Fluorinated isoquinoline [a] pyrrole compounds and preparation method thereof

An isoquinoline and compound technology, applied in the field of fluoroisoquinoline[a]pyrrole compounds and their preparation, can solve the problems of harsh conditions, cumbersome routes, hindering the wide application of isoquinoline[a]pyrrole compounds, and the like, Achieve low cost and good substrate compatibility

Inactive Publication Date: 2015-02-18
SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, there are not many methods for synthesizing isoquinoline[a]pyrrole compounds at present, and there are many problems such as cumbersome routes, poor substrate compatibility, and harsh conditions, which hinder the development of isoquinoline[a]pyrrole compounds. Widely used in medicine, pesticide and other fields

Method used

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  • Fluorinated isoquinoline [a] pyrrole compounds and preparation method thereof
  • Fluorinated isoquinoline [a] pyrrole compounds and preparation method thereof
  • Fluorinated isoquinoline [a] pyrrole compounds and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1: Preparation

[0032] Add 3.4mg (0.02mmol) of AgNO 3 , 5.0mg (0.02mmol) oxazoline ligand Ligand I, 22.2mg (0.3mmol) Li 2 CO 3 , 157.5mg (0.5mmol) of N-fluorobisbenzenesulfonamide (NFSI) was added to the reaction tube, 1.5mL of N,N-dimethylacetamide was added, and then 25.7mg (0.1mmol) of alkyne substrate Add 21.3mg (0.15mmol) of methyl butynyl dicarboxylate, stir and react at 60°C for 5 hours; add water, extract with ether, combine the extracts, concentrate, column chromatography, elution with ethyl acetate and petroleum ether gradient, 24.9mg product obtained The yield was 60%.

[0033] 1 H NMR(400MHz, CDCl 3 ): 8.48-8.39(m,1H),7.89-7.82(m,1H),7.61-7.51(m,2H),4.01(s,3H),3.98(s,3H),3.91(s,3H), 3.07(td,J=7.2,3.6Hz,2H),1.56(tt,J=7.2,7.2Hz,2H),1.34(tq,J=7.2,7.2Hz,2H),0.92(t,J=7.2Hz ,3H);

[0034] 13 C NMR(100MHz, CDCl 3 ): 166.5,163.9,162.7,148.4(d,J=236.1Hz),128.9,128.7,128.3,124.0(d,J=3.1Hz),123.9(d,J=33.7Hz),123.2(d,J= 6.8Hz),121.8(d,J=20.8Hz),121.4(d,J=3.7Hz),...

Embodiment 2

[0037] Example 2: Preparation

[0038] Add 3.4mg (0.02mmol) of AgNO 3 , 5.0mg (0.02mmol) oxazoline ligand Ligand I, 22.2mg (0.3mmol) Li 2 CO 3 , 157.5mg (0.5mmol) of N-fluorobisbenzenesulfonamide (NFSI) was added to the reaction tube, 1.5mL of N,N-dimethylacetamide was added, and then 28.1mg (0.1mmol) of alkyne substrate Add 21.3mg (0.15mmol) of methyl butynyl dicarboxylate, stir and react at 60°C for 5 hours; add water, extract with ether, combine the extracts, concentrate, column chromatography, elution with ethyl acetate and petroleum ether gradient, 36.4mg product is obtained The yield was 83%.

[0039] 1 H NMR(400MHz, CDCl 3 ): 8.48(dd,J=6.0,2.4Hz,1H),8.87(dd,J=6.0,2.8Hz,1H),7.61-7.53(m,2H),6.03-5.96(m,1H),4.00( s, 3H), 3.91(s, 3H), 3.88(s, 3H), 2.48-2.37(m, 2H), 2.26-2.07(m, 2H), 1.87-1.77(m, 2H), 1.76-1.64( m,2H);

[0040] 13 C NMR(100MHz, CDCl 3 ): .166.4,163.8,162.0,147.0(d,J=237.4Hz),133.3(d,J=1.1Hz),128.8,128.4,128.3(d,J=1.1Hz),128.1,123.9(d,J =2.6Hz),123.7(d,J=35.6H...

