3,3-disubstituted indolinone and its derivative, and synthesis method and application thereof

A technology of indolinone and synthetic method, which is applied in 3 fields, can solve the problems of poor selectivity and limited scope of application of substrates, and achieve the effects of easy purification, high atom economy and step economy, and high yield

Active Publication Date: 2019-06-18
EAST CHINA NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The present invention overcomes the defects such as the limited scope of substrate application and poor selectivity in the preparation method of 3,3-disubstituted indolinone compounds in the prior art, and proposes the use of propargyl cations to react active intermediates ——One-step efficient synthesis of 3,3-disubstituted indolinones and their derivatives by hydroxy ylide capture strategy

Method used

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  • 3,3-disubstituted indolinone and its derivative, and synthesis method and application thereof
  • 3,3-disubstituted indolinone and its derivative, and synthesis method and application thereof
  • 3,3-disubstituted indolinone and its derivative, and synthesis method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0111]

[0112] Under nitrogen protection, silver tetrafluoroborate and rhodium acetate were added to a dry 10ml test tube. After adding 1.5ml of dichloromethane, the temperature was raised to 40°C, propynyl alcohol hexacarbonyl dicobalt 1 (0.1mmol), benzyl alcohol 2 (0.15mmol), 3-diazoindolinone 3 (0.15mmol) were mixed and dissolved In 1 ml of dichloromethane, pour the mixed solution into a test tube within 2 hours using a peristaltic pump, and continue stirring for 0.5 hour after the dropwise addition. After the solvent was removed from the reaction solution under reduced pressure, a sample was taken and dissolved in deuterated chloroform for use 1 The d.r. value was determined by H NMR, and all the solutions were mixed and purified by column chromatography (petroleum ether: ethyl acetate = 70:1-20:1) to obtain pure product 4a. Yield: 90%, anti:syn=43:57.

[0113] Compound syn-4a: 1 H NMR (400MHz, CDCl 3 )δ7.36(t, J=7.7Hz, 1H), 7.31-7.21(m, 6H), 7.02(t, J=7.5Hz, 1H), ...

Embodiment 2

[0116]

[0117] Under nitrogen protection, silver tetrafluoroborate and rhodium acetate were added to a dry 10ml test tube. After adding 1.5ml of dichloromethane, the temperature was raised to 40°C, propynyl alcohol hexacarbonyl dicobalt 1 (0.1mmol), benzyl alcohol 2 (0.15mmol), 3-diazoindolinone 3 (0.15mmol) were mixed and dissolved In 1 ml of dichloromethane, pour the mixed solution into a test tube within 2 hours using a peristaltic pump, and continue stirring for 0.5 hour after the dropwise addition. After the solvent was removed from the reaction solution under reduced pressure, a sample was taken and dissolved in deuterated chloroform for use 1 The d.r. value was measured by H NMR, and all solutions were mixed and purified by column chromatography (petroleum ether: ethyl acetate = 70:1-20:1) to obtain pure product 4b. Yield: 66%, anti:syn=47:53.

[0118] Compound syn-4b: 1 H NMR (400MHz, CDCl 3 )δ7.36(t, J=7.7Hz, 1H), 7.24(s, 1H), 7.17(d, J=8.4Hz, 2H), 7.03(t, J=7...

Embodiment 3

[0121]

[0122] Under nitrogen protection, silver tetrafluoroborate and rhodium acetate were added to a dry 10ml test tube. After adding 1.5ml of dichloromethane, the temperature was raised to 40°C, propynyl alcohol hexacarbonyl dicobalt 1 (0.1mmol), benzyl alcohol 2 (0.15mmol), 3-diazoindolinone 3 (0.15mmol) were mixed and dissolved In 1 ml of dichloromethane, pour the mixed solution into a test tube within 2 hours using a peristaltic pump, and continue stirring for 0.5 hour after the dropwise addition. After the solvent was removed from the reaction solution under reduced pressure, a sample was taken and dissolved in deuterated chloroform for use 1 The d.r. value was determined by H NMR, and all the solutions were mixed and purified by column chromatography (petroleum ether: ethyl acetate = 70:1-20:1) to obtain pure product 4c. Yield: 77%, anti:syn=43:57.

[0123] Compound syn-4c: 1 H NMR (400MHz, CDCl 3 )δ7.38(dd, J=16.8, 8.0Hz, 3H), 7.22(d, J=7.2Hz, 1H), 7.13(d, J=8...

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Abstract

The invention discloses a 3,3-disubstituted indolinone and its derivative, and a synthesis method thereof. The product is obtained through a one-step three-component reaction of a diazo compound, a substituted benzyl alcohol and (propargyl alcohol)hexacarbonyldicobalt, which are used as raw materials, in an organic solvent with rhodium acetate and silver tetrafluoroborate as a catalyst at a high selectivity and a high yield. The method has the advantages of good selectivity, mild reaction conditions, high yield, and simplicity and safety in operation. The indolinone framework of the 3,3-disubstituted indolinone and its derivative is an important structural fragment for many bioactive complex natural products and medicine molecules, and the eneyne structure in the above compounds is also animportant intermediate and reaction building block in the synthesis of many medicine molecules, so the compounds can be used as important intermediates for medicines and chemical industry, and have abroad application prospect in the field of medicinal fields.

Description

technical field [0001] The invention belongs to the field of synthetic medicine and chemical industry, and specifically relates to a synthesis method and application of 3,3-disubstituted indolinone and derivatives thereof. Background technique [0002] 3,3-disubstituted indolinone compounds widely exist in natural products and drug molecules, based on their high biological activity, the synthesis of these compounds is one of the important fields of organic chemistry research. 3,3-disubstituted indolinone derivatives have good antibacterial activity, are an important skeleton structure for building natural products and drugs, and are important intermediates in organic synthesis and drug synthesis. At the same time, 3,3-disubstituted indolinone derivatives can also be used to synthesize many anti-tumor drugs, anti-leukemia and antibacterial drugs. However, due to the existence of regioselectivity in the reaction process, or the use of highly toxic heavy metal reagents, the po...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F15/00
Inventor 胡文浩寿家毅康正辉
Owner EAST CHINA NORMAL UNIV
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