CN105859695B - Synthesis method of 2-aryl-3- (4-hydroxy-2H-pyran-2-ketone-3-yl) indole derivative - Google Patents
Synthesis method of 2-aryl-3- (4-hydroxy-2H-pyran-2-ketone-3-yl) indole derivative Download PDFInfo
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- CN105859695B CN105859695B CN201610340319.8A CN201610340319A CN105859695B CN 105859695 B CN105859695 B CN 105859695B CN 201610340319 A CN201610340319 A CN 201610340319A CN 105859695 B CN105859695 B CN 105859695B
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- 150000002475 indoles Chemical class 0.000 title claims abstract description 47
- 238000001308 synthesis method Methods 0.000 title abstract description 5
- 238000000034 method Methods 0.000 claims abstract description 46
- 239000003054 catalyst Substances 0.000 claims abstract description 18
- VNZOLPIHDIJPBZ-UHFFFAOYSA-N 4-hydroxypyran-2-one Chemical class OC=1C=COC(=O)C=1 VNZOLPIHDIJPBZ-UHFFFAOYSA-N 0.000 claims abstract description 14
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000002994 raw material Substances 0.000 claims abstract description 7
- 230000005855 radiation Effects 0.000 claims abstract description 5
- 238000010490 three component reaction Methods 0.000 claims abstract description 5
- 125000002490 anilino group Chemical class [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 66
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 64
- 150000001875 compounds Chemical class 0.000 claims description 41
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- 230000015572 biosynthetic process Effects 0.000 claims description 15
- 238000003786 synthesis reaction Methods 0.000 claims description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 10
- 229940054051 antipsychotic indole derivative Drugs 0.000 claims description 10
- 235000019441 ethanol Nutrition 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- 238000010189 synthetic method Methods 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- ZXPNUUFATNGXAW-UHFFFAOYSA-N benzene;oxaldehyde Chemical class O=CC=O.C1=CC=CC=C1 ZXPNUUFATNGXAW-UHFFFAOYSA-N 0.000 claims description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000012046 mixed solvent Substances 0.000 claims description 4
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 3
- 150000002576 ketones Chemical class 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims 1
- -1 indole compound Chemical class 0.000 abstract description 24
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 abstract description 12
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 abstract description 7
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 abstract description 7
- 238000006452 multicomponent reaction Methods 0.000 abstract description 5
- 230000035484 reaction time Effects 0.000 abstract description 4
- MALOBWMOORWUQW-UHFFFAOYSA-N 4h-pyran-3-one Chemical group O=C1COC=CC1 MALOBWMOORWUQW-UHFFFAOYSA-N 0.000 abstract description 2
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 2
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 abstract 1
- 150000003935 benzaldehydes Chemical class 0.000 abstract 1
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzenecarboxaldehyde Natural products O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 abstract 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 abstract 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 68
- 238000006243 chemical reaction Methods 0.000 description 52
- 239000000047 product Substances 0.000 description 40
- 238000005160 1H NMR spectroscopy Methods 0.000 description 37
- 150000003983 crown ethers Chemical class 0.000 description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 14
- NSYSSMYQPLSPOD-UHFFFAOYSA-N triacetate lactone Chemical compound CC1=CC(O)=CC(=O)O1 NSYSSMYQPLSPOD-UHFFFAOYSA-N 0.000 description 13
- 239000002253 acid Substances 0.000 description 8
- OJUGVDODNPJEEC-UHFFFAOYSA-N phenylglyoxal Chemical compound O=CC(=O)C1=CC=CC=C1 OJUGVDODNPJEEC-UHFFFAOYSA-N 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 7
- 150000001448 anilines Chemical class 0.000 description 6
- WDFQBORIUYODSI-UHFFFAOYSA-N 4-bromoaniline Chemical compound NC1=CC=C(Br)C=C1 WDFQBORIUYODSI-UHFFFAOYSA-N 0.000 description 5
- WRDWWAVNELMWAM-UHFFFAOYSA-N 4-tert-butylaniline Chemical compound CC(C)(C)C1=CC=C(N)C=C1 WRDWWAVNELMWAM-UHFFFAOYSA-N 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 238000006555 catalytic reaction Methods 0.000 description 4
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- LRTFPLFDLJYEKT-UHFFFAOYSA-N para-isopropylaniline Chemical compound CC(C)C1=CC=C(N)C=C1 LRTFPLFDLJYEKT-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- JTIHSSVKTWPPHI-UHFFFAOYSA-N 2-amino-2-phenylacetonitrile Chemical group N#CC(N)C1=CC=CC=C1 JTIHSSVKTWPPHI-UHFFFAOYSA-N 0.000 description 2
- YSEMCVGMNUUNRK-UHFFFAOYSA-N 3-chloro-4-fluoroaniline Chemical compound NC1=CC=C(F)C(Cl)=C1 YSEMCVGMNUUNRK-UHFFFAOYSA-N 0.000 description 2
- RQKFYFNZSHWXAW-UHFFFAOYSA-N 3-chloro-p-toluidine Chemical compound CC1=CC=C(N)C=C1Cl RQKFYFNZSHWXAW-UHFFFAOYSA-N 0.000 description 2
- JJYPMNFTHPTTDI-UHFFFAOYSA-N 3-methylaniline Chemical compound CC1=CC=CC(N)=C1 JJYPMNFTHPTTDI-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- UCHDWCPVSPXUMX-TZIWLTJVSA-N Montelukast Chemical compound CC(C)(O)C1=CC=CC=C1CC[C@H](C=1C=C(\C=C\C=2N=C3C=C(Cl)C=CC3=CC=2)C=CC=1)SCC1(CC(O)=O)CC1 UCHDWCPVSPXUMX-TZIWLTJVSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- VTTONGPRPXSUTJ-UHFFFAOYSA-N bufotenin Chemical compound C1=C(O)C=C2C(CCN(C)C)=CNC2=C1 VTTONGPRPXSUTJ-UHFFFAOYSA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 229940125890 compound Ia Drugs 0.000 description 2
- 235000015177 dried meat Nutrition 0.000 description 2
- 239000000686 essence Substances 0.000 description 2
- 125000005909 ethyl alcohol group Chemical group 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- VAMXMNNIEUEQDV-UHFFFAOYSA-N methyl anthranilate Chemical compound COC(=O)C1=CC=CC=C1N VAMXMNNIEUEQDV-UHFFFAOYSA-N 0.000 description 2
- YLHXLHGIAMFFBU-UHFFFAOYSA-N methyl phenylglyoxalate Chemical compound COC(=O)C(=O)C1=CC=CC=C1 YLHXLHGIAMFFBU-UHFFFAOYSA-N 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 229960005127 montelukast Drugs 0.000 description 2
- FRCFWPVMFJMNDP-UHFFFAOYSA-N n-propan-2-ylaniline Chemical compound CC(C)NC1=CC=CC=C1 FRCFWPVMFJMNDP-UHFFFAOYSA-N 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- GNPHAOQLHRZODS-ZQWQDMLBSA-N (1s,2s,3s,4s)-3,4-bis[butyl-[(4-phenoxyphenyl)methyl]carbamoyl]cyclobutane-1,2-dicarboxylic acid Chemical compound O=C([C@H]1[C@@H]([C@@H]([C@H]1C(O)=O)C(O)=O)C(=O)N(CCCC)CC=1C=CC(OC=2C=CC=CC=2)=CC=1)N(CCCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 GNPHAOQLHRZODS-ZQWQDMLBSA-N 0.000 description 1
