d 6+CDCl3)δ154.9,151.7,135.1,132.0,130.6,128.3,127.3,127.0,126.0,124.9,122.0,113.5,109.0,64.0,14.5;HRMS(ESI-TOF)Calcd.forC15H14NO[M+H]+:224.1070;found:224.1070.
化合物5:Lightyellowsolid,mp101.1-102.4°C;1HNMR(400MHz,CDCl3)δ9.37(s,1H),8.56(d,J=8.4Hz,1H),8.46(d,J=8.4Hz,1H),8.06(d,J=8.0Hz,1H),7.89-7.82(m,2H),7.73(td,J=0.8,7.6Hz,1H),7.57(td,J=1.6,8.0Hz,1H);13CNMR(100MHz,CDCl3)δ154.2,140.8,134.4,132.4,131.6,129.2,129.1,128.3,127.1,126.4,126.0,122.2,121.3;HRMS(ESI-TOF)Calcd.forC13H9ClN[M+H]+:214.0418;found:214.0419.
化合物6:Lightyellowsolid,45.2mg,78%yield,mp90.1-91.3°C;1HNMR(400MHz,CDCl3)δ9.22(s,1H),8.58(d,J=8.4Hz,1H),8.34(s,1H),8.08(d,J=8.4Hz,1H),8.02(d,J=8.0Hz,1H),7.84(td,J=1.2,7.6Hz,1H),7.69(td,J=1.2,7.6Hz,1H),7.57(dd,J=1.2,8.4Hz,1H),2.63(s,3H).13CNMR(100MHz,CDCl3)δ152.7,142.8,137.1,132.4,130.9,130.5,129.9,128.8,127.4,126.6,124.0,121.9,22.1.HRMS(ESI-TOF)Calcd.forC14H12N[M+H]+:194.0964;found:194.0962.
化合物7:Whitesolid,39.5mg,63%yield,mp103.7-105.1°C;1HNMR(400MHz,CDCl3)δ9.09(s,1H),8.42(d,J=8.4Hz,1H),8.07(d,J=9.2Hz,1H),7.94(d,J=8.0Hz,1H),7.79(d,J=2.8Hz,1H),7.75(d,J=7,6Hz,1H),7.62(d,J=7,6Hz,1H),7.32(dd,J=2.4,8.8Hz,1H),3.95(s,3H);13CNMR(100MHz,CDCl3)δ158.4,151.0,139.7,132.0,131.4,130.5,128.6,127.5,126.5,125.1,121.8,118.5,103.0,55.6;HRMS(ESI-TOF)Calcd.forC14H12NO[M+H]+:210.0913;found:210.0912.
化合物8:Lightyellowsolid,mp130.8-132.5°C;1HNMR(400MHz,CDCl3)δ9.23(s,1H),8.48(d,J=8.4Hz,1H),8.19-8.15(m,2H),8.05(d,J=8.4Hz,1H),7.89-7.85(m,1H),7.76-7.73(m,1H),7.51-7.45(m,1H);13CNMR(100MHz,CDCl3)δ161.5(d,J=245.8Hz,1C),152.9(d,J=2.7Hz,1C),141.4,132.4(d,J=9.2Hz,1C),132.1(d,J=4.3Hz,1C),131.2,128.6(d,J=66.1Hz,1C),126.5,125.6(d,J=9.2Hz,1C),122.2,117.7(d,J=24.1Hz),107.3(d,J=23.0Hz).HRMS(ESI-TOF)Calcd.forC13H9FN[M+H]+:198.0714;found:198.0713.
化合物9:Whitesolid,mp155.8-157.2°C;1HNMR(400MHz,CDCl3)δ9.20(s,1H),8.43-8.42(m,2H),8.07(d,J=8.4Hz,1H),8.00(d,J=8.4Hz,1H),7.82(t,J=7.6Hz,1H),7.70(t,J=7.6Hz,1H),7.63(dd,J=0.4,8.4Hz,1H).13CNMR(100MHz,CDCl3)δ153.8,142.8,133.1,131.6,131.5,131.3,129.2,128.9,128.2,126.5,125.2,122.0,121.9;HRMS(ESI-TOF)Calcd.forC13H9ClN[M+H]+:214.0418;found:214.0417.
化合物10:Lightyellowsolid,mp141.9-143.3°C;1HNMR(400MHz,CDCl3)δ9.22(s,1H),8.85(d,J=8.4Hz,1H),8.07(d,J=8.4Hz,1H),7.90(s,1H),7.84(td,J=1.6,8.0Hz,1H),7.69(d,J=8.0Hz,1H),7.37(s,1H),3.10(s,3H),2.56(s,3H);13CNMR(100MHz,CDCl3)δ153.8,141.6,138.0,135.3,134.0,133.1,130.5,129.3,128.8,127.4,126.4,126.3,26.7,21.3;HRMS(ESI-TOF)Calcd.forC15H14N[M+H]+:208.1121;found:208.1119.
