CN116874482A - Synthesis method of gamma-carboline ketone compound - Google Patents
Synthesis method of gamma-carboline ketone compound Download PDFInfo
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- CN116874482A CN116874482A CN202310643537.9A CN202310643537A CN116874482A CN 116874482 A CN116874482 A CN 116874482A CN 202310643537 A CN202310643537 A CN 202310643537A CN 116874482 A CN116874482 A CN 116874482A
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- carboline
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- ketone compound
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- -1 gamma-carboline ketone compound Chemical class 0.000 title claims abstract description 76
- 238000001308 synthesis method Methods 0.000 title claims abstract description 6
- 238000000034 method Methods 0.000 claims abstract description 26
- 238000006243 chemical reaction Methods 0.000 claims abstract description 24
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 18
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 229910017052 cobalt Inorganic materials 0.000 claims abstract description 10
- 239000010941 cobalt Substances 0.000 claims abstract description 10
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000007800 oxidant agent Substances 0.000 claims abstract description 8
- 230000001590 oxidative effect Effects 0.000 claims abstract description 7
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 239000003513 alkali Substances 0.000 claims abstract description 6
- 150000001345 alkine derivatives Chemical class 0.000 claims abstract description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- RDMHXWZYVFGYSF-LNTINUHCSA-N (z)-4-hydroxypent-3-en-2-one;manganese Chemical compound [Mn].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O RDMHXWZYVFGYSF-LNTINUHCSA-N 0.000 claims description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical group OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- BKFAZDGHFACXKY-UHFFFAOYSA-N cobalt(II) bis(acetylacetonate) Chemical compound [Co+2].CC(=O)[CH-]C(C)=O.CC(=O)[CH-]C(C)=O BKFAZDGHFACXKY-UHFFFAOYSA-N 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 claims description 3
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 3
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 229910052709 silver Inorganic materials 0.000 claims description 2
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 claims description 2
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 239000002585 base Substances 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 abstract description 9
- 239000011572 manganese Substances 0.000 abstract description 4
- 229910052751 metal Inorganic materials 0.000 abstract description 4
- 239000002184 metal Substances 0.000 abstract description 4
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 abstract description 2
- 239000003446 ligand Substances 0.000 abstract description 2
- 229910052748 manganese Inorganic materials 0.000 abstract description 2
- DXGTUUQHTDOFFQ-UHFFFAOYSA-N [N].C1=CC=C2NC=CC2=C1 Chemical group [N].C1=CC=C2NC=CC2=C1 DXGTUUQHTDOFFQ-UHFFFAOYSA-N 0.000 abstract 1
- 230000003197 catalytic effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 238000005481 NMR spectroscopy Methods 0.000 description 22
- 239000007787 solid Substances 0.000 description 13
- LSGKMZLPZFPAIN-UHFFFAOYSA-N 1h-indole-3-carboxamide Chemical compound C1=CC=C2C(C(=O)N)=CNC2=C1 LSGKMZLPZFPAIN-UHFFFAOYSA-N 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 239000002994 raw material Substances 0.000 description 5
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 239000004215 Carbon black (E152) Substances 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 229930195733 hydrocarbon Natural products 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- FNHSKJJZSLFYAJ-UHFFFAOYSA-N 4-hydrazinyl-1h-quinolin-2-one Chemical compound C1=CC=C2C(NN)=CC(=O)NC2=C1 FNHSKJJZSLFYAJ-UHFFFAOYSA-N 0.000 description 2
- 230000005526 G1 to G0 transition Effects 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical group CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000006352 cycloaddition reaction Methods 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- KMAKOBLIOCQGJP-UHFFFAOYSA-N indole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CNC2=C1 KMAKOBLIOCQGJP-UHFFFAOYSA-N 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 2
- 229930185107 quinolinone Natural products 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 1
- VFHUJFBEFDVZPJ-UHFFFAOYSA-N 1h-indole-2-carboxamide Chemical compound C1=CC=C2NC(C(=O)N)=CC2=C1 VFHUJFBEFDVZPJ-UHFFFAOYSA-N 0.000 description 1
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 description 1
