Benzoxazole-containing ketopiprazine derivatives as well as synthetic method and application thereof

A technology of benzoxazole piperazinone and synthetic method, which is applied in the field of chemical synthesis containing benzoxazole piperazinone derivatives and their fast and high selectivity, and can solve the problems that are unfavorable to benzoxazole piperazine The application of quasi-derivatives and their industrial synthesis and industrialization are difficult to apply on a large scale, and the operation and post-processing are cumbersome, so as to achieve the effects of low cost, fast response and short reaction route

Inactive Publication Date: 2017-06-30
EAST CHINA NORMAL UNIV
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  • Abstract
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  • Claims
  • Application Information

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Problems solved by technology

Afterwards, new synthetic methods were discovered one after another. However, these synthetic methods and routes have the disadvantages of long steps, harsh reaction conditions, high cost, long time-consuming, low yield, cumbersome operation and post-processing, etc., and it is difficult to achieve large-scale industrialization. application, limited economic value
Therefore, above-mentioned method is all unfavorable for containing synthetic benzoxazole piperazine derivatives in the application in organic synthesis and its industrial synthesis

Method used

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  • Benzoxazole-containing ketopiprazine derivatives as well as synthetic method and application thereof
  • Benzoxazole-containing ketopiprazine derivatives as well as synthetic method and application thereof
  • Benzoxazole-containing ketopiprazine derivatives as well as synthetic method and application thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 13

[0088]

[0089] Propioyl diamino ester compound (0.2mmol) and Molecular sieves (300 mg) were mixed in 2 mL of DCM solvent, and silver trifluoromethanesulfonate (0.04 mmol) was added under nitrogen protection at 0° C., and the reaction was continued for 1 h. After 1 h, the temperature was raised to room temperature (25° C.), and stirring was continued for 2 h. The reaction mixture was purified by column chromatography to obtain a pure product whose structure is shown in formula (a) as methyl-10a-methyl-1-oxo-3-phenyl-4-(4-(trifluoromethyl yl)phenyl)-1,3,4,10a-tetrahydro-2H-benzo[4,5]oxazolone[3,2-a]pyrazine-3-carboxylate. The yield was 65%, and the dr value was equal to >95:5. Compound shown in formula (a) 1 H NMR schematic as figure 1 As shown, its 13 C NMR schematic as figure 2 As shown, its 19 F NMR schematic as image 3 shown.

[0090] 1 H NMR (400MHz, CDCl 3 )δ7.76(d, J=7.7Hz, 2H), 7.49(t, J=7.3Hz, 2H), 7.43(m, 4H), 7.32(d, J=8.1Hz, 2H), 6.72(dd, J=18.1,7....

Embodiment 14

[0092]

[0093] Propioyl diamino ester compound (0.2mmol) and Molecular sieves (300 mg) were mixed in 2 mL of DCM solvent, and silver trifluoromethanesulfonate (0.04 mmol) was added under nitrogen protection at 0° C., and the reaction was continued for 1 h. After 1 h, the temperature was raised to room temperature, and stirring was continued for 2 h. The reaction mixture was purified by column chromatography to obtain a pure product whose structure is shown in formula (b) as methyl-10a-methyl-1-oxo-3-phenyl-4-(4-bromophenyl) -1,3,4,10a-tetrahydro-2H-benzo[4,5]oxazolone[3,2-a]pyrazine-3-carboxylate. The yield was 60%, and the dr value was equal to >95:5. Compound shown in formula (b) 1 H NMR schematic as Figure 4 As shown, its 13 CNMR schematic diagram as Figure 5 shown.

[0094] 1 H NMR (400MHz, CDCl 3 )δ7.67(d, J=7.5Hz, 2H), 7.43-7.37(m, 3H), 7.19(m, 2H), 6.99(d, J=8.1Hz, 3H), 6.69-6.61(m, 2H ),6.61-6.50(m,2H),5.73(s,1H),3.46(s,3H),0.97(s,3H). 13 C NMR (100MH...

Embodiment 15

[0096]

[0097] Propioyl diamino ester compound (0.2mmol) and Molecular sieves (300 mg) were mixed in 2 mL of DCM solvent, silver trifluoromethanesulfonate (0.04 mmol) was added under nitrogen protection at 0°C, and the reaction was continued for 1 h. After 1 h, the temperature was raised to room temperature, and stirring was continued for 2 h. The reaction mixture was purified by column chromatography to obtain a pure product whose structure is shown in formula (c) as methyl-10a-methyl-1-oxo-3-(4-methoxyphenyl)-4- (4-Bromophenyl)-1,3,4,10a-tetrahydro-2H-benzo[4,5]oxazolone[3,2-a]pyrazine-3-carboxylate. The yield was 50%, and the dr value was equal to >95:5. Compound shown in formula (c) 1 H NMR schematic as Image 6 As shown, its 13 C NMR schematic as Figure 7 shown.

[0098] 1 H NMR (400MHz, CDCl 3 )δ7.56(d, J=8.7Hz, 2H), 7.19(s, 2H), 6.97(d, J=8.3Hz, 2H), 6.91(d, J=8.7Hz, 2H), 6.64(q, J=7.6Hz, 2H), 6.57(t, J=7.2Hz, 1H), 6.51(d, J=7.1Hz, 2H), 5.68(s, 1H), 3.77...

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Abstract

The invention discloses benzoxazole-containing ketopiprazine derivatives as well as a synthetic method and application thereof. The benzoxazole-containing ketopiprazine derivatives are obtained by using alpha-aryl-alpha and beta-diamino-acid ester compounds as raw materials, using a metal catalyst as a catalyst and carrying out one-step reaction in an organic solvent. The synthetic method disclosed by the invention has the advantages of high atomic economy, high selectivity, mild reaction conditions, and simple and safe operation; the benzoxazole-containing ketopiprazine derivatives prepared by the synthetic method disclosed by the invention can be used as important chemical and medical intermediates, have biological activity, and are suitable for preparing medicines for resisting colon cancer.

Description

technical field [0001] The invention relates to the field of synthetic medicine and chemical industry, and mainly relates to a benzoxazole-containing piperazinone derivative and its rapid and highly selective chemical synthesis method and application. Background technique [0002] Benzoxazole derivatives are the central framework for constructing natural products and synthesizing some important drugs. They have good biological activities such as sterilization, antiseptic, herbicide, and anticancer. Therefore, the synthesis and biological activities of their compounds are important in synthetic chemistry. and the medicinal chemistry community are of great interest to researchers. Farfán used o-aminophenol as the starting material to synthesize benzoxazole piperazine derivatives in four steps (Tetrahedron:Asymmetry 1999 10 799-811); Muthusubramanian found that benzoxazole piperazine derivatives can also be obtained by intermolecular cyclization Azine derivatives (Indian J. Ch...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D498/04A61K31/4985A61P35/00
CPCC07D498/04
Inventor 刘顺英雷锐锐陈云中吴永刘冬岚董素珍胡文浩
Owner EAST CHINA NORMAL UNIV
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