Indenopyrazolopyrrolidinone Compounds with Anticancer Activity and Their Synthesis Methods

Abstract

Specifically disclosed are indeno[1,2 - b]pyrazolo[3,4 - e]pyrrolidone compounds with anti - cancer activity and their synthesis methods, belonging to the technical fields of organic synthesis and drug discovery. Mix an arylazomethine imine compound 1, a 1 - substituted cyclopropanol compound 2, a catalyst, an additive and an organic solvent, and heat the reaction to obtain an indeno[1,2 - b]pyrazolo[3,4 - e]pyrrolidone compound 3A or 3B. This type of compound has significant anti - A - 549, anti - Ramos and anti - Hela activities, providing a new structural unit for drug screening. At the same time, the synthesis process of the present invention is simple and efficient. Through a one - pot tandem reaction of arylazomethine imine and 1 - substituted cyclopropanol compounds, a four - ring fused molecular skeleton can be conveniently constructed.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis and drug discovery, and particularly relates to indenopyrazolopyrazolidinone compounds with anticancer activity and a synthesis method thereof. Background Art

[0002] Aza-fused ring compounds possess diverse and highly effective pharmaceutical activities, playing an irreplaceable and important role in new drug development. Among them, pyrazolopyrazolidinone derivatives exhibit significant anticancer, anti-Alzheimer's, herbicidal, and insecticidal activities, while indene-fused pyrazoles exhibit antidepressant, antimycobacterial, antipsychotic, antihypertensive, and antitumor properties. Furthermore, indene-fused pyrazole backbones are the main components of several organic functional materials with promising optoelectronic applications.

[0003] Given the importance of pyrazolopyrazolidinone and indenopyrazole, it is very necessary to construct hybrid compounds composed of these two specific skeletons - indenopyrazolopyrazolidinone compounds, which is expected to discover lead compounds with stronger biological activity.

[0004] Therefore, researching and developing a new green and efficient method for synthesizing indenopyrazolopyrazolidinone compounds through simple and readily available raw materials through simple steps has very important theoretical significance and practical prospects. Summary of the Invention

[0005] The present invention addresses the technical problem of providing novel indenopyrazolopyrazolidinone compounds and a method for synthesizing them. This method, achieved through the reaction of an arylazomethine imine with a 1-substituted cyclopropanol, offers advantages such as simple and readily available raw materials, mild conditions, a wide range of substrate applicability, and high atom economy. Furthermore, these compounds exhibit significant anticancer activity and therefore have potential medicinal value.

[0006] The present invention provides indenopyrazolopyrazolidinone compounds 3 (including 3A and 3B) with anticancer activity, the general structural formula of which is:

[0007]

[0008] where R 1 For hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy, halogen or trifluoromethyl, R 1 is mono- or di-substituted; or R 1 Together with the benzene ring, it forms a dioxane-phenyl group, a naphthyl group or an N-substituted carbazole group, where the substituent on the N-substituted carbazole group is C 1-4 Alkyl; R 2 The methyl group is substituted, and the substituent on the methyl group is a mono- or di-substituted C 1-4alkyl, phenyl, substituted phenyl, benzyl or phenoxy, the substituent on the benzene ring of the substituted phenyl is a mono- or di-substituted C 1-4 alkyl, C 1-4 alkoxy or halogen; R 3 is C 1-4 alkyl, phenyl, substituted phenyl or benzyl, the substituent on the benzene ring of the substituted phenyl is a mono- or di-substituted C 1-4 alkyl, C 1-4 alkoxy or halogen; R 4 is C 1-4 alkyl.

[0009] The present invention also provides a method for synthesizing the above-mentioned indeno[1,2-b]pyrazolo[3,4-e]pyrazolidinone compound 3, and the technical solution adopted is as follows:

[0010] A. A method for synthesizing the indeno[1,2-b]pyrazolo[3,4-e]pyrazolidinone compound 3A, including the following operations: mixing an aryl azomethine imine compound 1, a 1-substituted cyclopropanol compound 2, a catalyst, an additive and an organic solvent, and heating the reaction to obtain the indeno[1,2-b]pyrazolo[3,4-e]pyrazolidinone compound 3A, and the reaction equation is:

[0011]

[0012] Wherein: R 1 is hydrogen, C 1-4 alkyl, C 1-4 alkoxy, halogen or trifluoromethyl, R 1 is mono- or di-substituted; or R 1 and the benzene ring together form a dioxane-fused phenyl, naphthyl or N-substituted carbazolyl, and the substituent on the N-substituted carbazolyl is C 1-4 alkyl; R 2 is a substituted methyl, and the substituent on the substituted methyl is a mono- or di-substituted C 1-4 alkyl, phenyl, substituted phenyl, benzyl or phenoxy, the substituent on the benzene ring of the substituted phenyl is a mono- or di-substituted C 1-4 alkyl, C 1-4 alkoxy or halogen; R 3 is C 1-4 alkyl, phenyl, substituted phenyl or benzyl, the substituent on the benzene ring of the substituted phenyl is a mono- or di-substituted C 1-4 alkyl, C 1-4 alkoxy or halogen.

[0013] Furthermore, in the above technical solution, the additive is copper acetate, copper acetate monohydrate, silver hexafluoroantimonate or a mixture thereof.

[0014] Furthermore, in the above technical solution, the organic solvent is methanol, ethanol, toluene or tetrahydrofuran.

[0015] Further, in the above technical solution, the catalyst is dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer ([RhCp*Cl2]2), dichloro(pentamethylcyclopentadienyl)iridium(III) dimer ([IrCp*Cl2]2), or tris(acetonitrile)(pentamethylcyclopentadienyl)rhodium(III) bis(hexafluoroantimonate) ([RhCp*(MeCN)3](SbF6)2).

[0016] Further, in the above technical solution, the molar ratio of the arylazomethine imine compound 1, 1-substituted cyclopropanol compound 2, catalyst, and additive is 1-2:1-3:0.01-0.1:0.5-2.

[0017] Further, in the above technical solution, the reaction temperature is 60-90 °C.

[0018] Further, in the above technical solution, the reaction can be carried out in an air or inert gas atmosphere.

[0019] B. A method for synthesizing indeno[1,2-b]pyrazolo[3,4-e]pyrrolidone compound 3B, comprising the following operations: Mix the arylazomethine imine compound 1, 1-substituted cyclopropanol compound 2, catalyst, additive, and C 1-4 alkanol, heat up the reaction to obtain indeno[1,2-b]pyrazolo[3,4-e]pyrrolidone compound 3B, and the reaction equation is:

[0020]

[0021] Where: R 1 is hydrogen, C 1-4 alkyl, C 1-4 alkoxy, halogen, or trifluoromethyl, R 1 is mono- or di-substituted; or R 1 and the benzene ring together form dioxane-fused phenyl, naphthyl, or N-substituted carbazolyl, and the substituent on the N-substituted carbazolyl is C 1-4 alkyl; R 2 is isopropyl or phenoxy-substituted methyl; R 4 is C 1-4 alkyl.

[0022] Further, in the above technical solution, the additive is copper acetate, copper acetate monohydrate, silver hexafluoroantimonate, or a mixture thereof.

[0023] Further, in the above technical solution, the catalyst is dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer ([RhCp*Cl2]2), dichloro(pentamethylcyclopentadienyl)iridium(III) dimer ([IrCp*Cl2]2), or tris(acetonitrile)(pentamethylcyclopentadienyl)rhodium(III) bis(hexafluoroantimonate) ([RhCp*(MeCN)3](SbF6)2).

[0024] Further, in the above technical solution, the molar ratio of the arylazomethine imine compound 1, 1-substituted cyclopropanol compound 2, catalyst, and additive is 1-2:1-3:0.01-0.1:0.5-2.

[0025] Further, in the above technical solution, the reaction temperature is 60-90 °C.

[0026] Further, in the above technical solution, the reaction can be carried out in an air or inert gas atmosphere.

[0027] The present invention also provides the application of the above indeno[1,2-b]pyrazolo[3,4-e]pyrazolidinone compound 3 in the synthesis of anti-cancer active drugs, and the anti-cancer activity is mainly against A-549, Ramos, and Hela.

[0028] Advantages of the invention:

[0029] Compared with the prior art, the present invention has the following advantages: (1) The synthesis process is simple and efficient. Through the one-pot tandem reaction of arylazomethine imine and 1-substituted cyclopropanol compounds, a tetracyclic fused molecular skeleton can be conveniently constructed to synthesize indeno[1,2-b]pyrazolo[3,4-e]pyrazolidinone compounds, with high reaction atom economy and efficiency; (2) The raw materials are cheap and easily available, the reaction conditions are mild, and the operation is simple; (3) It has a wide application range and good functional group tolerance; (4) Indeno[1,2-b]pyrazolo[3,4-e]pyrazolidinone compounds have significant anti-cancer activity, providing a new structural unit for drug screening.

[0030] Description of the drawings

[0031] Figure 1 It is the X-ray single crystal diffraction pattern of compound 3aa in Example 3;

[0032] Figure 2 It is the X-ray single crystal diffraction pattern of compound 3as in Example 3. Detailed implementation manners

[0033] The following further elaborates on the above content of the present invention through examples, but it should not be understood that the scope of the above subject matter of the present invention is limited to the following examples, and all technologies implemented based on the above content of the present invention belong to the scope of the present invention.

[0034] Example 1

[0035]

[0036] Compound 1a, 2a, a catalyst, additive 1, additive 2 and a solvent were successively added to a 15 mL reaction tube. Then, the reaction tube was sealed and placed in an oil bath for heating and stirring reaction. After the reaction was completed, it was cooled to room temperature, filtered by suction, the filtrate was concentrated, and separated by silica gel column (petroleum ether / ethyl acetate = 5 / 1) to obtain a white solid product 3aa.

