CN115197228A - Synthesis method of pyrazolone [ spiro ] dihydrophthalazine and 1,3-indenedione [ spiro ] dihydrophthalazine compounds - Google Patents
Synthesis method of pyrazolone [ spiro ] dihydrophthalazine and 1,3-indenedione [ spiro ] dihydrophthalazine compounds Download PDFInfo
- Publication number
- CN115197228A CN115197228A CN202210827565.1A CN202210827565A CN115197228A CN 115197228 A CN115197228 A CN 115197228A CN 202210827565 A CN202210827565 A CN 202210827565A CN 115197228 A CN115197228 A CN 115197228A
- Authority
- CN
- China
- Prior art keywords
- spiro
- dihydrophthalazine
- compound
- nmr
- pyrazolone
- 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.)
- Withdrawn
Links
- 125000003003 spiro group Chemical group 0.000 title claims abstract description 50
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical compound O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 title claims abstract description 24
- UHKAJLSKXBADFT-UHFFFAOYSA-N 1,3-indandione Chemical compound C1=CC=C2C(=O)CC(=O)C2=C1 UHKAJLSKXBADFT-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 238000001308 synthesis method Methods 0.000 title claims description 7
- 150000001875 compounds Chemical class 0.000 title abstract description 24
- 238000006243 chemical reaction Methods 0.000 claims abstract description 41
- -1 diazo pyrazolone Chemical compound 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 14
- 229940125898 compound 5 Drugs 0.000 claims abstract description 13
- 239000000654 additive Substances 0.000 claims abstract description 12
- 230000000996 additive effect Effects 0.000 claims abstract description 12
- 239000003054 catalyst Substances 0.000 claims abstract description 12
- 229940126214 compound 3 Drugs 0.000 claims abstract description 12
- 239000002994 raw material Substances 0.000 claims abstract description 9
- 125000003118 aryl group Chemical group 0.000 claims abstract description 8
- 239000003960 organic solvent Substances 0.000 claims abstract description 8
- 229940125782 compound 2 Drugs 0.000 claims abstract description 4
- 238000010438 heat treatment Methods 0.000 claims abstract description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 40
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 28
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 229910018286 SbF 6 Inorganic materials 0.000 claims description 7
- 230000002194 synthesizing effect Effects 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 claims description 4
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 claims description 3
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical group [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 claims description 3
- 239000011261 inert gas Substances 0.000 claims description 3
- 229940071536 silver acetate Drugs 0.000 claims description 3
- 229910001958 silver carbonate Inorganic materials 0.000 claims description 3
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 claims description 3
- 150000002466 imines Chemical class 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 125000000524 functional group Chemical group 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 3
- 238000010189 synthetic method Methods 0.000 abstract description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 68
- 238000004009 13C{1H}-NMR spectroscopy Methods 0.000 description 62
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 238000012512 characterization method Methods 0.000 description 8
- 239000003208 petroleum Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- 239000010948 rhodium Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- MNIPVWXWSPXERA-IDNZQHFXSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-(11-phenoxyundecanoyloxy)-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@@H]([C@@H](OC(=O)CCCCCCCCCCOC=3C=CC=CC=3)C(O1)(C(O)=O)C(O)(C(O2)C(O)=O)C(O)=O)O)C1=CC=CC=C1 MNIPVWXWSPXERA-IDNZQHFXSA-N 0.000 description 3
- 229940126650 Compound 3f Drugs 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- BUHSOHQFCFEMHJ-UHFFFAOYSA-N CC(C)=CC(N(C(C(C1=CC=CC=C11)=O)(C1=O)C1=C2)N=CC1=CC=C2Br)=O Chemical compound CC(C)=CC(N(C(C(C1=CC=CC=C11)=O)(C1=O)C1=C2)N=CC1=CC=C2Br)=O BUHSOHQFCFEMHJ-UHFFFAOYSA-N 0.000 description 2
- YQWHZMKVROWZLT-UHFFFAOYSA-N CC(C)=CC(N(C(C(C1=CC=CC=C11)=O)(C1=O)C1=C2)N=CC1=CC=C2Cl)=O Chemical compound CC(C)=CC(N(C(C(C1=CC=CC=C11)=O)(C1=O)C1=C2)N=CC1=CC=C2Cl)=O YQWHZMKVROWZLT-UHFFFAOYSA-N 0.000 description 2
- QNSUNAVSXSVQOF-UHFFFAOYSA-N CC(C)=CC(N(C(C(C1=CC=CC=C11)=O)(C1=O)C1=C2)N=CC1=CC=C2F)=O Chemical compound CC(C)=CC(N(C(C(C1=CC=CC=C11)=O)(C1=O)C1=C2)N=CC1=CC=C2F)=O QNSUNAVSXSVQOF-UHFFFAOYSA-N 0.000 description 2
- URBSBHWKWGPWJY-UHFFFAOYSA-N CC(C)=CC(N(C(C(C1=CC=CC=C11)=O)(C1=O)C1=CC=C2)N=CC1=C2Br)=O Chemical compound CC(C)=CC(N(C(C(C1=CC=CC=C11)=O)(C1=O)C1=CC=C2)N=CC1=C2Br)=O URBSBHWKWGPWJY-UHFFFAOYSA-N 0.000 description 2
- CTDSZABVOXPVPJ-UHFFFAOYSA-N CC(C)=CC(N(C(C(C1=CC=CC=C11)=O)(C1=O)C1=CC=C2)N=CC1=C2Cl)=O Chemical compound CC(C)=CC(N(C(C(C1=CC=CC=C11)=O)(C1=O)C1=CC=C2)N=CC1=C2Cl)=O CTDSZABVOXPVPJ-UHFFFAOYSA-N 0.000 description 2
- FJSPUPUDEGDJEK-UHFFFAOYSA-N CC(C)=CC(N(C1(C(C2=CC=CC=C22)=O)C2=O)N=CC2=C1C=CC1=C2C=CC=C1)=O Chemical compound CC(C)=CC(N(C1(C(C2=CC=CC=C22)=O)C2=O)N=CC2=C1C=CC1=C2C=CC=C1)=O FJSPUPUDEGDJEK-UHFFFAOYSA-N 0.000 description 2
- KTYRXGGNMAUQLX-UHFFFAOYSA-N CC(C)=CC(N1N=CC2=CC(Cl)=CC=C2C1(C(C1=CC=CC=C11)=O)C1=O)=O Chemical compound CC(C)=CC(N1N=CC2=CC(Cl)=CC=C2C1(C(C1=CC=CC=C11)=O)C1=O)=O KTYRXGGNMAUQLX-UHFFFAOYSA-N 0.000 description 2
- REWFIVWWKRXEBS-UHFFFAOYSA-N CC(C)=CC(N1N=CC2=CC=C(C)C=C2C1(C(C1=CC=CC=C11)=O)C1=O)=O Chemical compound CC(C)=CC(N1N=CC2=CC=C(C)C=C2C1(C(C1=CC=CC=C11)=O)C1=O)=O REWFIVWWKRXEBS-UHFFFAOYSA-N 0.000 description 2
- GYIZVSDSEJFDAP-UHFFFAOYSA-N CC(C)=CC(N1N=CC2=CC=CC(F)=C2C1(C(C1=CC=CC=C11)=O)C1=O)=O Chemical compound CC(C)=CC(N1N=CC2=CC=CC(F)=C2C1(C(C1=CC=CC=C11)=O)C1=O)=O GYIZVSDSEJFDAP-UHFFFAOYSA-N 0.000 description 2
- KGWHJGSRJUFDSF-UHFFFAOYSA-N CC(C)=CC(N1N=CC2=CC=CC=C2C1(C(C(C1=C2)=CC=C2Br)=O)C1=O)=O Chemical compound CC(C)=CC(N1N=CC2=CC=CC=C2C1(C(C(C1=C2)=CC=C2Br)=O)C1=O)=O KGWHJGSRJUFDSF-UHFFFAOYSA-N 0.000 description 2
- ZUCJQNUNNUGRER-UHFFFAOYSA-N CC(C)=CC(N1N=CC2=CC=CC=C2C1(C(C(C1=C2)=CC=C2Cl)=O)C1=O)=O Chemical compound CC(C)=CC(N1N=CC2=CC=CC=C2C1(C(C(C1=C2)=CC=C2Cl)=O)C1=O)=O ZUCJQNUNNUGRER-UHFFFAOYSA-N 0.000 description 2
- SLCWJGGRBLGYBY-UHFFFAOYSA-N CC(C)=CC(N1N=CC2=CC=CC=C2C1(C(C(C1=C2)=CC=C2F)=O)C1=O)=O Chemical compound CC(C)=CC(N1N=CC2=CC=CC=C2C1(C(C(C1=C2)=CC=C2F)=O)C1=O)=O SLCWJGGRBLGYBY-UHFFFAOYSA-N 0.000 description 2
- IZOWJFREWICKGJ-UHFFFAOYSA-N CC(C)=CC(N1N=CC2=CC=CC=C2C1(C(C1=CC=C(C)C=C11)=O)C1=O)=O Chemical compound CC(C)=CC(N1N=CC2=CC=CC=C2C1(C(C1=CC=C(C)C=C11)=O)C1=O)=O IZOWJFREWICKGJ-UHFFFAOYSA-N 0.000 description 2
- CPSORIMFZJROII-UHFFFAOYSA-N CC(C)=CC(N1N=CC2=CC=CC=C2C1(C(C1=CC=CC(Br)=C11)=O)C1=O)=O Chemical compound CC(C)=CC(N1N=CC2=CC=CC=C2C1(C(C1=CC=CC(Br)=C11)=O)C1=O)=O CPSORIMFZJROII-UHFFFAOYSA-N 0.000 description 2
- XSNYMSDYBIDNHQ-UHFFFAOYSA-N CC(C)=CC(N1N=CC2=CC=CC=C2C1(C(C1=CC=CC(Cl)=C11)=O)C1=O)=O Chemical compound CC(C)=CC(N1N=CC2=CC=CC=C2C1(C(C1=CC=CC(Cl)=C11)=O)C1=O)=O XSNYMSDYBIDNHQ-UHFFFAOYSA-N 0.000 description 2
- NVQCJWHGPQCTTP-UHFFFAOYSA-N CC(C)=CC(N1N=CC2=CC=CC=C2C1(C(C1=CC=CC(F)=C11)=O)C1=O)=O Chemical compound CC(C)=CC(N1N=CC2=CC=CC=C2C1(C(C1=CC=CC(F)=C11)=O)C1=O)=O NVQCJWHGPQCTTP-UHFFFAOYSA-N 0.000 description 2
- QVLTVILSYOWFRM-UHFFFAOYSA-L CC1=C(C)C(C)([Rh](Cl)Cl)C(C)=C1C Chemical group CC1=C(C)C(C)([Rh](Cl)Cl)C(C)=C1C QVLTVILSYOWFRM-UHFFFAOYSA-L 0.000 description 2
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- YLEIFZAVNWDOBM-ZTNXSLBXSA-N ac1l9hc7 Chemical compound C([C@H]12)C[C@@H](C([C@@H](O)CC3)(C)C)[C@@]43C[C@@]14CC[C@@]1(C)[C@@]2(C)C[C@@H]2O[C@]3(O)[C@H](O)C(C)(C)O[C@@H]3[C@@H](C)[C@H]12 YLEIFZAVNWDOBM-ZTNXSLBXSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- MMAGMBCAIFVRGJ-UHFFFAOYSA-J iridium(3+);1,2,3,4,5-pentamethylcyclopenta-1,3-diene;tetrachloride Chemical compound Cl[Ir+]Cl.Cl[Ir+]Cl.CC=1C(C)=C(C)[C-](C)C=1C.CC=1C(C)=C(C)[C-](C)C=1C MMAGMBCAIFVRGJ-UHFFFAOYSA-J 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 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 2
- 238000012827 research and development Methods 0.000 description 2
- 229910052709 silver Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 238000009987 spinning Methods 0.000 description 2
- SHAHPWSYJFYMRX-GDLCADMTSA-N (2S)-2-(4-{[(1R,2S)-2-hydroxycyclopentyl]methyl}phenyl)propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C[C@@H]1[C@@H](O)CCC1 SHAHPWSYJFYMRX-GDLCADMTSA-N 0.000 description 1
- VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 1
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- IUHHODLEEGNQCK-UHFFFAOYSA-N 2-diazonio-3-oxoinden-1-olate Chemical class C1=CC=C2C([O-])=C([N+]#N)C(=O)C2=C1 IUHHODLEEGNQCK-UHFFFAOYSA-N 0.000 description 1
- WQKHERPPDYPMNX-UHFFFAOYSA-N 6-chloro-3,4-dihydro-2h-naphthalen-1-one Chemical compound O=C1CCCC2=CC(Cl)=CC=C21 WQKHERPPDYPMNX-UHFFFAOYSA-N 0.000 description 1
- ZYKVRFMMRAPHAZ-UHFFFAOYSA-N 7-fluoro-3 Chemical compound C1S(=O)(=O)CC(C=2)=CC(F)=CC=2CS(=O)(=O)CC2=CC=C1C=C2 ZYKVRFMMRAPHAZ-UHFFFAOYSA-N 0.000 description 1
- GFCVQYCZHGSRMA-UHFFFAOYSA-L C(C)(=O)[O-].CC1=C(C(=C(C1([Rh+2])C)C)C)C.C(C)(=O)[O-] Chemical compound C(C)(=O)[O-].CC1=C(C(=C(C1([Rh+2])C)C)C)C.C(C)(=O)[O-] GFCVQYCZHGSRMA-UHFFFAOYSA-L 0.000 description 1
- AWUQMFLYMNGXRZ-UHFFFAOYSA-N CC(C)=CC(N(C(C(C1=CC=CC=C11)=O)(C1=O)C1=CC=C2)N=CC1=C2F)=O Chemical compound CC(C)=CC(N(C(C(C1=CC=CC=C11)=O)(C1=O)C1=CC=C2)N=CC1=C2F)=O AWUQMFLYMNGXRZ-UHFFFAOYSA-N 0.000 description 1
- AEMAPPGNJDTKQC-UHFFFAOYSA-N CC(C)=CC(N1N=CC2=C(C)C=CC=C2C1(C(C1=CC=CC=C11)=O)C1=O)=O Chemical compound CC(C)=CC(N1N=CC2=C(C)C=CC=C2C1(C(C1=CC=CC=C11)=O)C1=O)=O AEMAPPGNJDTKQC-UHFFFAOYSA-N 0.000 description 1
- SKUJRQNDSKZRDM-UHFFFAOYSA-N CC(C)=CC(N1N=CC2=CC(Br)=CC=C2C1(C(C1=CC=CC=C11)=O)C1=O)=O Chemical compound CC(C)=CC(N1N=CC2=CC(Br)=CC=C2C1(C(C1=CC=CC=C11)=O)C1=O)=O SKUJRQNDSKZRDM-UHFFFAOYSA-N 0.000 description 1
- FUJJMXIQXTXYRX-UHFFFAOYSA-N CC(C)=CC(N1N=CC2=CC(C)=CC=C2C1(C(C1=CC=CC=C11)=O)C1=O)=O Chemical compound CC(C)=CC(N1N=CC2=CC(C)=CC=C2C1(C(C1=CC=CC=C11)=O)C1=O)=O FUJJMXIQXTXYRX-UHFFFAOYSA-N 0.000 description 1
- ZWUDGDHBMVMRGR-UHFFFAOYSA-N CC(C)=CC(N1N=CC2=CC(OC)=CC=C2C1(C(C1=CC=CC=C11)=O)C1=O)=O Chemical compound CC(C)=CC(N1N=CC2=CC(OC)=CC=C2C1(C(C1=CC=CC=C11)=O)C1=O)=O ZWUDGDHBMVMRGR-UHFFFAOYSA-N 0.000 description 1