化合物11:Lightyellowsolid,mp86.7-88.2°C;1HNMR(400MHz,CDCl3)δ9.29(s,1H),8.88(d,J=8.4Hz,1H),8.09(d,J=8.0Hz,1H),7.86-7.82(m,1H),7.71(td,J=0.8,7.6Hz,1H),7.52(d,J=7.4Hz,1H),7.42(d,J=7.4Hz,1H),3.09(s,3H),2.86(s,3H);13CNMR(100MHz,CDCl3)δ152.3,144.7,136.0,134.2,133.1,130.8,130.2,129.1,128.9,127.5,126.7,126.6,123.8,26.9,19.4.HRMS(ESI-TOF)Calcd.forC15H14N[M+H]+:208.1121;found:208.1121.
化合物12:Lightyellowsolid,mp117.0-118.5°C;1HNMR(400MHz,CDCl3)δ9.22(s,1H),8.53(d,J=8.4Hz,1H),8.16(s,1H),7.99(d,J=8.0Hz,1H),7.78(d,J=7.6Hz,1H),7.64(d,J=7.6Hz,1H),7.41(s,1H),2.85(s,3H),2.56(s,3H).13CNMR(100MHz,CDCl3)δ151.3,141.6,137.3,136.4,132.6,131.3,130.6,128.6,127.1,126.3,123.9,122.1,119.7,22.0,18.7.HRMS(ESI-TOF)Calcd.forC15H14N[M+H]+:208.1121;found:208.1121.
化合物13:Lightyellowsolid,mp145.1-146.4°C;1HNMR(400MHz,CDCl3)δ9.27(s,1H),8.53(d,J=8.4Hz,1H),8.29(d,J=8.4Hz,1H),7.99(d,J=8.0Hz,1H),7.78(t,J=7.6Hz,1H),7.63(t,J=7.6Hz,1H),7.46(d,J=8.4Hz,1H),2.83(s,3H),2.53(s,3H);13CNMR(100MHz,CDCl3)δ152.1,143.2,136.9,135.5,133.0,130.7,129.3,128.6,126.9,125.7,122.0,121.9,119.2,20.8,14.0;HRMS(ESI-TOF)Calcd.forC15H14N[M+H]+:208.1121;found:208.1119.
化合物14:Lightyellowsolid,mp133.5-135.1°C;1HNMR(400MHz,CDCl3)δ9.48(s,1H),9.42(d,J=8.0Hz,1H),8.65(d,J=8.0Hz,1H),8.52(d,J=8.0Hz,1H),8.13(d,J=7.2Hz,1H),8.03-7.98(m,2H),7.87(t,J=6.8Hz,1H),7.79(t,J=7.2Hz,1H),7.74-7.67(m,2H);13CNMR(100MHz,CDCl3)δ152.1,141.6,133.4,132.9,132.1,130.9,128.8,128.0,127.8,127.5,127.2,127.1,127.0,124.8,122.3,121.2,120.0;HRMS(ESI-TOF)Calcd.forC17H12N[M+H]+:230.0964;found:230.0965.
化合物15:Yellowsolid,mp109.1-110.5°C;1HNMR(400MHz,CDCl3)δ9.23(s,1H),8.52-8.48(m,2H),8.17(d,J=8.0Hz,1H),7.71-7.64(m,2H),7.50-7.47(m,1H),7.38(s,1H),3.99(s,3H);13CNMR(100MHz,CDCl3)δ159.0,152.9,143.7,130.2,127.8,127.3,127.1,124.4,123.7,122.2,121.9,108.1,55.7;HRMS(ESI-TOF)Calcd.forC14H12NO[M+H]+:210.0913;found:210.0917.
化合物16:Lightyellowsolid,mp140.8-142.1°C;1HNMR(400MHz,CDCl3)δ9.19(s,1H),8.48(d,J=9.2Hz,1H),8.12(s,1H),7.44(dd,J=2.0,9.2Hz,1H),7.38(s,1H),7.34(d,J=2.0Hz,1H),3.98(s,3H),2.84(s,3H),2.57(s,3H);13CNMR(100MHz,CDCl3)δ158.7,150.6,140.9,137.3,136.6,130.5,127.7,127.2,124.2,123.9,121.9,119.3,107.7,55.7,22.1,18.7;HRMS(ESI-TOF)Calcd.forC16H16NO[M+H]+:238.1226;found:238.1225.