- HDHQZCHIXUUSMK-UHFFFAOYSA-N 4-hydroxy-2-quinolone Chemical compound C1=CC=C2C(O)=CC(=O)NC2=C1 HDHQZCHIXUUSMK-UHFFFAOYSA-N 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 229940113081 5 Hydroxytryptamine 3 receptor antagonist Drugs 0.000 description 1
- WREVVZMUNPAPOV-UHFFFAOYSA-N 8-aminoquinoline Chemical compound C1=CN=C2C(N)=CC=CC2=C1 WREVVZMUNPAPOV-UHFFFAOYSA-N 0.000 description 1
- KLYCPFXDDDMZNQ-UHFFFAOYSA-N Benzyne Chemical compound C1=CC#CC=C1 KLYCPFXDDDMZNQ-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 description 1
- 238000006617 Intramolecular Heck reaction Methods 0.000 description 1
- BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 1
- DCBDOYDVQJVXOH-UHFFFAOYSA-N azane;1h-indole Chemical compound N.C1=CC=C2NC=CC2=C1 DCBDOYDVQJVXOH-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- FCEOGYWNOSBEPV-FDGPNNRMSA-N cobalt;(z)-4-hydroxypent-3-en-2-one Chemical compound [Co].C\C(O)=C\C(C)=O.C\C(O)=C\C(C)=O FCEOGYWNOSBEPV-FDGPNNRMSA-N 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 238000005906 dihydroxylation reaction Methods 0.000 description 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
- 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229940078552 o-xylene Drugs 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- SJRDNQOIQZOVQD-UHFFFAOYSA-M sodium;2,2-dimethylpropanoate Chemical compound [Na+].CC(C)(C)C([O-])=O SJRDNQOIQZOVQD-UHFFFAOYSA-M 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/16—Catalysts comprising hydrides, coordination complexes or organic compounds containing coordination complexes
- B01J31/22—Organic complexes
- B01J31/2204—Organic complexes the ligands containing oxygen or sulfur as complexing atoms
- B01J31/2208—Oxygen, e.g. acetylacetonates
- B01J31/2226—Anionic ligands, i.e. the overall ligand carries at least one formal negative charge
- B01J31/223—At least two oxygen atoms present in one at least bidentate or bridging ligand
- B01J31/2234—Beta-dicarbonyl ligands, e.g. acetylacetonates
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2531/00—Additional information regarding catalytic systems classified in B01J31/00
- B01J2531/10—Complexes comprising metals of Group I (IA or IB) as the central metal
- B01J2531/16—Copper
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention discloses a synthesis method of gamma-carboline ketone compounds, which comprises the following steps: in the presence of a cobalt catalyst, an oxidant and alkali, reacting a 3-indolecarboxamide compound with alkyne in a solvent, and performing post-treatment after the reaction is finished to obtain the gamma-carboline ketone compound. The method uses cheap metal cobalt and manganese as a catalytic system, does not need additional ligand and indole nitrogen protecting groups, and provides an organic synthesis method for synthesizing gamma-carboline ketone compounds with wide application value.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a synthesis method of gamma-carboline ketone compounds.
Background
Compounds containing a gamma-carboline ketone skeleton are of great interest due to their good biological activity, e.g. Compound I is a 5-HT3 receptor antagonist, compound II is a topoisomerase I inhibitor, and Compound III is the natural product isofraxine with antibacterial activity.
The traditional synthesis of gamma-carboline ketone compounds usually adopts intramolecular cyclization reaction, and as reported by Clark subject group, N, 2-dimethyl indole-3-formamide is reacted with N-butyllithium and DMF first, and then dehydroxylation treatment is carried out by hydrochloric acid to obtain gamma-carboline ketone derivatives (formula 2, eq.1); the Fresnel subject group takes ylide reagent and aldehyde as raw materials to obtain 3- (2-azidophenyl) substituted quinolinone through eight steps, and then the 3- (2-azidophenyl) substituted quinolinone is heated to 150 ℃ in o-xylene to obtain a target compound (formula 2, eq.2); the Chen subject group develops that 4-hydroxyquinolinone is taken as a raw material, the raw material is reacted with hydrazine to obtain 4-hydrazinoquinolinone, then the 4-hydrazinoquinolinone is reacted with cyclohexanone to prepare hydrazone, and finally the synthesis of gamma-carboline ketone compounds is realized under Pd/C conditions (formula 2, eq.3); furthermore, the Beccalli group reports a method for synthesizing a gamma-carboline ketone compound based on an intramolecular Heck reaction (formula 2, eq.4). In summary, these methods require a long synthesis step and are costly to react. Therefore, developing efficient and rapid methods for synthesizing such compounds is of great research value.
