1-indanone derivative, and preparation method and application thereof

Abstract

The invention relates to the technical field of medicinal chemistry, and discloses a 1-indanone derivative as well as a preparation method and application thereof. The structural general formula of the 1-indanone derivative is as shown in formula I: # imgabs0 # R1 is Me-or naphthenic base; r2 is Me <->, alkyl or alkyl impurity; r3 is Me <->, aryl or substituted alkyl; r4 is selected from alkyl or halogen. The 1-indanone derivative prepared by the invention is a compound with a brand-new structure, has certain biological activity, and can be used as a potential drug or a candidate drug molecule for research in the aspects of cancer resistance, tumor resistance, inflammation resistance, bacteria resistance and the like. The invention also provides a preparation method of the 1-indanone derivative, cyclopropenone and olefin are used as raw materials, one-step synthesis is performed under the action of a catalyst, a solvent and a reducing agent, and the 1-indanone derivative has the advantages of simplicity in operation, higher yield, good selectivity, wide substrate adaptability, convenience in industrial production and the like.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical chemistry, and in particular, relates to 1-indanone derivatives, preparation methods thereof, and uses thereof. Background Art

[0002] Indanone is an important class of organic compounds, which are commonly found in drugs, natural products, pesticides, dyes, organic luminescent materials and a variety of fine chemicals. For example, ninhydrin, also known as hydrated ninhydrin, is a common reagent for identifying amino acids. Among them, 1-indanone compounds are an important drug structural scaffold, which has attracted extensive attention from synthetic chemists due to its anti-cancer, anti-inflammatory and other biological activities. Among them, the natural product pauuciflorol F is considered to be a potential cancer cell growth inhibitor, and euplectin isolated from moss exhibits strong anti-tumor activity. In addition, some indanone compounds have been used clinically, such as donepezil hydrochloride synthesized based on 5,6-dimethoxy-1-indanone, which has been approved by the US FDA for the treatment of Alzheimer's disease. In addition, indacrinone is used as a hypotensive drug. Based on this, it is extremely important to synthesize this class of compounds with 1-indanone structure.

[0003] At present, there are many reports on the synthesis of 1-indanone compounds, including intramolecular Friedel-Crafts acylation reaction ((a) Tetrahedron Lett. 2023, 123, 154523.), traditional Grignard reaction ((b) Angew. Chem. Int. Ed. 2021, 60, 15497-15502.), Vilsmeier-Haack cyclization reaction and the aromatic C (sp 2 )-H bond activation reaction, etc. ((c) Org. Chem. Front. 2021, 8, 1447-1453; (d) J. Org. Chem. 2021, 86, 14102-14112.). The existing synthesis methods have the following problems to varying degrees: such as the need for precious metal catalysis, the difficulty in obtaining raw materials, low regioselectivity or poor functional group compatibility, which seriously affect their industrial production. Summary of the invention

[0004] Technical problems solved by the present invention:

[0005] The invention is used to solve the problems existing in the synthesis method of the existing 1-indanone compounds, such as the need for precious metal catalysis, difficulty in obtaining raw materials, low regional selectivity or poor functional group compatibility.

[0006] The technical solution adopted by the present invention is:

[0007] In view of the above technical problems, the present invention provides a 1-indanone derivative, a preparation method thereof, and a use thereof. The 1-indanone derivative provided by the present invention has good biological activity. The preparation method provided by the present invention has simple operation, readily available raw materials, convenient and fast synthesis, and is easy to be applied to industrial production.

[0008] Specifically:

[0009] First, the present invention provides a 1-indanone derivative, the general structural formula of the 1-indanone is shown in Formula I:

[0010]

[0011] In Formula I,

[0012] R 1 is Me-, cyclopentyl, cyclohexyl, cycloheptyl, cyclododecyl;

[0013] R 2 C 10 Straight-chain or branched alkyl, oxocyclohexyl, N-pyrrolidone;

[0014] R 3 is Me-, cyclohexyl, phenyl, dimethyl tert-butylsilyl, or substituted alkyl; the substituted alkyl may be 4-oxopentyl or 1-hydroxy-3-methylhexyl;

[0015] R 4 Me-, Cl, F.

[0016] According to some preferred embodiments, in Formula I,

[0017] R 1 is Me-, cyclopentyl, cyclohexyl;

[0018] R 2 C 10 Straight-chain or branched alkyl, oxocyclohexyl, N-pyrrolidone;

[0019] R 3 is Me-, cyclohexyl, phenyl, substituted alkyl;

[0020] R 4 Me-, Cl, F.

[0021] Second, the present invention provides a method for preparing the above-mentioned 1-indanone derivative, comprising the following steps: adding 1,2-diphenylcyclopropene-3-one and 2-methyl-2-propene-1-ol into a reaction container, then adding a catalyst, a solvent and a reducing agent, and obtaining the 1-indanone derivative through reaction, separation and purification.