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical compound CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 description 1
- VVAKEQGKZNKUSU-UHFFFAOYSA-N 2,3-dimethylaniline Chemical compound CC1=CC=CC(N)=C1C VVAKEQGKZNKUSU-UHFFFAOYSA-N 0.000 description 1
- BNGOFPJWZUXKNR-UHFFFAOYSA-N 2-oxo-2-phenylacetyl chloride Chemical compound ClC(=O)C(=O)C1=CC=CC=C1 BNGOFPJWZUXKNR-UHFFFAOYSA-N 0.000 description 1
- GTCLFEMMPGBNOI-UHFFFAOYSA-N 2-phenylethynamine Chemical group NC#CC1=CC=CC=C1 GTCLFEMMPGBNOI-UHFFFAOYSA-N 0.000 description 1
- ZPSJGADGUYYRKE-UHFFFAOYSA-N 2H-pyran-2-one Chemical compound O=C1C=CC=CO1 ZPSJGADGUYYRKE-UHFFFAOYSA-N 0.000 description 1
- DHYHYLGCQVVLOQ-UHFFFAOYSA-N 3-bromoaniline Chemical compound NC1=CC=CC(Br)=C1 DHYHYLGCQVVLOQ-UHFFFAOYSA-N 0.000 description 1
- PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 description 1
- UDLXBNUJGMTDRA-UHFFFAOYSA-N 6-methyl-2H-pyran-4-ol Chemical compound CC1=CC(O)=CCO1 UDLXBNUJGMTDRA-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- ULRNUVYFVYPTKE-UHFFFAOYSA-N C(C)(=O)NC#CC1=CC=CC=C1 Chemical group C(C)(=O)NC#CC1=CC=CC=C1 ULRNUVYFVYPTKE-UHFFFAOYSA-N 0.000 description 1
- JBNBNDGMKZGCHD-UHFFFAOYSA-N C1=CC=C(C=C1)C(=O)CC(=O)Br Chemical compound C1=CC=C(C=C1)C(=O)CC(=O)Br JBNBNDGMKZGCHD-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- 229910015189 FeOx Inorganic materials 0.000 description 1
- 102000030595 Glucokinase Human genes 0.000 description 1
- 108010021582 Glucokinase Proteins 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 239000008896 Opium Substances 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 102100038824 Peroxisome proliferator-activated receptor delta Human genes 0.000 description 1
- VOLMSPGWNYJHQQ-UHFFFAOYSA-N Pyranone Natural products CC1=C(O)C(=O)C(O)CO1 VOLMSPGWNYJHQQ-UHFFFAOYSA-N 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000003972 antineoplastic antibiotic Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 208000029771 childhood onset asthma Diseases 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000009514 concussion Effects 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical class C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 description 1
- 229940103177 maxalt Drugs 0.000 description 1
- 239000003863 metallic catalyst Substances 0.000 description 1
- 229940102398 methyl anthranilate Drugs 0.000 description 1
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 229960001027 opium Drugs 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 150000004880 oxines Chemical class 0.000 description 1
- 125000006237 oxymethylenoxy group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 108091008765 peroxisome proliferator-activated receptors β/δ Proteins 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
- 229940067157 phenylhydrazine Drugs 0.000 description 1
- 230000008635 plant growth Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- UOWVMDUEMSNCAV-WYENRQIDSA-N rachelmycin Chemical compound C1([C@]23C[C@@H]2CN1C(=O)C=1NC=2C(OC)=C(O)C4=C(C=2C=1)CCN4C(=O)C1=CC=2C=4CCN(C=4C(O)=C(C=2N1)OC)C(N)=O)=CC(=O)C1=C3C(C)=CN1 UOWVMDUEMSNCAV-WYENRQIDSA-N 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- ULFRLSNUDGIQQP-UHFFFAOYSA-N rizatriptan Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CN1C=NC=N1 ULFRLSNUDGIQQP-UHFFFAOYSA-N 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 108010050939 thrombocytin Proteins 0.000 description 1
- UUXXSEDWABGXNW-UHFFFAOYSA-L zinc pentachloro-lambda5-phosphane dichloride Chemical compound [Cl-].[Zn+2].P(Cl)(Cl)(Cl)(Cl)Cl.[Cl-] UUXXSEDWABGXNW-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a synthesis method of a novel 2-aryl-3- (4-hydroxy-2H-pyran-2-ketone-3-yl) indole derivative, the 2-aryl-3- (4-hydroxy-2H-pyran-2-ketone-3-yl) indole derivative is a novel indole compound which is substituted by 2-aryl in one step by utilizing a multi-component reaction method, substituted by 3-pyrone and has two heterocyclic frameworks of pyran and indole, and the novel indole compound is obtained by taking substituted benzaldehyde, substituted aniline and 4-hydroxypyrone as raw materials and performing three-component reaction in one step under the action of a catalyst and microwave radiation. Compared with the existing indole compound synthesis method, the synthesis method has the advantages of short reaction time and simpler conditions.
Description
Technical field
The invention belongs to organic compounds into field, in particular to a kind of 2- aryl -3- (4- hydroxyl -2H- pyrans -2-
Ketone -3- base) indoles synthetic method.
Background technique
Benzazole compounds are that most wide heterocyclic compound is distributed in nature, as medicine, pesticide, dyestuff and other essences
The intermediate of chemical product is refined, application is more and more wider.Firstly, indole ring is an important skeleton in many drugs, than
Such as treat the new drug Singulair (Singulair) of adult and childhood asthma, and treatment migraine remedy (Maxalt)；Together
Sample, has indoles-chinol compound of highly selective anti-tumor activity for colon, breast cancer cell, and structural formula is(A.J.McCarroll,T.D.Bradshaw,A.D.Westwell,C.S.Matthews,
M.F.G.Stevens.J.Med.Chem.,2007,50,1707)；Indole derivatives can be used as nerve protection medicine, efficient opium
Receptor agonist treats osteoporosis agents PPAR-c, treats the drug of peripheral neuropathy and neurodegenerative disease, Portugal
Glucokinase activators, the pro-drug of cytotoxic antibiotics CC-1065 and it, and treatment cardiovascular disease catalyst
PPAR-delta(G.Bratulescu,Tetrahedron Lett.,2008,49,984)。
Secondly, having anesthesiophore bufotenine, structure in known more than 3000 kinds natural enatiomers of indole ring derivatives
Formula isSerotonine (thrombocytin) in animal blood, structural formula areIt is important neurotic mass transfer, can be used as the defensive drug for resisting microbial challenge；3- indoles second
Acid, structural formula areIt is a kind of plant growth regulating hormone, the 3-indolyl acetic acid derivative of synthesis (disappears
Scorching pain), have been used for treatment rheumatic arthritis.
There is highly important application value based on Benzazole compounds, people carry out the synthetic method of such compound
A large amount of research.It is reported that synthesizing a series of benzazolyl compounds using different metallic catalyst catalysis reactions in recent years.
Saa seminar utilizes the CpRu (PPh of 10mol%3)2Cl is catalyzed the indoles of adjacent amino phenylacetylene one-step synthesis different substituents
It closes object (A.Varela-Fernandez, J.A.Varela, C.Saa.Adv.Synth.Catal., 2011,353,1933).
