CN113173877B - 吲哚乙酰基亚氨基砜系列化合物及其制备方法 - Google Patents
吲哚乙酰基亚氨基砜系列化合物及其制备方法 Download PDFInfo
- Publication number
- CN113173877B CN113173877B CN202011190352.XA CN202011190352A CN113173877B CN 113173877 B CN113173877 B CN 113173877B CN 202011190352 A CN202011190352 A CN 202011190352A CN 113173877 B CN113173877 B CN 113173877B
- Authority
- CN
- China
- Prior art keywords
- reaction
- mmol
- organic solvent
- compound
- monitored
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 42
- -1 Indole acetyl imino sulfone Chemical class 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title abstract description 6
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 title abstract description 6
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 title abstract description 6
- 238000006243 chemical reaction Methods 0.000 claims abstract description 161
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims abstract description 30
- 229910002091 carbon monoxide Inorganic materials 0.000 claims abstract description 30
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000003446 ligand Substances 0.000 claims abstract description 9
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 7
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 7
- 229910052723 transition metal Inorganic materials 0.000 claims abstract description 7
- 150000003624 transition metals Chemical class 0.000 claims abstract description 7
- 230000009471 action Effects 0.000 claims abstract description 4
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 4
- 239000003513 alkali Substances 0.000 claims abstract description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 92
- 239000003960 organic solvent Substances 0.000 claims description 83
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 81
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 48
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 40
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 9
- 229910052763 palladium Inorganic materials 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 239000000460 chlorine Chemical group 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
- 239000011630 iodine Chemical group 0.000 claims description 5
- 229910052740 iodine Chemical group 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 4
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 claims description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- VSTXCZGEEVFJES-UHFFFAOYSA-N 1-cycloundecyl-1,5-diazacycloundec-5-ene Chemical compound C1CCCCCC(CCCC1)N1CCCCCC=NCCC1 VSTXCZGEEVFJES-UHFFFAOYSA-N 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- WXNOJTUTEXAZLD-UHFFFAOYSA-L benzonitrile;dichloropalladium Chemical compound Cl[Pd]Cl.N#CC1=CC=CC=C1.N#CC1=CC=CC=C1 WXNOJTUTEXAZLD-UHFFFAOYSA-L 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical group [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 3
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 3
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 3
- 235000011009 potassium phosphates Nutrition 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 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
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 claims 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 claims 1
- 239000012298 atmosphere Substances 0.000 abstract description 45
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 3
- 150000004982 aromatic amines Chemical class 0.000 abstract description 2
- 238000006713 insertion reaction Methods 0.000 abstract description 2
- 125000005843 halogen group Chemical group 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 71
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 44
- 239000000047 product Substances 0.000 description 33
- BWNBLGQCCSCCHF-UHFFFAOYSA-N 2-ethyl-1h-indole Chemical class C1=CC=C2NC(CC)=CC2=C1 BWNBLGQCCSCCHF-UHFFFAOYSA-N 0.000 description 22
- 229910000027 potassium carbonate Inorganic materials 0.000 description 22
- 238000004440 column chromatography Methods 0.000 description 21
- 239000012299 nitrogen atmosphere Substances 0.000 description 21
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 21
- 238000009987 spinning Methods 0.000 description 21
- TZKVYDXSGFMXDH-UHFFFAOYSA-N n-(2-iodophenyl)-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC1=CC=CC=C1I TZKVYDXSGFMXDH-UHFFFAOYSA-N 0.000 description 13
- 239000003814 drug Substances 0.000 description 10
- 229940079593 drug Drugs 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 5
- 125000004076 pyridyl group Chemical group 0.000 description 5
- 125000001544 thienyl group Chemical group 0.000 description 5
