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Spiro-heterocyclic compound containing indole structures and preparation method of spiro-heterocyclic compound

A compound and catalyst technology, applied in the field of spiro heterocyclic compounds and their preparation, can solve the problems of cumbersome processing, and achieve the effects of simple post-processing, high yield, and simple operation

Inactive Publication Date: 2012-07-18
SUZHOU UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the above method effectively utilizes the multi-component reaction to prepare a series of heterospiro compounds containing indole structure, which reduces the steps of intermediate separation, the post-processing of the final product of these methods is cumbersome and requires multi-step purification reactions.

Method used

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  • Spiro-heterocyclic compound containing indole structures and preparation method of spiro-heterocyclic compound
  • Spiro-heterocyclic compound containing indole structures and preparation method of spiro-heterocyclic compound
  • Spiro-heterocyclic compound containing indole structures and preparation method of spiro-heterocyclic compound

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Isatin (1mmol, 0.147g), 1-phenyl-5-aminopyrazole (1mmol, 0.173g) and thioglycolic acid (1mmol, 0.092g) were added together in a 50mL short-necked round bottom flask, and 5mL of acetonitrile was added, and Add 0.057g of p-toluenesulfonic acid after adding 0.057g of p-toluenesulfonic acid, add a reflux condenser to reflux for 24 hours, monitor the reaction progress with TLC, spin the reaction system to dry after the reaction is completed, wash with absolute ethanol, and suction filter. Drying gave a white solid as 3'-methyl-1'-phenyl-6',8'-dihydrospiro[indole-3,4'-pyrazolo[3,4-e][1,4 ]thiazepine]-2,7'(1'H)-dione 0.32 g, yield 86%. As determined by nuclear magnetic resonance spectroscopy, the melting point is 256-257°C; 1 H NMR (300MHz, DMSO-d 6 ):δ H 1.46(s, 3H, CH 3 ), 3.11 (d, J=15.0Hz, 1H, CH 2 ), 4.54 (d, J=15.0Hz, 1H, CH 2 ), 6.96-7.04(m, 2H, ArH), 7.15(d, J=7.2Hz, 1H, ArH), 7.32(t, J=7.8Hz, 1H, ArH), 7.40(t, J=6.9Hz, 1H, ArH), 7.47-7.56 (m, 4H, ArH), 9.94 (s,...

Embodiment 2

[0048] Isatin (2mmol, 0.294g), 1-methyl-5-aminopyrazole (1mmol, 0.111g) and 2-mercaptopropionic acid (1.5mmol, 0.159g) were added together in a 50mL short-necked round bottom flask, and 5mL of ethanol, shake slightly to mix the substrate evenly, add 0.001g of p-toluenesulfonic acid, add a reflux condenser to reflux for 8h, monitor the reaction progress with TLC, spin the reaction system to dry after the reaction is completed, and wash with absolute ethanol , suction filtration, and drying to obtain a white solid, 1',3',6'-trimethyl-6',8'-dihydrospiro[indole-3,4'-pyrazolo[3,4-e ][1,4]Thiazepine]-2,7'(1'H)-dione 0.27g, yield 83%. As determined by nuclear magnetic resonance spectroscopy, the melting point is 181-183°C; 1 H NMR (400MHz, DMSO-d 6 ):δ H 1.24(d, J=6.8Hz, 3H, CH 3 ), 1.38 (s, 3H, CH 3 ), 3.66(s, 3H, CH 3 ), 4.53(q, J=7.2Hz, 1H, CH), 6.94-7.00(m, 2H, ArH), 7.05(d, 1H, J=7.2Hz, ArH), 7.29(t, 1H, J=7.6 Hz, ArH), 10.11(s, 1H, NH), 10.75(s, 1H, NH). 13 C NMR (75MHz...

Embodiment 3-20

[0050] According to the method of embodiment 1 and embodiment 2, isatin is replaced with 5-methyl isatin, 5-bromoisatin, 6-bromoisatin, 5-chloroisatin, 5-fluoroisatin and 1-methyl isatin Any one of isatins, the aminopyrazole is 1-phenyl-5-aminopyrazole or 1-methyl-5-aminopyrazole, and the mercaptocarboxylic acid is thioglycolic acid or 2-mercaptopropionic acid. Reflux for 8-24 hours, wash with absolute ethanol, filter with suction, and dry to obtain a solid product. The results of nuclear magnetic resonance spectroscopy are as follows:

[0051] 3',6'-Dimethyl-1'-phenyl-6',8'-dihydrospiro[indole-3,4'-pyrazolo[3,4-e][1,4]sulfur Azepine]-2,7'(1'H)-dione, yield 83%, white solid. Melting point 270-271°C; 1 H NMR (400MHz, DMSO-d 6 ):δ H 1.27(d, J=7.2Hz, 3H, CH 3 ), 1.49 (s, 3H, CH 3 ), 4.73(q, J=7.2Hz, 1H, CH), 6.98-7.03(m, 2H, ArH), 7.11(d, J=7.6Hz, 1H, ArH), 7.33(t, J=7.6Hz, 1H, ArH), 7.41(t, J=7.2Hz, 1H, ArH), 7.51(t, J=7.6Hz, 2H, ArH), 7.58(d, J=7.6Hz, 2H, ArH), 9.98(s ...

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Abstract

The invention relates to the field of pharmaceutical chemistry, and discloses a spiro-heterocyclic compound containing indole structures and a preparation method of the spiro-heterocyclic compound. The spiro-heterocyclic compound containing the indole structures comprises a dihydro-spiro[indole-3,4'-pyrazolo[3,4-e][1,4]thiazepine] diketones compound and a dihydro-spiro[acenaphthylene-1,4'-pyrazolo[3,4-e][1,4]thiazepine] diketones compound, and adopts the structure which is shown in a formula I and a formula II, wherein R1 is -CH3 or -Ph, R2 is -H, -CH3, -F, -Cl or -Br, R3 is -H or -CH3, and R4 is -H or -CH3; in addition, the preparation method comprises the steps as follows: isatin or acenaphthylenedione, a 5-aminopyrazole compound and mercapto carboxylic acid are dissolved in a solvent, organic acid or mineral acid is taken as catalytic agents, and reaction is performed for 8 to 24 hours at the temperature ranging from 65 to 95 DEG C. The spiro-heterocyclic compound has stable properties, the preparation method is simple to operate, the productivity of reaction products is high, and the post-processing is simple.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a spiro heterocyclic compound containing an indole structure and a preparation method thereof. Background technique [0002] Indole derivatives widely exist in nature, such as many natural products with important physiological and pharmacological activities, the essential amino acid tryptophan in the human body, plant growth hormone indole-3-acetic acid, etc. Indole-containing alkaloids exist in the metabolism of many marine invertebrates, such as the indole-containing alkaloids Meridianins A-E, alkaloids Nortopsentins A-C and Aplysinopsins isolated from deep-sea mollusk sponges. Many alkaloids containing indole structures have attracted extensive attention due to their unique antibacterial, antifungal, anti-inflammatory and antitumor activities. [0003] Indole and indoline fragments are important structural fragments of most natural biologically active compounds, especially ...

Claims

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Application Information

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IPC IPC(8): C07D513/20C07D513/10
Inventor 史达清陈辉
Owner SUZHOU UNIV
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