Method for synthesizing gamma-carboline ketone compound in formula II
In recent years, transition metal catalyzed hydrocarbon bond activation reaction is becoming an important way to synthesize and modify complex molecules, so that the catalyst has wide application in biomedicine, material science, pharmacy and other industries. Based on this method, the Li group developed a method based on palladium-catalyzed indole-2-carboxamide with intramolecular double C (sp 2 ) -H activation and 1, 2-acyl migration reaction to prepare gamma-carboline ketone (formula 3, eq.1); yao&Lin group reports a method for synthesizing target compound (formula 3, eq.2) by palladium-catalyzed indole-3-carboxamide and iodobenzene through twice hydrocarbon bond activation reaction; furthermore, the Jiao group reports palladium catalyzed indole-3-Formamide and internal alkyne [4+2 ]]Preparation of gamma-carboline ketone (formula 3, eq.3) by cycloaddition, after which the Zhang group developed [4+2 ] based on copper-catalyzed bis-director-assisted indole-3-carboxamide and benzyne]A method for preparing the compound by cyclization reaction (formula 3, eq.4). However, all of the above methods require noble metal palladium or use a relatively large amount of copper as a catalyst, and the development of a method for synthesizing gamma-carboline ketone by using inexpensive metal catalysis is favored by chemists. Based on the working basis of the subject group and other subject groups in cobalt-catalyzed hydrocarbon bond activation reaction, we developed a method for preparing [4+2 ] based on cobalt-catalyzed indole-3-carboxamide and diyne, endone and monoacetylene]The method for efficiently synthesizing the gamma-carboline ketone compound by cycloaddition reaction has the advantages that: (1) using inexpensive metallic cobalt as a catalyst; (2) no ligand is added; (3) using inexpensive metal manganese as an oxidizing agent; (4) The indole nitrogen does not need a protecting group, so that the cost of the reaction (formula 3, eq.6) is reduced.
Method for synthesizing gamma-carboline ketone compound by hydrocarbon bond activation reaction catalyzed by three transition metals
In conclusion, the development of the method for synthesizing the gamma-carboline ketone compound is environment-friendly and nontoxic, and has very important research significance and wide application value.
Disclosure of Invention
The invention provides a synthesis method of gamma-carboline ketone compounds, which has the advantages of low-cost and easily obtained raw materials and high atom economy.
A method for synthesizing gamma-carboline ketone compounds comprises the following steps:
in the presence of a cobalt catalyst, an oxidant and alkali, reacting a 3-indolecarboxamide compound with alkyne in a solvent, and performing aftertreatment after the reaction to obtain the gamma-carboline ketone compound;
the structure of the 3-indolecarboxamide compound is shown as a formula (I):
the structure of the gamma-carboline ketone compound is shown as a formula (II):
in the formulae (I) to (II), R 1 Is a substituted alkynyl, a substituted or unsubstituted phenyl, a substituted or unsubstituted C1-C10 alkyl; r is R 2 Is a substituted or unsubstituted phenyl, a substituted or substituted C1-C10 alkyl or hydrogen;
the substituent on the alkynyl is substituted or unsubstituted phenyl, substituted or unsubstituted C1-C10 alkyl
The substituent on the phenyl is selected from C1-C4 alkyl and C1-C4 alkoxy;
the substituent group on the C1-C10 alkyl selects halogen or phenoxy.
Preferably, said R 1 Is a phenylalkynyl group, a p-toluynyl group, a p-ethylbenzene alkynyl group, a p-tert-butylphenynyl group, a p-methoxyphenylalkynyl group, a 6-chloro-n-hex-1-ynyl group, a cyclohexylalkynyl group, a 3-phenoxypropynyl group, a phenyl group, a p-nitrophenyl group, a p-cyanophenyl group or a phenoxymethyl group;
R 2 is phenyl, p-tolyl, p-ethylphenyl, p-tert-butylphenyl, p-methoxyphenyl, 4-chloro-n-butyl, cyclohexyl, phenoxymethyl or hydrogen.
Preferably, the cobalt catalyst is Co (OAc) 2 、CoCl 2 、CoF 2 、CoSO 4 ·7H 2 O、Co(acac) 2 。
Preferably, the oxidant is Mn (OAc) 2 、AgOAc、Ag 2 O、Ag 2 CO 3 Or Mn (acac) 3 。
Preferably, the alkali is NaOPiv, naH 2 PO4、K 2 HPO 4 、Na 2 CO 3 、NaHCO 3 、KHCO 3 、NaOAc。
Preferably, the solvent is trifluoroethanol, methanol, ethanol, hexafluoroisopropanol, 1, 2-dichloroethane, toluene.
Preferably, the cobalt catalyst is Co (acac) 2 The oxidant is Mn (acac) 3 The alkali is NaOPiv, and the solvent is trifluoroethanol.
Preferably, the reaction temperature is 80 to 140 ℃ and the reaction time is 3 to 24 hours.
Compared with the prior art, the invention has the beneficial effects that:
according to the invention, 3-indolecarboxamide and alkyne are used as raw materials, and under the catalysis of cheap and easily available cobalt metal, the synthesis of gamma-carboline ketone compounds is realized by a C-H/N-H bond activation method, so that the atom economy is higher, and the reaction operability is stronger.