- 125000002252 acyl group Chemical group 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 125000000304 alkynyl group Chemical group 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 125000002541 furyl group Chemical group 0.000 description 4
- 150000002475 indoles Chemical class 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 229910052710 silicon Inorganic materials 0.000 description 4
- 239000010703 silicon Substances 0.000 description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- CISNNLXXANUBPI-UHFFFAOYSA-N cyano(nitro)azanide Chemical compound [O-][N+](=O)[N-]C#N CISNNLXXANUBPI-UHFFFAOYSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- IBXMKLPFLZYRQZ-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 IBXMKLPFLZYRQZ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- GLZSNJSQOJXSMI-UHFFFAOYSA-N imino-methyl-phenyl-$l^{4}-sulfane Chemical compound CS(=N)C1=CC=CC=C1 GLZSNJSQOJXSMI-UHFFFAOYSA-N 0.000 description 2
- ZOAMBXDOGPRZLP-UHFFFAOYSA-N indole-3-acetamide Chemical group C1=CC=C2C(CC(=O)N)=CNC2=C1 ZOAMBXDOGPRZLP-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- QAZLUNIWYYOJPC-UHFFFAOYSA-M sulfenamide Chemical class [Cl-].COC1=C(C)C=[N+]2C3=NC4=CC=C(OC)C=C4N3SCC2=C1C QAZLUNIWYYOJPC-UHFFFAOYSA-M 0.000 description 2
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 2
- HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 1
- HHXBZEIOUIMZET-UHFFFAOYSA-N (2,3-dichlorophenyl)-phenylphosphane Chemical compound ClC1=CC=CC(PC=2C=CC=CC=2)=C1Cl HHXBZEIOUIMZET-UHFFFAOYSA-N 0.000 description 1
- PHDIJLFSKNMCMI-ITGJKDDRSA-N (3R,4S,5R,6R)-6-(hydroxymethyl)-4-(8-quinolin-6-yloxyoctoxy)oxane-2,3,5-triol Chemical compound OC[C@@H]1[C@H]([C@@H]([C@H](C(O1)O)O)OCCCCCCCCOC=1C=C2C=CC=NC2=CC=1)O PHDIJLFSKNMCMI-ITGJKDDRSA-N 0.000 description 1
- JNPGUXGVLNJQSQ-BGGMYYEUSA-M (e,3r,5s)-7-[4-(4-fluorophenyl)-1,2-di(propan-2-yl)pyrrol-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound CC(C)N1C(C(C)C)=C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)C(C=2C=CC(F)=CC=2)=C1 JNPGUXGVLNJQSQ-BGGMYYEUSA-M 0.000 description 1
- VAVHMEQFYYBAPR-ITWZMISCSA-N (e,3r,5s)-7-[4-(4-fluorophenyl)-1-phenyl-2-propan-2-ylpyrrol-3-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound CC(C)C1=C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)C(C=2C=CC(F)=CC=2)=CN1C1=CC=CC=C1 VAVHMEQFYYBAPR-ITWZMISCSA-N 0.000 description 1
- XXFUZSHTIOFGNV-UHFFFAOYSA-N 1-bromoprop-1-yne Chemical compound CC#CBr XXFUZSHTIOFGNV-UHFFFAOYSA-N 0.000 description 1
- IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical class C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 description 1
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 1
- 125000006304 2-iodophenyl group Chemical group [H]C1=C([H])C(I)=C(*)C([H])=C1[H] 0.000 description 1
- HZYLVYNCWLAIGF-UHFFFAOYSA-N 4-[[[2-(cyclohexylamino)-2-oxoethyl]-(4-propan-2-ylbenzoyl)amino]methyl]-N-hydroxybenzamide Chemical compound CC(C)c1ccc(cc1)C(=O)N(CC(=O)NC1CCCCC1)Cc1ccc(cc1)C(=O)NO HZYLVYNCWLAIGF-UHFFFAOYSA-N 0.000 description 1
- MWVKLRSIDOXBSE-UHFFFAOYSA-N 5-(1-piperidin-4-ylpyrazol-4-yl)-3-(6-pyrrolidin-1-yl-1,3-benzoxazol-2-yl)pyridin-2-amine Chemical compound NC1=NC=C(C2=CN(N=C2)C2CCNCC2)C=C1C(OC1=C2)=NC1=CC=C2N1CCCC1 MWVKLRSIDOXBSE-UHFFFAOYSA-N 0.000 description 1
- HIHOEGPXVVKJPP-JTQLQIEISA-N 5-fluoro-2-[[(1s)-1-(5-fluoropyridin-2-yl)ethyl]amino]-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyridine-3-carbonitrile Chemical compound N([C@@H](C)C=1N=CC(F)=CC=1)C(C(=CC=1F)C#N)=NC=1NC=1C=C(C)NN=1 HIHOEGPXVVKJPP-JTQLQIEISA-N 0.000 description 1
- VCUKKMIXURRDKL-UHFFFAOYSA-N 9-(dimethylamino)-3-(4-ethylphenyl)pyrido[1,2]thieno[3,4-d]pyrimidin-4-one Chemical compound C1=CC(CC)=CC=C1N1C(=O)C(SC=2C3=C(N(C)C)C=CN=2)=C3N=C1 VCUKKMIXURRDKL-UHFFFAOYSA-N 0.000 description 1
- 206010003557 Asthma exercise induced Diseases 0.000 description 1
- 229930192334 Auxin Natural products 0.000 description 1
- KIAGNFTYHASIME-UHFFFAOYSA-N BrC1=C(C=CC=C1)S(=N)C Chemical compound BrC1=C(C=CC=C1)S(=N)C KIAGNFTYHASIME-UHFFFAOYSA-N 0.000 description 1
- DGJMHKMYSDYOFP-MRXNPFEDSA-N C=CC(N(CCC1)C[C@@H]1N1N=C(C2=CN(CC(C3=CC=CC=C3)(F)F)N=N2)C2=C(N)N=CN=C12)=O Chemical compound C=CC(N(CCC1)C[C@@H]1N1N=C(C2=CN(CC(C3=CC=CC=C3)(F)F)N=N2)C2=C(N)N=CN=C12)=O DGJMHKMYSDYOFP-MRXNPFEDSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 208000004657 Exercise-Induced Asthma Diseases 0.000 description 1
- RNKCCKSNQJCLBS-UHFFFAOYSA-N N-(4-chloro-2-iodophenyl)-4-methylbenzenesulfonamide Chemical compound ClC1=CC(=C(C=C1)NS(=O)(=O)C1=CC=C(C=C1)C)I RNKCCKSNQJCLBS-UHFFFAOYSA-N 0.000 description 1