Bratulescu using phenylhydrazine, pyruvic acid, phosphorus pentachloride zinc chloride catalysis next step synthesis of indole compound
(G.Bratulescu.Tetrahedron Lett.,2008,49,984).Inoue etc. utilizes Ru catalyst under protection of argon gas
The adjacent Aminophenethyl alcohol synthesis of indole compound of catalysis reaction (S.Shimura, H.Miura, K.Wada, S.Hosokawa,
M.Inoue.Catal.Sci.Technol.,2011,1,1340).Muldoon etc. is using adjacent Aminophenethyl alcohol at Cu (OTf)2/
One-step synthesis benzazolyl compounds under the conditions of 2,2 '-bipyridyls/TEMPO/DBU/NMI (J.C.A.Flanagan, L.M.Dornan,
M.G.McLaughlin,N.G.McCreanor,M.J.Cook,M.J.Muldoon.Green Chem.,2012,14,1281)。
Hirota etc. at room temperature, using methanol as solvent Pd/C be catalyzed adjacent aminopheny-lacetonitrile obtain benzazolyl compounds (H.Sajiki,
K.Hirota.Org.Lett.,2004,6,4977).Sajiki etc. is catalyzed adjacent aminopheny-lacetonitrile using Pd/C under hydrogen protection
One-step synthesis Benzazole compounds (T.Ikawa, Y.Fujita, T.Mizusaki, S.Betsuin, H.Takamaysu,
T.Maegawa,Y.Monguchi,H.Sajiki.Org.Biomol.Chem.,2012,10,293).Li Xingwei et al. utilizes neighbour
Acetylamino phenylacetylene utilizes Cs in toluene2CO3Catalytic one-stage synthesis of indole compound (F.Xie, Z.Qi, S.Yu,
X.Li.J.Am.Chem.Soc.,2014,136,4780).For Beller using (FeOx@NGr-C-NL) as catalyst, catalysis is anti-
Answer indoline dehydrogenation obtain target product indoles (X.Cui, Y.Li, S.Bachmann, M.Scalone, A.E.Surkus,
K.Junge,C.Topf,M.Beller.J.Am.Chem.Soc.,2015,137,10652).Although the effective land productivity of the above method
With a series of benzazolyl compounds of synthesis, but these above-mentioned reactions are most of to obtain target product using metal catalytic, reacts
Time is longer, and condition is more complex.
Multi-component reaction refers to three or three or more starting materials is primary or sequentially adds reaction, passes through one pot
The method boiled obtains target product, and each intermediate is the raw material of reaction in next step, and in the structure of final product includes institute
There is a kind of high-efficiency synthesis method of raw material segment.It can use some raw materials simple and easy to get by multi-component reaction, it is convenient, high
The building of effect ground has the compound of structure diversity and complexity, and this method has been widely used for the conjunction of various heterocyclic compounds
At.
Summary of the invention
Replaced the object of the present invention is to provide a kind of using 2- aryl of method one-step synthesis of multi-component reaction, 3- pyrroles
The new indole class compound that ketone of muttering replaces.
To realize above-mentioned technical purpose and the technique effect, the invention is realized by the following technical scheme:
A kind of 2- aryl -3- (4- hydroxyl -2H- pyran-2-one -3- base) indole derivatives have structure shown in Formulas I:
Wherein, R1For H, 4-CH3O、4-CH3, one of 4-Cl or 3-Br, R2For 4-CH3、4-CH3O、3-CH3、4-n-
Bu、4-i-Pr、3-i-Pr、2,3-(CH3)2、3-Cl、4-Cl、3-Br、4-Br、4-F、3-Cl-4-F、3-Cl-4-CH3Or 2-
CO2CH3One of.
A kind of synthetic method of 2- aryl -3- (4- hydroxyl -2H- pyran-2-one -3- base) indole derivatives (Formulas I), be with
Substituted benzene formyl formaldehyde (Formula II), substituted aniline (formula III) and 4- hydroxy pyrone (formula IV) be raw material, with alcohol, ether, nitrile, water,
Acetic acid or arene compound are solvent, using inorganic base, inorganic acid, organic acid or organic micromolecule compound as catalyst,
Under microwave radiation, target compound is obtained by three component reaction one-step synthesis:
Its reaction equation is as follows:
Preparation method of the present invention, substituted benzene formyl formaldehyde (Formula II), substituted aniline (formula III), 4- hydroxyl pyrans
Reaction system composed by ketone (formula IV), catalyst and appropriate solvent carries out under microwave radiation.Wherein, the substituted benzene formyl
Formaldehyde (Formula II), the substituted aniline (formula III), the 4- hydroxy pyrone (formula IV) and the catalyst molar ratio be 1:
1:1:0.2。
Catalyst, which refers to, can improve chemical reaction rate, and the substance permanently sexually revised does not occur for this body structure.The present invention
Catalyst in the preparation method can be sodium carbonate, ferric trichloride, acetic acid, trifluoroacetic acid, p-methyl benzenesulfonic acid or L- dried meat
One of propylhomoserin.Wherein, preferably, so stating catalyst is trifluoroacetic acid.
Preparation method of the present invention, the substituted benzene formyl formaldehyde (Formula II), the substituted aniline (formula III) and institute
Three component reactions for stating 4- hydroxy pyrone (formula IV) carry out in a solvent, and the solvent can be ethyl alcohol, acetonitrile, two
One of first sulfoxide, tetrahydrofuran, toluene, acetic acid, water, water and mixed solvent of ethyl alcohol composition.In view of the effect of reaction
With the principle of Green Chemistry, preferably, the solvent is the mixed solvent that water and ethyl alcohol form (volume ratio 1:1).
Preferably, the reaction time of preparation method of the present invention is 40 minutes.
Preferably, the reaction temperature of preparation method of the present invention is 90~110 DEG C.
The beneficial effects of the present invention are:
The present invention provides one kind not to need metal catalytic, is taken using 2- aryl of method one-step synthesis of multi-component reaction
Generation, a kind of new indole class compound with two kinds of heterocyclic skeletons of pyrans and indoles that 3- pyranone replace are and existing
Benzazolyl compounds synthetic method is compared, and the reaction time of synthetic method of the invention is shorter, and condition is relatively simple.
The above description is only an overview of the technical scheme of the present invention, in order to better understand the technical means of the present invention,
And can be implemented in accordance with the contents of the specification, it is described in detail below with presently preferred embodiments of the present invention.Specific reality of the invention
Mode is applied to be shown in detail by following embodiment.
Specific embodiment
Below in conjunction with embodiment, next the present invention will be described in detail.
A kind of 2- aryl -3- (4- hydroxyl -2H- pyran-2-one -3- base) indole derivatives, are the chemical combination with Formulas I structure
Object:
Wherein, R1For H, 4-CH3O、4-CH3, one of 4-Cl or 3-Br, R2For 4-CH3、4-CH3O、3-CH3、4-n-
Bu、4-i-Pr、3-i-Pr、2,3-(CH3)2、3-Cl、4-Cl、3-Br、4-Br、4-F、3-Cl-4-F、3-Cl-4-CH3Or 2-
CO2CH3One of.
A kind of synthetic method of 2- aryl -3- (4- hydroxyl -2H- pyran-2-one -3- base) indole derivatives (Formulas I), be with
Substituted benzene formyl formaldehyde (Formula II), substituted aniline (formula III) and 4- hydroxy pyrone (formula IV) be raw material, with alcohol, ether, nitrile, water,
Acetic acid or arene compound are solvent, using inorganic base, inorganic acid, organic acid or organic micromolecule compound as catalyst,
Under microwave radiation, target compound is obtained by three component reaction one-step synthesis:
Its reaction equation is as follows:
Further, the substituted benzene formyl formaldehyde (Formula II), the substituted aniline (formula III), the 4- hydroxyl
The molar ratio of base pyranone (formula IV) and the catalyst is 1:1:1:0.2.
Further, the catalyst is sodium carbonate, ferric trichloride, acetic acid, trifluoroacetic acid, p-methyl benzenesulfonic acid, L- dried meat ammonia
One of acid.
Further, the solvent is ethyl alcohol, acetonitrile, dimethyl sulfoxide, tetrahydrofuran, toluene, acetic acid, water, water and ethyl alcohol
One of mixed solvent.
Further, the reaction time of the preparation method is 10~50 minutes.
Further, the reaction temperature of the preparation method is 60~110 DEG C.
