CN115403501A - Preparation method and application of 3,3' -diarylmethane compound - Google Patents
Preparation method and application of 3,3' -diarylmethane compound Download PDFInfo
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- CN115403501A CN115403501A CN202211147203.4A CN202211147203A CN115403501A CN 115403501 A CN115403501 A CN 115403501A CN 202211147203 A CN202211147203 A CN 202211147203A CN 115403501 A CN115403501 A CN 115403501A
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title claims abstract description 24
- 238000006243 chemical reaction Methods 0.000 claims abstract description 200
- 238000000034 method Methods 0.000 claims abstract description 16
- 125000003118 aryl group Chemical group 0.000 claims abstract description 9
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 5
- 229940041181 antineoplastic drug Drugs 0.000 claims abstract description 5
- 239000002904 solvent Substances 0.000 claims description 95
- -1 aniline compound Chemical class 0.000 claims description 88
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical group FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 46
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 17
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000003172 aldehyde group Chemical group 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000004185 ester group Chemical group 0.000 claims description 6
- 150000001448 anilines Chemical class 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 150000002989 phenols Chemical class 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 2
- 230000003078 antioxidant effect Effects 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 3
- 239000003963 antioxidant agent Substances 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 abstract description 150
- 239000002994 raw material Substances 0.000 abstract description 7
- 229940124599 anti-inflammatory drug Drugs 0.000 abstract description 4
- 230000003064 anti-oxidating effect Effects 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 4
- 239000003054 catalyst Substances 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 2
- 125000001664 diethylamino group Chemical class [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 abstract 1
- 230000007613 environmental effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 523
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 172
- 239000000047 product Substances 0.000 description 138
- 239000012074 organic phase Substances 0.000 description 88
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 86
- 239000000203 mixture Substances 0.000 description 79
- 239000012264 purified product Substances 0.000 description 71
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 46
- PSWCIARYGITEOY-UHFFFAOYSA-N 6-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2C=CNC2=C1 PSWCIARYGITEOY-UHFFFAOYSA-N 0.000 description 45
- 238000004440 column chromatography Methods 0.000 description 45
- 238000010791 quenching Methods 0.000 description 45
- 238000003786 synthesis reaction Methods 0.000 description 45
- 230000015572 biosynthetic process Effects 0.000 description 44
- 238000004821 distillation Methods 0.000 description 44
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 43
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 43
- 238000012512 characterization method Methods 0.000 description 43
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 43
- 239000003480 eluent Substances 0.000 description 43
- 239000003208 petroleum Substances 0.000 description 43
- 239000000843 powder Substances 0.000 description 43
- 239000011734 sodium Substances 0.000 description 41
- 239000008346 aqueous phase Substances 0.000 description 35
- 238000001035 drying Methods 0.000 description 17
- 238000009987 spinning Methods 0.000 description 15
- 230000000171 quenching effect Effects 0.000 description 10
- 238000005406 washing Methods 0.000 description 10
- 239000012071 phase Substances 0.000 description 9
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 8
- NXXYKOUNUYWIHA-UHFFFAOYSA-N 2,6-Dimethylphenol Chemical compound CC1=CC=CC(C)=C1O NXXYKOUNUYWIHA-UHFFFAOYSA-N 0.000 description 5
- CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical compound NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 description 5
- CRBJBYGJVIBWIY-UHFFFAOYSA-N 2-isopropylphenol Chemical compound CC(C)C1=CC=CC=C1O CRBJBYGJVIBWIY-UHFFFAOYSA-N 0.000 description 5
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 5
- LLEMOWNGBBNAJR-UHFFFAOYSA-N biphenyl-2-ol Chemical compound OC1=CC=CC=C1C1=CC=CC=C1 LLEMOWNGBBNAJR-UHFFFAOYSA-N 0.000 description 5
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 5
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 5
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 5
- AYYOZKHMSABVRP-UHFFFAOYSA-N methyl 1h-indole-6-carboxylate Chemical compound COC(=O)C1=CC=C2C=CNC2=C1 AYYOZKHMSABVRP-UHFFFAOYSA-N 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- KUFFULVDNCHOFZ-UHFFFAOYSA-N 2,4-xylenol Chemical compound CC1=CC=C(O)C(C)=C1 KUFFULVDNCHOFZ-UHFFFAOYSA-N 0.000 description 3
- IXQGCWUGDFDQMF-UHFFFAOYSA-N 2-Ethylphenol Chemical compound CCC1=CC=CC=C1O IXQGCWUGDFDQMF-UHFFFAOYSA-N 0.000 description 3
- QIRNGVVZBINFMX-UHFFFAOYSA-N 2-allylphenol Chemical compound OC1=CC=CC=C1CC=C QIRNGVVZBINFMX-UHFFFAOYSA-N 0.000 description 3
- ONMSBNJJCUCYED-UHFFFAOYSA-N 2-bromo-n,n-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1Br ONMSBNJJCUCYED-UHFFFAOYSA-N 0.000 description 3
- WGNNILPYHCKCFF-UHFFFAOYSA-N 2-chloro-n-methylaniline Chemical compound CNC1=CC=CC=C1Cl WGNNILPYHCKCFF-UHFFFAOYSA-N 0.000 description 3
- KXPBTNCFONSVIA-UHFFFAOYSA-N 2-iodo-5-methylaniline Chemical compound CC1=CC=C(I)C(N)=C1 KXPBTNCFONSVIA-UHFFFAOYSA-N 0.000 description 3
- KLLLJCACIRKBDT-UHFFFAOYSA-N 2-phenyl-1H-indole Chemical compound N1C2=CC=CC=C2C=C1C1=CC=CC=C1 KLLLJCACIRKBDT-UHFFFAOYSA-N 0.000 description 3
- MOYHVSKDHLMMPS-UHFFFAOYSA-N 3-methoxy-n,n-dimethylaniline Chemical compound COC1=CC=CC(N(C)C)=C1 MOYHVSKDHLMMPS-UHFFFAOYSA-N 0.000 description 3
- DPKTVUKEPNBABS-UHFFFAOYSA-N 3-tert-butylaniline Chemical compound CC(C)(C)C1=CC=CC(N)=C1 DPKTVUKEPNBABS-UHFFFAOYSA-N 0.000 description 3
- QHPQWRBYOIRBIT-UHFFFAOYSA-N 4-tert-butylphenol Chemical compound CC(C)(C)C1=CC=C(O)C=C1 QHPQWRBYOIRBIT-UHFFFAOYSA-N 0.000 description 3
- OLSJHVZRUFFIPL-UHFFFAOYSA-N 5-bromo-2-methoxyphenol Chemical compound COC1=CC=C(Br)C=C1O OLSJHVZRUFFIPL-UHFFFAOYSA-N 0.000 description 3
- OONJCAWRVJDVBB-UHFFFAOYSA-N 5-bromo-2-methylphenol Chemical compound CC1=CC=C(Br)C=C1O OONJCAWRVJDVBB-UHFFFAOYSA-N 0.000 description 3
- ONYNOPPOVKYGRS-UHFFFAOYSA-N 6-methyl-1h-indole Chemical compound CC1=CC=C2C=CNC2=C1 ONYNOPPOVKYGRS-UHFFFAOYSA-N 0.000 description 3
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 3
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 3
- IENZCGNHSIMFJE-UHFFFAOYSA-N indole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2NC=CC2=C1 IENZCGNHSIMFJE-UHFFFAOYSA-N 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- FBGJJTQNZVNEQU-UHFFFAOYSA-N n,3-dimethylaniline Chemical compound CNC1=CC=CC(C)=C1 FBGJJTQNZVNEQU-UHFFFAOYSA-N 0.000 description 3
- QCIFLGSATTWUQJ-UHFFFAOYSA-N n,4-dimethylaniline Chemical compound CNC1=CC=C(C)C=C1 QCIFLGSATTWUQJ-UHFFFAOYSA-N 0.000 description 3
- GTWJETSWSUWSEJ-UHFFFAOYSA-N n-benzylaniline Chemical compound C=1C=CC=CC=1CNC1=CC=CC=C1 GTWJETSWSUWSEJ-UHFFFAOYSA-N 0.000 description 3
- TXTHKGMZDDTZFD-UHFFFAOYSA-N n-cyclohexylaniline Chemical compound C1CCCCC1NC1=CC=CC=C1 TXTHKGMZDDTZFD-UHFFFAOYSA-N 0.000 description 3
- FRCFWPVMFJMNDP-UHFFFAOYSA-N n-propan-2-ylaniline Chemical compound CC(C)NC1=CC=CC=C1 FRCFWPVMFJMNDP-UHFFFAOYSA-N 0.000 description 3
- GOFIUEUUROFVMA-UHFFFAOYSA-N 1-(1h-indol-5-yl)ethanone Chemical compound CC(=O)C1=CC=C2NC=CC2=C1 GOFIUEUUROFVMA-UHFFFAOYSA-N 0.000 description 2
- BLRHMMGNCXNXJL-UHFFFAOYSA-N 1-methylindole Chemical compound C1=CC=C2N(C)C=CC2=C1 BLRHMMGNCXNXJL-UHFFFAOYSA-N 0.000 description 2
- ZXDMUHFTJWEDEF-UHFFFAOYSA-N 1h-indol-4-yl acetate Chemical compound CC(=O)OC1=CC=CC2=C1C=CN2 ZXDMUHFTJWEDEF-UHFFFAOYSA-N 0.000 description 2
- SZSZDBFJCQKTRG-UHFFFAOYSA-N 1h-indole-6-carbonitrile Chemical compound N#CC1=CC=C2C=CNC2=C1 SZSZDBFJCQKTRG-UHFFFAOYSA-N 0.000 description 2
- MNVMYTVDDOXZLS-UHFFFAOYSA-N 4-methoxyguaiacol Natural products COC1=CC=C(O)C(OC)=C1 MNVMYTVDDOXZLS-UHFFFAOYSA-N 0.000 description 2
- ILINOHVVKWYAFM-UHFFFAOYSA-N 5,6-dichloro-1h-indole Chemical compound C1=C(Cl)C(Cl)=CC2=C1NC=C2 ILINOHVVKWYAFM-UHFFFAOYSA-N 0.000 description 2
- SBOITLSQLQGSLO-UHFFFAOYSA-N 5-bromo-1-methylindole Chemical compound BrC1=CC=C2N(C)C=CC2=C1 SBOITLSQLQGSLO-UHFFFAOYSA-N 0.000 description 2
- ODFFPRGJZRXNHZ-UHFFFAOYSA-N 5-fluoroindole Chemical compound FC1=CC=C2NC=CC2=C1 ODFFPRGJZRXNHZ-UHFFFAOYSA-N 0.000 description 2
- TVQLYTUWUQMGMP-UHFFFAOYSA-N 5-iodo-1h-indole Chemical compound IC1=CC=C2NC=CC2=C1 TVQLYTUWUQMGMP-UHFFFAOYSA-N 0.000 description 2
- DWAQDRSOVMLGRQ-UHFFFAOYSA-N 5-methoxyindole Chemical compound COC1=CC=C2NC=CC2=C1 DWAQDRSOVMLGRQ-UHFFFAOYSA-N 0.000 description 2
- BPYBYPREOVLFED-UHFFFAOYSA-N 6-(trifluoromethyl)-1h-indole Chemical compound FC(F)(F)C1=CC=C2C=CNC2=C1 BPYBYPREOVLFED-UHFFFAOYSA-N 0.000 description 2
- MAWGHOPSCKCTPA-UHFFFAOYSA-N 6-bromo-1h-indole Chemical compound BrC1=CC=C2C=CNC2=C1 MAWGHOPSCKCTPA-UHFFFAOYSA-N 0.000 description 2
- FPMICYBCFBLGOZ-UHFFFAOYSA-N 6-phenylmethoxy-1h-indole Chemical compound C=1C=C2C=CNC2=CC=1OCC1=CC=CC=C1 FPMICYBCFBLGOZ-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical group OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- KPFSQBKJYHWFME-UHFFFAOYSA-N methyl 6-bromo-1h-indole-4-carboxylate Chemical compound COC(=O)C1=CC(Br)=CC2=C1C=CN2 KPFSQBKJYHWFME-UHFFFAOYSA-N 0.000 description 2
- 235000010292 orthophenyl phenol Nutrition 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- LSMXNZJFLGIPMS-UHFFFAOYSA-N 3-nitro-1h-indole Chemical compound C1=CC=C2C([N+](=O)[O-])=CNC2=C1 LSMXNZJFLGIPMS-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical group O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000001315 anti-hyperlipaemic effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- UBXYXCRCOKCZIT-UHFFFAOYSA-N biphenyl-3-ol Chemical compound OC1=CC=CC(C=2C=CC=CC=2)=C1 UBXYXCRCOKCZIT-UHFFFAOYSA-N 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
Abstract
The invention provides a preparation method of 3,3 '-diarylmethane compounds, which takes aryl, dichloromethane and diethylamine compounds as preparation raw materials and can efficiently synthesize 3,3' -diarylmethane compounds. The method has the advantages of environmental friendliness, low price and the like, the reaction condition is mild, no catalyst is needed, the operation is simple, the yield is high, the post-treatment of the reaction is simple and convenient, and the method is suitable for industrial production. The invention also provides application of the 3,3' -diarylmethane compound prepared by the preparation method in preparation of anti-inflammatory drugs, anti-oxidation drugs and anti-cancer drugs.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method and application of a 3,3' -diarylmethane compound.