[0037] By changing the reaction conditions such as the reaction solvent, catalyst, additives, material ratio and reaction temperature, a series of results were obtained, as shown in Table 1.

[0038] Table 1 Synthesis of 3aa under different conditions a

[0039]

[0040]

[0041] Example 2

[0042]

[0043] 1a (40.4 mg, 0.2 mmol), 2a (88.8 mg, 0.6 mmol), [RhCp*Cl2]2 (4.9 mg, 0.008 mmol), silver hexafluoroantimonate (6.9 mg, 0.02 mmol), copper acetate (72.7 mg, 0.4 mmol) and ethanol (2 mL) were successively added to a 15 mL pressure-resistant tube. After evacuating and filling with argon, the reaction tube was sealed and placed in an 80 °C oil bath for reaction for 3 h. After the reaction was completed, the reaction system was cooled to room temperature, filtered by suction, the filtrate was concentrated, and separated by silica gel column (petroleum ether / ethyl acetate = 5 / 1) to obtain a white solid product 3aa (49.5 mg, 75%). The characterization data of this compound are as follows: 1 H NMR (600 MHz, CDCl3): δ 7.36 - 7.31 (m, 4H), 7.29 - 7.25 (m, 3H), 7.23 - 7.17 (m, 3H), 4.68 (d, J = 7.2 Hz, 1H), 4.40 - 4.35 (m, 1H), 3.45 (dd, J1 = 16.2 Hz, J2 = 9.0, 1H), 3.27 (dd, J1 = 16.8 Hz, J2 = 7.8, 1H), 2.89 (d, J = 15.6 Hz, 1H), 2.45 (d, J = 16.2, 1H), 1.40 (s, 3H), 1.36 (s, 3H). 13 C{ 11H NMR (150 MHz, CDCl3): δ 163.9, 143.3, 140.7, 136.4, 135.1, 128.8, 128.5, 127.8, 126.9, 126.2, 125.4, 125.2, 109.2, 64.2, 61.7, 51.3, 51.1, 37.6, 26.5, 20.3. HRMS (ESI) m / z: [M+H] + Calcd for C 22 H 23 N2O 331.1805; Found 331.1799.

[0044] Example 3

[0045] According to the methods and steps of Example 2, by changing Reactant 1 and Reactant 2, various indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-ones 3 can be synthesized. The specific results are as follows:

[0046] Table 2 Synthesis of Indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-ones 3 a,b

[0047]

[0048]

[0049] The characterization data of the representative products are as follows:

[0050] (E)-10-Benzylidene-3,3,7-trimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one (3ba)

[0051] 1 1H NMR (600 MHz, CDCl3): δ 7.35 - 7.31 (m, 4H), 7.25 (d, J = 1.2 Hz, 1H), 7.20 - 7.15 (m, 2H), 7.03 (d, J = 7.2 Hz, 2H), 4.63 (d, J = 7.8 Hz, 1H), 4.38 - 4.34 (m, 1H), 3.41 (dd, J1 = 16.2 Hz, J2 = 9.0 Hz, 1H), 3.24 (dd, J1 = 16.2 Hz, J2 = 7.8 Hz, 1H), 2.89 (d, J = 15.6 Hz, 1H), 2.44 (d, J = 15.6 Hz, 1H), 2.33 (s, 3H), 1.39 (s, 3H), 1.35 (s, 3H). 13 C{ 1H}NMR(150MHz,CDCl3):δ163.8,143.5,138.7,137.7,136.4,135.1,128.5,127.8,127.7,126.2,125.8,125.2,109.1,63.9,61.6,51.5,51.4,37.5,26.5,21.4,20.3.HRMS(ESI)m / z:[M+Na] + Calcdfor C 23 H 24 N2NaO 367.1781;Found 367.1783.

[0052] (E)-10-Benzylidene-7-(tert-butyl)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3ca)

[0053] 1 H NMR(400MHz,CDCl3):δ7.36-7.30(m,4H),7.26-7.24(m,3H),7.21-7.16(m,2H),4.65(d,J=8.0Hz,1H),4.42-4.35(m,1H),3.45(dd,J1=16.4Hz,J2=9.2Hz,1H),3.24(dd,J1=16.0Hz,J2=7.2Hz,1H),2.89(d,J=16.0Hz,1H),2.44(d,J=15.6Hz,1H),1.39(s,3H),1.38(s,3H),1.29(s,9H). 13 C{ 1 H}NMR(150MHz,CDCl3):δ163.9,152.1,143.0,137.7,136.4,135.2,128.5,127.9,126.2,125.0,124.2,122.1,109.2,63.9,61.9,51.3,37.8,34.8,31.5,31.4,26.4,20.2.HRMS(ESI)m / z:[M+Na] + Calcd for C 26 H 30 N2NaO 409.2250;Found409.2242.

[0054] (E)-10-Benzylidene-7-methoxy-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3da)

[0055] 1 1H NMR (600 MHz, CDCl3): δ 7.35 - 7.30 (m, 4H), 7.25 (d, J = 1.8 Hz, 1H), 7.20 - 7.16 (m, 2H), 6.76 (dd, J1 = 8.4 Hz, J2 = 2.4 Hz, 1H), 6.73 (s, 1H), 4.61 (d, J = 7.8 Hz, 1H), 4.39 - 4.35 (m, 1H), 3.76 (s, 3H), 3.40 (dd, J1 = 16.2 Hz, J2 = 9.0 Hz, 1H), 3.23 (J1 = 16.8 Hz, J2 = 7.8 Hz, 1H), 2.88 (d, J = 16.2 Hz, 1H), 2.43 (d, J = 15.6 Hz, 1H), 1.37 (s, 3H), 1.35 (s, 3H). 13 C{ 1 1H} NMR (150 MHz, CDCl3): δ 163.8, 160.4, 145.0, 136.4, 135.1, 132.8, 128.5, 127.8, 126.2, 126.1, 113.2, 110.1, 109.1, 63.6, 61.6, 55.4, 51.6, 51.4, 37.8, 26.5, 20.3. HRMS (ESI) m / z: [M + Na] + Calcd for C 23 H 24 N2NaO2 383.1730; Found 383.1732.

[0056] (E)-10-Benzylidene-7-fluoro-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3ea)

[0057] 11H NMR (600 MHz, CDCl3): δ 7.34 - 7.31 (m, 4H), 7.24 (d, J = 1.8 Hz, 1H), 7.23 - 7.18 (m, 2H), 6.93 - 6.88 (m, 2H), 4.63 (d, J = 7.8 Hz, 1H), 4.42 - 4.39 (m, 1H), 3.40 (dd, J1 = 16.8 Hz, J2 = 9.0 Hz, 1H), 3.23 (dd, J1 = 16.8 Hz, J2 = 7.2 Hz, 1H), 2.89 (d, J = 15.6 Hz, 1H), 2.44 (d, J = 16.2 Hz, 1H), 1.38 (s, 3H), 1.35 (s, 3H). 13 13C{1H}NMR (150 MHz, CDCl3): δ 163.9, 163.3 (d, 1 1 J C-F = 245.0), 145.7 (d, 3 J C-F = 7.7), 136.4 (d, 4 J C-F = 3.3), 136.2, 134.7, 128.6, 127.8, 126.6 (d, 3 J C-F = 9.9), 126.3, 114.1 (d, 2 J C-F = 23.0), 112.2 (d, 2 J C-F = 21.9), 109.4, 63.4, 61.8, 51.5, 51.2, 37.6 (d, 4 J C-F = 2.3), 26.5, 20.3. 19 19F NMR (565 MHz, CDCl3): δ -113.49--113.53 (m). HRMS (ESI) m / z: [M+Na] + Calcd for C 22 H 21 19FN2NaO 371.1530; Found 371.1521.

[0058] (E)-10-Benzylidene-7-chloro-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one (3fa)

[0059] 11H NMR (600 MHz, CDCl3): δ 7.34 - 7.32 (m, 4H), 7.23 (d, J = 1.2 Hz, 1H), 7.20 - 7.17 (m, 4H), 4.62 (d, J = 7.8 Hz, 1H), 4.40 - 4.36 (m, 1H), 3.39 (dd, J1 = 16.8 Hz, J2 = 9.6 Hz, 1H), 3.22 (dd, J1 = 16.8 Hz, J2 = 7.2 Hz, 1H), 2.88 (d, J = 15.6 Hz, 1H), 2.44 (d, J = 15.6 Hz, 1H), 1.37 (s, 3H), 1.34 (s, 3H). 13 C{ 1 13C{1H}NMR (150 MHz, CDCl3): δ 163.9, 145.2, 139.3, 136.1, 134.64, 134.55, 128.6, 127.9, 127.2, 126.5, 126.3, 125.4, 109.4, 63.5, 61.8, 51.2, 51.1, 37.4, 26.5, 20.2. HRMS(ESI) m / z: [M+Na] + Calcd for C 22 13H 21 17ClN2NaO 387.1235; Found 387.1223.