- BKCMGLFIGLWCHG-UHFFFAOYSA-N CC(C)=CC(N1N=CC2=CC=CC=C2C1(C(C1=CC=CC(I)=C11)=O)C1=O)=O Chemical compound CC(C)=CC(N1N=CC2=CC=CC=C2C1(C(C1=CC=CC(I)=C11)=O)C1=O)=O BKCMGLFIGLWCHG-UHFFFAOYSA-N 0.000 description 1
- UDHXJZHVNHGCEC-UHFFFAOYSA-N Chlorophacinone Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC=CC=1)C(=O)C1C(=O)C2=CC=CC=C2C1=O UDHXJZHVNHGCEC-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
The invention discloses a synthetic method of pyrazolone [ spiro ] dihydrophthalazine and 1,3-indenedione [ spiro ] dihydrophthalazine compounds, belonging to the technical field of organic synthesis. Taking aryl azomethine 1, diazo pyrazolone compound 2 or diazo-1,3-indandione compound 4 as raw materials, and carrying out heating reaction in an organic solvent in the presence of a catalyst and an additive to obtain pyrazolone [ spiro ] dihydrophthalazine compound 3 or 1,3-indandione [ spiro ] dihydrophthalazine compound 5; the synthetic process is simple and efficient, the two compounds are efficiently synthesized through the series reaction of the aryl azomethine compound and the diazo pyrazolone compound or the diazo-1,3-indene diketone compound, and the reaction atom economy is high; the raw materials are cheap and easy to obtain, the reaction conditions are mild, the application range of the substrate is wide, and the tolerance of the functional group is good.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthetic method of pyrazolone [ spiro ] dihydrophthalazine and 1,3-indenedione [ spiro ] dihydrophthalazine compounds.
Background
The compound containing the dihydrophthalazine structural unit has various obvious medicinal activities, such as antibiosis, antiphlogosis, antianaphylaxis, anticancer, asthma relieving, blood pressure reducing, arrhythmia resisting and the like, and becomes an important pharmacophore for the research and development of new drugs. The spiro ring has stronger rigidity and unique three-dimensional geometrical shape, and the introduction of the spiro ring structure into the compound can generally effectively improve the physical and chemical properties and the biological activity of a parent compound. If the spiro structural unit is introduced into the dihydrophthalazine structural framework, the active addition of two advantageous structures can be realized, and a more valuable chemical entity can be obtained.
So far, the effective construction method of dihydrophthalazine skeleton is limited, and the preparation reports of pyrazolone [ spiro ] dihydrophthalazine and 1,3-indenedione [ spiro ] dihydrophthalazine compounds are not sufficient. Therefore, the research and development of the novel method for synthesizing pyrazolone [ spiro ] dihydrophthalazine and 1,3-indandione [ spiro ] dihydrophthalazine compounds by simple and convenient steps from simple and easily obtained raw materials have very important theoretical significance and practical prospect.
Disclosure of Invention
The invention mainly provides pyrazolone [ spiro ] dihydrophthalazine and 1,3-indenedione [ spiro ] dihydrophthalazine compounds and a synthesis method thereof, and the synthesis method efficiently synthesizes the pyrazolone [ spiro ] dihydrophthalazine and 1,3-indenone [ spiro ] dihydrophthalazine compounds through the series reaction between aryl azomethine and diazo pyrazolone or diazo-1,3-indenedione compounds. The method has the advantages of easily obtained substrate, good functional group compatibility, mild reaction conditions, high efficiency, good selectivity, high atom economy and the like.
The pyrazolone [ spiro ] dihydrophthalazine compound synthesized by the invention has the structural general formula:
wherein R is 1 Is hydrogen, C 1-4 Alkyl radical, C 1-4 Alkoxy, halogen, trifluoromethyl, phenyl or substituted phenyl, wherein the substituent on the phenyl ring of the substituted phenyl is C 1-4 Alkyl radical, C 1-4 Alkoxy, trifluoromethyl or halogenElement, R 1 Is mono-or di-substituted, R 2 Is phenyl, substituted phenyl or naphthyl, and the substituent on the benzene ring of the substituted phenyl is C 1-4 Alkyl radical, C 1-4 Alkoxy, trifluoromethyl or halogen, R 3 Is C 1-4 An alkyl group.
The invention also provides a synthesis method of the pyrazolone [ spiro ] dihydrophthalazine compound 3, which comprises the following steps: aryl azomethine 1 and diazo pyrazolone compounds 2 are used as raw materials, and react in an organic solvent under the existence of a catalyst and an additive by heating to obtain pyrazolone [ spiro ] dihydrophthalazine compounds 3. The reaction equation is:
wherein: r 1 Is hydrogen, C 1-4 Alkyl radical, C 1-4 Alkoxy, halogen, trifluoromethyl, phenyl or substituted phenyl, wherein the substituent on the benzene ring of the substituted phenyl is C 1-4 Alkyl radical, C 1-4 Alkoxy, trifluoromethyl or halogen, R 1 Is mono-or di-substituted, R 2 Is phenyl, substituted phenyl or naphthyl, and the substituent on the benzene ring of the substituted phenyl is C 1-4 Alkyl radical, C 1-4 Alkoxy, trifluoromethyl or halogen, R 3 Is C 1-4 An alkyl group.
Further, in the above technical solution, the organic solvent is used to dissolve the raw material, and preferably acetonitrile, 1,2-dichloroethane, toluene or hexafluoroisopropanol.
Further, in the above technical solution, the additive is copper acetate, silver carbonate or silver acetate.
Further, in the above technical scheme, the catalyst is dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ Cp × RhCl) 2 ] 2 ) Pentamethylcyclopentadienyl rhodium (III) acetate (Cp Rh (OAc) 2 ) And (pentamethylcyclopentadienyl) iridium (III) dichloride dimer ([ Cp IrCl) 2 ] 2 ) Or bis (hexafluoroantimonic acid) trisacetonitrile (pentamethylcyclopentadienyl) rhodium (III) (CpRh (MeCN) 3 (SbF 6 ) 2 )。
Further, in the above technical scheme, the molar ratio of the arylazomethine 1, the diazopyrazolone compound 2, the catalyst and the additive is 1:1-2.025-0.05.
Further, in the above technical scheme, the reaction temperature is 60-120 ℃.
Further, in the above technical solution, the reaction is performed in air or an inert gas atmosphere.
The invention also provides 1,3-indenedione [ spiro ] dihydrophthalazine compounds, which have the structural general formula:
wherein: r 1 Is hydrogen, C 1-4 Alkyl radical, C 1-4 Alkoxy, halogen, trifluoromethyl, phenyl or substituted phenyl, wherein the substituent on the benzene ring of the substituted phenyl is C 1-4 Alkyl radical, C 1-4 Alkoxy, trifluoromethyl or halogen, R 1 Is mono-or disubstituted, R 4 Is hydrogen, C 1-4 Alkyl or halogen.
The invention provides a synthesis method of the 1,3-indenedione [ spiro ] dihydrophthalazine compound 5, which comprises the following operations: aryl azomethine 1 and diazo-1,3-indenedione compound 4 are used as raw materials, and react in an organic solvent under the existence of a catalyst and an additive by heating to obtain 1,3-indenedione [ spiro ] dihydrophthalazine compound 5. The reaction equation is:
wherein: r 1 Is hydrogen, C 1-4 Alkyl radical, C 1-4 Alkoxy, halogen, trifluoromethyl, phenyl or substituted phenyl, wherein the substituent on the benzene ring of the substituted phenyl is C 1-4 Alkyl radical, C 1-4 Alkoxy, trifluoromethyl or halogen, R 1 Is mono-or disubstituted, R 4 Is hydrogen, C 1-4 Alkyl or halogen.
Further, in the above technical solution, the organic solvent is used to dissolve the raw material, and preferably acetonitrile, 1,2-dichloroethane, toluene or hexafluoroisopropanol.
Further, in the above technical solution, the additive is copper acetate, silver carbonate or silver acetate.
Further, in the above technical scheme, the catalyst is dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ Cp × RhCl) 2 ] 2 ) Pentamethylcyclopentadienyl rhodium (III) acetate (CpRh (OAc) 2 ) (pentamethylcyclopentadienyl) iridium (III) dichloride dimer ([ Cp IrCl ] 2 ] 2 ) Or bis (hexafluoroantimonic acid) trisacetonitrile (pentamethylcyclopentadienyl) rhodium (III) (CpRh (MeCN) 3 (SbF 6 ) 2 )。
Further, in the above technical scheme, the molar ratio of the arylazomethine 1, the diazo-1,3-indandione compound 4, the catalyst to the additive is 1:1-2, and is in the range of 0.025-0.05.
Further, in the above technical scheme, the reaction temperature is 60-120 ℃.
Further, in the above technical solution, the reaction is performed in air or an inert gas atmosphere.
The invention has the beneficial effects that:
compared with the prior art, the invention has the following advantages: (1) The synthesis process is simple and efficient, the pyrazolone [ spiro ] dihydrophthalazine compound or 1,3-indandione [ spiro ] dihydrophthalazine compound can be efficiently synthesized through the series reaction of the aryl azomethine imine compound and the diazo pyrazolone compound or the diazo-1,3-indandione compound, and the reaction atom economy is high; (2) The raw materials are cheap and easy to obtain, the reaction condition is mild, and the operation is simple and convenient; and (3) the substrate has wide application range and good functional group tolerance.
Drawings
FIG. 1 is an X-ray single crystal diffractogram of Compound 3a of example 1;
FIG. 2 is an X-ray single crystal diffractogram of Compound 5a of example 4.
Detailed Description
The present invention is described in further detail below with reference to examples, but it should not be construed that the scope of the above subject matter of the present invention is limited to the following examples, and that all the technologies realized based on the above subject matter of the present invention belong to the scope of the present invention.
Example 1
A15 mL reaction tube was charged with the compound 1a, the compound 2a, the catalyst, the additive and the organic solvent in this order, sealed under air conditions, and placed in an oil bath to be heated and stirred for reaction. After the reaction is finished, cooling to room temperature, performing suction filtration, concentrating the filtrate, and separating by a silica gel column (petroleum ether/ethyl acetate = 10/1) to obtain a light yellow solid product 3a.
A series of results are obtained by changing reaction conditions such as solvent, catalyst, additive, temperature and material ratio of the reaction, and the like, and are shown in Table 1.
