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A kind of preparation method of polysubstituted dihydropyrimidoindolinone derivatives

A technology of dihydropyrimidine and indolinone, which is applied in the field of preparation of dihydropyrimidoindolinone derivatives, and achieves the effects of high yield, scientific and reasonable synthesis method, and simple synthesis method

Active Publication Date: 2020-09-08
QINGDAO UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Obvious disadvantages of the above-mentioned process for the preparation of dihydropyrimidoindolinone derivatives: the use of the noble metal rhodium

Method used

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  • A kind of preparation method of polysubstituted dihydropyrimidoindolinone derivatives
  • A kind of preparation method of polysubstituted dihydropyrimidoindolinone derivatives
  • A kind of preparation method of polysubstituted dihydropyrimidoindolinone derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] 1) Preparation of dihydropyrimidoindolinone derivative 3aa

[0023]

[0024] Add N-methoxyindolecarboxamide 1a (0.2mmol, 38.0mg), 2a (0.4mmol, 41.7mg) and cobalt acetate (0.02mmol, 5.0mg) and silver acetate (0.4 mmol, 66.8mg), sodium acetate (0.4mmol, 54.4mg) and tricyclohexylphosphine (0.04mmol, 11.2mg) were added to hexafluoroisopropanol (2mL), stirred in an oil bath at 120°C, and reacted for 3 hours. After the reaction is complete, use a rotary evaporator to remove the solvent to obtain a crude product, which is separated by column chromatography (200-300 mesh silica gel) (petroleum ether / ethyl acetate=8 / 1), and uses a rotary evaporator to remove the solvent to obtain the target The product is unsubstituted dihydropyrimidindolinone 3aa, and its yield is 95%.

[0025] Spectrum analysis data 3aa:

[0026] 1 H NMR (500MHz, CDCl 3 )δ8.45(d,J=8.3Hz,1H),7.46–7.29(m,7H),7.22(t,J=7.5Hz,1H),6.07(s,1H),4.57(dd,J=9.8 ,5.4Hz, 1H),3.98–3.85(m,2H),3.85(s,3H). 13 CNMR (125...

Embodiment 2

[0028] Replace 1a in Example 1 with 1b, and other conditions are the same as Example 1. The experimental results are shown in Table 1.

[0029] Spectrum analysis data 3ba:

[0030]

[0031] 1 H NMR (500MHz, CDCl 3 )δ8.39(dd, J=9.0,4.7Hz,1H),7.40 (dt,J=11.6,6.7Hz,3H),7.33(d,J=6.8Hz,2H),7.08(dd,J=8.8 ,2.3 Hz,1H),7.04(td,J=9.2,2.4Hz,1H),6.03(s,1H),4.57(dd,J=9.6,5.5Hz,1H),3.98–3.87(m,2H) ,3.85(s,3H). 13 C NMR (125MHz, CDCl 3 )δ160.4, 158.5, 152.3, 138.9, 138.0, 131.8, 130.4, 130.4, 129.0, 1228.2, 116.4, 116.4, 112.1, 111.9, 105.9, 105.7, 104.9, 62.8, 54.6, 40.9.

Embodiment 3

[0033] Replace 1a in Example 1 with 1c, and other conditions are the same as Example 1. The experimental results are shown in Table 1.

[0034]

[0035] Spectrum analysis data 3ca:

[0036] 1 H NMR (500MHz, CDCl 3 )δ8.36(d,J=8.8Hz,1H),7.46–7.33(m,5H),7.34–7.30(m,3H),7.29–7.23(m,2H),6.00(s,5H),4.56 (dd, J=9.1,5.6Hz,1H),3.98–3.85(m,2H),3.85(s,3H). 13 C NMR (125 MHz, CDCl 3 )δ152.1, 138.7, 137.9, 133.8, 130.7, 129.0, 128.7, 128.2, 124.4, 119.8, 116.4, 104.4, 62.8, 54.5, 40.9.

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Abstract

The invention discloses a preparation method of a novel polysubstitution dihydropyrimidine indolone derivative, which belongs to the technical field of organic synthesis. The preparation method comprises the following steps: adding substitution N-methoxyindolamide into a reactor, substituting styrene, cobaltous acetate, silver acetate, sodium acetate, 4-methylpyridine and tricyclohexylphosphine, stirring in a solvent, after the reaction is finished, concentrating filtrate by using a rotary evaporator to obtain a crude product, separating the crude product by virtue of silica gel column chromatography to obtain a target compound. The synthetic method of the polysubstitution dihydropyrimidine indolone derivative provided by the invention has the characteristics of science, reasonability, simple synthetic method, high yield of target compounds, ease in purifying the product and the like. A reaction equation is shown in the description.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a preparation method of dihydropyrimidoindolinone derivatives. Background technique [0002] Nitrogen-containing heterocycles are widely found in natural products and molecules with biological and pharmaceutical activities. Among these heterocyclic compounds, pyrimidone and indole are two important nuclei. Pyrimidinones have promising applications in many fields, for example, anticancer and antibacterial activities. (J.Med.Chem.1987,30,1256-1261.) Indole compounds also play an indispensable role in drug design and synthesis of natural products. For example, compounds with indole as the core are used in the treatment of hypertension and antibacterial drugs, respectively. ((a) Hypertension. 1997, 29, 651-658. (b) J. Antimicrob. Chemother. 2004, 54, 549-552.) [0003] As a combination of two nitrogen-containing heterocycles, pyrimidinone and indole, dihydro...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D487/04
CPCC07D487/04
Inventor 张林宝朱明辉文丽荣李明
Owner QINGDAO UNIV OF SCI & TECH