Synthetic method of 2-trifluoromethylindenemethylindole derivative

A technology of trifluoromethylindenylmethyleneindole and synthesis method, which is applied in the field of synthesis of 2-trifluoromethylindenylmethyleneindole derivatives to protect the health of environmental operators and achieve high yield efficiency, and the effect of saving synthesis costs

Active Publication Date: 2019-02-12
WENZHOU UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, up to now, the synthesis of molecular fragments that can have both indene and indole in one molecule has not been reported. Due to the presence of trifluoromethyl fragments, these polycyclic compounds are very useful in the discovery process of new drugs

Method used

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  • Synthetic method of 2-trifluoromethylindenemethylindole derivative
  • Synthetic method of 2-trifluoromethylindenemethylindole derivative
  • Synthetic method of 2-trifluoromethylindenemethylindole derivative

Examples

Experimental program
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Effect test

specific Embodiment 1

[0019] Specific example one: 0.1mmol of 1-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2-(phenylethynyl)benzene, 0.12mmol of indole , 0.01 mmol of palladium chloride, 0.02 mmol of 2-dicyclohexylphosphobiphenyl, and 0.2 mmol of sodium tert-butoxide were added to 1.0 ml of toluene, and stirred at 120° C. for 24 hours under a nitrogen atmosphere. After the reaction, ethyl acetate was added to the mixture, and washed with saturated brine. After extracting the aqueous layer with ethyl acetate, the combined organic layers were dried over anhydrous sodium sulfate and evaporated in vacuo. The residue was purified by flash column chromatography to give 27.9 mg of yellow solid (Z)-1-(phenyl(2-(trifluoromethyl)-1H-inden-1-ylidene)methyl)-1H-indene Indole, yield 72%, Z / E=98:2, m.p.104-106°C; 1 HNMR (500MHz, CDCl 3 ,TMS)δ:7.65(d,J=8.0Hz,1H),7.50(s,1H),7.47(d,J=7.5Hz,1H),7.41-7.38(m,3H),7.32-7.30(m ,2H),7.16-7.11(m,2H),7.01-7.00(m,1H),6.99-6.96(m,1H),6.94-6.91(m,1H),6.74-6.72(m,2H),6.01 (d...

specific Embodiment 2

[0020] Specific example two: 0.1mmol of 1-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2-(phenylethynyl)benzene, 0.12mmol of 3- Methylindole, 0.01mmol of palladium chloride, 0.02mmol of 2-dicyclohexylphosphobiphenyl, 0.2mmol of sodium tert-butoxide were added to 1.0ml of toluene, and stirred at 120°C for 24 Hour. After the reaction, ethyl acetate was added to the mixture, and washed with saturated brine. After extracting the aqueous layer with ethyl acetate, the combined organic layers were dried over anhydrous sodium sulfate and evaporated in vacuo. The residue was purified by flash column chromatography to give 27.3 mg of (Z)-3-methyl-1-(phenyl(2-(trifluoromethyl)-1H-inden-1-ylidene)methyl as an orange solid )-1H-indole, yield 68%, Z / E=97:3, m.p.121-124°C; 1 H NMR (500MHz, CDCl 3 ,TMS)δ:7.62(d,J=8.0Hz,1H),7.54-7.51(m,2H),7.47-7.43(m,2H),7.39-7.36(m,3H),7.21-7.17(m, 2H),7.02-7.00(m,1H),6.98-6.96(m,1H),6.83(s,1H),6.69(d,J=8.5Hz,1H),6.15(d,J=8.5Hz,1H ),2.37(s,3H); 13 C NMR (...

specific Embodiment 3

[0021] Specific example three: 0.1mmol of 1-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2-(phenylethynyl)benzene, 0.12mmol of 5- Methylindole, 0.01mmol of palladium chloride, 0.02mmol of 2-dicyclohexylphosphobiphenyl, 0.2mmol of sodium tert-butoxide were added to 1.0ml of toluene, and stirred at 120°C for 24 Hour. After the reaction, ethyl acetate was added to the mixture, and washed with saturated brine. After extracting the aqueous layer with ethyl acetate, the combined organic layers were dried over anhydrous sodium sulfate and evaporated in vacuo. The residue was purified by flash column chromatography to give 29.7 mg of (Z)-5-methyl-1-(phenyl(2-(trifluoromethyl)-1H-inden-1-ylidene)methyl as an orange oily liquid )-1H-indole, yield 74%, Z / E=98:2; 1 H NMR (500MHz, CDCl 3 ,TMS)δ:7.53(s,1H),7.52(d,J=7.5Hz,1H),7.46-7.43(m,4H),7.38-7.35(m,1H),7.32-7.31(m,1H) ,7.22-7.19(m,1H),7.01(d,J=3.0Hz,1H),6.99-6.97(m,1H),6.83(d,J=8.5Hz,1H),6.70(d,J=3.0 Hz,1H),6.60(d,J=8.5Hz,1H),6.10(d,J...

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Abstract

The invention relates to a synthetic method of a 2-trifluoromethylindenemethylindole derivative. The synthetic method comprises the following steps: placing a mixture of 1-(2- chloro-3,3,3-trifluoropropyl-1-alkene-1-yl)-2-phenylacetenyl)benzene, indole or pyrrole serving as a substrate, palladium chloride serving as a catalyst, sodium tert-butoxide serving as an alkali and 2-dicyclohexyl phosphobiphenyl serving as a ligand into a methylbenzene solution at the temperature of 120 DEG C; stirring the mixture in a nitrogen atmosphere for 24 hours. The synthetic method has the advantages of readily-available raw materials, novel and simple preparation process, easiness, low pollution, low energy consumption and higher yield.

Description

technical field [0001] The invention relates to a synthesis method utilizing 2-trifluoromethylindenylmethyleneindole derivatives. Background technique [0002] In organic molecules, indene or indole is an important molecular skeleton in some natural products, drugs and materials, such as sulindac (Synlett2001,1,41-44) and ellipticine (Angew.Chem. Synthesis of Int. Ed. 1988, 27, 1113-1126). Therefore, in recent years, a lot of explorations and attempts have been made on the methods of synthesizing indene or indole skeleton molecules, and many trifluoromethyl substituted indene (Org. Lett. 2018, 20, 5190-5193) or indole Indole (Org. Chem. Front. 2018, 5, 3133-3137). Fluorine atoms or fluoroalkyl groups often make great differences in chemistry, physics and pharmacology (J. Fluor. Chem. 2001, 109, 3). However, up to now, the synthesis of molecular fragments that can have both indene and indole in one molecule has not been reported. Due to the presence of trifluoromethyl frag...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/10C07D209/12C07D409/10C07D405/10
CPCC07D209/10C07D209/12C07D405/10C07D409/10
Inventor 张兴国章涛陈帆张小红
Owner WENZHOU UNIVERSITY
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