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Preparation method for polysubstituted isoquinoline derivative

A derivative and multi-substitution technology, which is applied in the field of preparation of multi-substituted isoquinoline derivatives, can solve the problems of high production cost, large environmental pollution, cumbersome synthesis steps, etc., achieve high yield, scientific and reasonable synthesis method, and comprehensive The effect of simple method

Inactive Publication Date: 2016-08-17
QINGDAO UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] The preparation of isoquinoline derivatives by the above method has obvious disadvantages: 1) most of the existing methods use benzaldehyde or toxic aniline as raw materials, and the synthesis steps are cumbersome; 2) the reaction is under strong acid or strong alkali conditions, or expensive It is carried out under the condition of metal catalysis, the equipment is seriously corroded, the production cost is high, and the environmental pollution is great.

Method used

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  • Preparation method for polysubstituted isoquinoline derivative
  • Preparation method for polysubstituted isoquinoline derivative
  • Preparation method for polysubstituted isoquinoline derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Preparation of isoquinoline derivative 3a

[0031]

[0032] Into a 10ml reactor, add isothiocyanate 1a (0.4mmol, 89.2mg), diaryl hypervalent iodide 2a (0.6mmol, 255.6mg), cuprous chloride (0.04mmol), and replace nitrogen three times Finally, dichloroethane (2ml) was added, and after the addition was completed, the reaction was carried out at 80°C for 1.5h. After the reaction system was cooled, 5 ml of saturated sodium bicarbonate solution was added to quench the reaction, and extracted three times with 30 ml of ethyl acetate. The organic phases were combined, dried by adding magnesium sulfate for 30 minutes, filtered, and the filtrate was concentrated by rotary evaporation to obtain a crude product. The crude product was separated by eluent column (200-300 mesh silica gel), and the white solid product was confirmed to be isoquinoline derivative 3a by NMR and HRMS, and the yield was 90%.

[0033] Spectrum analysis data 3a:

[0034] 1 H NMR (CDCl 3 ,500MHz): δ2.68(...

Embodiment 2

[0036] Replace 2a in Example 1 with 2b, and other experimental conditions are the same as Example 1. The experimental results are shown in Table 1.

[0037]

[0038] Spectrum analysis data 3b:

[0039] 1 H NMR (CDCl 3 ,500MHz): δ2.36(s,3H),2.65(t,J=7.4Hz,2H),3.64(t,J=7.2Hz,2H),3.91(s,3H),3.92(s,3H) ,6.69(s,1H),7.21(d,J=7.9Hz,2H),7.30(s,1H),7.43(d,J=8.0Hz,2H). 13 C NMR (CDCl 3 ,125MHz):δ21.3,26.0,48.6,56.0,56.1,108.4,110.0,121.6,125.9,130.0,131.1,135.0,138.8,147.3,151.0,163.5.HRMS(ESI-TOF,[M+H] + ):Calcd for C 18 h 19 NO 2 S, 313.1262; Found, 313.1265.

Embodiment 3

[0041] Replace 2a in Example 1 with 2c, and other experimental conditions are the same as Example 1, and the experimental results are shown in Table 1.

[0042]

[0043] Spectral analysis data 3c:

[0044] 1 H NMR (CDCl 3,500MHz):δ2.65(t,J=7.4Hz,2H),3.63(t,J=7.2Hz,2H),3.92(s,3H),3.93(s,3H),6.70(s,1H) ,7.09(t,J=8.6Hz,2H),7.28(s,1H),7.51-7.54(m,2H). 13 C NMR (CDCl 3 ,125MHz): δ26.0,48.6,56.0,56.1,108.3,110.1,116.2(d,J C-F =21.94Hz), 121.5, 124.6, 131.1, 137.2 (d, J C-F =248.34Hz),147.4,151.2,162.1,163.1,164.0.HRMS(ESI-TOF,[M+H] + ): Calcd for C 17 h 16 FNO 2 S, 317.1012; Found, 317.1015.

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Abstract

The invention discloses a preparation method for a polysubstituted isoquinoline derivative and belongs to the technical field of organic synthesis. The method includes the steps that isothiocyanate and diaryl high-price iodate are added into a reactor, heating is conducted in a solvent under copper catalysis, the material is cooled to room temperature after the reaction is completed, the system is extracted with ethyl acetate, filtrate is concentrated with a rotary evaporator, a crude product is obtained, and finally the product is obtained after column chromatography isolation. The synthesis method is easy to operate, the raw materials are easy to prepare, multiple substituent groups can be introduced at the same time, the product is easy to purify and separate, the yield is high, and the method is suitable for synthesizing the polysubstituted isoquinoline derivative. The reaction equation in the method is shown in the description.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, in particular to a preparation method of multi-substituted isoquinoline derivatives. Background technique [0002] Isoquinoline is not only the core structural unit of many natural products, but also the basic skeleton of many important drug molecules ( figure 1 ). Alkaloids containing the basic structural unit of isoquinoline include benzylisoquinolines (such as papaverine), protoberberines (such as berberine), bisbenzylisoquinolines (such as tetrandrine), Morphine (such as morphine, codeine), phenphenidine (such as chelidonine), phenol isoquinoline (such as narcotine), etc. These isoquinoline alkaloids have extensive and unique biological and pharmacological activities, including antifungal, anticancer, antiarrhythmic, analgesic anesthesia and blood pressure lowering effects. [0003] [0004] With the continuous development of organic synthetic chemistry, the synthetic applicat...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D217/22C07D217/26C07D491/056
CPCC07D217/22C07D217/26C07D491/056
Inventor 文丽荣窦谦郭维斯李明
Owner QINGDAO UNIV OF SCI & TECH
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