Drawings
FIG. 1 is a nuclear magnetic resonance spectrum of the product obtained in example 2;
FIG. 2 is a nuclear magnetic resonance spectrum of the product obtained in example 2.
Detailed Description
The invention is further described below in connection with specific embodiments.
Example 1 the synthesis of the starting 3-indoleamide is as follows:
into a dry, stirred, 100mL round bottom flask, 3-indolecarboxylic acid (1611.6 mg,10mmol,1.0 equiv.) is added, DMF (3 drops) dissolved in anhydrous dichloromethane (20 mL), nitrogen protected, and cooled to 0deg.C in an ice-water bath. Oxalyl chloride (12 mmol,1.2 equiv.) was added dropwise to the reaction system. The reaction was stirred at room temperature and TLC monitored the progress of the reaction. After the reaction, the mixture was concentrated under reduced pressure to give 3-indolecarboxchloride (dark red solid).
Into a dry, stirred, 100mL round bottom flask, 8-aminoquinoline (1874.2 mg,13mmol,1.3 equiv.) is added, triethylamine (2.8 mL,20mmol,2.0 equiv.) is added, anhydrous dichloromethane (20 mL) is added, nitrogen blanketed, and the mixture is stirred at room temperature to dissolve. The reaction system was cooled to 0 ℃ in an ice-water bath, and 3-indolecarboxchloride dissolved in anhydrous dichloromethane was added dropwise. The reaction was gradually warmed to room temperature. TLC monitored the progress of the reaction. At the end of the reaction, the reaction was quenched by addition of saturated sodium bicarbonate solution (30 mL). The solution was separated and the aqueous phase (30 mL. Times.3) was extracted with dichloromethane. The organic phases were combined, washed sequentially with dilute hydrochloric acid (50 mL,1 mol/L), saturated brine (50 mL), dried over anhydrous sodium sulfate, filtered through celite, concentrated under reduced pressure, and separated to give 1a (86%) using silica gel as the stationary phase and acetone and dichloromethane as the eluent (1:100-1:50).
Example 2 synthesis of gamma-carboline ketone steps:
into a dry 25mL high temperature pressure tube equipped with a stirrer, N- (quinolin-8-yl) -3-indolecarboxamide (1 a,0.1 mmol), alkyne (0.2 mmol,2.0 equiv.) cobalt (II) acetylacetonate (0.01 mmol,10 mol%), manganese (III) acetylacetonate (0.1 mmol,1.0 equiv.) trifluoroethanol (2 mL) and sodium pivalate (0.2 mmol,2.0 equiv.) were charged and reacted at 120℃for 24 hours. At the end of the reaction, cool to room temperature, dilute with dichloromethane, filter through celite and wash three times with dichloromethane (5 ml×3). Concentrating the filtrate under reduced pressure, and separating by using silica gel as stationary phase, acetone and dichloromethane as eluent to obtain target product, wherein the reaction conditions and the reaction results are shown in Table 1:
c Mn(acac) 3 (1.0equiv.)； d Mn(acac) 3 (0.5equiv.)； e Mn(OAc) 2 (1.0equiv.)； f the temperature is 80 ℃; g the temperature is 120 ℃; h the temperature was 140 degrees.
Example 3 synthesis of a series of gamma-carboline ketones:
the characterization data of the obtained product are as follows: 4-phenyl-3- (phenylethynyl) -2- (8-quinolinyl) -2, 5-dihydro-1H-pyrido [4,3 ]b]Indol-1-one (3 a), 44mg,90%yield.Yellow solid.m.p.>300℃； 1 H NMR(400MHz,DMSO-d 6 )δ:11.68(s,1H),8.85–8.87(m,1H),8.54–8.56(m,1H),8.22 -8.24(m,1H),8.12(d,J＝8.0Hz,1H),7.98–8.01(m,1H),7.84(t,J＝8.0Hz,1H),7.73–7.74(m,2H),7.52–7.64(m,5H),7.35–7.37(m,1H),7.20–7.28(m,2H),7.13–7.15(m,2H),6.34(d,J＝8.0Hz,2H). 13 C NMR(100MHz,DMSO-d 6 )δ:158.6,151.0,144.6,142.3,138.7,137.7,136.4,133.6,130.8,130.5,130.2,129.3,129.1,128.7,128.6,128.4,126.7,126.2,124.5,124.4,121.9,121.2,120.6,120.5,114.9,112.1,107.8,97.8,84.4.HRMS(ESI+)exact mass calculated for[M+H] + (C 34 H 22 N 3 O):488.1757,found:488.1760.