Background
3,3' -diarylmethane compound (DIM) is a special nitrogen-containing benzoheterocyclic compound, is an important skeleton of natural products, and has numerous physiological activities, such as antihyperlipidemic activity, antioxidant activity, antimicrobial activity, anti-inflammatory activity, anticancer activity and the like.
At present, 3,3' -diarylmethane compounds are mainly constructed by Friedel-crafts reaction of indole, aldehyde, ketone and amine compounds, but most of the diarylmethane derivatives synthesized by the construction methods are symmetrical, and the synthesis of unsymmetrical diarylmethane derivatives still faces a plurality of challenges.
How to construct diarylmethane and derivatives thereof from cheap and easily available raw materials by a simple and rapid operation method is a problem which needs to be solved urgently in the field at present.
Disclosure of Invention
The present invention is directed to solving at least one of the above problems in the prior art. Therefore, the invention provides a preparation method of 3,3' -diarylmethane compounds, and the preparation method has the advantages of easily obtained raw materials and low preparation cost.
The invention also provides a 3,3' -diarylmethane compound prepared by the preparation method.
The invention also provides application of the 3,3' -diarylmethane compound prepared by the preparation method in preparation of anti-inflammatory drugs, anti-oxidation drugs and anti-cancer drugs.
The invention provides a method for preparing 3,3' -diarylmethane compounds, which comprises the following steps:
mixing compounds shown in a formula (I), a formula (II), a formula (III) and a formula (IV) in a solvent, and reacting to prepare 3,3' -diarylmethane compounds shown in a formula (VI);
or mixing the compounds shown in the formulas (I), (II) and (III) and the phenol or aniline compound shown in the formula (V) in a solvent for reaction to prepare 3,3' -diarylmethane compound shown in the formula (VII);
in the formula (VI), R 1 Independently selected from hydrogen, alkyl, alkoxy, halogen atom, ester group, aldehyde group, carboxyl or aryl;
in the formula (VII), R 2 Independently selected from substituted phenols or substituted anilines.
The invention relates to a technical scheme in a preparation method of 3,3' -diarylmethane compounds, which at least has the following beneficial effects:
in the preparation raw materials of the preparation method, methylene dichloride is one of carbon-one synthons, and the 3,3-diarylmethane compound can be constructed by a two-step one-pot method. Specifically, the asymmetric diarylmethane is constructed by two-step Friedel-crafts reaction of aryl and carbon-one synthon dichloromethane under the action of diethylamine.
Other types of asymmetric diarylmethanes can also be constructed by the methods of the invention.
The preparation method provided by the invention does not need a catalyst, the preparation raw materials are simple and easy to obtain, the environment is friendly, the cost is low, the reaction condition is mild, the operation is simple, the yield is high, the reaction post-treatment is simple and convenient, and the method is suitable for industrial production.
According to some embodiments of the invention, the compound of formula (I) is a 6-nitroindole.
According to some embodiments of the invention, the compound of formula (II) is Dichloromethane (DCM).
In the preparation method of the invention, dichloromethane is used as a reaction raw material and one of reaction solvents.
According to some embodiments of the invention, the compound represented by formula (III) is a diethylamine compound (Et 2 NH).
According to some embodiments of the invention, the compound of formula (IV) is an R1 substituted indole.
R1 represents a substituent at all positions of the indole on the right side in the formula (VI).
According to some embodiments of the invention, the compound of formula (V) is R 2 Substituted phenols.
According to some embodiments of the invention, the alkyl is C 1 ～C 5 Alkyl group of (1).
According to some embodiments of the invention, the alkyl group comprises at least one of a methyl group, a trifluoromethyl group.
According to some embodiments of the invention, the alkoxy group comprises C 1 ～C 10 An alkoxy group of (2).
According to some embodiments of the invention, the alkoxy group comprises at least one of methoxy, benzyloxy.
According to some embodiments of the invention, the ester group comprises C 1 ～C 5 Ester group of (a).
According to some embodiments of the invention, the ester group comprises at least one of a formate group and a formate group.
According to some embodiments of the invention, the aldehyde group is C 1 ～C 5 An aldehyde group of (a).
According to some embodiments of the invention, the aldehyde group comprises a formaldehyde group.
According to some embodiments of the invention, the aryl group is C 1 ～C 10 Aryl group of (2).
According to some embodiments of the invention, the aryl group is 2-phenylindole.
According to some embodiments of the invention, the substituted phenol is C 1 ～C 10 Phenol (b) is used.
According to some embodiments of the invention, C is 1 ～C 10 The phenol of (a) includes at least one of 2-aminophenol, o-isopropylphenol, o-allylphenol, o-ethylphenol, o-phenylphenol, p-tert-butylphenol, 2,4-dimethylphenol, 2-methoxy-5-bromophenol, catechol, 2-methyl-5-bromophenol, and 2,6-dimethylphenol.
According to some embodiments of the invention, the carboxy group is C 1 ～C 5 A carboxyl group of (2).
According to some embodiments of the invention, the carboxy group is a 5-carboxyindole.
According to some embodiments of the invention, the substituted aniline is C 1 ～C 10 The aniline of (1).
According to some embodiments of the invention, the aniline comprises at least one of o-chloro-N-methylaniline, o-bromo-N, N-dimethylaniline, N-isopropylaniline, m-methoxy-N, N-dimethylaniline, N-cyclohexylaniline, N-benzylaniline, N-diethylaniline, m-methyl-N-methylaniline, 2-iodo-5-methylaniline, N-methylaniline, m-tert-butylaniline and p-methyl-N-methylaniline.
According to some embodiments of the invention, the halogen atom comprises at least one of a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
According to some embodiments of the invention, the compound or aniline compound of formula (I), formula (III), formula (IV) and formula (V) is in a molar ratio of 1.
According to some embodiments of the invention, the solvent is hexafluoroisopropanol.
According to some embodiments of the invention, the molar ratio of the solvent to the compound of formula (I) is between 5mL and 10mL of the solvent per millimole of the compound of formula (I).
According to some embodiments of the invention, the temperature of the reaction is between 80 ℃ and 90 ℃.
According to some embodiments of the invention, the reaction time is between 4h and 12h.
According to some embodiments of the invention, after the reaction is completed, quenching, extraction, washing, concentration and column chromatography are further included.
According to some embodiments of the invention, after the reaction is finished, pure water is added to quench the reaction, ethyl acetate is added to wash the reaction, the organic phase is obtained by layering, the aqueous phase is extracted with ethyl acetate again, the organic phases are combined, dried, the solvent is removed by distillation under reduced pressure, and the product is subjected to column chromatography.
The second aspect of the invention provides 3,3' -diarylmethanes prepared by the preparation method of the invention.
The third aspect of the invention provides the application of the 3,3' -diarylmethane compound prepared by the preparation method in preparing anti-inflammatory drugs, anti-oxidation drugs and anti-cancer drugs.
The 3,3' -diarylmethane compound prepared by the preparation method has good metabolic stability when being used for preparing anti-inflammatory drugs, anti-oxidation drugs and anti-cancer drugs.
