Method for synthesizing 3-quinoline derivatives

A technology of derivatives and fluoroquinoline, applied in the field of synthesizing 3-fluoroquinoline derivatives, can solve the problem of large amount of catalyst, and achieve the effects of convenient separation, mild reaction conditions, and easy availability of raw materials

Active Publication Date: 2015-06-03
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

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However, this type of reaction still cannot get rid of the shortcomings

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  • Method for synthesizing 3-quinoline derivatives
  • Method for synthesizing 3-quinoline derivatives
  • Method for synthesizing 3-quinoline derivatives

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Embodiment 1

[0026] Embodiment 1: the synthesis of compound 2a

[0027] In a nitrogen-protected reaction flask, add 1a (0.2 mmol), p-toluenesulfonic acid monohydrate (0.01 mmol), HEH (0.22 mmol), and then add 3 ml of dry acetonitrile. After reacting at room temperature for 2 hours, Add Selectfluor (0.3 mmol) and continue the reaction for 5 minutes, then add potassium tert-butoxide (0.4 mmol) to the system, continue stirring at room temperature for 2 hours, remove the solvent under reduced pressure, and obtain the compound by silica gel column chromatography 2a, its isolated yield reached 94%. The reaction formula is as follows:

[0028]

[0029] 3-Fluoro-2-phenylquinoline(2a):94%yield,white solid,m.p.=36-38℃,R f =0.50(petroleum ether / EtOAc=20:1); 1 H NMR (400MHz, CDCl 3 )δ8.16(d,J=8.5Hz,1H),8.07(d,J=7.3Hz,2H),7.87-7.61(m,3H),7.56-7.44(m,4H); 13 C NMR (100MHz, CDCl 3 )δ155.2(d, 1 J F C=261.0Hz),149.2(d, 2 J FC =14.5Hz), 145.4(d, 5 J FC =2.9Hz), 135.9(d, 4 J FC =5.2Hz), 129....

Embodiment 2

[0031] The synthesis process of compounds 2b-2p is the same as that of Example 1, the difference from Example 1 is that only the substituents R and R' on the raw material 1a are different.

[0032] 3-Fluoro-2-o-tolylquinoline (2b): 95% yield, white solid, m.p.=69-71℃, R f =0.40(petroleum ether / EtOAc=20:1); 1 H NMR (400MHz, CDCl 3 )δ8.17(d,J=8.4Hz,1H),7.87-7.54(m,4H),7.46-7.30(m,4H),2.30(s,3H); 13 C NMR (100MHz, CDCl 3 )δ154.8(d, 1 J FC =257.8Hz), 151.7(d, 2 J FC =19.2Hz), 145.3(d, 4 J FC =2.9Hz),137.0,135.7(d, 4 J FC =3.6Hz),130.7,130.0(d, 5 J FC =1.6Hz),129.8,129.4,128.95(d, 5 J FC =2.5Hz), 128.66(d, 3 J FC =5.1Hz), 127.6, 127.15(d, 3 J FC =4.9Hz), 126.1, 119.2(d, 2 J FC =18.9Hz), 19.9(d, 4 J FC =2.9Hz); 19 F NMR (376MHz, CDCl 3 )δ-123.4(d,J=5.4Hz);HRMS(ESI)m / z Calculated for C 16 h 12 FN[M+H] + 238.1027, found 238.1034.

[0033] 3-Fluoro-2-m-tolylquinoline (2c):93%yield,colorless oil,R f =0.50(petroleum ether / EtOAc=20:1); 1 H NMR (400MHz, CDCl ...

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Abstract

The invention discloses a method for synthesizing 3-quinoline derivatives. The method comprises the following steps: based on a simple 3-nitroquinoline, with bronsted acid as a catalyst, substituting 1,4-dihydropyridine (HEH) as a reducing agent, realizing 1,4- reduction of quinoline to obtain enamine, performing electrophilic addition on the enamine intermediate and a fluorinated reagent, and then repeatedly aromatizing under an alkali condition to obtain various substituted 3-quinoline derivatives. The method for synthesizing the 3-quinoline derivatives has the advantages that the operation is simple, convenient and practical, the raw materials are easy to obtain, the reaction is quick, the post-treatment is convenient, and the yield is high.

Description

technical field [0001] The invention relates to aromatic heterocyclic compounds containing fluorine atoms, in particular to a method for synthesizing 3-fluoroquinoline derivatives. Background technique [0002] Fluorine-containing organic compounds are widely used in the fields of medicine, pesticides, and materials due to their stable carbon-fluorine bonds, fluorocarbon phase characteristics, lipophilicity, pseudo-mimetic effect, metabolic stability, and hydrogen bonding. Especially in medicine, a class of drugs with fluorine-containing aromatic compounds as active groups plays a pivotal role. According to reports, among all commercialized medicines and pesticides, the proportion of fluorine-containing drugs is as high as about 20%. [Document 1: a) H.Schofield, J.Fluorine Chem.1999,100,7; b) H.J.Bohm, D.Banner, S.Bendels, M.Kansy, B Kuhn, K.Muller, U.Obst-Sander , M.Stahl, ChemBioChem2004, 5, 637; c) K.Muller, C.Faeh, F.Diederich, Science2007, 317, 1881; d) W.K.Hagmann, J...

Claims

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Application Information

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IPC IPC(8): C07D215/18C07D215/20
CPCC07D215/18C07D215/20
Inventor 周永贵郭冉柠时磊
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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