[0060] (E)-10-Benzylidene-7-bromo-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one (3ga)

[0061] 1 1H NMR (600 MHz, CDCl3): δ 7.36 - 7.32 (m, 6H), 7.24 (d, J = 1.8 Hz, 1H), 7.21 - 7.18 (m, 1H), 7.14 (d, J = 7.8 Hz, 1H), 4.62 (d, J = 7.8 Hz, 1H), 4.40 - 4.36 (m, 1H), 3.40 (dd, J1 = 16.2 Hz, J2 = 9.0 Hz, 1H), 3.24 (dd, J1 = 16.2 Hz, J2 = 7.2 Hz, 1H), 2.89 (d, J = 15.6 Hz, 1H), 2.45 (d, J = 16.2 Hz, 1H), 1.38 (s, 3H), 1.35 (s, 3H). 13 C{ 11H NMR (150 MHz, CDCl3): δ 163.9, 145.6, 139.8, 136.1, 134.6, 130.1, 128.6, 128.4, 127.8, 126.9, 126.3, 122.7, 109.4, 63.6, 61.9, 51.2, 51.1, 37.3, 26.5, 20.2. HRMS (ESI) m / z: [M+Na] + Calcd for C 22 H 21 BrN2NaO4 31.0729; Found 431.0727.

[0062] (E)-10-Benzylidene-3,3-dimethyl-7-(trifluoromethyl)-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one (3ha)

[0063] 1 1H NMR (400 MHz, CDCl3): δ 7.51 - 7.46 (m, 2H), 7.39 (d, J = 7.6 Hz, 1H), 7.34 - 7.33 (m, 4H), 7.24 - 7.18 (m, 2H), 4.71 (d, J = 8.0 Hz, 1H), 4.43 (q, J = 7.6 Hz, 1H), 3.47 (dd, J1 = 16.4 Hz, J2 = 8.8 Hz, 1H), 3.28 (dd, J1 = 16.4 Hz, J2 = 6.8 Hz, 1H), 2.90 (d, J = 16.0 Hz, 1H), 2.46 (d, J = 16.0 Hz, 1H), 1.40 (s, 3H), 1.37 (s, 3H). 13 13C{ 1 1H} NMR (150 MHz, CDCl3): δ 164.1, 144.7, 144.1, 136.0, 134.5, 131.1 (q, 2 J C-F = 31.7 Hz), 128.6, 127.9, 126.4, 125.8, 124.2 (q, 3 J C-F = 3.3 Hz), 124.1 (q, 1 J C-F = 270.2 Hz), 122.2 (q, 3 J C-F =19 19F NMR(565MHz,CDCl3):δ -62.32(s).HRMS(ESI) m / z: [M+Na] + Calcd for C 23 H 21 F3N2NaO 421.1498; Found 421.1501.

[0064] (E)-10-Benzylidene-6-chloro-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3ia)

[0065] 1 1H NMR(400MHz,CDCl3):δ 7.33 - 7.32(m,4H), 7.24 - 7.17(m,4H), 7.11(d,J = 8.0Hz,1H), 4.64(d,J = 8.0Hz,1H), 4.43 - 4.436(m,1H), 3.38(dd,J1 = 16.4Hz,J2 = 8.8Hz,1H), 3.17(dd,J1 = 16.8Hz,J2 = 7.2Hz,1H), 2.90(d,J = 15.6Hz,1H), 2.44(d,J = 15.6Hz,1H), 1.39(s,3H), 1.37(s,3H). 13 13C{ 1 1H}NMR(150MHz,CDCl3):δ 164.2, 142.8, 141.5, 136.1, 134.8, 132.6, 128.9, 128.5, 127.9, 126.31, 126.29, 125.6, 109.4, 63.8, 62.2, 51.1, 50.9, 37.0, 26.5, 20.1.HRMS(ESI) m / z: [M+Na] + Calcd for C 22 H 21 ClN2NaO 387.1235; Found 387.1231.

[0066] (E)-10-Benzylidene-6-bromo-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3ja)

[0067] 11H NMR (600 MHz, CDCl3): δ 7.40 - 7.38 (m, 2H), 7.35 - 7.33 (m, 4H), 7.22 - 7.18 (m, 2H), 7.07 (d, J = 8.4 Hz, 1H), 4.65 (d, J = 7.8 Hz, 1H), 4.42 - 4.37 (m, 1H), 3.37 (dd, J1 = 16.2 Hz, J2 = 9.0 Hz, 1H), 3.16 (dd, J1 = 16.2 Hz, J2 = 6.6 Hz, 1H), 2.91 (d, J = 15.6 Hz, 1H), 2.45 (d, J = 15.6 Hz, 1H), 1.39 (s, 3H), 1.37 (s, 3H). 13 C{ 1 13C{1H}NMR (100 MHz, CDCl3): δ 164.2, 143.2, 142.1, 136.1, 134.7, 131.8, 128.6, 128.5, 127.9, 126.7, 126.3, 120.4, 109.4, 63.8, 62.2, 51.1, 50.8, 37.1, 26.5, 20.1. HRMS(ESI) m / z: [M+Na] + Calcd for C 22 1H 21 13BrN2NaO 431.0729; Found 431.0717.

[0068] (E)-10-Benzylidene-3,3,6-trimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]py razolo[1,2-a]pyrazol-1-one (3ka)

[0069] 1 1H NMR (600 MHz, CDCl3): δ 7.35 - 7.31 (m, 4H), 7.26 (s, 1H), 7.21 - 7,15 (m, 2H), 7.03 (d, J = 7.8 Hz, 2H), 4.63 (d, J = 7.8 Hz, 1H), 4.38 - 4.33 (m, 1H), 3.40 (dd, J1 = 16.2 Hz, J2 = 9.0 Hz, 1H), 3.23 (dd, J1 = 16.2 Hz, J2 = 7.2 Hz, 1H), 2.89 (d, J = 15.6 Hz, 1H), 2.44 (d, J = 15.6 Hz, 1H), 2.33 (s, 3H), 1.39 (s, 3H), 1.35 (s, 3H). 13 C{ 11H NMR (150 MHz, CDCl3): δ 163.8, 143.5, 138.7, 137.7, 136.4, 135.1, 128.5, 127.8, 127.7, 126.1, 125.8, 125.1, 109.2, 63.9, 61.6, 51.45, 51.38, 37.5, 26.5, 21.4, 20.3. HRMS (ESI) m / z: [M+Na] + Calcd for C 23 H 24 N2NaO3 67.1781; Found 367.1785.

[0070] (E)-10-Benzylidene-6-methoxy-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one & (E)-10-Benzylidene-8-methoxy-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one (3la + 3la’)

[0071] 11H NMR (600 MHz, CDCl3): δ 7.35 - 7.30 (m, 5.32H), 7.27 - 7.22 (m, 1.33H), 7.20 - 7.16 (m, 1.66H), 7.11 - 7.08 (m, 1H), 7.00 (d, J = 8.4 Hz, 0.33H), 6.83 - 6.81 (m, 2H), 6.74 (d, J = 8.4 Hz, 0.33H), 4.70 (d, J = 6.6 Hz, 0.33H), 4.63 (d, J = 7.8 Hz, 1H), 4.41 - 4.37 (m, 1H), 4.12 - 4.08 (m, 0.33H), 3.80 (s, 3H), 3.75 (s, 0.99H), 3.61 (d, J = 14.4 Hz, 0.33H), 3.55 (d, J = 15.0 Hz, 0.33H), 3.38 (dd, J1 = 16.2 Hz, J2 = 9.0 Hz, 1H), 3.17 (dd, J1 = 16.2 Hz, J2 = 7.2 Hz, 1H), 2.91 (d, J = 15.6 Hz, 1H), 2.68 (d, J = 15.6 Hz, 0.33H), 2.45 (d, J = 16.2 Hz, 1H), 2.30 (d, J = 15.6 Hz, 0.33H), 1.39 (s, 3H), 1.38 (s, 3H), 1.36 (s, 0.99H), 1.20 (s, 0.99H). 13 C{ 1 13C{1H}NMR (150 MHz, CDCl3): δ 165.6, 164.0, 159.0, 156.7, 142.1, 141.1, 136.5, 136.32, 136.27, 135.23, 135.17, 135.0, 129.3, 128.7, 128.5, 128.4, 127.9, 126.3, 126.2, 126.0, 125.8, 114.4, 111.2, 110.9, 109.2, 108.0, 64.2, 63.7, 62.9, 61.9, 55.61, 55.56, 51.9, 51.6, 51.4, 51.3, 41.5, 36.8, 26.5, 24.9, 22.7, 19.7. HRMS (ESI) m / z: [M+Na] + Calcd for C 23 13 24 1H14N2NaO2 383.1730; Found 383.1720.

[0072] (E)-10-Benzylidene-3,3,5-trimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3ma)

[0073] 1 1H NMR(600MHz,CDCl3):δ7.33 - 7.29(m,4H),7.261 - 7.255(m,1H),7.20 - 7.16(m,2H),7.08(d,J = 7.8Hz,1H),7.00(d,J = 7.2Hz,1H),4.62(d,J = 6.6Hz,1H),4.21 - 4.17(m,1H),3.42(dd,J1 = 16.2Hz,J2 = 8.4Hz,1H),3.36(dd,J1 = 16.2Hz,J2 = 9.0Hz,1H),2.90(d,J = 15.6Hz,1H),2.45 - 2.42(m,4H),1.42(s,3H),1.28(s,3H). 13 C{ 1 H}NMR(100MHz,CDCl3):δ164.5,143.9,139.3,136.5,135.4,134.1,128.9,128.7,128.5,127.7,126.1,122.7,108.4,63.6,61.7,52.6,51.9,37.6,25.4,20.1,19.8.HRMS(ESI)m / z:[M+Na] + Calcd forC 23 H 24 N2NaO: 367.1781;Found 367.1785.