Below by following embodiment to this kind of 2- aryl -3- (4- hydroxyl -2H- pyran-2-one -3- base) indole derivatives
Synthetic method is illustrated and is illustrated in detail:
Embodiment 1
Phenylglyoxal (1mmol), open-chain crown ether (1mmol), 4- hydroxyl -6- Methylpyrane -2- ketone (1mmol) are added
Enter microwave reaction tube, 3mL EtOH/H is added2O (1:1), slightly concussion are uniformly mixed substrate, and (0.2mmol) trifluoro second is added dropwise
Acid monitors reaction process with TLC, is produced to be chromatographed after reaction by column in 90 DEG C of reaction 40min in microwave reactor
Object, is 5- methyl -2- phenyl -3- (4- hydroxyl -6- methyl -2H- pyran-2-one -3- base) indoles (compound Ia), and yield is
60%.The structure of compound determines that fusing point is 260-263 DEG C by nuclear magnetic resonance spectroscopy；1H NMR(400MHz,DMSO-d6)δ
(ppm): 11.32 (s, 1H, OH), 10.95 (s, 1H, NH), 7.61 (d, J=7.2Hz, 2H, ArH), 7.40 (t, J=7.2Hz,
2H, ArH), 7.32-7.26 (m, 2H, ArH), 6.96 (d, J=7.6Hz, 2H, ArH), 6.14 (s, 1H, ArH), 2.36 (s, 3H,
CH3),2.26(s,3H,CH3)。
Embodiment 2
According to the method for embodiment 1, open-chain crown ether is changed into P-nethoxyaniline, using trifluoroacetic acid as catalyst,
In 90 DEG C, microwave reaction 40min, column chromatographs to obtain target product 5- methoxyl group -2- phenyl -3- (4- hydroxyl -6- methyl -2H- pyrrole
Mutter -2- ketone -3- base) indoles (compound Ib), yield 51%；Fusing point is 276-278 DEG C；1H NMR(400MHz,DMSO-d6)δ
(ppm):11.29(s,1H,OH),10.93(s,1H,NH),7.57(s,2H,ArH),7.39-7.29(m,4H,ArH),6.77
(d, J=6.4Hz, 1H, ArH), 6.62 (s, 1H, ArH), 6.13 (s, 1H, ArH), 3.71 (s, 3H, CH3O),2.26(s,3H,
CH3)。
Embodiment 3
According to the method for embodiment 1, open-chain crown ether is changed into m-toluidine, using trifluoroacetic acid as catalyst, in
90 DEG C, microwave reaction 40min, column chromatographs to obtain target product 6- methyl -2- phenyl -3- (4- hydroxyl -6- methyl -2H- pyrans -
2- ketone -3- base)-indoles (compound Ic), yield 57%；236-239 DEG C of fusing point；1H NMR(400MHz,DMSO-d6)δ(ppm):
11.26 (s, 1H, OH), 10.95 (s, 1H, NH), 7.57 (d, J=7.2Hz, 2H, ArH), 7.39 (t, J=7.6Hz, 2H,
), ArH 7.26 (t, J=7.2Hz, 1H, ArH), 7.19 (s, 1H, ArH), 7.03 (d, J=8.0Hz, 1H, ArH), 6.79 (d, J
=7.2Hz, 1H, ArH), 6.11 (s, 1H, ArH), 2.41 (s, 3H, CH3),2.25(s,3H,CH3)。
Embodiment 4
According to the method for embodiment 1, open-chain crown ether is changed into p-tert-butyl-aniline, using trifluoroacetic acid as catalyst,
In 90 DEG C, microwave reaction 40min, column chromatographs to obtain target product 6- tert-butyl -2- phenyl -3- (4- hydroxyl -6- methyl -2H- pyrrole
Mutter -2- ketone -3- base) indoles (compound Id), yield 72%；259-260 DEG C of fusing point；1H NMR(400MHz,DMSO-d6)δ
(ppm): 11.30 (s, 1H, OH), 10.93 (s, 1H, NH), 7.57 (d, J=7.2Hz, 2H, ArH), 7.41-7.34 (m, 3H,
ArH),7.28-7.21(m,2H,ArH),7.10(s,1H,ArH),6.13(s,1H,ArH),2.26(s,3H,CH3),1.31(s,
9H,(CH3)3C)。
Embodiment 5
According to the method for embodiment 1, it changes open-chain crown ether into isopropyl aniline, the trifluoroacetic acid of 0.2mmol is added,
In 90 DEG C, microwave reaction 40min, column chromatographs to obtain target product 5- isopropyl -2- phenyl -3- (4- hydroxyl -6- methyl -2H- pyrrole
Mutter -2- ketone -3- base) indoles (compound Ie), yield 64%；Fusing point > 300 DEG C；1H NMR(400MHz,DMSO-d6)δ(ppm):
11.29 (s, 1H, OH), 10.93 (s, 1H, NH), 7.59 (d, J=6.0Hz, 2H, ArH), 7.42-7.38 (m, 2H, ArH),
7.28-7.25 (m, 2H, ArH), 7.08 (d, J=7.2Hz, 1H, ArH), 6.90 (d, J=7.2Hz, 1H, ArH), 6.13 (s,
1H,ArH),3.01-2.98(m,1H,CH),2.26(s,3H,CH3), 1.28 (d, J=5.2Hz, 6H, (CH3)2C)。
Embodiment 6
According to the method for example 1, changes open-chain crown ether into 2,3- dimethylaniline, the trifluoroacetic acid of 0.2mmol is added,
In 90 DEG C, microwave reaction 40min, column chromatographs to obtain target product 6,7- dimethyl -2- phenyl -3- (4- hydroxyl -6- methyl -2H-
Pyran-2-one -3- base)-indoles (compound If), yield 38%；210-211 DEG C of fusing point；1H NMR(400MHz,DMSO-d6)δ
(ppm): 10.98 (s, 1H, OH), 10.90 (s, 1H, NH), 7.63 (d, J=7.2Hz, 2H, ArH), 7.41 (t, J=7.2Hz,
2H,ArH),7.31-7.26(m,1H,ArH),6.79(s,1H,ArH),6.75(s,1H,ArH),6.12(s,1H,ArH),2.52
(s,3H,CH3),2.32(s,1H,CH3),2.25(s,3H,CH3)。
Embodiment 7
According to the method for example 1, changes open-chain crown ether into 3,4- methylene dioxo group aniline, the trifluoro of 0.2mmol is added
Acetic acid, in 90 DEG C, microwave reaction 40min, column chromatographs to obtain target product 5,6- methylene-dioxy -2- phenyl -3- (4- hydroxyl -
6- methyl -2H- pyran-2-one -3- base) indoles (Compound Ig per), yield 69%；248-249 DEG C of fusing point；1H NMR(400MHz,
DMSO-d6) δ (ppm): 11.28 (s, 1H, OH), 10.98 (s, 1H, NH), 7.53 (d, J=7.2Hz, 2H, ArH), 7.36 (t, J
=7.6Hz, 2H, ArH), 7.22 (t, J=7.2Hz, 1H, ArH), 6.92 (s, 1H, ArH), 6.56 (s, 1H, ArH), 6.12 (s,
1H,ArH),5.93(s,2H,OCH2O),2.25(s,3H,CH3)。
Embodiment 8
According to the method for example 1, open-chain crown ether is changed into m-chloroaniline, the trifluoroacetic acid of 0.2mmol is added, in 90
DEG C, microwave reaction 40min, column chromatographs to obtain the chloro- 2- phenyl -3- of target product 5- (4- hydroxyl -6- methyl -2H- pyran-2-one -
3- yl) indoles (compound Ih), yield 66%；275-277 DEG C of fusing point；1H NMR(400MHz,DMSO-d6)δ(ppm):11.62