[0022] The chemical reaction formula is,

[0023]

[0024] According to some preferred embodiments, the molar ratio of 1,2-diphenylcyclopropene-3-one to 2-methyl-2-propene-1-ol is 1:1-5, and more preferably 1:3.

[0025] According to some preferred embodiments, the molar ratio of 1,2-diphenylcyclopropene-3-one to the catalyst is 0.01-2, and more preferably 1:0.3.

[0026] According to some preferred embodiments, the catalyst comprises FeBr 3 、FeCl 3 、Fe(OTf) 3 、FeC 2 O 4 、FeSO 4 7H 2 0.FeCl 2 ·4H 2 O、Fe(OAc) 2 、Fe(acac) 3 、Fe(ox) 2 6H 2 O、Cu(acac) 2 、Cu(OTf) 2 、Ni(acac) 3 、Ni(OTf) 2 、Co(acac) 2 、Co(acac) 3 At least one of .

[0027] According to some preferred embodiments, the solvent includes 1-Phenylethanol, EtOH, MeOH, THFtoluene (toluene), (CH 2 OH) 2 , MeCN, DMF, DCE, DMSO.

[0028] According to some preferred embodiments, the reaction temperature is from room temperature to 120°C, and the reaction time is 6 to 30 hours, more preferably 60°C for 24 hours.

[0029] The beneficial effects achieved by the present invention are:

[0030] (1) The 1-indanone derivatives provided by the present invention have certain biological activities and can be used as potential drugs or candidate drug molecules for research in anti-cancer, anti-tumor, anti-inflammatory, antibacterial and other aspects.

[0031] (2) The synthesis method provided by the present invention has the advantages of simple operation, low cost, high yield, and wide substrate adaptability. DETAILED DESCRIPTION

[0032] In order to make the purpose, technical scheme and advantages of the embodiments of the present invention clearer, the technical scheme in the embodiments of the present invention will be described clearly and completely below. If the specific conditions are not specified in the embodiments, they are carried out according to conventional conditions or conditions recommended by the manufacturer. If the manufacturer of the reagents or instruments used is not specified, they are all conventional products that can be purchased commercially.

[0033] The 1-indanone derivative and the preparation method thereof of the present invention are specifically described below with reference to the examples.

[0034] Example 1 Synthesis of Indane Derivative 6a

[0035]

[0036] To the test tube, 61.8 mg of 1,2-diphenylcyclopropene-3-one, 167.5 mg of tert-butyldimethyl((2-methylallyl)oxy)silane, and 31.8 mg of Fe(acac) were added in sequence. 3 And 64.9 mg of phenylsilane, then add 1.5 mL of methanol, react at 60 ° C for 24 hours, cool to room temperature, add saturated brine, and then extract with dichloromethane. The organic phases are combined, dried over anhydrous magnesium sulfate, and column chromatography is used to obtain a yellow solid 6a with a yield of 55%.

[0037] White solid, melting point: 76-77℃. 1 H NMR(400MHz,Chloroform-d)δ7.58(dd,J=14.04,7.27Hz,2H),7.49-7.41(m,4H),7.35-7.24(m,4H),3.79(s,2H),1.32(s,6H),0.90(s,9H),0.00(s,6H). 13 C NMR(101MHz,Chloroform-d)δ165.0,162.2,136.4,134.9,130.4,129.3,128.1,127.9,127.6,127.5,127.1,35.9,23.7.HRMS(ESI):m / z:[M+H] + Calcd.ForC 25 H 33 O 2 Si + :393.2250;Found:393.2249.

[0038] Example 2 Synthesis of indanone derivative 6b

[0039]

[0040] Add 61.8 mg of 1,2-diphenylcyclopropene-3-one, 63.1 mg of 2-methyl-2-butene, and 45.3 mg of Fe(OTf) to the test tube in sequence. 3 And 64.9 mg of phenylsilane, then add 1.5 mL of ethanol, react at 60 ° C for 24 hours, cool to room temperature, add saturated brine, and then extract with dichloromethane. The organic phases are combined, dried over anhydrous magnesium sulfate, and column chromatography is used to obtain a yellow solid 6b with a yield of 68%.

[0041] White solid, melting point: 64-65℃. 1 H NMR(400MHz,Chloroform-d)δ7.51(dt,J=6.99,1.17Hz,2H),7.43-7.28(m,4H),7.19-7.1 1(m,1H),7.19-7.11(m,2H),1.83(q,J=7.48Hz,2H),1.17(s,6H),0.87(t,J=7.46Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ198.0,163.4,145.1,135.9,134.3,133.3,131.3,130. 1,128.1,127.6,127.4,123.7,122.4,40.3,34.1,28.8,9.6.HRMS(ESI):m / z:[M+Na] + Calcd.For C 20 H 20 ON + :299.1412;Found:299.1415.

