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Preparation method of 4-aryl-2-(2-(thiotrifluoromethyl)aryl)quinazoline

A technology for sulfur trifluoromethyl and diaryl quinazoline, which is applied in the field of synthesis of fluorine-containing quinazoline compounds, can solve the problems of complex reaction, low nucleophilicity and the like, and achieves high yield, clean spectrum, The effect of good potential application prospects

Active Publication Date: 2018-12-11
JIANGXI NORMAL UNIV
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  • Summary
  • 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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  • Preparation method of 4-aryl-2-(2-(thiotrifluoromethyl)aryl)quinazoline
  • Preparation method of 4-aryl-2-(2-(thiotrifluoromethyl)aryl)quinazoline
  • Preparation method of 4-aryl-2-(2-(thiotrifluoromethyl)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] Yellow oil (91%)

[0055] 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– 7.54(m,2H),7.33–7.27(m,4H),2.37(s,3H),2.22(s,3H). 13 C NMR (100MHz, CDCl ...

example 2

[0057] 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).

[0058]

[0059] Yellow oil (88%)

[0060] 1 H NMR (400MHz, CDCl 3 )δ7.99(d,J=8.8Hz,1H),7.65(d,J=8.0Hz,1H),7.53–7.50(m,2H),7.33–7.23(m,5H),6.85(d,J =2.8Hz,1H),3.68(s,3H),2.11(s,3H); 13 C NM...

example 3

[0062] 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).

[0063]

[0064] Yellow oil (69%)

[0065] 1 H NMR (400MHz, CDCl 3 )δ8.07(d,J=9.2Hz,1H),7.66(d,J=7.6Hz,1H),7.61(dd,J=9.2,2.8Hz,1H),7.43–7.33(m,6H), 6.92(d, J=2.8Hz, 1H), 3.78(s, 3H), 2.27(s, 3H), 2.20(s, 3H); ...

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Abstract

The invention discloses a 4-aryl-2-(2-(thiotrifluoromethyl)aryl)quinazoline compound and a preparation method thereof. 2,4-diarylquinazoline is used as a reaction substrate to react with NIS under thecatalytic effect of dichloro(pentamethylcyclopentadienyl) rhodium(III) dipolymer / silver hexafluoroantimonate and then react with a thiotrifluoromethy reagent for 7 to 10 hours at the reaction temperature of 85 DEG C by adopting cuprous iodide as a catalyst by virtue of a carbon-hydrogen-bond activation process, so that the 4-aryl-2-(2-(thiotrifluoromethyl)aryl)quinazoline compound is obtained. The preparation method of the invention is mild in reaction condition, simple in operation, low in cost, less in side reaction, high in product purify, convenient in separation purification and suitablefor mass preparation, and the prepared product is good in drug activity and good in potential application prospect.

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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Patent Type & Authority Applications(China)
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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