2- (8-quinolinyl) -4- (4-methylphenyl) -3- (4-methylphenylethynyl) -2, 5-dihydro-1H-pyrido [4,3-b ]]Indol-1-one (3 b), 31mg,64%yield.Yellow solid,m.p.>300℃； 1 H NMR(400MHz,DMSO-d 6 )δ:11.61(s,1H),8.84 8.86(m,1H),8.53–8.55(m,1H),8.20-8.23(m,1H),8.11(d,J＝8.0Hz,1H),7.96-7.98(m,1H),7.82(t,J＝8.0Hz,1H),7.57–7.62(m,4H),7.42(d,J＝8.0Hz,2H),7.33–7.37(m,1H),7.23–7.27(m,1H),6.96(d,J＝8.0Hz,2H),6.25(d,J＝8.0Hz,2H),2.44(s,3H),2.17(s,3H). 13 C NMR(100MHz,DMSO-d 6 )δ:158.6,150.9,144.6,143.0,142.4,139.2,138.6,137.8,137.6,136.3,130.7,130.6,130.2,130.1,129.6,129.2,129.0,128.7,126.7,126.2,124.4,121.9,121.1,120.4,117.6,114.4,112.1,107.6,98.1,84.0,20.9(2C).HRMS(ESI+)exact mass for[M+H] + (C 36 H 26 N 3 O) 516.2070, found 516.2072.4- (4-ethylphenyl) -3- ((4-ethylphenyl) ethynyl) -2- (8-quinolinyl) -2, 5-dihydro-1H-pyrido [4,3-b ]]Indol-1-one (3 c), 46mg,86%yield.Yellow solid,m.p.>300℃； 1 H NMR(400MHz,DMSO-d 6 )δ11.68(s,1H),8.84–8.85(m,1H),8.54(dd,J＝8.0,4.0Hz,1H),8.20–8.22(m,1H),8.13(d,J＝8.0Hz,1H),7.95–7.97(m,1H),7.79–7.83(m,1H),7.56–7.65(m,4H),7.43(d,J＝8.0Hz,2H),7.33–7.38(m,1H),7.23–7.27(m,1H),6.97(d,J＝8.3Hz,2H),6.26(d,J＝8.0Hz,2H),2.72(q,J＝16.0Hz,8.0Hz,2H),2.44(q,J＝16.0Hz,8.0Hz,2H),1.26(t,J＝8.0Hz,3H),1.01(t,J＝8.0Hz,3H). 13 C NMR(100MHz,DMSO-d 6 )δ158.7,151.0,145.5,144.7,143.9,142.5,138.7,137.9,136.4,130.9,130.8,130.4,130.3,129.1,128.7,128.1,128.0,126.9,126.3,124.5,124.4,122.0,121.2,120.5,118.0,114.6,112.2,107.7,98.2,84.1,28.1,28.0,15.6,15.1.HRMS(ESI+)exact mass calculated for[M+H] + (C 38 H 30 N 3 O):544.2383,found:544.2390.
4- (4-butylphenyl) -3- ((4-butylphenyl) ethynyl) -2- (8-quinolinyl) -2, 5-dihydro-1H-pyrido [4,3-b ]]Indol-1-one (3 d), 53mg,88%yield.Yellow solid,m.p.>300℃； 1 H NMR(400MHz,DMSO-d 6 )δ:11.66(s,1H),8.84–8.86(m,1H),8.52–8.54(m,1H),8.21(d,J＝8.0Hz,1H),8.14(d,J＝8.0Hz,1H),7.95–7.96(m,1H),7.80(t,J＝8.0Hz,1H),7.56–7.64(m,4H),7.34–7.41(m,3H),7.25(t,J＝8.0Hz,1H),6.94(d,J＝8.0Hz,2H),6.26(d,J＝8.0Hz,2H),2.69(t,J＝8.0Hz,2H),2.41(t,J＝8.0Hz,2H),1.60–1.67(m,2H),1.31–1.41(m,4H),1.12–1.18(m,2H),0.92(t,J＝8.0Hz,3H),0.79(t,J＝8.0Hz,3H). 13 CNMR(100MHz,DMSO-d 6 )δ:158.7,151.0,144.7,144.0,142.5,142.4,138.7,137.9,136.4,130.9,130.7,130.3,130.2,129.1,128.7,128.5,126.9,126.2,124.4,121.9,121.2,120.5,118.0,114.7,112.1,107.7,98.2,84.1,34.7,34.6,33.1,32.6,21.7,21.5,13.8,13.7.HRMS(ESI+)exact mass calculated for[M+H] + (C 42 H 38 N 3 O):600.3009,found:600.3027.
