Trifluoromethyl containing quinazoline derivative and preparation method and application thereof

A quinazolinone, trifluoromethyl technology, applied in the field of medicinal chemistry, can solve the problems of harsh reaction conditions, low yield, change, etc., and achieve the effects of rich diversity, short reaction time and convenient operation

Inactive Publication Date: 2015-11-04
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Due to the strong electron-withdrawing properties, lipophilicity and stable C-F bond of trifluoromethyl, the introduction of it into organic compounds can significantly change the acidity, dipole moment, polarity and chemical and metabolic stability of the compound, so Compounds containing trifluoromethyl groups have been widely used in the fields of medicine and pesticides, and the development of methods for introducing trifluoromethyl groups into organic molecules has become a hot topic in current research. For decades, chemists have developed various types of vectors The reaction of organic molecules introducing trifluorom

Method used

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  • Trifluoromethyl containing quinazoline derivative and preparation method and application thereof
  • Trifluoromethyl containing quinazoline derivative and preparation method and application thereof
  • Trifluoromethyl containing quinazoline derivative and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049]

[0050] In a Schlenk reaction tube, add 5.8 mg (20% mmol) Cu 2 O, 11.2 mg (40% mmol) 2,2'-bipyridyl, Togni reagent (chemical name: 1-(trifluoromethyl)-1,2-phenyliodyl-3(1H)-one, CAS: 887144 -94-7, 126mg, 0.4mmol), evacuate, under argon protection, add N-cyano-N-(3-methylbutyl-3-en-1-yl)benzamide (42mg, 0.2mmol ) of 2ml CH 3The CN solution was stirred and reacted at an external temperature of 80° C. for 10 h. After the reaction was completed, it was transferred to a 25 ml single-necked bottle, and the solid was loaded as a sample, and separated by column chromatography using petroleum ether and ethyl acetate as eluents. 46 mg of the product was obtained with a yield of 82%.

[0051] The physical properties and spectrogram data of the product are as follows: Pale yellow solid; m.p.91-92°C; 1 H NMR (CDCl 3 ,400MHz), δ:8.29(dd,J 1 =8.0Hz,J 2 =1.2Hz,1H),7.76-7.72(m,1H),7.67(dd,J 1 =8.4Hz,J 2 =0.8Hz,1H),7.46(dq,J 1 =7.4Hz,J 2 =1.2Hz,1H),4.30(dq,J 1 =11.2Hz,J 2...

Embodiment 2

[0054]

[0055] In a Schlenk reaction tube, add 5.8 mg (20% mmol) Cu 2 O, 11.2mg (40%mmol) 2,2'-bipyridyl, Togni reagent (126mg, 0.2mmol), vacuum, argon protection, add N-cyano-1-methyl-N-(3-methylbut-3 -en-1-yl)-1H-indole-2-carboxamide (57mg, 0.2mmol) in 2ml CH 3 The CN solution was stirred and reacted at an external temperature of 80° C. for 10 h. After the reaction was completed, it was transferred to a 25 ml single-necked bottle, and the solid was loaded as a sample, and separated by column chromatography using petroleum ether and ethyl acetate as eluents. 51 mg of the product was obtained with a yield of 77%.

[0056] The physical properties and spectrogram data of the product are as follows: Pale yellow solid; m.p.196-197°C; 1 H NMR (CDCl 3 ,400MHz),δ:8.24(d,J=6.0Hz,1H),7.43-7.37(m,2H),7.33(m,1H),4.38(s,1H),4.12(d,J=7.2Hz, 1H),3.85(s,3H),2.96-2.85(m,1H),2.63-2.51(m,1H),2.44(s,1H),2.31-2.29(m,1H),1.49(s,3H) ; 13 C NMR (CDCl 3 ,100MHz), δ:164.92,154.53,137.48,126...

Embodiment 3～10

[0059] The preparation methods of Examples 3-10 are the same as that of Example 1, except that the two raw materials are replaced with other similar structures, and the structures of the obtained products are listed in Table 1.

[0060] The product structure of embodiment 3~10

[0061]

[0062]

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PUM

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Abstract

The present invention discloses a trifluoromethyl containing quinazoline derivative and a preparation method and application thereof. The preparation method comprises the following steps of: under the condition that copper and ligand exist, an N-cyano substituted aryl carboxamides compound reacting with a togni reagent in a solvent, and after completion of the reaction, obtaining the trifluoromethyl containing quinazoline derivative after treatment. The reaction substrate is readily available, the operation is convenient, the obtained quinazolinone derivative is of rich diversity, the required reaction condition is mild, and the reaction time is short. The all-in-one-pot reaction is realized, and not only a structural mother kernel of quinazoline is obtained, but also trifluoromethyl is introduced into the mother kernel structure. And the quinazolinone compound contains the spiropyran compound can be synthesized, which cannot be achieved by the prior art. The obtained product has good activity in inhibiting enzyme acetylcholinesterase and butyrylcholinesterase.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a preparation method of a trifluoromethyl-containing quinazolinone derivative, and the inhibitory activity of the compound on acetylcholinesterase and butyrylcholinesterase is tested. Background technique [0002] Quinazolinones are a class of substances with biological activity or medicinal value. Many natural products contain the structural nucleus of quinazolinones, and are favored by the majority of medical workers, showing good biological activity. The following are the structural representatives of quinazolinones with biological activity: [0003] [0004] Due to the strong electron-withdrawing properties, lipophilicity and stable C-F bond of trifluoromethyl, the introduction of it into organic compounds can significantly change the acidity, dipole moment, polarity and chemical and metabolic stability of the compound, so Compounds containing trifluoromethy...

Claims

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Application Information

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IPC IPC(8): C07D487/04C07D487/14C07D471/04C07D487/10C07D487/20A61P25/28
CPCC07D471/04C07D487/04C07D487/10C07D487/14C07D487/20
Inventor 崔孙良郑晶
Owner ZHEJIANG UNIV
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