According to some embodiments of the present invention, the, 3,3' -diarylmethanes comprising 1-methyl-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole, 5-iodo-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole, 5-fluoro-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole, 5,6-dichloro-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole, 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-5-carboxylic acid, 6-methyl-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole, 6-nitro-3- ((6- (trifluoromethyl) -1H-indol-3-yl) methyl) -1H-indole, 3-nitro-1H-indol-3-yl) methyl) -1H-indole, 4- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole, 3-nitro-1H-indole, 2-3H-indole-3-indole, 4H-indole-2 Indole, methyl 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-6-carboxylate, methyl 5-methoxy-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole, methyl 6-bromo-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-4-carboxylate, methyl 5-bromo-1-methyl-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole, 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-4-acetic acid, 6- (benzyloxy) -3- (6-nitro-1H-indol-3-yl) methyl) -1H-indole, 1- (3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole, 1- (3-nitro-1H-indol-3-yl) methyl) -1H-indole, 1H-indole-3-ethyl-1H-indole-3-yl) ethyl-1H-indole-3-yl) methyl-1H-indole-3-indole-3-yl Indole-5-aldehyde, 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-6-carbonitrile, 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-6-carboxylic acid methyl ester, 2-chloro-N-methyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline, 2-bromo-N, N-dimethyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline, N-isopropyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline, 3-methoxy-N, N-dimethyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline, N-cyclohexyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline, N-benzyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline, 8978-diethyl-3H-indol-3-yl) aniline, N, 3-dimethyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline, 2-iodo-5-methyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline, N-methyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline, 3- (tert-butyl) -4- (6-nitro-1H-indol-3-yl) methyl) aniline, N, 4-dimethyl-3- ((6-nitro-1H-indol-3-yl) methyl) aniline, 2-amino-5- ((6-nitro-1H-indol-3-yl) methyl) phenol, 2-isopropyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol, 2-allyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol, 2-ethyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol, 5-nitro-3-indol-3-yl) biphenyl-3-ol, 8978' -nitro-1H-indol-3-yl) methyl ] phenol, 4- (tert-butyl) -3- (6-nitro-1H-indol-3-yl) methyl) phenol, 3,5-dimethyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol, 5-bromo-2-methoxy-4- ((6-nitro-1H-indol-3-yl) methyl) phenol, 4- ((6-nitro-1H-indol-3-yl) methyl) benzene-1,2-diol, 5-bromo-2-methyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol, and 2,6-dimethyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol.
Detailed Description
The following are specific examples of the present invention, and the technical solutions of the present invention are further described with reference to the examples, but the present invention is not limited to the examples.
Specific examples of the present invention are described in detail below.
The yield calculation method of the embodiment of the invention comprises the following steps: yield = product mass/(molecular weight x amount of charged substance) specific examples of the invention are described in detail below.
The yield calculation method of the embodiment of the invention comprises the following steps: yield = product mass/(molecular weight the amount of material charged).
Example 1: synthesis of 1-methyl-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole
A15 mL pressure resistant tube is taken, added with 32.4mg (0.20 mmol) of 6-nitroindole (CAS number: 4769-96-4), 62.0 μ L (0.60 mmol) of diethylamine (CAS number: 109-89-7) and 1mL (0.2M) of dichloromethane (CAS number: 75-09-2), reacted at 90 ℃ overnight, and the solvent is dried after the reaction is completed, then added with 26.2mg (0.2 mmol) of 1-methylindole (CAS number: 603-76-9) and 2mL of hexafluoroisopropanol (CAS number: 920-66-1), reacted at 80 ℃ for 5h to obtain the product. After the reaction is finished, 5mL of water is added for quenching reaction, 10mL of ethyl acetate (CAS number: 141-78-6) and 5mL of saturated saline solution are added for washing, organic phases are collected by layering, the water phase is extracted for 2 times by ethyl acetate, the amount of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, a solvent is removed by reduced pressure distillation, a product is obtained by column chromatography, an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.87), the weight of the purified product is 36.3mg, the purified product is yellow powder, and the yield is 59%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.59(s,1H),8.31(d,J＝1.8Hz,1H),7.83(dd,J＝8.8,1.8Hz,1H),7.69(d,J＝8.8Hz,1H),7.64–7.62(d,1H),7.53(d,J＝7.9Hz,1H),7.35(d,J＝8.2Hz,1H),7.13–7.09(m,2H),6.97(t,J＝7.5Hz,1H),4.18(s,2H).
13 C NMR(125MHz,DMSO-d6)δ141.7,131.8,130.3,127.3,121.1,118.9,118.8,118.3,113.5,113.0,109.6,108.3,32.3,20.4.
ESI-MS:calculated for C 18 H 15 N 3 O 2 [M+Na] - :328.1056,found:328.1052.
example 2: synthesis of 5-iodo-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole:
a15 mL pressure resistant tube was taken, and added with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacted at 90 ℃ overnight, after completion of the reaction, the solvent was spin-dried, and then added with 48.6mg (0.2 mmol) of 5-iodoindole (CAS number: 16066-91-4) and 2mL of hexafluoroisopropanol, reacted at 80 ℃ for 5 hours to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.76), the weight of the purified product is 49.2mg, the purified product is yellow powder, and the yield is 59%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.60(s,1H),11.03(s,1H),8.30(d,J＝2.0Hz,1H),7.84–7.81(m,2H),7.68(d,J＝8.8Hz,1H),7.64(d,J＝2.3Hz,1H),7.29(dd,J＝8.5,1.5Hz,1H),7.19(d,J＝8.5Hz,2H),4.15(s,2H).
13 C NMR(125MHz,DMSO-d6)δ141.8,135.5,134.8,131.8,130.3,129.8,128.9,127.1,124.2,118.9,115.6,114.0,113.5,113.1,108.4,82.1,20.4.
ESI-MS:calculated for C 17 H 12 IN 3 O 2 [M+Na]-:439.9866,found:439.9862.
example 3: 5-fluoro-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole:
a15 mL pressure resistant tube was charged with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane at 90 ℃ for overnight reaction, after completion of the reaction, the solvent was spin-dried, and then 27.0mg (0.2 mmol) of 5-fluoroindole (CAS No.: 399-52-0) and 2mL of hexafluoroisopropanol were added at 80 ℃ for 5 hours to obtain the product. After the reaction is finished, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added for washing, organic phases are collected by layering, the water phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, a solvent is removed by reduced pressure distillation, and a product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.70), the weight of the purified product is 35.0mg, the purified product is brown powder, and the yield is 57%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.59(s,1H),10.92(s,1H),8.29(d,J＝2.1Hz,1H),7.83(dd,J＝8.8,2.1Hz,1H),7.71–7.68(m,2H),7.31(dd,J＝8.8,4.6Hz,1H),7.28(d,J＝2.2Hz,1H),7.24(dd,J＝10.1,2.5Hz,1H),6.89–6.85(m,1H),4.15(s,2H).
13 C NMR(125MHz,DMSO-d6)δ155.6-155.6(d,J＝229.37),141.7,134.7,133.1,130.30,125.1,118.9,115.6,113.9,113.4,112.3,108.3,103.3,20.5.
ESI-MS:calculated for C 17 H 12 FN3O 2 [M+Na] - :332.0805,found:332.0802.
example 4: synthesis of 5,6-dichloro-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole:
taking 15mL of a pressure resistant tube, adding 32.4mg (0.20 mmol) of 6-nitroindole, 62.0 mu L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacting at 90 ℃ overnight, after the reaction is completed, spin-drying the solvent, then adding 37.2mg (0.2 mmol) of 5,6-dichloroindole (CAS number: 121859-57-2) and 2mL of hexafluoroisopropanol, reacting at 80 ℃ for 5h to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.69), the purified product is 59.0mg and is light yellow powder, and the yield is 82%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.61(s,1H),11.13(s,1H),8.30(s,1H),7.82(d,J＝8.0Hz,1H),7.73–7.66(m,3H),7.58(s,1H),7.32(s,1H),4.17(s,2H).
13 C NMR(125MHz,DMSO-d6)δ141.8,135.3,134.8,131.8,130.4,127.1,125.9,123.3,120.9,119.8,118.9,115.4,113.8,113.6,113.0,108.4,20.4.
ESI-MS:calculated for C 17 H 11 Cl 2 N 3 O 2 [M+Na] - :382.0120,found:382.0111.
example 5: synthesis of 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-5-carboxylic acid:
a15 mL pressure resistant tube was added with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, the mixture was reacted overnight at 90 ℃, after completion of the reaction, the solvent was dried by spinning, and then 32.2mg (0.2 mmol) of indole-5-carboxylic acid (CAS No. 1670-81-1) and 2mL of hexafluoroisopropanol were added, the mixture was reacted at 80 ℃ for 5 hours to obtain a product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.19), the weight of the purified product is 44.4mg, the purified product is light yellow powder, and the yield is 66%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ12.35(s,1H),11.60(s,1H),11.19(s,1H),8.30(s,1H),8.16(s,1H),7.83(dd,J＝8.8,2.1Hz,1H),7.70–7.66(m,2H),7.60(d,J＝2.1Hz,1H),7.38(d,J＝8.5Hz,1H),7.30–7.28(d,1H),4.23(s,2H).
13 C NMR(125MHz,DMSO-d6)δ141.8,139.0,134.8,131.8,130.3,126.6,124.7,122.3,121.4,120.9,118.9,115.6,115.0,113.5,111.2,108.3,20.5.
ESI-MS:calculated for C 18 H 13 N 3 O 4 [M+Na]-:385.0798,found:358.0792.
example 6: synthesis of 6-methyl-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole:
a15 mL pressure resistant tube was charged with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane at 90 ℃ for overnight reaction, after completion of the reaction, the solvent was spin-dried, and then 26.2mg (0.2 mmol) of 6-methylindole (CAS number: 3420-02-8) and 2mL of hexafluoroisopropanol were added at 80 ℃ for 5 hours to obtain a product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.80), the weight of the purified product is 35.0mg, the purified product is light yellow powder, and the yield is 53%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.57(s,1H),10.63(s,1H),8.30–8.27(d,1H),7.83–7.80(dd,1H),7.68(d,J＝8.8Hz,1H),7.61–7.59(d,1H),7.35(d,J＝8.0Hz,1H),7.10(s,1H),7.07(s,1H),6.74(d,J＝8.0Hz,1H),4.14(s,2H),2.34(s,3H).
13 C NMR(126MHz,DMSO-d6)δ141.7,136.9,134.7,131.9,130.2,129.8,125.0,122.2,119.9,118.9,118.3,116.0,113.4,113.4,111.3,108.3,21.4,20.7.
ESI-MS:calculated for C 18 H 15 N 3 O 2 [M+Na]-:328.1056,found:328.1051.
example 7: synthesis of 6-nitro-3- ((6- (trifluoromethyl) -1H-indol-3-yl) methyl) -1H-indole:
a15 mL pressure resistant tube was charged with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane at 90 ℃ for overnight reaction, after completion of the reaction, the solvent was spin-dried, and then 37.0mg (0.2 mmol) of 6-trifluoromethylindole (CAS No.: 13544-43-9) and 2mL of hexafluoroisopropanol were added at 80 ℃ for 5 hours to obtain a product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, a solvent is removed by reduced pressure distillation, a product is obtained by column chromatography, an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.51), the weight of the purified product is 31.6mg, the purified product is brown yellow powder, and the yield is 44%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.61(s,1H),11.29(s,1H),8.30(d,J＝1.9Hz,1H),7.83(dd,J＝8.8,1.9Hz,1H),7.69(d,J＝7.9Hz,3H),7.64(d,J＝1.8Hz,1H)),7.45(s,1H),7.21(d,J＝8.5Hz,1H),4.23(s,2H).