[0042] Example 3 Synthesis of indanone derivative 6c

[0043]

[0044] Add 61.8 mg of 1,2-diphenylcyclopropene-3-one, 113.6 mg of 6-methyl-5-heptene-2-one, and 31.8 mg of Fe(acac) to the test tube. 3 And 64.9 mg of phenylsilane, and then add 1.5 mL of toluene, react at 60 ° C for 24 hours, cool to room temperature, add saturated brine, and then extract with dichloromethane. The organic phases are combined, dried over anhydrous magnesium sulfate, and column chromatography is used to obtain a yellow solid 6c with a yield of 60%.

[0045] White solid, melting point: 111-112℃. 1 H NMR(400MHz,Chloroform-d)δ7.53-7.48(m,2H),7.42-7.31(m,4H),7.26-7.22(m,1H),7.15(dd,J=7.4 7,1.91Hz,2H),2.30(t,J=7.10Hz,2H),2.04(s,3H),1.78-1.71(m,2H),1.59-1.51(m,2H),1.21(s,6H). 13 C NMR(101MHz,Chloroform-d)δ208.5,197.8,163.0,145.0,135.6,134.1,133.4,131.3,130.1, 128.2,127.6,127.5,123.6,122.5,43.8,40.9,39.8,29.8,29.1,19.5.HRMS(ESI):m / z:[M+Na] + Calcd.For C 23 H 24 O 2 Na + :355.1674;Found:355.1675.

[0046] Example 4 Synthesis of Indane Derivative 6d

[0047]

[0048] Add 61.8 mg 1,2-diphenylcyclopropene-3-one, 151.4 mg 1-dodecene, and 31.8 mg Fe(acac) to the test tube in sequence. 3 And 64.9 mg of phenylsilane, then add 1.5 mL of ethylene glycol, react at 60°C for 24 hours, cool to room temperature, add saturated brine, extract with dichloromethane, combine the organic phases, dry over anhydrous magnesium sulfate, and obtain a yellow liquid 6d by column chromatography with a yield of 75%.

[0049] White solid, 1 H NMR(400MHz,Chloroform-d)δ7.44(d,J=6.77Hz,1H),7.37-7.25(m,5H),7.19(m,3H),3.08(dp,J=8.53,7.01Hz,1H ),1.75(m,1H),1.61-1.53(m,1H),1.31(d,J=7.07Hz,3H),1.22-1.12(m,10H),1.09(s,6H),0.80(t,J=6.95Hz,3H). 13C NMR(101MHz,Chloroform-d)δ195.9,162.0,142.6,132.9,132.3,130.6,130.4,128.6,127.4,127.2,126.7 ,121.5,121.0,33.6,32.4,30.9,28.5,28.44,28.40,28.3,27.0,21.6,17.9,13.1.HRMS(ESI):m / z:[M+Na] + Calcd.For C 27 H 34 ON + :397.2507;Found:397.2510.

[0050] Example 5 Synthesis of indanone derivative 6e

[0051]

[0052] Add 61.8 mg of 1,2-diphenylcyclopropene-3-one, 118.9 mg of 2-methyl-1-phenylpropene, and 15.7 mg of Fe(acac) into the test tube. 3 Fe(OAc) 2 And 64.9 mg of phenylsilane, then add 1.5 mL of ethanol, react at 60 ° C for 24 hours, cool to room temperature, add saturated brine, and then extract with dichloromethane. The organic phases are combined, dried over anhydrous magnesium sulfate, and column chromatography is used to obtain a yellow solid 6e with a yield of 61%.

[0053] Yellow solid, melting point: 117-118°C. 1 H NMR(400MHz,Chloroform-d)δ7.63(d,J=7.48Hz,1H),7.52-7.37(m,2H),7.27-7.13(m,5H),7 .13-6.99(m,3H),6.92(dd,J=7.46,2.06Hz,2H),6.33-6.26(m,2H),3.04(s,2H),1.12(s,5H). 13 C NMR(101MHz,Chloroform-d)δ196.7,160.9,144.3,137.2,135.4,132.6,132.4,130.2,129. 1,128.7,127.1,127.0,126.1,125.5,123.1,121.6,45.9,40.4,28.3.HRMS(ESI):m / z:[M+H] + Calcd.For C 25 H 23O + :339.1749;Found:339.1752.

[0054] Example 6 Synthesis of Indane Derivative 6f

[0055]

[0056] Add 61.8 mg of 1,2-diphenylcyclopropene-3-one, 99.1 mg of vinylcyclohexane, and 12.9 mg of Fe(acac) to the test tube. 3 FeC 2 O 4 And 64.9 mg of phenylsilane, then add 1.5 mL of ethanol, react at 60 ° C for 24 hours, cool to room temperature, add saturated brine, and then extract with dichloromethane. The organic phases are combined, dried over anhydrous magnesium sulfate, and column chromatography is used to obtain a yellow solid 6f with a yield of 75%.