- QECVIPBZOPUTRD-UHFFFAOYSA-N N=S(=O)=O Chemical class N=S(=O)=O QECVIPBZOPUTRD-UHFFFAOYSA-N 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- BEXZJJQVPWJPOA-VOTSOKGWSA-N [(e)-hept-2-enyl] 6-methyl-4-(4-nitrophenyl)-2-oxo-3,4-dihydro-1h-pyrimidine-5-carboxylate Chemical compound CCCC\C=C\COC(=O)C1=C(C)NC(=O)NC1C1=CC=C([N+]([O-])=O)C=C1 BEXZJJQVPWJPOA-VOTSOKGWSA-N 0.000 description 1
- HGDWHTASNMRJMP-UHFFFAOYSA-N [1-(hydroxyamino)-1-oxo-5-(3-phenoxyphenyl)pentan-2-yl]phosphonic acid Chemical compound ONC(=O)C(P(O)(O)=O)CCCC1=CC=CC(OC=2C=CC=CC=2)=C1 HGDWHTASNMRJMP-UHFFFAOYSA-N 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002363 auxin Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- JHRWWRDRBPCWTF-OLQVQODUSA-N captafol Chemical compound C1C=CC[C@H]2C(=O)N(SC(Cl)(Cl)C(Cl)Cl)C(=O)[C@H]21 JHRWWRDRBPCWTF-OLQVQODUSA-N 0.000 description 1
- YBFBENHWPRGUMU-UHFFFAOYSA-N chembl398496 Chemical compound OC(=O)C1=CC=CC=C1NC(=O)N1CCN(C=2N=C3C=CC(O)=CC3=NC=2)CC1 YBFBENHWPRGUMU-UHFFFAOYSA-N 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- HDRXZJPWHTXQRI-BHDTVMLSSA-N diltiazem hydrochloride Chemical compound [Cl-].C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CC[NH+](C)C)C2=CC=CC=C2S1 HDRXZJPWHTXQRI-BHDTVMLSSA-N 0.000 description 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- AVAACINZEOAHHE-VFZPANTDSA-N doripenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](CNS(N)(=O)=O)C1 AVAACINZEOAHHE-VFZPANTDSA-N 0.000 description 1
- XXWYROCOUDNEBV-UHFFFAOYSA-N ethyl-imino-phenyl-lambda4-sulfane Chemical compound CCS(=N)C1=CC=CC=C1 XXWYROCOUDNEBV-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 208000024695 exercise-induced bronchoconstriction Diseases 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- LEXXWUCMDYEREL-UHFFFAOYSA-N imino(diphenyl)-$l^{4}-sulfane Chemical compound C=1C=CC=CC=1S(=N)C1=CC=CC=C1 LEXXWUCMDYEREL-UHFFFAOYSA-N 0.000 description 1
- SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- UPRXASXBDQTMPR-UHFFFAOYSA-N n-(4-fluoro-2-iodophenyl)-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC1=CC=C(F)C=C1I UPRXASXBDQTMPR-UHFFFAOYSA-N 0.000 description 1
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000012495 reaction gas Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000001603 reducing effect Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 125000005555 sulfoximide group Chemical group 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000979 synthetic dye Substances 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/26—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an acyl radical attached to the ring nitrogen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C381/00—Compounds containing carbon and sulfur and having functional groups not covered by groups C07C301/00 - C07C337/00
- C07C381/10—Compounds containing sulfur atoms doubly-bound to nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
- C07D209/16—Tryptamines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Psychiatry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
本发明提供了吲哚乙酰基亚氨基砜系列化合物及其制备方法。采用邻位卤素取代的芳胺、炔丙基卤代物以及亚砜磺酰亚胺作为反应底物,在碱的作用下反应合成中间体;中间体无须分离,在过渡金属催化剂和膦配体的催化作用下,在常压一氧化碳的氛围下可进一步发生羰基插入的反应,高效高选择性地合成吲哚乙酰基亚氨基砜系列化合物。
Description
技术领域
本发明涉及过渡金属催化的多组分合成技术,具体涉及亚氨基砜类化合物及其制备方法。
背景技术
亚氨基砜是一种化学性质稳定的多功能化合物,它在药物化学方向有重要作用。含有亚磺酰亚胺结构的有机小分子广泛运用于临床药物中,该类化合物具有良好的药物疗效。已经成功上市用于临床的含亚磺酰胺分子骨架的药物有降压特效药(Dillard,R.;Yen,T.;Stark,P.;Pavey,D.J.Med.Chem.1980,23,717),用于治疗骨质疏松症以及用于酪氨酸激酶的抑制剂(Walker,D.P,Zawistoski M P,Mcglynn,M.A.,etal.Bioorg.Med.Chem.Lett.2009,19,3253.),磺草胺除草剂(Zhu,Y.;Loso,M.R.;Watson,G.B.;et al.J.Agric.Food Chem.2011,59,2950.),临床治疗运动诱发性或过敏性哮喘的药物(Miller,P.;James,G.W.L.Arch.Int.Pharmacodyn.Ther.1978,231,328.),pan-CDK抑制剂(U.Lgcking,et al.,ChemMedChem.2013,8,1067.),以及用于PYK2的抑制剂(D.P.Walker,et al.,Bioorg.Med.Chem.Lett.2009,19,3253.)。除此之外,跟该类化合物相关的专利文献有:(a)PCT Int.Appl.(2009),WO 2009051910.;(b)PCT Int.Appl.(2013),WO 2013006738等等。
另一方面,吲哚类化合物是在自然界中广泛存在的一种含氮杂环化合物。吲哚衍生物可用作天然香料、合成染料、植物生长素、饲料添加剂等。此外,吲哚衍生物还可以作为高效药物中间体,在药理方面的也具有重要的抗肿瘤、降血压、抗炎、抗菌等作用。研究发现,吲哚衍生物分子中的吡咯的2-位或3-位含有氨基结构的化合物对于常见的疾病具有良好的疗效。例如,5-羟基衍生物(Tryptamine,5-羟色胺,5-HT)存在于哺乳类的血浆和两栖类的皮肤中,具有血管收缩作用。吲哚-3-乙酰胺骨架同样广泛存在于天然产物和现代药物分子中,许多含有吲哚-3-乙酰胺结构的化合物展现出非常优异的生物或药物活性。
发明内容
本发明目的在于提供一种吲哚乙酰基亚氨基砜系列化合物的高效率制备方法。
本发明的第一方面,提供结构如式IV所示的化合物:
其中,R选自酰基、叔丁氧羰基、磺酰基、C1~C8烷基、芳基;R1、R2、R3、R4和R5独立地选自氢、C1~C8烷基、C1~C8烷氧基、环烷基、卤素、酯基、硝基、氰基、酰胺基、呋喃基、噻吩基、吡啶基、烯基、炔基、硅基。
在一些优选的实施例中,所述R选自乙酰基、叔丁氧羰基、甲磺酰基、苯磺酰基、对甲苯磺酰基、甲基、乙基、苄基;R1、R2、R3、R4和R5独立地选自氢、甲基、乙基、甲氧基、乙氧基、环丙基、氟、氯、溴、碘、乙酰氧基、硝基、氰基、乙酰氨基、呋喃基、噻吩基、吡啶基、乙烯基、乙炔基、硅基。。
在一些优选的实施例中,所述结构如式IV所示的化合物具体为下列结构式所示化合物中的一种:
本发明的第二方面,提供所述结构如式IV所示的化合物的制备方法,该制备方法包括以下步骤:
在过渡金属钯催化剂和膦配体的催化作用下,使结构如式V或VI所示的化合物、结构如式III所示的化合物与一氧化碳反应,得到所述结构如式IV所示的化合物;
其中,R选自酰基、叔丁氧羰基、磺酰基、C1~C8烷基、芳基;R1、R2、R3、R4和R5独立地选自氢、C1~C8烷基、C1~C8烷氧基、环烷基、卤素、酯基、硝基、氰基、酰胺基、呋喃基、噻吩基、吡啶基、烯基、炔基、硅基;X选自氟、氯、溴、碘。
在一些优选的实施例中,所述结构如式V或VI所示的化合物按照以下步骤制备得到:
