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Tetrahydroindole compound, and preparation method and application thereof

A tetrahydroindoline compound and compound technology, applied in organic chemistry, drug combination, antineoplastic drugs, etc., can solve the problems of relatively little functionalization research, poor regioselectivity, and easy side reactions, etc., and achieve good practicability And the effects of economic value, yield and purity improvement, high practical value and academic value

Inactive Publication Date: 2013-12-25
SHAOXING UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although there are many methods for synthesizing indole compounds at present, the commonly used methods still have their limitations: (1) Fischer indole synthesis methods usually have low yields, are prone to side reactions, and have poor regioselectivity
(2) Some metal catalysts are often used in reductive cyclization or condensation reactions, which are troublesome in post-processing, unfriendly to the environment, and poor in versatility
(3) The functionalization of indole is mainly at the 1-position, 2-position or 3-position of the indole core, and there are relatively few studies on the functionalization of other positions

Method used

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  • Tetrahydroindole compound, and preparation method and application thereof
  • Tetrahydroindole compound, and preparation method and application thereof
  • Tetrahydroindole compound, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Weigh 0.5mmol of 5,5-dimethyl-1,3-cyclohexanedione, 0.5mmol of aniline, 0.5mmol of (E)-β-nitro-β-methyl-p-chlorostyrene and 0.05mmol of Add L-proline into the reactor, and then add 3mL of water, and act under microwave for 10 minutes. After the reaction was completed, it was cooled to room temperature, extracted with ethyl acetate, and separated by column chromatography with petroleum ether / ethyl acetate to obtain an analytically pure product with a yield of 83%.

[0037] Product Confirmation:

[0038]

[0039] 1 H NMR (400MHz, CDCl 3 ):δ=7.58-7.50(m,4H,ArH),7.40-7.33(m,5H,ArH),2.45(s,2H,CH 2 ),2.44(s,2H,CH 2 ),2.38(s,3H,CH 3 ),1.08(s,6H,CH 3 ). 13 C NMR (100MHz, CDCl 3 ):δ=194.5,146.2,143.2,137.1,132.0,131.7,129.6,129.0,128.8,128.7,128.2,127.8,127.7,53.1,37.0,35.2,28.5,11.1.HRMS(ESI)C 23 h 23 ClNO:[M+H] + calcd 364.1468, found: 364.1463.

Embodiment 2

[0041] Weigh 0.5mmol of 5,5-dimethyl-1,3-cyclohexanedione, 0.5mmol of p-chloroaniline, 0.5mmol of (E)-β-nitro-β-methyl-p-methylstyrene and 0.05 mmol of L-proline were added to the reactor, and then 3 mL of water was added, and the reaction was performed under microwave for 15 minutes. After the reaction was completed, it was cooled to room temperature, extracted with ethyl acetate, and separated by column chromatography with petroleum ether / ethyl acetate to obtain an analytically pure product with a yield of 79%.

[0042] Product Confirmation:

[0043]

[0044] 1 H NMR (400MHz, CDCl 3):δ=7.54-7.52(m,2H,ArH),7.32(d,J=8.0Hz,2H,ArH),7.24(d,J=8.8Hz,2H,ArH),7.19(d,J=7.6 Hz,2H,ArH),2.43(s,2H,CH 2 ),2.38(s,3H,CH 3 ),2.37(s,2H,CH 2 ),2.01(s,3H,CH 3 ),1.09(s,6H,CH 3 ). 13 C NMR (100MHz, CDCl 3 ):δ=193.0,142.6,135.9,135.8,134.7,131.3,130.2,129.8,129.1,128.4,128.2,120.6,116.7,53.1,37.1,35.2,28.5,21.3,11.1.HRMS(ESI)C 24 h 25 ClNO:[M+H] + calcd 378.1625, found: 378.1619.

Embodiment 3

[0046] Weigh 0.5mmol of 5,5-dimethyl-1,3-cyclohexanedione, 0.5mmol of cyclopropylamine, 0.5mmol of (E)-β-nitro-β-methylstyrene and 0.05mmol of L-proline was added to the reactor, and then 3 mL of water was added, and the reaction was performed under microwave for 8 minutes. After the reaction was completed, it was cooled to room temperature, extracted with ethyl acetate, and separated by column chromatography with petroleum ether / ethyl acetate to obtain an analytically pure product with a yield of 85%.

[0047] Product Confirmation:

[0048]

[0049] 1 H NMR (400MHz, CDCl 3 ):δ=7.37-7.34(m,4H,ArH),7.26-7.24(m,1H,ArH),3.03-3.00(m,1H,CH),2.80(s,2H,CH 2 ),2.32(s,2H,CH 2 ),2.28(s,3H,CH 3 ),1.91(s,3H,CH 3 ),1.17-1.13(m,8H,CH 3 ,CH 2 ),1.00-0.96(m,2H,CH 2 ). 13 C NMR (100MHz, CDCl 3 ):δ=193.0,144.1,134.8,130.4,129.9,127.5,126.1,120.0,115.9,53.0,37.6,35.1,28.7,26.0,11.3,7.6. HRMS(ESI)C 20 h 24 NO:[M+H] + calcd 294.1858, found: 294.1852.

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Abstract

The invention discloses a tetrahydroindole compound, and a preparation method and an application thereof, and belongs to the technical field of the chemical synthesis. Raw materials comprising a 1,3-cyclohexanedione compound, nitroalkene and amine undergo a one-pot process under microwave radiation in water as a solvent under the action of L-proline as a catalyst to prepare the tetrahydroindole compound in high yield. The catalyst used in the invention is a non-transition metal catalyst having a low price, so the synthesis cost is substantially reduced; the reaction condition in a catalysis system is mild and can be easily controlled, and the product can be obtained through a domino cyclized multi-component one-step reaction; and the method has the advantages of green and pollution-free experiment program, simple and effective experiment operation, and diversified product structure. The method which uses water as a solvent has the characteristics of simple post-treatment, small pollution to the environment, no damages to the health of the body of an operation worker, and easy realization of the industrialized production.

Description

Technical field: [0001] The invention relates to a tetrahydroindole compound and its preparation method and application, in particular to a tetrahydroindole compound prepared through a domino cyclization reaction catalyzed by L-proline, and belongs to the technical field of chemical synthesis. technical background: [0002] Indole nuclei are an important class of heterocyclic skeletons, which widely exist in natural products and have many important biological activities, such as anxiolytic, antihypertensive, vasodilator, antihistamine, anti-inflammatory, anti-tumor, etc. Although there are many methods for synthesizing indole compounds, the currently commonly used methods still have their limitations: (1) Fischer indole synthesis usually has low yields, is prone to side reactions, and has poor regioselectivity. (2) Some metal catalysts are often used in reductive cyclization or condensation reactions, which are troublesome in post-processing, unfriendly to the environment, a...

Claims

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Application Information

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IPC IPC(8): C07D209/10C07D209/08C07D209/12A61P35/00
Inventor 齐陈泽张富仁李春梅
Owner SHAOXING UNIVERSITY
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