[0057] Yellow solid, melting point: 84-85℃. 1 H NMR(400MHz,Chloroform-d)δ7.51(d,J=7.08Hz,1H),7.42(dq,J=8.15,2.06Hz,2H),7.38-7.32(m,3H),7.28-7.24(m,3H),2.82(dq,J=10.36,7.04Hz ,1H),2.02(d,J=14.75Hz,1H),1.80-1.71(m,2H),1.69-1.59(m,2H),1.37( d,J=7.06Hz,3H),1.29-1.23(m,2H),1.12-1.04(m,2H),0.88-0.75(m,2H). 13 C NMR(101MHz,Chloroform-d)δ196.8,163.2,143.8,134.5,133.4,131.6,131.4,129.7,128 .5,128.2,127.7,122.5,122.1,40.9,39.5,32.2,31.2,29.7,16.6.HRMS(ESI):m / z:[M+Na] + Calcd.For C 23 H 24 ON + :339.1725;Found:339.1728.

[0058] Example 7 Synthesis of 6 g of indanone derivative

[0059]

[0060] Add 61.8 mg of 1,2-diphenylcyclopropene-3-one, 61.3 mg of cyclopentene, and 31.8 mg of Fe(acac) to the test tube. 3 And 64.9 mg of phenylsilane, then add 1.5 mL of 1,2-dichloroethane, react at 60°C for 24 hours, cool to room temperature, add saturated brine, extract with dichloromethane, combine the organic phases, dry over anhydrous magnesium sulfate, and obtain 6 g of yellow solid by column chromatography, with a yield of 74%.

[0061] Yellow solid, melting point: 84-85℃. 1 H NMR(400MHz,Chloroform-d)δ7.52(d,J=6.83Hz,1H),7.48-7.39(m,2H),7.39-7.26(m,4H),7.26-7.22 (m,2H),3.49-3.35(m,1H),2.08-1.97(m,2H),1.97-1.85(m,4H),1.76(dq,J=13.99,6.02,4.51Hz,2H). 13 C NMR(101MHz,Chloroform-d)δ196.6,161.8,143.3,134.0,133.2,131.6,131.6,1 29.7,128.4,128.3,127.7,122.5,121.5,39.0,31.1,27.0.HRMS(ESI):m / z:[M+H] + Calcd.For C 20 H 19 O + :275.1436;Found:275.1435.

[0062] Example 8 Synthesis of Indane Derivative 6h

[0063]

[0064] Add 61.8 mg of 1,2-diphenylcyclopropene-3-one, 86.5 mg of 1-methyl-1-cyclohexene, and 25.0 mg of FeSO to the test tube in sequence. 4 7H 2 0 and 64.9 mg of phenylsilane, then add 1.5 mL of ethanol, react at 60°C for 24 h, cool to room temperature, add saturated brine, extract with dichloromethane, combine the organic phases, dry over anhydrous magnesium sulfate, and obtain a yellow solid 6h by column chromatography, with a yield of 48%.

[0065] Yellow solid, melting point: 106-107°C. 1H NMR(400MHz,Chloroform-d)δ7.52(dd,J=13.03,7.00Hz,2H),7.34(dt,J=13.60,6.59Hz ,4H),7.24-7.15(m,3H),1.96-1.88(m,2H),1.52-1.45(m,2H),1.38(d,J=18.34Hz,9H). 13 CNMR(101MHz,Chloroform-d)δ197.9,164.4,145.2,135.0,134.4,133.1,131.5,130 .3,127.9,127.5,124.1,122.5,40.3,37.3,25.8,25.2,22.5.HRMS(ESI):m / z:[M+Na] + Calcd.For C 22 H 22 ON + :325.1568;Found:325.1573.

[0066] Example 9 Synthesis of Indane Derivative 6i

[0067]

[0068] Add 61.8 mg of 1,2-diphenylcyclopropene-3-one, 84.7 mg of norbornene, and 31.8 mg of Fe(acac) to the test tube in sequence. 3 And 64.9 mg of phenylsilane, then add 1.5 mL of acetonitrile, react at 60 ° C for 24 hours, cool to room temperature, add saturated brine, and then extract with dichloromethane. The organic phases are combined, dried over anhydrous magnesium sulfate, and column chromatography is used to obtain a yellow solid 6i with a yield of 62%.

[0069] Yellow solid, melting point: 84-85℃. 1 H NMR(400MHz,Chloroform-d)δ7.48(dd,J=7.07,1.13Hz,1H),7.46-7.32(m,4H),7.32-7.18(m,4H),2.86-2.77(m,1H),2.45(s,1H),2 .25(s,1H),1.75(dt,J=12.70,6.37Hz,1H),1.67-1.57(m,1H),1.57-1.46(m,2H),1.44-1.17(m,3H),1.07(dp,J=9.96,1.57Hz,1H). 13C NMR(101MHz,Chloroform-d)δ197.6,161.4,145.7,133.31,133.27,132.7,131.1,130.2,128.4 ,127.9,127.7,122.2,121.6,43.1,41.0,37.5,37.1,36.4,30.6,28.8.HRMS(ESI):m / z:[M+Na] + Calcd.For C 22 H 20 ON + :323.1412;Found:323.1417.