4- (4-methoxyphenyl) -3- ((4-methoxyphenyl) ethynyl) -2- (8-quinolinyl) -2, 5-dihydro-1H-pyrido [4,3-b]Indol-1-one (3 e), 41mg,75%yield.Yellow solid,m.p.>300℃； 1 H NMR(400MHz,DMSO-d 6 )δ:11.63(s,1H),8.86(d,J＝4.0Hz,1H),8.53(d,J＝8.0Hz,1H),8.21(d,J＝8.0Hz,1H),8.15(d,J＝4.0Hz,1H),7.97(d,J＝8.0Hz,1H),7.81(t,J＝8.0Hz,1H),7.67(d,J＝8.0Hz,2H),7.56–7.62(m,2H),7.36(t,J＝8.0Hz,1H),7.26(t,J＝8.0Hz,1H),7.17(d,J＝8.0Hz,2H),6.73(d,J＝8.0Hz,2H),6.34(d,J＝8.0Hz,2H),3.85(s,3H),3.65(s,3H). 13 C NMR(100MHz,DMSO-d 6 )δ:159.9,159.2,158.7,151.0,144.7,142.8,138.7,138.0,136.4,132.0,131.7,130.8,129.0,128.7,127.0,126.2,125.7,124.5,124.4,121.9,121.1,120.5,114.4,114.1,113.9,112.6,112.1,107.5,98.4,83.4,55.3(2C).HRMS(ESI+)exact mass calculated for[M+H] + (C 36 H 26 N 3 O 3 ):548.1969,found:548.1971.
4- (4-chlorobutyl) -3- (6-chlorohex-1-yn-1 yl) -2- (8-quinolinyl) -2, 5-dihydro-1H-pyrido [4,3-b ]]Indol-1-one (3 f), 35mg,68%yield.Yellow solid,m.p.>300℃； 1 H NMR(400MHz,DMSO-d 6 )δ:12.01(s,1H),8.78–8.79(m,1H),8.48–8.51(m,1H),8.14(dd,J＝8.0,4.0Hz,1H),8.05(d,J＝8.0Hz,1H),7.72–7.81(m,2H),7.56–7.61(m,2H),7.34–7.40(m,1H),7.22(t,J＝8.0Hz,1H),3.69(t,J＝4.0Hz,2H),3.27–3.29(m,2H),2.93(t,J＝8.0Hz,2H),2.00–2.01(m,2H),1.77–1.90(m,4H),1.22–1.25(m,2H),0.98–1.04(m,2H). 13 C NMR(100MHz,DMSO-d 6 )δ:158.8,150.8,144.6,143.5,138.3,138.0,136.4,130.6,128.9,128.8,127.3,126.2,124.5,124.3,121.9,121.0,120.5,112.4,111.6,107.2,100.5,74.8,45.3,44.6,31.8,30.3,27.2,26.6,24.6,17.7.HRMS(ESI+)exact mass calculated for[M+H] + (C 30 H 28 Cl 2 N 3 O):516.1604,found:516.1600.
4-cyclohexyl-3- (cyclohexylethynyl) -2- (8-quinolinyl) -2, 5-dihydro-1H-pyrido [4,3-b]Indol-1-one (3 g), 28mg,55%yield.Yellow solid,m.p =285-286 ℃; 1 H NMR(400MHz,DMSO-d 6 )δ:11.67(s,1H),8.79–8.80(m,1H),8.48(d,J＝8.0Hz,1H),8.09(dd,J＝24.0,8.0Hz,2H),7.70–7.77(m,2H),7.65(d,J＝8.0Hz,1H),7.56(dd,J＝8.0,4.0Hz,1H),7.35(t,J＝8.0Hz,1H),7.21(t,J＝8.0Hz,1H),2.18–2.24(m,3H),1.86–1.91(m,2H),1.72–1.75(m,3H),0.78–1.25(m,14H). 13 C NMR(100MHz,DMSO-d 6 )δ158.7,150.7,144.8,142.6,138.3,136.2,130.6,128.8,128.7,126.4,126.1,124.3,124.2,121.7,120.9,120.4,117.0,111.7,107.7,105.2,79.2,75.5,30.7,29.9,29.0,28.1,26.9,25.1,23.2,23.1.HRMS(ESI+)exact mass calculated for[M+H] + (C 34 H 34 N 3 O):500.2696,found:500.2698.