13 C NMR(125MHz,DMSO-d6)δ141.8,135.2,134.8,131.7,130.3,129.4,126.7,126.6,124.5,121.5,121.3,119.4,118.9,115.5,114.5,114.2,113.5,108.8,108.3,20.4..
ESI-MS:calculated for C 18 H 12 F 3 N 3 O 2 [M+Na] - :382.0773,found:382.0770.
example 8: synthesis of 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-4-aldehyde:
a15 mL pressure resistant tube was taken, added with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacted at 90 ℃ overnight, after completion of the reaction, the solvent was spin-dried, and then added with 29.0mg (0.2 mmol) of 4-indolylaldehyde (CAS No.: 1074-86-8) and 2mL of hexafluoroisopropanol, reacted at 80 ℃ for 5 hours to obtain the product. After the reaction is finished, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated common salt are added for washing, organic phases are collected by layering, the water phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, and then the product is obtained by column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.23), the weight of the purified product is 46.1mg, the product is yellow powder, and the yield is 72%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.61(s,1H),11.39(s,1H),9.92(s,1H),8.30(d,J＝2.0Hz,1H),8.16(s,1H),7.84(dd,J＝8.8,2.1Hz,1H),7.72(d,J＝8.8Hz,1H),7.66(d,J＝2.4Hz,1H),7.60(dd,J＝8.5,1.5Hz,1H),7.48(d,J＝8.4Hz,1H),7.35(d,J＝2.1Hz,1H),4.26(s,2H).
13 C NMR(125MHz,DMSO-d6)δ192.5,139.9,131.7,130.3,128.3,126.9,125.2,124.1,121.1,118.9,115.4,113.5,112.2,108.3,20.4.
ESI-MS:calculated for C 18 H 13 N 3 O 3 [M+Na] - :342.0849,found:342.0845.
example 9: synthesis of 6-nitro-3- ((2-phenyl-1H-indol-3-yl) methyl) -1H-indole:
a15 mL pressure resistant tube was charged with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane at 90 ℃ for overnight reaction, after completion of the reaction, the solvent was spin-dried, and then 38.6mg (0.2 mmol) of 2-phenylindole (CAS number: 948-65-2) and 2mL of hexafluoroisopropanol were added at 80 ℃ for 5 hours to obtain a product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.83), the weight of the purified product is 38.9mg, the purified product is yellow powder, and the yield is 53%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.52(s,1H),11.31(s,1H),8.31(d,J＝2.1Hz,1H),7.81(dd,J＝8.8,2.1Hz,1H),7.65(d,J＝7.3Hz,2H),7.55(d,J＝8.8Hz,1H),7.47(t,J＝7.7Hz,2H),7.62(d,J＝8.5Hz,2H),7.36(t,J＝7.4Hz,1H),7.28(d,J＝2.3Hz,1H),7.12–7.08(td,1H),6.96–6.92(td,1H),4.33(s,2H).
13 C NMR(125MHz,DMSO-d6)δ141.8,136.3,13.6,134.7,134.6,132.9,131.5,130.1,128.9,127.7,127.5,121.6,118.8,118.8,118.6,117.2,116.0,113.5,111.3,109.8,108.4,20.2.
ESI-MS:calculated for C 23 H 17 N 3 O 2 [M+Na] - :390.1212,found:390.1207.
example 10: synthesis of methyl 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-6-carboxylate:
a15 mL pressure resistant tube was charged with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacted overnight at 90 ℃ and after completion of the reaction, the solvent was dried by spinning, and then 35.0mg (0.2 mmol) of indole-6-carboxylic acid methyl ester (CAS No.: 50820-65-0) and 2mL of hexafluoroisopropanol were added, reacted at 80 ℃ for 5 hours to obtain a product. After the reaction is finished, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated common salt are added for washing, organic phases are collected by layering, the water phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, and then the product is obtained by column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.30), the weight of the purified product is 34.9mg, the product is yellow powder, and the yield is 50%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.61(s,1H),11.26(s,1H),8.30(d,J＝2.1Hz,1H),8.03(s,1H),7.82(dd,J＝8.8,2.1Hz,1H),7.68(d,J＝8.8Hz,1H),7.63(d,J＝2.3Hz,1H),7.60(d,J＝8.4Hz,1H),7.56(dd,J＝8.4,1.1Hz,1H),7.45(d,J＝2.2Hz,1H),4.21(s,2H),3.83(s,3H).
13 C NMR(125MHz,DMSO-d6)δ167.4,141.8,135.7,134.8,131.8,130.5,130.3,127.2,122.0,119.0,118.9,118.4,115.6,114.3,113.5,113.5,108.3,51.8,20.4
ESI-MS:calculated for C 19 H 15 N 3 O 4 [M+Na]-:372.0954,found:372.0952.
example 11: synthesis of 5-methoxy-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole:
a15 mL pressure resistant tube was taken, and added with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacted at 90 ℃ overnight, after completion of the reaction, the solvent was spin-dried, and then added with 29.4mg (0.2 mmol) of 5-methoxyindole (CAS number: 1006-94-6) and 2mL of hexafluoroisopropanol, reacted at 80 ℃ for 5 hours to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.37), the weight of the purified product is 35.8mg, the purified product is yellow powder, and the yield is 56%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.57(s,1H),10.63(s,1H),8.30(d,J＝2.1Hz,1H),7.85–7.82(m,1H),7.71(d,J＝8.8Hz,1H),7.64(d,J＝2.4Hz,1H),7.22(d,J＝8.7Hz,1H),7.11(d,J＝2.3Hz,1H),6.99(d,J＝2.4Hz,1H),6.71–6.68(m,1H),4.15(s,2H),3.70(s,3H).
13 C NMR(125MHz,DMSO-d6)δ152.9,141.7,134.7,131.9,131.6,130.2,127.3,123.6,118.9,115.9,113.4,113.3,112.0,110.9,108.3,100.6,55.4,20.6.
ESI-MS:calculated for C 18 H 15 N 3 O 3 [M+Na]-:344.1005,found:344.1001.
example 12: synthesis of 6-bromo-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole:
taking 15mL of a pressure resistant tube, adding 32.4mg (0.20 mmol) of 6-nitroindole, 62.0 mu L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacting at 90 ℃ overnight, after the reaction is completed, spin-drying the solvent, then adding 39.2mg (0.2 mmol) of 6-bromoindole (CAS number: 52415-29-9) and 2mL of hexafluoroisopropanol, reacting at 80 ℃ for 5h to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.42), the weight of the purified product is 47.2mg, the purified product is yellow powder, and the yield is 64%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.59(s,1H),10.96(s,1H),8.30(d,J＝2.1Hz,1H),7.83–7.81(m,1H),7.66(d,J＝8.8Hz,1H),7.62(d,J＝2.4Hz,1H),7.52(d,J＝1.7Hz,1H),7.44(d,J＝8.4Hz,1H),7.22(d,J＝2.3Hz,1H),7.05(d,J＝6.7Hz,1H),4.17(s,2H).
13 C NMR(125MHz,DMSO-d6)δ141.8,137.3,134.7,131.8,130.2,126.1,124.1,121.1,120.4,118.9,115.6,114.0,114.0,113.8,113.5,108.3,20.5.
ESI-MS:calculated for C 17 H 12 BrN 3 O 2 [M+Na] - :392.0005found：391.9999.
example 13: synthesis of methyl 6-bromo-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-4-carboxylate:
taking 15mL of a pressure resistant tube, adding 32.4mg (0.20 mmol) of 6-nitroindole, 62.0 mu L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacting at 90 ℃ overnight, after the reaction is completed, spin-drying the solvent, then adding 50.8mg (0.2 mmol) of 6-bromo-indole-4-carboxylic acid methyl ester (CAS number: 107650-22-6) and 2mL of hexafluoroisopropanol, reacting at 80 ℃ for 5h to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.34), the purified product weighs 57.4mg and is yellow powder, and the yield is 67%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.50–11.49(m,1H),11.41(d,J＝2.0Hz,1H),8.30(d,J＝2.1Hz,1H),7.82(dd,J＝8.8,2.1Hz,1H),7.79(d,J＝1.8Hz,1H),7.60(d,J＝8.8Hz,1H),7.44(d,J＝1.8Hz,1H),7.32(d,J＝2.4Hz,1H),7.22(d,J＝2.5Hz,1H),4.26(s,2H),3.58(s,3H).
13 C NMR(125MHz,DMSO-d6)δ167.0,141.8,138.8,134.7,131.7,130.0,127.9,125.2,123.2,122.6,118.8,117.9,115.9,114.0,113.3,112.1,108.2,52.0,22.4.
ESI-MS:calculated for C 19 H 14 BrN 3 O 4 [M+Na]-:450.0059,found:450.0051.
example 14: synthesis of 5-bromo-1-methyl-3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole:
a15 mL pressure resistant tube is taken, added with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0 μ L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacted at 90 ℃ overnight, after the reaction is completed, the solvent is dried by spinning, and then added with 42.0mg (0.2 mmol) of 5-bromo-1-methylindole (CAS number: 10075-52-2) and 2mL of hexafluoroisopropanol, reacted at 80 ℃ for 5h to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.53), the weight of the purified product is 23.8mg, the purified product is yellow powder, and the yield is 31%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.61(s,1H),8.30(d,J＝2.1Hz,1H),7.84–7.82(m,1H),7.69–7.67(m,3H),7.35(d,J＝8.7Hz,1H),7.22–7.20(m,1H),7.19(s,1H),4.15(s,2H),3.70(s,3H).
13 C NMR(125MHz,DMSO-d6)δ141.8,135.5,134.7,131.7,130.3,129.0,128.9,123.5,121.0,118.9,115.4,113.5,112.8,111.8,111.1,108.3,32.5,20.2.
ESI-MS:calculated for C 18 H 14 BrN 3 O 2 [M+Na] - :406.0161,found:406.0154.
example 15: synthesis of 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-4-acetic acid:
a15 mL pressure resistant tube was taken, and added with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacted at 90 ℃ overnight, after completion of the reaction, the solvent was spin-dried, and then added with 35.0mg (0.2 mmol) of 4-acetoxyindole (CAS No.: 5585-96-6) and 2mL of hexafluoroisopropanol, reacted at 80 ℃ for 5 hours to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.36), the weight of the purified product is 34.0mg, the purified product is yellow powder, and the yield is 49%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.56(s,1H),11.04(s,1H),8.33(d,J＝2.1Hz,1H),7.85(dd,J＝8.8,2.1Hz,1H),7.66(d,J＝8.8Hz,1H),7.33(d,J＝2.2Hz,1H),7.26(d,J＝8.0Hz,1H),7.05(t,J＝7.9Hz,1H),6.99(d,J＝2.0Hz,1H),6.65(d,J＝7.5Hz,1H),4.16(s,2H),2.01(s,3H).