使结构如式I所示的化合物与结构如式II所示的化合物在碱的作用下发生反应,得到所述结构如式V或VI所示的化合物;
其中,R选自酰基、叔丁氧羰基、磺酰基、C1~C8烷基、芳基;R1、R2和R3独立地选自氢、C1~C8烷基、C1~C8烷氧基、环烷基、卤素、酯基、硝基、氰基、酰胺基、呋喃基、噻吩基、吡啶基、烯基、炔基、硅基;X和Y独立地选自氟、氯、溴、碘。
在一些优选的实施例中,所述过渡金属钯催化剂为醋酸钯、氯化钯、二氯二三苯基膦钯、三二亚苄基丙酮二钯(Pd2(dba)3)、二苯甲腈二氯化钯中的一种或多种;所述膦配体为含有磷元素P的有机化合物配体。
在一些优选的实施例中,所述碱为碳酸铯、碳酸钠、氢氧化钾、氢氧化钠、叔丁醇钾、磷酸钾、三乙胺、吡啶、1,8-二氮杂二环十一碳-7-烯(DBU)、三乙烯二胺(DABCO)中的一种或多种。
在一些优选的实施例中,所述反应在有机溶剂中进行,有机溶剂为乙醇、丙酮、氯仿、二氯甲烷、四氢呋喃、苯或甲苯、1,4-二氧六环、二甲亚砜中的一种或多种。
本发明的第三方面,提供所述结构如式IV所示的化合物的应用,其中,所述结构如式IV所示的化合物用于制备治疗精神病的药物。
在本发明具有以下有益效果:
(1)利用三种商业化可得的原料作为起始物质,以及常压的一氧化碳作为反应气体,即可高效地发生多步反应;可以采用多组分一锅法反应,中间体无须分离,即可高产率地生成目标产物;对反应设备无特殊的要求,操作简单,成本极低;反应时间短,反应条件温和,底物适用性广,副产物少,产率高,有利于分离提纯,产品纯度高,可适用于较大规模的制备;
(2)产物结构相对较为复杂,产物分子中同时含有吲哚环系以及亚砜磺酰亚胺结构,这两类骨架结构均具有潜在的生物或药物活性;产物可经羰基还原反应而成为N-亚氨基砜基吲哚乙胺,该化合物具有临床治疗精神病药物Tryptamine的核心骨架结构,因此,产物亦将具有潜在的生物或药物活性,具有重要的药用价值。
附图说明
图1显示了本发明实施例一所得到的产物的结构式。
具体实施方式
下面将对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
根据本发明,在有机溶剂中,邻卤代的芳胺I与炔丙基卤代物II首先在碱的作用下发生反应,生成关键的中间体V和VI。随后,该中间体再与亚砜磺酰亚胺III以及常压一氧化碳在过渡金属钯催化剂和膦配体的催化作用下发生羰基插入的反应,中间体无须分离,即可高效高选择性地形成吲哚乙酰基亚氨基砜衍生物IV。反应通式如下:
其中,R为氮上保护基,可以为酰基、叔丁氧羰基、磺酰基、烷基或芳基等;R1、R2、R3、R4和R5可以为H,或供电子基团(烷基、烷氧基、环烷基等),或吸电子基团(氟、氯、溴、碘、酯基、硝基、氰基、酰胺基等),或呋喃基、噻吩基、吡啶基、烯基、炔基、硅基等。X和Y均为卤素(氟、氯、溴、碘)。
中间体V和VI是反应底物I和II在体系内反应生成的,因此,也可以直接使用中间体V或VI与亚砜磺酰亚胺III以及一氧化碳发生反应,生成最终产物IV。
反应在有机溶剂中进行,有机溶剂为实验室常用的溶剂,例如乙醇、丙酮、氯仿、二氯甲烷、四氢呋喃、苯或甲苯、1,4-二氧六环或二甲亚砜。所用的碱为碳酸铯、碳酸钠、氢氧化钾、氢氧化钠、叔丁醇钾、磷酸钾、三乙胺、吡啶、1,8-二氮杂二环十一碳-7-烯(DBU)或三乙烯二胺(DABCO)。反应在常压的一氧化碳(CO)气体存在的条件下发生反应。所用的钯催化剂为醋酸钯(Pd(OAc)2)、氯化钯、二氯二三苯基膦钯、三二亚苄基丙酮二钯(Pd2(dba)3)或二苯甲腈二氯化钯。所用的膦配体为含有磷元素P的有机化合物配体,例如三苯基膦(PPh3)。
实施例一:
在空气氛围下将N-(2-碘苯基)-4-甲基苯磺酰胺(89.6mg)、碳酸钾(165.6mg)、3-溴丙炔(0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、甲基苯基亚磺酰亚胺(31.0mg)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产物3-亚氨基砜乙基吲哚衍生物系列化合物1a。产率:94%。以下是产物1a的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ7.97(d,J=8.3Hz,1H),7.75(t,J=7.1Hz,4H),7.63-7.57(m,2H),7.54(d,J=7.8Hz,1H),7.47(t,J=7.7Hz,2H),7.30(t,J=7.7Hz,1H),7.22-7.15(m,3H),3.75(s,2H),3.27(s,3H),2.29(s,3H).
13C NMR(100MHz,CDCl3)δ179.2,144.8,138.4,135.4,135.1,133.8,131.0,129.8,129.6,127.0,126.8,124.6,124.6,123.1,120.1,117.1,113.6,44.1,36.3,21.5.
实施例二:
在空气氛围下将N-(2-碘苯基)-4-甲基苯磺酰胺(89.6mg)、碳酸钾(165.6mg)、溴丙炔(0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、二苯基亚磺酰亚胺(43.5mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1b。产率:87%。以下是产物1b磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.01(d,J=8.3Hz,1H),7.75-7.70(m,6H),7.60(s,1H),7.56(d,J=7.9Hz,1H),7.49(t,J=7.4Hz,2H),7.39–7.30(m,5H),7.20(t,J=7.5Hz,1H),7.12(d,J=8.2Hz,2H),3.81(s,2H),2.25(s,3H).
13C NMR(100MHz,CDCl3)δ178.7,144.8,139.4,135.4,135.2,133.2,131.1,129.8,129.4,127.5,126.8,124.7,124.6,123.1,120.3,117.5,113.6,36.6,21.5.
实施例三:
在空气氛围下将N-(2-碘苯基)-4-甲基苯磺酰胺(89.6mg)、碳酸钾(165.6mg,1.2mmol)、3-溴丙炔(53uL)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、甲基萘基亚磺酰亚胺(41.1mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1c。产率:92%。以下是产物1c的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.26(d,J=1.3Hz,1H),8.00(d,J=8.3Hz,1H),7.85-7.82(m,2H),7.70(d,J=8.3Hz,3H),7.64–7.60(m,3H),7.55(t,J=7.7Hz,2H),7.32-7.28(m,1H),7.20-7.16(m,1H),7.03(d,J=8.1Hz,2H),3.79(s,2H),3.32(s,3H),2.14(s,3H).
13C NMR(100MHz,CDCl3)δ179.2,144.8,135.3,135.2,135.2,135.1,132.1,131.1,130.0,129.8,129.5,129.4,129.2,127.9,127.9,126.7,124.7,124.7,123.2,121.3,120.2,117.4,113.7,44.1,36.3,21.4.
实施例四:
在空气氛围下将N-(2-碘苯基)-4-甲基苯磺酰胺(89.6mg,0.24mmol)、碳酸钾(165.6mg,1.2mmol)、3-溴丙炔(53ul,0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg,0.28mmol),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、甲基邻溴苯基亚磺酰亚胺(46.8mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1d。产率:86%。以下是产物1d的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.18(d,J=7.9Hz,1H),7.94(d,J=8.3Hz,1H),7.73(d,J=8.2Hz,2H),7.67(d,J=7.8Hz,1H),7.56(s,1H),7.52-7.47(m,2H),7.45-7.41(m,1H),7.28-7.26(m,1H),7.19–7.15(m,3H),3.74(s,2H),3.42(s,3H),2.29(s,3H).
13C NMR(100MHz,CDCl3)δ178.3,144.7,137.6,135.7,135.5,135.0,134.7,131.8,131.1,129.8,128.5,126.8,124.7,124.5,123.0,120.0,119.2,116.7,113.5,41.7,35.7,21.5.
实施例五:
在空气氛围下将N-(2-碘苯基)-4-甲基苯磺酰胺(89.6mg,0.24mmol)、碳酸钾(165.6mg,1.2mmol)、3-溴丙炔(53ul,0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg,0.28mmol),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、甲基邻甲基苯基亚磺酰亚胺(33.9mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1e。产率:90%。以下是产物1e的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ7.95(d,J=8.3Hz,1H),7.90(d,J=8.0Hz,1H),7.72(d,J=8.3Hz,2H),7.55(s,1H),7.51(d,J=7.8Hz,1H),7.46–7.43(m,1H),7.29–7.25(m,2H),7.22–7.17(m,2H),7.13(d,J=8.2Hz,2H),3.73(s,2H),3.27(s,3H),2.37(s,3H),2.26(s,3H).
13C NMR(100MHz,CDCl3)δ178.8,144.8,137.0,136.4,135.4,135.1,133.7,133.2,131.0,129.8,129.0,126.9,126.8,124.6,124.6,123.1,120.1,117.1,113.5,42.9,36.2,21.5,20.0.