[0070] Example 10 Synthesis of Indane Derivative 6j

[0071]

[0072] Add 61.8 mg of 1,2-diphenylcyclopropene-3-one, 86.5 mg of cycloheptene, and 17.9 mg of Fe(acac) to the test tube in sequence. 3 FeCl 2 ·4H 2 O and 64.9 mg of phenylsilane, then add 1.5 mL of ethanol, react at 60 ° C for 24 hours, cool to room temperature, add saturated brine, extract with dichloromethane, combine the organic phases, dry over anhydrous magnesium sulfate, and obtain a yellow solid 6j by column chromatography with a yield of 77%.

[0073] Yellow solid, melting point: 141-142°C. 1 H NMR(400MHz,Chloroform-d)δ7.50(d,J=8.18Hz,1H),7.43(t,J=7.42Hz,2H),7.36(q,J=7.59Hz,2H),7.31- 7.20(m,4H),3.12(tt,J=11.04,3.28Hz,1H),1.99(q,J=10.10Hz,2H),1.90-1.79(m,4H),1.67-1.51(m,6H). 13 C NMR(101MHz,Chloroform-d)δ197.1,163.9,143.9,133.2,131.54,131.52,131.46,12 9.7,128.4,128.2,127.7,122.4,122.1,39.8,32.0,28.2,27.9.HRMS(ESI):m / z:[M+H] + Calcd.ForC 22 H 23 O+ :303.1749;Found:303.1751.

[0074] Example 11 Synthesis of Indane Derivative 6k

[0075]

[0076] Add 61.8 mg 1,2-diphenylcyclopropene-3-one, 149.5 mg cyclododecene, and 31.8 mg Fe(acac) to the test tube in sequence. 3 And 64.9 mg of phenylsilane, then add 1.5 mL of benzyl alcohol, react at 60°C for 24 hours, cool to room temperature, add saturated brine, extract with dichloromethane, combine the organic phases, dry over anhydrous magnesium sulfate, and obtain a yellow solid 6k by column chromatography with a yield of 46%.

[0077] Yellow solid, melting point: 152-153°C. 1 H NMR(400MHz,Chloroform-d)δ7.50(dd,J=7.09,1.09Hz,1H),7.43-7.38(m,2H),7.36-7.21(m,6H),3.24 (m,1H),1.93(m,2H),1.67(m,2H),1.44-1.26(m,8H),1.26-1.14(m,5H),1.10(dd,J=10.02,4.38Hz,5H). 13 C NMR(101MHz,Chloroform-d)δ197.0,163.1,143.7,135.1,133.2,131.71,131.68,129.6,128.4 ,128.2,127.8,122.4,122.3,32.6,28.3,24.2,24.1,23.6,22.2,21.9.HRMS(ESI):m / z:[M+Na] + Calcd.ForC 27 H 32 ON + :395.2352;Found:395.2351.

[0078] Example 12 Synthesis of Indane Derivative 61

[0079]

[0080] Add 61.8 mg of 1,2-diphenylcyclopropene-3-one, 113.5 mg of cyclohexyl vinyl ether, and 31.8 mg of Fe(acac) to the test tube in sequence. 3And 64.9 mg of phenylsilane, then add 1.5 mL of ethanol, react at 60°C for 24 hours, cool to room temperature, add saturated brine, extract with dichloromethane, combine the organic phases, dry over anhydrous magnesium sulfate, and obtain a yellow solid 6l by column chromatography with a yield of 50%.

[0081] Yellow solid, melting point: 85-86°C. 1 H NMR(400MHz,Chloroform-d)δ7.67(d,J=7.32Hz,1H),7.61-7.46(m,1H),7.46-7.30(m,4H),7.30-7.23(m,3H),4.93(q,J=6.65Hz,1H),3.22(tt ,J=9.24,3.58Hz,1H),1.76-1.64(m,2H),1.63(d,J=6.68Hz,5H),1.44( d, J=5.62Hz, 1H), 1.24 (d, J=10.72Hz, 1H), 1.13 (q, J=9.85, 6.72Hz, 4H). 13 C NMR(101MHz,Chloroform-d)δ196.7,158.8,143.2,133.7,133.6,130.9,130.7,129.4,128.6,12 8.4,128.1,123.4,122.6,75.6,68.1,33.1,31.4,25.7,24.1,23.9,20.9.HRMS(ESI):m / z:[M+Na] + Calcd.ForC 23 H 24 O 2 Na + :355.1674;Found:355.1678.