TABLE 1 Synthesis of 3a under different conditions a
Example 2
To a 15mL pressure tube, 1a (40.4 mg, 0.2mmol), compound 2a (48.0 mg,0.24 mmol), [ Cp. Multidot.Rh (MeCN) 3 ](SbF 6 ) 2 (6.6mg,0.008mmol)、AgOAc (66.8mg, 0.4 mmol) and acetonitrile (2 mL), then the reaction tube was sealed and placed in a 100 ℃ oil bath for reaction for 10h. After completion of the reaction, the reaction system was cooled to room temperature, filtered with suction, the filtrate was concentrated, and separated on a silica gel column (petroleum ether/ethyl acetate = 10/1) to obtain a pale yellow solid product 3a (61.1mg, 82%). Characterization data for this compound are: 1 H NMR(400MHz,CDCl 3 ):δ7.97(d,J＝7.6Hz,2H),7.44-7.40(m,4H),7.39 (s,1H),7.34-7.32(m,1H),7.20(t,J＝7.6Hz,1H),7.06-7.04(m,1H),6.72-6.71(m, 1H),2.11(d,J＝1.2Hz,3H),1.97-1.96(m,6H). 13 C{ 1 H}NMR(100MHz,CDCl 3 ):δ 171.7,167.0,159.1,156.7,138.3,136.1,132.8,130.1,128.9,127.6,126.3,125.1, 124.2,121.6,119.2,114.7,68.7,28.0,21.0,13.5.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 21 N 4 O 2 373.1659；Found 373.1650.
example 3
Method and procedure according to example 2 a,b By changing reactant 1 and reactant 2, a series of pyrazolone [ spiro ] is synthesized]The specific results of the dihydrophthalazine compound 3 are as follows:
a reaction conditions are as follows: 1 (0.2 mmol), 2 (0.24 mmol), [ Cp × Rh (MeCN) 3 ](SbF 6 ) 2 (0.008 mmol) in vinegarAcid(s) b Silver (0.4 mmol), acetonitrile (2 mL), 100 ℃,10h, air atmosphere; the isolation yield.
Representative product characterization data are as follows:
3',7-Dimethyl-2-(3-methylbut-2-enoyl)-1'-phenyl-2H-spiro[phthalazine-1,4'-pyra zol]-5'(1'H)-one(3b)
1 H NMR(600MHz,CDCl 3 ):δ7.99(d,J＝7.8Hz,2H),7.42(t,J＝7.8Hz,2H),7.35 (s,1H),7.22-7.19(m,3H),6.82(s,1H),6.71-6.70(m,1H),2.29(s,3H),2.10(d,J＝ 1.2Hz,3H),1.96(s,3H),1.95(d,J＝0.6Hz,3H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ): δ171.9,167.0,159.0,156.4,143.7,138.4,136.3,131.0,128.9,127.6,126.3,125.1, 124.5,119.2,114.9,68.8,27.9,21.9,20.9,13.5.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 23 N 4 O 2 387.1816；Found 387.1810.
7-Methoxy-3'-methyl-2-(3-methylbut-2-enoyl)-1'-phenyl-2H-spiro[phthalazine-1, 4'-pyrazol]-5'(1'H)-one(3c)
1 H NMR(600MHz,CDCl 3 ):δ7.95(d,J＝7.8Hz,2H),7.41(t,J＝7.2Hz,2H),7.32 (s,1H),7.27(d,J＝8.4Hz,1H),7.19(t,J＝7.2Hz,1H),6.89(dd,J 1 ＝8.4Hz,J 2 ＝ 1.8Hz,1H),6.71(s,1H),6.56(d,J＝1.8Hz,1H),3.72(s,3H),2.10(d,J＝1.2Hz,3 H),1.96(s,3H),1.95(d,J＝0.6Hz,3H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ171.7, 167.0,163.0,159.0,156.2,138.3,136.1,129.6,128.9,128.1,125.2,119.3,115.1, 114.93,114.89,109.9,68.9,55.6,27.9,20.9,13.5.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 23 N 4 O 3 403.1765；Found 403.1757.
7-Fluoro-3'-methyl-2-(3-methylbut-2-enoyl)-1'-phenyl-2H-spiro[phthalazine-1,4'- pyrazol]-5'(1'H)-one(3d)
1 H NMR(600MHz,CDCl 3 ):δ7.96(d,J＝7.8Hz,2H),7.43(t,J＝7.8Hz,2H),7.35 (s,1H),7.34-7.33(m,1H),7.21(t,J＝7.2Hz,1H),7.09(td,J 1 ＝8.4Hz,J 2 ＝2.4Hz, 1H),6.77(dd,J 1 ＝9.0Hz,J 2 ＝1.8Hz,1H),6.709-6.705(m,1H),2.11(d,J＝1.2Hz, 3H),1.97(s,3H),1.96(d,J＝1.2Hz,3H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ 171.3,166.9,165.0(d, 1 J C-F ＝252.8Hz),158.7,157.1,138.1,134.9,129.9(d, 3 J C-F ＝ 8.7Hz),129.0,128.8(d, 3 J C-F ＝7.7Hz),125.4,119.3,118.3(d, 4 J C-F ＝3.3Hz),117.7 (d, 2 J C-F ＝21.9Hz),114.5,111.7(d, 2 J C-F ＝24.0Hz),68.6,28.0,21.0,13.5. 19 F NMR (565MHz,CDCl 3 ):δ-104.10–-104.14(m).HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 20 FN 4 O 2 391.1565；Found 391.1559.
7-Chloro-3'-methyl-2-(3-methylbut-2-enoyl)-1'-phenyl-2H-spiro[phthalazine-1,4' -pyrazol]-5'(1'H)-one(3e)
1 H NMR(600MHz,CDCl 3 ):δ7.97(d,J＝7.8Hz,2H),7.43(t,J＝7.8Hz,2H),7.36 (dd,J 1 ＝8.4Hz,J 2 ＝1.8Hz,1H),7.34(s,1H),7.26(d,J＝8.4Hz,1H),7.22(t,J＝7.2Hz,1H),7.01(d,J＝1.8Hz,1H),6.70-6.69(m,1H),2.11(d,J＝0.6Hz,3H), 1.98(s,3H),1.96(d,J＝0.6Hz,3H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ171.4, 166.9,158.7,157.3,138.7,138.1,134.9,130.6,129.0,128.8,128.0,125.4,124.5, 120.2,119.4,114.5,68.3,28.0,21.0,13.5.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 20 ClN 4 O 2 407.1269；Found 407.1256.
7-Bromo-3'-methyl-2-(3-methylbut-2-enoyl)-1'-phenyl-2H-spiro[phthalazine-1,4' -pyrazol]-5'(1'H)-one(3f)
1 H NMR(400MHz,CDCl 3 ):δ7.96(d,J＝7.6Hz,2H),7.52(dd,J 1 ＝8.4Hz,J 2 ＝2.0Hz,1H),7.43(t,J＝7.2Hz,2H),7.33(s,1H),7.22(t,J＝7.2Hz,1H),7.18(d,J ＝8.0Hz,1H),7.15(d,J＝1.6Hz,1H),6.69-6.68(m,1H),2.10(d,J＝0.8Hz,3H), 1.98(s,3H),1.95(d,J＝0.8Hz,3H). 13 C{ 1 H}NMR(100MHz,CDCl 3 ):δ171.4, 166.9,158.7,157.3,138.1,135.0,133.6,129.0,128.9,128.1,127.3,127.0,125.4, 120.6,119.4,114.5,68.1,28.1,21.0,13.6.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 20 BrN 4 O 2 451.0764；Found 451.0756.
3'-Methyl-2-(3-methylbut-2-enoyl)-1'-phenyl-7-(trifluoromethyl)-2H-spiro[phtha lazine-1,4'-pyrazol]-5'(1'H)-one(3g)
1 H NMR(600MHz,CDCl 3 ):δ7.93(d,J＝7.8Hz,2H),7.64(d,J＝7.2Hz,1H),7.45 -7.42(m,3H)7.41(s,1H),7.25-7.22(m,2H),6.714-6.710(m,1H),2.12(d,J＝1.2 Hz,3H)1.99(s,3H),1.97(d,J＝1.2Hz,3H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ 171.4,166.9,158.7,157.9,138.0,134.4,134.3(q, 2 J C-F ＝32.7Hz),129.0,128.0, 127.3(q, 3 J C-F ＝3.2Hz),127.2,125.6,124.5,123.0(q, 1 J C-F ＝271.2Hz),121.2(q, 3 J C-F ＝4.4Hz),119.7,114.2,68.4,28.1,21.0,13.5. 19 F NMR(565MHz,CDCl 3 ):δ -63.08(s).HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 20 F 3 N 4 O 2 441.1533；Found 441.1528.
3'-Methyl-2-(3-methylbut-2-enoyl)-1',7-diphenyl-2H-spiro[phthalazine-1,4'-pyra zol]-5'(1'H)-one(3h)
1 H NMR(400MHz,CDCl 3 ):δ7.96(d,J＝7.6Hz,2H),7.61(dd,J 1 ＝8.0Hz,J 2 ＝ 1.6Hz,1H),7.45-7.34(m,9H),7.23(s,1H),7.20(t,J＝7.6Hz,1H),6.74-6.73(m,1 H),2.12(d,J＝1.2Hz,3H),2.01(s,3H),1.96(d,J＝1.2Hz,3H). 13 C{ 1 H}NMR (100MHz,CDCl 3 ):δ171.9,167.1,159.2,156.8,145.8,139.1,138.3,135.9,129.1, 129.0,128.9,128.6,128.1,127.1,126.8,125.3,122.6,120.5,119.5,114.8,68.8,28.0, 21.0,13.6.HRMS(ESI)m/z:[M+H] + Calcd for C 28 H 25 N 4 O 2 449.1972；Found 449.1958.
3',6-Dimethyl-2-(3-methylbut-2-enoyl)-1'-phenyl-2H-spiro[phthalazine-1,4'-pyra zol]-5'(1'H)-one(3i)
1 H NMR(600MHz,CDCl 3 ):δ7.97(d,J＝7.2Hz,2H),7.41(t,J＝7.2Hz,2H),7.34 (s,1H),7.20-7.17(m,2H),7.13(s,1H),6.92(d,J＝7.8Hz,1H),6.72-6.71(m,1H), 2.33(s,3H),2.10(d,J＝0.6Hz,3H),1.95(s,6H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ): δ171.8,167.0,159.2,156.5,140.4,138.3,136.4,133.6,128.9,128.1,125.1,124.0, 123.4,121.5,119.2,114.8,68.7,28.0,21.04,20.95,13.4.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 23 N 4 O 2 387.1816；Found 387.1809.
6-Methoxy-3'-methyl-2-(3-methylbut-2-enoyl)-1'-phenyl-2H-spiro[phthalazine-1, 4'-pyrazol]-5'(1'H)-one(3j)
1 H NMR(600MHz,CDCl 3 ):δ7.96(d,J＝7.8Hz,2H),7.41(t,J＝7.2Hz,2H),7.34 (s,1H),7.19(t,J＝7.2Hz,1H),6.96-6.91(m,2H),6.81(d,J＝2.4Hz,1H),6.71(s, 1H),3.82(s,3H),2.11(s,3H),1.96(s,6H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ 171.9,167.0,160.7,159.3,156.7,138.3,136.0,128.9,125.6,125.1,122.8,119.2, 118.7,118.1,114.7,112.1,68.5,55.6,28.0,21.0,13.4.HRMS(ESI)m/z:[M+H] + Calcdfor C 23 H 23 N 4 O 3 403.1765；Found 403.1759.
6-Chloro-3'-methyl-2-(3-methylbut-2-enoyl)-1'-phenyl-2H-spiro[phthalazine-1,4' -pyrazol]-5'(1'H)-one(3k)
1 H NMR(600MHz,CDCl 3 ):δ7.95(d,J＝7.8Hz,2H),7.42(t,J＝7.2Hz,2H),7.36 (dd,J 1 ＝8.4Hz,J 2 ＝1.8Hz,1H),7.323-7.315(m,2H),7.21(t,J＝7.8Hz,1H),6.98 (d,J＝8.4Hz,1H),6.70-6.69(m,1H),2.11(d,J＝0.6Hz,3H),1.97(s,3H),1.96(d, J＝0.6Hz,3H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ171.4,166.9,158.9,157.5, 138.1,136.2,134.5,132.6,128.9,127.3,125.8,125.3,124.7,123.2,119.2,114.4, 68.4,28.0,21.0,13.5.HRMS(ESI)m/z:[M+H] + Calcdfor C 22 H 20 ClN 4 O 2 407.1269； Found 407.1258.
6-Bromo-3'-methyl-2-(3-methylbut-2-enoyl)-1'-phenyl-2H-spiro[phthalazine-1,4' -pyrazol]-5'(1'H)-one(3l)
1 H NMR(600MHz,CDCl 3 ):δ7.95(d,J＝7.8Hz,2H),7.51(dd,J 1 ＝8.4Hz,J 2 ＝ 2.4Hz,1H),7.47(d,J＝1.8Hz,1H),7.42(t,J＝8.4Hz,2H),7.32(s,1H),7.21(t,J ＝7.2Hz,1H),6.91(d,J＝8.4Hz,1H),6.69(s,1H),2.11(d,J＝0.6Hz,3H),1.97(s, 3H),1.96(d,J＝1.2Hz,3H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ171.4,166.9, 158.8,157.5,138.1,135.6,134.3,130.2,128.9,126.0,125.3,125.2,124.1,123.4, 119.2,114.4,68.4,28.0,21.0,13.5.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 20 BrN 4 O 2 451.0764；Found 451.0753.
