CN115124542A - Synthetic method of hydroxyphenyl-substituted pyrazolone indazole [ spiro ] pyrazolone compound - Google Patents
Synthetic method of hydroxyphenyl-substituted pyrazolone indazole [ spiro ] pyrazolone compound Download PDFInfo
- Publication number
- CN115124542A CN115124542A CN202210804999.XA CN202210804999A CN115124542A CN 115124542 A CN115124542 A CN 115124542A CN 202210804999 A CN202210804999 A CN 202210804999A CN 115124542 A CN115124542 A CN 115124542A
- Authority
- CN
- China
- Prior art keywords
- pyrazolone
- spiro
- substituted
- compound
- hydroxyphenyl
- 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- Withdrawn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
- -1 hydroxyphenyl-substituted pyrazolone indazole Chemical class 0.000 title claims abstract description 47
- 125000003003 spiro group Chemical group 0.000 title claims abstract description 27
- 238000010189 synthetic method Methods 0.000 title description 4
- 239000000654 additive Substances 0.000 claims abstract description 13
- 230000000996 additive effect Effects 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 13
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical class O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000003054 catalyst Substances 0.000 claims abstract description 9
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 8
- QCPORYSHAZPBCG-UHFFFAOYSA-N n-phenoxyacetamide Chemical compound CC(=O)NOC1=CC=CC=C1 QCPORYSHAZPBCG-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052703 rhodium Inorganic materials 0.000 claims abstract description 7
- 239000010948 rhodium Substances 0.000 claims abstract description 7
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229940125904 compound 1 Drugs 0.000 claims abstract description 5
- 229940125782 compound 2 Drugs 0.000 claims abstract description 5
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 238000001308 synthesis method Methods 0.000 claims abstract description 5
- 229940126214 compound 3 Drugs 0.000 claims abstract description 4
- 238000010438 heat treatment Methods 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 38
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 239000012298 atmosphere Substances 0.000 claims description 4
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 claims description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical group ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 2
- 229910018286 SbF 6 Inorganic materials 0.000 claims description 2
- ZOAIGCHJWKDIPJ-UHFFFAOYSA-M caesium acetate Chemical group [Cs+].CC([O-])=O ZOAIGCHJWKDIPJ-UHFFFAOYSA-M 0.000 claims description 2
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims description 2
- 229910000396 dipotassium phosphate Inorganic materials 0.000 claims description 2
- 235000019797 dipotassium phosphate Nutrition 0.000 claims description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 claims description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 claims description 2
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 claims description 2
- 235000011056 potassium acetate Nutrition 0.000 claims description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 2
- 235000011009 potassium phosphates Nutrition 0.000 claims description 2
- 239000007810 chemical reaction solvent Substances 0.000 claims 1
- 239000000758 substrate Substances 0.000 abstract description 4
- 238000010523 cascade reaction Methods 0.000 abstract description 3
- 238000005580 one pot reaction Methods 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 33
- 238000004009 13C{1H}-NMR spectroscopy Methods 0.000 description 31
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 28
- 239000011734 sodium Substances 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 238000009987 spinning Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000012300 argon atmosphere Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000010791 quenching Methods 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 150000003413 spiro compounds Chemical class 0.000 description 2
- 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 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- 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 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 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
- 230000007935 neutral effect Effects 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 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
- C07D487/12—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 three hetero rings
- C07D487/20—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention discloses a novel method for synthesizing hydroxybenzene-substituted pyrazolone indazole [ spiro ] pyrazolone compounds, belonging to the technical field of organic synthesis. Taking an N-phenoxyacetamide compound 1 and a diazopyrazolone compound 2 as raw materials, and heating in an organic solvent in the presence of a rhodium catalyst and an additive to react to obtain a hydroxyphenyl-substituted pyrazolone indazole [ spiro ] pyrazolone compound 3; the invention efficiently synthesizes the hydroxyphenyl-substituted pyrazolone indazole [ spiro ] pyrazolone compound through one-pot tandem reaction between the easily obtained N-phenoxy acetamide compound and diazo pyrazolone. The synthesis method has the advantages of simple and easily obtained raw materials, simple and convenient operation, wide substrate application range and the like.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a synthetic method of a hydroxybenzene-substituted pyrazolone indazole [ spiro ] pyrazolone compound.
Background
The spiro compound has higher rigidity and unique three-dimensional structure, and the introduction of the spiro can effectively improve the physical and chemical properties and the biological activity of a parent compound. Among the spiro compounds, indazole [ spiro ] pyrazolone has abundant and significant pharmaceutical activity and luminescence property, and thus is widely applied in the fields of pharmaceutical chemistry, pesticide chemistry, fine chemical chemistry and the like.
Although indazole [ spiro ] pyrazolone compounds have important application values, the existing synthetic method is very limited, and the defects of complicated steps, harsh conditions, poor functional group tolerance and the like exist.
Therefore, research and development of a novel method for synthesizing indazole [ spiro ] pyrazolone compounds by simple operation under relatively mild reaction conditions from cheap and easily available raw materials have important research significance.
Disclosure of Invention
The invention mainly provides a novel method for synthesizing hydroxyphenyl-substituted pyrazolone indazolo [ spiro ] pyrazolone compounds, which is characterized in that hydroxyphenyl-substituted pyrazolone indazolo [ spiro ] pyrazolone compounds are efficiently synthesized through one-pot tandem reaction between easily-obtained N-phenoxyacetamide compounds and diazo pyrazolone compounds. The synthesis method has the advantages of simple and easily obtained raw materials, simple and convenient operation, wide substrate application range and the like.
The structural general formula of the synthesized hydroxyphenyl-substituted pyrazolone indazole [ spiro ] pyrazolone compound is as follows:
wherein R is 1 Is hydrogen, C 1-6 Chain alkyl, C 1-4 Alkoxy, phenyl, substituted phenyl, C 1-4 Alkoxycarbonyl or halogen, the substituent on the phenyl ring of the substituted phenyl being C 1-4 Alkyl radical, C 1-4 Alkoxy, trifluoromethyl or halogen, R 1 Is mono-or di-substituted, R 2 Is hydrogen, C 1-6 Chain alkyl, 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 hydroxyphenyl-substituted pyrazolone indazole [ spiro ] pyrazolone compound, which adopts the following technical scheme:
the synthesis method of the hydroxybenzene-substituted pyrazolone indazole [ spiro ] pyrazolone compound comprises the following operations: taking an N-phenoxyacetamide compound 1 and a diazopyrazolone compound 2 as raw materials, and heating in an organic solvent in the presence of a rhodium catalyst and an additive to react to obtain a hydroxyphenyl-substituted pyrazolone indazole [ spiro ] pyrazolone compound 3; the reaction equation is:
wherein R is 1 Is hydrogen, C 1-6 Chain alkyl, C 1-4 Alkoxy, phenyl, substituted phenyl, C 1-4 Alkoxycarbonyl or halogen, the substituent on the phenyl ring of the substituted phenyl being C 1-4 Alkyl radical, C 1-4 Alkoxy, trifluoromethyl or halogen, R 1 Is mono-or di-substituted, R 2 Is hydrogen, C 1-6 Chain alkyl, 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 plays a role of dissolving the raw material, and 1, 2-dichloroethane, chloroform or dichloromethane is preferable.
