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Axially chiral aryl indole compound and synthesis method thereof

An aryl indole compound, a technology for a synthesis method, applied in the directions of organic chemistry, organic active ingredients, organic chemistry, etc., can solve problems such as limitation, achieve mild reaction conditions, high yield, and be suitable for industrialized large-scale production.

Active Publication Date: 2019-11-19
XUZHOU NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Despite these methods, they are still very limited, so there is an urgent need to develop new methods and strategies for the synthesis of axially chiral indole-naphthalene and indole-benzene compounds

Method used

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  • Axially chiral aryl indole compound and synthesis method thereof
  • Axially chiral aryl indole compound and synthesis method thereof
  • Axially chiral aryl indole compound and synthesis method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Embodiment 1: in 1 milliliter of dichloromethane, add the formula 1c compound of 0.1 millimole and the formula 2b compound of 0.3 millimole as reactant, 100 milligrams Molecular sieves are used as additives, 0.01 mmol of chiral phosphoric acid (i.e. the compound of formula 61) is used as a catalyst, reacted at 25 ° C for 48 hours, TLC traced the reaction to the end, and filtered to remove Molecular sieves, wash the filter cake with ethyl acetate, and separate the obtained filtrate through silica gel column chromatography (the eluent is a mixed solution with a volume ratio of petroleum ether and ethyl acetate of 10:1) after concentration to obtain the axial chiral indole Inole-naphthalene 3cb, white solid.

[0032] The structural characterization data of product 3cb in Example 1 are as follows:

[0033] m.p.86.6-87.6°C; [α] D 20 = -44.7(c 0.81, acetone); 1 H NMR (400MHz, DMSO-d 6 )δ11.48(s,1H),10.05(s,1H),8.15(d,J=9.1Hz,1H),8.08(d,J=8.2Hz,1H),7.62–7.55(m,2H), 7.5...

Embodiment 18

[0041] Embodiment 18: in 4 milliliters of dichloromethane, add 0.1 millimole formula 1a compound and 0.12 millimole formula 2a compound as reactant, 100 milligrams Molecular sieves are used as additives, 0.01 mmol of chiral phosphoric acid (i.e. the compound of formula 61) is used as a catalyst, react at 25°C for 5 hours, TLC tracks the reaction to the end, and removes by filtration Molecular sieves, wash the filter cake with ethyl acetate, and separate the obtained filtrate through silica gel column chromatography (the eluent is a mixed solution with a volume ratio of petroleum ether and ethyl acetate of 10:1) after concentration to obtain the axial chiral indole Inole-naphthalene 3aa, white solid.

[0042] The structural characterization data of product 3aa in Example 18 are as follows:

[0043] m.p.85.1-85.8℃; [α] D 20 = -13.7(c 1.85, acetone); 1 H NMR (400MHz, CDCl 3 )δ 1 HNMR (400MHz, CDCl 3 )δ9.36(s,1H),7.93(d,J=9.0Hz,1H),7.87(d,J=7.7Hz,1H),7.72–7.55(m,2H),7.50(...

Embodiment 25

[0050] Example 25: Add 0.1 mmol of the compound of formula 4u and 0.3 mmol of the compound of formula 2b in 1 ml of dichloromethane as a reactant, 100 mg Molecular sieves are used as additives, 0.01 mmol of chiral phosphoric acid (i.e. the compound of formula 61) is used as a catalyst, reacted at 25 ° C for 48 hours, TLC traced the reaction to the end, and filtered to remove Molecular sieves, wash the filter cake with ethyl acetate, and separate the obtained filtrate through silica gel column chromatography (the eluent is a mixed solution with a volume ratio of petroleum ether and ethyl acetate of 10:1) after concentration to obtain the axial chiral indole Indole-naphthalene 5ub, white solid, yield 86%.

[0051] The structural characterization data of product 5ub in Example 25 are as follows:

[0052] m.p.113.2-113.8°C; [α] D 20 = -5.1(c 0.71, acetone); 1 H NMR (400MHz, DMSO-d 6 )δ11.48(s,1H),10.16(s,1H),7.46(d,J=8.1Hz,1H),7.40–7.20(m,10H),7.19–7.09(m,2H),6.98(d ,J=4.9...

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Abstract

The invention discloses an axially chiral aryl indole compound and a synthesis method thereof, wherein the compound has a chemical structure formula represented by a formula 3 or formula 5. The synthesis method comprises: using a compound represented by a formula 1 or a compound represented by a formula 4 and a compound represented by a formula 2 as reaction raw materials, using dichloromethane asa solvent, adding a molecular sieve, carrying out a stirring reaction under the action of a chiral phosphoric acid catalyst, tracking through TLC until the reaction is completely performed, filtering, concentrating, and purifying to prepare the product. According to the present invention, the test results of the biological activity of the compounds show that the compound has a certain cytotoxic activity on MCF-7 breast cancer cells; the synthesis method has advantages of simple operation, mild reaction conditions and economical and easily available raw materials; and the prepared axially chiral indole-naphthalene compound and the prepared indole-benzene compound have high optical purity, and are widely used in the field of pharmaceutical research and development.

Description

technical field [0001] The invention belongs to the field of organic synthesis chemistry, and specifically relates to an axial chiral arylindole compound and a synthesis method thereof. Background technique [0002] Axial chiral indole-naphthalene and indole-benzene compounds have a variety of biological activities, for example: document J.Med.Chem.2015,58,6607 reports that such compounds can be used as glucocorticoid receptor antagonists; document Bioorg .Med.Chem.Lett.2011,21,5336 reported that this type of compound can be used as an HCV NS5B polymerase inhibitor; the literature Res.Chem.Intermediat.2017,43,2387 reported that this type of compound has antioxidant and antibacterial activity . [0003] Axial chiral indole-naphthalene and indole-benzene compounds have broad application prospects in the field of life sciences. At the same time, because the biological activity of drug molecules is often an enantiomer in the racemate, not Symmetric catalysis also requires opti...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/40A61P35/00A61K31/404
CPCA61P35/00C07B2200/07C07D209/40
Inventor 石枫张宇辰蒋飞陈科伟
Owner XUZHOU NORMAL UNIVERSITY
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