(s, 1H, OH), 11.10 (s, 1H, NH), 7.58 (d, J=7.6Hz, 2H, ArH), 7.44-7.40 (m, 3H, ArH), 7.30 (t, J
=7.2Hz, 1H, ArH), 7.16 (d, J=8.4Hz, 1H, ArH), 7.00-6.97 (m, 1H, ArH), 6.12 (s, 1H, ArH),
2.25(s,3H,CH3)。
Embodiment 9
According to the method for example 1, open-chain crown ether is changed into parachloroanilinum, the trifluoroacetic acid of 0.2mmol is added, in 90
DEG C, microwave reaction 40min, column chromatographs to obtain the chloro- 2- phenyl -3- of target product 6- (4- hydroxyl -6- methyl -2H- pyran-2-one -
3- yl) indoles (compound Ii), yield 77%；270-273 DEG C of fusing point；1H NMR(400MHz,DMSO-d6)δ(ppm):11.67
(s, 1H, OH), 11.12 (s, 1H, NH), 7.60 (d, J=7.2Hz, 2H, ArH), 7.44-7.40 (m, 3H, ArH), 7.31 (t, J
=7.2Hz, 1H, ArH), 7.16 (s, 1H, ArH), 7.13-7.10 (m, 1H, ArH), 6.13 (s, 1H, ArH), 2.26 (s, 3H,
CH3)。
Embodiment 10
According to the method for example 1, open-chain crown ether is changed into m-bromoaniline, the trifluoroacetic acid of 0.2mmol is added, in 90
DEG C, microwave reaction 40min, column chromatographs to obtain the bromo- 2- phenyl -3- of target product 5- (4- hydroxyl -6- methyl -2H- pyran-2-one -
3- yl) indoles (compound Ij), yield 72%；285-287 DEG C of fusing point；1H NMR(400MHz,DMSO-d6)δ(ppm):11.62
(s, 1H, OH), 11.10 (s, 1H, NH), 7.57 (t, J=8.0Hz, 3H, ArH), 7.42 (t, J=7.6Hz, 2H, ArH), 7.31
(t, J=7.2Hz, 1H, ArH), 7.13-7.08 (m, 2H, ArH), 6.12 (s, 1H, ArH), 2.25 (s, 3H, CH3)。
Embodiment 11
According to the method for example 1, open-chain crown ether is changed into para-bromoaniline, the trifluoroacetic acid of 0.2mmol is added, in 90
DEG C, microwave reaction 40min, column chromatographs to obtain the bromo- 2- phenyl -3- of target product 6- (4- hydroxyl -6- methyl -2H- pyran-2-one -
3- yl) indoles (compound Ik), yield 81%；218-220 DEG C of fusing point；1H NMR(400MHz,DMSO-d6)δ(ppm):11.68
(s, 1H, OH), 11.13 (s, 1H, NH), 7.61 (d, J=7.6Hz, 2H, ArH), 7.44-7.37 (m, 3H, ArH), 7.33-
7.30(m,2H,ArH),7.24-7.22(m,1H,ArH),6.13(s,1H,ArH),2.26(s,3H,CH3)。
Embodiment 12
According to the method for example 1, open-chain crown ether is changed into para-fluoroaniline, the trifluoroacetic acid of 0.2mmol is added, in 90
DEG C, microwave reaction 40min, column chromatographs to obtain the fluoro- 2- phenyl -3- of target product 6- (4- hydroxyl -6- methyl -2H- pyran-2-one -
3- yl) indoles (compound Il), yield 76%；210-212 DEG C of fusing point；1H NMR(400MHz,DMSO-d6)δ(ppm):11.59
(s, 1H, OH), 11.11 (s, 1H, NH), 7.62 (d, J=7.6Hz, 2H, ArH), 7.47-7.41 (m, 3H, ArH), 7.34 (t, J
=7.2Hz, 1H, ArH), 7.01-6.96 (m, 1H, ArH), 6.90 (d, J=10.0Hz, 1H, ArH), 6.16 (s, 1H, ArH),
2.29(s,3H,CH3)。
Embodiment 13
According to the method for example 1, changes open-chain crown ether into 3- chloro- 4- fluoroaniline, the trifluoroacetic acid of 0.2mmol is added,
In 90 DEG C, microwave reaction 40min, column chromatographs to obtain the fluoro- 2- phenyl -3- of the chloro- 6- of target product 5- (4- hydroxyl -6- methyl -2H-
Pyran-2-one -3- base) indoles (compound Im), yield 80%；288-290 DEG C of fusing point；1H NMR(400MHz,DMSO-d6)δ
(ppm): 11.70 (s, 1H, OH), 11.16 (s, 1H, NH), 7.58 (d, J=7.2Hz, 2H, ArH), 7.51 (d, J=6.4Hz,
1H, ArH), 7.42 (t, J=7.6Hz, 2H, ArH), 7.32 (t, J=7.6Hz, 1H, ArH), 7.09 (d, J=10.4Hz, 1H,
ArH),6.12(s,1H,ArH),2.25(s,3H,CH3)。
Embodiment 14
According to the method for example 1, changes open-chain crown ether into 3- chloro- 4- methylaniline, the trifluoro second of 0.2mmol is added
Acid, in 90 DEG C, microwave reaction 40min, column chromatographs to obtain the chloro- 6- methyl -2- phenyl -3- of target product 5- (4- hydroxyl -6- first
Base -2H- pyran-2-one -3- base) indoles (compound In), yield 71%；276-278 DEG C of fusing point；1H NMR(400MHz,
DMSO-d6) δ (ppm): 11.48 (s, 1H, OH), 11.06 (s, 1H, NH), 7.59 (d, J=7.6Hz, 2H, ArH), 7.41 (t, J
=7.6Hz, 3H, ArH), 7.30 (t, J=7.2Hz, 1H, ArH), 7.11 (s, 1H, ArH), 6.13 (s, 1H, ArH), 2.36 (s,
3H,CH3),2.26(s,3H,CH3)。
Embodiment 15
According to the method for example 1, open-chain crown ether is changed into methyl anthranilate, the trifluoro second of 0.2mmol is added
Acid, in 90 DEG C, microwave reaction 40min, column chromatographs to obtain target product 2- phenyl -4- methoxycarbonyl group -3- (4- hydroxyl -6- methyl -
2H- pyran-2-one -3- base) indoles (compound Io), yield 27%；214-217 DEG C of fusing point；1H NMR(400MHz,DMSO-d6)
δ (ppm): 11.11 (s, 1H, OH), 10.83 (s, 1H, NH), 7.80 (d, J=7.2Hz, 1H, ArH), 7.59 (d, J=7.2Hz,
2H, ArH), 7.48 (d, J=7.6Hz, 1H, ArH), 7.43 (t, J=7.6Hz, 2H, ArH), 7.36-7.32 (m, 1H, ArH),
7.13 (t, J=7.6Hz, 1H, ArH), 6.11 (s, 1H, ArH), 3.98 (s, 3H, CH3O),2.25(s,3H,CH3)。
Embodiment 16
According to the method for example 1 into, phenylglyoxal is changed to the trifluoro for methoxybenzoyl formaldehyde being added 0.2mmol
Acetic acid, in 90 DEG C, microwave reaction 40min, column chromatographs to obtain target product 6- methyl -2- p-methoxyphenyl -3- (4- hydroxyl -
6- methyl -2H- pyran-2-one -3- base) indoles (compound Ip), yield 62%；266-268 DEG C of fusing point；1H NMR(400MHz,
DMSO-d6) δ (ppm): 11.20 (s, 1H, OH), 10.89 (s, 1H, NH), 7.53 (d, J=8.4Hz, 2H, ArH), 7.28 (d, J
=8.4Hz, 1H, ArH), 6.99-6.91 (m, 4H, ArH), 6.13 (s, 1H, ArH), 3.77 (s, 3H, CH3O),2.35(s,3H,
CH3),2.26(s,3H,CH3)。
Embodiment 17
