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Method for preparing substituted indole-3-methanal compound

A technology of compound and compound structural formula, which is applied in the field of preparation of substituted indole-3-carboxaldehyde compounds, can solve problems such as industrialization difficulties and operational difficulties, and achieve the effects of reducing side reactions, increasing reaction yield, and reducing adsorption

Active Publication Date: 2012-10-24
上海泰坦科技股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since there is a carboxyl group attached to the 2-position of the indole ring synthesized by the first two methods, a high temperature (generally above 200°C) is required to remove the carboxyl group at the 2-position, which is difficult to operate and also gives Industrialization has brought certain difficulties

Method used

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  • Method for preparing substituted indole-3-methanal compound
  • Method for preparing substituted indole-3-methanal compound
  • Method for preparing substituted indole-3-methanal compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] The synthesis of embodiment 1 indole-3 formaldehyde

[0031]

[0032] Add 5.6 g of 2-nitrotoluene (compound 1a, 0.041 mol) and 24.3 g of DMFDMA (0.205 mol) into 80 ml of acetonitrile, raise the reaction temperature to 85°C-95°C, and reflux for 5 hours. The reaction solution was cooled, the solvent was spin-dried, and washed with water and a small amount of ethanol to obtain 7.7 g of crude product 2a (0.0402 mol, yield 98.0%).

[0033] The obtained compound 2a was added to 130ml of methanol containing 10wt% hydrazine (hydrazine content 0.4mol, 10eq), and the temperature was raised to 50°C, reacted for 8 hours, and cooled to room temperature. The solvent was spin-dried to obtain product 3a (4.5 g, 0.0385 mol, yield 96.1%), which was dissolved in 20 ml of acetonitrile.

[0034] Add 11.2 grams of DMF (0.154mol, 4eq) and 3 grams of 4A molecular sieve into 100ml of acetonitrile, and cool the reaction to 0°C to 5°C, slowly add 11.6g of POCl dropwise under ice bath conditio...

Embodiment 2

[0037] Example 2 Synthesis of 5-fluoroindole-3-carbaldehyde

[0038]

[0039] Add 7.2 g of 5-fluoro-2-nitrotoluene (compound 1b, 0.046 mol) and 27.4 g of DMFDMA (0.232 mol) into 80 ml of acetonitrile, raise the reaction temperature to 85°C-95°C, and reflux for 5 hours. The reaction was cooled, the solvent was spin-dried, and washed with water and a small amount of ethanol to obtain 9.3 g of crude product 2b (0.0443 mol, yield 96.2%).

[0040] The obtained intermediate 2b was added to 147ml of methanol containing 10wt% hydrazine (hydrazine content 0.45mol, 10eq), and the temperature was raised to 50°C, reacted for 8 hours, and cooled to room temperature. The solvent was spin-dried to obtain 5.7 g of product 3b (0.0424 mol, yield 95.8%), which was dissolved in 20 ml of acetonitrile.

[0041] Add 12.3 grams of DMF (0.168mol, 4eq) and 3.3 grams of 4A molecular sieve into 100ml of acetonitrile, and cool the reaction to 0°C-5°C, slowly add 12.8g of POCl dropwise under ice bath c...

Embodiment 3

[0043] The synthesis of embodiment 3 6-chloroindole-3-formaldehyde

[0044]

[0045] Add 6.6 g of 4-chloro-2-nitrotoluene (compound 1c, 0.039 mol) and 23.0 g of DMFDMA (0.193 mol, 5 eq) into acetonitrile (80 ml), raise the reaction temperature to 85°C to 95°C, and reflux for 5 hours . The reaction was cooled, the solvent was spin-dried, and washed with water and a small amount of ethanol to obtain 8.4 g of crude product 2c (0.0369 mol, yield 94.6%).

[0046] The resulting intermediate 2c was added to 118ml of methanol containing 10wt% hydrazine (hydrazine content: 0.36mol, 10eq), heated to 50°C, reacted for 8 hours, and cooled to room temperature. The solvent was spin-dried to obtain 5.4 g of product 3c (0.0355 mol, yield 96.3%), which was dissolved in 20 ml of acetonitrile.

[0047] Add 10.4 grams of DMF (0.142mol, 4eq) and 3 grams of 4A molecular sieves into acetonitrile (100ml), and cool the reaction to 0°C to 5°C, slowly add 10.8g of POCl dropwise under ice bath condi...

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Abstract

The invention relates to the field of organic synthesis and medical intermediate preparation and especially relates to a method for preparing a substituted indole-3-methanal compound. The method comprises the following steps that N,N-dimethylformamidodimethylacetal or N,N-methylformamidodiethylacetal and substituted 2-nitrotoluene undergo a reflux reaction to produce beta-dimethylamino-2-nitrostyrene; beta-dimethylamino-2-nitrostyrene and a mixed solution of hydrazine and alcohol undergo a reaction to produce a substituted indole; and the substituted indole, dimethylformamide (DMF) and phosphorus oxyhalogen undergo a reaction to produce the substituted indole-3-methanal compound. Yields of all processes of the method provided by the invention are more than 90%. A total yield of the method is more than 80%.

Description

technical field [0001] The invention relates to the fields of organic synthesis and preparation of pharmaceutical intermediates, in particular to a preparation method of substituted indole-3-carboxaldehyde compounds. Background technique [0002] Substituted indole-3-carbaldehyde compounds are an important class of intermediates in organic synthetic chemistry, such as indole-3-carbaldehyde (CAS 487-89-8), 5-fluoroindole-3-carbaldehyde (CAS 2338- 71-8), 6-fluoroindole-3-carbaldehyde (CAS 2795-41-7), 6-chloroindole-3-carbaldehyde (CAS 703-82-2), 5-methoxyindole-3 -Formaldehyde (CAS 10601-19-1), has a wide range of uses: it is used to synthesize some tryptamines and their derivatives with pharmaceutical activity; to synthesize some tryptophan compounds; to synthesize some plant growth regulators, such as indole- 3-acetonitrile and indole-3-acetic acid compounds; synthesis of various biologically active pharmaceutical intermediates. Therefore, the synthetic method of substitut...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/12
Inventor 谢应波张庆张华姚为建
Owner 上海泰坦科技股份有限公司
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