[0082] Example 13 Synthesis of Indane Derivative 6m

[0083]

[0084] Add 61.8 mg 1,2-diphenylcyclopropene-3-one, 99.9 mg vinyl pyrrolidone, and 31.8 mg Fe(acac) to the test tube in sequence. 3 And 64.9 mg of phenylsilane, then add 1.5 mL of dimethyl sulfoxide, react at 60°C for 24 hours, cool to room temperature, add saturated brine, extract with dichloromethane, combine the organic phases, dry over anhydrous magnesium sulfate, and obtain a yellow solid 6m by column chromatography with a yield of 41%.

[0085] Yellow solid, melting point: 157-158°C. 1H NMR(400MHz,Chloroform-d)δ7.52(d,J=7.09Hz,1H),7.47-7.30(m,5H),7.29-7.22(m,3H),5.33(q,J=7.24Hz,1H),3.45 -3.34(m,1H),3.20(td,J=8.93,4.56Hz,1H),2.40-2.23(m,2H),1.91(m,1H),1.75-1.63(m,1H),1.38(d,J=7.25Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ196.9,174.9,155.1,144.4,135.6,134.1,131.6,130.2,129. 6,128.9,128.20,128.17,122.8,120.9,46.2,44.5,31.1,17.8,17.0.HRMS(ESI):m / z:[M+H] + Calcd.For C 21 H 20 NO 2 + :318.1494;Found:318.1504.

[0086] Example 14 Synthesis of Indane Derivative 6n

[0087]

[0088] Add 61.8 mg 1,2-diphenylcyclopropene-3-one, 127.9 mg citronellol, and 23.6 mg Fe(acac) to the test tube in sequence. 3 Cu(acac) 2 And 64.9 mg of phenylsilane, then add 1.5 mL of ethanol, react at 60°C for 24 hours, cool to room temperature, add saturated brine, extract with dichloromethane, combine the organic phases, dry over anhydrous magnesium sulfate, and obtain a yellow solid 6n by column chromatography with a yield of 65%.

[0089] Yellow solid, melting point: 157-158°C, 1H NMR(400MHz,Chloroform-d)δ7.58-7.43(m,2H),7.43-7.29(m,4H),7.26-7.22(m,1H),7.20-7.10(m,2H),3.65-3.56(m,2H), 1.74(dt,J=10.18,5.79Hz,2H),1.53-1.47(m,2H),1.39-1.23(m,4H),1.18(s,7H),1.08-1.01(m,1H),0.81(d,J=6.39Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ198.0,163.6,145.1,135.5,134.3,133.3,131.3,130.1,128.8,128.1,127.6,1 27.5,123.6,122.4,61.1,61.0,41.8,40.0,39.9,39.8,37.5,29.3,29.2,22.5,19.5.HRMS(ESI):m / z:[M+Na] + Calcd.For C 25 H 30 O 2 Na + :385.2143;Found:385.2145.

[0090] Example 15 Synthesis of Indanone Derivative 6p

[0091]

[0092] Add 61.8 mg of 1,2-diphenylcyclopropene-3-one, 135.2 mg of hydroxydicyclopentadiene, and 31.8 mg of Fe(acac) to the test tube in sequence. 3 And 64.9 mg of phenylsilane, then add 1.5 mL of tetrahydrofuran, react at 60°C for 24 hours, cool to room temperature, add saturated brine, extract with dichloromethane, combine the organic phases, dry over anhydrous magnesium sulfate, and obtain a yellow solid 6p by column chromatography with a yield of 59%.

[0093] Yellow solid, melting point: 207-208°C, 1H NMR(400MHz,Chloroform-d)δ7.54(d,J=7.01Hz,1H),7.45-7.40(m,2H),7.39-7.3 2(m,2H),7.31-7.27(m,2H),7.24(dd,J=7.12,4.19Hz,2H),3.67(d,J=6.59Hz,1H) ,2.98(m,1H),2.22(t,J=8.55Hz,1H),2.13-1.98(m,4H),1.92-1.81(m,2H),1.63( m,1H),1.40(d,J=11.12Hz,2H),1.32-1.24(m,2H),1.19(dd,J=9.23,6.52Hz,1H). 13 C NMR(101MHz,Chloroform-d)δ196.5,160.4,143.3,134.7,133.2,131.5,131.2,129.6,128.5,128.3,1 27.8,122.7,121.9,74.0,48.4,48.3,47.5,44.3,41.2,39.7,33.3,32.0,28.7.HRMS(ESI):m / z:[M+H] + Calcd.For C 25 H 25 O 2 + :357.1855;Found:357.1858.

[0094] Example 16 Synthesis of Indane Derivative 6q

[0095]

[0096] Add 61.8 mg 1,2-diphenylcyclopropene-3-one, 138.8 mg α-terpineol, 23.1 mg Fe(acac) 3 Ni(acac) 3 And 64.9 mg of phenylsilane, then add 1.5 mL of ethanol, react at 60°C for 24 hours, cool to room temperature, add saturated brine, extract with dichloromethane, combine the organic phases, dry over anhydrous magnesium sulfate, and obtain a yellow solid 6q by column chromatography with a yield of 55%.