13 C NMR(125MHz,DMSO-d6)δ169.6,143.8,141.8,138.9,134.8,131.7,130.3,124.3,121.2,119.6,118.8,116.2,113.6,111.9,111.8,109.6,108.4,21.6,20.7.
ESI-MS:calculated for C 19 H 15 N 3 O 4 [M+Na]-:372.0954,found:372.0951.
example 16: synthesis of 6- (benzyloxy) -3- (6-nitro-1H-indol-3-yl) methyl) -1H-indole:
a15 mL pressure resistant tube was charged with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacted overnight at 90 ℃ and after completion of the reaction, the solvent was dried by spinning, and then 44.6mg (0.2 mmol) of 6-benzyloxyindole (CAS No. 15903-94-3) and 2mL of hexafluoroisopropanol were added and reacted at 80 ℃ for 5 hours to obtain a product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.49), the weight of the purified product is 32.2mg, the purified product is yellow powder, and the yield is 41%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.57(s,1H),10.59(s,1H),8.29(d,J＝2.1Hz,1H),7.82(dd,J＝8.8,2.1Hz,1H),7.68(d,J＝8.8Hz,1H),7.61(d,J＝2.2Hz,1H),7.44(d,J＝7.2Hz,2H),7.37(t,J＝6.4Hz,3H),7.30(d,J＝7.3Hz,1H),7.02(d,J＝1.9Hz,1H),6.90(d,J＝2.2Hz,1H),6.66(dd,J＝8.6,2.2Hz,1H),5.07(s,2H),4.13(s,2H).
13 C NMR(125MHz,DMSO-d6)δ154.5,141.7,137.7,137.1,134.7,131.9,130.2,128.4,127.7,127.5,121.7,119.2,118.9,116.0,113.6,113.4,109.1,108.3,96.0,69.5,20.7.
ESI-MS:calculated for C 24 H 19 N 3 O 3 [M+Na] - :420.1318,found:420.1313.
example 17: synthesis of 1- (3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indol-5-yl) ethan-1-one:
a15 mL pressure resistant tube was charged with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane at 90 ℃ for overnight reaction, after completion of the reaction, the solvent was spin-dried, and then 31.8mg (0.2 mmol) of 5-acetylindole (CAS No.: 53330-94-2) and 2mL of hexafluoroisopropanol were added at 80 ℃ for 5 hours to obtain a product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.21), the weight of the purified product is 44.9mg, the purified product is yellow powder, and the yield is 67%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.60(s,1H),11.21(s,1H),8.30(d,J＝2.1Hz,1H),8.23–8.23(m,1H),7.84(dd,J＝8.8,2.1Hz,1H),7.72(d,J＝8.9Hz,1H),7.69(dd,J＝8.7,1.7Hz,1H),7.66(d,J＝2.2Hz,1H),7.39(d,J＝8.6Hz,1H),7.27(d,J＝2.0Hz,1H),4.26(s,2H),2.55(s,3H).
13 C NMR(125MHz,DMSO-d6)δ197.5,141.8,139.1,134.8,131.8,130.3,128.3,126.6,124.8,121.3,120.9,118.9,115.7,115.6,113.5,111.4,108.4,26.6,20.4.
ESI-MS:calculated for C 19 H 15 N 3 O 3 [M+Na]-:356.1005,found:356.0999.
example 18: synthesis of 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-5-aldehyde:
a15 mL pressure resistant tube is taken, 6-nitroindole 32.4mg (0.20 mmol), diethylamine 62.0 μ L (0.60 mmol) and dichloromethane 1mL (0.2M) are added, the temperature is 90 ℃, the reaction is carried out overnight, after the reaction is completed, the solvent is dried by spinning, and then 5-indolylaldehyde (CAS number: 1196-69-6) 29.0mg (0.2 mmol) and hexafluoroisopropanol 2mL are added, the temperature is 80 ℃, and the reaction is carried out for 5h, thus obtaining the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, a solvent is removed by reduced pressure distillation, and a product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.23), and the purified product weighs 46.1mg and is yellow powder, and the yield is 72%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.60(s,1H),11.38(s,1H),9.92(s,1H),8.30(d,J＝2.0Hz,1H),8.16–8.15(m,1H),7.84(dd,J＝8.8,2.1Hz,1H),7.72(d,J＝8.8Hz,1H),7.66(s,1H),7.61–7.59(m,1H),7.48(d,J＝8.5Hz,1H),7.35(d,J＝1.6Hz,1H),4.26(s,2H).
13 C NMR(125MHz,DMSO-d6)δ192.5,141.8,139.9,134.8,131.8,130.3,128.3,126.9,125.2,124.1,121.1,118.9,115.9,115.4,113.5,112.2,108.3,20.4.
ESI-MS:calculated for C 18 H 13 N 3 O 3 [M+Na] - :342.0849found:342.0844.
example 19: synthesis of 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-6-carbonitrile:
a15 mL pressure resistant tube was taken, and added with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacted at 90 ℃ overnight, after completion of the reaction, the solvent was spin-dried, and then added with 28.4mg (0.2 mmol) of 6-cyanoindole (CAS number: 15861-36-6) and 2mL of hexafluoroisopropanol, reacted at 80 ℃ for 5 hours to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.38), the purified product weighs 22.1mg and is yellow powder, and the yield is 35%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.61(s,1H),11.42(s,1H),8.29(d,J＝2.0Hz,1H),7.82(dd,J＝8.9,2.0Hz,2H),7.67(dd,J＝8.9,8.2Hz,2H),7.65(d,J＝2.4Hz,1H),7.51(d,J＝2.4Hz,1H),7.26(dd,J＝8.2,1.4Hz,1H),4.22(s,2H).
13 C NMR(125MHz,DMSO-d6)δ141.8,135.2,134.7,131.7,130.3,130.0,127.8,121.0,120.8,119.8,118.8,116.4,115.4,114.8,113.5,108.3,102.3,20.3.
ESI-MS:calculated for C 18 H 12 N 4 O 2 [M+Na]-:339.0852,found:339.0851.
example 20: synthesis of methyl 3- ((6-nitro-1H-indol-3-yl) methyl) -1H-indole-6-carboxylate:
a15 mL pressure resistant tube was taken, added with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacted at 90 ℃ overnight, after completion of the reaction, the solvent was spin-dried, and then added with 35.0mg (0.2 mmol) of indole-6-carboxylic acid methyl ester (CAS No.: 50820-65-0) and 2mL of hexafluoroisopropanol at 80 ℃ for 5 hours to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, a solvent is removed by reduced pressure distillation, and a product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.30), the weight of the purified product is 34.9mg, the purified product is yellow powder, and the yield is 50%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.61(s,1H),11.26(s,1H),8.30(d,J＝2.1Hz,1H),8.03(s,1H),7.82(dd,J＝8.8,2.1Hz,1H),7.68(d,J＝8.8Hz,1H),7.63(d,J＝2.3Hz,1H),7.60(d,J＝8.4Hz,1H),7.56(dd,J＝8.4,1.1Hz,1H),7.45(d,J＝2.2Hz,1H),4.21(s,2H),3.83(s,3H).
13 C NMR(125MHz,DMSO-d6)δ167.4,141.8,135.7,134.8,131.8,130.5,130.3,127.2,122.0,119.0,118.9,118.4,115.6,114.3,113.5,113.5,108.3,51.8,20.4.
ESI-MS:calculated for C 19 H 15 N 3 O 4 [M+Na]-:372.0954,found:372.0952.
example 21: synthesis of 2-chloro-N-methyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure resistant tube was charged with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacted overnight at 90 ℃ and after completion of the reaction, the solvent was dried by spinning, and then 28.3mg (0.2 mmol) of o-chloro-N-methylaniline (CAS No.: 932-32-1) and 2mL of hexafluoroisopropanol were added, reacted at 80 ℃ for 5 hours to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.75), the purified product is 39.8mg in weight and is yellow powder, and the yield is 63%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.64(s,1H),8.30(d,J＝2.1Hz,1H),7.83(dd,J＝8.8,2.1Hz,1H),7.61(d,J＝2.1Hz,1H),7.59(d,J＝8.8Hz,1H),7.12(d,J＝1.9Hz,1H),7.07(dd,J＝8.3,1.8Hz,1H),6.54(d,J＝8.3Hz,1H),5.28(d,J＝4.9Hz,1H),3.95(s,2H),2.70(d,J＝5.0Hz,3H).
13 C NMR(125MHz,DMSO-d6)δ143.4,141.8,134.8,131.6,130.4,129.1,128.6,128.0,118.8,117.6,115.9,113.6,110.6,108.3,30.0,29.3.
ESI-MS:calculated for C 16 H 14 ClN 3 O 2 [M+Na]-:338.0666,found:338.0661.
example 22: synthesis of 2-bromo-N, N-dimethyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure resistant tube is taken, added with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0 μ L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacted at 90 ℃ overnight, after the reaction is completed, the solvent is dried by spinning, and then added with 40.0mg (0.2 mmol) of o-bromo-N, N-dimethylaniline (CAS number: 698-00-0) and 2mL of hexafluoroisopropanol, reacted at 80 ℃ for 5h to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, a solvent is removed by reduced pressure distillation, a product is obtained by column chromatography, an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.75), the weight of the purified product is 19.0mg, the purified product is yellow powder, and the yield is 25%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.68(s,1H),8.31(d,J＝2.0Hz,1H),7.85(dd,J＝8.8,2.0Hz,1H),7.67(d,J＝2.4Hz,1H),7.63(d,J＝8.8Hz,1H),7.46(d,J＝2.0Hz,1H),7.23(dd,J＝8.2,2.0Hz,1H),7.07(d,J＝8.2Hz,1H),4.03(s,2H),2.63(s,6H).
13 C NMR(125MHz,DMSO-d6)δ149.4,141.9,137.4,134.7,133.1,131.5,130.6,128.4,120.9,118.8,118.4,115.2,113.7,108.4,43.9,29.2.
ESI-MS:calculated for C 17 H 16 BrN 3 O 2 [M+Na] - :396.0318,found:396.0315.
example 23: synthesis of N-isopropyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline:
taking 15mL of a pressure resistant tube, adding 32.4mg (0.20 mmol) of 6-nitroindole, 62.0 mu L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacting at 90 ℃ overnight, after the reaction is completed, spin-drying the solvent, then adding 27.0mg (0.2 mmol) of N-isopropylaniline (CAS number: 768-52-5) and 2mL of hexafluoroisopropanol, reacting at 80 ℃ for 5h to obtain the product. After the reaction is finished, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated common salt are added for washing, organic phases are collected by layering, the water phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, and then the product is obtained by column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.69), the weight of the purified product is 28.1mg, the product is yellow powder, and the yield is 45%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.59(s,1H),8.29(d,J＝2.1Hz,1H),7.82(dd,J＝8.8,2.1Hz,1H),7.59(d,J＝8.8Hz,1H),7.56(d,J＝2.4Hz,1H),6.97(d,J＝8.4Hz,2H),6.45(d,J＝8.4Hz,2H),5.11(d,J＝7.9Hz,1H),3.90(s,2H),3.47–3.43(m,1H),1.08(d,J＝6.3Hz,6H).