实施例六:
在空气氛围下将N-(2-碘苯基)-4-甲基苯磺酰胺(89.6mg,0.24mmol)、碳酸钾(165.6mg,1.2mmol)、3-溴丙炔(53ul,0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg,0.28mmol),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、4-二氯二苯基亚磺酰亚胺(57.3mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1f。产率:77%。以下是产物1f的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.02(d,J=8.3Hz,1H),7.76(d,J=8.4Hz,2H),7.58–7.52(m,6H),7.37–7.31(m,5H),7.24–7.20(m,1H),7.16(d,J=8.2Hz,2H),3.79(s,2H),2.29(s,3H).
13C NMR(100MHz,CDCl3)δ178.6,144.9,140.3,137.5,135.4,135.2,130.9,129.9,129.8,128.9,126.8,124.8,124.6,123.2,120.3,117.2,113.7,36.6,21.5.
实施例七:
在空气氛围下将N-(2-碘苯基)-4-甲基苯磺酰胺(89.6mg,0.24mmol)、碳酸钾(165.6mg,1.2mmol)、3-溴丙炔(53ul,0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg,0.28mmol),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、甲基对氯苯基亚磺酰亚胺(38.0mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1g。产率:89%。以下是产物1g的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.14–8.12(m,1H),7.93(d,J=8.3Hz,1H),7.72(d,J=8.3Hz,2H),7.55–7.49(m,3H),7.46–7.41(m,2H),7.28–7.24(m,1H),7.19–7.14(m,3H),3.73(s,2H),3.40(s,3H),2.28(s,3H).
13C NMR(100MHz,CDCl3)δ178.4,144.7,135.9,135.5,135.1,134.8,132.1,131.6,131.1,131.0,129.8,127.9,126.8,124.7,124.5,123.0,120.0,116.8,113.5,42.1,35.7,21.5.
实施例八:
在空气氛围下将N-(2-碘苯基)-4-甲基苯磺酰胺(89.6mg,0.24mmol)、碳酸钾(165.6mg,1.2mmol)、3-溴丙炔(53ul,0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg,0.28mmol),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、苯基对甲基苯基亚磺酰亚胺(46.3mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1h。产率:88%。以下是产物1h的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.01(d,J=8.3Hz,1H),7.74–7.69(m,4H),7.61–7.59(m,3H),7.55(d,J=7.8Hz,1H),7.47–7.43(m,1H),7.35–7.29(m,3H),7.21–7.17(m,1H),7.14(d,J=8.1Hz,2H),7.08(d,J=8.4Hz,2H),3.80(s,2H),2.30(s,3H),2.20(s,3H).
13C NMR(100MHz,CDCl3)δ178.7,144.7,144.3,139.7,136.2,135.4,135.2,133.1,131.1,130.1,129.8,129.3,127.5,127.4,126.8,124.6,124.6,123.1,120.3,117.5,113.6,36.6,21.5.
实施例九:
在空气氛围下将N-(2-碘苯基)-4-甲基苯磺酰胺(89.6mg,0.24mmol)、碳酸钾(165.6mg,1.2mmol)、3-溴丙炔(53ul,0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg,0.28mmol),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、亚磺酰亚胺(67.1mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1i。产率:74%。以下是产物1i的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.00(d,J=8.3Hz,1H),7.79–7.70(m,8H),7.66–7.56(m,5H),7.48(t,J=7.7Hz,2H),7.33–7.29(m,1H),7.23–7.19(m,3H),7.13(d,J=8.1Hz,2H),3.83–3.82(m,2H),2.37(s,3H),2.25(s,3H).
13C NMR(100MHz,CDCl3)δ195.0,178.8,144.9,144.8,143.1,141.6,136.3,135.4,135.2,133.3,131.0,130.4,130.3,130.1,129.8,128.6,127.7,127.3,126.8,124.7,124.6,123.1,120.3,117.3,113.6,36.6,21.5,21.5.
实施例十:
在空气氛围下将N-(2-碘苯基)-4-甲基苯磺酰胺(89.6mg,0.24mmol)、碳酸钾(165.6mg,1.2mmol)、3-溴丙炔(53ul,0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg,0.28mmol),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、苄基苯基亚磺酰亚胺(46.3mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1j。产率:75%。以下是产物1j的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ7.99(d,J=8.3Hz,1H),7.73(d,J=8.4Hz,2H),7.58(s,1H),7.54–7.50(m,2H),7.40–7.38(m,2H),7.30(t,J=7.9Hz,3H),7.23–7.16(m,2H),7.12(d,J=8.1Hz,2H),7.04(t,J=7.8Hz,2H),6.76(d,J=7.2Hz,2H),4.75(d,J=13.6Hz,1H),4.60(d,J=13.6Hz,1H),3.77(s,2H),2.24(s,3H).
13C NMR(100MHz,CDCl3)δ179.5,144.8,135.4,135.2,135.1,133.8,131.1,131.0,129.8,129.1,129.0,128.4,128.4,127.0,126.8,124.6,124.6,123.1,120.2,117.4,113.6,61.9,36.5,21.5.
实施例十一:
在空气氛围下将N-(2-碘苯基)-4-甲基苯磺酰胺(89.6mg,0.24mmol)、碳酸钾(165.6mg,1.2mmol)、3-溴丙炔(53ul,0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg,0.28mmol),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、甲基邻氯苯基亚磺酰亚胺(38.0mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1k。产率:72%。以下是产物1k的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.14–8.11(m,1H),7.93(d,J=8.3Hz,1H),7.72(d,J=8.4Hz,2H),7.55-7.49(m,3H),7.45–7.40(m,2H),7.28-7.24(m,1H),7.19-7.13(m,3H),3.73(s,2H),3.39(s,3H),2.27(s,3H).
13C NMR(100MHz,CDCl3)δ178.4,144.7,135.9,135.5,135.1,134.8,132.1,131.6,131.1,131.1,129.8,127.9,126.8,124.7,124.5,123.1,120.0,116.8,113.5,42.1,35.7,21.5.
实施例十二:
在空气氛围下将N-(2-碘苯基)-4-甲基苯磺酰胺(89.6mg,0.24mmol)、碳酸钾(165.6mg,1.2mmol)、3-溴丙炔(53ul,0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg,0.28mmol),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、乙基苯基亚磺酰亚胺(33.9mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1l。产率:68%。以下是产物1l的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ7.98(d,J=8.3Hz,1H),7.74–7.68(m,4H),7.60–7.54(m,3H),7.44(t,J=7.8Hz,2H),7.31–7.27(m,1H),7.21–7.17(m,1H),7.14(d,J=8.0Hz,2H),3.75-3.74(m,2H),3.43–3.33(m,2H),2.27(s,3H),1.11(t,J=7.4Hz,3H).
13C NMR(100MHz,CDCl3)δ179.1,144.8,136.0,135.4,135.1,133.7,131.0,129.8,129.5,127.8,126.8,124.6,124.5,123.1,120.2,117.4,113.6,50.3,36.3,21.5,7.0.
