Synthetic method of 3,4-disubstituted isoxazole compound

A synthesis method and technology for aldehyde compounds, applied in the field of organic compound process application, can solve the problems of low yield and the like, and achieve the effects of high efficiency, anti-allergic activity, anti-tumor activity, and easy operation

Inactive Publication Date: 2012-09-12
EAST CHINA NORMAL UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, there are few methods for efficiently synthesizing 3,4-disubstituted isoxazoles disclosed in the prior art, and all of them require either multi-step reactions, metal catalysis, or very low yields

Method used

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  • Synthetic method of 3,4-disubstituted isoxazole compound
  • Synthetic method of 3,4-disubstituted isoxazole compound
  • Synthetic method of 3,4-disubstituted isoxazole compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] The synthetic method of substrate 1:

[0026]

[0027] Substrate A (10.0 mmol) was dissolved in 10 mL of ethanol and 0.5 mL of pyridine, and heated to 80°C. After stirring for 5 minutes, hydroxylamine hydrochloride (12.0 mmol) was added in one portion. React at 80° C. for 2 hours, detect the reaction on a TLC plate, and spin off the solvent after substrate A disappears. Add 5 mL of DCM, stir at 0oC for 10 minutes, and a suspension appears. The solid was filtered off, and the filtrate was spin-dried to obtain product B. The product B (8.75 mmol) was dissolved in 10 mL of DCM, 5 drops of pyridine was added dropwise, and the mixture was lowered to 0°C and stirred for 5 minutes. Then, NCS (10.5 mmol) was added in portions over 30 minutes. After the addition was complete, the reaction was warmed to room temperature and the reaction was stirred until B disappeared. 20 mL of water was added and extracted with DCM, and the yellow powder product 1 (N-hydroxychloroimide c...

Embodiment 2

[0032]

[0033] In a reaction flask, dissolve substrate 3a (74.5 μL, 0.88 mmol) and TEA (53.9 μtL, 0.4 mmol) in 4 mL of toluene, and after adjusting the temperature to 0 ° C, add substrate 2a (173.9 μL, 1.6 mmol) into the reaction. Then, the substrate 1a (62.2mg, 0.4mmol) was dissolved in 0.2mL toluene, and added to the reaction system in 5 times. After the reaction was carried out at 0°C for 10 minutes, the temperature was adjusted to room temperature, and the reaction was carried out for 1.5 hours. TLC tracking point plate, after the end of the reaction, flash column chromatography purification to obtain product 4aa (100mg, 98%). 1 H NMR (300MHz; CDCl 3): δ=7.75-7.69(m, 2H), 7.48-7.41(m, 3H), 5.41(d, J=2.7Hz, 1H), 3.40(dd, J=3.5, 2.8Hz, 1H), 2.91- 2.68(m, 4H), 2.22-2.13(m, 1H), 1.83-1.78(m, 4H), 1.10(d, J=6.9Hz, 3H), 0.83(d, J=6.9Hz, 3H); 13 C NMR (75MHz, CDCl 3 ): δ=157.2, 129.6, 128.8, 126.8, 95.3, 56.2, 46.9, 28.1, 23.8, 20.6, 17.1; HRMS (ESI) calcd for C 16 h 2...

Embodiment 3

[0035]

[0036] The operation was the same as in Example 2, and THF was used as the solvent, and the yield was 93%. The product was detected as compound 4aa by spectrogram.

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Abstract

The invention discloses a synthetic method of a 3,4-disubstituted isoxazole compound. The 3,4-disubstituted isoxazole compound is obtained by reacting an N-hydroxychloroimide compound, an aldehyde compound and secondary amine which are treated as reaction raw materials in a reaction solvent under the action of a base to obtain a 4,5-dihydroisoxazole compound, and oxidizing the 4,5-dihydroisoxazole compound under the action of an oxidant mCPBA. The 3,4-disubstituted isoxazole compound widely exists in medicinal active molecules and natural products, has very good biological activities and pharmacological activities, such as anticancer activities, antiallergic activities and antitumor activities, and also has very high medicinal values. The synthetic method which has the advantages of mild reaction conditions, easily available and cheap raw materials, simple operation and high yield is widely suitable for industrialized scale production.

Description

technical field [0001] The invention specifically relates to a synthesis method of 3,4-disubstituted isoxazole compounds, which belongs to the technical field of organic compound technology application. Background technique [0002] 3,4-disubstituted isoxazole compounds are a very important class of pharmaceutical and chemical intermediates with very high application value. Such products widely exist in pharmaceutically active molecules and natural products, and have very good biological and pharmacological activities, such as anticancer activity, antiallergic activity and antitumor activity, and their medicinal value is very high. Natural products and drug molecules with this core skeleton, such as: Antianaphylactic agent, Drug candidate for liver fibrosis, Cognitive enhancer, Leflunomide, Cloxacillin, NVP-AUY922 (anticancer drug), etc., are as follows: [0003] [0004] However, there are few methods for efficiently synthesizing 3,4-disubstituted isoxazole compounds di...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D261/08C07D413/04A61P35/00A61P37/08
Inventor 姜雪峰汪舰刘会李文军
Owner EAST CHINA NORMAL UNIV
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