Method for producing 2-alkyl-2H-(halo)isoquinoline-1-ketone

An isoquinoline and alkyl technology, applied in the production field of isoquinoline derivatives, can solve the problems of low yield, complicated operation, etc., and achieve the effects of high purity, wide sources, and large-scale production.

Inactive Publication Date: 2010-06-09
大连凯飞精细化工有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0002] Isoquinoline is an important medicinal chemical intermediate, and its derivative 2-alkyl-2H-(halogenated) isoquinolin-1-one is also an important medicinal chemical intermediate, and the current literature reports the production of 2-alkyl The method of -2H-(halogenated) isoquinolin-1-one is produced by a two-step method, that is, the intermediate product is first separated, and then acidified to obtain the product. The method is complicated to operate and the yield is low

Method used

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  • Method for producing 2-alkyl-2H-(halo)isoquinoline-1-ketone
  • Method for producing 2-alkyl-2H-(halo)isoquinoline-1-ketone

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Embodiment 1

[0013] The method for producing 2-alkyl-2H-(halogenated) isoquinolin-1-ones, the specific reaction formula is as follows:

[0014]

[0015] Benzoylalkylamine (207g, 1.17mol) was dissolved in 650ml of anhydrous tetrahydrofuran, cooled to 0°C, 0.5L of 2.5M n-butyllithium solution was added dropwise, the temperature was maintained at 5°C, and stirred for 1 hour. At 15°C, start to add 97ml of N,N-dimethylformamide dropwise, maintain the temperature at 0-9°C, after the dropwise addition is completed. After the addition was complete, allow to gradually warm to room temperature and stir for 1 hour. At 0-10°C, add 400ml of 18% aqueous hydrochloric acid solution dropwise, keep the temperature not exceeding 30°C, stir for about 0.5-1 hour, separate the liquids, take the organic phase, dry over magnesium sulfate, and concentrate to obtain the crude product. Recrystallize from petroleum ether / ethyl acetate to obtain a white solid. Yield 25%, weighing 50g, purity 90%.

Embodiment 2

[0017] Benzoylalkylamine (207g, 1.17mol) was dissolved in 650ml of anhydrous tetrahydrofuran, cooled to 10°C, 1L of 2.5M n-butyllithium solution was added dropwise, the temperature was maintained at 0°C, and stirred for 1 hour. At 0°C, 146ml of N,N-dimethylformamide was started to be added dropwise, and the temperature was maintained at 0°C. After the dropwise addition was completed. After the addition was complete, allow to gradually warm to room temperature and stir for 1 hour. At 5°C, add 451ml of 18% hydrochloric acid solution dropwise, keep the temperature not exceeding 30°C, stir for about 1 hour, separate the liquids, take the organic phase, dry over magnesium sulfate, and concentrate to obtain a crude product. Recrystallize from petroleum ether / ethyl acetate to obtain a white solid. Yield 51%, weighing 100g, purity 99.9%.

Embodiment 3

[0019] Benzoylalkylamine (207g, 1.17mol) was dissolved in 650ml of anhydrous tetrahydrofuran, cooled to 0°C, and 1L of 2.5M n-butyllithium solution was added dropwise, maintaining the temperature at 5°C, and stirred for 1 hour. At 30°C, 146ml of N,N-dimethylformamide was added dropwise, and the temperature was maintained at 9°C. After the dropwise addition was completed. After the addition was complete, allow to gradually warm to room temperature and stir for 1 hour. At 0-10°C, add 250ml of 18% hydrochloric acid solution dropwise, keep the temperature not exceeding 30°C, stir for about 1 hour, separate the liquids, take the organic phase, dry over magnesium sulfate, and concentrate to obtain a crude product. Recrystallize from petroleum ether / ethyl acetate to obtain a white solid. Yield 45%, weighing 88g, purity 95%.

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Abstract

The invention relates to a method for producing an isoquinoline derivative. In the method for producing 2-alkyl-2H-(halo)isoquinoline-1-ketone, acid amide is subjected to n-butyl lithium metallization, ring closing and dehydration to finally generate the isoquinoline derivative, namely 2-alkyl-2H-(halo)isoquinoline-1-ketone. The method has the advantages of wide sources of reaction raw materials, mild reaction conditions and easy operation, rapid reaction, simple process, high purity of the prepared product, capability of realizing large-scale production and high yield so as to meet the application requirements of industries such as medicine and the like.

Description

Technical field: [0001] The present invention relates to the production method of organic compound, especially the production method of isoquinoline derivatives. Background technique: [0002] Isoquinoline is an important medicinal chemical intermediate, and its derivative 2-alkyl-2H-(halogenated) isoquinolin-1-one is also a kind of important medicinal chemical intermediate, and the current literature reports the production of 2-alkyl The method of -2H-(halogenated) isoquinolin-1-one is produced by a two-step method, that is, the intermediate product is first separated, and then acidified to obtain the product. The method is complicated to operate and the yield is low. Contents of the invention [0003] The purpose of the present invention is to provide a method for producing 2-alkyl-2H-(halo)isoquinolin-1-one, which has mild conditions, rapid reaction, simple process and easy operation. [0004] The technical solution adopted by the present invention for realizing the ab...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D217/24
Inventor 王乃伟王延波姜人武范德印
Owner 大连凯飞精细化工有限公司
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