Synthetic method and anticancer activity of 4-amino dihydroquinolinone compound

A technology of aminodihydroquinolinone and synthesis method, which is applied in organic chemistry, drug combination, antineoplastic drugs, etc., can solve the problems of poor functional group tolerance, harsh reaction conditions, and difficult to obtain raw materials, etc., and achieve functional group tolerance Good, raw materials are easy to get, and the effect of raw materials is cheap

Active Publication Date: 2021-12-07
HENAN NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] Although 4-aminodihydroquinolinones have important application value, the synthesis methods of such compounds are very limited at present, and these literature methods still have problems such as unavailable raw materials, long synthetic routes, harsh reaction conditions, and poor functional group tolerance. question

Method used

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  • Synthetic method and anticancer activity of 4-amino dihydroquinolinone compound
  • Synthetic method and anticancer activity of 4-amino dihydroquinolinone compound
  • Synthetic method and anticancer activity of 4-amino dihydroquinolinone compound

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029]

[0030] Into a 15mL reaction tube, sequentially add compound 2a, catalyst 1, catalyst 2, additives, Molecular sieves and an organic solvent were stirred at room temperature for 5 minutes, and then compound 1a and cesium fluoride were added sequentially, the reaction tube was sealed under air conditions, and placed in a heating module to raise the temperature and stir for reaction. After the reaction is finished, cool to room temperature, add saturated sodium bicarbonate solution to quench the reaction, filter with diatomaceous earth, and extract the filtrate with ethyl acetate. / ethyl acetate=3 / 1) afforded the product 3a as a white solid.

[0031] A series of results were obtained by changing the reaction solvent, catalyst 1, catalyst 2, additives, reaction temperature and material ratio, etc., as shown in Table 1.

[0032] Synthesis of 3a under different conditions in table 1 a

[0033]

[0034]

Embodiment 2

[0036]

[0037] Into a 15mL pressure-resistant tube, add 2a (38mg, 0.2mmol), palladium acetate (2.2mg, 0.01mmol), silver carbonate (27.6mg, 0.1mmol), Molecular sieves (40mg), 1-adamantanecarboxylic acid (36.0mg, 0.2mmol) and acetonitrile (2mL), stirred at room temperature for 5 minutes, then added 1a (59.7mg, 0.2mmol) and cesium fluoride (60.8mg, 0.4 mmol), then the reaction tube was sealed and placed in an oil bath at 100°C for 10 h. After the reaction, the reaction system was cooled to room temperature, and saturated sodium bicarbonate solution was added to quench the reaction, filtered with diatomaceous earth, the filtrate was extracted with ethyl acetate, after the organic phase was dried, suction filtered, spin-dried, and separated by a silica gel column ( Petroleum ether / ethyl acetate=3 / 1) gave the product 3a as a white solid (29.3 mg, 55%). The characterization data of this compound are: 1 H NMR (400MHz, CDCl 3 ):δ9.47(s,1H),7.24(d,J=7.6Hz,1H),7.20-7.16(m,3H),6.9...

Embodiment 3

[0039] According to the method and steps of embodiment 2 a,b , by changing reactant 1 and reactant 2, various 4-aminodihydroquinolinone compounds 3 can be synthesized, and the specific results are as follows:

[0040]

[0041]

[0042] Representative product characterization data are as follows:

[0043] 3,3-Dimethyl-4-(p-tolylamino)-3,4-dihydroquinolin-2(1H)-one(3b)

[0044] 1 H NMR (400MHz, CDCl3 ):δ8.97(s,1H),7.26-7.24(m,1H),7.21(t,J=7.6Hz,1H),7.00-6.94(m,3H),6.86(d,J=7.6Hz, 1H), 6.61(d, J=8.4Hz, 2H), 4.46(s, 1H), 3.70(br s, 1H), 2.24(s, 3H), 1.32(s, 3H), 1.21(s, 3H) . 13 C NMR (100MHz, CDCl 3 ): δ176.4, 145.6, 135.5, 130.0, 128.5, 127.3, 127.2, 126.2, 123.4, 115.3, 113.5, 59.6, 43.3, 22.9, 20.4, 19.1. HRMS (ESI) m / z: [M+Na] + Calcd for C 18 h 20 N 2 NaO 303.1468; Found 303.1459.

[0045] 4-((4-Ethylphenyl)amino)-3,3-dimethyl-3,4-dihydroquinolin-2(1H)-one(3c)

[0046] 1 H NMR (600MHz, CDCl 3 ):δ8.86(s,1H),7.26(d,J=7.8Hz,1H),7.21(td,J 1 =7.8Hz,J 2 =1.2Hz...

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Abstract

The invention discloses a synthesis method and anticancer activity of a 4-amino dihydroquinolinone compound, which belongs to the technical field of organic synthesis and drug discovery. 2-(trimethylsilyl) aryl trifluoromethanesulfonate 1 and a 1-substituted pyrazolidinone compound 2 are used as raw materials and react in an organic solvent in the presence of a catalyst and cesium fluoride to obtain the 4-amino dihydroquinolinone compound 3, and the compound shows remarkable anti-proliferative activity on cancer cells such as REC-1 and Ramos. The synthesis method disclosed by the invention has the advantages of wide substrate range, mild reaction conditions, good functional group tolerance and the like, and the obtained product has potential medicinal value.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis and drug discovery, and specifically relates to a synthesis method and anticancer activity of 4-aminodihydroquinolinone compounds. Background technique [0002] 4-Aminodihydroquinolinones are an important class of nitrogen-containing heterocyclic compounds, which have significant antipsychotic, blocking β-adrenoceptor, inhibiting CYP11B2, anti-inflammatory and inhibiting phosphodiesterase activities. It has a wide range of applications in the development of new drugs. In addition, this type of compound also has a variety of reactive properties, and is often used in the preparation of fine chemicals such as alkaloids, dyes, pesticides and fluorescence enhancers. [0003] Although 4-aminodihydroquinolinones have important application value, the synthesis methods of such compounds are very limited at present, and these literature methods still have problems such as unavailable raw material...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D215/44C07D491/056A61P35/00
CPCC07D215/44C07D491/056A61P35/00Y02P20/55
Inventor 张新迎沈檬洋徐园双赵杰范学森
Owner HENAN NORMAL UNIV
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