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Method for preparing 4-aryl-2-(2-(trifluoromethyl)aryl)quinazoline

A technology of sulfur trifluoromethyl and phenylquinazoline, which is applied in the field of synthesis of fluorine-containing quinazoline compounds, can solve the problems of complex reaction and low nucleophilicity, and achieve high yield, clean and good spectrum The effect of biological activity

Inactive Publication Date: 2017-05-10
JIANGXI NORMAL UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Because the electrophilic fluorination reaction is usually not selective, the nucleophilic fluorination reaction is complex due to the presence of strong hydrogen bonds and high hydration energy in the fluoride anion, the nucleophilicity of the fluoride containing water is low, and the dry fluoride exists strong alkaline

Method used

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  • Method for preparing 4-aryl-2-(2-(trifluoromethyl)aryl)quinazoline
  • Method for preparing 4-aryl-2-(2-(trifluoromethyl)aryl)quinazoline
  • Method for preparing 4-aryl-2-(2-(trifluoromethyl)aryl)quinazoline

Examples

Experimental program
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Effect test

example 1

[0052]2-o-tolyl-4-p-tolylquinazoline (0.3mmol), iodination reagent NIS (0.45mmol, 1.5equiv), catalyst dichloro(pentamethylcyclopentadienyl) rhodium (III) Dimer (0.006mmol, 0.02equiv) and silver hexafluoroantimonate (0.024mmol, 0.08equiv) were dissolved in the organic solvent 1,2-dichloroethane, stirred and reacted in air at 80°C for 1 to 4 hours After that, add AgSCF 3 (0.6mmol, 2.0equiv), CuI (0.03mmol, 10%equiv), reacted at 85°C for 3-4 hours, TLC detected that the reaction was complete. When processing, add a small amount of silica gel to absorb the crude product and spin the solvent to dry, and directly separate the pure product 2-(2-methyl-6-(sulfotrifluoromethyl)phenyl)-4-p-toluene through silica gel column chromatography Quinazolines (3a).

[0053]

[0054] 2-(2-methyl-6(trifluoromethylthio)phenyl)-4-p-tolylquinazoline 3a

[0055] Yellow oil (91%)

[0056] 1 H NMR (400MHz, CDCl 3 )δ8.14(d, J=8.0Hz,1H),8.06(d,J=8.4Hz,1H),7.87–7.83(m,1H),7.65(d,J=8.0Hz,2H),7.61– ...

example 2

[0058] 2-(2-chlorophenyl)-6-methoxy-4-o-tolylquinazoline (0.3mmol), iodination reagent NIS (0.45mmol, 1.5equiv), catalyst dichloro(pentamethylcyclo Pentadienyl) rhodium (III) dimer (0.006mmol, 0.02equiv) and silver hexafluoroantimonate (0.024mmol, 0.08equiv) were dissolved in the organic solvent 1,2-dichloroethane, at 80°C After stirring the reaction in the air for 1 to 4 hours, add AgSCF 3 (0.6mmol, 2.0equiv), CuI (0.03mmol, 10%equiv), reacted at 85°C for 3-4 hours, TLC detected that the reaction was complete. When processing, add a small amount of silica gel to absorb the crude product and spin the solvent to dryness, and directly separate the pure product 2-(2-chloro-6-(sulfurtrifluoromethyl)phenyl)-6-methoxy through silica gel column chromatography -4-o-tolylquinazoline (3b).

[0059]

[0060] 2-(2-chloro-6-(trifluoromethylthio)phenyl)-6-methoxy-4-o-tolylquinazoline 3b

[0061] Yellow oil (88%)

[0062] 1 H NMR (400MHz, CDCl 3 )δ7.99(d,J=8.8Hz,1H),7.65(d,J=8.0Hz,1...

example 3

[0064] Combine 6-methoxy-2,4-two-o-tolylquinazoline (0.3mmol), iodination reagent NIS (0.45mmol, 1.5equiv), catalyst dichloro(pentamethylcyclopentadienyl) Rhodium(III) dimer (0.006mmol, 0.02equiv) and silver hexafluoroantimonate (0.024mmol, 0.08equiv) were dissolved in the organic solvent 1,2-dichloroethane, stirred and reacted in air at 80°C After 1-4 hours, add AgSCF 3 (0.6mmol, 2.0equiv), CuI (0.03mmol, 10%equiv), reacted at 85°C for 3-4 hours, and TLC detected that the reaction was complete. When processing, add a small amount of silica gel to absorb the crude product and spin the solvent to dry, and directly separate the pure product 6-methoxy-2-(2-methyl-6-(sulfurtrifluoromethyl)phenyl through silica gel column chromatography )-4-o-tolylquinazoline (3c).

[0065]

[0066] 6-methoxy-2-(2-methyl-6-(trifluoromethylthio)phenyl)-4-o-tolylquinazoline 3c

[0067] Yellow oil (69%)

[0068] 1 H NMR (400MHz, CDCl 3 )δ8.07(d,J=9.2Hz,1H),7.66(d,J=7.6Hz,1H),7.61(dd,J=9.2,2.8...

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Abstract

The invention discloses a 4-aryl-2-(2-(trifluoromethyl)aryl)quinazoline compound and a preparation method thereof. The preparation method comprises the following steps: taking 2,4-diarylquinazoline as a reaction substrate, carrying out a reaction with NIS under the catalytic action of pentamethylcyclopentadienylrhodium (III) chloride dimer / silver hexafluoroantimonate under a condition of 80 DEG C, carrying out a reaction with a sulfur trifluoromethylation reagent, and taking copper iodide as a catalyst, wherein the reaction temperatire is 85 DEG C, and the reaction time is 7-10 hours; performing carbon hydrogen bond activation process, thereby obtaining the 4-aryl-2-(2-(trifluoromethyl)aryl)quinazoline compound. The preparation method disclosed by the invention is mild in reaction conditions, easy and convenient to operate, low in cost, few in side reactions, high in product purity and convenient for separation and purification and can be suitable for large-scale preparation, and the obtained product has high drug activity and excellent potential application prospects.

Description

technical field [0001] The invention relates to a synthesis method of fluorine-containing quinazoline compounds, in particular to a preparation method of 4-aryl-2-(2-(thiotrifluoromethyl)aryl)quinazoline. Background technique [0002] The introduction of fluorine atoms into the structure of organic compounds can lead to great changes in their physical, chemical properties and biological activities. Fluorine-containing organic molecules play an important role in the fields of medicinal chemistry, natural product chemistry, and pesticides because of their excellent properties. Related literature reports that about 20% of the latest registered medicines contain one or more fluorine atoms, and more than 40% of the pesticides are fluorine-containing compounds. For example: fluazinam (fluazinam, a pesticide, fungicide), picoxystrobin (picoxystrobin, a broad-spectrum fungicide), celecoxib (celecoxib, a drug for the treatment of cervical cancer), efavirenz (favirenz , an antiviral...

Claims

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Application Information

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IPC IPC(8): C07D239/74A61P35/00
CPCA61P35/00C07D239/74C07F1/08B01J31/2295
Inventor 高伟彭以元丁秋平
Owner JIANGXI NORMAL UNIV
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