Further, in the above technical scheme, the rhodium catalyst is dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer ([ RhCp Cl [ ] 2 ] 2 ) Or tris (acetonitrile) (pentamethylcyclopentadienyl) rhodium (III) bis (hexafluoroantimonate) ([ RhCp (MeCN) 3 ](SbF 6 ) 2 )。
Further, in the above technical solution, the additive is cesium acetate or cesium fluoride.
Further, in the above technical solution, the additive further comprises potassium phosphate, potassium dihydrogen phosphate, potassium hydrogen phosphate or potassium acetate.
Further, in the technical scheme, the molar ratio of the N-phenoxyacetamide compound 1, the diazopyrazolone compound 2, the rhodium catalyst and the additive is 1-1.2:1-3:0.02-0.07: 0.1-3.
Further, in the above technical solution, the reaction is performed in an air atmosphere; the reaction temperature is 40-70 ℃.
The invention has the beneficial effects that:
compared with the prior art, the invention has the following advantages: (1) through one-pot tandem reaction of N-phenoxyacetamide compounds and diazopyrazolone compounds, a spiroheterocyclic skeleton can be directly constructed from a simple and easily obtained substrate, and the synthetic process is simple and efficient; (2) the raw materials are cheap and easy to obtain; (3) the redox is neutral, no oxidant is needed, the operation is simple and convenient, and the application range of the substrate is wide.
Drawings
FIG. 1 is an X-ray single crystal diffractogram of Compound 3a in example 1.
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
Adding the compound 1a, the organic solvent, the catalyst, the additive 1 and/or the additive 2 and the compound 2a into a 15mL reaction tube in sequence, sealing the reaction tube under the air condition, and placing the reaction tube in a heating module to be heated and stirred for reaction. After the reaction is finished, cooling to room temperature, adding water to quench the reaction, extracting with dichloromethane, drying the organic phase, performing suction filtration, spin-drying, and separating by a silica gel column (petroleum ether/ethyl acetate: 5/1) to obtain a white solid product 3 a.
A series of results were obtained by varying the reaction conditions of the solvent, catalyst, additive 1, additive 2, reaction temperature and material ratio of the reaction, as shown in Table 1.
TABLE 1 Synthesis of 3a under different conditions a
Example 2
To a 15mL reaction tube, 1a (30.2mg,0.2mmol), dichloroethane (2mL), and [ RhCp. multidot. Cl were added in this order 2 ] 2 (3.1mg,0.005mmol)、CsOAc(38.4mg,0.2mmol)、K 3 PO 4 (42.5 mg,0.2mmol) and 2a (88.1mg,0.44mmol), the reaction tube was sealed under an air atmosphere and placed in a 50 ℃ reaction block to stir for 24 h. After the reaction, the reaction system was cooled to room temperature, water was added to quench the reaction, the mixture was extracted with dichloromethane, the organic phase was dried, filtered under suction, dried by spinning, and separated by a silica gel column (petroleum ether/ethyl acetate: 5/1) to obtain a white solid product 3a (56.7mg, 65%). 1 H NMR(CDCl 3 ,400 MHz):δ9.55(s,1H),7.96-7.92(m,3H),7.57(td,J 1 ＝8.0Hz,J 2 ＝1.2Hz,1H),7.51 -7.46(m,2H),7.32-7.22(m,3H),7.14(d,J＝7.6Hz,1H),7.12-7.07(m,2H),6.91 (td,J 1 ＝7.6Hz,J 2 ＝1.2Hz,1H),2.22(s,3H),2.11(s,3H). 13 C{ 1 H}NMR(CDCl 3 , 150MHz):δ166.4,159.6,156.4,156.0,143.9,137.2,134.7,131.9,129.3,129.2, 129.0,126.3,126.2,125.9,122.2,120.1,119.8,118.7,118.4,113.4,112.9,74.4,13.6, 11.8.HRMS(ESI)m/z:[M+H] + Calcd for C 26 H 21 N 4 O 3 437.1608；Found 437.1604.
Example 3
Method and procedure according to example 2 a,b Various hydroxyphenyl-substituted pyrazolone indazoles [ spiro ] can be synthesized by changing the reactant 1 and the reactant 2]The pyrazolone compound 3a-3aa has the following specific results:
a reaction conditions 1a (0.2mmol),2a (0.44mmol), [ RhCp. multidot. Cl 2 ] 2 (0.005mmol),K 3 PO 4 (0.2mmol), CsOAc (0.2mmol), dichloroethane (2mL),50 ℃,24h, air atmosphere; b the isolation yield.
Representative product characterization data are as follows:
2'-(2-Hydroxy-5-methylphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4,9'-p yrazolo[1,2-a]indazole]-3',5(1H)-dione(3b)
1 H NMR(DMSO-d 6 ,400MHz):δ9.36(s,1H),7.85(d,J＝7.6Hz,2H),7.72(d,J＝ 8.0Hz,1H),7.63(t,J＝8.0Hz,1H),7.52(t,J＝8.0Hz,2H),7.43(d,J＝8.0Hz,1H), 7.35-7.28(m,2H),7.03-6.97(m,2H),6.81(d,J＝8.0Hz,1H),2.22(s,3H),2.13(s, 3H),1.97(s,3H). 13 C{ 1 H}NMR(DMSO-d 6 ,100MHz):δ167.4,161.0,157.9,153.1, 148.8,137.3,135.5,132.2,132.0,129.9,129.8,127.8,126.7,126.4,126.2,123.7, 119.6,117.2,116.5,112.6,111.7,74.6,20.5,13.8,12.3.HRMS(ESI)m/z:[M+Na] + Calcd for C 27 H 22 N 4 NaO 3 473.1584；Found 473.1569.
2'-(2-Hydroxy-5-isopropylphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4,9 '-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3c)
1H NMR(CDCl 3 ,400MHz):δ9.30(s,1H),7.96-7.91(m,3H),7.56(t,J＝7.6Hz, 1H),7.48(t,J＝8.4Hz,2H),7.32-7.24(m,2H),7.14(d,J＝7.6Hz,1H),7.10(dd,J 1 ＝8.4Hz,J 2 ＝2.0Hz,1H),7.00(d,J＝8.4Hz,1H),6.94(d,J＝2.0Hz,1H), 2.88-2.81(m,1H),2.23(s,3H),2.10(s,3H),1.21(d,J＝7.2Hz,6H).13C{1H} NMR(CDCl 3 ,100MHz):δ166.4,159.6,156.5,153.9,143.8,140.4,137.2,134.7, 131.9,129.3,127.3,126.9,126.3,126.1,125.9,122.2,119.5,118.7,117.9,113.4, 113.2,74.3,33.3,24.3,24.2,13.6,11.9.HRMS(ESI)m/z:[M+Na]+Calcd for C 29 H 26 N 4 NaO 3 501.1897；Found 501.1879.
2'-(5-(tert-Butyl)-2-hydroxyphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4, 9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3d)
1 H NMR(CDCl 3 ,600MHz):δ9.37(s,1H),7.96-7.92(m,3H),7.57(t,J＝7.8Hz, 1H),7.48(t,J＝7.8Hz,2H),7.31-7.27(m,3H),7.14(d,J＝7.8Hz,1H),7.09(d,J＝ 2.4Hz,1H),7.01(d,J＝8.4Hz,1H),2.24(s,3H),2.10(s,3H),1.29(s,9H). 13 C{ 1 H} NMR(CDCl 3 ,150MHz):δ166.4,159.5,156.5,153.6,143.7,142.6,137.2,134.7, 131.9,129.3,126.3,126.2,126.1,126.0,125.9,122.2,119.1,118.7,117.5,113.40, 113.38,74.3,34.1,31.6,13.6,11.9.HRMS(ESI)m/z:[M+Na] + Calcd for C 30 H 28 N 4 NaO 3 515.2054；Found 515.2041.
