Synthesis method of C-3-position difluoromethyl-substituted quinoxalinone derivative

A kind of quinoxalinone and difluoromethyl technology, which is applied in the field of synthesis of C-3-position difluoromethyl substituted quinoxalinone derivatives, can solve problems such as harsh conditions, and achieve reaction safety and reaction selectivity. Good, rich effect of synthetic methods

Active Publication Date: 2019-08-09
ZHEJIANG UNIV OF TECH
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the introduction of fluorine-containing groups at the C-3 position of quinoxalinones has been achieved through oxidative decarboxylation coupling or the catalysis of metal copper complexes (G. F. Hong, J. W. Yuan, J. H. Fu, G. Y. Pan, Z. W. Wang, L. R. Yang, Y. M. Xiao, P. Mao, X. M. Zhang, Org. Chem. Front. 2019, 6 , 1173; L. P. Wang, H. Y. Liu, F. F. Li, J. Q. Zhao, H. Y. Zhang, Y. C. Zhang, Adv. Synth. Catal. 2019, 361 , 2354), but the existing methods still have defects such as harsh conditions and excessive oxidant participation

Method used

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  • Synthesis method of C-3-position difluoromethyl-substituted quinoxalinone derivative
  • Synthesis method of C-3-position difluoromethyl-substituted quinoxalinone derivative

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Experimental program
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Embodiment 1

[0024] Combine 1-methylquinoxalinone (0.25 mmol, 40 mg), ethyl bromodifluoromethyl acetate (0.5 mmol, 101 mg), Ir(ppy) 3 (1.25 μmol, 0.8 mg), potassium carbonate (0.5 mmol, 69 mg) and N,N -Diisopropylethylamine (0.025mmol, 3.2 mg) was added to a 10 mL solvent storage bottle, and MeCN (1.0 mL) was added as a solvent. 2 Under the protection of the atmosphere, the reaction was carried out for 12 h under 3 w blue light irradiation and 25 ℃. After the reaction, the reaction system was washed with water and extracted with dichloromethane, and then separated into an organic layer and an aqueous layer. After the organic layer was dried with anhydrous sodium sulfate, the solvent was evaporated and concentrated under reduced pressure to obtain a yellow oil. The yellow oil was separated by column chromatography, using a mixture of petroleum ether and ethyl acetate with a volume ratio of 30:1 as the eluent, collecting the eluent containing the target compound, evaporating the solvent and dr...

Embodiment 2

[0027] The inorganic base (potassium carbonate) in the system was replaced with sodium carbonate (0.5 mmol, 52.9 mg), and other operations were the same as in Example 1, to obtain 46 mg of white solid 2,2-difluoro-2-(4-methyl-3) -Oxo-3,4-dihydroquinoxalin-2-yl)-ethyl acetate, the yield is 65%.

Embodiment 3

[0029] will N,N -The dosage of diisopropylethylamine was changed to 0.05 mmol, and the other operations were the same as in Example 1, to obtain 44 mg of white solid 2,2-difluoro-2-(4-methyl-3-oxo-3,4- Dihydroquinoxalin-2-yl)-ethyl acetate, the yield is 62%.

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Abstract

The invention discloses a synthesis method of a C-3-position difluoromethyl-substituted quinoxalinone derivative. The method comprises the steps of dissolving a quinoxalinone derivative, a bromodifluoromethyl compound, a photocatalyst, an inorganic base and an organic amine in an organic solvent for a reaction for 6-36 hours at the temperature of 20-60 DEG C under the irradiation of visible light;after the reaction is finished, carrying out posttreatment on a reaction system to obtain a target product, namely the C-3-position difluoromethyl-substituted quinoxalinone derivative. According to the method, light is adopted as a reaction energy source to realize C-3 difluoro methylation of quinoxalinone, so that the reaction is safer, environmentally friendly and lower in cost, the applicationrange of reaction substrates is expanded, and synthesis methods of C-3 substituted quinoxalinone compounds are diversified.

Description

Technical field [0001] The present invention relates to a method for synthesizing C-3 difluoromethyl substituted quinoxalinone derivatives. Background technique [0002] The structure of quinoxalinone is a commonly used pharmacophore in the field of drug design. Studies have confirmed that the derivatives containing the nucleus of this structure have a variety of pharmacological activities, including anti-tumor, anti-(true) bacteria, anti-coagulation, etc. As potential lead compounds, quinoxalinone structures have broad research prospects in the field of new drug development. In recent years, some progress has been made in the synthesis of quinoxalinone derivatives substituted at the C-3 position, which mainly include: (1) the introduction of an aromatic ring at the C-3 position of quinoxalinone (K. Yin, RH Zhang, Org. Lett . 2017, 19 , 1530; J. W. Yuan, S. N. Liu, L. B. Qu, Adv. Synth. Catal . 2017, 359 , 4197); (2) The introduction of amino groups at the C-3 position of quino...

Claims

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Application Information

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IPC IPC(8): C07D241/44
CPCC07D241/44
Inventor 金灿孙彬庄小慧
Owner ZHEJIANG UNIV OF TECH
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