3',6,7-Trimethyl-2-(3-methylbut-2-enoyl)-1'-phenyl-2H-spiro[phthalazine-1,4'-py razol]-5'(1'H)-one(3m)
1 H NMR(400MHz,CDCl 3 ):δ7.99(d,J＝7.6Hz,2H),7.42(t,J＝7.6Hz,2H),7.33 (s,1H),7.20(t,J＝7.2Hz,1H),7.09(s,1H),6.77(s,1H),6.702-6.696(m,1H),2.25 (s,3H),2.20(s,3H),2.10(d,J＝0.8Hz,3H),1.951-1.946(m,6H). 13 C{ 1 H}NMR (100MHz,CDCl 3 ):δ172.0,167.0,159.1,156.2,142.4,139.0,138.4,136.4,128.9, 128.6,125.0,124.9,123.7,119.4,119.2,114.9,68.6,27.9,20.9,20.2,19.5,13.4. HRMS(ESI)m/z:[M+H] + Calcd for C 24 H 25 N 4 O 2 401.1972；Found 401.1965.
3',5-Dimethyl-2-(3-methylbut-2-enoyl)-1'-phenyl-2H-spiro[phthalazine-1,4'-pyra zol]-5'(1'H)-one(3n)
1 H NMR(600MHz,CDCl 3 ):δ7.97(d,J＝7.8Hz,2H),7.63(s,1H),7.41(t,J＝7.8 Hz,2H),7.27-7.24(m,1H),7.20-7.18(m,2H),6.87(d,J＝7.8Hz,1H),6.72-6.71(m, 1H),2.49(s,3H),2.11(d,J＝0.6Hz,3H),1.97(s,3H),1.96(d,J＝1.2Hz,3H). 13 C { 1 H}NMR(150MHz,CDCl 3 ):δ171.9,167.0,159.1,156.6,138.3,136.1,133.4, 132.4,132.0,128.9,126.4,125.1,121.9,119.7,119.2,114.7,68.7,28.0,21.0,18.1, 13.5.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 23 N 4 O 2 387.1816；Found 387.1799.
5-Fluoro-3'-methyl-2-(3-methylbut-2-enoyl)-1'-phenyl-2H-spiro[phthalazine-1,4'- pyrazol]-5'(1'H)-one(3o)
1 H NMR(600MHz,CDCl 3 ):δ7.95(d,J＝7.8Hz,2H),7.68(s,1H),7.42(t,J＝7.2 Hz,2H),7.39-7.35(m,1H),7.20(t,J＝7.2Hz,1H),7.10(t,J＝8.4Hz,1H),6.85(d, J＝8.4Hz,1H),6.72(s,1H),2.12(s,3H),1.98(s,3H),1.97(s,3H). 13 C{ 1 H}NMR (150MHz,CDCl 3 ):δ171.4,166.9,159.1(d, 1 J C-F ＝254.9Hz),158.7,157.4,138.1, 134.1(d, 3 J C-F ＝8.9Hz),128.9,128.8(d, 3 J C-F ＝5.4Hz),128.1(d, 3 J C-F ＝3.3Hz), 125.3,119.9(d, 4 J C-F ＝3.3Hz),119.2,116.9(d, 2 J C-F ＝20.7Hz),114.5,110.8(d, 2 J C-F ＝15.3Hz),68.0,28.0,21.0,13.5. 19 F NMR(565MHz,CDCl 3 ):δ-120.76–-120.79(m).HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 20 FN 4 O 2 391.1565；Found 391.1551.
3'-Methyl-3-(3-methylbut-2-enoyl)-1'-phenyl-3H-spiro[benzo[f]phthalazine-4,4'- pyrazol]-5'(1'H)-one(3p)
1 H NMR(600MHz,CDCl 3 ):δ8.26(d,J＝9.0Hz,1H),8.18(s,1H),8.01(d,J＝7.8 Hz,2H),7.87(d,J＝8.4Hz,1H),7.83(d,J＝7.8Hz,1H),7.66(t,J＝7.2Hz,1H), 7.57(t,J＝7.2Hz,1H),7.43(t,J＝7.8Hz,2H),7.21(t,J＝7.2Hz,1H),7.08(d,J＝ 9.0Hz,1H),6.79(s,1H),2.14(s,3H),2.00(s,3H),1.98(s,3H). 13 C{ 1 H}NMR(150 MHz,CDCl 3 ):δ171.9,167.0,158.7,156.9,138.3,133.8,133.5,132.0,128.94, 128.92,128.6,128.5,127.5,125.2,124.9,121.5,120.5,119.3,117.0,114.6,69.3, 28.0,21.0,13.6.HRMS(ESI)m/z:[M+H] + Calcd for C 26 H 23 N 4 O 2 423.1816；Found 423.1804.
2-(2-Cyclohexylideneacetyl)-3'-methyl-1'-phenyl-2H-spiro[phthalazine-1,4'-pyra zol]-5'(1'H)-one(3q)
1 H NMR(600MHz,CDCl 3 ):δ7.97(d,J＝7.8Hz,2H),7.43-7.39(m,4H),7.39(s, 1H),7.33-7.32(m,1H),7.20(t,J＝7.2Hz,1H),7.05-7.04(m,1H),6.61(s,1H),2.76 -2.69(m,2H),2.28(t,J＝6.0Hz,2H),1.97(s,3H),1.68-1.65(m,2H),1.60-1.55(m, 4H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ171.7,167.0,163.4,159.1,138.3,136.1, 132.8,130.1,128.9,127.6,126.3,125.1,124.2,121.6,119.2,112.0,68.7,38.5,30.4, 28.6,27.8,26.3,13.5.HRMS(ESI)m/z:[M+H] + Calcd for C 25 H 25 N 4 O 2 413.1972； Found 413.1955.
3'-Methyl-2-(3-methylbut-2-enoyl)-1'-(p-tolyl)-2H-spiro[phthalazine-1,4'-pyrazol] -5'(1'H)-one(3r)
1 H NMR(600MHz,CDCl 3 ):δ7.84(d,J＝8.4Hz,2H),7.40-7.38(m,2H),7.37(s, 1H),7.32-7.30(m,1H),7.22(d,J＝8.4Hz,2H),7.05-7.03(m,1H),6.711-6.707(m, 1H),2.35(s,3H),2.11(d,J＝1.2Hz,3H),1.96(s,6H). 13 C{ 1 H}NMR(150MHz, CDCl 3 ):δ171.7,167.0,159.0,156.6,136.1,135.8,134.9,132.8,130.1,129.4,127.6, 126.4,124.2,121.7,119.3,114.7,68.7,28.0,21.01,20.96,13.5.HRMS(ESI)m/z: [M+H] + Calcd for C 23 H 23 N 4 O 2 387.1816；Found 387.1804.
1'-(4-(tert-Butyl)phenyl)-3'-methyl-2-(3-methylbut-2-enoyl)-2H-spiro[phthalazine -1,4'-pyrazol]-5'(1'H)-one(3s)
1 H NMR(600MHz,CDCl 3 ):δ7.89(d,J＝9.0Hz,2H),7.44(d,J＝9.0Hz,2H),7.40 -7.37(m,3H),7.31-7.30(m,1H),7.05-7.03(m,1H),6.71(s,1H),2.11(s,3H),1.95 (s,6H),1.33(s,9H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ171.7,166.9,159.0,156.6, 148.1,136.1,135.8,132.8,130.1,127.6126.4125.7,124.2,121.7,119.0,114.7,68.7, 34.5,31.4,28.0,21.0,13.5.HRMS(ESI)m/z:[M+H] + Calcd for C 26 H 29 N 4 O 2 429.2285；Found 429.2267.
1'-(4-Methoxyphenyl)-3'-methyl-2-(3-methylbut-2-enoyl)-2H-spiro[phthalazine-1, 4'-pyrazol]-5'(1'H)-one(3t)
1 H NMR(600MHz,CDCl 3 ):δ7.84(d,J＝9.0Hz,2H),7.40-7.39(m,2H),7.37(s, 1H),7.32-7.30(m,1H),7.06-7.05(m,1H),6.95(d,J＝9.0Hz,2H),6.71(s,1H), 3.81(s,3H),2.12(s,3H),1.96(s,3H),1.95(s,3H). 13 C{ 1 H}NMR(150MHz, CDCl 3 ):δ171.7,167.0,159.0,157.3,156.6,136.1,132.8,131.6,130.1,127.6,126.4, 124.1,121.7,121.3,114.8,114.1,68.5,55.6,28.0,21.0,13.4.HRMS(ESI)m/z:[M+ H] + Calcd for C 23 H 23 N 4 O 3 403.1765；Found 403.1747.
1'-(4-Fluorophenyl)-3'-methyl-2-(3-methylbut-2-enoyl)-2H-spiro[phthalazine-1,4' -pyrazol]-5'(1'H)-one(3u)
1 H NMR(600MHz,CDCl 3 ):δ7.94-7.92(m,2H),7.43-7.40(m,2H),7.39(s,1H), 7.34-7.33(m,1H),7.10(t,J＝8.4Hz,2H),7.04-7.03(m,1H),6.71(s,1H),2.12(d,J ＝0.6Hz,3H),1.97(s,3H),1.96(s,3H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ171.7, 167.0,160.1(d, 1 J C-F ＝242.9Hz),159.2,156.9,136.1,134.4(d, 4 J C-F ＝2.3Hz),132.8, 130.2,127.6,126.2,124.1,121.6,121.1(d, 3 J C-F ＝8.7Hz),115.6(d, 2 J C-F ＝21.9Hz), 114.6,68.6,28.0,21.0,13.4. 19 FNMR(565MHz,CDCl 3 ):δ-117.12--117.16(m). HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 20 FN 4 O 2 391.1565；Found 391.1548.
1'-(4-Chlorophenyl)-3'-methyl-2-(3-methylbut-2-enoyl)-2H-spiro[phthalazine-1,4 '-pyrazol]-5'(1'H)-one(3v)
1 H NMR(600MHz,CDCl 3 ):δ7.94(d,J＝9.0Hz,2H),7.42-7.40(m,2H),7.39(s, 1H),7.37(d,J＝9.0Hz,2H),7.34-7.33(m,1H),7.01-7.00(m,1H),6.71(s,1H), 2.11(d,J＝1.2Hz,3H),1.96(s,6H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ171.7, 167.0,159.3,157.0,136.9,136.1,132.9,130.3,130.2,128.9,127.7,126.1,124.1, 121.6,120.2,114.6,68.6,28.0,21.0,13.4.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 20 ClN 4 O 2 407.1269；Found 407.1247.
1'-(4-Bromophenyl)-3'-methyl-2-(3-methylbut-2-enoyl)-2H-spiro[phthalazine-1,4 '-pyrazol]-5'(1'H)-one(3w)
1 H NMR(600MHz,CDCl 3 ):δ7.89(d,J＝8.4Hz,2H),7.52(d,J＝8.4Hz,2H),7.41 -7.40(m,2H),7.39(s,1H),7.34-7.32(m,1H),7.01-6.99(m,1H),6.71(m,1H),2.11 (s,3H),1.96(s,6H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ171.7,167.0,159.3,157.0, 137.4,136.1,132.9,131.9,130.3,127.7,126.1,124.1,121.6,120.5,117.9,114.6, 68.7,28.0,21.0,13.5.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 20 BrN 4 O 2 451.0764； Found 451.0761.
1'-(4-Iodophenyl)-3'-methyl-2-(3-methylbut-2-enoyl)-2H-spiro[phthalazine-1,4'-p yrazol]-5'(1'H)-one(3x)
1 H NMR(600MHz,CDCl 3 ):δ7.78(d,J＝9.0Hz,2H),7.71(d,J＝9.0Hz,2H),7.42 -7.39(m,2H),7.34(s,1H),7.34-7.33(m,1H),7.00-6.99(m,1H),6.71-6.70(m,1H), 2.11(d,J＝1.2Hz,3H),1.962(d,J＝1.2Hz,3H),1.957(s,3H). 13 C{ 1 H}NMR(150 MHz,CDCl 3 ):δ171.7,167.0,159.4,157.1,138.1,137.8,136.1,132.9,130.3,127.7, 126.1,124.1,121.6,120.8,114.5,88.8,68.7,28.0,21.0,13.5.HRMS(ESI)m/z:[M+ H] + Calcd for C 22 H 20 IN 4 O 2 499.0625；Found 499.0624.