化合物17:Lightyellowsolid,mp146.3-147.3°C;1HNMR(400MHz,CDCl3)δ9.22(s,1H),8.46(d,J=8.8Hz,1H),8.24(d,J=8.8Hz,1H),7.47-7.42(m,2H),7.34-7.33(m,1H),3.98(s,3H),2.82(s,3H),2.53(s,3H);13CNMR(100MHz,CDCl3)δ158.5,151.4,142.5,135.9,135.4,129.5,127.6,127.0,123.7,122.2,122.0,118.8,107.7,55.7,20.8,14.0;HRMS(ESI-TOF)Calcd.forC16H16NO[M+H]+:238.1226;found:238.1226.
化合物18:Yellowsolid,mp273.8-275.6°C;1HNMR(400MHz,DMSO-d 6+CDCl3)δ9.61-9.58(m,2H),9.51(s,1H),9.12(d,J=8.0Hz,1H),8.40(d,J=9.2Hz,1H),8.36-8.31(m,2H),8.29-8.24(m,2H),8.19-8.13(m,1H),8.09-8.02(m,2H),7.86(t,J=7.6Hz,1H);13CNMR(100MHz,DMSO-d 6+CDCl3)δ153.0,138.2,132.5,131.7,131.5,131.1,130.1,129.3,128.9,128.6,128.3,128.2,128.1,127.0,126.5,126.1,125.7,124.3,123.9,123.1,121.6,119.1;HRMS(ESI-TOF)Calcd.forC23H14N[M+H]+:304.1121;found:304.1119.
化合物19:Lightyellowsolid,mp108.7-110.1°C;1HNMR(400MHz,CDCl3)δ9.31(s,1H),9.18-9.12(m,1H),9.08-9.03(m,1H),8.32(dd,J=1.2,8.0Hz,1H),8.05-8.02(m,1H),7.98-7.95(m,1H),7.91-7.87(m,1H),7.81-7.77(m,1H),7.73-7.70(m,3H);13CNMR(100MHz,CDCl3)δ152.7,146.6,135.2,131.2,130.3,129.0,128.8,128.3,128.2,127.9,127.1,127.0,126.9,125.3,125.1,124.7;HRMS(ESI-TOF)Calcd.forC17H12N[M+H]+:230.0964;found:230.0962。
Claims (10)
1.一种6-H-菲啶类化合物的“一锅法”制备方法,其特征是:反应过程如下:
;
其中,为N-保护的芳胺化合物,PG(ProtectedGroup)为保护基,包括-Ms(甲磺酰基)、-Ts(对甲基苯磺酰基)、-Ns(对硝基苯磺酰基)和-Ac(乙酰基);取代基R1和R2为烷基、烷氧基、酰基、硝基、氰基、卤素中的任意一种。
2.根据权利要求1所述的制备方法,其特征是:所述反应中的金属钯催化剂为零价钯或/和二价钯,包括四(三苯基膦)钯、三(二亚苄基丙酮)二钯、醋酸钯、三氟乙酸钯、特戊酸钯和氯化钯。
3.根据权利要求1所述的制备方法,其特征是:所述反应中的配体为膦配体或/和氮配体,包括三苯基膦、三正丁基膦、1,3-双(二苯基膦)丙烷、4,5-双二苯基膦-9,9-二甲基氧杂蒽、2,2'-双-(二苯膦基)-1,1'-联萘、1,1'-双(二苯基膦)二茂铁、吡啶和1,10-菲啰啉。
4.根据权利要求1所述的制备方法,其特征是:所述反应中的碱为无机碱,包括氢氧化钠、氢氧化钾、碳酸锂、碳酸钠、碳酸钾、碳酸铯或特戊酸钠。
5.根据权利要求1所述的制备方法,其特征是:所述反应中溶剂为N,N-二甲基甲酰胺,二甲基亚砜,甲苯,1,4-二氧六环或乙腈。
6.根据权利要求1所述的制备方法,其特征是:所述反应中惰性气体为氩气或氮气。
7.根据权利要求1-6之一所述的制备方法,其特征是:所述反应温度为120~160℃。
8.根据权利要求1-6之一所述的制备方法,其特征是:所述反应的时间为20-28小时。
9.根据权利要求1所述的制备方法,其特征是:所述反应所得物采用色谱法、结晶法、层析法或萃取法进行分离。
10.根据权利要求1所述的制备方法,其特征是:所述反应所得物采用柱色谱方法进行分离。
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106518761A (zh) * | 2016-11-09 | 2017-03-22 | 遵义医学院 | 一种菲啶类化合物的制备方法 |
CN107312164A (zh) * | 2017-06-09 | 2017-11-03 | 浙江工业大学义乌科学技术研究院有限公司 | 基于二茂铁与菲咯啉衍生物的共轭聚合物及其聚合方法和应用 |
CN107619468A (zh) * | 2017-09-18 | 2018-01-23 | 浙江工业大学义乌科学技术研究院有限公司 | 二茂铁与菲咯啉衍生物的共轭聚合物及其聚合方法和应用 |
WO2022166441A1 (zh) * | 2021-02-06 | 2022-08-11 | 台州市生物医化产业研究院有限公司 | 一种2-乙酰基-1,10-菲啰啉的制备方法 |
CN115028581A (zh) * | 2022-05-05 | 2022-09-09 | 常州大学 | 氢化菲啶类衍生物的制备方法以及在制备抗肿瘤药物中的应用 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1203781B (de) * | 1958-07-02 | 1965-10-28 | May & Baker Ltd | Verfahren zur Herstellung von trypanocid wirksamen Phenanthridiniumderivaten |