4- (phenoxymethyl) -3- (phenoxyprop-1-yn-1-yl)) -2- (8-quinolinyl) -2, 5-dihydro-1H-pyrido [4,3-b]Indol-1-one (3 h), 29mg,53%yield.Yellow solid,m.p =274-275 ℃; 1 H NMR(400MHz,DMSO-d 6 )δ:12.21(s,1H),8.75–8.77(m,1H),8.47–8.49(m,1H),8.10–8.13(m,1H),8.07(d,J＝8.0Hz,1H),7.82–7.84(m,1H),7.70(t,J＝8.0Hz,1H),7.55–7.62(m,2H),7.31–7.40(m,3H),7.25(t,J＝8.0Hz,1H),7.05–7.10(m,4H),7.00(t,J＝8.0Hz,1H),6.88(t,J＝8.0Hz,1H),6.45(d,J＝8.0Hz,2H),5.33(s,2H),4.50(s,2H). 13 C NMR(100MHz,DMSO-d 6 )δ:158.7,158.5,156.7,150.9,144.3,142.6,138.5,137.1,136.4,130.5,129.5,129.3,128.6,128.4,126.1,124.7,124.1,121.9,121.2,121.1,120.9,120.5,114.9,114.3,111.9,109.0,107.8,95.9,78.8,64.0,55.0(2C).HRMS(ESI+)exact mass calculated for[M+H] + (C 36 H 26 N 3 O 3 ):548.1969,found:548.1971.
3-phenyl-2- (8-quinolinyl) -2, 5-dihydro-1H-pyrido [4,3, b]Indol-1-one (3 i), 23mg,60%yield.Yellow solid,m.p.>300℃； 1 H NMR(400MHz,DMSO-d 6 )δ:11.97(s,1H),8.84(d,J＝4.0Hz,1H),8.30(d,J＝8.0Hz,1H),8.14(d,J＝8.0Hz,1H),7.87(d,J＝8.0Hz,1H),7.74(d,J＝8.0Hz,1H),7.60(d,J＝8.0Hz,1H),7.46–7.52(m,2H),7.36(t,J＝8.0Hz,1H),7.25(t,J＝8.0Hz,1H),7.16(d,J＝8.0Hz,2H),6.97–7.06(m,3H),6.66(s,1H). 13 C NMR(100MHz,DMSO-d 6 )δ:159.6,150.6,147.8,144.6,144.1,137.9,137.1,136.5,136.2,131.6,128.6(2C),128.3,128.1,127.2,125.7,124.4,123.8,121.7,120.8,120.3,111.5,105.8,96.3.HRMS(ESI+)exact mass calculated for[M+H] + (C 26 H 18 N 3 O):388.1444,found:388.1448.
3- (4-nitrophenyl) -2- (8-quinolinyl) -2, 5-dihydro-1H-pyrido [4,3, b]Indol-1-one (3 j), 12mg,28%yield.Yellow solid,m.p.>300℃； 1 H NMR(400MHz,DMSO-d 6 )δ:12.04(s,1H),8.82 -8.84(m,1H),8.33–8.35(m,1H),8.07(d,J＝8.0Hz,1H),7.93–7.95(m,1H),7.85–7.87(m,3H),7.56–7.61(m,2H),7.52(dd,J＝8.0,4.0Hz,1H),7.45–7.47(m,2H),7.34–7.38(m,1H),7.24(t,J＝8.0Hz,1H),6.74(s,1H). 13 CNMR(100MHz,DMSO)δ:159.3,150.9,146.7,145.5,144.1,143.5,142.8,137.9,136.3,131.9,130.0,129.0,128.3,125.8,124.2,124.1,122.3,121.8,121.0,120.4,111.6,106.2,97.0.HRMS(ESI+)exact mass calculated for[M+H] + (C 26 H 17 N 4 O 3 ):433.1295,found:433.1305.
4- (1-oxo-2 (8-quinolinyl) -2, 5-dihydro-1H-pyrido [4,3-b ]]Indol-3-yl) benzonitrile (3 k), 13mg,32%yield.Yellow solid,m.p.>300℃； 1 H NMR(400MHz,DMSO-d 6 )δ:12.35(s,1H),8.81 -8.83(m,1H),8.34 -8.36(m,1H),8.05(d,J＝8.0Hz,1H),7.92 -7.95(m,1H),7.81–7.83(m,1H),7.48–7.61(m,5H),7.32–7.36(m,3H),7.20 -7.24(m,1H),6.72(s,1H). 13 C NMR(100MHz,DMSO-d 6 )δ:159.4,150.9,145.8,144.2,143.7,141.0,138.0,136.4,136.3,131.9,131.2,129.6,128.9,128.3,125.8,124.2,124.0,121.9,120.9,120.4,118.2,111.7,110.7,106.0,96.9.HRMS(ESI+)exact mass calculated for[M+H] + (C 27 H 17 N 4 O):413.1397,found:413.1402.