3'-Methyl-2-(3-methylbut-2-enoyl)-1'-(4-(trifluoromethyl)phenyl)-2H-spiro[phth alazine-1,4'-pyrazol]-5'(1'H)-one(3y)
1 H NMR(400MHz,CDCl 3 ):δ8.15(d,J＝8.8Hz,2H),7.67(d,J＝8.8Hz,2H),7.44 -7.39(m,3H),7.36-7.33(m,1H),7.01-6.99(m,1H),6.724-6.718(m,1H),2.11(d,J ＝0.8Hz,3H),1.98(s,3H),1.97(d,J＝0.8Hz,3H). 13 C{ 1 H}NMR(100MHz, CDCl 3 ):δ171.9,167.0,159.6157.2,141.1,136.2,132.9,130.4,127.8,126.6(q, 2 J C-F ＝31.8Hz),126.1(q, 3 J C-F ＝3.6Hz),125.9,124.2(q, 1 J C-F ＝270.1Hz),124.1121.6, 118.4,114.5,68.7,28.0,21.0,13.5. 19 FNMR(376MHz,CDCl 3 ):δ-62.06(s).HRMS (ESI)m/z:[M+H] + Calcd for C 23 H 20 F 3 N 4 O 2 441.1533；Found 441.1525.
3'-Methyl-2-(3-methylbut-2-enoyl)-1'-(m-tolyl)-2H-spiro[phthalazine-1,4'-pyrazo l]-5'(1'H)-one(3z)
1 H NMR(600MHz,CDCl 3 ):δ7.81(s,1H),7.77(d,J＝8.4Hz,1H),7.40-7.38(m, 2H),7.37(s,1H),7.32-7.28(m,2H),7.05-7.03(m,1H),7.02(d,J＝7.8Hz,1H), 6.72-6.71(m,1H),2.39(s,3H),2.11(d,J＝1.2Hz,3H),1.96(s,3H),1.95(d,J＝1.2 Hz,3H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ171.8,167.0,159.1,156.7,138.8, 138.2,136.1,132.8,130.1,128.7,127.6,126.3,126.0,124.2,121.6,119.8,116.4, 114.7,68.7,28.0,21.6,21.0,13.5.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 23 N 4 O 2 387.1816；Found 387.1802.
1'-(3-Fluorophenyl)-3'-methyl-2-(3-methylbut-2-enoyl)-2H-spiro[phthalazine-1,4' -pyrazol]-5'(1'H)-one(3aa)
1 H NMR(600MHz,CDCl 3 ):δ7.81(d,J＝8.4Hz,1H),7.79-7.77(m,1H),7.42-7.40 (m,2H),7.39(s,1H),7.37-7.35(m,1H),7.34-7.32(m,1H),7.01-7.00(m,1H),6.88 (td,J 1 ＝8.4Hz,J 2 ＝2.4Hz,1H),6.72-6.71(m,1H),2.11(d,J＝1.2Hz,3H),1.96(s, 6H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ171.7,167.0,163.0(d, 1 J C-F ＝242.9Hz), 159.3,157.0,139.7(d, 3 J C-F ＝11.0Hz),136.2,132.9,130.3,130.1(d, 3 J C-F ＝8.7Hz), 127.7,126.1,124.1,121.6,114.6,114.2(d, 4 J C-F ＝2.1Hz),111.7(d, 2 J C-F ＝20.9Hz), 106.3(d, 2 J C-F ＝26.3Hz),68.8,28.0,21.0,13.4. 19 FNMR(565MHz,CDCl 3 ):δ -111.47--111.51(m).HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 20 FN 4 O 2 391.1565； Found 391.1553.
1'-(3-Chlorophenyl)-3'-methyl-2-(3-methylbut-2-enoyl)-2H-spiro[phthalazine-1,4 '-pyrazol]-5'(1'H)-one(3bb)
1 H NMR(600MHz,CDCl 3 ):δ8.05-8.04(m,1H),7.92(dd,J 1 ＝8.4Hz,J 2 ＝1.2Hz, 1H),7.42-7.40(m,2H),7.39(s,1H),7.34-7.31(m,2H),7.16(dd,J 1 ＝7.8Hz,J 2 ＝ 1.2Hz,1H),7.01-7.00(m,1H),6.71(s,1H),2.12(s,3H),1.97(s,6H). 13 C{ 1 H} NMR(150MHz,CDCl 3 ):δ171.7,167.0,159.4,157.1,139.3,136.1,134.6,132.9, 130.3,129.9,127.7,126.0,125.0,124.1,121.6,119.0,116.8,114.5,68.7,28.0,21.0, 13.4.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 20 ClN 4 O 2 407.1269；Found 407.1263.
1'-(3-Bromophenyl)-3'-methyl-2-(3-methylbut-2-enoyl)-2H-spiro[phthalazine-1,4 '-pyrazol]-5'(1'H)-one(3cc)
1 H NMR(600MHz,CDCl 3 ):δ8.20-8.19(m,1H),7.98(d,J＝7.8Hz,1H),7.42-7.41 (m,2H),7.39(s,1H),7.34-7.31(m,2H),7.28-7.25(m,1H),7.01-7.00(m,1H),6.71 (s,1H),2.11(d,J＝0.6Hz,3H),1.96(s,6H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ 171.7,167.0,159.4,157.1,139.4,136.1,132.9,130.3,130.2,127.9,127.7,126.0, 124.1,122.6,121.8,121.6,117.3,114.5,68.7,28.0,21.0,13.5.HRMS(ESI)m/z:[M +H] + Calcd for C 22 H 20 BrN 4 O 2 451.0764；Found 451.0750.
3'-Methyl-2-(3-methylbut-2-enoyl)-1'-(o-tolyl)-2H-spiro[phthalazine-1,4'-pyrazol] -5'(1'H)-one(3dd)
1 H NMR(600MHz,CDCl 3 ):δ7.53(d,J＝7.8Hz,1H),7.47(td,J 1 ＝7.8Hz,J 2 ＝1.2 Hz,1H),7.42(t,J＝7.2Hz,1H),7.37(s,1H),7.33(d,J＝6.6Hz,1H),7.30-7.26(m, 4H),6.71(s,1H),2.43(s,3H),2.16(s,3H),1.97(s,3H),1.94(s,3H). 13 C{ 1 H}NMR (150MHz,CDCl 3 ):δ172.8,167.1,158.9,156.3,136.4,136.1,135.3,132.7,131.0, 130.1,128.4,127.7,126.6,126.5,126.3,124.0,121.8,114.9,67.8,27.9,20.9,18.5, 13.5.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 23 N 4 O 2 387.1816；Found 387.1813.
1'-(2-Fluorophenyl)-3'-methyl-2-(3-methylbut-2-enoyl)-2H-spiro[phthalazine-1,4' -pyrazol]-5'(1'H)-one(3ee)
1 H NMR(600MHz,CDCl 3 ):δ7.69(td,J 1 ＝7.2Hz,J 2 ＝1.8Hz,1H),7.47(td,J 1 ＝ 7.8Hz,J 2 ＝1.2Hz,1H),7.42(td,J 1 ＝7.8Hz,J 2 ＝1.2Hz,1H),7.38(s,1H),7.34 -7.31(m,3H),7.25-7.19(m,2H),6.714-6.710(m,1H),2.17(d,J＝1.2Hz,3H),1.98 (d,J＝0.6Hz,3H),1.93(s,3H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ172.6,167.1, 159.2,157.2(d, 1 J C-F ＝250.5Hz),156.6,136.4,133.0,130.2,129.5(d, 3 J C-F ＝7.7Hz), 127.7,127.5,126.1,125.3(d, 2 J C-F ＝12.0Hz),124.6(d, 4 J C-F ＝3.2Hz),124.4,121.7, 116.5(d, 2 J C-F ＝18.6Hz),114.8,67.5,28.0,20.9,13.4. 19 F NMR(376MHz,CDCl 3 ): δ-112.08(dd,J 1 ＝9.8Hz,J 2 ＝4.1Hz).HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 20 FN 4 O 2 391.1565；Found 391.1558.
3'-Methyl-2-(3-methylbut-2-enoyl)-1'-(naphthalen-2-yl)-2H-spiro[phthalazine-1,4 '-pyrazol]-5'(1'H)-one(3ff)
1 H NMR(600MHz,CDCl 3 ):δ8.44(d,J＝1.8Hz,1H),8.18(dd,J 1 ＝9.0Hz,J 2 ＝ 2.4Hz,1H),7.89(d,J＝9.0Hz,1H),7.85(d,J＝7.8Hz,1H),7.82(d,J＝7.8Hz, 1H),7.48-7.45(m,1H),7.44-7.40(m,4H),7.34-7.32(m,1H),7.10-7.08(m,1H),6.73 (s,1H),2.11(d,J＝0.6Hz,3H),2.01(s,3H),1.96(s,3H). 13 C{ 1 H}NMR(150MHz, CDCl 3 ):δ172.0,167.0,159.3,156.9,136.1,135.8,133.6,132.9,131.2,130.2,128.7, 128.1,127.6,126.4,126.3,125.3,124.2,121.7,118.7,116.3,114.6,68.8,28.0,21.0, 13.5.HRMS(ESI)m/z:[M+H] + Calcd for C 26 H 23 N 4 O 2 423.1816；Found 423.1799.
3'-Ethyl-2-(3-methylbut-2-enoyl)-1'-phenyl-2H-spiro[phthalazine-1,4'-pyrazol]-5' (1'H)-one(3gg)
1 H NMR(600MHz,CDCl 3 ):δ8.00(d,J＝7.8Hz,2H),7.42(t,J＝7.8Hz,2H), 7.39-7.38(m,3H),7.32-7.30(m,1H),7.20(t,J＝7.8Hz,1H),7.04-7.03(m,1H),6.70 -6.69(m,1H),2.36-2.21(m,2H),2.10(d,J＝1.2Hz,3H),1.95(d,J＝0.6Hz,3H), 1.11(t,J＝7.8Hz,3H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ172.0,167.0,162.9, 156.4,138.4,136.1,132.7,130.0,128.9,127.6,126.8,125.1,124.2,121.5,119.2, 114.8,68.6,27.9,21.6,21.0,9.6.HRMS(ESI)m/z:[M+H] + Calcd for C 23 H 23 N 4 O 2 387.1816；Found 387.1804.
3'-Isopropyl-2-(3-methylbut-2-enoyl)-1'-phenyl-2H-spiro[phthalazine-1,4'-pyraz ol]-5'(1'H)-one(3hh)
1 H NMR(600MHz,CDCl 3 ):δ8.00(d,J＝7.8Hz,2H),7.41(t,J＝7.2Hz,2H),7.39 (s,1H),7.37-7.36(m,2H),7.30-7.28(m,1H),7.19(t,J＝7.8Hz,1H),7.02-7.00(m, 1H),6.69(s,1H),2.61-2.54(m,1H),2.09(s,3H),1.95(s,3H),1.12(d,J＝7.2Hz, 3H),0.98(d,J＝7.2Hz,3H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ172.0,167.0, 165.5,156.2,138.4,136.0,132.6,129.9,128.8,127.5,127.2,125.0,124.3,121.5, 119.2,114.9,68.5,29.3,27.9,20.9,20.6,20.0.HRMS(ESI)m/z:[M+H] + Calcd for C 24 H 25 N 4 O 2 401.1972；Found 401.1967.
example 4
To a 15mL pressure tube, compound 1a (40.4 mg, 0.2mmol), compound 4a (41.3 mg, 0.24mmol), [ Cp. Multidot.Rh (MeCN) 3 ](SbF 6 ) 2 (6.6mg, 0.008mmol), agOAc (66.8 mg,0.4 mmol) and acetonitrile (2 mL), and the reaction tube was sealed and placed in a 100 ℃ oil bath for reaction for 10h. After completion of the reaction, the reaction system was cooled to room temperature, filtered with suction, the filtrate was concentrated, and the filtrate was separated on a silica gel column (petroleum ether/ethyl acetate = 5/1) to obtain product 5a (51.8mg, 75%) as an orange solid. Characterization data for this compound are: 1 H NMR(600MHz,CDCl 3 ):δ8.08-8.06(m,2H),7.92-7.90(m,2H),7.39(s,1H), 7.31-7.30(m,2H),7.19-7.16(m,1H),6.72(s,1H),6.52(d,J＝7.8Hz,1H),1.99(s, 3H),1.93(s,3H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ194.6,167.1,156.5,140.7, 136.3,135.9,131.8,129.5,128.4,127.7,124.33,124.29,122.1,114.4,68.2,28.0, 20.9.HRMS(ESI)m/z:[M+H] + Calcd for C 21 H 17 N 2 O 3 345.1234；Found 345.1225.
example 5
Method and procedure according to example 4 a,b By changing reactant 1 and reactant 4, the series 1,3-indenedione [ spiro ] is synthesized]The specific results of the dihydrophthalazine compound 5 are as follows:
a the reaction conditions are as follows: 1 (0.2 mmol), 2 (0.24 mmol), [ Cp.. Multidot.Rh (MeCN) 3 ](SbF 6 ) 2 (0.008 mmol) in vinegarAcid(s) b Silver (0.4 mmol), acetonitrile (2 mL), 100 ℃,10h, air atmosphere; the isolation yield.