2'-(4-Hydroxy-[1,1'-biphenyl]-3-yl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4, 9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3e)
1 H NMR(CDCl 3 ,600MHz):δ9.69(s,1H),7.95-7.92(m,3H),7.57(t,J＝7.8Hz, 1H),7.51(d,J＝7.2Hz,2H),7.48-7.46(m,3H),7.39(t,J＝7.8Hz,2H),7.31-7.25 (m,4H),7.15-7.13(m,2H),2.27(s,3H),2.11(s,3H). 13 C{ 1 H}NMR(CDCl 3 ,100 MHz):δ166.4,159.5,156.4,155.7,143.9,140.9,137.2,134.6,133.3,131.9,129.3, 128.8,128.0,127.7,126.8,126.7,126.4,126.2,125.9,122.3,120.1,118.7,118.6, 113.4,112.7,74.4,13.6,12.0.HRMS(ESI)m/z:[M+Na] + Calcd for C 32 H 24 N 4 NaO 3 535.1741；Found 535.1716.
2'-(5-Fluoro-2-hydroxyphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4,9'-p yrazolo[1,2-a]indazole]-3',5(1H)-dione(3f)
1 H NMR(CDCl 3 ,400MHz):δ9.40(s,1H),7.96-7.91(m,3H),7.58(td,J 1 ＝8.0Hz, J 2 ＝1.2Hz,1H),7.50-7.46(m,2H),7.32-7.28(m,2H),7.15(d,J＝7.6Hz,1H), 7.03-6.99(m,1H),6.93(td,J 1 ＝8.8Hz,J 2 ＝2.8Hz,1H),6.80(dd,J 1 ＝9.6Hz,J 2 ＝ 3.2Hz,1H),2.23(s,3H),2.11(s,3H). 13 C{ 1 H}NMR(CDCl 3 ,150MHz):δ166.2, 159.1,156.5(d, 1 J C-F ＝236.3Hz),156.2,152.1(d, 4 J C-F ＝2.3Hz),143.8,137.1,134.5, 131.9,129.3,126.4,126.3,125.8,122.2,120.7(d, 3 J C-F ＝8.9Hz),119.3(d, 3 J C-F ＝8.7 Hz),118.7,115.6(d, 2 J C-F ＝23.0Hz),114.7(d, 2 J C-F ＝23.1Hz),113.4,111.9,74.4, 13.6,11.7. 19 F NMR(376MHz,CDCl 3 )δ:-124.59--124.65.HRMS(ESI)m/z: [M+Na] + Calcd for C 26 H 19 FN 4 NaO 3 477.1333；Found 477.1313.
2'-(5-Chloro-2-hydroxyphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4,9'-p yrazolo[1,2-a]indazole]-3',5(1H)-dione(3g)
1 H NMR(CDCl 3 ,400MHz):δ9.69(s,1H),7.95-7.91(m,3H),7.58(td,J 1 ＝8.0Hz, J 2 ＝1.2Hz,1H),7.50-7.46(m,2H),7.33-7.26(m,2H),7.19-7.14(m,2H),7.06(d,J ＝2.4Hz,1H),7.00(d,J＝8.8Hz,1H),2.24(s,3H),2.12(s,3H). 13 C{ 1 H}NMR (CDCl 3 ,100MHz):δ166.2,159.1,156.2,154.8,143.8,137.1,134.5,131.9,129.3, 128.9,128.2,126.4,126.3,125.8,124.7,122.2,121.1,119.9,118.7,113.4,111.6,74.4, 13.6,11.8.HRMS(ESI)m/z:[M+Na] + Calcd for C 26 H 19 ClN 4 NaO 3 493.1038；Found 493.1019.
2'-(5-Bromo-2-hydroxyphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4,9'-p yrazolo[1,2-a]indazole]-3',5(1H)-dione(3h)
1 H NMR(CDCl 3 ,400MHz):δ9.72(s,1H),7.95-7.91(m,3H),7.60-7.56(m,1H), 7.50-7.46(m,2H),7.32-7.26(m,3H),7.20(d,J＝2.4Hz,1H),7.15(d,J＝7.6Hz, 1H),6.94(d,J＝8.8Hz,1H),2.24(s,3H),2.12(s,3H). 13 C{ 1 H}NMR(CDCl 3 ,100 MHz):δ166.2,159.1,156.2,155.3,143.8,137.1,134.5,131.9,131.8,131.1,129.3, 126.4,126.3,125.8,122.3,121.6,120.5,118.7,113.4,111.9,111.5,74.4,13.6,11.7. HRMS(ESI)m/z:[M+Na] + Calcd for C 26 H 19 BrN 4 NaO 3 537.0533；Found 537.0522.
2'-(2-Hydroxy-5-iodophenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4,9'-pyr azolo[1,2-a]indazole]-3',5(1H)-dione(3i)
1 H NMR(CDCl 3 ,400MHz):δ9.76(s,1H),7.95-7.91(m,3H),7.60-7.56(m,1H), 7.51-7.47(m,3H),7.38(d,J＝2.0Hz,1H),7.33-7.29(m,2H),7.15(d,J＝8.0Hz, 1H),6.83(d,J＝8.8Hz,1H),2.23(s,3H),2.12(s,3H). 13 C{ 1 H}NMR(CDCl 3 ,100 MHz):δ166.2,159.1,156.2,156.1,143.7,137.7,137.1,134.5,131.9,129.3,126.4, 126.3,125.8,122.2,122.1,121.2,118.7,113.4,111.3,81.6,74.4,13.6,11.7.HRMS (ESI)m/z:[M+Na] + Calcd for C 26 H 19 IN 4 NaO 3 585.0394；Found 585.0378.
Ethyl 3-(1',3-dimethyl-3',5-dioxo-1-phenyl-1,5-dihydro-3'H-spiro[pyrazole-4,9'-p yrazolo[1,2-a]indazol]-2'-yl)-4-hydroxybenzoate(3j)
1 H NMR(CDCl 3 ,400MHz):δ10.5(s,1H),7.96-7.90(m,4H),7.86(d,J＝2.0Hz, 1H),7.59(td,J 1 ＝8.0Hz,J 2 ＝0.8Hz,1H),7.50-7.46(m,2H),7.32-7.27(m,2H), 7.16(d,J＝8.0Hz,1H),7.06(d,J＝8.4Hz,1H),4.33(q,J＝7.2Hz,2H),2.27(s, 3H),2.13(s,3H),1.36(t,J＝7.2Hz,3H). 13 C{ 1 H}NMR(CDCl 3 ,100MHz):δ166.4, 166.2,160.6,159.3,156.2,143.9,137.1,134.4,131.9,130.9,130.7,129.3,126.44, 126.37,125.8,122.3,122.2,119.5,118.7,118.2,113.4,111.8,74.4,60.7,14.4,13.6, 11.8.HRMS(ESI)m/z:[M+Na] + Calcd for C 29 H 24 N 4 NaO 5 531.1639；Found 531.1626.
