Practical synthesis method of 3-acetyl-4-azaindole

A technique for the synthesis of azaindole, which is applied in the fields of medicine and chemical industry, can solve the problems of unavailable products, unsuitable for scale-up and industrial production, and low reaction yield, and achieve mild conditions, shorten the production process, and improve the reaction rate. The effect of temperature

Inactive Publication Date: 2015-02-25
苏州科捷生物医药有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] We have tried this method many times and found that the reaction yield is extremely low, and almost no product can be obtained. At the

Method used

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  • Practical synthesis method of 3-acetyl-4-azaindole
  • Practical synthesis method of 3-acetyl-4-azaindole
  • Practical synthesis method of 3-acetyl-4-azaindole

Examples

Experimental program
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Effect test

Example Embodiment

[0015] Example 1: Synthesis of 4-azaindole (Compound 2)

[0016]

[0017] 2-Methyl-3-nitropyridine (23.4g, 0.17mol), DMF-DMA (60g, 0.51mol) and DMF (100ml) were heated to 90°C and stirred for 8 hours. Cool to room temperature, pour the reaction solution into 300 ml of cold water, filter with suction to obtain a red solid, dissolve the solid in ethanol (500 ml), add 10% Pd / C (5 g), and stir at room temperature for 10 hours under a hydrogen atmosphere , Suction filtration (spread a layer of diatomaceous earth), wash with ethanol, and concentrate to obtain 18.1 g of brown solid 4-azaindole, yield: 90.5%.

[0018] EI-MS MS(m / z): 119.1(M + )

[0019] 1 H-NMR (DMSO-d6, 400MHz): δ8.29~8.27(m,1H), 7.76(d,1H), 7.61(d,1H), 7.08~7.04(m,1H), 6.54~6.52(m , 1H).

Example Embodiment

[0020] Example 2: Synthesis of 3-acetyl-4-azaindole (Compound 3)

[0021]

[0022] 4-azaindole (21g, 0.18mol) was added to anhydrous aluminum trichloride (106.8g, 0.80mol), suspended in dichloroethane (800ml), heated to 50℃, stirred for 1 hour, and cooled to room temperature , Acetyl chloride (18.8g, 0.24mol) was added dropwise, after the addition, heated to 50°C and stirred for 2 hours, cooled, slowly added dropwise methanol (300ml) to quench the reaction, concentrated to dryness, added water (100ml), Sodium carbonate solution was added dropwise until a large amount of solids precipitated out, filtered with suction, the solids were washed with ethyl acetate (400 ml), the solids were discarded, the ethyl acetate layer was washed with saturated brine (50 ml), dried with anhydrous sodium sulfate, and filtered with suction , Concentrated to obtain a crude product, added n-hexane (60 ml), stirred, filtered with suction, and dried to obtain 20.2 g of off-white solid 3-acetyl-4-azaindo...

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Abstract

The invention discloses a practical synthesis method of 3-acetyl-4-azaindole. The synthesis method comprises the following steps: taking 2-methyl-3-nitropyridine as the primary raw material, making 2-methyl-3-nitropyridine carry out condensation reactions with DMF-DMA, then subjecting the reaction products to hydrogenation and ring-closure reactions in the presence of a catalyst Pd/C so as to obtain 4-azaindole, and finally subjecting 4-azaindole to Friedel-Crafts reactions so as to obtain 3-acetyl-4-azaindole. The provided method has the advantages of mild conditions, easily-available raw materials, low cost, high yield, and convenient operation, and thus is suitable for industrial production.

Description

technical field [0001] The invention relates to a practical synthesis method of 3-acetyl-4-azaindole, which belongs to the technical fields of medicine and chemical industry. Background technique [0002] 3-acetyl-4-azaindole is a very important intermediate, which is widely used in the field of biomedicine (JMC2012, 55: 9531-9540; BMCL2013, 23: 213-217; US2004 / 63744; US2010 / 22581; WO2011 / 73092), can be used to synthesize complement factor D inhibitors to treat age-related macular degeneration (WO2012093101); can also be used to synthesize FAAH enzyme inhibitors for the treatment of pain, inflammation, neurodegenerative diseases, etc. (WO2012 / 88469 ). [0003] The synthesis of 3-acetyl-4-azaindole, the method reported in literature (JOC2002,67:6226-6227) is: use 4-azaindole as raw material, methylene chloride as solvent, anhydrous trichloride Aluminum is used as a catalyst, reacts with acetyl chloride at room temperature for several hours, and is separated by silica gel co...

Claims

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Application Information

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IPC IPC(8): C07D471/04
CPCC07D471/04
Inventor 邵东黄传满
Owner 苏州科捷生物医药有限公司
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