[0074] (E)-10-Benzylidene-5-fluoro-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3na)

[0075] 11H NMR (600 MHz, CDCl3): δ 7.35 - 7.31 (m, 5H), 7.29 - 7.26 (m, 1H), 7.21 - 7.18 (m, 1H), 7.04 (d, J = 7.8 Hz, 1H), 6.91 (t, J = 9.0 Hz, 1H), 4.76 (d, J = 6.6 Hz, 1H), 4.37 - 4.33 (m, 1H), 3.48 (dd, J1 = 16.2 Hz, J2 = 9.0 Hz, 1H), 3.38 (dd, J1 = 16.2 Hz, J2 = 9.0 Hz, 1H), 2.91 (d, J = 16.2 Hz, 1H), 2.49 (d, J = 16.2 Hz, 1H), 1.43 (s, 3H), 1.31 (s, 3H). 13 13C{1H}NMR (100 MHz, CDCl3): δ 163.3, 159.0 (d, 1 1 J C-F = 220.3 Hz), 147.2 (d, 3 J C-F = 4.3 Hz), 136.4, 134.0, 131.1 (d, 3 J C-F = 7.2 Hz), 128.6, 127.6, 127.0 (d, 2 J C-F = 15.9 Hz), 126.3, 121.0 (d, 4 J C-F = 3.6 Hz), 113.8 (d, 2 J C-F = 20.9 Hz), 109.3, 61.0, 60.6, 52.7, 51.7, 37.8, 25.4 (d, 6 J C-F = 5.0 Hz), 20.0. 19 19F NMR (565 MHz, CDCl3): δ -115.38--115.40 (m). HRMS (ESI) m / z: [M + H] + Calcd for C 22 H 21 F N2NaO 371.1530; Found 371.1529.

[0076] (E)-10-Benzylidene-5-chloro-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one (3oa)

[0077] 1 1H NMR (400 MHz, CDCl3): δ 7.35 (s, 1H), 7.34 - 7.28 (m, 4H), 7.26 - 7.16 (m, 4H), 4.66 (d, J = 6.4 Hz, 1H), 4.26 - 4.20 (m, 1H), 3.52 (dd, J1 = 16.0 Hz, J2 = 8.8 Hz, 1H), 3.44 (dd, J1 = 16.0 Hz, J2 = 8.8 Hz, 1H), 2.89 (d, J = 16.0 Hz, 1H), 2.47 (d, J = 16.0 Hz, 1H), 1.51 (s, 3H), 1.33 (s, 3H). 13 13C{ 1 1H} NMR (150 MHz, CDCl3): δ 163.4, 146.6, 138.8, 136.5, 134.0, 130.6, 130.5, 128.6, 127.6, 127.5, 126.3, 123.8, 108.7, 63.6, 61.1, 53.3, 52.2, 38.4, 25.3, 19.7. HRMS (ESI) m / z: [M + Na] + Calcd for C 22 17 21 11ClN2NaO3 87.1235; Found 387.1220.

[0078] (E)-10-Benzylidene-3,3,6,7-tetramethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one (3pa)

[0079] 1 1H NMR (600 MHz, CDCl3): δ 7.35 - 7.30 (m, 4H), 7.23 (d, J = 1.8 Hz, 1H), 7.19 - 7.17 (m, 1H), 7.04 (s, 1H), 6.97 (s, 1H), 4.62 (d, J = 7.8 Hz, 1H), 4.36 - 4.32 (m, 1H), 3.37 (dd, J1 = 16.2 Hz, J2 = 9.6 Hz, 1H), 3.18 (dd, J1 = 16.2 Hz, J2 = 7.2 Hz, 1H), 2.89 (d, J = 15.6 Hz, 1H), 2.43 (d, J = 15.6 Hz, 1H), 2.25 (s, 3H), 2.23 (s, 3H), 1.38 (s, 6H). 13 13C{ 11H NMR (150 MHz, CDCl3): δ 164.1, 140.6, 138.3, 137.3, 136.4, 135.4, 135.3, 128.5, 127.9, 126.3, 126.2, 126.1, 109.1, 64.0, 61.8, 51.31, 51.26, 37.2, 26.5, 20.2, 20.0, 19.9. HRMS (ESI) m / z: [M+Na] + Calcd for C 24 H 26 N2NaO 381.1937; Found 381.1938.

[0080] (E)-10-Benzylidene-7-fluoro-3,3,6-trimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one (3qa)

[0081] 1 1H NMR (400 MHz, CDCl3): δ 7.33 - 7.30 (m, 4H), 7.22 - 7.17 (m, 2H), 7.06 (d, J = 7.2 Hz, 1H), 6.82 (d, J = 9.6 Hz, 1H), 4.61 (d, J = 7.6 Hz, 1H), 4.38 (q, J = 7.6 Hz, 1H), 3.36 (dd, J1 = 16.4 Hz, J2 = 9.2 Hz, 1H), 3.18 (dd, J1 = 16.4 Hz, J2 = 7.2 Hz, 1H), 2.90 (d, J = 16.0 Hz, 1H), 2.44 (d, J = 15.6 Hz, 1H), 2.25 (s, 3H), 1.38 (s, 6H). 13 13C{ 1 1H} NMR (150 MHz, CDCl3): δ 164.2, 161.7 (d, 1 J C-F = 243.9 Hz), 142.5 (d, 3 J C-F = 8.7 Hz), 136.2, 135.0, 128.5, 127.90, 127.85 (d, 3 J C-F = 5.6 Hz), 126.2, 123.6 (d, 2 J C-F = 18.6 Hz), 111.7 (d, 2 J C-F= 23.0 Hz), 109.3, 63.5, 62.0, 51.25, 51.16, 37.3, 26.5, 20.2, 14.7 (d, 3 J C-F = 3.2 Hz). 19 19F NMR (565 MHz, CDCl3): δ -117.19--117.22 (m). HRMS (ESI) m / z: [M+Na] + Calcd for C 23 H 23 FN2NaO 385.1687; Found 385.1670.

[0082] (E)-10-Benzylidene-6,7-dimethoxy-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one (3ra)

[0083] 1 1H NMR (600 MHz, CDCl3): δ 7.36 - 7.31 (m, 4H), 7.21 - 7.18 (m, 2H), 6.76 (s, 1H), 6.70 (s, 1H), 4.65 (d, J = 7.8 Hz, 1H), 4.42 (q, J = 7.2 Hz, 1H), 3.88 (s, 3H), 3.83 (s, 3H), 3.38 (dd, J1 = 16.2 Hz, J2 = 9.6 Hz, 1H), 3.16 (dd, J1 = 16.2 Hz, J2 = 6.6 Hz, 1H), 2.90 (d, J = 15.6 Hz, 1H), 2.44 (d, J = 15.6 Hz, 1H), 1.42 (s, 3H), 1.38 (s, 3H). 13 13C{ 1 1H}NMR (150 MHz, CDCl3): δ 164.3, 150.0, 148.5, 136.3, 135.4, 135.0, 132.3, 128.5, 128.0, 126.1, 109.2, 108.1, 107.7, 64.3, 62.0, 56.2, 56.0, 51.1, 51.0, 37.6, 26.4, 20.1. HRMS (ESI) m / z: [M+Na] + Calcd for C 24 H 26 N2NaO3 413.1836; Found 413.1837.

[0084] (E)-11-Benzylidene-7,7-dimethyl-2,3,5b,7,8,11,11a,12-octahydro-9H-[1,4]dioxino[2',3':5,6]indeno[1,2-c]pyrazolo[1,2-a]pyrazol-9-one(3sa)

[0085] 1 1H NMR(600MHz,CDCl3):δ7.34 - 7.30(m,4H),7.23(d,J=1.8Hz,1H),7.20 - 7.17(m,1H),6.77(s,1H),6.69(s,1H),4.58(d,J=7.8Hz,1H),4.38 - 4.34(m,1H),4.24 - 4.20(m,4H),3.33(dd,J1=16.2Hz,J2=9.6Hz,1H),3.14(dd,J1=16.2Hz,J2=7.8Hz,1H),2.89(d,J=15.6Hz,1H),2.43(d,J=15.6Hz,1H),1.38(s,3H),1.36(s,3H). 13 C{ 1 H}NMR(150MHz,CDCl3):δ164.0,144.2,142.7,136.3,136.0,135.1,133.6,128.5,127.9,126.1,113.9,113.5,109.1,64.32,64.28,63.9,61.8,51.5,51.3,37.1,26.5,20.2.HRMS(ESI)m / z:[M + Na] + Calcd for C 24 H 24 N2NaO3411.1679;Found 411.1675.

[0086] (E)-12-Benzylidene-8,8-dimethyl-2,3,6b,8,9,12,12a,13-octahydro-10H-[1,4]dioxino[2',3':4,5]indeno[1,2-c]pyrazolo[1,2-a]pyrazol-10-one(3ta)

[0087] 11H NMR (600 MHz, CDCl3): δ 7.36 - 7.30 (m, 4H), 7.28 (d, J = 1.2 Hz, 1H), 7.18 (t, J = 6.6 Hz, 1H), 6.77 - 6.74 (m, 2H), 4.61 (d, J = 7.2 Hz, 1H), 4.40 - 4.35 (m, 1H), 4.27 - 4.22 (m, 4H), 3.45 (dd, J1 = 16.8 Hz, J2 = 9.6 Hz, 1H), 3.11 (dd, J1 = 16.2 Hz, J2 = 7.2 Hz, 1H), 2.89 (d, J = 15.6 Hz, 1H), 2.44 (d, J = 15.6 Hz, 1H), 1.37 (s, 3H), 1.36 (s, 3H). 13 C{ 1 13C{1H} NMR (150 MHz, CDCl3): δ 163.7, 143.8, 140.0, 136.4, 134.9, 134.3, 131.4, 128.5, 127.8, 126.1, 117.7, 116.5, 109.2, 64.5, 64.3, 64.1, 61.6, 51.8, 51.4, 34.4, 26.5, 20.3. HRMS (ESI) m / z: [M + Na] + Calcd for C 24 13H 24 11N2NaO3 411.1679; Found 411.1677.