According to the method for example 16, open-chain crown ether is changed into p-tert-butyl-aniline, the trifluoroacetic acid of 0.2mmol is added,
In 90 DEG C, microwave reaction 40min, column chromatographs to obtain target product 6- tert-butyl -2- p-methoxyphenyl -3- (4- hydroxyl -6- first
Base -2H- pyran-2-one -3- base) indoles (compound Iq), yield 76%；248-250 DEG C of fusing point；1H NMR(400MHz,
DMSO-d6) δ (ppm): 11.20 (s, 1H, OH), 10.87 (s, 1H, NH), 7.51 (d, J=8.8Hz, 2H, ArH), 7.33 (d, J
=8.4Hz, 1H, ArH), 7.21-7.18 (m, 1H, ArH), 7.09 (s, 1H, ArH), 6.98 (d, J=8.8Hz, 2H, ArH),
6.14(s,1H,ArH),3.78(s,3H,CH3O),2.26(s,3H,CH3),1.32(s,9H,(CH3)3C)。
Embodiment 18
According to the method for example 16, open-chain crown ether is changed into cumidine, the trifluoroacetic acid of 0.2mmol is added,
In 90 DEG C, microwave reaction 40min, column chromatographs to obtain target product 6- isopropyl -2- p-methoxyphenyl -3- (4- hydroxyl -6- first
Base -2H- pyran-2-one -3- base) indoles (compound Ir), yield 73%；228-229 DEG C of fusing point；1H NMR(400MHz,
DMSO-d6) δ (ppm): 11.20 (s, 1H, OH), 10.87 (s, 1H, NH), 7.51 (d, J=8.8Hz, 2H, ArH), 7.31 (d, J
=8.0Hz, 1H, ArH), 7.02-6.95 (m, 4H, ArH), 6.13 (s, 1H, ArH), 3.77 (s, 3H, CH3O),2.95-2.89
(m,1H,CH),2.26(s,3H,CH3), 1.22 (d, J=6.8Hz, 6H, (CH3)2C)。
Embodiment 19
According to the method for example 16, open-chain crown ether is changed into P-nethoxyaniline, the trifluoroacetic acid of 0.2mmol is added,
In 90 DEG C, microwave reaction 40min, column chromatographs to obtain target product 6- methoxyl group -2- p-methoxyphenyl -3- (4- hydroxyl -6- first
Base -2H- pyran-2-one -3- base) indoles (compound Is), yield 58%；256-258 DEG C of fusing point；1H NMR(400MHz,
DMSO-d6) δ (ppm): 11.19 (s, 1H, OH), 10.91 (s, 1H, NH), 7.51 (d, J=8.8Hz, 2H, ArH), 7.28 (d, J
=8.8Hz, 1H, ArH), 6.98 (d, J=8.8Hz, 2H, ArH), 6.75-6.73 (m, 1H, ArH), 6.60 (s, 1H, ArH),
6.13(s,1H,ArH),3.77(s,3H,CH3O),3.71(s,3H,CH3O),2.26(s,3H,CH3)。
Embodiment 20
According to the method for example 16, changes open-chain crown ether into isopropyl aniline, the trifluoroacetic acid of 0.2mmol is added,
In 90 DEG C, microwave reaction 40min, column chromatographs to obtain target product 5- isopropyl -2- p-methoxyphenyl -3- (4- hydroxyl -6- first
Base -2H- pyran-2-one -3- base) indoles (compound It), yield 66%；280-282 DEG C of fusing point；1H NMR(400MHz,
DMSO-d6) δ (ppm): 11.17 (s, 1H, OH), 10.85 (s, 1H, NH), 7.50 (d, J=8.8Hz, 2H, ArH), 7.21 (s,
1H, ArH), 7.03 (d, J=8.4Hz, 1H, ArH), 6.97 (d, J=8.8Hz, 2H, ArH), 6.86 (d, J=8.0Hz, 1H,
ArH),6.11(s,1H,ArH),3.77(s,3H,CH3O),3.01-2.94(m,1H,CH),2.25(s,3H,CH3),1.26(d,J
=7.2Hz, 6H, (CH3)2C)。
Embodiment 21
According to the method for example 16, open-chain crown ether is changed into parachloroanilinum, the trifluoroacetic acid of 0.2mmol is added, in 90
DEG C, microwave reaction 40min, column chromatographs to obtain the chloro- 2- p-methoxyphenyl -3- of target product 6- (4- hydroxyl -6- methyl -2H- pyrrole
Mutter -2- ketone -3- base) indoles (compound Iu), yield 81%；293-295 DEG C of fusing point；1H NMR(400MHz,DMSO-d6)δ
(ppm): 11.56 (s, 1H, OH), 11.07 (s, 1H, NH), 7.54 (d, J=8.8Hz, 2H, ArH), 7.39 (d, J=8.4Hz,
1H, ArH), 7.12 (s, 1H, ArH), 7.10-7.07 (m, 1H, ArH), 7.00 (d, J=8.8Hz, 2H, ArH), 6.14 (s, 1H,
ArH),3.78(s,3H,CH3O),2.26(s,3H,CH3)。
Embodiment 22
According to the method for example 16, open-chain crown ether is changed into para-bromoaniline, the trifluoroacetic acid of 0.2mmol is added, in 90
DEG C, microwave reaction 40min, column chromatographs to obtain the bromo- 2- p-methoxyphenyl -3- of target product 6- (4- hydroxyl -6- methyl -2H- pyrrole
Mutter -2- ketone -3- base) indoles (compound Iv), yield 84%；Fusing point > 300 DEG C；1H NMR(400MHz,DMSO-d6)δ(ppm):
11.58 (s, 1H, OH), 11.09 (s, 1H, NH), 7.54 (d, J=8.8Hz, 2H, ArH), 7.35 (d, J=8.8Hz, 1H,
), ArH 7.26 (s, 1H, ArH), 7.21-7.18 (m, 1H, ArH), 7.00 (d, J=8.8Hz, 2H, ArH), 6.13 (s, 1H,
ArH),3.78(s,3H,CH3O),2.26(s,3H,CH3)。
Embodiment 23
According to the method for example 16, open-chain crown ether is changed into para-fluoroaniline, the trifluoroacetic acid of 0.2mmol is added, in 90
DEG C, microwave reaction 40min, column chromatographs to obtain the fluoro- 2- p-methoxyphenyl -3- of target product 6- (4- hydroxyl -6- methyl -2H- pyrrole
Mutter -2- ketone -3- base) indoles (compound Iw), yield 72%；272-274 DEG C of fusing point；1H NMR(400MHz,DMSO-d6)δ
(ppm): 11.44 (s, 1H, OH), 10.03 (s, 1H, NH), 7.52 (d, J=8.4Hz, 2H, ArH), 7.37-7.34 (m, 1H,
), ArH 6.99 (d, J=8.8Hz, 2H, ArH), 6.94-6.88 (m, 1H, ArH), 6.84-6.81 (m, 1H, ArH), 6.12 (s,
1H,ArH)3.78(s,3H,CH3O)2.25(s,3H,CH3)。
Embodiment 24
According to the method for example 16, changes open-chain crown ether into 3- chloro- 4- fluoroaniline, the trifluoroacetic acid of 0.2mmol is added,
In 90 DEG C, microwave reaction 40min, column chromatographs to obtain the fluoro- 2- p-methoxyphenyl -3- of the chloro- 6- of target product 5- (4- hydroxyl -6-
Methyl -2H- pyran-2-one -3- base) indoles (compound Ix), yield 89%；290-292 DEG C of fusing point；1H NMR(400MHz,
DMSO-d6) δ (ppm): 11.59 (s, 1H, OH), 11.11 (s, 1H, NH), 7.52 (d, J=8.4Hz, 2H, ArH), 7.48 (d, J
=6.4Hz, 1H, ArH), 7.05 (d, J=10.0Hz, 1H, ArH), 7.01 (d, J=8.4Hz, 2H, ArH), 6.12 (s, 1H,
ArH),3.78(s,3H,CH3O),2.25(s,3H,CH3)。
Embodiment 25