13 C NMR(125MHz,DMSO-d6)δ146.8,142.2,135.2,132.2,130.6,129.4,127.9,119.3,117.1,113.9,112.9,108.7,43.5,30.2,23.0.
ESI-MS:calculated for C 18 H 19 N 3 O 2 [M+Na] - :332.1369,found:332.1365.
example 24: synthesis of 3-methoxy-N, N-dimethyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline:
taking 15mL of a pressure resistant tube, adding 32.4mg (0.20 mmol) of 6-nitroindole, 62.0 mu L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacting at 90 ℃ overnight, after the reaction is completed, spin-drying the solvent, then adding 30.2mg (0.2 mmol) of M-methoxy-N, N-dimethylaniline (CAS number: 15799-79-8) and 2mL of hexafluoroisopropanol, reacting at 80 ℃ for 5h to obtain the product. After the reaction is finished, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated common salt are added for washing, organic phases are collected by layering, the water phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, and then the product is obtained by column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.63), the weight of the purified product is 20.7mg, the product is yellow powder, and the yield is 32%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.57(s,1H),8.29(d,J＝2.0Hz,1H),7.83(dd,J＝8.8,2.0Hz,1H),7.61(d,J＝8.8Hz,1H),7.48(d,J＝2.1Hz,1H),6.88(d,J＝8.3Hz,1H),6.31(d,J＝2.1Hz,1H),6.17(dd,J＝8.3,2.1Hz,1H),3.89(s,2H),3.80(s,3H),2.84(s,6H).
13 C NMR(125MHz,DMSO-d6)δ157.4,150.5,141.7,134.6,131.9,130.4,129.8,118.9,116.7,116.0,113.5,108.3,104.5,96.4,55.1,40.5,23.9.
ESI-MS:calculated for C 18 H 19 N 3 O 3 [M+Na] - :348.1318,found:348.1314.
example 25: synthesis of N-cyclohexyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure resistant tube was charged with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane at 90 ℃ for overnight reaction, after completion of the reaction, the solvent was spin-dried, and then 35.1mg (0.2 mmol) of N-cyclohexylaniline (CAS number: 1821-36-9) and 2mL of hexafluoroisopropanol were added at 80 ℃ for 5 hours to obtain a product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, a solvent is removed by reduced pressure distillation, and a product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.75), the weight of the purified product is 43.0mg, the purified product is yellow powder, and the yield is 62%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.59(s,1H),8.29(d,J＝2.1Hz,1H),7.82(dd,J＝8.8,2.1Hz,1H),7.59(d,J＝8.8Hz,1H),7.56(d,J＝2.4Hz,1H),6.95(d,J＝8.5Hz,2H),6.46(d,J＝8.5Hz,2H),5.16(d,J＝7.6Hz,1H),3.89(s,2H),1.87(d,J＝12.4Hz,2H),1.67(dt,J＝12.7,3.4Hz,2H),1.58–1.54(m,1H),1.30–1.22(m,3H),1.16–1.06(m,3H).
13 C NMR(125MHz,DMSO-d6)δ146.2,141.7,134.7,131.7,130.2,128.9,127.4,118.9,116.7,113.5,112.4,108.2,50.6,32.7,29.8,25.7,24.6.
ESI-MS:calculated for C 21 H 23 N 3 O 2 [M+Na]-:372.1682,found:372.1674.
example 26: synthesis of N-benzyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure resistant tube was charged with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacted overnight at 90 ℃, after completion of the reaction, the solvent was dried by spinning, and then 36.7mg (0.2 mmol) of N-benzylaniline (CAS No. 103-32-2) and 2mL of hexafluoroisopropanol were added, reacted at 80 ℃ for 5 hours to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, a solvent is removed by reduced pressure distillation, a product is obtained by column chromatography, an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.75), the weight of the purified product is 32.2mg, the purified product is yellow powder, and the yield is 45%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.59(s,1H),8.28(d,J＝2.1Hz,1H),7.81(dd,J＝8.8,2.1Hz,1H),7.57(d,J＝8.8Hz,1H),7.55(s,1H),7.32(d,J＝7.2Hz,2H),7.29(t,J＝7.6Hz,2H),7.20(d,J＝7.2Hz,1H),6.95(d,J＝8.4Hz,2H),6.48(d,J＝8.4Hz,2H),6.05(t,J＝6.0Hz,1H),4.20(d,J＝6.0Hz,2H),3.89(s,2H).
13 C NMR(125MHz,DMSO-d6)δ146.8,141.7,140.5,134.7,131.7,130.2,128.8,128.3,128.1,127.2,126.6,118.9,116.6,113.5,112.3,108.3,46.7,29.8.
ESI-MS:calculated for C 22 H 19 N 3 O 2 [M+Na] - :380.1369,found:380.1362.
example 27: synthesis of N, N-diethyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure resistant tube was taken, added with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacted at 90 ℃ overnight, after the reaction was completed, the solvent was spin-dried, and then added with 29.9mg (0.2 mmol) of N, N-diethylaniline (CAS number: 91-66-7) and 2mL of hexafluoroisopropanol, reacted at 80 ℃ for 5h to obtain the product. After the reaction is finished, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated common salt are added for washing, organic phases are collected by layering, the water phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, and then the product is obtained by column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.69), the purified product is 41.8mg in weight and is yellow powder, and the yield is 65%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.62(s,1H),8.30(s,1H),7.83(dd,J＝8.8,2.1Hz,1H),7.59(d,J＝11.0Hz,2H),7.04(d,J＝8.5Hz,2H),6.53(d,J＝8.5Hz,2H),3.92(s,2H),3.24(q,J＝5.9,5.1Hz,4H),1.01(t,J＝6.9Hz,6H).
13 C NMR(125MHz,DMSO-d6)δ145.7,141.8,134.8,131.7,130.2,129.1,127.3,118.9,116.6,113.5,111.7,108.3,43.7,29.6,12.4.
ESI-MS:calculated for C 19 H 21 N 3 O 2 [M+Na] - :346.1525,found:346.1520.
example 28: synthesis of N, 3-dimethyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure resistant tube was charged with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane at 90 ℃ for overnight reaction, after completion of the reaction, the solvent was spin-dried, and then 24.2mg (0.2 mmol) of M-methyl-N-methylaniline (CAS No.: 696-44-6) and 2mL of hexafluoroisopropanol were added at 80 ℃ for 5 hours to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.56), the weight of the purified product is 23.0mg, the purified product is yellow powder, and the yield is 39%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.59(s,1H),8.30(d,J＝2.1Hz,1H),7.82(dd,J＝8.8,2.1Hz,1H),7.58(d,J＝8.8Hz,1H),7.37(d,J＝2.3Hz,1H),6.87(d,J＝8.2Hz,1H),6.35(d,J＝2.1Hz,1H),6.28(dd,J＝8.2,2.3Hz,1H),5.34(s,1H),3.90(s,2H),2.62(s,3H),2.15(s,3H).
13 C NMR(125MHz,DMSO-d6)δ148.3,141.8,136.1,134.8,131.8,130.3,129.7,125.8,118.9,115.8,113.8,113.5,109.3,108.3,30.0,27.7,19.6.
ESI-MS:calculated for C 17 H 17 N 3 O 2 [M+H] - :296.1393,found:296.1390.
example 29: synthesis of 2-iodo-5-methyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure resistant tube was charged with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacted overnight at 90 ℃ and after completion of the reaction, the solvent was dried by spinning, and then 46.6mg (0.2 mmol) of 2-iodo-5-methylaniline (CAS No.: 13194-69-9) and 2mL of hexafluoroisopropanol were added, reacted at 80 ℃ for 5 hours to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.63), the weight of the purified product is 30.3mg, the purified product is yellow powder, and the yield is 37%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.64(s,1H),8.31(d,J＝2.0Hz,1H),7.84(dd,J＝8.8,2.0Hz,1H),7.58(d,J＝8.8Hz,1H),7.40(d,J＝2.3Hz,1H),7.26(s,1H),6.59(s,1H),4.95(s,2H),3.88(s,2H),2.10(s,3H).
13 C NMR(125MHz,DMSO-d6)δ146.7,141.9,138.2,137.1,134.7,131.0,130.5,129.2,118.8,116.3,115.1,113.6,108.4,80.0,27.0,19.1.
ESI-MS:calculated for C 16 H 14 IN 3 O 2 [M+Na] - :430.0022,found:430.0019.
example 30: synthesis of N-methyl-4- ((6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure resistant tube was taken, and 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane were added thereto, the reaction was carried out overnight at 90 ℃ and after completion of the reaction, the solvent was dried by spinning, and then 21.4mg (0.2 mmol) of N-methylaniline (CAS No.: 100-61-8) and 2mL of hexafluoroisopropanol were added thereto, the reaction was carried out at 80 ℃ for 5 hours to obtain a product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, a solvent is removed by reduced pressure distillation, and a product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.56), the weight of the purified product is 16.6mg, the purified product is yellow powder, and the yield is 30%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.60(s,1H),8.29(s,1H),7.82(dd,J＝8.8,1.9Hz,1H),7.57(d,J＝9.3Hz,2H),6.99(d,J＝8.3Hz,2H),6.44(d,J＝8.3Hz,2H),5.41(s,1H),3.91(s,2H),2.61(s,3H).
13 C NMR(125MHz,DMSO-d6)δ148.2,141.8,134.8,131.8,130.2,128.9,127.8,118.9,116.7,113.5,111.7,108.3,30.0,29.9.
ESI-MS:calculated for C 16 H 15 N 3 O 2 [M+Na] - :304.1056,found:304.1053.
example 31: synthesis of 3- (tert-butyl) -4- (6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure resistant tube was charged with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane at 90 ℃ for overnight reaction, after completion of the reaction, the solvent was dried by spinning, and then, 29.9mg (0.2 mmol) of M-t-butylaniline (CAS No.: 5369-19-7) and 2mL of hexafluoroisopropanol were added at 80 ℃ for 5 hours to obtain a product. After the reaction is finished, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated common salt are added for washing, organic phases are collected by layering, the water phase is extracted by ethyl acetate for 2 times, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, and then the product is obtained by column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.44), the weight of the purified product is 21.6mg, the product is yellow powder, and the yield is 33%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.62(s,1H),8.31(d,J＝2.1Hz,1H),7.84(dd,J＝8.8,2.1Hz,1H),7.64(d,J＝8.8Hz,1H),7.62(d,J＝2.3Hz,1H),6.79(d,J＝7.9Hz,1H),6.67(d,J＝1.9Hz,1H),6.48(dd,J＝7.9,1.9Hz,1H),4.83(s,2H),3.86(s,2H),1.19(s,9H).