[0097] Yellow solid, melting point: 139-140℃. 1H NMR(400MHz,Chloroform-d)δ7.53-7.48(m,2H),7.41-7.33(m,3H),7.23(dd,J=14.18,6.37Hz,2H),7.13(d d,J=7.53,1.93Hz,2H),1.95-1.86(m,2H),1.68-1.59(m,4H),1.37(s,3H),1.33-1.20(m,4H),1.15(s,6H). 13 C NMR(101MHz,Chloroform-d)δ198.2,165.1,145.0,134.6,133.7,133.0,132.7,131.52,131.47,130.2,1 29.4,127.9,127.5,127.4,124.3,122.5,72.6,48.2,39.1,36.7,27.1,22.4,21.5.HRMS(ESI):m / z:[M+H] + Calcd.For C 25 H 29 O 2 + :361.2168;Found:361.2173.

[0098] Example 17 Synthesis of Indane Derivative 6r

[0099]

[0100] Add 70.23 mg of 2,3-di(4-methyl)cycloprop-2-en-1-one, 63.1 mg of 2-methyl-2-butene, and 31.8 mg of Fe(acac) to the test tube. 3 And 64.9 mg of phenylsilane, then add 1.5 mL of ethanol, react at 60°C for 24 hours, cool to room temperature, add saturated brine, extract with dichloromethane, combine the organic phases, dry over anhydrous magnesium sulfate, and obtain a yellow solid 6r by column chromatography with a yield of 70%.

[0101] Yellow solid, melting point: 109-110℃. 1 H NMR(400MHz,Chloroform-d)δ7.39-7.31(m,2H),7.20-7.11(m,3H),7.05-6.99(m,2H) ,2.35(d,J=11.31Hz,6H),1.80(q,J=7.50Hz,2H),1.16(s,6H),0.86(t,J=7.47Hz,3H). 13C NMR(101MHz,Chloroform-d)δ198.5,163.5,142.3,138.1,137.0,135.4,133.2,131.7,131 .3,130.0,128.3,123.4,123.4,40.3,34.1,28.8,21.3,21.1,9.6.HRMS(ESI):m / z:[M+Na] + Calcd.For C 22 H 24 ON + :327.1725;Found:327.1725.

[0102] Example 18 Synthesis of Indane Derivative 6s

[0103]

[0104] 82.1 mg 2,3-di(4-chloro)cycloprop-2-en-1-one, 63.1 mg 2-methyl-2-butene, and 23.3 mg Co(acac) were added to the test tube in sequence. 3 And 64.9 mg of phenylsilane, then add 1.5 mL of ethanol, react at 60°C for 24 hours, cool to room temperature, add saturated brine, extract with dichloromethane, combine the organic phases, dry over anhydrous magnesium sulfate, and obtain a yellow solid 6s by column chromatography with a yield of 65%.

[0105] Yellow solid, melting point: 112-113°C. 1 H NMR (400MHz, Chloroform-d) δ7.40-7.30(m,2H),7.30-7.24(m,3H),7.03-6.97(m,2H),1.73(q,J=7.50Hz,2H),1.09(s,6H),0.78(t,J=7.48Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ195.2,163.1,141.8,134.0,133.4,132.8,131.9,131. 5,131.2,130.3,127.0,123.7,122.0,39.4,33.0,27.8,8.6.HRMS(ESI):m / z:[M+Na] + Calcd.For C 20 H 18 OCl 2 Na + :367.0632;Found:367.0626.

[0106] Example 19 Synthesis of Indane Derivative 6t

[0107]

[0108] Add 72.6 mg of 2,3-di(4-fluoro)cycloprop-2-en-1-one, 63.1 mg of 2-methyl-2-butene, and 31.8 mg of Fe(acac) to the test tube. 3 And 64.9 mg of phenylsilane, then add 1.5 mL of ethanol, react at 60°C for 24 hours, cool to room temperature, add saturated brine, extract with dichloromethane, combine the organic phases, dry over anhydrous magnesium sulfate, and obtain a yellow solid 6t by column chromatography with a yield of 68%.

