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A kind of preparation method of 8-amide-5-haloquinoline derivatives

A technology of haloquinoline and derivatives, which is applied in the field of preparation of 8-amide-5-haloquinoline derivatives, can solve the problems of not meeting the environmental protection requirements of green chemistry and poor environmental friendliness, and achieve easy amplification and promotion The effect of high growth and yield

Active Publication Date: 2021-06-29
CHANGZHOU VOCATIONAL INST OF ENG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] Many documents (J.Am.Chem.Soc.,2013,135(26):9797-9804., Tetrahedron,2015,46(19):70-76, Org.Chem.Front.,2017,4:1046 -1050, Chem.Sci., 2018,9(7):1782-1788, etc.) have reported the synthetic method of 8-amido-5-haloquinoline, and they all use 8-amidoquinoline derivative as The starting materials are respectively mixed with halogen sources (metal halides, N-halogenated succinimides, trihaloisocyanuric acid, etc.) under the action of catalysts, catalyzed by oxidants and reacted with different ligands to obtain C- 5-position halogenated products, these methods are carried out under acidic conditions with high temperature, or require the use of oxidants or even metal catalysts such as palladium or copper, and the reaction requires a large amount of organic solvents, which is poor in environmental friendliness and does not even conform to green chemistry. Environmental requirements

Method used

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  • A kind of preparation method of 8-amide-5-haloquinoline derivatives
  • A kind of preparation method of 8-amide-5-haloquinoline derivatives
  • A kind of preparation method of 8-amide-5-haloquinoline derivatives

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Effect test

Embodiment 1

[0021] Adopt the preparation method of a kind of 8-amide-5-haloquinoline derivative of the present invention, prepare N-(5-chloroquinolin-8-base) acetamide (1aa), English name is N-(5-chloroquinolin- 8-yl)acetamide (1aa), its chemical reaction formula is as follows:

[0022]

[0023] The specific operation steps are: put 8-acetylaminoquinoline (186mg, 1mmol), dichlorohydantoin (140mg, 0.7mmol), benzyltriethylammonium chloride (TEBA) (45.6mg, 0.2mmol) into a 25ml reaction bottle mmol) and water 10mL, stirred and reacted at room temperature for 12h; the reaction solution was filtered and concentrated under reduced pressure to obtain a crude product, which was separated by column chromatography (eluent: petroleum ether: dichloromethane = 3:1~1:1) , to obtain 213.3 mg of white powdery solid (target compound I, 1aa), with a yield of 96.7% (calculated as 8-acetylaminoquinoline).

[0024] The NMR data of target compound I are:

[0025] 1 H NMR (300MHz, CDCl 3 )δ (ppm): 9.75 (s...

Embodiment 2

[0027] Adopt a kind of preparation method of 8-amide-5-haloquinoline derivatives of the present invention, prepare N-(5-bromoquinolin-8-base) acetamide (1ab), English name is N-(5-bromoquinolin -8-yl)acetamide (1ab), its chemical reaction formula is as follows:

[0028]

[0029] The specific operation steps are: put 8-acetamidoquinoline (93mg, 0.5mmol), dibromohydantoin (74.4mg, 0.26mmol), TEBA (22.8mg, 0.1mmol) and 10mL of water into a 25ml reaction bottle, and stir at room temperature Reacted for 12 hours; the reaction solution was filtered and concentrated under reduced pressure to obtain a crude product, which was separated by column chromatography (eluent: petroleum ether: dichloromethane = 3:1~1:1) to obtain a white powdery solid (target compound Ⅰ, 1ab) 123.7 mg, the yield was 93.4% (based on 8-acetylaminoquinoline).

[0030] The NMR data of target compound I are:

[0031] 1 H NMR (300MHz, DMSO-d 6 )δ (ppm): 10.20 (s, 1H), 9.00 (dd, J = 4.2, 1.4Hz, 1H), 8.57 (d, ...

Embodiment 3

[0033] Adopt a kind of preparation method of 8-amide-5-haloquinoline derivative of the present invention, prepare N-(5-iodoquinolin-8-base) acetamide (1ac), English name is N-(5-iodoquinolin -8-yl)acetamide (1ac), its chemical reaction formula is as follows:

[0034]

[0035] The specific operation steps are: put 8-acetamidoquinoline (93mg, 0.5mmol), diiodhydantoin (140mg, 0.35mmol), TEBA (22.8mg, 0.1mmol) and 10mL of water into a 20mL reaction bottle, and stir the reaction at room temperature 12h; the reaction solution was filtered and concentrated under reduced pressure to obtain a crude product, which was separated by column chromatography (eluent: petroleum ether:dichloromethane=3:1~1:1) to obtain a light brown solid (target compound I, 1ac) 142.0 mg, yield 91.0% (calculated as 8-acetylaminoquinoline).

[0036] The NMR data of target compound I are:

[0037] 1 H NMR (300MHz, DMSO-d 6 )δ (ppm): 10.22 (s, 1H), 9.02 (d, J = 2.6Hz, 1H), 8.56 (dd, J = 12.4, 8.5Hz, 2H), 7...

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Abstract

The invention discloses a preparation method of 8-amidoquinoline derivatives (compound II) and dihalohydantoin (compound III) at a certain reaction temperature. ) as a raw material, in the presence of a phase transfer catalyst, stirred and reacted for a certain period of time in a reaction solvent; R 1 It is one of C1~C6 alkyl, cycloalkyl and aromatic groups, R 2 or R 3 is H, F, Cl, Br, CH 3 、CF 3 , OCH 3 , NO 2 , one of CN; after the reaction is finished, the 8-amide-5-halogenated quinoline derivative (compound I) is obtained through aftertreatment. The method of the present invention has the characteristics of environmental protection, atom economy, high yield, simple operation, no need to use metals, easy amplification, etc., promotes the development of halogenated quinoline derivatives, and provides a powerful tool for the development of halogenated quinoline derivatives drugs protection.

Description

technical field [0001] The invention relates to the technical field of chemical synthesis, in particular to a preparation method of 8-amide-5-haloquinoline derivatives. Background technique [0002] (Eur.J.Med.Chem., 2015,97,871-910) reported that quinoline compounds have anti-HIV and antidepressant effects, literature (Bioorg.Med.Chem., Lett., 2008,18(13):3737 -3740) reported that quinoline compounds have antitumor activity, and a large number of studies have shown that better biological activity can be obtained by introducing the quinoline core to modify the structure of the lead. [0003] Many documents (J.Am.Chem.Soc.,2013,135(26):9797-9804., Tetrahedron,2015,46(19):70-76, Org.Chem.Front.,2017,4:1046 -1050, Chem.Sci., 2018,9(7):1782-1788, etc.) have reported the synthetic method of 8-amido-5-haloquinoline, and they all use 8-amidoquinoline derivative as The starting materials are respectively mixed with halogen sources (metal halides, N-halogenated succinimides, trihal...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D215/40
CPCC07D215/40
Inventor 贺新周海平王菲朱亚娟
Owner CHANGZHOU VOCATIONAL INST OF ENG
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