[0088] (E)-5-Benzylidene-8-ethyl-1,1-dimethyl-1,2,5a,6,8,13b-hexahydro-3H,5H-pyrazolo[1”,2”:1',2']pyrazolo[3',4':3,4]cyclopenta[1,2-b]carbazol-3-one (3ua)

[0089] 11H NMR (600 MHz, CDCl3): δ 8.07 (d, J = 7.8 Hz, 1H), 7.94 (s, 1H), 7.46 - 7.44 (m, 1H), 7.40 - 7.38 (m, 3H), 7.35 - 7.32 (m, 3H), 7.24 - 7.18 (m, 3H), 4.82 (d, J = 7.8 Hz, 1H), 4.47 - 4.43 (m, 1H), 4.33 (q, J = 7.2 Hz, 2H), 3.63 (dd, J1 = 16.2 Hz, J2 = 9.0 Hz, 1H), 3.52 (dd, J1 = 16.8 Hz, J2 = 8.4 Hz, 1H), 2.91 (d, J = 15.6 Hz, 1H), 2.48 (d, J = 15.6 Hz, 1H), 1.50 (s, 3H), 1.42 - 1.39 (m, 6H). 13 13C{ 1 1H} NMR (150 MHz, CDCl3): δ 163.6, 141.6, 140.9, 140.3, 136.6, 135.2, 131.4, 128.6, 127.8, 126.1, 125.6, 122.8, 122.3, 120.1, 118.9, 117.1, 109.1, 108.6, 104.8, 64.2, 61.5, 52.5, 51.6, 37.9, 37.6, 26.7, 20.6, 13.7. HRMS (ESI) m / z: [M + Na] + Calcd for C 30 19 29 H21N3NaO 470.2203; Found 470.2208.

[0090] (E)-8-Benzylidene-12,12-dimethyl-7,7a,8,11,12,13a-hexahydro-10H-benzo[6,7]indeno[1,2-c]pyrazolo[1,2-a]pyrazol-10-one (3va)

[0091] 1H NMR(400MHz,CDCl3):δ7.96(d,J=8.0Hz,1H),7.88(d,J=8.4Hz,1H),7.81(d,J=8.4Hz,1H),7.55(t,J=7.6Hz,1H),7.46(t,J=7.6Hz,1H),7.40-7.31(m,6H),7.19(t,J=7.2Hz,1H),5.07(d,J=6.8Hz,1H),4.39(q,J=7.6Hz,1H),3.62-3.51(m,2H),2.87(d,J=15.6Hz,1H),2.44(d,J=15.6Hz,1H),1.58(s,3H),1.15(s,3H). 13 C{ 1 H}NMR(150MHz,CDCl3):δ164.4,142.0,136.6,135.8,135.2,133.0,130.1,129.9,129.1,128.6,127.7,126.4,126.2,125.2,123.8,123.5,108.5,63.2,61.9,52.8,52.1,38.6,25.5,20.1.HRMS(ESI)m / z:[M+Na] + Calcd for C 26 H 24 N2NaO 403.1781;Found 403.1776.

[0092] (E)-3,3-Dimethyl-10-(4-methylbenzylidene)-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3ab)

[0093] 1 H NMR(600MHz,CDCl3):δ7.29-7.20(m,7H),7.13(d,J=7.8Hz,2H),4.67(d,J=7.8Hz,1H),4.39-4.35(m,1H),3.44(dd,J1=16.2Hz,J2=9.0Hz,1H),3.25(dd,J1=16.2Hz,J2=7.2Hz,1H),2.89(d,J=15.6Hz,1H),2.44(d,J=15.6Hz,1H),2.34(s,3H),1.40(s,3H),1.36(s,3H). 13 C{ 11H NMR (150 MHz, CDCl3): δ 163.7, 143.3, 140.7, 136.0, 134.3, 133.4, 129.3, 128.7, 127.8, 126.9, 125.5, 125.2, 109.3, 64.2, 61.7, 51.4, 51.0, 37.6, 26.5, 21.2, 20.3. HRMS (ESI) m / z: [M+Na] + Calcd for C 23 H 24 N2NaO 367.1781; Found 367.1772.

[0094] (E)-10-(4-Methoxybenzylidene)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one (3ac)

[0095] 1 1H NMR (600 MHz, CDCl3): δ 7.29 - 7.26 (m, 4H), 7.23 - 7.21 (m, 3H), 6.88 (d, J = 9.0 Hz, 2H), 4.68 (d, J = 7.2 Hz, 1H), 4.37 - 4.33 (m, 1H), 3.82 (s, 3H), 3.43 (dd, J1 = 16.2 Hz, J2 = 9.0 Hz, 1H), 3.26 (dd, J1 = 16.2 Hz, J2 = 7.2 Hz, 1H), 2.89 (d, J = 15.6 Hz, 1H), 2.44 (d, J = 16.2 Hz, 1H), 1.40 (s, 3H), 1.36 (s, 3H). 13 13C{ 1 1H NMR (150 MHz, CDCl3): δ 163.6, 158.1, 143.3, 140.7, 133.5, 129.0, 128.9, 128.7, 126.9, 125.4, 125.2, 114.0, 109.1, 64.2, 61.7, 55.3, 51.3, 50.9, 37.5, 26.5, 20.3. HRMS (ESI) m / z: [M+Na] + Calcd for C 23 H 24 N2NaO2 383.1730; Found 383.1733.

[0096] (E)-10-(4-Chlorobenzylidene)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3ad)

[0097] 1 1H NMR(600MHz,CDCl3):δ7.30 - 7.17(m,9H),4.68(d,J = 7.8Hz,1H),4.35 - 4.31(m,1H),3.41(dd,J1 = 16.2Hz,J2 = 9.0Hz,1H),3.23(dd,J1 = 16.2Hz,J2 = 7.2Hz,1H),2.89(d,J = 16.2Hz,1H),2.44(d,J = 16.2Hz,1H),1.39(s,3H),1.37(s,3H). 13 C{ 1 H}NMR(150MHz,CDCl3):δ164.1,143.0,140.5,135.6,134.9,131.7,129.0,128.8,128.7,127.0,125.4,125.2,108.0,64.2,61.9,51.2,50.9,37.4,26.4,20.2.HRMS(ESI)m / z:[M+Na] + Calcd forC 22 H 21 ClN2NaO 387.1235;Found 387.1225.

[0098] (E)-10-(4-Bromobenzylidene)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3ae)

[0099] 11H NMR (600 MHz, CDCl3): δ 7.44 - 7.42 (m, 2H), 7.29 - 7.26 (m, 2H), 7.24 - 7.20 (m, 4H), 7.17 (d, J = 1.8 Hz, 1H), 4.69 (d, J = 8.4 Hz, 1H), 4.35 - 4.31 (m, 1H), 3.41 (dd, J1 = 16.2 Hz, J2 = 9.0 Hz, 1H), 3.23 (dd, J1 = 16.2 Hz, J2 = 7.2 Hz, 1H), 2.88 (d, J = 15.6 Hz, 1H), 2.44 (d, J = 15.6 Hz, 1H), 1.39 (s, 3H), 1.37 (s, 3H). 13 13C{ 1 1H}NMR (150 MHz, CDCl3): δ 164.1, 143.0, 140.5, 135.7, 135.4, 131.6, 129.3, 128.9, 127.0, 125.4, 125.2, 119.8, 107.9, 64.2, 61.9, 51.2, 51.0, 37.4, 26.5, 20.2. HRMS (ESI) m / z: [M + Na] + Calcd for C 22 1H 21 1BrN2NaO 431.0729; Found 431.0716.

[0100] (E)-10-(3-Methoxybenzylidene)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one (3af)

[0101] 1 1H NMR (600 MHz, CDCl3): δ 7.29 - 7.21 (m, 6H), 6.96 (d, J = 7.8 Hz, 1H), 6.89 (s, 1H), 6.75 (dd, J1 = 7.8 Hz, J2 = 2.4 Hz, 1H), 4.67 (d, J = 7.8 Hz, 1H), 4.40 - 4.35 (m, 1H), 3.81 (s, 3H), 3.46 (dd, J1 = 16.2 Hz, J2 = 9.0 Hz, 1H), 3.28 (dd, J1 = 16.2 Hz, J2 = 7.8 Hz, 1H), 2.89 (d, J = 15.6 Hz, 1H), 2.45 (d, J = 15.6 Hz, 1H), 1.40 (s, 3H), 1.36 (s, 3H). 13 13C{ 1H}NMR(150MHz,CDCl3):δ163.9,159.7,143.3,140.6,137.8,135.3,129.4,128.8,126.9,125.4,125.2,120.3,113.5,111.8,109.1,64.2,61.7,55.2,51.4,51.2,37.7,26.5,20.3.HRMS(ESI)m / z:[M+H] + Calcd for C 23 H 25 N2O2361.1911;Found 361.1903.