13 C NMR(125MHz,DMSO-d6)δ149.0,145.5,141.7,134.7,132.0,130.7,128.8,121.2,119.0,114.4,113.5,113.3,111.9,108.3,33.9,31.3,25.8.
ESI-MS:calculated for C 19 H 21 N 3 O 2 [M+Na] - :346.1525,found:346.1522.
example 32: synthesis of N, 4-dimethyl-3- ((6-nitro-1H-indol-3-yl) methyl) aniline:
a15 mL pressure resistant tube was taken, added with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacted at 90 ℃ overnight, after completion of the reaction, the solvent was spin-dried, and then added with 24.2mg (0.2 mmol) of p-methyl-N-methylaniline (CAS number: 623-08-5) and 2mL of hexafluoroisopropanol at 80 ℃ and reacted for 5 hours to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, a solvent is removed by reduced pressure distillation, and a product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.62), the weight of the purified product is 11.9mg, the purified product is yellow powder, and the yield is 20%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.63(s,1H),8.32(d,J＝1.8Hz,1H),7.84(dd,J＝8.8,2.1Hz,1H),7.59(d,J＝8.8Hz,1H),7.55(d,J＝2.1Hz,1H),6.84(d,J＝8.0Hz,1H),6.69(d,J＝1.8Hz,1H),6.43(d,J＝8.0Hz,1H),4.97(s,1H),3.88(s,2H),2.70(s,3H),2.06(s,3H).
13 C NMR(125MHz,DMSO-d6)δ145.0,141.8,134.7,132.1,130.8,129.5,127.4,124.4,123.8,119.0,114.1,113.6,109.3,108.4,30.5,26.0,20.2.
ESI-MS:calculated for C 17 H 17 N 3 O 2 [M+H] - :296.1393,found:296.1390.
example 33: synthesis of 2-amino-5- ((6-nitro-1H-indol-3-yl) methyl) phenol:
a15 mL pressure resistant tube was taken, and added with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacted at 90 ℃ overnight, after completion of the reaction, the solvent was spin-dried, and then added with 21.8mg (0.2 mmol) of 2-aminophenol (CAS number: 95-55-6) and 2mL of hexafluoroisopropanol, reacted at 80 ℃ for 5 hours to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =1/1, rf = 0.20), the weight of the purified product is 29.0mg, the purified product is yellow powder, and the yield is 51%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.61(s,1H),8.84(s,1H),8.30(d,J＝2.0Hz,1H),7.82(dd,J＝8.8,2.0Hz,1H),7.56(d,J＝1.8Hz,1H),7.54(d,J＝8.8Hz,1H),6.50(d,J＝6.2Hz,3H),4.34(s,2H),3.87(s,2H).
13 C NMR(125MHz,DMSO-d6)δ144.1,141.8,134.8,134.5,131.8,130.3,129.1,119.4,119.0,116.5,114.6,114.4,113.5,108.3,30.1.
ESI-MS:calculated for C 15 H 13 N 3 O 3 [M+Na] - :306.0849,found:306.0848.
example 34: synthesis of 2-isopropyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol:
a15 mL pressure resistant tube is taken, added with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0 μ L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacted at 90 ℃ overnight, after the reaction is completed, the solvent is dried by spinning, and then added with 27.2mg (0.2 mmol) of o-isopropylphenol (CAS number: 88-69-7) and 2mL of hexafluoroisopropanol, reacted at 80 ℃ for 5h to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.54), the weight of the purified product is 28.3mg, the purified product is yellow powder, and the yield is 46%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.59(s,1H),9.02(s,1H),8.29(d,J＝2.1Hz,1H),7.83(dd,J＝8.8,2.1Hz,1H),7.60(d,J＝8.8Hz,1H),7.56(d,J＝2.4Hz,1H),7.06(d,J＝2.3Hz,1H),6.83(dd,J＝8.1,2.2Hz,1H),6.65(d,J＝8.1Hz,1H),3.96(s,2H),3.16–3.12(m,1H),1.11(d,J＝6.9Hz,6H).
13 C NMR(125MHz,DMSO-d6)δ152.4,141.8,134.7,133.9,131.7,131.1,130.2,126.1,126.0,118.9,116.4,114.8,113.5,108.3,30.1,26.4,22.6.
ESI-MS:calculated for C 18 H 18 N 2 O 3 [M+Na] - :333.1209,found:333.1210.
example 35: synthesis of 2-allyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol:
a15 mL pressure resistant tube was charged with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane at 90 ℃ for overnight reaction, after completion of the reaction, the solvent was spin-dried, and then 26.8mg (0.2 mmol) of o-allylphenol (CAS No.: 1745-81-9) and 2mL of hexafluoroisopropanol were added at 80 ℃ for 5 hours to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, a solvent is removed by reduced pressure distillation, and a product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.60), the weight of the purified product is 25.2mg, the purified product is yellow powder, and the yield is 41%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.62(s,1H),9.15(s,1H),8.29(d,J＝2.1Hz,1H),7.82(dd,J＝8.8,2.1Hz,1H),7.58–7.55(m,2H),6.95(d,J＝2.1Hz,1H),6.90(dd,J＝8.1,2.1Hz,1H),6.69(d,J＝8.1Hz,1H),5.94–5.88(m,1H),5.01–4.94(m,2H),3.94(s,2H),3.22(d,J＝6.6Hz,2H).
13 C NMR(125MHz,DMSO-d6)δ153.1,141.8,137.2,134.7,131.7,131.2,130.3,129.8,127.0,125.7,118.9,116.3,115.2,114.8,113.5,108.3,33.9,29.9.
ESI-MS:calculated for C 18 H 16 N 2 O 3 [M+Na] - :331.1053,found:331.1049.
example 36: synthesis of 2-ethyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol:
a15 mL pressure resistant tube is taken, 6-nitroindole 32.4mg (0.20 mmol), diethylamine 62.0 μ L (0.60 mmol) and dichloromethane 1mL (0.2M) are added, the temperature is 90 ℃, the reaction is carried out overnight, after the reaction is completed, the solvent is dried by spinning, and then o-ethylphenol (CAS number: 90-00-6) 24.4mg (0.2 mmol) and hexafluoroisopropanol 2mL are added, the temperature is 80 ℃, and the reaction is carried out for 5h, thus obtaining the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, a solvent is removed by reduced pressure distillation, and a product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.44), the purified product weighs 24.2mg and is yellow powder, and the yield is 41%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.60(s,1H),9.01(s,1H),8.29(d,J＝2.0Hz,1H),7.83(dd,J＝8.8,2.1Hz,1H),7.59(d,J＝8.8Hz,1H),7.57(d,J＝2.5Hz,1H),6.98(d,J＝2.1Hz,1H),6.87(dd,J＝8.1,2.2Hz,1H),6.65(d,J＝8.1Hz,1H),3.94(s,2H),2.46(t,J＝7.5Hz,2H),1.07(t,J＝7.5Hz,3H).
13 C NMR(125MHz,DMSO-d6)δ153.1,141.8,134.7,131.7,131.2,130.3,129.7,129.1,126.5,118.9,116.4,114.7,113.6,108.3,29.9,22.9,14.4.
ESI-MS:calculated for C 17 H 16 N 2 O 3 [M+Na] - :319.1053,found:319.1050.
example 37: synthesis of 5- ((6-nitro-1H-indol-3-yl) methyl) - [1,1' -biphenyl ] -2-ol:
a15 mL pressure resistant tube was taken, added with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacted at 90 ℃ overnight, after completion of the reaction, the solvent was spin-dried, and then added with 34.0mg (0.2 mmol) of o-phenylphenol (CAS number: 90-43-7) and 2mL of hexafluoroisopropanol at 80 ℃ for 5 hours to obtain the product. After the reaction is finished, 5mL of water is added for quenching reaction, 10mL of ethyl acetate and 5mL of saturated common salt are added for washing, organic phases are collected by layering, the water phase is extracted by ethyl acetate for 2 times, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added for drying, the solvent is removed by reduced pressure distillation, and then the product is obtained by column chromatography, the eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.38), the weight of the purified product is 16.6mg, the product is yellow powder, and the yield is 24%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.64(s,1H),9.35(s,1H),8.30(d,J＝2.1Hz,1H),7.84(dd,J＝8.8,2.1Hz,1H),7.64(m,2H),7.50–7.47(m,2H),7.36(t,J＝7.6Hz,2H),7.26(t,J＝7.4Hz,1H),7.17(d,J＝2.1Hz,1H),7.06(dd,J＝8.2,2.1Hz,1H),6.84(d,J＝8.2Hz,1H),4.03(s,2H).
13 C NMR(125MHz,DMSO-d6)δ152.4,141.8,138.7,134.7,131.9,131.7,130.4,130.3,129.1,128.4,127.9,127.5,126.5,118.9,116.1,116.0,113.6,108.3,29.8.
ESI-MS:calculated for C 21 H 16 N 2 O 3 [M+Na] - :367.1053,found:367.1048.
example 38: synthesis of 4- (tert-butyl) -3- (6-nitro-1H-indol-3-yl) methyl) phenol:
a15 mL pressure resistant tube was taken, added with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacted at 90 ℃ overnight, after completion of the reaction, the solvent was dried by spinning, then added with 30.0mg (0.2 mmol) of p-tert-butylphenol (CAS number: 98-54-4) and 2mL of hexafluoroisopropanol, reacted at 80 ℃ for 5 hours to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, a solvent is removed by reduced pressure distillation, and a product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.43), the weight of the purified product is 11.0mg, the purified product is yellow powder, and the yield is 17%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.57(s,1H),9.23(s,1H),8.29(d,J＝1.9Hz,1H),7.84(dd,J＝8.8,1.9Hz,1H),7.73(d,J＝8.8Hz,1H),7.54(s,1H),7.14(d,J＝2.1Hz,1H),6.99(dd,J＝8.3,2.1Hz,1H),6.71(d,J＝8.3Hz,1H),3.97(s,2H),1.15(s,9H).
13 C NMR(125MHz,DMSO-d6)δ152.5,141.7,140.9,134.5,131.9,130.5,126.8,126.3,123.5,119.0,115.7,114.5,113.4,108.3,33.6,31.5,25.0.