2'-(2-Hydroxy-4-methylphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4,9'-p yrazolo[1,2-a]indazole]-3',5(1H)-dione(3k)
1 H NMR(CDCl 3 ,400MHz):δ9.48(s,1H),7.95-7.91(m,3H),7.56(t,J＝7.6Hz, 1H),7.47(t,J＝8.4Hz,2H),7.31-7.25(m,2H),7.13(d,J＝7.6Hz,1H),6.98(d,J＝ 7.6Hz,1H),6.90(s,1H),6.73(d,J＝8.0Hz,1H),2.32(s,3H),2.20(s,3H),2.09(s, 3H). 13 C{ 1 H}NMR(CDCl 3 ,150MHz):δ166.5,159.7,156.5,155.9,143.7,139.5, 137.2,134.7,131.8,129.3,128.8,126.3,126.1,125.9,122.2,121.0,120.3,118.7, 115.3,113.4,113.0,74.4,21.2,13.6,11.8.HRMS(ESI)m/z:[M+Na] + Calcd for C 27 H 22 N 4 NaO 3 473.1584；Found 473.1567.
2'-(2-Hydroxy-4-isopropylphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4,9 '-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3l)
1 H NMR(CDCl 3 ,400MHz):δ9.50(s,1H),7.95-7.91(m,3H),7.56(t,J＝8.0Hz, 1H),7.47(t,J＝8.0Hz,2H),7.31-7.23(m,2H),7.12(d,J＝7.6Hz,1H),7.02(d,J＝ 7.6Hz,1H),6.96(d,J＝1.6Hz,1H),6.78(dd,J 1 ＝8.0Hz,J 2 ＝1.2Hz,1H), 2.90-2.84(m,1H),2.21(s,3H),2.09(s,3H),1.25(d,J＝6.8Hz,6H). 13 C{ 1 H}NMR (CDCl 3 ,150MHz):δ166.5,159.8,156.5,155.9,150.5,143.8,137.2,134.7,131.8, 129.3,128.8,126.3,126.1,125.9,122.2,118.7,118.5,117.6,115.6,113.4,113.0,74.4, 33.8,23.84,23.82,13.6,11.9.HRMS(ESI)m/z:[M+Na] + Calcd for C 29 H 26 N 4 NaO 3 501.1897；Found 501.1881.
2'-(3-Hydroxy-[1,1'-biphenyl]-4-yl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4, 9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3m)
1 H NMR(CDCl 3 ,400MHz):δ9.77(s,1H),7.96-7.92(m,3H),7.63-7.61(m,2H), 7.59-7.55(m,1H),7.48(t,J＝8.4Hz,2H),7.42(t,J＝7.6Hz,2H),7.34-7.25(m, 4H),7.17-7.13(m,3H),2.25(s,3H),2.10(s,3H). 13 C{ 1 H}NMR(CDCl 3 ,100MHz): δ166.4,159.6,156.4,156.3,143.8,142.1,140.4,137.2,134.6,131.9,129.3,129.27, 128.8,127.4,127.0,126.4,126.2,125.9,122.2,118.8,118.7,118.2,117.4,113.4, 112.6,74.4,13.6,11.9.HRMS(ESI)m/z:[M+Na] + Calcd for C 32 H 24 N 4 NaO 3 535.1741； Found 535.1720.
2'-(4-Bromo-2-hydroxyphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4,9'-p yrazolo[1,2-a]indazole]-3',5(1H)-dione(3n)
1 H NMR(CDCl 3 ,400MHz):δ9.97(s,1H),7.95-7.90(m,3H),7.58(t,J＝7.6Hz, 1H),7.48(t,J＝8.4Hz,2H),7.32-7.23(m,3H),7.15(d,J＝8.0Hz,1H),7.03(dd,J 1 ＝8.4Hz,J 2 ＝2.0Hz,1H),6.95(d,J＝8.0Hz,1H),2.20(s,3H),2.11(s,3H). 13 C{ 1 H} NMR(CDCl 3 ,100MHz):δ166.2,159.2,157.1,156.2,143.6,137.1,134.5,131.9, 129.7,129.3,126.4,126.3,125.8,123.1,123.0,122.3,122.2,118.7,117.5,113.4, 112.0,74.4,13.6,11.8.HRMS(ESI)m/z:[M+Na] + Calcd for C 26 H 19 BrN 4 NaO 3 537.0533；Found 537.0526.
2'-(2-Hydroxy-4,5-dimethylphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4, 9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3o)
1 H NMR(CDCl 3 ,600MHz):δ9.23(s,1H),7.95(d,J＝8.4Hz,2H),7.91(d,J＝8.4 Hz,1H),7.55(t,J＝7.8Hz,1H),7.48(t,J＝7.8Hz,2H),7.31-7.24(m,2H),7.13(d, J＝7.8Hz,1H),6.87(s,1H),6.85(s,1H),2.23(s,3H),2.21(s,3H),2.18(s,3H), 2.10(s,3H). 13 C{ 1 H}NMR(CDCl 3 ,150MHz):δ166.5,159.8,156.6,153.8,143.7, 137.8,137.2,134.8,131.8,129.8,129.3,127.9,126.3,126.0,125.9,122.2,120.8, 118.7,115.4,113.4,113.0,74.4,19.6,18.9,13.6,11.9.HRMS(ESI)m/z:[M+Na] + Calcd for C 28 H 24 N 4 NaO 3 487.1741；Found 487.1721.
2'-(2-Hydroxy-3-methylphenyl)-1',3-dimethyl-1-phenyl-3'H-spiro[pyrazole-4,9'-p yrazolo[1,2-a]indazole]-3',5(1H)-dione(3p)
1 H NMR(CDCl 3 ,600MHz):δ9.40(s,1H),7.95-7.92(m,3H),7.57(t,J＝7.8Hz, 1H),7.48(t,J＝8.4Hz,2H),7.30(t,J＝7.8Hz,1H),7.27-7.25(m,1H),7.14-7.11 (m,2H),6.94(d,J＝7.2Hz,1H),6.82(t,J＝7.8Hz,1H),2.33(s,3H),2.20(s,3H), 2.09(s,3H). 13 C{ 1 H}NMR(CDCl 3 ,100MHz):δ166.4,159.6,156.5,154.2,144.0, 137.2,134.7,131.8,130.4,129.3,128.6,126.8,126.3,126.1,125.9,122.2,119.7, 118.7,117.8,113.4,113.2,74.4,16.7,13.6,11.8.HRMS(ESI)m/z:[M+Na] + Calcd for C 27 H 22 N 4 NaO 3 473.1584；Found 473.1564.
2'-(2-Hydroxyphenyl)-1',3,7'-trimethyl-1-(p-tolyl)-3'H-spiro[pyrazole-4,9'-pyrazo lo[1,2-a]indazole]-3',5(1H)-dione(3q)
1 H NMR(CDCl 3 ,400MHz):δ9.67(s,1H),7.84-7.78(m,3H),7.35(dd,J 1 ＝8.0Hz, J 2 ＝0.4Hz,1H),7.28(d,J＝8.4Hz,2H),7.25-7.21(m,1H),7.11-7.06(m,2H), 6.92-6.88(m,2H),2.39(s,3H),2.37(s,3H),2.20(s,3H),2.08(s,3H). 13 C{ 1 H} NMR(CDCl 3 ,100MHz):δ166.3,159.3,156.4,156.1,143.4,136.6,136.2,134.8, 132.5,132.4,129.8,129.1,129.0,126.1,122.5,120.0,119.8,118.7,118.5,113.1, 112.8,74.3,21.2,21.0,13.6,11.7.HRMS(ESI)m/z:[M+Na] + Calcd for C 28 H 24 N 4 Na O 3 487.1741；Found 487.1721.