Embodiment 3

[0043] Example 3: Preparation

[0044] Add 3.4mg (0.02mmol) of AgNO 3 , 5.0mg (0.02mmol) oxazoline ligand Ligand I, 22.2mg (0.3mmol) Li 2 CO 3 , 157.5mg (0.5mmol) of N-fluorobisbenzenesulfonamide (NFSI) was added to the reaction tube, 1.5mL of N,N-dimethylacetamide was added, and then 28.3mg (0.1mmol) of alkyne substrate Add 21.3mg (0.15mmol) of methyl butynyl dicarboxylate, stir and react at 60°C for 5 hours; add water, extract with ether, combine the extracts, concentrate, column chromatography, elution with ethyl acetate and petroleum ether gradient, 27.8mg product The yield was 63%.

[0045] 1 H NMR(400MHz, CDCl 3 ): 7.69-7.61 (m, 1H), 7.56-7.38 (m, 6H), 3.97-3.91 (m, 6H), 3.24 (s, 3H);

[0046] 13 C NMR(100MHz, CDCl 3 ): .165.6,163.3,159.5,147.3(d,J=241.5Hz),132.8,131.3,130.4,129.9(d,J=18.2Hz),129.8,129.2,128.9,128.5,127.8(d,J=2.0 Hz),122.6(d,J=29.8Hz),119.2,118.6,102.7,52.7,51.7,51.6;

[0047] 19 F NMR(376MHz, CDCl 3 ): .-139.5(s);

[0048] MS: m / z(ESI)calculated[M+Na] + :464...

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Abstract

The present invention discloses a class of fluorinated isoquinoline [a] pyrrole compounds and a preparation method thereof. The fluorinated isoquinoline [a] pyrrole compound has the following structural general formula, wherein R1-R5 are respectively and independently selected from hydrogen, alkyl, naphthenic base, aryl and heterocyclic group, R7 is selected from alkyl, naphthenic base, aryl and heterocyclic group, and R8 and R9 are electron withdrawing substituents. The preparation method comprises that: an alkyne substrate I, N-fluorobenzenesulfonimide II and an electrophilic alkyne III are subjected to a fluorine amination cycloaddition reaction in an anhydrous organic solvent under a basic condition in the presence of a silver catalyst and an oxazoline ligand, wherein the reaction formula is as the follow, R1-R5 are respectively and independently selected from hydrogen, alkyl, naphthenic base, aryl and heterocyclic group, R6 is selected from methylene ester, R7 is selected from alkyl, naphthenic base, aryl and heterocyclic group, and R8 and R9 are electron withdrawing substituents. According to the present invention, wide applications of the isoquinoline [a] pyrrole compounds in medicine, pesticides and other fields can be promoted.

Description

Technical field [0001] The invention relates to a class of fluoroisoquinoline [a]pyrrole compounds and a preparation method thereof, and belongs to the technical field of organic synthesis. Background technique [0002] The isoquinoline [a] pyrrole structure is one of the most common structural fragments in natural products and drug molecules. Many molecular structures contain isoquinoline [a] pyrrole skeleton units, and they often have good biological activity and medical value. For example: the natural product Lamellarin D is a good enzyme inhibitor; the compound of formula I can inhibit cell growth, has antiproliferative activity and anti-tumor activity; the compound of formula II has the activity of inhibiting the growth of PDH enzyme and bacteria; the compound of formula III It has anti-multiple tumor activity; the compound of formula IV is also a good enzyme inhibitor; the compound of formula V has anti-HIV activity; the compound of formula VI and the compound of formula V...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D471/04C07D495/14
CPCC07D471/04C07D495/14
Inventor 刘国生徐涛
Owner SHANGHAI INST OF ORGANIC CHEM CHINESE ACAD OF SCI
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