实施例十三:
在空气氛围下将N-(2-碘苯基)-4-甲基苯磺酰胺(89.6mg,0.24mmol)、碳酸钾(165.6mg,1.2mmol)、3-溴丙炔(53ul,0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg,0.28mmol),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、环丙基苯基亚磺酰亚胺(36.3mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1m。产率:63%。以下是产物1m的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ7.97(d,J=8.3Hz,1H),7.74(d,J=8.3Hz,2H),7.68-7.66(m,2H),7.57-7.50(m,3H),7.41(t,J=7.8Hz,2H),7.31-7.27(m,1H),7.20-7.14(m,3H),3.77-3.65(m,2H),2.55–2.50(m,1H),2.27(s,3H),1.40-1.35(m,1H),1.20-1.05(m,2H),0.97-0.82(m,2H).
13C NMR(100MHz,CDCl3)δ178.5,144.,138.7,135.4,135.11,133.4,131.0,129.8,129.4,127.1,126.8,124.6,124.5,123.1,120.1,117.3,113.5,36.3,33.1,21.5,6.8,5.2.
实施例十四:
在空气氛围下将N-(3-氯-6-碘苯基)-4-甲基苯磺酰胺(97.9mg,0.24mmol)、碳酸钾(165.6mg,1.2mmol)、3-溴丙炔(53ul,0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg,0.28mmol),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、甲基苯基亚磺酰亚胺(31.0mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1n。产率:88%。以下是产物1n的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ7.98(d,J=1.6Hz,1H),7.79–7.77(m,2H),7.73(d,J=8.3Hz,2H),7.61(t,J=7.5Hz,1H),7.55(s,1H),7.50–7.43(m,3H),7.19–7.14(m,3H),3.72(s,2H),3.27(s,3H),2.29(s,3H).
13C NMR(100MHz,CDCl3)δ178.9,145.2,138.3,135.4,135.1,133.9,130.6,130.0,129.6,129.5,127.0,126.8,125.1,123.8,121.1,116.9,113.7,44.1,36.1,21.5.
实施例十五:
在空气氛围下将N-(3-氟-6-碘苯基)-4-甲基苯磺酰胺(93.9mg,0.24mmol)、碳酸钾(165.6mg,1.2mmol)、3-溴丙炔(53ul,0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg,0.28mmol),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、甲基苯基亚磺酰亚胺(31.0mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1o。产率:83%。以下是产物1o的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ7.78(d,J=7.6Hz,2H),7.73(d,J=8.3Hz,2H),7.70–7.67(m,1H),7.61(t,J=7.5Hz,1H),7.54(s,1H),7.50–7.44(m,3H),7.18(d,J=8.2Hz,2H),6.96–6.91(m,1H),3.73(s,2H),3.27(s,3H),2.29(s,3H).
13C NMR(100MHz,CDCl3)δ178.9,162.1,159.7,145.1,138.4,135.3,135.2,135.1,133.9,130.0,129.6,127.3,127.0,126.8,124.8,124.8,121.1,121.0,117.0,111.6,111.4,101.0,100.7,44.1,36.2,21.5.
实施例十六:
在空气氛围下将N-(3-溴-6-碘苯基)-4-甲基苯磺酰胺(108.5mg,0.24mmol)、碳酸钾(165.6mg,1.2mmol)、3-溴丙炔(53ul,0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg,0.28mmol),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%),DBU(60.9mg)、甲基苯基亚磺酰亚胺(31.0mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1p。产率:70%。以下是产物1p的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.14(d,J=1.5Hz,1H),7.79–7.76(m,2H),7.73(d,J=8.4Hz,2H),7.64–7.60(m,1H),7.54(s,1H),7.48(t,J=7.9Hz,2H),7.39(d,J=8.4Hz,1H),7.30–7.28(m,1H),7.18(d,J=8.1Hz,2H),3.72(s,2H),3.27(s,3H),2.30(s,3H).
13C NMR(100MHz,CDCl3)δ178.8,145.2,138.4,135.7,135.1,133.9,130.0,129.9,129.6,127.0,126.8,126.4,125.1,121.4,118.3,117.0,116.6,44.1,36.1,21.6.
实施例十七:
在空气氛围下将N-(3-甲基-6-碘苯基)-4-甲基苯磺酰胺(93.0mg,0.24mmol)、碳酸钾(165.6mg,1.2mmol)、3-溴丙炔(53ul,0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg,0.28mmol),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%),DBU(60.9mg)、甲基苯基亚磺酰亚胺(31.0mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1q。产率:88%。以下是产物1q的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ7.78–7.71(m,5H),7.59(t,J=7.5Hz,1H),7.49–7.39(m,4H),7.14(d,J=8.2Hz,2H),7.02(d,J=8.0Hz,1H),3.72(s,2H),3.25(s,3H),2.45(s,3H),2.26(s,3H).
13C NMR(100MHz,CDCl3)δ179.2,144.7,138.5,135.5,134.7,133.8,129.8,129.6,128.8,127.0,126.7,124.7,123.9,119.8,117.1,113.7,44.0,36.3,21.9,21.5.
实施例十八:
在空气氛围下将N-(3-氯-2-碘苯基)-4-甲基苯磺酰胺(97.9mg,0.24mmol)、碳酸钾(165.6mg,1.2mmol)、3-溴丙炔(53ul,0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg,0.28mmol),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、甲基苯基亚磺酰亚胺(31.0mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1r。产率:70%。以下是产物1r的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ7.79(d,J=7.6Hz,1H),7.67(d,J=7.9Hz,2H),7.60(d,J=7.3Hz,2H),7.51–7.45(m,2H),7.35(t,J=7.3Hz,2H),7.10–7.02(m,4H),4.00–3.89(m,2H),3.26(s,3H),2.16(s,3H).
13C NMR(100MHz,CDCl3)δ179.6,145.1,138.7,136.5,135.0,133.7,129.9,129.5,127.9,127.1,126.8,126.4,125.1,124.2,117.0,112.4,43.9,37.1,21.5.
实施例十九:
在空气氛围下将N-(4-氟-2-碘苯基)-4-甲基苯磺酰胺(93.9mg,0.24mmol)、碳酸钾(165.6mg,1.2mmol)、3-溴丙炔(53ul,0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg,0.28mmol),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、甲基苯基亚磺酰亚胺(31.0mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1s。产率:79%。以下是产物1s的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ7.92–7.88(m,1H),7.80–7.78(m,2H),7.71(d,J=8.3Hz,2H),7.63–7.60(m,2H),7.48(t,J=7.8Hz,2H),7.20–7.15(m,3H),7.03–6.98(m,1H),3.70(s,2H),3.28(s,3H),2.28(s,3H).
13C NMR(100MHz,CDCl3)δ178.8,160.8,158.4,145.0,138.4,135.1,133.9,132.2,132.1,131.4,129.9,129.6,127.0,126.8,126.4,117.1,117.0,114.7,114.6,112.7,112.4,106.0,105.7,44.1,36.1,21.5.