CN102911090A (zh) * | 2012-11-20 | 2013-02-06 | 成都理工大学 | 手性n-芳甲基-n-芳基叔丁基亚磺酰胺 |
CN103408492A (zh) * | 2013-08-21 | 2013-11-27 | 中国药科大学 | 一种6-取代-5, 6-二氢菲啶衍生物的制备方法 |
CN104844651A (zh) * | 2015-05-05 | 2015-08-19 | 洛阳师范学院 | 一种6-二氟甲基膦酸二乙酯基菲啶衍生物的合成方法 |
-
2015
- 2015-10-13 CN CN201510668949.3A patent/CN105153032A/zh active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1203781B (de) * | 1958-07-02 | 1965-10-28 | May & Baker Ltd | Verfahren zur Herstellung von trypanocid wirksamen Phenanthridiniumderivaten |
CN102911090A (zh) * | 2012-11-20 | 2013-02-06 | 成都理工大学 | 手性n-芳甲基-n-芳基叔丁基亚磺酰胺 |
CN103408492A (zh) * | 2013-08-21 | 2013-11-27 | 中国药科大学 | 一种6-取代-5, 6-二氢菲啶衍生物的制备方法 |
CN104844651A (zh) * | 2015-05-05 | 2015-08-19 | 洛阳师范学院 | 一种6-二氟甲基膦酸二乙酯基菲啶衍生物的合成方法 |
Non-Patent Citations (3)
Title |
---|
JOYDEV K. LAHA等: "Palladium-Catalyzed Regiocontrolled Domino Synthesis of N-Sulfonyl Dihydrophenanthridines and Dihydrodibenzo[c,e]azepines: Control over the Formation of Biaryl Sultams in the Intramolecular Direct Arylation", 《THE JOURNAL OF ORGANIC CHEMISTRY》 * |
PRANAB K. PATRA等: "A New Regiospecific Method for the Synthesis of Substituted Phenanthridines and Benzo[j]phenanthridines via Aromatic Annelation of 1-N-Benzenesulfonyi-3-[Bis(methyithio)methylene]-1,2,3,4-tetrahydroquinoline-4-one", 《TETRAHEDRON》 * |
SUBHADIP DE等: "Expeditious Approach to Pyrrolophenanthridones, Phenanthridines, and Benzo[c]phenanthridines via Organocatalytic Direct Biaryl-Coupling Promoted by Potassium tert-Butoxide", 《THE JOURNAL OF ORGANIC CHEMISTRY》 * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106518761A (zh) * | 2016-11-09 | 2017-03-22 | 遵义医学院 | 一种菲啶类化合物的制备方法 |
CN107312164A (zh) * | 2017-06-09 | 2017-11-03 | 浙江工业大学义乌科学技术研究院有限公司 | 基于二茂铁与菲咯啉衍生物的共轭聚合物及其聚合方法和应用 |
CN107619468A (zh) * | 2017-09-18 | 2018-01-23 | 浙江工业大学义乌科学技术研究院有限公司 | 二茂铁与菲咯啉衍生物的共轭聚合物及其聚合方法和应用 |
WO2022166441A1 (zh) * | 2021-02-06 | 2022-08-11 | 台州市生物医化产业研究院有限公司 | 一种2-乙酰基-1,10-菲啰啉的制备方法 |
GB2614199A (en) * | 2021-02-06 | 2023-06-28 | Taizhou Biomedical And Chemistry Industry Res Institute Co Ltd | Preparation method for 2-acetyl-1, 10-phenanthroline |
CN115028581A (zh) * | 2022-05-05 | 2022-09-09 | 常州大学 | 氢化菲啶类衍生物的制备方法以及在制备抗肿瘤药物中的应用 |
CN115028581B (zh) * | 2022-05-05 | 2024-04-30 | 常州大学 | 氢化菲啶类衍生物的制备方法以及在制备抗肿瘤药物中的应用 |
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