7'-Ethyl-1-(4-ethylphenyl)-2'-(2-hydroxyphenyl)-1',3-dimethyl-3'H-spiro[pyrazol e-4,9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3r)
1 H NMR(CDCl 3 ,600MHz):δ9.69(s,1H),7.87(d,J＝8.4Hz,2H),7.81(d,J＝8.4 Hz,1H),7.38(d,J＝7.8Hz,1H),7.31(d,J＝8.4Hz,2H),7.23-7.20(m,1H), 7.11-7.05(m,2H),6.91-6.88(m,2H),2.71-2.63(m,4H),2.20(s,3H),2.08(s,3H), 1.26(t,J＝7.8Hz,3H),1.21(t,J＝7.8Hz,3H). 13 C{ 1 H}NMR(CDCl 3 ,150MHz):δ 166.4,159.3,156.4,156.1,143.5,143.0,142.6,135.0,132.6,131.3,129.1,129.0, 128.6,126.1,121.3,120.0,119.7,118.8,118.5,113.2,112.7,74.4,28.6,28.5,15.7, 15.5,13.6,11.7.HRMS(ESI)m/z:[M+H] + Calcd for C 30 H 29 N 4 O 3 493.2234；Found 493.2214.
7'-(tert-Butyl)-1-(4-(tert-butyl)phenyl)-2'-(2-hydroxyphenyl)-1',3-dimethyl-3'H-sp iro[pyrazole-4,9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3s)
1 H NMR(CDCl 3 ,400MHz):δ9.68(s,1H),7.90(d,J＝8.8Hz,2H),7.82(d,J＝8.4 Hz,1H),7.59(dd,J 1 ＝8.4Hz,J 2 ＝1.6Hz,1H),7.51(d,J＝8.8Hz,2H),7.24-7.20 (m,1H),7.11-7.04(m,3H),6.92-6.88(m,1H),2.20(s,3H),2.08(s,3H),1.36(s,9H), 1.29(s,9H). 13 C{ 1 H}NMR(CDCl 3 ,150MHz):δ166.4,159.3,156.5,156.1,150.3, 149.5,143.6,134.8,132.4,129.1,129.06,129.02,126.2,125.9,120.2,119.8,118.61, 118.55,118.51,112.9,112.8,74.5,35.1,34.7,31.4,31.3,13.6,11.7.HRMS(ESI)m/z: [M+Na] + Calcd for C 34 H 36 N 4 NaO 3 571.2680；Found 571.2661.
2'-(2-Hydroxyphenyl)-7'-methoxy-1-(4-methoxyphenyl)-1',3-dimethyl-3'H-spiro[ pyrazole-4,9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3t)
1 H NMR(CDCl 3 ,400MHz):δ9.71(s,1H),7.84-7.82(m,3H),7.25-7.21(m,1H), 7.11-7.06(m,3H),7.01-6.98(m,2H),6.92-6.88(m,1H),6.64(d,J＝2.4Hz,1H), 3.85(s,3H),3.81(s,3H),2.20(s,3H),2.09(s,3H). 13 C{ 1 H}NMR(CDCl 3 ,100 MHz):δ166.0,159.2,158.3,157.9,156.3,156.1,143.2,130.4,129.1,129.0,128.4, 127.2,120.5,120.0,119.8,118.5,116.5,114.4,114.2,112.9,108.4,74.3,56.1,55.6, 13.6,11.7.HRMS(ESI)m/z:[M+Na] + Calcd for C 28 H 24 N 4 NaO 5 519.1639；Found 519.1619.
7'-Fluoro-1-(4-fluorophenyl)-2'-(2-hydroxyphenyl)-1',3-dimethyl-3'H-spiro[pyra zole-4,9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3u)
1 H NMR(CDCl 3 ,400MHz):δ9.39(s,1H),7.94-7.88(m,3H),7.32-7.22(m,2H), 7.19-7.15(m,2H),7.11-7.06(m,2H),6.94-6.87(m,2H),2.20(s,3H),2.14(s,3H). 13 C{ 1 H}NMR(CDCl 3 ,100MHz):δ165.8,160.6(d, 1 J C-F ＝245.5Hz),160.5(d, 1 J C-F ＝247.0Hz),159.8,156.2,156.0,144.5,133.1(d, 4 J C-F ＝2.9Hz),131.2(d, 4 J C-F ＝2.2 Hz),129.4,129.0,127.1(d, 3 J C-F ＝8.6Hz),120.5(d, 3 J C-F ＝8.7Hz),120.2,119.8, 119.0(d, 2 J C-F ＝23.8Hz),118.1,116.2(d, 2 J C-F ＝23.1Hz),114.6(d, 3 J C-F ＝8.0Hz), 113.3,110.2(d, 2 J C-F ＝26.7Hz),74.2(d, 4 J C-F ＝2.9Hz),13.7,11.8. 19 F NMR(376 MHz,CDCl 3 )δ:-113.51--113.56(m),-114.63--114.70(m).HRMS(ESI)m/z: [M+Na] + Calcd for C 26 H 18 F 2 N 4 NaO 3 495.1239；Found 495.1223.
7'-Chloro-1-(4-chlorophenyl)-2'-(2-hydroxyphenyl)-1',3-dimethyl-3'H-spiro[pyra zole-4,9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3v)
1 H NMR(CDCl 3 ,400MHz):δ9.28(s,1H),7.93-7.90(m,2H),7.86(d,J＝8.4Hz, 1H),7.55(dd,J 1 ＝8.4Hz,J 2 ＝2.0Hz,1H),7.46-7.43(m,2H),7.27-7.23(m,1H), 7.11-7.06(m,3H),6.92(td,J 1 ＝7.6Hz,J 2 ＝1.2Hz,1H),2.19(s,3H),2.15(s,3H). 13 C{ 1 H}NMR(CDCl 3 ,100MHz):δ165.8,159.9,156.3,155.9,144.7,135.5,133.3, 132.2,131.8,131.7,129.5,129.4,129.1,127.1,122.6,120.2,119.9,119.8,118.0, 114.3,113.4,74.1,13.7,11.9.HRMS(ESI)m/z:[M+Na] + Calcd for C 26 H 18 Cl 2 N 4 Na O 3 527.0648；Found 527.0633.
7'-Bromo-1-(4-bromophenyl)-2'-(2-hydroxyphenyl)-1',3-dimethyl-3'H-spiro[pyra zole-4,9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3w)
1 H NMR(CDCl 3 ,400MHz):δ9.26(s,1H),7.86(d,J＝8.8Hz,2H),7.80(d,J＝8.8 Hz,1H),7.70(dd,J 1 ＝8.8Hz,J 2 ＝2.0Hz,1H),7.60(d,J＝8.8Hz,2H),7.27-7.24 (m,2H),7.10-7.06(m,2H),6.94-6.90(m,1H),2.19(s,3H),2.14(s,3H). 13 C{ 1 H} NMR(CDCl 3 ,100MHz):δ165.8,159.9,156.4,155.9,144.7,136.0,135.1,133.7, 132.4,129.5,129.1,127.4,125.4,120.2,120.1,119.9,119.5,118.8,118.0,114.7, 113.4,74.0,13.7,11.9.HRMS(ESI)m/z:[M+Na] + Calcd for C 26 H 18 Br 2 N 4 NaO 3 614.9638；Found 614.9632.