[0102] (E)-10-(3-Chlorobenzylidene)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3ag)

[0103] 1 H NMR(400MHz,CDCl3):δ7.34(s,1H),7.30-7.14(m,8H),4.69(d,J=7.6Hz,1H),4.39-4.33(m,1H),3.45(dd,J1=16.4Hz,J2=9.2Hz,1H),3.26(dd,J1=16.4Hz,J2=7.6Hz,1H),2.89(d,J=15.6Hz,1H),2.45(d,J=15.6Hz,1H),1.40(s,3H),1.37(s,3H). 13 C{ 1 H}NMR(100MHz,CDCl3):δ164.2,143.0,140.5,138.3,136.2,134.4,129.7,128.9,127.4,127.0,126.12,126.05,125.4,125.3,107.7,64.2,61.8,51.2,51.1,37.5,26.4,20.2.HRMS(ESI)m / z:[M+Na] + Calcd for C 22 H 21 ClN2NaO387.1235;Found 387.1222.

[0104] (E)-10-(3-Bromobenzylidene)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3ah)

[0105] 1 1H NMR(600MHz,CDCl3):δ7.50(s,1H),7.31 - 7.28(m,3H),7.26 - 7.21(m,3H),7.20 - 7.17(m,2H),4.69(d,J=7.8Hz,1H),4.38 - 4.34(m,1H),3.45(dd,J1=16.2Hz,J2=9.0Hz,1H),3.26(d,J1=16.2Hz,J2=7.2Hz,1H),2.89(d,J=16.2Hz,1H),2.45(d,J=16.2Hz,1H),1.40(s,3H),1.37(s,3H). 13 C{ 1 H}NMR(150MHz,CDCl3):δ164.2,143.0,140.5,138.6,136.2,130.3,130.0,128.94,128.87,127.0,126.5,125.4,125.3,122.7,107.6,64.3,61.9,51.2,51.1,37.5,26.4,20.2.HRMS(ESI)m / z:[M + Na] + Calcd for C 22 H 21 BrN2NaO 431.0729;Found 431.0720.

[0106] (E)-3,3-Dimethyl-10-(2-methylbenzylidene)-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3ai)

[0107] 11H NMR (600 MHz, CDCl3): δ 7.33 (d, J = 6.6 Hz, 1H), 7.27 (d, J = 7.2 Hz, 1H), 7.25 - 7.12 (m, 7H), 4.67 (d, J = 8.4 Hz, 1H), 4.30 - 4.25 (m, 1H), 3.16 (dd, J1 = 16.2 Hz, J2 = 9.0 Hz, 1H), 3.10 (dd, J1 = 16.2 Hz, J2 = 6.6 Hz, 1H), 2.90 (d, J = 15.6 Hz, 1H), 2.45 (d, J = 15.6 Hz, 1H), 2.31 (s, 3H), 1.40 (s, 3H), 1.39 (s, 3H). 13 13C{1H}NMR (150 MHz, CDCl3): δ 164.1, 143.2, 140.9, 136.7, 135.4, 135.3, 130.0, 128.7, 127.6, 126.9, 126.6, 125.7, 125.4, 125.2, 108.0, 64.1, 62.1, 51.1, 50.1, 37.8, 26.5, 20.3, 20.2. HRMS (ESI) m / z: [M + Na] 1 + Calcd for C 23 17 24 H17N2NaO 367.1781; Found 367.1794.

[0108] (E)-10-(2-Methoxybenzylidene)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one (3aj)

[0109] 11H NMR (600 MHz, CDCl3): δ 7.36 - 7.34 (m, 2H), 7.27 (d, J = 7.2 Hz, 1H), 7.24 - 7.19 (m, 3H), 7.17 (d, J = 7.2 Hz, 1H), 6.93 (t, J = 7.2 Hz, 1H), 6.87 (d, J = 8.4 Hz, 1H), 4.67 (d, J = 7.8 Hz, 1H), 4.33 - 4.29 (m, 1H), 3.83 (s, 3H), 3.28 (dd, J1 = 16.2 Hz, J2 = 9.0 Hz, 1H), 3.20 (dd, J1 = 16.2 Hz, J2 = 7.2 Hz, 1H), 2.89 (d, J = 15.6 Hz, 1H), 2.44 (d, J = 16.2 Hz, 1H), 1.39 (s, 3H), 1.37 (s, 3H). 13 13C{ 1 1H} NMR (150 MHz, CDCl3): δ 163.9, 156.8, 143.3, 140.9, 135.0, 128.6, 128.1, 127.7, 126.8, 125.4, 125.3, 125.2, 120.2, 110.6, 104.5, 64.1, 61.9, 55.5, 51.2, 50.5, 37.7, 26.5, 20.2. HRMS (ESI) m / z: [M + Na] + Calcd for C 23 19 24 H15N2NaO2 383.1730; Found 383.1721.

[0110] (E)-10-(2-Fluorobenzylidene)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one (3ak)

[0111] 11H NMR (600 MHz, CDCl3): δ 7.37 (td, J1 = 7.8 Hz, J2 = 1.2 Hz, 1H), 7.28 (d, J = 7.8 Hz, 1H), 7.25 - 7.16 (m, 5H), 7.10 (td, J1 = 7.8 Hz, J2 = 1.2 Hz, 1H), 7.07 - 7.04 (m, 1H), 4.69 (d, J = 8.4 Hz, 1H), 4.33 - 7.29 (m, 1H), 3.27 (dd, J1 = 16.2 Hz, J2 = 9.0 Hz, 1H), 3.17 (dd, J1 = 16.2 Hz, J2 = 6.6 Hz, 1H), 2.90 (d, J = 15.6 Hz, 1H), 2.45 (d, J = 16.2 Hz, 1H), 1.39 (s, 6H). 13 13C{ 1 1H}NMR (150 MHz, CDCl3): δ 164.5, 159.8 (d, 1 J C-F = 246.2 Hz), 142.9, 140.8, 136.8, 128.9 (d, 4 J C-F = 3.2 Hz), 128.7, 127.9 (d, 3 J C-F = 7.7 Hz), 127.0, 125.4, 125.2, 124.3, 123.8 (d, 4 J C-F = 3.2 Hz), 115.6 (d, 2 J C-F = 21.9 Hz), 101.5 (d, 3 J C-F = 4.4 Hz), 64.1, 62.2, 51.0, 50.6 (d, 5 J C-F = 2.3 Hz), 37.4, 26.4, 20.1. 19 19F NMR (565 MHz, DMSO): δ -116.89--116.93 (m). HRMS (ESI) m / z: [M + Na] + Calcd for C 22 19H 21 19FN2NaO 371.1530; Found 371.1523.

[0112] (E)-10-(2-Chlorobenzylidene)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3al)

[0113] 1 1H NMR(600 MHz, CDCl3): δ 7.42 (d, J = 7.2 Hz, 1H), 7.39 (d, J = 7.8 Hz, 1H), 7.33 (s, 1H), 7.28 - 7.20 (m, 4H), 7.16 - 7.14 (m, 2H), 4.68 (d, J = 7.8 Hz, 1H), 4.30 - 4.25 (m, 1H), 3.21 - 3.13 (m, 2H), 2.90 (d, J = 16.2 Hz, 1H), 2.45 (d, J = 15.6 Hz, 1H), 1.40 (s, 3H), 1.38 (s, 3H). 13 C{ 1 1H}NMR(150 MHz, CDCl3): δ 164.4, 143.0, 140.7, 136.6, 134.8, 133.8, 129.7, 128.8, 128.7, 127.6, 127.0, 126.5, 125.4, 125.1, 106.0, 64.1, 62.1, 51.1, 50.4, 37.7, 26.5, 20.2. HRMS(ESI) m / z: [M + Na] + Calcd for C 22 H 21 ClN2NaO387.1235; Found 387.1231.

[0114] (E)-10-(2-Bromobenzylidene)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3am)

[0115] 11H NMR (600 MHz, CDCl3): δ 7.60 (dd, J1 = 7.8 Hz, J2 = 1.2 Hz, 1H), 7.41 (dd, J1 = 7.8 Hz, J2 = 1.2 Hz, 1H), 7.28 - 7.27 (m, 3H), 7.25 - 7.20 (m, 2H), 7.16 (d, J = 7.8 Hz, 1H), 7.08 (td, J1 = 7.8 Hz, J2 = 1.2 Hz, 1H), 4.68 (d, J = 7.8 Hz, 1H), 4.26 (qd, J1 = 8.4 Hz, J2 = 1.8 Hz, 1H), 3.15 (d, J = 8.4 Hz, 2H), 2.91 (d, J = 15.6 Hz, 1H), 2.46 (d, J = 15.6 Hz, 1H), 1.41 (s, 3H), 1.39 (s, 3H). 13 13C{ 1 1H} NMR (150 MHz, CDCl3): δ 164.4, 143.0, 140.7, 136.7, 136.5, 132.9, 129.0, 128.7, 127.8, 127.1, 127.0, 125.4, 125.2, 124.6, 108.6, 64.1, 62.1, 51.1, 50.3, 37.7, 26.5, 20.2. HRMS (ESI) m / z: [M + Na] + Calcd for C 22 18 21 H11BrN2NaO 431.0729; Found 431.0723.

[0116] (E)-10-(3,4-Dimethoxybenzylidene)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one (3an)

[0117] 1H NMR(600MHz,CDCl3):δ7.30-7.27(m,2H),7.24-7.21(m,3H),6.94(dd,J1=8.4Hz,J2=1.8Hz,1H),6.87(d,J=1.8Hz,1H),6.85(d,J=8.4Hz,1H),4.68(d,J=7.8Hz,1H),4.38-4.34(m,1H),3.89(s,3H),3.88(s,3H),3.44(dd,J1=16.8Hz,J2=9.6Hz,1H),3.29(dd,J1=16.2Hz,J2=7.2Hz,1H),2.89(d,J=15.6Hz,1H),2.45(d,J=15.6Hz,1H),1.40(s,3H),1.36(s,3H). 13 C{ 1 H}NMR(150MHz,CDCl3):δ163.6,148.8,147.6,143.2,140.7,133.7,129.2,128.8,127.0,125.5,125.2,120.0,111.6,111.3,109.2,64.2,61.7,55.93,55.91,51.3,51.0,37.6,26.5,20.3.HRMS(ESI)m / z:[M+Na] + Calcd forC 24 H 26 N2NaO3413.1836;Found 413.1826.