Representative product characterization data are as follows:
7'-Methyl-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dione (5b)
1 H NMR(400MHz,CF 3 COOD):δ8.56-8.53(m,2H),8.44-8.42(m,2H),8.17(s,1 H),7.79(d,J＝8.0Hz,1H),7.66(d,J＝8.0Hz,1H),6.85-6.83(m,2H),2.51(s,3H), 2.34(s,3H),2.30(s,3H). 13 C{ 1 H}NMR(100MHz,CF 3 COOD):δ192.7,170.1, 162.8,146.5,143.6,140.3,137.8,131.6,129.8,126.4,125.4,125.1,118.6,112.6, 69.7,26.1,20.1,20.0.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 19 N 2 O 3 359.1390； Found 359.1381.
7'-(tert-Butyl)-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-di one(5c)
1 H NMR(600MHz,CF 3 COOD):δ8.56-8.55(m,2H),8.45-8.44(m,2H),8.15(s, 1H),7.90-7.82(m,2H),7.05(s,1H),6.84(s,1H),2.32(s,3H),2.29(s,3H),1.38 -1.37(m,9H). 13 C{ 1 H}NMR(150MHz,CF 3 COOD):δ193.8,170.2,159.4,143.0, 140.4,137.8,129.6,128.1,126.2,125.3,121.5,118.5,112.9,70.1,34.9,29.2,26.1, 20.0.HRMS(ESI)m/z:[M+H] + Calcd for C 25 H 25 N 2 O 3 401.1860；Found 401.1858.
7'-Fluoro-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dione (5d)
1 H NMR(600MHz,CF 3 COOD):δ8.30-8.28(m,2H),8.19-8.18(m,2H),7.85(s, 1H),7.65(dd,J 1 ＝8.4Hz,J 2 ＝5.4Hz,1H),7.23(td,J 1 ＝7.8Hz,J 2 ＝1.8Hz,1H), 6.61(s,1H),6.43(dd,J 1 ＝8.4Hz,J 2 ＝1.8Hz,1H),2.07(s,3H),2.02(s,3H). 13 C{ 1 H} NMR(100MHz,CF 3 COOD):δ194.1,170.2,165.4(d, 1 J C-F ＝256.4Hz),140.8139.8, 137.8,131.8(d, 3 J C-F ＝9.4Hz),128.8(d, 3 J C-F ＝8.6Hz),125.3,117.8(d, 2 J C-F ＝23.1 Hz),117.6(d, 4 J C-F ＝3.6Hz),112.7,112.0(d, 2 J C-F ＝26.0Hz),69.2(d, 4 J C-F ＝2.2 Hz),25.9,19.6. 19 F NMR(565MHz,CDCl 3 )δ:-104.88–104.92(m).HRMS(ESI) m/z:[M+H] + Calcd for C 21 H 16 FN 2 O 3 363.1139；Found 363.1135.
7'-Chloro-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dione (5e)
1 H NMR(600MHz,CDCl 3 ):δ8.10-8.09(m,2H),7.96-7.95(m,2H),7.36(s,1H), 7.30(dd,J 1 ＝8.4Hz,J 2 ＝1.8Hz,1H),7.27-7.26(m,1H),6.70(s,1H),6.47(s,1H), 1.99(s,3H),1.94(s,3H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ194.1,167.1,157.0, 140.4,137.7,136.2,135.0,130.1,129.9,128.8,124.7,124.5,120.7,114.2,67.8,28.0, 20.9.HRMS(ESI)m/z:[M+Na] + Calcd for C 21 H 15 ClN 2 NaO 3 401.0663；Found 401.0659.
7'-Bromo-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dione (5f)
1 H NMR(600MHz,CF 3 COOD):δ8.30-8.29(m,2H),8.19-8.17(m,2H),7.82(s,1 H),7.69(dd,J 1 ＝7.8Hz,J 2 ＝1.2Hz,1H),7.45(d,J＝8.4Hz,1H),6.88(s,1H),6.62 (s,1H),2.07(s,3H),2.02(s,3H). 13 C{ 1 H}NMR(150MHz,CF 3 COOD):δ194.3, 170.2,140.7,139.9,137.8,134.0,130.2,128.1,128.0,127.6,125.4,119.8,112.7, 68.7,26.0,19.7.HRMS(ESI)m/z:[M+H] + Calcd for C 21 H 16 BrN 2 O 3 423.0339； Found 423.0337.
6'-Methyl-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dione (5g)
1 H NMR(600MHz,CF 3 COOD):δ8.29-8.27(m,2H),8.17-8.16(m,2H),7.87(s,1 H),7.44(s,1H),7.27(d,J＝7.8Hz,1H),6.61(d,J＝8.4Hz,1H),6.59(s,1H),2.42 (s,3H),2.08(s,3H),2.03(s,3H). 13 C{ 1 H}NMR(150MHz,CF 3 COOD):δ193.9, 170.1,162.2,142.9,142.3,140.1,137.6,134.4,130.0,125.2,124.0,123.2,120.7, 112.6,69.4,25.9,19.7,18.9.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 19 N 2 O 3 359.1390；Found 359.1391.
6'-Chloro-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dione (5h)
1 H NMR(600MHz,CF 3 COOD):δ8.29-8.27(m,2H),8.18-8.16(m,2H),7.76(s,1 H),7.57(d,J＝1.8Hz,1H),7.37(dd,J 1 ＝8.4Hz,J 2 ＝1.8Hz,1H),6.66-6.64(m,2 H),2.07(s,3H),2.02(s,3H). 13 C{ 1 H}NMR(150MHz,CF 3 COOD):δ195.2,170.3, 162.0,140.0,139.9,137.8,137.5,133.1,128.8,125.4,125.3,124.5,122.5,112.9, 68.9,26.0,19.6.HRMS(ESI)m/z:[M+H] + Calcd for C 21 H 16 ClN 2 O 3 379.0844； Found 379.0835.
6'-Bromo-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dione (5i)
1 H NMR(600MHz,CF 3 COOD):δ8.28-8.27(m,2H),8.18-8.16(m,2H),7.75(s,1 H),7.73(s,1H),7.53(d,J＝8.4Hz,1H),6.65(s,1H),6.57(d,J＝8.4Hz,1H),2.07 (s,3H),2.02(s,3H). 13 C{ 1 H}NMR(150MHz,CF 3 COOD):δ195.0,170.3,162.1, 140.0,139.8,137.8,136.2,131.9,125.4,125.3,125.0,124.9,122.6,112.9,69.0,26.0, 19.7.HRMS(ESI)m/z:[M+H] + Calcd for C 21 H 16 BrN 2 O 3 423.0339；Found 423.0337.
8'-Fluoro-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dione (5j)
1 H NMR(600MHz,CF 3 COOD):δ8.18-8.17(m,2H),8.09-8.08(m,2H),7.87(d,J＝ 1.8Hz,1H),7.59(td,J 1 ＝8.4Hz,J 2 ＝5.4Hz,1H),7.43(d,J＝7.2Hz,1H),7.17(dd, J 1 ＝10.8Hz,J 2 ＝9.0Hz,1H),6.59(s,1H),2.06(s,3H),2.00(s,3H). 13 C{ 1 H}NMR (150MHz,CF 3 COOD):δ194.7,170.5,162.6,158.2(d, 1 J C-F ＝251.6Hz),141.3, 139.7(d, 3 J C-F ＝4.4Hz),137.2,132.8(d, 3 J C-F ＝9.9Hz),124.9(d, 4 J C-F ＝2.1Hz), 124.1,123.5(d, 4 J C-F ＝2.3Hz),120.8(d, 2 J C-F ＝21.9Hz),113.6(d, 2 J C-F ＝13.1Hz), 112.9,66.5(d, 3 J C-F ＝4.4Hz),26.1,19.7. 19 FNMR(565MHz,CDCl 3 ):δ-104.39– -104.41(m).HRMS(ESI)m/z:[M+H] + Calcd for C 21 H 16 FN 2 O 3 363.1139；Found 363.1135.
6'-Methoxy-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dion e(5k)and 8'-Methoxy-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazi ne]-1,3-dione(5k')
1 H NMR(600MHz,CF 3 COOD):δ8.29-8.27(m,2H),8.17-8.16(m,2H),8.15-8.13 (m,2H),8.07-8.05(m,2H),7.91(s,1H),7.86(s,1H),7.58(t,J＝7.8Hz,1H),7.23 (d,J＝7.8Hz,1H),7.22(d,J＝2.4Hz,1H),7.07(d,J＝7.8Hz,1H),7.02(dd,J 1 ＝ 9.0Hz,J 2 ＝2.4Hz,1H),6.66(d,J＝8.4Hz,1H),6.61(s,1H),6.53(s,1H),3.95(s, 3H),3.32(s,3H),2.07(s,3H),2.06(s,3H),2.02(s,6H). 13 C{ 1 H}NMR(150MHz, CF 3 COOD):δ195.0,193.2,170.3,163.2,160.6,155.2,144.1,141.8,140.3,140.1, 137.7,136.4,132.4,125.7,125.3,123.2,123.1,122.4,121.8,119.5,118.9,116.6, 114.5,114.2,112.8,112.5,69.2,67.8,55.0,54.0,26.1,25.9,19.9,19.7.HRMS(ESI) m/z:[M+H] + Calcd for C 22 H 19 N 2 O 4 375.1339；Found 375.1335.
5'-Methyl-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dione (5l)
1 H NMR(600MHz,CF 3 COOD):δ8.28-8.27(m,2H),8.22(s,1H),8.16-8.15(m,2 H),7.36(d,J＝7.8Hz,1H),7.29(t,J＝7.2Hz,1H),6.59(s,1H),6.55(d,J＝7.8Hz, 1H),2.63(s,3H),2.08(s,3H),2.03(s,3H). 13 C{ 1 H}NMR(150MHz,CF 3 COOD):δ 193.9,170.0,162.3,140.2,140.0,139.4,137.6,133.3,132.6,126.5,125.2,122.1, 119.0,112.6,69.3,25.9,19.7,16.2.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 19 N 2 O 3 359.1390；Found 359.1386.
5'-Fluoro-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dione (5m)
1 H NMR(600MHz,CF 3 COOD):δ8.29-8.26(m,2H),8.18-8.16(m,2H),8.12(s,1 H),7.40(td,J 1 ＝8.4Hz,J 2 ＝6.0Hz,1H),7.22(t,J＝8.4Hz,1H),6.68(s,1H),6.50 (d,J＝8.4Hz,1H),2.08(s,3H),2.03(s,3H). 13 C{ 1 H}NMR(150MHz,CF 3 COOD): δ194.7,170.3,160.4(d, 1 J C-F ＝259.2Hz),140.1,137.7,134.9(d, 3 J C-F ＝8.7Hz), 134.2(d, 3 J C-F ＝6.5Hz),127.9,125.3,119.9(d, 4 J C-F ＝3.3Hz),117.4(d, 2 J C-F ＝20.9 Hz),112.8,110.1(d, 2 J C-F ＝15.3Hz),68.6,26.0,19.7. 19 FNMR(565MHz,CDCl 3 ): δ-120.60(dd,J 1 ＝8.5Hz,J 2 ＝6.2Hz).HRMS(ESI)m/z:[M+H] + Calcd for C 21 H 16 FN 2 O 3 363.1139；Found 363.1119.
5'-Chloro-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dione (5n)
1 H NMR(600MHz,CF 3 COOD):δ8.56(s,1H),8.54-8.53(m,2H),8.43-8.42(m,2 H),7.80(d,J＝8.4Hz,1H),7.57(t,J＝7.8Hz,1H),6.94(s,1H),6.88(d,J＝7.8Hz, 1H),2.34(s,3H),2.29(s,3H). 13 C{ 1 H}NMR(150MHz,CF 3 COOD):δ195.1,170.4, 162.5,140.4,138.0,137.3,135.8,133.8,131.8,128.6,125.5,122.9,118.9,113.0, 68.7,26.3,19.9.HRMS(ESI)m/z:[M+H] + Calcd for C 21 H 16 ClN 2 O 3 379.0844； Found 379.0842.
5'-Bromo-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dione (5o)
1 H NMR(600MHz,CF 3 COOD):δ8.54-8.53(m,3H),8.43-8.42(m,2H),7.98(d,J＝ 8.4Hz,1H),7.47(t,J＝8.4Hz,1H),6.94(s,1H),6.92(d,J＝7.8Hz,1H),2.34(s,3 H),2.29(s,3H). 13 C{ 1 H}NMR(150MHz,CF 3 COOD):δ195.1,170.4,162.4,140.4, 139.7,137.9,135.2,133.8,128.9,125.5,125.3,123.6,120.4,113.0,68.6,26.3,19.9. HRMS(ESI)m/z:[M+H] + Calcd for C 21 H 16 BrN 2 O 3 423.0339；Found 423.0337.
3-(3-Methylbut-2-enoyl)-3H-spiro[benzo[f]phthalazine-4,2'-indene]-1',3'-dione (5p)
1 H NMR(600MHz,CF 3 COOD):δ8.72(s,1H),8.37(d,J＝8.4Hz,1H),8.32-8.29 (m,2H),8.20-8.17(m,2H),7.88(d,J＝8.4Hz,1H),7.84(d,J＝7.8Hz,1H),7.77(t, J＝7.2Hz,1H),7.65(t,J＝7.2Hz,1H),6.74(d,J＝9.0Hz,1H),6.65(s,1H),2.09 (s,3H),2.05(s,3H). 13 C{ 1 H}NMR(150MHz,CF 3 COOD):δ195.1,170.2,162.0, 140.3,138.2,137.8,134.7,133.7,129.5,129.1,128.7,128.1,125.2,125.1,120.8, 119.6,116.5,112.9,69.9,26.0,19.8.HRMS(ESI)m/z:[M+H] + Calcd for C 25 H 19 N 2 O 3 395.1390；Found 395.1388.
