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A kind of 3-aryl oxide indole derivative and its synthetic method

A technology of an indole derivative and a synthesis method, which is applied in the field of p-3-aryloxide indole derivatives and chemical synthesis thereof, and can solve the problem of unfavorable 3-aryloxide indole application in industrial synthesis and harsh reaction conditions. Chemical waste , the problem of high cost, to achieve the effect of low cost, few reaction steps and short time-consuming

Active Publication Date: 2018-04-24
广东和博制药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the above methods have defects such as harsh reaction conditions, use of air-sensitive reagents or transition metal catalysts, and mostly involve multi-step reactions, which will generate a lot of chemical waste in the intermediate process, and are time-consuming and costly. Facilitate the application of 3-aryloxindole in organic synthesis and its industrial synthesis

Method used

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  • A kind of 3-aryl oxide indole derivative and its synthetic method
  • A kind of 3-aryl oxide indole derivative and its synthetic method
  • A kind of 3-aryl oxide indole derivative and its synthetic method

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069]

[0070] At 0°C, a solution of N-benzyl-3-diazoindole (1.50 g, 6.0 mmol) in toluene (12 mL) was slowly dropped into toluene (10 mL) and trifluoromethanesulfonate over 60 minutes Acid (53uL, 10mol%) mixed solution, while stirring vigorously. After the dropwise addition was completed, stirring was continued at room temperature for 60 minutes until the 3-diazoindole was completely consumed. Then add excess NaHCO to the reaction solution 3 Solid to quench the reaction, filter off the solid and remove the solvent under reduced pressure; the crude product is subjected to column chromatography (ethyl acetate:petroleum ether=1:30~1:10) to obtain the pure product N-benzyl-3- (p-Tolyl)oxindole (1.41 g, 85%). 1 H NMR (CDCl 3 ,400MHz):δ7.31–7.24(m,5H),7.21–7.09(m,6H),7.02–6.98(m,1H),6.77(d,J=7.8Hz 1H),4.99(d,J= 15.6Hz 1H), 4.88(d, J=15.6Hz 1H), 4.66(s, 1H), 2.33(s, 3H). 13 C NMR (100MHz, CDCl 3 ):δ176.3,143.6,137.3,136.0,133.8,129.7,129.2,128.8,128.3,128.2,127.6,127.4,125....

Embodiment 2

[0072]

[0073] At 0°C, a solution of N-methyl-3-diazoindole (1.07g, 6.0mmol) in toluene (12mL) was slowly dropped into toluene (10mL) and trifluoromethanesulfonate over 60 minutes Acid (53uL, 10mol%) mixed solution, while stirring vigorously. After the dropwise addition was completed, stirring was continued at room temperature for 60 minutes until the 3-diazoindole was completely consumed. Then add excess NaHCO to the reaction solution 3 Solid to quench the reaction, filter off the solid and remove the solvent under reduced pressure; the crude product is subjected to column chromatography (ethyl acetate:petroleum ether=1:30~1:10) to obtain the pure product N-methyl-3- (p-Tolyl)oxindole (1.04 g, 73%). 1 H NMR (CDCl 3 ,400MHz):δ7.33–7.29(m,1H),7.16–7.03(m,6H),6.88(d,J=8.0Hz 1H),4.56(s,1H),3.24(s,3H),2.31 (s,3H). 13 C NMR (100MHz, CDCl 3 ):δ176.2,144.5,137.3,133.6,129.6,129.1,128.3,128.3,125.0,122.7,108.1,51.7,26.4,21.1.FTIR(KBr):3054,2922,1693,1607,1495,1468,13476, ,1...

Embodiment 3

[0075]

[0076] At 0°C, a solution of N-ethoxycarbonyl-3-diazoindole (6.0 mmol) in toluene (12 mL) was slowly dropped into toluene (10 mL) and trifluoromethanesulfonic acid ( 53uL, 10mol%) in the mixed solution while vigorously stirring. After the dropwise addition was completed, stirring was continued at room temperature for 60 minutes until the 3-diazoindole was completely consumed. Then add excess NaHCO to the reaction solution 3 solid to quench the reaction, filter off the solid and remove the solvent under reduced pressure; the crude product is subjected to column chromatography (ethyl acetate:petroleum ether=1:30~1:10) to obtain the pure product N-ethoxycarbonyl-3 -(p-Tolyl)oxindole (1.38 g, 78%). 1 H NMR (CDCl 3 ,400MHz):δ7.97(d,J=8.2Hz 1H),7.38–7.34(m,1H),7.21–7.06(m,6H),4.71(s,1H),4.45(q,J=7.1Hz 2H), 2.32(s, 3H), 1.42(t, J=7.1Hz 3H). 13 C NMR (100MHz, CDCl 3 ):δ174.0,151.1,140.2,137.7,133.2,130.0,128.7,128.4,127.8,125.1,124.9,115.2,63.4,52.2,21.1,14.2.FTIR(KB...

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Abstract

The invention discloses a synthetic method of 3-aryloxoindole as shown in the formula (I). According to the synthetic method, 3-diazooxoindole and aromatic hydrocarbon are used as raw materials and protonic acid is used as a catalyst to prepare 3-aryloxoindole by a one-step reaction. According to the method, use of expensive transition metal catalysts is avoided, aromatic hydrocarbon which is cheap and easily available is used as a raw material, reaction condition is mild, reaction steps are few, reaction is fast, cost is low, generated waste is few, atom economy is high, and operation is simple, safe and reliable.

Description

technical field [0001] The invention relates to the fields of synthetic medicine and chemical industry, and mainly relates to a rapid and green p-3-aryloxindole derivative and a chemical synthesis method thereof. Background technique [0002] 3-Aryloxindoles are widely used in the synthesis of 3,3-disubstituted oxindoles and indolines, which are a series of biologically active natural products and synthetic drugs The skeleton structure of such as SM-130686, BMS-204352, hodgkinsine, qudrigemine C, etc. (as shown below). A series of synthetic methods for 3-aryloxindoles have been developed in the past decades, such as strong acid-promoted intramolecular Friedel-Crafts reactions starting from α-haloacetamides, strong bases or light-promoted molecules Internal cyclization reaction, intramolecular coupling reaction catalyzed by divalent palladium; addition of isatin by Grignard reagent and then reductive deoxygenation reaction catalyzed by Lewis acid; molecule of indolone and ar...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D209/34
CPCC07D209/34
Inventor 胡文浩翟昌伟荆常诚周俊汪成进王东伟马超群邢栋
Owner 广东和博制药有限公司