ESI-MS:calculated for C 19 H 20 N 2 O 3 [M+Na] - :347.1366,found:347.1364.
example 39: 8978 Synthesis of zxft 8978-dimethyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol:
taking 15mL of a pressure resistant tube, adding 32.4mg (0.20 mmol) of 6-nitroindole, 62.0 mu L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacting at 90 ℃ overnight, after the reaction is completed, spin-drying the solvent, then adding 2,4-dimethylphenol (CAS number: 105-67-9), 24.4mg (0.2 mmol) and 2mL of hexafluoroisopropanol, reacting at 80 ℃ for 5h to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.58), the weight of the purified product is 14.4mg, the purified product is yellow powder, and the yield is 28%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.59(s,1H),8.29(d,J＝2.1Hz,1H),8.13(s,1H),7.84(dd,J＝8.8,2.1Hz,1H),7.66(d,J＝8.8Hz,1H),7.52(d,J＝2.4Hz,1H),6.69(d,J＝13.8Hz,2H),3.99(s,2H),2.14(s,3H),2.06(s,3H).
13 C NMR(125MHz,DMSO-d6)δ150.3,141.7,134.5,131.9,130.6,129.1,127.8,127.7,127.6,124.5,118.9,115.5,113.5,108.3,24.9,20.2,16.7.
ESI-MS:calculated for C 17 H 16 N 2 O 3 [M+Na] - :319.1053,found:319.1049.
example 40: synthesis of 5-bromo-2-methoxy-4- ((6-nitro-1H-indol-3-yl) methyl) phenol:
a15 mL pressure resistant tube is taken, 6-nitroindole 32.4mg (0.20 mmol), diethylamine 62.0 μ L (0.60 mmol) and dichloromethane 1mL (0.2M) are added, the temperature is 90 ℃, the reaction is carried out overnight, after the reaction is completed, the solvent is dried by spinning, then 2-methoxy-5-bromophenol (CAS number: 37942-01-1) 40.6mg (0.2 mmol) and hexafluoroisopropanol 2mL are added, the temperature is 80 ℃, and the product is obtained after the reaction is carried out for 5 hours. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.31), the purified product weighs 37.0mg and is yellow powder, and the yield is 49%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.66(s,1H),9.39(s,1H),8.31(d,J＝2.1Hz,1H),7.87(dd,J＝8.8,2.1Hz,1H),7.70(d,J＝8.8Hz,1H),7.48(d,J＝2.3Hz,1H),6.97(s,1H),6.96(s,1H),4.06(s,2H),3.46(s,3H).
13 C NMR(125MHz,DMSO-d6)δ147.4,146.1,141.9,134.7,131.5,130.7,130.0,118.9,118.8,114.6,114.5,113.7,113.4,108.4,55.8,30.6.
ESI-MS:calculated for C 16 H 13 BrN 2 O 4 [M+Na] - :398.9950,found:398.9948.
example 41: synthesis of 4- ((6-nitro-1H-indol-3-yl) methyl) benzene-1,2-diol:
taking 15mL of pressure resistant tube, adding 32.4mg (0.20 mmol) of 6-nitroindole, 62.0 mu L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacting at 90 ℃ overnight, after the reaction is completed, spin-drying the solvent, then adding 22.0mg (0.2 mmol) of catechol (CAS number: 120-80-9) and 2mL of hexafluoroisopropanol, reacting at 80 ℃ for 5h to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, a solvent is removed by reduced pressure distillation, and a product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =1/1, rf = 0.58), the weight of the purified product is 7.0mg, the purified product is yellow powder, and the yield is 11%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.62(s,1H),8.68(d,J＝34.2Hz,2H),8.30(d,J＝2.1Hz,1H),7.83(dd,J＝8.8,2.1Hz,1H),7.58(s,1H),7.55(d,J＝8.8Hz,1H),6.61(d,J＝8.0Hz,1H),6.59(d,J＝2.0Hz,1H),6.53(dd,J＝8.0,2.0Hz,1H),3.90(s,2H).
13 C NMR(125MHz,DMSO-d6)δ145.1,143.4,141.8,134.7,131.9,131.8,130.4,119.0,118.9,116.1,115.8,115.4,113.5,108.3,29.9.
ESI-MS:calculated for C 15 H 12 N 2 O 4 [M+Na] - :307.0689,found:307.0685.
example 42: synthesis of 5-bromo-2-methyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol:
a15 mL pressure resistant tube was taken, added with 32.4mg (0.20 mmol) of 6-nitroindole, 62.0. Mu.L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacted at 90 ℃ overnight, after completion of the reaction, the solvent was spin-dried, and then added with 37.4mg (0.2 mmol) of 2-methyl-5-bromophenol (CAS No.: 36138-76-8) and 2mL of hexafluoroisopropanol at 80 ℃ for 5 hours to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.54), the weight of the purified product is 54.9mg, the purified product is yellow powder, and the yield is 76%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.65(s,1H),9.64(s,1H),8.31(d,J＝2.1Hz,1H),7.85(dd,J＝8.8,2.1Hz,1H),7.63(d,J＝8.8Hz,1H),7.48(d,J＝2.3Hz,1H),7.00(d,J＝6.0Hz,2H),4.02(s,2H),1.99(s,3H).
13 C NMR(125MHz,DMSO-d6)δ154.7,141.9,134.7,132.3,131.6,130.7,129.5,124.0,120.2,118.7,118.0,114.7,113.7,108.4,30.0,15.6.
ESI-MS:calculated for C 16 H 13 BrN 2 O 3 [M+Na] - :383.0001,found:383.0001.
example 43: 8978 Synthesis of zxft 8978-dimethyl-4- ((6-nitro-1H-indol-3-yl) methyl) phenol:
taking 15mL of a pressure resistant tube, adding 32.4mg (0.20 mmol) of 6-nitroindole, 62.0 mu L (0.60 mmol) of diethylamine and 1mL (0.2M) of dichloromethane, reacting at 90 ℃ overnight, after the reaction is completed, spin-drying the solvent, then adding 2,6-dimethylphenol (CAS number: 576-26-1) 24.4mg (0.2 mmol) and hexafluoroisopropanol 2mL, reacting at 80 ℃ for 5h to obtain the product. After the reaction is finished, 5mL of water is added to quench the reaction, 10mL of ethyl acetate and 5mL of saturated saline solution are added to wash the reaction solution, organic phases are collected by layering, the aqueous phase is extracted for 2 times by ethyl acetate, the dosage of ethyl acetate is 5mL each time, the organic phases are combined, anhydrous sodium sulfate is added to dry the mixture, the solvent is removed by reduced pressure distillation, and the product is obtained by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate (PE/EA =2/1, rf = 0.57), the purified product is 39.7mg in weight, is yellow powder, and the yield is 67%.
The characterization data of the product are:
1 H NMR(500MHz,DMSO-d6)δ11.61(s,1H),8.29(d,J＝2.1Hz,1H),7.97(s,1H),7.82(dd,J＝8.8,2.1Hz,1H),7.58(d,J＝8.9Hz,2H),6.80(s,2H),3.90(s,2H),2.08(s,6H).
13 C NMR(125MHz,DMSO-d6)δ151.2,141.8,134.7,131.7,131.4,130.3,128.1,124.0,118.8,116.3,113.5,108.3,29.8,16.7.
ESI-MS:calculated for C 17 H 16 N 2 O 3 [M+Na] - :319.1053,found:319.1051.
as can be seen from the above examples 1 to 43: the reaction applicable substrate is mainly alkyl, alkoxy, halogenated group, halogenated alkyl, phenyl, phenolic group and anilino group substituted 3,3' -diarylmethane compound compounds. The reaction is carried out by indole and carbon-one synthon dichloromethane under the action of diethylamine to construct 3,3' -diarylmethane compound through two-step Friedel-crafts reaction. Therefore, compared with the synthesis of other 3,3' -diarylmethane compounds, the method has the advantages of simple operation, no need of catalyst, and cheap and easily-obtained reaction raw materials. The reaction is applicable to various types of substrates, and the reaction functional group has good tolerance, so that the application range is wide; the reaction yield is high, and the partial reaction yield is up to more than 80%; the reaction process is quick, the operation is simple and safe, and the method has the potential of large-scale production.
While the embodiments of the present invention have been described in detail with reference to the specific embodiments, the present invention is not limited to the embodiments, and various changes can be made without departing from the spirit of the present invention within the knowledge of those skilled in the art. Furthermore, the embodiments of the present invention and features of the embodiments may be combined with each other without conflict.
Claims (10)
1. A preparation method of 3,3' -diarylmethane compounds is characterized by comprising the following steps: the method comprises the following steps:
mixing the compounds shown in the formulas (I), (II), (III) and (IV) in a solvent and reacting to prepare 3,3' -diarylmethane compounds shown in the formula (VI);
or mixing the compounds shown in the formulas (I), (II) and (III) and the phenol or aniline compound shown in the formula (V) in a solvent and reacting to prepare the 3,3' -diarylmethane compound shown in the formula (VII);
in the formula (IV), R 1 Independently selected from hydrogen, alkyl, alkoxy, halogen atom, ester group, aldehyde group, carboxyl or aryl;
in the formula (V), R 2 Independently selected from substituted phenols or substituted anilines.
2. The method of claim 1, wherein: the alkyl group is C 11 ～C 5 Alkyl groups of (a); preferably, the alkoxy group comprises C 1 ～C 10 An alkoxy group of (2).
3. The method of claim 1, wherein: the ester group includes C 1 ～C 5 An ester group of (a); preferably, the aldehyde group is C 1 ～C 5 An aldehyde group of (a).
4. The method of claim 1, wherein: said aryl group is C 1 ～C 10 Aryl group of (2).
5. The method of claim 1, wherein: the substituted phenol is C 1 ～C 10 Phenol of (a); preferably, the substituted aniline is C 1 ～C 10 Aniline of (2).
6. The method of claim 1, wherein: the molar ratio of the compounds or aniline compounds represented by the formula (I), formula (III), formula (IV) and formula (V) is 1.
7. The production method according to any one of claims 1 to 6, characterized in that: the solvent is hexafluoroisopropanol.
8. The production method according to any one of claims 1 to 6, characterized in that: the reaction temperature is 80-90 ℃.
9. The production method according to any one of claims 1 to 6, characterized in that: the reaction time is 4-12 h.
10. The use of 3,3' -diarylmethane compounds prepared by the method of any of claims 1 to 9 in the preparation of anti-inflammatory, antioxidant and anticancer drugs.
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| 田岩 等: "六氟异丙醇在碳碳成键反应中应用的研究进展", 《山东化工》, vol. 48, pages 40 - 42 * |
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