2'-(2-Hydroxyphenyl)-1',3-dimethyl-7'-(trifluoromethyl)-1-(4-(trifluoromethyl)p henyl)-3'H-spiro[pyrazole-4,9'-pyrazolo[1,2-a]indazole]-3',5(1H)-dione(3x)
1 H NMR(CDCl 3 ,400MHz):δ9.03(s,1H),8.13(d,J＝8.8Hz,2H),8.04(d,J＝8.4 Hz,1H),7.88(d,J＝8.4Hz,1H),7.75(d,J＝8.4Hz,2H),7.35(s,1H),7.29-7.24(m, 1H),7.12-7.07(m,2H),6.94(td,J 1 ＝7.6Hz,J 2 ＝1.2Hz,1H),2.22(s,3H),2.19(s, 3H). 13 C{ 1 H}NMR(CDCl 3 ,150MHz):δ166.1,160.2,156.6,155.9,145.8,139.6, 137.1,129.9(q, 3 J C-F ＝4.4Hz),129.7,129.1,128.6(q, 2 J C-F ＝32.9Hz),128.3(q, 2 J C-F ＝32.9Hz),126.6(q, 3 J C-F ＝4.4Hz),126.2,123.8(q, 1 J C-F ＝270.1Hz),123.2(q, 1 J C-F ＝270.1Hz),120.4,119.9,119.6(q, 3 J C-F ＝4.4Hz),118.4,117.7,113.63,113.61, 74.2,13.8,12.0. 19 F NMR(376MHz,CDCl 3 )δ:-61.82(s),-62.39(s).HRMS(ESI) m/z:[M+Na] + Calcd for C 28 H 18 F 6 N 4 NaO 3 595.1175；Found 595.1166.
2'-(2-Hydroxyphenyl)-1',3,6'-trimethyl-1-(m-tolyl)-3'H-spiro[pyrazole-4,9'-pyraz olo[1,2-a]indazole]-3',5(1H)-dione(3y)
1 H NMR(DMSO-d 6 ,400MHz):δ9.63(s,1H),7.67-7.63(m,2H),7.56(s,1H),7.39 (t,J＝8.0Hz,1H),7.27(d,J＝8.0Hz,1H),7.23-7.10(m,4H),6.91(d,J＝8.0Hz, 1H),6.86(t,J＝7.6Hz,1H),2.43(s,3H),2.37(s,3H),2.11(s,3H),1.96(s,3H). 13 C{ 1 H}NMR(CDCl 3 ,100MHz):δ166.4,159.4,156.4,156.1,143.6,142.9,139.4, 137.2,134.7,129.2,129.1,129.0,127.1,126.9,123.1,121.8,120.0,119.8,119.3, 118.4,115.9,113.9,112.7,74.2,21.7,21.6,13.5,11.7.HRMS(ESI)m/z:[M+Na] + Calcd for C 28 H 24 N 4 NaO 3 487.1741；Found 487.1725.
2-(2-Hydroxyphenyl)-1,3'-dimethyl-1'-(naphthalen-2-yl)-3H-spiro[benzo[f]pyraz olo[1,2-a]indazole-11,4'-pyrazole]-3,5'(1'H)-dione(3z)
1 H NMR(CDCl 3 ,400MHz):δ8.46(d,J＝2.0Hz,1H),8.31(s,1H),8.18-8.15(m, 1H),7.98-7.95(m,2H),7.89(t,J＝7.6Hz,2H),7.79(d,J＝8.0Hz,1H),7.66(s,1H), 7.63-7.59(m,1H),7.56-7.49(m,3H),7.27-7.23(m,1H),7.15-7.09(m,2H),6.93(td, J 1 ＝7.6Hz,J 2 ＝1.2Hz,1H),2.28(s,3H),2.18(s,3H). 13 C{ 1 H}NMR(CDCl 3 ,100 MHz):δ166.7,159.3,156.9,156.1,143.4,134.75,134.71,133.4,131.5,131.0,130.9, 129.4,129.3,129.0,128.6,128.51,128.47,128.1,127.8,127.1,126.7,126.2,126.1, 122.6,120.1,119.9,118.4,117.7,116.3,113.1,110.3,73.9,13.7,11.8.HRMS(ESI) m/z:[M+Na] + Calcd for C 34 H 24 N 4 NaO 3 559.1741；Found 559.1736.
1',3-Diethyl-2'-(2-hydroxyphenyl)-1-phenyl-3'H-spiro[pyrazole-4,9'-pyrazolo[1,2- a]indazole]-3',5(1H)-dione(3aa)
1 H NMR(CDCl 3 ,400MHz):δ9.50(s,1H),7.98-7.92(m,3H),7.55(td,J 1 ＝8.0Hz, J 2 ＝1.2Hz,1H),7.48(t,J＝8.4Hz,2H),7.32-7.22(m,3H),7.16-7.11(m,2H),7.07 (dd,J 1 ＝8.4Hz,J 2 ＝1.2Hz,1H),6.91(td,J 1 ＝7.6Hz,J 2 ＝1.2Hz,1H),2.60-2.48 (m,2H),2.44-2.36(m,1H),2.33-2.23(m,1H),1.24-1.16(m,6H). 13 C{ 1 H}NMR (CDCl 3 ,100MHz):δ166.8,160.9,159.9,155.9,150.0,137.3,134.4,131.7,129.30, 129.27,128.6,126.5,126.3,126.1,122.1,120.2,119.8,118.8,118.6,113.4,112.2, 74.4,21.6,19.5,12.6,9.3.HRMS(ESI)m/z:[M+Na] + Calcd for C 28 H 24 N 4 NaO 3 487.1741；Found487.1727.
example 4
The product hydroxyphenyl-substituted pyrazolone indazole [ spiro ] pyrazolone compound 3 synthesized by the method is subjected to a series of reactions, so that a further derivative is synthesized. For example:
to a 15mL reaction tube, 3a (43.6mg,0.1mmol), DMF (1mL), MeI (29.8 mg,0.21mmol), and K were added sequentially 2 CO 3 (27.6mg,0.2mmol), the tube was sealed and the reaction stirred at room temperature for 12 h. The reaction was quenched with water and extracted with ethyl acetate (10 mL. times.3). The combined organic phases were dried over anhydrous sodium sulfate, filtered with suction, dried by spinning, and separated by silica gel column (petroleum ether/ethyl acetate: 1/1) to give product 4(42.2mg, 94%) as a colorless liquid.
1 H NMR(CDCl 3 ,400MHz):δ7.95(d,J＝7.6Hz,2H),7.87(d,J＝8.0Hz,1H), 7.51-7.41(m,4H),7.33-7.26(m,2H),7.18-7.15(m,1H),7.07-7.00(m,2H),6.94(d,J ＝8.4Hz,1H),3.80(s,3H),2.08(s,3H),1.94(s,3H). 13 C{ 1 H}NMR(CDCl 3 ,100 MHz):δ167.4,161.3,157.4,157.1,148.2,137.5,136.0,132.1,131.5,129.3,129.2, 126.3,126.0,125.1,122.1,120.8,118.9,118.7,113.3,111.8,111.2,74.6,55.6,13.6, 12.1.HRMS(ESI)m/z:[M+H] + Calcd for C 27 H 23 N 4 O 3 Exact Mass:451.1765；Found 451.1748.