实施例二十:
在空气氛围下将N-(4-氯-2-碘苯基)-4-甲基苯磺酰胺(97.9mg,0.24mmol)、碳酸钾(165.6mg,1.2mmol)、3-溴丙炔(53ul,0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg,0.28mmol),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、甲基苯基亚磺酰亚胺(31.0mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1t。产率:83%。以下是产物1t的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ7.88(d,J=8.8Hz,1H),7.80–7.78(m,2H),7.71(d,J=8.3Hz,2H),7.63–7.58(m,2H),7.52–7.47(m,3H),7.25–7.22(m,1H),7.16(d,J=7.9Hz,2H),3.71(s,2H),3.27(s,3H),2.28(s,3H).
13C NMR(100MHz,CDCl3)δ178.7,145.2,138.3,135.1,133.9,133.5,132.3,130.0,129.7,129.0,127.0,126.8,126.0,124.8,119.9,116.6,114.7,44.1,36.1,21.5.
实施例二十一:
在空气氛围下将N-(4-甲基-2-碘苯基)-4-甲基苯磺酰胺(93mg,0.24mmol)、碳酸钾(165.6mg,1.2mmol)、3-溴丙炔(53ul,0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg,0.28mmol),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、甲基苯基亚磺酰亚胺(31.0mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1u。产率:93%。以下是产物1u的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ7.84(d,J=8.4Hz,1H),7.77–7.74(m,2H),7.70(d,J=8.4Hz,2H),7.58(t,J=7.5Hz,1H),7.52(s,1H),7.44(t,J=7.8Hz,2H),7.30(s,1H),7.13–7.09(m,3H),3.72(s,2H),3.25(s,3H),2.35(s,3H),2.24(s,3H).
13C NMR(100MHz,CDCl3)δ179.2,144.7,138.5,135.4,133.8,133.4,132.7,131.3,129.8,129.6,127.0,126.7,126.0,124.7,120.0,117.1,113.3,44.0,36.3,21.5,21.3.
实施例二十二:
在空气氛围下将N-(4-甲氧基-2-碘苯基)-4-甲基苯磺酰胺(96.8mg,0.24mmol)、碳酸钾(165.6mg,1.2mmol)、3-溴丙炔(53ul,0.6mmol)溶于有机溶剂丙酮(2.4mL)中,在60℃下搅拌反应1小时,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在氮气氛围下加入THF(0.5mL),再在0℃下慢慢滴加溶于THF(1.0mL)的叔丁醇钾(32.3mg,0.28mmol),滴加完毕后在室温下搅拌反应30min,反应过程中用TLC板监测至完全反应。直接旋干有机溶剂,在一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、甲基苯基亚磺酰亚胺(31.0mg,0.2mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1v。产率:75%。以下是产物1v的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ7.86(d,J=9.0Hz,1H),7.75–7.69(m,4H),7.60(t,J=7.5Hz,1H),7.52(s,1H),7.45(t,J=7.9Hz,2H),7.14(d,J=8.1Hz,2H),6.96(d,J=2.4Hz,1H),6.91–6.89(m,1H),3.72–3.70(m,5H),3.26(s,3H),2.28(s,3H).
13C NMR(100MHz,CDCl3)δ179.1,156.4,144.7,138.4,135.3,133.8,132.0,129.8,129.8,129.6,127.0,126.7,125.4,117.3,114.5,113.8,102.5,55.6,44.1,36.4,21.5.
实施例二十三:
一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、甲基苯基亚磺酰亚胺(31.0mg,0.2mmol)和N-(2-碘苯基)-N-(丙基1,2-二烯-1-基)(71.8mg,0.24mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1w。产率:94%。以下是产物1w的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.42(d,J=8.0Hz,1H),7.84–7.79(m,2H),7.63–7.55(m,2H),7.49(t,J=7.8Hz,2H),7.43(s,1H),7.36–7.30(m,1H),7.28–7.25(m,1H),3.80(d,J=0.7Hz,2H),3.29(s,3H),2.56(s,3H).
13C NMR(100MHz,CDCl3)δ179.5,168.6,138.4,135.8,133.9,130.6,129.6,127.0,125.2,123.8,123.5,119.3,116.8,116.6,44.1,36.1,23.9.
实施例二十四:
一氧化碳氛围下将Pd(OAc)2(5mol%)、PPh3(20mol%)、DBU(60.9mg)、甲基苯基亚磺酰亚胺(31.0mg,0.2mmol)和(2-碘苯基)(1,2-二烯-1-基)氨基甲酸叔丁酯(85.8mg,0.24mmol)溶于有机溶剂甲苯(1mL)中,在室温下搅拌反应2小时,反应过程中用TLC板监测至完全反应。后处理通过快速柱层析分离得纯净的产品3-亚氨基砜乙基吲哚衍生物系列化合物1x。产率:94%。以下是产物1x的核磁共振实验数据:
1H NMR(400MHz,CDCl3)δ8.15(d,J=7.8Hz,1H),7.81–7.79(m,2H),7.61–7.56(m,3H),7.47(t,J=7.8Hz,2H),7.32–7.28(m,1H),7.23–7.19(m,1H),3.78(s,2H),3.28(s,3H),1.64(s,9H).
13C NMR(100MHz,CDCl3)δ179.7,149.7,138.6,135.5,133.8,130.6,129.5,127.1,124.3,124.3,122.4,119.6,115.1,115.0,83.4,44.0,36.4,28.2.