[0118] (E)-10-(3,4-Dichlorobenzylidene)-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3ao)

[0119] 11H NMR (600 MHz, CDCl3): δ 7.42 (d, J = 1.8 Hz, 1H), 7.37 (d, J = 8.4 Hz, 1H), 7.30 - 7.28 (m, 2H), 7.24 (t, J = 7.2 Hz, 2H), 7.15 (dd, J1 = 8.4 Hz, J2 = 2.4 Hz, 1H), 7.13 (d, J = 1.2 Hz, 1H), 4.70 (d, J = 7.8 Hz, 1H), 4.36 - 4.32 (m, 1H), 3.43 (dd, J1 = 16.2 Hz, J2 = 9.0 Hz, 1H), 3.24 (dd, J1 = 16.2 Hz, J2 = 7.8 Hz, 1H), 2.89 (d, J = 15.6 Hz, 1H), 2.45 (d, J = 16.2 Hz, 1H), 1.39 (s, 3H), 1.37 (s, 3H). 13 13C{ 1 1H} NMR (150 MHz, CDCl3): δ 164.3, 142.8, 140.4, 136.62, 136.59, 132.5, 130.4, 129.6, 129.1, 128.9, 127.15, 127.11, 125.4, 125.2, 106.6, 64.3, 61.9, 51.2, 51.0, 37.4, 26.4, 20.2. HRMS (ESI) m / z: [M + Na] + Calcd for C 22 17 20 H15Cl2N2NaO4 421.0845; Found 421.0841.

[0120] (E)-10-Ethylidene-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one (3ap)

[0121] 1 1H NMR (600 MHz, CDCl3): δ 7.29 - 7.20 (m, 4H), 6.09 (qd, J1 = 7.2 Hz, J2 = 1.8 Hz, 1H), 4.59 (d, J = 7.8 Hz, 1H), 4.09 - 4.05 (m, 1H)), 3.36 (dd, J1 = 16.2 Hz, J = 9.6 Hz, 1H), 3.22 (dd, J1 = 16.2 Hz, J2 = 7.8 Hz, 1H), 2.82 (d, J = 16.2 Hz, 1H), 2.39 (d, J = 15.6 Hz, 1H), 1.77 (d, J = 7.2 Hz, 3H), 1.38 (s, 3H), 1.33 (s, 3H).13 C{ 1 H} NMR (150 MHz, CDCl3): δ 162.7, 143.7, 140.7, 134.4, 128.7, 126.8, 125.5, 125.2, 103.2, 63.9,

[0122] 61.6, 51.3, 50.2, 37.5, 26.7, 20.5, 13.4. HRMS (ESI) m / z: [M+Na] + Calcd for C 17 H 20 N2NaO 291.1468; Found 291.1467.

[0123] (E)-3,3-Dimethyl-10-(2-phenylethylidene)-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one (3aq)

[0124] 1 H NMR (400 MHz, CDCl3): δ 7.31 - 7.18 (m, 9H), 6.31 (td, J1 = 8.0 Hz, J2 = 1.6 Hz, 1H), 4.61 (d, J = 8.0 Hz, 1H), 4.14 (q, J = 8.0 Hz, 1H), 3.49 (d, J = 8.0 Hz, 2H), 3.38 - 3.25 (m, 2H), 2.83 (d, J = 16.0 Hz, 1H), 2.40 (d, J = 16.0 Hz, 1H), 1.40 (s, 3H), 1.32 (s, 3H). 13 C{ 1 H} NMR (150 MHz, CDCl3): δ 163.0, 143.7, 140.6, 140.5, 134.5, 128.8, 128.5, 128.3, 126.8, 126.2, 125.5, 125.3, 106.8, 64.1, 61.5, 51.4, 50.6, 37.9, 34.6, 26.7, 20.6. HRMS (ESI) m / z: [M+Na] + Calcd for C 23 H 24 N2NaO 367.1781; Found 367.1770.

[0125] 10-Ethoxy-10-isopropyl-3,3-dimethyl-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3ar)

[0126] 1 1H NMR(600MHz,CDCl3):δ7.22-7.16(m,4H),4.61(d,J=9.6Hz,1H),3.57-3.52(m,1H),3.47-3.43(m,2H),3.36-3.28(m,2H),2.88(dd,J1=17.4Hz,J2=9.6Hz,1H),2.79(d,J=15.6Hz,1H),2.37(d,J=15.0Hz,1H),1.47(s,3H),1.30(s,3H),1.09(d,J=6.6Hz,3H),1.02(d,J=7.2Hz,3H),0.86(t,J=6.6Hz,3H). 13 C{ 1 H}NMR(150MHz,CDCl3):δ164.9,144.5,142.1,127.7,126.2,124.6,124.2,93.1,64.1,61.8,58.1,50.9,50.3,32.9,28.3,27.0,20.0,18.1,17.5,15.1.HRMS(ESI)m / z:[M+Na] + Calcd for C 20 H 28 N2NaO 351.2043;Found351.2026.

[0127] 10-Ethoxy-3,3-dimethyl-10-(phenoxymethyl)-2,3,4a,9,9a,10-hexahydro-1H-indeno[1,2-c]pyrazolo[1,2-a]pyrazol-1-one(3as)

[0128] 11H NMR (400 MHz, CDCl3): δ 7.31 - 7.25 (m, 3H), 7.24 - 7.18 (m, 3H), 6.98 - 6.94 (m, 3H), 4.85 (d, J = 9.6 Hz, 1H), 4.74 (d, J = 8.8 Hz, 1H), 4.29 (d, J = 9.6 Hz, 1H), 3.71 (td, J1 = 8.8 Hz, J2 = 1.6 Hz, 1H), 3.53 - 3.46 (m, 1H), 3.38 (dd, J1 = 16.4 Hz, J2 = 1.6 Hz, 1H), 3.32 - 3.25 (m, 1H), 2.95 (dd, J1 = 16.4 Hz, J2 = 8.4 Hz, 1H), 2.80 (d, J = 15.2 Hz, 1H), 2.33 (d, J = 15.2 Hz, 1H), 1.50 (s, 3H), 1.38 (s, 3H), 0.76 (t, J = 6.8 Hz, 3H). 13 C{ 1 1H}NMR (100 MHz, CDCl3): δ 166.9, 158.4, 143.7, 142.8, 129.5, 127.8, 126.4, 124.4, 124.1, 121.2, 114.7, 89.8, 65.0, 64.2, 63.9, 59.9, 53.1, 49.9, 31.5, 26.3, 19.4, 15.1. HRMS (ESI) m / z: [M+Na] + Calcd for C 24 1H 28 N2NaO3 415.1992; Found 415.1989.

[0129] Example 4

[0130] The synthesized product indeno - pyrazolo - pyrazolidinone compound 3 of the present invention can undergo a series of reactions to synthesize further derivatives, thereby showing its important application value in organic synthesis. For example:

[0131]

[0132] 3aa (33.0 mg, 0.1 mmol) and Lawesson's reagent (30.3 mg, 0.075 mmol) were successively added into a 15 mL round - bottom flask, and then toluene (1 mL) was added to dissolve them. Then the reaction system was reacted at 100 °C for 12 hours. After the reaction was completed, it was cooled to room temperature, and water was added to quench the reaction. It was extracted with ethyl acetate, and the organic phases were combined, washed with water, dried, filtered, concentrated, and separated by silica gel column (petroleum ether / ethyl acetate = 10 / 1) to obtain the yellow solid product 4 (31.1 mg, 90%). The characterization data of this compound are as follows: 11H NMR (600 MHz, CDCl3): δ 9.00 (s, 1H), 7.40 (d, J = 7.8 Hz, 2H), 7.36 (t, J = 7.8 Hz, 2H), 7.30 - 7.20 (m, 5H), 4.69 (d, J = 7.8 Hz, 1H), 4.45 - 4.41 (m, 1H), 3.44 (dd, J1 = 15.6 Hz, J2 = 9.0 Hz, 1H), 3.33 (dd, J1 = 16.2 Hz, J2 = 8.4 Hz, 1H), 3.28 (d, J = 16.2 Hz, 1H), 3.02 (d, J = 16.2 Hz, 1H), 1.41 (s, 3H), 1.31 (s, 3H). 13 13C{1H} NMR (150 MHz, CDCl3): δ 177.4, 143.7, 139.6, 135.64, 135.62, 129.0, 128.7, 128.5, 127.2, 126.8, 125.6, 125.3, 116.0, 64.5, 63.3, 61.7, 51.7, 38.1, 26.0, 20.4. HRMS (ESI) m / z: [M + Na] 1 + Calcd for C 22 19 22 11N2NaS 369.1396; Found 369.1392.