According to the method for example 16, changes open-chain crown ether into 3- chloro- 4- methylaniline, the trifluoro second of 0.2mmol is added
Acid, in 90 DEG C, microwave reaction 40min, column chromatographs to obtain chloro- 6- methyl -2- p-methoxyphenyl -3- (the 4- hydroxyl of target product 5-
Base -6- methyl -2H- pyran-2-one -3- base) indoles (compound Iy), yield 86%；281-283 DEG C of fusing point；1H NMR
(400MHz,DMSO-d6) δ (ppm): 11.36 (s, 1H, OH), 11.02 (s, 1H, NH), 7.51 (d, J=8.8Hz, 2H, ArH),
7.38 (s, 1H, ArH), 7.06 (s, 1H, ArH), 6.98 (d, J=8.8Hz, 2H, ArH), 6.12 (s, 1H, ArH), 3.77 (s,
3H,CH3O),2.35(s,3H,CH3),2.25(s,3H,CH3)。
Embodiment 26
According to the method for example 19, methoxybenzoyl formaldehyde will be changed into toluyl formaldehyde, 0.2mmol is added
Trifluoroacetic acid, in 90 DEG C, microwave reaction 40min, column chromatographs to obtain target product 6- methoxyl group Iz), yield 62%；Fusing point
266-268℃；1H NMR(400MHz,DMSO-d6)δ(ppm):11.23(s,1H,OH),10.93(s,1H,NH),7.47(d,J
=6.4Hz, 2H, ArH), 7.30 (d, J=8.0Hz, 1H, ArH), 7.20 (d, J=6.4Hz, 2H, ArH), 6.76 (d, J=
7.2Hz,1H,ArH),6.61(s,1H,ArH),6.12(s,1H,ArH),3.71(s,3H,CH3O),2.31(s,3H,CH3),
2.26(s,3H,CH3)。
Embodiment 27
According to the method for example 26, P-nethoxyaniline is changed into cumidine, the trifluoro second of 0.2mmol is added
Acid, in 90 DEG C, microwave reaction 40min, column chromatographs to obtain target product 6- isopropyl -2- p-methylphenyl -3- (4- hydroxyl -6-
Methyl -2H- pyran-2-one -3- base) indoles (compound Ia '), yield 69%；242-243 DEG C of fusing point；1H NMR(400MHz,
DMSO-d6) δ (ppm): 11.26 (s, 1H, OH), 10.90 (s, 1H, NH), 7.48 (d, J=8.0Hz, 2H, ArH), 7.33 (d, J
=8.0Hz, 1H, ArH), 7.20 (d, J=8.0Hz, 2H, ArH), 7.04-7.01 (m, 1H, ArH), 6.98 (s, 1H, ArH),
6.13(s,1H,ArH),2.98-2.88(m,1H,CH),2.32(s,3H,CH3),2.26(s,3H,CH3), 1.23 (d, J=
6.8Hz,6H,(CH3)2C)。
Embodiment 28
According to the method for example 26, P-nethoxyaniline is changed into p-tert-butyl-aniline, the trifluoro second of 0.2mmol is added
Acid, in 90 DEG C, microwave reaction 40min, column chromatographs to obtain target product 6- tert-butyl -2- p-methylphenyl -3- (4- hydroxyl -6-
Methyl -2H- pyran-2-one -3- base) indoles (compound Ib '), yield 71%；234-235 DEG C of fusing point；1H NMR(400MHz,
DMSO-d6) δ (ppm): 11.24 (s, 1H, OH), 10.88 (s, 1H, NH), 7.46 (d, J=8.4Hz, 2H, ArH), 7.34 (d, J
=8.4Hz, 1H, ArH), 7.22-7.19 (m, 3H, ArH), 7.10 (s, 1H, ArH), 6.13 (s, 1H, ArH), 2.32 (s, 3H,
CH3),2.27(s,3H,CH3),1.31(s,9H,(CH3)3C)。
Embodiment 29
According to the method for example 26, P-nethoxyaniline is changed into para-fluoroaniline, the trifluoroacetic acid of 0.2mmol is added, in
90 DEG C, microwave reaction 40min, column chromatographs to obtain the fluoro- 2- p-methylphenyl -3- of target product 6- (4- hydroxyl -6- methyl -2H- pyrrole
Mutter -2- ketone -3- base) indoles (compound Ic '), yield 67%；282-284 DEG C of fusing point；1H NMR(400MHz,DMSO-d6)δ
(ppm): 11.50 (s, 1H, OH), 11.04 (s, 1H, NH), 7.48 (d, J=7.6Hz, 2H, ArH), 7.40-7.36 (m, 1H,
), ArH 7.22 (d, J=7.6Hz, 2H, ArH), 6.93 (t, J=8.4Hz, 1H, ArH), 6.86 (d, J=9.6Hz, 1H, ArH),
6.12(s,1H,ArH),2.32(s,3H,CH3),2.66(s,3H,CH3)。
Embodiment 30
According to the method for example 26, P-nethoxyaniline is changed into parachloroanilinum, the trifluoroacetic acid of 0.2mmol is added, in
90 DEG C, microwave reaction 40min, column chromatographs to obtain the chloro- 2- p-methylphenyl -3- of target product 6- (4- hydroxyl -6- methyl -2H- pyrrole
Mutter -2- ketone -3- base) indoles (compound Id '), yield 73%；Fusing point > 300 DEG C；1H NMR(400MHz,DMSO-d6)δ(ppm):
11.61 (s, 1H, OH), 11.10 (s, 1H, NH), 7.49 (d, J=8.4Hz, 2H, ArH), 7.40 (d, J=8.4Hz, 1H,
), ArH 7.23 (d, J=8.0Hz, 2H, ArH), 7.14 (s, 1H, ArH), 7.11-7.09 (m, 1H, ArH), 6.12 (s, 1H,
ArH),2.32(s,3H,CH3),2.26(s,3H,CH3)。
Embodiment 31
According to the method for example 26, P-nethoxyaniline is changed into para-bromoaniline, the trifluoroacetic acid of 0.2mmol is added, in
90 DEG C, microwave reaction 40min, column chromatographs to obtain the bromo- 2- p-methylphenyl -3- of target product 6- (4- hydroxyl -6- methyl -2H- pyrrole
Mutter -2- ketone -3- base) indoles (compound Ie '), yield 74%；Fusing point > 300 DEG C；1H NMR(400MHz,DMSO-d6)δ(ppm):
11.62 (s, 1H, OH), 11.09 (s, 1H, NH), 7.49 (d, J=8.0Hz, 2H, ArH), 7.36 (d, J=8.4Hz, 1H,
ArH),7.28(s,1H,ArH),7.24-7.20(m,3H,ArH),6.12(s,1H,ArH),2.32(s,3H,CH3),2.26(s,
3H,CH3)。
Embodiment 32
According to the method for example 1, changes phenylglyoxal into Bromophenacyl formaldehyde, the trifluoroacetic acid of 0.2mmol is added,
In 90 DEG C, microwave reaction 40min, column chromatographs to obtain target product 6- methyl -2- m-bromophenyl -3- (4- hydroxyl -6- methyl -2H-
Pyran-2-one -3- base) indoles (compound If '), yield 64%；218-220 DEG C of fusing point；1H NMR(400MHz,DMSO-d6)δ
(ppm): 11.43 (s, 1H, OH), 11.08 (s, 1H, NH), 7.80 (s, 1H, ArH), 7.55 (d, J=8.0Hz, 1H, ArH),
7.46 (d, J=8.0Hz, 1H, ArH), 7.37-7.29 (m, 2H, ArH), 6.97 (d, J=4.8Hz, 2H, ArH), 6.15 (s,
1H,ArH),2.35(s,3H,CH3),2.27(s,3H,CH3)。
Embodiment 33
According to the method for example 32, open-chain crown ether is changed into cumidine, the trifluoroacetic acid of 0.2mmol is added,
In 90 DEG C, microwave reaction 40min, column chromatographs to obtain target product 6- isopropyl -2- m-bromophenyl -3- (4- hydroxyl -6- methyl -
