Preparation method for 5-sulfuryl-fluoride-substitued isoxazoles compound

A technology for isoxazoles and compounds, which is applied in the field of preparation of 5-sulfonyl fluoride-substituted isoxazoles, can solve problems such as the lack of synthetic methods, and achieve the effects of simple and easy-to-obtain raw materials, mild reaction conditions, and simple operations

Inactive Publication Date: 2018-09-14
WUHAN UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, combined with the existing literature, there is still a lack of an effective synthetic method for simultaneously introducing isoxazole and sulfonyl fluoride groups into the molecular structure through one-step synthesis.

Method used

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  • Preparation method for 5-sulfuryl-fluoride-substitued isoxazoles compound
  • Preparation method for 5-sulfuryl-fluoride-substitued isoxazoles compound
  • Preparation method for 5-sulfuryl-fluoride-substitued isoxazoles compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026]

[0027] In a 50mL reaction flask, add phenyl chloroxime (0.78g, 5mmol), tert-butanol (10mL), tripropylamine (1.79g, 12.5mmol), stir at room temperature for 15min, then take 1-bromovinylsulfonyl Fluorine (3.78g, 20mmol) was dissolved in tert-butanol (10mL), placed in a 20mL constant pressure dropping funnel, and added dropwise to the above reaction system within 30min. The reaction process was detected by thin-layer chromatography. After the reaction, the reaction liquid was extracted with water and dichloromethane (3×10mL). The dichloromethane layer was dried with anhydrous sodium sulfate, filtered, and spin-dried. Analysis and purification (eluent is petroleum ether: ethyl acetate = 20:1 (v / v)), that is, 3-phenyl-5-sulfonyl fluoride isoxazole (885mg, 78%. M.p.69-70 ℃). 1 H NMR (500MHz,) δ7.83 (d, J=7.2Hz, 2H), 7.58–7.49 (m, 4H), 7.47 (s, 1H). 19 F NMR (471MHz, CDCl 3 )δ64.5(s,1F). 13 CNMR (126MHz,) δ163.3(s), 158.8(d, J=39.0Hz), 131.8(s), 129.6(s), 127.2(s), 12...

Embodiment 2

[0029]

[0030] In a 50mL reaction flask, add 4-benzyloxyphenyl chloroxime (1.31g, 5mmol), tert-butanol (10mL), tripropylamine (1.79g, 12.5mmol), stir at room temperature for 15min, then take 1-bromo Vinylsulfonyl fluoride (3.78g, 20mmol) was dissolved in tert-butanol (10mL), placed in a 20mL constant pressure dropping funnel, and added dropwise to the above reaction system within 30min. The reaction process was detected by thin-layer chromatography. After the reaction, the reaction liquid was extracted with water and dichloromethane (3×10mL). The dichloromethane layer was dried with anhydrous sodium sulfate, filtered, and spin-dried. Analysis and purification (eluent is sherwood oil: ethyl acetate=20:1 (v / v)), obtains 3-(4-benzyloxyphenyl)-5-sulfonyl fluoride isoxazole (1.33g , 80%.M.p.131-132°C). 1 H NMR (500MHz, CDCl 3 )δ7.76(d, J=8.4Hz, 2H), 7.47–7.39(m, 5H), 7.36(t, J=7.0Hz, 1H), 7.10(d, J=8.4Hz, 2H), 5.14( s,2H). 19 F NMR (471MHz, CDCl 3 )δ64.3(s,1F). 13 C NMR (...

Embodiment 3

[0032]

[0033] In a 50mL reaction flask, add 2-bromophenylchloroxime (1.17g, 5mmol), tert-butanol (10mL), tripropylamine (1.79g, 12.5mmol), stir at room temperature for 15min, then take 1-bromoethylene Sulfonyl fluoride (3.78g, 20mmol) was dissolved in tert-butanol (10mL), placed in a 20mL constant pressure dropping funnel, and added dropwise to the above reaction system within 30min. The reaction process was detected by thin-layer chromatography. After the reaction, the reaction liquid was extracted with water and dichloromethane (3×10mL). The dichloromethane layer was dried with anhydrous sodium sulfate, filtered, and spin-dried. Analysis and purification (eluent is petroleum ether: ethyl acetate = 20:1 (v / v)), to obtain 3-(2-bromophenyl)-5-sulfonyl fluoride isoxazole (793mg, 52% ). 1 H NMR (500MHz, CDCl 3)δ7.74(d, J=7.9Hz, 1H), 7.69(d, J=7.4Hz, 1H), 7.65(s, 1H), 7.48(t, J=7.4Hz, 1H), 7.42(t, J=7.3Hz,1H). 19 F NMR (471MHz, CDCl 3 )δ64.8(s,1F). 13 C NMR (126MHz, CDC...

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Abstract

The invention discloses a preparation method for a 5-sulfuryl-fluoride-substitued isoxazoles compound. The method comprises the following steps: using substituted 2-aryl chlorinated oxime containing different functional groups as a raw material, mixing with 1-brominated vinyl sulfonyl fluorine in a solvent, adding a basic catalyst, reacting for 1-12 hours in 20-40 DEG C, separating and purifying,to obtain the 5-sulfuryl-fluoride-substitued isoxazoles compound. The obtained product by the preparation method is the isoxazoles compound substituted by 5-sulfuryl-fluoride. The preparation method comprises the following steps: through a simple 1,3-dipolar-cycloaddition reaction, using tripropylamine as alkali, to obtain an activity 1,3-dipole, performing a cycloaddition reaction, and under thealkali action of another molecule, removing molecular hydrogen bromide, to obtained a final product of isoxazole. The preparation method is capable of creatively constructing a synthetic method whichis moderate in reaction conditions, wide application range in substrate, low in requirements to apparatuses, simple and easy in acquisition of raw materials, simple in operation and high in yield.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to a preparation method of 5-sulfonyl fluoride-substituted isoxazole compounds. Background technique [0002] Isoxazole compounds are a kind of five-membered heterocyclic compounds containing nitrogen and oxygen atoms, which have important applications in the fields of drug molecule design and organic synthesis. In medicinal chemistry research, various drug molecules and biologically active natural products contain isoxazole structures. For example: COX-2 inhibitor prodrug parecoxib, broad-spectrum antibacterial drug sulfamethoxazole, β-lactam antibiotic oxacillin, antidepressant drug isocarboxazid, and rheumatic drug leflunomide. In addition, in 1977, Shell Oil Company of the United States found that 3,5-disubstituted isoxazole compounds had insecticidal activity (J.Med.Chem.1977,20,934-939); It is reported that 4-halogenated isoxazole compounds are potential antagoni...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D261/10C07D413/04
CPCC07D261/10C07D413/04
Inventor 秦华利冷静
Owner WUHAN UNIV OF TECH
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