5-Methyl-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dione (5q)
1 H NMR(400MHz,CDCl 3 ):δ7.96(d,J＝8.0Hz,1H),7.87(s,1H),7.71(d,J＝7.6 Hz,1H),7.38(s,1H),7.30-7.29(m,2H),7.19-7.15(m,1H),6.722-6.716(m,1H), 6.54(d,J＝8.0Hz,1H),2.58(s,3H),1.99(d,J＝0.8Hz,3H),1.93(d,J＝0.8Hz,3 H). 13 C{ 1 H}NMR(100MHz,CDCl 3 ):δ194.7,194.3,167.1,156.2,147.5,141.1, 138.4,136.9,136.2,131.7,129.4,128.6,127.7,124.4,124.3,124.2,122.1,114.5, 68.5,27.9,22.2,20.9.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 19 N 2 O 3 359.1390； Found 359.1398.
5-Fluoro-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dione (5r)
1 H NMR(600MHz,CF 3 COOD):δ8.35(dd,J 1 ＝8.4Hz,J 2 ＝4.2Hz,1H),7.94(dd, J 1 ＝6.6Hz,J 2 ＝1.8Hz,1H),7.92(s,1H),7.85(td,J 1 ＝8.4Hz,J 2 ＝1.8Hz,1H), 7.66(d,J＝7.8Hz,1H),7.61(t,J＝7.2Hz,1H),7.50(t,J＝7.8Hz,1H),6.80(d,J＝ 8.4Hz,1H),6.65(s,1H),2.12(s,3H),2.08(s,3H). 13 C{ 1 H}NMR(150MHz, CF 3 COOD):δ194.2,191.3,170.4,169.2(d, 1 J C-F ＝263.6Hz),162.3,143.7(d, 3 J C-F ＝9.8Hz),142.5,136.3,133.8,130.9,129.7,128.4(d, 3 J C-F ＝11.0Hz),126.3,125.4(d, 2 J C-F ＝24.0Hz),124.3,121.1,113.0,112.0(d, 2 J C-F ＝24.2Hz),69.7,26.2,20.0. 19 F NMR(565MHz,CDCl 3 ):δ-98.62–-98.66(m).HRMS(ESI)m/z:[M+H] + Calcd for C 21 H 16 FN 2 O 3 363.1139；Found 363.1139.
5-Chloro-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dione (5s)
1 H NMR(400MHz,CF 3 COOD):δ8.26(d,J＝1.6Hz,1H),8.24(d,J＝8.0Hz,1H), 8.13(dd,J 1 ＝8.4Hz,J 2 ＝1.6Hz,1H),7.91(s,1H),7.65(d,J＝7.6Hz,1H),7.60(t, J＝7.6Hz,1H),7.49(td,J 1 ＝7.6Hz,J 2 ＝1.2Hz,1H),6.80(d,J＝8.0Hz,1H),6.65 (s,1H),2.11(d,J＝0.8Hz,3H),2.07(d,J＝0.4Hz,3H). 13 C{ 1 H}NMR(100MHz, CF 3 COOD):δ194.2,192.0,170.4,145.9,142.4,141.9,138.1,137.9,133.8,130.9, 129.7,126.5,126.3,125.3,124.3,121.1,112.9,69.6,26.2,20.0.HRMS(ESI)m/z: [M+H] + Calcd for C 21 H 16 ClN 2 O 3 379.0844；Found 379.0830.
5-Bromo-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dione (5t)
1 H NMR(600MHz,CF 3 COOD):δ8.40(s,1H),8.27(d,J＝8.4Hz,1H),8.11(d,J＝ 8.4Hz,1H),7.87(s,1H),7.61(d,J＝7.2Hz,1H),7.56(t,J＝7.8Hz,1H),7.44(t,J ＝7.8Hz,1H),6.75(d,J＝7.8Hz,1H),6.61(s,1H),2.07(s,3H),2.03(s,3H). 13 C { 1 H}NMR(150MHz,CF 3 COOD):δ194.3,192.2,170.2,142.1,141.4,140.7,138.3, 133.9,133.6,130.7,129.5,128.3,126.2,126.0,124.1,120.8,112.7,69.2,25.9,19.7. HRMS(ESI)m/z:[M+H] + Calcd for C 21 H 16 BrN 2 O 3 423.0339；Found 423.0322.
4-Fluoro-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dione (5u)
1 H NMR(600MHz,CF 3 COOD):δ8.23-8.19(m,1H),8.15(d,J＝7.2Hz,1H),7.93 (s,1H),7.81(t,J＝8.4Hz,1H),7.67(d,J＝7.8Hz,1H),7.62(t,J＝7.8Hz,1H), 7.52(t,J＝7.8Hz,1H),6.86(d,J＝8.4Hz,1H),6.66(s,1H),2.13(s,3H),2.09(s, 3H). 13 C{ 1 H}NMR(100MHz,CF 3 COOD):δ192.0,191.9,170.4,162.5,159.5(d, 1 J C-F ＝268.0Hz),142.5,141.8,140.5(d, 3 J C-F ＝8.0Hz),133.9,131.0,129.7,126.5(d, 2 J C-F ＝12.3Hz),126.2,125.0(d, 2 J C-F ＝18.7Hz),124.4,121.5(d, 4 J C-F ＝3.6Hz), 121.1,112.9,69.6,26.2,20.0. 19 FNMR(565MHz,CDCl 3 ):δ-109.67(dd, 1 J＝7.9 Hz, 2 J＝4.0Hz,).HRMS(ESI)m/z:[M+H] + Calcd for C 21 H 16 FN 2 O 3 363.1139； Found 363.1136.
4-Chloro-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dione (5v)
1 H NMR(600MHz,CF 3 COOD):δ8.24(dd,J 1 ＝6.6Hz,J 2 ＝1.8Hz,1H),8.12-8.08 (m,2H),7.95(s,1H),7.68(d,J＝7.8Hz,1H),7.63(t,J＝7.8Hz,1H),7.52(t,J＝ 7.8Hz,1H),6.84(d,J＝8.4Hz,1H),6.67(s,1H),2.14(s,3H),2.11(s,3H). 13 C{ 1 H} NMR(150MHz,CF 3 COOD):δ191.6,191.2,170.2,163.1,142.9,142.4,139.2, 138.1,135.7,134.6,133.9,131.0,129.8,126.2,124.4,123.7,121.2,112.7,69.5,26.3, 20.1.HRMS(ESI)m/z:[M+H] + Calcd for C 21 H 16 ClN 2 O 3 379.0844；Found 379.0837.
4-Bromo-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dione (5w)
1 H NMR(600MHz,CF 3 COOD):δ8.57(d,J＝7.8Hz,1H),8.54(d,J＝7.2Hz,1H), 8.25(t,J＝7.8Hz,1H),8.21(s,1H),7.94(d,J＝7.8Hz,1H),7.89(t,J＝7.8Hz,1H), 7.78(t,J＝7.8Hz,1H),7.09(d,J＝7.8Hz,1H),6.93(s,1H),2.40(s,3H),2.37(s,3 H). 13 C{ 1 H}NMR(150MHz,CF 3 COOD):δ191.5,191.0,170.2,163.2,143.0,142.8, 142.7,137.9,137.5,134.0,131.0,129.8,126.3,124.4,124.3,121.5,121.2,112.7, 69.5,26.4,20.1.HRMS(ESI)m/z:[M+H] + Calcd for C 21 H 16 BrN 2 O 3 423.0339； Found 423.0337.
4-Iodo-2'-(3-methylbut-2-enoyl)-2'H-spiro[indene-2,1'-phthalazine]-1,3-dione (5x)
1 H NMR(600MHz,CF 3 COOD):δ8.85(d,J＝7.8Hz,1H),8.53(d,J＝7.2Hz,1H), 8.17(s,1H),8.03(t,J＝7.2Hz,1H),7.90(d,J＝7.2Hz,1H),7.84(t,J＝7.2Hz,1H), 7.73(t,J＝7.8Hz,1H),7.02(d,J＝7.8Hz,1H),6.89(s,1H),2.36(s,3H),2.33(s, 3H). 13 C{ 1 H}NMR(150MHz,CF 3 COOD):δ192.7,191.0,170.2,162.9,149.7,142.8, 140.3,137.4,133.9,130.9,129.7,126.3,124.9,124.4,121.2,112.8,90.8,69.2,26.3, 20.1.HRMS(ESI)m/z:[M+H] + Calcd for C 21 H 16 IN 2 O 3 471.0200；Found 471.0201.
example 6
The pyrazolone [ spiro ] dihydrophthalazine compound 3 synthesized by the invention is subjected to a series of reactions, so as to synthesize a further derivative. For example:
to a solution of compound 3a (74.4 mg, 0.2mmol) MeOH/DCM (1.5 mL, 10/3) in a 25mL two-necked flask was added Pd/C (10 wt%,10 mg). The mixture is then left at room temperature H 2 (1 atm) was stirred in an atmosphere for 24 hours. After completion of the reaction, the reaction mixture was filtered through celite and concentrated under reduced pressure. The residue was separated by column on silica gel (petroleum ether/ethyl acetate = 10/1) to give product 6 (52.5mg, 70%) as a white solid. The characterization data for this compound are as follows: 1 H NMR(600MHz,CDCl 3 ):δ7.94(d,J＝7.8Hz,2H),7.42- 7.39(m,5H),7.32-7.31(m,1H),7.19(t,J＝7.2Hz,1H),7.05-7.03(m,1H),2.75- 2.68(m,2H),2.26-2.19(m,1H),1.95(s,3H),0.99(d,J＝2.4Hz,3H),0.97(d,J＝ 2.4Hz,3H). 13 C{ 1 H}NMR(100MHz,CDCl 3 ):δ174.4,171.6,158.7,138.1,136.8, 132.9,130.2,128.9,127.8,126.2,125.2,124.1,131.4,119.2,68.8,42.2,25.5,22.7, 13.4.HRMS(ESI)m/z:[M+H] + Calcd for C 22 H 23 N 4 O 2 375.1816；Found 375.1804.
to a 15mL pressure tube, compound 3f (45.1mg, 0.1mmol), DMSO (1 mL), pd (OAc) 2 (1.1mg,0.005mmol)、PPh 3 (5.2mg,0.02mmol)、K 3 PO 4 (25.5 mg,0.12 mmol) and phenylacetylene (16.5. Mu.L, 0.15 mmol), the reaction tube was sealed under argon and placed in a 80 ℃ block for reaction for 24h. After the reaction was completed, the reaction mixture was diluted with water and extracted with ethyl acetate (10 mL. Times.3). The organic phase was dried over anhydrous sodium sulfate, filtered with suction, dried by spinning, and separated by silica gel column (petroleum ether/ethyl acetate = 10/1) to obtain product 7 (33.6 mg, 71%) as a yellow solid. The characterization data for this compound are as follows: 1 H NMR(600MHz, CDCl 3 ):δ8.00(d,J＝7.8Hz,2H),7.55(dd,J 1 ＝7.8Hz,J 2 ＝1.2Hz,1H),7.50-7.49 (m,2H),7.44(t,J＝7.8Hz,2H),7.38(s,1H),7.34-7.33(m,3H),7.31(d,J＝8.4Hz, 1H),7.22(t,J＝7.2Hz,1H),7.16(s,1H),6.70(s,1H),2.11(s,3H),2.00(s,3H), 1.96(s,3H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ171.6,166.9,158.8,157.1,138.3, 135.4,133.3,131.8,129.0,128.9,128.4,128.0,127.4,127.1,126.6,125.2,122.3, 120.9,119.3,114.6,93.2,87.9,68.4,28.0,21.0,13.6.HRMS(ESI)m/z:[M+H] + Calcd for C 30 H 25 N 4 O 2 473.1972；Found 473.1954.