To a 15mL reaction tube were added 4(42.2mg,0.09mmol), DME (1mL), ethyl acrylate (19.6. mu.L, 0.18mmol) and [ RhCp. Cl ] in that order 2 ] 2 (2.8mg,0.0045mmol)、AgSbF 6 (6.2mg, 0.018mmol) and Cu (OAc) 2 (32.7mg,0.18mmol), the reaction tube was sealed under an argon atmosphere and placed in a 110 ℃ block for reaction for 14 h. After the reaction was complete, it was cooled to room temperature, quenched with water and extracted with ethyl acetate (10 mL. times.3). The combined organic phases were dried over anhydrous sodium sulfate, filtered with suction, dried by spinning and separated on a silica gel column (petroleum ether/ethyl acetate 3/1) to give product 5(23.2mg, 47%) as a colorless liquid.
1 H NMR(CDCl 3 ,400MHz):δ8.95(d,J＝16.0Hz,1H),7.94(d,J＝8.4Hz, 2H),7.73(d,J＝8.0Hz,1H),7.47-7.44(m,3H),7.34-7.29(m,2H),7.21(t,J＝8.0 Hz,1H),7.04-7.00(m,2H),6.93(d,J＝8.4Hz,1H),6.43(d,J＝16.0Hz,1H),4.26 (q,J＝7.2Hz,2H),3.80(s,3H),2.09(s,3H),1.93(s,3H),1.31(t,J＝7.2Hz,3H). 13 C{ 1 H}NMR(CDCl 3 ,150MHz):δ167.4,166.5,161.8,157.5,156.9,150.1,141.4, 137.4,135.9,132.2,129.5,129.2,128.9,128.5,126.1,125.9,123.0,122.6,120.8, 120.1,118.69,118.67,112.8,111.1,74.4,60.6,55.6,14.3,13.7,12.2.HRMS(ESI) m/z:[M+Na] + Calcd for C 32 H 28 N 4 NaO 5 571.1952；Found 571.1957.
To a 15mL reaction tube were added 3a (43.6mg,0.1mmol), acetone (1mL), DMCC (32.3mg,0.3mmol), and Cs in that order 2 CO 3 (81.5mg,0.25mmol) and DMAP (2.4mg,0.02mmol), the reaction tube was sealed under an argon atmosphere and reacted at room temperature for 10 hours. After completion of the reaction, the reaction mixture was quenched by addition of saturated brine, and then transferred to a separatory funnel and extracted with ethyl acetate (10mL × 3). The combined organic phases were dried over anhydrous sodium sulfate, filtered with suction, dried by spinning and separated on a silica gel column (petroleum ether/ethyl acetate. RTM. 1/1) to give product 6(42.1mg, 83%) as a white solid.
1 H NMR(CDCl 3 ,600MHz):δ7.92(d,J＝7.8Hz,2H),7.87(d,J＝7.8Hz,1H), 7.52-7.50(m,1H),7.46(t,J＝8.4Hz,2H),7.37-7.32(m,2H),7.28-7.22(m,3H), 7.19(t,J＝7.2Hz,1H),7.07(d,J＝7.2Hz,1H),3.00(s,3H),2.91(s,3H),2.11(s, 3H),1.94(s,3H). 13 C{ 1 H}NMR(CDCl 3 ,100MHz):δ167.0,160.4,157.1,154.5, 150.2,148.0,137.3,135.8,131.8,131.5,129.3,129.2,126.1,126.0,125.3,125.2, 123.2,123.1,122.1,118.7,113.2,111.7,74.5,36.7,36.5,13.6,11.2.HRMS(ESI)m/z: [M+Na] + Calcd for C 29 H 25 N 5 NaO 4 530.1799；Found 530.1789.
To a 15mL reaction tube were added 6(50.8mg,0.1mmol), DME (1mL), ethyl acrylate (21.7. mu.L, 0.2mmol) and [ RhCp. multidot. Cl ] in that order 2 ] 2 (3.1mg,0.005mmol)、AgSbF 6 (6.9mg,0.02 mmol) and Cu (OAc) 2 (36.3mg,0.2mmol), the reaction tube was sealed under an argon atmosphere and placed in a 110 ℃ block for reaction for 14 h. After the reaction was completed, water was added to quench, and then the reaction mixture was transferred to a separatory funnel and extracted with ethyl acetate (10 mL. times.3). The combined organic phases were dried over anhydrous sodium sulfate, filtered with suction, dried by spinning and separated by a silica gel column (petroleum ether/ethyl acetate 3/1) to give product 7(42.9mg, 61%) as a colorless liquid.
1 H NMR(DMSO-d 6 ,600MHz):δ8.88(d,J＝16.2Hz,1H),8.13(d,J＝7.8Hz, 1H),8.04(d,J＝7.8Hz,1H),7.65-7.54(m,5H),7.44-7.39(m,3H),7.30(t,J＝7.8 Hz,1H),7.24(d,J＝8.4Hz,1H),6.73-6.69(m,2H),4.21-4.14(m,4H),2.84(s,3H), 2.73(s,3H),2.14(s,3H),2.07(s,3H),1.25(t,J＝7.2Hz,3H),1.20(t,J＝7.2Hz, 3H). 13 C{ 1 H}NMR(DMSO-d 6 ,100MHz):δ168.6,166.34,166.26,160.6,158.3, 153.9,150.4,150.1,141.6,139.0,135.4,135.2,132.1,131.8,131.0,130.2,129.69, 129.66,128.4,128.1,127.30,127.28,125.7,124.6,123.7,123.5,121.6,121.3,120.3, 112.1,73.3,60.8,60.5,36.6,36.3,14.7,14.6,13.7,11.9.HRMS(ESI)m/z:[M+Na] + Calcd for C 39 H 37 N 5 NaO 8 726.2534；Found 726.2514.
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 merely illustrative 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 the invention is intended to be covered by the appended claims.
Claims (8)
1. The hydroxybenzene-substituted pyrazolone indazole [ spiro ] pyrazolone compound is characterized by having a general structural formula as follows:
wherein R is 1 Is hydrogen, C 1-6 Chain alkyl, C 1-4 Alkoxy, phenyl, substituted phenyl, C 1-4 Alkoxycarbonyl or halogen, the substituent on the phenyl ring of the substituted phenyl being C 1-4 Alkyl radical, C 1-4 Alkoxy, trifluoromethyl or halogen, R 2 Is hydrogen, C 1-6 Chain alkyl, C 1-4 Alkoxy, trifluoromethyl or halogen, R 3 Is C 1-4 An alkyl group.
2. The method of synthesizing a hydroxyphenyl-substituted pyrazolone indazolo [ spiro ] pyrazolone compound in accordance with claim 1, comprising the steps of: taking an N-phenoxyacetamide compound 1 and a diazopyrazolone compound 2 as raw materials, and heating in an organic solvent in the presence of a rhodium catalyst and an additive to react to obtain a hydroxyphenyl-substituted pyrazolone indazole [ spiro ] pyrazolone compound 3; the reaction equation is:
wherein R is 1 Is hydrogen, C 1-6 Chain alkyl, C 1-4 Alkoxy, phenyl, substituted phenyl, C 1-4 Alkoxycarbonyl or halogen, the substituent on the phenyl ring of the substituted phenyl being C 1-4 Alkyl radical, C 1-4 Alkoxy, trifluoromethyl or halogen, R 1 Is mono-or di-substituted, R 2 Is hydrogen, C 1-6 Chain alkyl, C 1-4 Alkoxy radical,Trifluoromethyl or halogen, R 3 Is C 1-4 An alkyl group.