[0109] Yellow solid, melting point: 85-86°C. 1 H NMR(400MHz,Chloroform-d)δ7.46(dd,J=8.31,4.37Hz,1H),7.21(dd,J=7.10,2.46 Hz,1H),7.14-7.00(m,5H),1.81(q,J=7.47Hz,2H),1.16(s,6H),0.89-0.83(m,3H). 13 C NMR (101MHz, Chloroform-d) δ196.3, 164.2 (d, J = 1.94Hz), 163.9 (d, J = 51.26Hz), 161.4 (d, J = 47.32Hz), 140.2 (d, J = 3.72Hz), 135.3 (d, J = 4.51Hz), 1 33.8(d,J=6.95Hz),131.7(d,J=8.08Hz),124.8(d,J=7.42Hz),118.6(d,J =22.34Hz), 114.8 (d, J = 21.57Hz), 110.9 (d, J = 24.11Hz), 40.4, 34.0, 28.7. 19 F NMR(376MHz,Chloroform-d)δ-112.7,-114.5.HRMS(ESI):m / z:[M+Na] + Calcd.For C 20 H 18 OF 2 Na + :335.1223;Found:335.1226.

[0110] Example 20 Synthesis of Indene Derivative 6u

[0111]

[0112] 82.2 mg 2,3-di(3-chloro)cycloprop-2-en-1-one, 63.1 mg 2-methyl-2-butene, and 23.3 mg Co(acac) were added to the test tube in sequence. 2 And 64.9 mg of phenylsilane, then add 1.5 mL of ethanol, react at 60°C for 24 hours, cool to room temperature, add saturated brine, extract with dichloromethane, combine the organic phases, dry over anhydrous magnesium sulfate, and obtain a yellow solid 6u by column chromatography with a yield of 53%.

[0113] Yellow solid, melting point: 98-99°C. 1 H NMR(400MHz,Chloroform-d)δ7.50-7.44(m,1H),7.35-7.26(m,3H),7.26-7.11(m,2H),7. 03(dt,J=7.13,1.56Hz,1H),1.82(q,J=7.49Hz,2H),1.18(s,6H),0.86(t,J=7.49Hz,3H). 13 CNMR(101MHz,Chloroform-d)δ194.2,162.1,147.1,135.7,135.3,133.9,133.5,131.0,130 .5,130.1,128.8,128.4,127.8,126.3,122.3,40.3,34.2,29.1,9.6.HRMS(ESI):m / z:[M+Na] + Calcd.For C 20 H 18 OCl 2 Na + :367.0632;Found:367.0630.

[0114] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A 1-indanone derivative, characterized in that: The general structural formula of the 1-indanone derivative is shown in Formula I: In Formula I, R1 is Me-, cyclopentyl, cyclohexyl, cycloheptyl, cyclododecyl; R2 is C 10 Straight-chain or branched alkyl, oxocyclohexyl, N-pyrrolidone; R3 is Me-, cyclohexyl, phenyl, dimethyl tert-butylsilyl, or substituted alkyl; R4 is Me-, Cl, or F.

2. The 1-indanone derivative according to claim 1, characterized in that In Formula I, R1 is Me-, cyclopentyl, or cyclohexyl; R2 is C 10 Straight-chain or branched alkyl, oxocyclohexyl, N-pyrrolidone; R3 is Me-, cyclohexyl, phenyl, or substituted alkyl; R4 is Me-, Cl, or F.

3. A method for preparing a 1-indanone derivative as claimed in claim 1 or 2, characterized in that: The steps include: 1,2-Diphenylcyclopropene-3-one and 2-methyl-2-propene-1-ol are added into a reaction container, and then a catalyst and a solvent are added, and a 1-indanone derivative is obtained through reaction, separation and purification.

4. The method for preparing a 1-indanone derivative according to claim 3, characterized in that: The chemical reaction formula is, 5. The method for preparing a 1-indanone derivative according to claim 3, characterized in that: The molar ratio of 1,2-diphenylcyclopropene-3-one to 2-methyl-2-propene-1-ol is 1:1-5.

6. The method for preparing a 1-indanone derivative according to claim 3, characterized in that: The molar ratio of 1,2-diphenylcyclopropene-3-one to the catalyst is 0.01-2.

7. The method for preparing a 1-indanone derivative according to any one of claims 3 to 6, characterized in that: The catalyst includes at least one of FeBr3, FeCl3, Fe(OTf)3, FeC2O4, FeSO4·7H20, FeCl2·4H2O, Fe(OAc)2, Fe(acac)3, Fe(ox)2·6H2O, Cu(acac)2, Cu(OTf)2, Ni(acac)3, Ni(OTf)2, Co(acac)2, and Co(acac)3.

8. The method for preparing a 1-indanone derivative according to any one of claims 3 to 6, characterized in that: The solvent includes at least one of 1-Phenylethanol, EtOH, MeOH, THFtoluene (toluene), (CH2OH)2, MeCN, DMF, DCE, and DMSO.

9. The method for preparing a 1-indanone derivative according to any one of claims 3 to 6, characterized in that: The reaction temperature is from room temperature to 120°C, and the reaction time is from 6 to 30 hours.

10. A 1-indanone derivative as claimed in any one of claims 1 to 2, or a 1-indanone derivative obtained by the preparation method as claimed in any one of claims 3 to 9, for use as a pharmaceutical material and an organic synthetic material.

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