2H- pyran-2-one -3- base) and indoles (Compound Ig per '), yield 62%；231-233 DEG C of fusing point；1H NMR(400MHz,DMSO-
d6) δ (ppm): 11.43 (s, 1H, OH), 11.08 (s, 1H, NH), 7.78 (s, 1H, ArH), 7.54 (d, J=6.8Hz, 1H,
), ArH 7.46 (d, J=7.2Hz, 1H, ArH), 7.34 (d, J=4.8Hz, 2H, ArH), 7.06 (d, J=8.0Hz, 1H, ArH),
7.00(s,1H,ArH),6.15(s,1H,ArH),2.96-2.89(m,1H,CH),2.27(s,3H,CH3), 1.22 (d, J=
6.0Hz.6H,(CH3)2C)。
Embodiment 34
According to the method for example 32, open-chain crown ether is changed into p-tert-butyl-aniline, the trifluoroacetic acid of 0.2mmol is added,
In 90 DEG C, microwave reaction 40min, column chromatographs to obtain target product 6- tert-butyl -2- m-bromophenyl -3- (4- hydroxyl -6- methyl -
2H- pyran-2-one -3- base) indoles (compound Ih '), yield 65%；228-229 DEG C of fusing point；1H NMR(400MHz,DMSO-
d6) δ (ppm): 11.42 (s, 1H, OH), 11.07 (s, 1H, NH), 7.78 (s, 1H, ArH), 7.54 (d, J=7.6Hz, 1H,
), ArH 7.46 (d, J=8.0Hz, 1H, ArH), 7.34 (t, J=8.0Hz, 2H, ArH), 7.26-7.24 (m, 1H, ArH), 7.13
(s,1H,ArH),6.16(s,1H,ArH),2.28(s,3H,CH3),1.31(s,9H,(CH3)3C)。
Embodiment 35
According to the method for example 32, open-chain crown ether is changed into para-bromoaniline, the trifluoroacetic acid of 0.2mmol is added, in 90
DEG C, microwave reaction 40min, column chromatographs to obtain the bromo- 2- m-bromophenyl -3- of target product 6- (4- hydroxyl -6- methyl -2H- pyrans -
2- ketone -3- base) indoles (compound Ii '), yield 72%；Fusing point > 300 DEG C；1H NMR(400MHz,DMSO-d6)δ(ppm):
11.79 (s, 1H, OH), 11.26 (s, 1H, NH), 7.80 (s, 1H, ArH), 7.56 (d, J=7.6Hz, 1H, ArH), 7.51 (d, J
=8.0Hz, 1H, ArH), 7.37 (t, J=8.4Hz, 2H, ArH), 7.32 (s, 1H, ArH), 7.25 (d, J=8.4Hz, 1H,
ArH),6.15(s,1H,ArH),2.27(s,3H,CH3)。
Embodiment 36
According to the method for example 4 into, phenylglyoxal is changed to the trifluoroacetic acid for chlorobenzoyl formaldehyde being added 0.2mmol,
In 90 DEG C, microwave reaction 40min, column chromatographs to obtain target product 6- tert-butyl -2- rubigan -3- (4- hydroxyl -6- methyl -
2H- pyran-2-one -3- base) indoles (compound 5j '), yield 66%；278-280 DEG C of fusing point；1H NMR(400MHz,DMSO-
d6) δ (ppm): 11.37 (s, 1H, OH), 11.00 (s, 1H, NH), 7.56 (d, J=8.8Hz, 2H, ArH), 7.46 (d, J=
8.4Hz, 2H, ArH), 7.34 (d, J=8.8Hz, 1H, ArH), 7.24-7.22 (m, 1H, ArH), 7.11 (s, 1H, ArH), 6.13
(s,1H,ArH),2.26(s,3H,CH3),1.30(s,9H,(CH3)3C)。
Embodiment 37
According to the method for example 36, p-tert-butyl-aniline is changed into para-bromoaniline, the trifluoroacetic acid of 0.2mmol is added, in
90 DEG C, microwave reaction 40min, column chromatographs to obtain the bromo- 2- rubigan -3- of target product 6- (4- hydroxyl -6- methyl -2H- pyrrole
Mutter -2- ketone -3- base) indoles (compound Ik '), yield 72%；Fusing point > 300 DEG C；1H NMR(400MHz,DMSO-d6)δ(ppm):
11.74 (s, 1H, OH), 11.21 (s, 1H, NH), 7.60 (d, J=8.4Hz, 2H, ArH), 7.50 (d, J=8.0Hz, 2H,
), ArH 7.42 (d, J=8.4Hz, 1H, ArH), 7.17 (s, 1H, ArH), 7.13 (d, J=8.4Hz, 1H, ArH), 6.13 (s,
1H,ArH),2.26(s,3H,CH3)。
Simply to illustrate that technical concepts and features of the invention, its purpose is allows in the art above-described embodiment
Those of ordinary skill cans understand the content of the present invention and implement it accordingly, and it is not intended to limit the scope of the present invention.It is all
It is changes or modifications equivalent made by the essence of content according to the present invention, should be covered by the scope of protection of the present invention.
Claims (2)
1. a kind of synthetic method of 2- aryl -3- (4- hydroxyl -2H- pyran-2-one -3- base) indole derivatives, the indoles spread out
Biology has structure shown in Formulas I:
Wherein, R1For H, 4-CH3O、4-CH3, one of 4-Cl or 3-Br, R2For 4-CH3、4-CH3O、3-CH3、4-n-Bu、4-
i-Pr、3-i-Pr、2,3-(CH3)2、3-Cl、4-Cl、3-Br、4-Br、4-F、3-Cl-4-F、3-Cl-4-CH3Or 2-CO2CH3In
One kind；
It is characterized in that, the synthetic method of the indole derivatives is as follows:
With substituted benzene formyl formaldehyde shown in Formula II, with substituted aniline shown in formula III and with 4- hydroxyl pyrans shown in formula IV
Ketone is raw material, is molten with one of mixed solvent of ethyl alcohol, acetonitrile, dimethyl sulfoxide, tetrahydrofuran, toluene, water, water and ethyl alcohol
Agent, with one of sodium carbonate, ferric trichloride, trifluoroacetic acid, L-PROLINE for catalyst, in microwave radiation at a temperature of 90 °C
Under, target compound is obtained by 40 minutes three component reaction one-step synthesis:
2. the synthesis of 2- aryl -3- (4- hydroxyl -2H- pyran-2-one -3- base) indole derivatives according to claim 1
Method, it is characterised in that: the substituted benzene formyl formaldehyde, the substituted aniline, the 4- hydroxy pyrone and described
The molar ratio of catalyst is 1:1:1:0.2.
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| "Three-component domino [3+2] heterocyclization leading to pyran-3-yl-substituted fused pyrroles";Shuang-Shuang Wang，等;《Res Chem Intermed》;20130924;第41卷;第2879-2889页 * |
| Shaik Karamthulla，等."Microwave-assisted synthesis of novel 2,3-disubstituted imidazo[1,2-a]pyridines via one-pot three component reactions".《RSC Adv.》.2015,第5卷第19724-19733页. * |
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