3. The method of synthesizing a hydroxyphenyl-substituted pyrazolone indazolo [ spiro ] pyrazolone compound according to claim 2, further comprising: the reaction solvent is selected from 1, 2-dichloroethane, chloroform or dichloromethane.
4. The hydroxybenzene-substituted pyrazolone indazole [ spiro ] according to claim 2]The synthesis method of the pyrazolone compound is characterized by comprising the following steps: the rhodium catalyst is selected from [ RhCp Cl ] 2 ] 2 Or [ RhCp (MeCN) 3 ](SbF 6 ) 2 。
5. The method for synthesizing hydroxybenzene-substituted pyrazolone indazolo [ spiro ] pyrazolone compounds according to claim 2, characterized in that: the additive is selected from cesium acetate or cesium fluoride.
6. The method of synthesizing a hydroxyphenyl-substituted pyrazolone indazolo [ spiro ] pyrazolone compound according to claim 5, further comprising: the additive also comprises potassium phosphate, potassium dihydrogen phosphate, potassium hydrogen phosphate or potassium acetate.
7. The method of synthesizing a hydroxyphenyl-substituted pyrazolone indazolo [ spiro ] pyrazolone compound according to claim 2, further comprising: the molar ratio of the N-phenoxyacetamide compound 1, the diazopyrazolone compound 2, the rhodium catalyst and the additive is 1-1.2:1-3:0.02-0.07: 0.1-3.
8. The method of synthesizing a hydroxyphenyl-substituted pyrazolone indazolo [ spiro ] pyrazolone compound according to claim 2, further comprising: the reaction is carried out in an air atmosphere; the reaction temperature is 40-70 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210804999.XA CN115124542A (en) | 2022-07-08 | 2022-07-08 | Synthetic method of hydroxyphenyl-substituted pyrazolone indazole [ spiro ] pyrazolone compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210804999.XA CN115124542A (en) | 2022-07-08 | 2022-07-08 | Synthetic method of hydroxyphenyl-substituted pyrazolone indazole [ spiro ] pyrazolone compound |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115124542A true CN115124542A (en) | 2022-09-30 |
Family
ID=83381411
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210804999.XA Withdrawn CN115124542A (en) | 2022-07-08 | 2022-07-08 | Synthetic method of hydroxyphenyl-substituted pyrazolone indazole [ spiro ] pyrazolone compound |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115124542A (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 (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110111046A1 (en) * | 2009-11-10 | 2011-05-12 | Pfizer Inc | N1-Pyrazolospiroketone Acetyl-CoA Carboxylase Inhibitors |
| CN107849053A (en) * | 2015-04-03 | 2018-03-27 | 卡利拉制药公司 | Spiro-compound |
| CN110759920A (en) * | 2019-11-05 | 2020-02-07 | 绍兴文理学院 | P-methoxyphenyl substituted spiro [ indazole-pyrazoline ] derivative containing pyrazole structure and preparation method and application thereof |
| CN111675712A (en) * | 2020-06-23 | 2020-09-18 | 河南师范大学 | Synthesis method of pyrazolone benzodiazepine compound |
| CN113185536A (en) * | 2021-04-29 | 2021-07-30 | 河南师范大学 | Synthesis method of pyrazolidone benzo 1, 3-oxygen-nitrogen hetero-compound |
-
2022
- 2022-07-08 CN CN202210804999.XA patent/CN115124542A/en not_active Withdrawn
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20110111046A1 (en) * | 2009-11-10 | 2011-05-12 | Pfizer Inc | N1-Pyrazolospiroketone Acetyl-CoA Carboxylase Inhibitors |
| CN107849053A (en) * | 2015-04-03 | 2018-03-27 | 卡利拉制药公司 | Spiro-compound |
| CN110759920A (en) * | 2019-11-05 | 2020-02-07 | 绍兴文理学院 | P-methoxyphenyl substituted spiro [ indazole-pyrazoline ] derivative containing pyrazole structure and preparation method and application thereof |
| CN111675712A (en) * | 2020-06-23 | 2020-09-18 | 河南师范大学 | Synthesis method of pyrazolone benzodiazepine compound |
| CN113185536A (en) * | 2021-04-29 | 2021-07-30 | 河南师范大学 | Synthesis method of pyrazolidone benzo 1, 3-oxygen-nitrogen hetero-compound |
Non-Patent Citations (1)
| Title |
|---|
| XIA SONG ET AL.: ""Coupling partner-dependent unsymmetrical C–H functionalization of N-phenoxyacetamides leading to sophisticated spirocyclic scaffolds"", 《ORGANIC CHEMISTRY FRONTIERS》, vol. 9, pages 4583 * |
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 |
|---|---|---|
| RU2659792C1 (en) | Oxazolidinones and the method of their cleaning | |
| CN108409625B (en) | Preparation method of 2-pyrrolidone compound | |
| CN115124542A (en) | Synthetic method of hydroxyphenyl-substituted pyrazolone indazole [ spiro ] pyrazolone compound | |
| CN107216307A (en) | A kind of method for efficiently synthesizing 1,1 diaryl alkane hydro carbons compounds | |
| CN113214129A (en) | Method for iodination/sulfonylation reaction of 1, 6-diene compound initiated by sulfonyl free radical | |
| CN110437124B (en) | Preparation method of indoloquinone derivative | |
| CN113185536B (en) | Synthesis method of pyrazolidone benzo 1, 3-oxygen-nitrogen hetero-compound | |
| CN110606850A (en) | 3-benzo [4,5] imidazo [1,2-a ] pyrazine-1-amine compound and preparation method and application thereof | |
| CN106083539B (en) | A kind of synthetic method of list fluorine methoxyl group or the deuterated methoxy base class compound of single fluorine | |
| CN114149379B (en) | Synthesis method for synthesizing multi-substituted oxazole product from simple aromatic carboxylic acid and cyano-substituted ester compound | |
| KR101845935B1 (en) | preparation method of pyridoisoindole derivatives | |
| CN110724094A (en) | Quinoline compound and synthesis method thereof | |
| CN115353514B (en) | Fluoro-pyridopyrimidinone compounds and synthesis method thereof | |
| CN115925720A (en) | Quinoline cyclobutane compound and synthesis method thereof | |
| CN114805268B (en) | Synthesis method of visible light mediated cyclopenta [ b ] benzofuran derivative | |
| CN109896989B (en) | Synthesis method of 5-oxo-2H-aromatic ring [ g ] indole-1-oxide | |
| CN113402445B (en) | Method for preparing carbazole compound and dibenzothiophene compound | |
| KR102147971B1 (en) | Method for preparing chemoselective triazole derivatives through miscibility with reaction solvent | |
| CN116836100A (en) | 2-aminopyrrole compound and preparation method and application thereof | |
| CN118084831A (en) | Tetra-substituted furan compound and preparation method thereof | |
| CN118324603A (en) | Method for synthesizing chrysene derivatives through palladium-catalyzed cycloaromatization reaction | |
| SU1634669A1 (en) | Process for preparing 4-amino-5-tosyl-imidazo (1,2:1,6) pyrido (2,3) pyrazine | |
| CN113956276A (en) | Polysubstituted alkylaryl azo compound, and synthesis method and application thereof | |
| RU2076104C1 (en) | Method for production of derivatives of 5,6-phthalyl phenothiazine | |
| RU2065440C1 (en) | Method for production of derivatives of 3-phenylthioanthra[1,9-cd]-isoxazol-6-on |
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 |
Application publication date: 20220930 |
|
| WW01 | Invention patent application withdrawn after publication |