3-methylene-indol-2-one derivates and preparation method thereof

A technology of methylene indole and its derivatives, which is applied in the field of 3 methylene-indol-2-one derivatives and its preparation, and can solve problems such as limited applications

Inactive Publication Date: 2009-04-29
WENZHOU UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there are basically two routes: one is through a series reaction based on a cross-coupling reaction, which uses expensive o-iodoaniline or o-alkynyl phenyl is

Method used

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  • 3-methylene-indol-2-one derivates and preparation method thereof
  • 3-methylene-indol-2-one derivates and preparation method thereof
  • 3-methylene-indol-2-one derivates and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Take the preparation of (E)-1-methyl-3-(1`-phenyl-1`-acetoxy)methylene-indol-2-one as an example:

[0033] The compound N-methyl-N-phenyl-phenylpropanamide (0.047g), Pd(OAc) 2 (0.0045g), PhI(OAc) 2 (0.0773 g) was placed in a 25 mL round bottom flask, then HOAc (3 mL) was injected and the flask was sealed. React at a temperature of 60°C-100°C, but preferably at a temperature of 80°C. After the reaction (usually about 2 hours), add ethyl acetate, then wash with salt water, and extract the aqueous phase with ethyl acetate. The organic layer was collected, dried, concentrated, and column chromatography gave (E)-1-methyl-3-(1`-phenyl-1`-acetoxy)methylene-indol-2-one, yellow solid , melting point 171.1-172.6 °C yield 90%.

[0034] Structure Characterization: 1 H NMR (400MHz) δ: 7.68(d, J=9.6Hz, 2H), 7.55(d, J=7.6Hz, 1H), 7.45-7.43(m, 3H), 7.30(t, J=8.0Hz, 1H ), 7.05(t, J=7.6Hz, 1H), 6.82(d, J=7.6Hz, 1H), 3.19(s, 3H), 2.37(s, 3H); 13 C NMR (100MHz) δ: 167.6, 166.1, 156.9...

Embodiment 2

[0054] Take the preparation of (E)-1-methyl-3-(1`-phenyl-1`-(4-nitrobenzoyloxy))methylene-indol-2-one as an example:

[0055] The compound N-methyl-N-phenyl-phenylpropanamide (0.047g), Pd(OAc) 2 (0.0045g),

[0056] PhI(OAc) 2 (0.0773g), 4-nitrobenzoic acid (0.167g) was placed in the round bottom flask of 25mL, then inject CH 3 CN (3mL), react in a sealed flask at a temperature of 60°C-100°C, but it is best to react at a temperature of 80°C. After the reaction (usually about 2-3 hours), add ethyl acetate, then wash with salt water, water The phase was extracted with ethyl acetate. The organic layer was collected, dried, concentrated, and column chromatography gave (E)-1-methyl-3-(1`-phenyl-1`-(4-nitrobenzoyloxy))methylene-ind Indol-2-one, yellow solid, melting point 172.7-173.1°C, yield 90%.

[0057] Structure Characterization: 1 H NMR (400MHz) δ: 8.42(s, 4H), 7.75(d, J=8.0Hz, 2H), 7.48-7.39(m, 4H), 7.29-7.26(m, 3H), 6.92(t, J= 7.2Hz, 1), 6.84(d, J=8.0Hz, 1H), 3.23(s, 3H...

Embodiment 3

[0071] Take the preparation of (E)-1-methyl-3-(1`-phenyl-1`-phthalimido)methylene-indol-2-one as an example:

[0072] N methyl N phenyl phenylpropanamide (0.047g), phthalimide (0.0882g), Pd(OAc) 2 (0.0045g), PhI(OAc) 2 (0.1288g) was placed in a 25mL round-bottomed flask with polyvinyl fluoride seal, then injected with DCE (3mL), sealed the flask, and reacted at a temperature of 60°C-100°C, but preferably at a temperature of 80°C After 3-10 hours, add ethyl acetate after the reaction is completed, then wash with salt water, extract the aqueous phase with ethyl acetate, collect the organic layer, dry, concentrate, and column chromatography to obtain (E)-1-methyl-3- (1`-phenyl-1`-phthalimido)methylene-indol-2-one, yield 61%, yellow solid, melting point: 202.3204.6°C.

[0073] Structure Characterization: 1 H NMR (400MHz) δ: 7.98-7.96(m, 2H), 7.96-7.84(m, 2H), 7.58(d, J=8.0Hz, 2H), 7.44-7.41(m, 3H), 7.25(t, J=7.6Hz, 1H), 6.99(d, J=7.6Hz, 1H), 6.85-6.80(m, 2H), 3.21(s, 3H); 13 ...

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Abstract

The invention relates to a 3-methylene-indole-2-ketone derivative and a preparation method thereof. The derivative is synthesized by taking N-methyl-N-phenyl-hydrocinnamamide or N-aryl phenylpropargyl acylamide and phthalic imide as substrates through tandem reactions such as C-H activation/ acetylene hydrocarbon palladinization/cross coupling and so on, based on the catalysis of Pd<II>/Pd<IV> under the coaction of a palladium catalyst and an oxidizing agent, then ethyl acetate is added, the mixture is scrubbed by common salt, an aqueous phase is then extracted by the ethyl acetate, an organic layer is collected, and the 3-methylene-indole-2-ketone derivative is prepared through drying, condensation and column chromatography. The preparation method has the advantages of simple and convenient reaction operation, short reaction steps, simple conditions, short time, low cost, and high yield, and is worthy to be popularized and applied.

Description

technical field [0001] The present invention relates to 3 methylene-indol-2-one derivatives and a preparation method thereof. Background technique [0002] According to the statistics of the World Health Organization, about 11 million people in the world are diagnosed with cancer every year, and about 7 million patients die of cancer every year. According to the data of the Ministry of Health, about 1.8 million people died of cancer in my country in 2006, there are no less than 2 million cancer patients, and about 1.6 million new cases occur every year. Therefore, the prevention and treatment of cancer has become an urgent and arduous task. [0003] 3-methylene indol-2-one derivatives are currently the most promising class of targeted therapy tumor drugs, about 80 derivatives are undergoing clinical phase II and phase III studies, the results of these studies show that different 3-methylene The inhibitory effects of indol-2-one derivatives on different tumor virus proteins...

Claims

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Application Information

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IPC IPC(8): C07D209/34C07D209/48
Inventor 李金恒唐石汤日元谢叶香
Owner WENZHOU UNIVERSITY
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