3- (phenoxymethyl) -2- (8-quinolinyl) -2, 5-dihydro-1H-pyridine [4,3, b]Indol-1-one (3 l), 20mg,48%yield.Yellow solid,m.p.>300℃； 1 H NMR(400MHz,DMSO-d 6 )δ:11.94(s,1H),8.85–8.87(m,1H),8.47–8.49(m,1H),8.07 -8.09(m,1H),8.03(d,J＝8.0Hz,1H),7.91–7.93(m,1H),7.70(t,J＝8.0Hz,1H),7.54–7.62(m,2H),7.31–7.35(m,1H),7.12–7.23(m,3H),6.83–6.90(m,2H),6.64(d,J＝12.0Hz,2H),4.56(q,J＝20.0Hz,12Hz,2H). 13 C NMR(100MHz,DMSO-d 6 )δ:159.9,157.4,151.1,144.3,143.9,142.2,137.8,136.6,135.2,131.1,129.4,129.3,128.8,126.3,124.3,123.9,122.1,121.1,120.8,120.3,114.5,111.5,106.1,95.1,66.5.HRMS(ESI+)exact mass calculated for[M+H] + (C 27 H 20 N 3 O 2 ):418.1550,found:418.1553。
Claims (9)
1. The synthesis method of the gamma-carboline ketone compound is characterized by comprising the following steps of:
in the presence of a cobalt catalyst, an oxidant and alkali, reacting a 3-indolecarboxamide compound with alkyne in a solvent, and performing aftertreatment after the reaction to obtain the gamma-carboline ketone compound;
the structure of the 3-indolecarboxamide compound is shown as a formula (I):
the structure of the gamma-carboline ketone compound is shown as a formula (II):
in the formulae (I) to (II), R 1 Is substituted alkynyl, substituted or unsubstituted phenyl, substituted or unsubstituted C 1 ～C 10 An alkyl group; r is R 2 Substituted or unsubstituted phenyl, substituted or substituted C 1 ～C 10 Alkyl or hydrogen;
the substituent on the alkynyl is a substituted or unsubstituted phenyl, a substituted or unsubstituted C 1 ～C 10 An alkyl group;
the substituents on the phenyl groups are selected from C 1 ～C 4 Alkyl, C 1 ～C 4 Alkoxy, nitro or cyano;
the C is 1 ～C 10 The substituent on the alkyl group is selected from halogen or phenoxy.
2. The method for synthesizing gamma-carboline ketone compound according to claim 1, wherein R 1 Is a phenylalkynyl group, a p-toluynyl group, a p-ethylbenzene alkynyl group, a p-tert-butylphenynyl group, a p-methoxyphenylalkynyl group, a 6-chloro-n-hex-1-ynyl group, a cyclohexylalkynyl group, a 3-phenoxypropynyl group, a phenyl group, a p-nitrophenyl group, a p-cyanophenyl group or a phenoxymethyl group;
R 2 is phenyl, p-tolyl, p-ethylphenyl, p-tert-butylphenyl, p-methoxyphenyl, 4-chloro-n-butyl, cyclohexyl or phenoxyMethyl or hydrogen.
3. The method for synthesizing gamma-carboline ketone compound according to claim 1, wherein the cobalt catalyst is Co (OAc) 2 、CoCl 2 、CoF 2 、CoSO 4 ·7H 2 O or Co (acac) 2 。
4. The method for synthesizing gamma-carboline ketone compound according to claim 1, wherein the oxidant is Mn (OAc) 2 、AgOAc、Ag 2 O、Ag 2 CO 3 Or Mn (acac) 3 。
5. The method for synthesizing gamma-carboline ketone compound according to claim 1, wherein the base is NaOPiv, naH 2 PO4、K 2 HPO 4 、Na 2 CO 3 、NaHCO 3 、KHCO 3 Or NaOAc.
6. The method for synthesizing gamma-carboline ketone compound according to claim 1, wherein the solvent is trifluoroethanol, methanol, ethanol, hexafluoroisopropanol, 1, 2-dichloroethane or toluene.
7. The method for synthesizing gamma-carboline ketone compound according to claim 1, wherein the cobalt catalyst is Co (acac) 2 The oxidant is Mn (acac) 3 The alkali is NaOPiv, and the solvent is trifluoroethanol.
8. The method for synthesizing gamma-carboline ketone compound according to claim 1, wherein the reaction temperature is 80-140 ℃ and the reaction time is 3-24 hours.
9. The method for synthesizing the gamma-carboline ketone compound according to claim 1, wherein the structural formula of the gamma-carboline ketone compound is as follows:
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