Method for preparing isoquinoline ketone and derivatives thereof

A compound and reaction technology, which is applied in the field of preparation of isoquinolinone and its derivatives, can solve the problems of harsh reaction conditions, many by-products, difficult purification, etc., and achieve high synthesis yield, simple operation, and simple and easy-to-obtain raw materials Effect

Inactive Publication Date: 2012-03-21
TSINGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Although there have been many reports of methods for synthesizing isoquinolinone derivatives in recent years, because their reaction conditions are often harsh, the yield is not high, and there are many by-products, the purification is difficult, and some methods must use expensive catalysts. Therefore, it is urgent to develop simple and effective new methods for the synthesis of isoquinolinones and their derivatives.

Method used

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  • Method for preparing isoquinoline ketone and derivatives thereof
  • Method for preparing isoquinoline ketone and derivatives thereof
  • Method for preparing isoquinoline ketone and derivatives thereof

Examples

Experimental program
Comparison scheme
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Embodiment 1

[0023] The preparation of embodiment 1,3-methylisoquinolinone (R in structural formula I 1 = methyl, R 2 =R=H)

[0024] In the 25mL reactor, add o-iodobenzamide (1.0mmol, 248.0mg), CuI (0.1mmol, 19.0mg), K 3 PO 4 (2.0mmol, 424.0mg), finally add acetylacetone (1.0mmol, 102.0μL), DMF (2mL), seal the reactor, and stir at 120°C for 24h. After the reaction system was cooled, 5 mL of water was added to quench the reaction, and 15 mL of ethyl acetate was used to extract three times. The filtrates were combined and washed twice with water and once with saturated brine. Magnesium sulfate was added to dry for 30 minutes, filtered, and the filtrate was concentrated by rotary evaporation to obtain a crude product. The crude product was separated by column (200-300 mesh silica gel) with a mixture of petroleum ether:ethyl acetate=5:1 (v / v) as eluent to obtain a yellow solid product 3-methylisocyanate with a purity greater than 99%. Quinolinone 102.0mg, isolated yield 65%.

[0025] The...

Embodiment 2

[0029] The preparation of embodiment 2,3-ethylisoquinolinone (R in structural formula I 1 = ethyl, R 2 =R=H)

[0030] In the reactor of 25mL, add o-iodobenzamide (1.0mmol, 248.0mg) successively, CuI (0.1mmol, 20.0mg), K 3 PO 4 (2.0mmol, 424.0mg), finally added 3,5-heptanedione (1.0mmol, 138.0μL), DMF (2mL), sealed the reactor, and stirred at 120°C for 24h. After the reaction system was cooled, 5 mL of water was added to quench the reaction, and 15 mL of ethyl acetate was used to extract three times. The filtrates were combined and washed twice with water and once with saturated brine. Magnesium sulfate was added to dry for 30 minutes, filtered, and the filtrate was concentrated by rotary evaporation to obtain a crude product. The crude product was separated by column (200-300 mesh silica gel) with a mixture of petroleum ether:ethyl acetate=10:1 (v / v) as eluent to obtain a yellow solid product 3-ethylisocyanate with a purity of more than 99%. Quinolinone 98.0 mg, isolated ...

Embodiment 3

[0035] The preparation of embodiment 3,3-phenylisoquinolinone (R in structural formula I 1 = phenyl, R 2 =R=H)

[0036] In a 25mL reactor, add o-iodobenzamide (1.0mmol, 248.0mg), benzoylacetone (1.0mmol, 162mg), CuI (0.1mmol, 20.0mg), K 3 PO 4 (2.0 mmol, 424.0 mg), and finally 2 mL of DMF was added as a solvent, the reactor was sealed, and the mixture was stirred at 120° C. for 24 h. After the reaction system was cooled, 5 mL of water was added to quench the reaction, and 15 mL of ethyl acetate was used to extract three times. The filtrates were combined and washed twice with water and once with saturated brine. Magnesium sulfate was added to dry for 30 minutes, filtered, and the filtrate was concentrated by rotary evaporation to obtain a crude product. The crude product was separated by column (200-300 mesh silica gel) with a mixture of petroleum ether: ethyl acetate = 12:1 (v / v) as eluent to obtain a yellow solid product 3-phenyliso Quinolinone 115.0mg, isolated yield 5...

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Abstract

The invention discloses a method for preparing isoquinoline ketone and derivatives thereof, comprising the following steps of: placing o-halogen benzamide, a 1, 3-dicarbonyl compound, cuprous salt and alkali into a reaction vessel, adding a dimethyl formamide (DMF) or toluene as a solvent into the reaction vessel, hermetically stirring at a temperature of 100-120 DEG C for reacting for 12-36 hours, and quenching the reaction, extracting, washing, drying, concentrating and purifying the reaction liquid to obtain an end product. The synthetic method of the isoquinoline ketone and the derivatives thereof is scientific and reasonable and has the characteristics of high synthetic yield, good selectivity, easiness in purifying the product and the like; and the isoquinoline ketone derivatives with various substituent groups, which cannot be synthetized by utilizing the other methods, can be synthetized and obtained.

Description

technical field [0001] The invention relates to a preparation method of isoquinolinone and its derivatives. Background technique [0002] Isoquinolinone compounds widely exist in nature, and their derivatives have various biological activities such as vasodilation and antitumor. In addition, isoquinolinone compounds are important chemical intermediates. For example, tetrahydroisoquinolinone derivatives prepared from them are not only used in the manufacture of high-efficiency insecticides, color films and dyes, but also have important pharmacological effects. Such as antihypertensive, antiarrhythmic, antithrombotic activity, etc., but also an important intermediate of antigastric ulcer drugs. The key to the synthesis of tetrahydroisoquinolinone and its derivatives is the synthesis of isoquinoline ring. The synthesis of isoquinoline ring has always been paid special attention by organic synthetic chemists and pharmaceutical synthetic chemists. Although there have been many...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D217/24
Inventor 席婵娟蔡尚军王飞
Owner TSINGHUA UNIV
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