[0133]

[0134] 3aa (66.1 mg, 0.2 mmol) and meta-chloroperoxybenzoic acid (69.0 mg, 0.4 mmol) were added to a 15 mL round-bottom flask, and then chloroform (2 mL) was added to dissolve them. Subsequently, the reaction flask was placed at room temperature for 12 h. After the reaction was completed, it was cooled to room temperature and concentrated under reduced pressure. The residue was separated by silica gel column chromatography (petroleum ether / ethyl acetate = 15 / 1) to obtain the yellow solid product 5 (15.1 mg, 31%). The characterization data of this compound are as follows: 1H NMR (600MHz, CDCl3): δ7.78(d,J=7.8Hz,1H),7.67(d,J=2.4Hz,1H),7.63(d,J=7 .2Hz,2H),7.48(t,J=7.8Hz,2H),7.41(t,J=7.2Hz,1H),7.31(t,J=7.2Hz,1H),7 .26(t,J=8.4Hz,1H),7.14(d,J=7.8Hz,1H),6.29(d,J=7.2Hz,1H),3.87-3.85(m ,1H),3.62(dd,J1=16.8Hz,J2=10.2Hz,1H),2.89(dd,J1=16.2Hz,J2=3.0Hz,1H). 13 C{ 1 H}NMR (150MHz, CDCl3): δ167.1,141.2,138.2,134.2,131.1,129.4,129.4,129.0,128.9,127.3,125.8,125.3,99.0,38.2,36.3.HRMS(ESI)m / z:[M+Na] + Calcd for C 17 H 14 N2Na 269.1049; Found 269.1048.

[0135]

[0136] To a reaction tube were added 3ja (40.9 mg, 0.1 mmol), phenylacetylene (16.5 μL, 0.15 mmol), triphenylphosphine (5.2 mg, 0.02 mmol), potassium phosphate (25.5 mg, 0.12 mmol), palladium acetate (1.1 mg, 0.005 mmol), and DMSO (1 mL). The mixture was evacuated and filled with argon. The system was then reacted at 80°C (oil bath) for 24 hours. The reaction was then quenched with water and extracted with ethyl acetate. The organic phase was washed with water, dried, filtered, concentrated, and separated on a silica gel column (petroleum ether / ethyl acetate = 10 / 1) to obtain a yellow solid product 6 (39.1 mg, 91%). The characterization data of this compound are as follows: 11H NMR (400 MHz, CDCl3): δ 7.52 - 7.48 (m, 2H), 7.40 (d, J = 8.0 Hz, 1H), 7.36 - 7.30 (m, 8H), 7.25 - 7.17 (m, 3H), 7.21 - 7.17 (m, 1H), 4.65 (d, J = 8.0 Hz, 1H), 4.40 - 4.34 (m, 1H), 3.41 (dd, J1 = 16.4 Hz, J2 = 9.2 Hz, 1H), 3.24 (dd, J1 = 16.4 Hz, J2 = 7.6 Hz, 1H), 2.89 (d, J = 15.6 Hz, 1H), 2.45 (d, J = 16.0 Hz, 1H), 1.38 (s, 3H), 1.35 (s, 3H). 13 13C{1H} NMR (150 MHz, CDCl3): δ 163.9, 143.6, 140.9, 136.2, 134.8, 131.7, 130.5, 128.6, 128.4, 128.3, 127.9, 126.3, 125.4, 123.8, 123.2, 109.4, 89.7, 89.3, 64.0, 61.8, 51.3, 51.0, 37.3, 26.5, 20.3. HRMS (ESI) m / z: [M+Na] 1 + Calcd for C 30 1H 26 2N2NaO453.1937; Found 453.1922.

[0137]

[0138] Add 3ja (40.9 mg, 0.1 mmol), styrene (11.5 μL, 0.1 mmol), Pd(dppf)Cl2 (7.3 mg, 0.01 mmol), triethylamine (20.2 mg, 0.2 mmol) and DMF (1 mL) into a reaction tube. Evacuate and backfill with argon. Then react the system at 100 °C (oil bath) for 24 h. Subsequently, quench the reaction with water and extract with ethyl acetate. Wash the organic phase with water, dry, filter, concentrate, and separate by silica gel column (petroleum ether / ethyl acetate = 10 / 1) to obtain the yellow solid product 7 (21.8 mg, 50%). The characterization data of this compound are as follows: 11H NMR (400 MHz, CDCl3): δ 7.51 - 7.49 (m, 2H), 7.37 - 7.29 (m, 8H), 7.28 - 7.24 (m, 3H), 7.22 - 7.17 (m, 1H), 7.08 (s, 2H), 4.66 (d, J = 8.0 Hz, 1H), 4.42 - 4.36 (m, 1H), 3.46 (dd, J1 = 16.4 Hz, J2 = 9.2 Hz, 1H), 3.28 (dd, J1 = 16.4 Hz, J2 = 7.6 Hz, 1H), 2.90 (d, J = 16.0 Hz, 1H), 2.46 (d, J = 16.0 Hz, 1H), 1.40 (s, 3H), 1.37 (s, 3H). 13 C{ 1 13C{1H}NMR (150 MHz, CDCl3): δ 163.9, 143.9, 140.1, 138.2, 137.2, 136.3, 135.0, 129.1, 128.7, 128.5, 128.3, 127.9, 127.8, 126.6, 126.2, 125.6, 122.9, 109.3, 63.9, 61.7, 51.3, 37.5, 26.5, 20.3. HRMS (ESI) m / z: [M+Na] + Calcd for C 30 H 28 N2NaO 455.2094; Found 455.2088.

[0139] Example 5

[0140] The anti - cancer activity of the compound was evaluated by studying the cell anti - proliferation activity using the CCK8 assay. First, cells were seeded into 96 - well plates containing 100 μL of medium per well at a density of 5000 cells per well and incubated overnight at 37 °C and 5% CO2. The next day, 100 μL of the test compound diluted with medium (concentrations from 0.03 nM - 30 μM) was added to each well. Then, the cells were incubated at 37 °C and 5% CO2 for 72 hours. Subsequently, 10 μL of CCK8 was added to each well, and the 96 - well plate was incubated at 37 °C for 2 hours. The absorbance was measured at 450 nm (using 630 nm as the reference wavelength) using an EnVision multilatelbel Reader (Perkinermer), and the IC 50 value was calculated using GraphPad Prism 6.0 software. All experiments were performed with three parallel samples and repeated three times. Three types of cancer cells, A - 549, Ramos, and Hela, were selected as the research objects, and 5 - fluorouracil (5 - FU) was used as the positive control drug.

[0141] The anti-cancer activity results of some compounds are as follows:

[0142]

[0143] The above embodiments have described the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above embodiments. What is described in the above embodiments and the specification is only to illustrate the principles of the present invention. Without departing from the scope of the principles of the present invention, the present invention will have various changes and improvements, and these changes and improvements all fall within the scope of protection of the present invention.

Claims

1. An indenopyrazolopyrazolidinone compound, characterized in that: The chemical structure is:

2. A method for synthesizing an indenopyrazolopyrazolidinone compound 3A, characterized in that: The method comprises the following steps: mixing an arylazomethine imine compound 1, a 1-substituted cyclopropanol compound 2, a catalyst, an additive and an organic solvent, and heating the mixture to react to obtain an indenopyrazolopyrazolidinone compound 3A. The reaction equation is: Wherein: Compound 1 is selected from: Compound 2 is selected from: Compound 3A is selected from: The additives are copper acetate and silver hexafluoroantimonate, or copper acetate monohydrate and silver hexafluoroantimonate; and the catalyst is [RhCp*Cl2]2, [IrCp*Cl2]2 or [RhCp*(MeCN)3](SbF6)2.

3. The method for synthesizing the indenopyrazolopyrazolidinone compound 3A according to claim 2, characterized in that: The organic solvent is methanol, ethanol, toluene or tetrahydrofuran; and the reaction temperature is 60-90°C.

4. The method for synthesizing the indenopyrazolopyrazolidinone compound 3A according to claim 2, characterized in that: The molar ratio of the aromatic azomethine imine compound 1, the 1-substituted cyclopropanol compound 2, the catalyst, and the additive is 1-2:1-3:0.01-0.1:0.5-2.

5. A method for synthesizing an indenopyrazolopyrazolidinone compound 3B, characterized in that: The method comprises the following steps: mixing an arylazomethine imine compound 1, a 1-substituted cyclopropanol compound 2, a catalyst, an additive, and ethanol, and heating the mixture to react to obtain an indenopyrazolopyrazolidinone compound 3B. The reaction equation is: Wherein: Compound 1 is selected from Compound 2 is selected from Compound 3B is selected from The additives are copper acetate and silver hexafluoroantimonate, or copper acetate monohydrate and silver hexafluoroantimonate; and the catalyst is [RhCp*Cl2]2, [IrCp*Cl2]2 or [RhCp*(MeCN)3](SbF6)2.

6. The method for synthesizing the indenopyrazolopyrazolidinone compound 3B according to claim 5, characterized in that: The reaction temperature is 60-90°C.

7. The method for synthesizing the indenopyrazolopyrazolidinone compound 3B according to claim 5, characterized in that: The molar ratio of the aromatic azomethine imine compound 1, the 1-substituted cyclopropanol compound 2, the catalyst, and the additive is 1-2:1-3:0.01-0.1:0.5-2.

8. Use of the indenopyrazolopyrazolidinone compound according to claim 1 in the synthesis of an anti-A-549 active drug, wherein the compound is 3aa, 3ca, 3ha, 3ja, 3sa, 3ta, 3ab, 3ak, or 3ar.

9. Use of the indenopyrazolopyrazolidinone compound according to claim 1 in the synthesis of an anti-Ramos active drug, wherein the compound is 3aa, 3ca, 3ha, 3ja, 3sa, 3ta, 3ab, 3ak, 3ar, or 3as.

10. Use of the indenopyrazolopyrazolidinone compound according to claim 1 in the synthesis of anti-Hela active drugs, wherein the compound is 3ca, 3ha, 3ja, or 3ak.

Images