to a 15mL pressure resistant tube, compound 3f (45.1mg, 0.1mmol), phenol (14.1 mg, 0.15 mmol), N-dimethylglycinate hydrochloride (4.2mg, 0.03mmol), cs were added in this order 2 CO 3 (65.2 mg,0.2 mmol), cuI (1.9 mg, 0.01mmol) and 1,4-dioxane (1 mL), the reaction tube was sealed under argon and reacted at 90 ℃ for 24h. After completion of the reaction, the reaction mixture was diluted with water, extracted with ethyl acetate (10 mL. Times.3), and washed with water and brine. The organic phase was dried over anhydrous sodium sulfate, filtered with suction, dried by spinning, and separated by silica gel column (petroleum ether/ethyl acetate = 10/1) to obtain product 8 (30.1mg, 65%) as a yellow solid. The characterization data for this compound are as follows: 1 H NMR(600MHz,CDCl 3 ):δ7.83(d,J＝7.8Hz,2H),7.39(t,J＝7.8Hz,2H),7.34 (s,1H),7.31(t,J＝7.8Hz,2H),7.26(d,J＝7.8Hz,1H),7.20(t,J＝7.2Hz,1H), 7.14(t,J＝7.8Hz,1H),6.98(d,J＝7.2Hz,2H),6.90(dd,J 1 ＝8.4Hz,J 2 ＝1.8Hz,1 H),6.72-6.71(m,1H),6.69(d,J＝2.4Hz,1H),2.11(d,J＝1.2Hz,3H),1.97(s,3H) 1.96(d,J＝0.6Hz,3H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ171.6,167.0,161.7, 158.9,156.6,154.7,138.0,135.6,130.1,129.4,128.8,128.4,125.3,125.0,120.2, 119.6,118.3,116.3,114.7,113.1,68.7,28.0,21.0,13.4.HRMS(ESI)m/z:[M+H] + Calcd for C 28 H 25 N 4 O 3 465.1921；Found 465.1907.
to a 15mL pressure tube, compound 3f (45.1mg, 0.1mmol), styrene (11.5. Mu.L, 0.1 mmol), pd (dppf) Cl were added in that order 2 (7.3mg,0.01mmol)、Et 3 N (20.2 mg,0.2 mmol) and DMF (0.5 mL) were sealed under argon and placed in a block at 100 ℃ for reaction for 24h. After completion of the reaction, the reaction mixture was diluted with water and extracted with ethyl acetate (10 mL. Times.3). The organic phases were combined, dried over anhydrous sodium sulfate, filtered with suction, spun-dried, and separated by a silica gel column (petroleum ether/ethyl acetate = 10/1) to give product 9 (29.4 mg, 62%) as a pale yellow solid. The characterization data for this compound are as follows: 1 H NMR(600MHz,CDCl 3 ):δ 8.00(d,J＝7.8Hz,2H),7.59(dd,J 1 ＝7.8Hz,J 2 ＝1.2Hz,1H),7.46-7.43(m,4H), 7.38(s,1H),7.35-7.31(m,3H),7.27(t,J＝7.2Hz,1H),7.23(t,J＝7.2Hz,1H),7.08 -7.05(m,2H),6.97(d,J＝16.2Hz,1H),6.719-6.715(m,1H),2.12(d,J＝1.2Hz,3 H),2.00(s,3H),1.96(d,J＝0.6Hz,3H). 13 C{ 1 H}NMR(150MHz,CDCl 3 ):δ171.9, 167.0,159.2,156.7,142.0,138.3,136.3,135.9,131.8,129.0,128.8,128.5,127.9, 127.3,126.9,126.78,126.76,125.2,122.5,120.5,119.4,114.8,68.8,28.0,21.0,13.6. HRMS(ESI)m/z:[M+H] + Calcd for C 30 H 27 N 4 O 2 475.2129；Found 475.2118.
the foregoing embodiments have described the general principles, principal features and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are given by way of illustration of the principles of the present invention, and that various changes and modifications may be made without departing from the scope of the principles of the present invention, and such changes and modifications are within the scope of the present invention.
Claims (8)
1. Pyrazolone [ spiro ] dihydrophthalazine compound 3 and 1,3-indenedione [ spiro ] dihydrophthalazine compound 5 have the structural general formulas:
wherein: r 1 Is hydrogen, C 1-4 Alkyl radical, C 1-4 Alkoxy, halogen, trifluoromethyl, phenyl or substituted phenyl, wherein the substituent on the benzene ring of the substituted phenyl is C 1-4 Alkyl radical, C 1-4 Alkoxy, trifluoromethyl or halogen, R 1 Is mono-or di-substituted, R 2 Is phenyl, substituted phenyl or naphthyl, and the substituent on the benzene ring of the substituted phenyl is C 1-4 Alkyl radical, C 1-4 Alkoxy, trifluoromethyl or halogen, R 3 Is C 1-4 Alkyl radical, R 4 Is hydrogen, C 1-4 Alkyl or halogen.
2. The method for synthesizing the pyrazolone [ spiro ] dihydrophthalazine compound 3 and 1,3-indenedione [ spiro ] dihydrophthalazine compound 5 according to claim 1, comprising the steps of: taking aryl azomethine 1, diazo pyrazolone compound 2 or diazo-1,3-indandione compound 4 as raw materials, and heating to react in an organic solvent in the presence of a catalyst and an additive to obtain pyrazolone [ spiro ] dihydrophthalazine compound 3 or 1,3-indandione [ spiro ] dihydrophthalazine compound 5;
wherein: r 1 Is hydrogen, C 1-4 Alkyl radical, C 1-4 Alkoxy, halogen, trifluoromethyl, phenyl or substituted phenyl, wherein the substituent on the benzene ring of the substituted phenyl is C 1-4 Alkyl radical, C 1-4 Alkoxy, trifluoromethyl or halogen, R 1 Is mono-or di-substituted, R 2 Is phenyl, substituted phenyl or naphthyl, and the substituent on the benzene ring of the substituted phenyl is C 1-4 Alkyl radical, C 1-4 Alkoxy, trifluoromethyl or halogen, R 3 Is C 1-4 Alkyl radical, R 4 Is hydrogen, C 1-4 Alkyl or halogen.
3. The method for synthesizing the pyrazolone [ spiro ] dihydrophthalazine compound 3 and 1,3-indenedione [ spiro ] dihydrophthalazine compound 5 according to claim 2, characterized in that: the organic solvent is selected from acetonitrile, 1,2-dichloroethane, toluene or hexafluoroisopropanol.
4. The method for synthesizing the pyrazolone [ spiro ] dihydrophthalazine-based compound 3 and the 1,3-indenedione [ spiro ] dihydrophthalazine-based compound 5 according to claim 2, characterized in that: the additive is copper acetate, silver carbonate or silver acetate.
5. The pyrazolone [ spiro ] according to claim 2]Dihydrophthalazines 3 and 1,3-indenedione [ spiro]The synthesis method of the dihydrophthalazine compound 5 is characterized by comprising the following steps: the catalyst is CpRh (MeCN) 3 (SbF 6 ) 2 、[Cp*RhCl 2 ] 2 、Cp*Rh(OAc) 2 Or [ Cp IrCl ] 2 ] 2 。
6. The method for synthesizing the pyrazolone [ spiro ] dihydrophthalazine-based compound 3 and the 1,3-indenedione [ spiro ] dihydrophthalazine-based compound 5 according to claim 2, characterized in that: the aryl azomethine imine 1, the diazo pyrazolone compound 2 or the diazo-1,3-indandione compound 4, and the molar ratio of the catalyst to the additive is 1:1-2.025-0.05.
7. The method for synthesizing the pyrazolone [ spiro ] dihydrophthalazine-based compound 3 and 1,3-indenedione [ spiro ] dihydrophthalazine-based compound 5 according to any one of claims 2 to 6, characterized in that: the reaction temperature is 60-120 ℃.
8. The method for synthesizing the pyrazolone [ spiro ] dihydrophthalazine-based compound 3 and 1,3-indenedione [ spiro ] dihydrophthalazine-based compound 5 according to any one of claims 2 to 6, characterized in that: the reaction is carried out in air or an inert gas atmosphere.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210827565.1A CN115197228A (en) | 2022-07-13 | 2022-07-13 | Synthesis method of pyrazolone [ spiro ] dihydrophthalazine and 1,3-indenedione [ spiro ] dihydrophthalazine compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210827565.1A CN115197228A (en) | 2022-07-13 | 2022-07-13 | Synthesis method of pyrazolone [ spiro ] dihydrophthalazine and 1,3-indenedione [ spiro ] dihydrophthalazine compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115197228A true CN115197228A (en) | 2022-10-18 |
Family
ID=83582463
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210827565.1A Withdrawn CN115197228A (en) | 2022-07-13 | 2022-07-13 | Synthesis method of pyrazolone [ spiro ] dihydrophthalazine and 1,3-indenedione [ spiro ] dihydrophthalazine compounds |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115197228A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115785096A (en) * | 2022-11-22 | 2023-03-14 | 河南师范大学 | Method for high-selectivity synthesis of pyrazolone spirodihydroquinoline or pyrazolone spiroindoline compound |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020103211A1 (en) * | 2000-11-29 | 2002-08-01 | Cell Therapeutics, Inc. | Tricyclic fused xanthine compounds and their uses |
| US20060154944A1 (en) * | 2003-06-23 | 2006-07-13 | Kazuyuki Ohmoto | Novel tricyclic heterocycle compound |
| CN1934094A (en) * | 2004-03-05 | 2007-03-21 | 万有制药株式会社 | Diaryl-substituted five-membered heterocycle derivative |
| WO2008096746A1 (en) * | 2007-02-06 | 2008-08-14 | Takeda Pharmaceutical Company Limited | Spiro compound and use thereof |
-
2022
- 2022-07-13 CN CN202210827565.1A patent/CN115197228A/en not_active Withdrawn
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020103211A1 (en) * | 2000-11-29 | 2002-08-01 | Cell Therapeutics, Inc. | Tricyclic fused xanthine compounds and their uses |
| US20060154944A1 (en) * | 2003-06-23 | 2006-07-13 | Kazuyuki Ohmoto | Novel tricyclic heterocycle compound |
| CN1934094A (en) * | 2004-03-05 | 2007-03-21 | 万有制药株式会社 | Diaryl-substituted five-membered heterocycle derivative |
| WO2008096746A1 (en) * | 2007-02-06 | 2008-08-14 | Takeda Pharmaceutical Company Limited | Spiro compound and use thereof |
Non-Patent Citations (1)
| Title |
|---|
| YAN MING CHEN，ET AL.: "Three-Component Triple Organocascade Synthesis of Hexahydropyridazine Derivatives via a Sequential Michael/Amination/Cyclization Reaction", 《JOURNAL OF THE CHINESE CHEMICAL SOCIETY》, vol. 62, pages 843 - 846 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115785096A (en) * | 2022-11-22 | 2023-03-14 | 河南师范大学 | Method for high-selectivity synthesis of pyrazolone spirodihydroquinoline or pyrazolone spiroindoline compound |
| CN115785096B (en) * | 2022-11-22 | 2023-11-28 | 河南师范大学 | Method for synthesizing pyrazolone spiro dihydroquinoline or pyrazolone spiro indoline compound with high selectivity |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102358739B (en) | Synthetic method for imidazole[1,2-a]pyridine and 2-butyl-5-chloro-1H-imidazole-4-carboxaldehyde compounds | |
| CN115197228A (en) | Synthesis method of pyrazolone [ spiro ] dihydrophthalazine and 1,3-indenedione [ spiro ] dihydrophthalazine compounds | |
| CN110437124B (en) | Preparation method of indoloquinone derivative | |
| CN113185536B (en) | Synthesis method of pyrazolidone benzo 1, 3-oxygen-nitrogen hetero-compound | |
| CN114716361B (en) | Method for synthesizing chiral spiro indenone-pyrrole compound | |
| CN112500339B (en) | Synthesis method of 8-acylquinoline derivative | |
| CN105820174A (en) | Polysubstituted thienoindole derivative and preparation method thereof | |
| CN109134351B (en) | Synthesis method of S-3- (4-aminophenyl) piperidine | |
| CN109134342B (en) | Preparation method of 3, 4-disubstituted pyrrole | |
| CN109400629B (en) | Indole spirooxazine heterocyclic compound and preparation method thereof | |
| CN102464626B (en) | Method for preparing 5-(4-(N,N-diphenyl-amino) phenmethylene)-3-(2-phenethyl)-2,4-oxazolidinedione | |
| CN112174901A (en) | Synthesis method and anticancer activity of 1, 3-benzodiazepine compound | |
| CN107021968B (en) | The method of the polysubstituted organic photochemical catalyst catalyzing indole quinoline class compound oxidation dehydrogenation synthesis of indole class compound of BODIPY | |
| CN107531662B (en) | Synthesis method of nebivolol and intermediate compound thereof | |
| CN103435542B (en) | 2-biaryl-6-arylquinazoline and preparation method thereof | |
| CN111718363A (en) | Preparation method of borate compound | |
| CN114634427B (en) | Preparation method of indeno polycyclic compound containing spiro | |
| CN103242379A (en) | 2-ferrocenyl-arylquinoline and preparation method thereof | |
| CN114213431A (en) | Spiro [ benzo [ d ] [1,3] oxazine-isoquinoline dione ] compound and synthetic method thereof | |
| CN109810036B (en) | Synthesis method of 4-oxo-5- (arylformyl acetate-2-yl) naphthalene-sulfoxide ylide hybrid | |
| CN110872295A (en) | Method for synthesizing imidazo [1,2-a ] indole compound | |
| CN113717107B (en) | Synthesis method of N-acyl benzimidazole compound | |
| CN110467558B (en) | Reaction method for synthesizing 3-aminoisoindolinone under catalysis of nickel | |
| CN110372722B (en) | Method for synthesizing sulfur-nitrogen-containing bis-heterocyclic compound | |
| CN105949143A (en) | Synthesis method of diaryloxazepine ketone compound |
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 | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20221018 |