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Preparation method of 2-nitro-4-(1H-pyrrylmethyl)-N-substituted aniline derivatives

A technology of aniline derivatives and pyrrole methyl is applied in the field of preparation of 2-nitro-4--N-substituted aniline derivatives, and can solve the problems of harsh reaction conditions, complicated reaction process and the like

Active Publication Date: 2015-07-01
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method does not need to separate intermediates, is economical, efficient, practical, and environmentally friendly, and overcomes the shortcomings of the prior art in many aspects such as complex reaction process and harsh reaction conditions.

Method used

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  • Preparation method of 2-nitro-4-(1H-pyrrylmethyl)-N-substituted aniline derivatives
  • Preparation method of 2-nitro-4-(1H-pyrrylmethyl)-N-substituted aniline derivatives
  • Preparation method of 2-nitro-4-(1H-pyrrylmethyl)-N-substituted aniline derivatives

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preparation example Construction

[0029] In the preparation method of the present invention, thin layer chromatography (TLC) can be used to judge the end point of the preparation reaction (petroleum ether / ethyl acetate=5:1 (v / v)); and the obtained formula I The crude product of the compound shown can be purified by existing conventional purification methods such as column chromatography (column chromatography uses a silica gel column, and the eluent is petroleum ether / ethyl acetate=10:1 (v / v)).

[0030] The method for preparing 2-nitro-4-(1H-pyrrolemethyl)-N-substituted aniline derivatives of the present invention has the advantages of wide source of raw materials, cheap and easy to obtain, simple and easy to operate, and can be used in the whole preparation process. No need for inert gas protection and high yield.

Embodiment 1

[0032] The preparation of embodiment 11-(2-nitro-4-(1H-pyrrole methyl) phenyl) piperidine

[0033]

[0034] In a 25ml three-neck flask connected with a thermometer sleeve and a reflux condenser, add 4-fluoro-3-nitrobenzaldehyde (0.1691g, 1.0mmol), trans-4-hydroxyl-L-proline (0.1966g , 1.5mmol), N, N-dimethylformamide (6ml) and piperidine (0.0989ml, 1.0mmol), stirred and heated, heated to 140°C for 5h, TLC tracking showed that the reaction was over, and the reaction solution was naturally cooled to At room temperature, the reaction solution was washed with a large amount of water, extracted with dichloromethane, dried over anhydrous sodium sulfate, filtered, and the solvent was removed under reduced pressure, followed by column chromatography to obtain 1-(2-nitro-4-(1H-pyrrolemethyl)benzene Base) piperidine 0.2309g, reddish-brown oily liquid, yield 81%.

[0035] Calcd.HRMS for C 16 h 20 N 3 o 2 (M+H), 286.1556; Found, 286.1555; 1 H NMR (400MHz, CDC1 3 ) ppm 7.57 (s, 1...

Embodiment 2

[0036] Example 2 Preparation of 1-(2-nitro-4-(1H-pyrrolemethyl)phenyl)piperidine

[0037] Except that ethanol was used instead of N,N-dimethylformamide, the others were the same as in Example 1, and the yield was 60%.

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Abstract

The invention relates to a preparation method of 2-nitro-4-(1H-pyrrylmethyl)-N-substituted aniline derivatives, which mainly comprises the following steps: reacting 3-nitro-4-halo-benzaldehyde, trans-4-hydroxy-L-proline or trans-4-benzoyloxy-L-proline, secondary amine and solvent at 25-140 DEG C in a redox aromatization reaction and SN2 substitution reaction mode to synthesize the target compounds by a one-pot method. The compounds are important intermediates for synthesizing anticancer drugs EGFRis and HDACis. The method provided by the invention can quickly and effectively prepare the compounds, and lower the synthesis cost.

Description

technical field [0001] The invention relates to a preparation method of 2-nitro-4-(1H-pyrrole methyl)-N-substituted aniline derivatives. Background technique [0002] 2-Nitro-4-(1H-pyrrolemethyl) N-substituted aniline derivatives are important intermediates in the synthesis of epidermal factor receptor inhibitors (EGFRis) and histone deacetylase inhibitors (HDACis). 2-nitro-4-(1H-pyrrole methyl) N-substituted aniline derivative literature synthetic method takes is step-by-step method, that is: utilize secondary amine to react with 3-nitro-4-chlorobenzaldehyde earlier, with Pd and bipyridine are catalysts to generate 3-nitro-4-piperidine benzaldehyde with a yield of 54% (Chinese Chemical Letters, 2010, 21:935-938): [0003] [0004] or use Cs 2 CO 3 It is an alkaline reagent, using DMSO as a solvent, reacting at room temperature to 100°C for 30 minutes, with a yield of 43% (PCT Int.Appl., 2008057282): [0005] [0006] Or react in water with a yield of 56% (Vestnik ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D207/325
Inventor 虞心红张洋刘傲霞吴旭娟封丛鹏
Owner EAST CHINA UNIV OF SCI & TECH