以上实施方式仅用于说明本发明,而并非对本发明的限制,有关技术领域的普通技术人员,在不脱离本发明的精神和范围的情况下,还可以做出各种变化和变型,因此所有等同的技术方案也属于本发明的范畴,本发明的保护范围应由权利要求限定。
Claims (4)
1.结构如式IV所示的化合物的制备方法,包括以下步骤:
在过渡金属钯催化剂和膦配体的催化作用下,使结构如式V或VI所示的化合物、结构如式III所示的化合物与一氧化碳反应,得到所述结构如式IV所示的化合物;
其中,R选自乙酰基、叔丁氧羰基、甲磺酰基、苯磺酰基、对甲苯磺酰基、C1~C8烷基、苄基;R1、R2、R3、R4和R5独立地选自氢、C1~C8烷基、C1~C8烷氧基、环烷基、卤素;X选自氟、氯、溴、碘;
所述过渡金属钯催化剂为醋酸钯、氯化钯、二氯二(三苯基膦)钯、三(二亚苄基丙酮)二钯(Pd2(dba)3)、二(苯甲腈)二氯化钯中的一种或多种;所述膦配体为三苯基膦。
2.根据权利要求1所述的制备方法,其特征在于,所述结构如式V或VI所示的化合物按照以下步骤制备得到:
使结构如式I所示的化合物与结构如式II所示的化合物在碱的作用下发生反应,得到所述结构如式V或VI所示的化合物;
其中,R选自乙酰基、叔丁氧羰基、甲磺酰基、苯磺酰基、对甲苯磺酰基、C1~C8烷基、苄基;R1、R2和R3独立地选自氢、C1~C8烷基、C1~C8烷氧基、环烷基、卤素;X和Y独立地选自氟、氯、溴、碘。
3.根据权利要求2所述的制备方法,其特征在于,所述碱为碳酸铯、碳酸钠、氢氧化钾、氢氧化钠、叔丁醇钾、磷酸钾、三乙胺、吡啶、1,8-二氮杂二环十一碳-7-烯(DBU)、三乙烯二胺(DABCO)中的一种或多种。
4.根据权利要求1所述的制备方法,其特征在于,所述反应在有机溶剂中进行,有机溶剂为乙醇、丙酮、氯仿、二氯甲烷、四氢呋喃、苯、甲苯、1,4-二氧六环、二甲亚砜中的一种或多种。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202011190352.XA CN113173877B (zh) | 2020-10-30 | 2020-10-30 | 吲哚乙酰基亚氨基砜系列化合物及其制备方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202011190352.XA CN113173877B (zh) | 2020-10-30 | 2020-10-30 | 吲哚乙酰基亚氨基砜系列化合物及其制备方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN113173877A CN113173877A (zh) | 2021-07-27 |
CN113173877B true CN113173877B (zh) | 2023-10-27 |
Family
ID=76921492
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202011190352.XA Active CN113173877B (zh) | 2020-10-30 | 2020-10-30 | 吲哚乙酰基亚氨基砜系列化合物及其制备方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113173877B (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115028569B (zh) * | 2022-06-22 | 2023-12-22 | 浙大城市学院 | 一种吲哚啉-2-酮-3-乙酰胺系列化合物及其制备方法 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008019357A2 (en) * | 2006-08-07 | 2008-02-14 | Ironwood Pharmaceuticals, Inc. | Indole compounds |
CN101146770A (zh) * | 2005-01-26 | 2008-03-19 | 安万特药物公司 | 作为前列腺素d2受体拮抗剂的2-苯基吲哚类 |
CA2826459A1 (en) * | 2011-03-02 | 2012-09-07 | Lead Discovery Center Gmbh | Pharmaceutically active disubstituted pyridine derivatives |
CA2961570A1 (en) * | 2014-09-19 | 2016-03-24 | Lars Barfacker | Benzyl substituted indazoles |
WO2018130174A1 (zh) * | 2017-01-11 | 2018-07-19 | 江苏豪森药业集团有限公司 | 吡咯并[2,3-c]吡啶类衍生物、其制备方法及其在医药上的应用 |
-
2020
- 2020-10-30 CN CN202011190352.XA patent/CN113173877B/zh active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101146770A (zh) * | 2005-01-26 | 2008-03-19 | 安万特药物公司 | 作为前列腺素d2受体拮抗剂的2-苯基吲哚类 |
WO2008019357A2 (en) * | 2006-08-07 | 2008-02-14 | Ironwood Pharmaceuticals, Inc. | Indole compounds |
CA2826459A1 (en) * | 2011-03-02 | 2012-09-07 | Lead Discovery Center Gmbh | Pharmaceutically active disubstituted pyridine derivatives |
CA2961570A1 (en) * | 2014-09-19 | 2016-03-24 | Lars Barfacker | Benzyl substituted indazoles |
WO2018130174A1 (zh) * | 2017-01-11 | 2018-07-19 | 江苏豪森药业集团有限公司 | 吡咯并[2,3-c]吡啶类衍生物、其制备方法及其在医药上的应用 |
CN110167939A (zh) * | 2017-01-11 | 2019-08-23 | 江苏豪森药业集团有限公司 | 吡咯并[2,3-c]吡啶类衍生物、其制备方法及其在医药上的应用 |
Non-Patent Citations (1)
Title |
---|
CAS 2191718-33-7.《STN Registry》.2018,第1页. * |
Also Published As
Publication number | Publication date |
---|---|
CN113173877A (zh) | 2021-07-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN110041327B (zh) | 吡啶酮衍生物、其组合物及作为抗流感病毒药物的应用 | |
Li et al. | Catalytic enantioselective addition of alcohols to isatin-derived N-Boc ketimines | |
Chen et al. | Highly efficient synthesis of spiro [oxazolidine-2-thione-oxindoles] with 3-isothiocyanato oxindoles and aldehydes via an organocatalytic cascade aldol-cyclization reaction | |
CN108314658B (zh) | 一种多取代噁唑衍生物的制备方法 | |
CN113173877B (zh) | 吲哚乙酰基亚氨基砜系列化合物及其制备方法 | |
CN106456645B (zh) | 用于放射性标记的方法和试剂 | |
Qiao et al. | Palladium-catalyzed ortho-nitration of 2-arylbenzoxazoles | |
CN112028814A (zh) | 基于新型催化Curtius重排反应制备胺类化合物的方法 | |
Wu et al. | Development of highly enantioselective new Lewis basic N-formamide organocatalysts for hydrosilylation of imines with an unprecedented substrate profile | |
Li et al. | Asymmetric synthesis of isoxazole and trifluoromethyl-containing 3, 2′-pyrrolidinyl dispirooxindoles via squaramide-catalysed [3+ 2] cycloaddition reactions | |
Hu et al. | Highly enantioselective Michael/cyclization tandem reaction between dimedone and isatylidene malononitriles | |
Ren et al. | Effective and diastereoselective preparation of dispiro [cyclopent-3′-ene] bisoxindoles via novel [3+ 2] annulation of isoindigos and MBH carbonates | |
CN102180828A (zh) | 手性吲哚啉酮螺五环骨架化合物及不对称合成 | |
CN115124450B (zh) | 一种含有丁烯胺结构的吲哚酮衍生物的合成方法 | |
Liu et al. | Phosphine-promoted [4+ 3] annulation of allenoate with aziridines for synthesis of tetrahydroazepines: phosphine-dependent [3+ 3] and [4+ 3] pathways | |
CN113912609B (zh) | 一种天然生物碱色胺酮及其衍生物的制备方法 | |
CN112876524B (zh) | 一种瑞德西韦中间体的制备方法 | |
CN108276420B (zh) | 一种8,13-二氢苯并[5,6]色烯并[2,3-b]吲哚类化合物及其合成方法 | |
CN109134478B (zh) | 含连续三季碳的硫代吡咯酮拼接双螺环氧化吲哚化合物及其制备方法及应用 | |
US20200216390A1 (en) | Process for the preparation of zafirlukast and analogs thereof | |
WO1999046252A1 (fr) | Production de derives d'oxazolidin-2-one | |
CN109400629B (zh) | 吲哚螺噁嗪杂环类化合物及其制备方法 | |
JP2010531886A (ja) | ナトリウム/プロトン交換輸送体3型阻害剤として有用なベンゾイミダゾールチエニルアミン化合物及びその誘導体の製造方法 | |
CN114369053B (zh) | 磺酰化吡咯烷酮系列化合物及其制备方法 | |
CN111704620B (zh) | [3,2’]-吡咯烷手性螺环氧化吲哚骨架类化合物、其制备方法及应用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |