Synthesis method of 4-carbonyl-5-hydrobenzo [f] [1, 4] thiaza derivative

A synthesis method and derivative technology are applied in the field of synthesis of 4-carbonyl-5-hydrobenzo[f][1,4]thiazepine derivatives, which can solve the problems of complex preparation of reaction substrates, and achieve The effect of convenient access to raw materials, good yield and mild reaction conditions

Inactive Publication Date: 2021-06-22
NANTONG UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The reported benzo[f][1,4]thiazepine derivatives usually have complicated preparation of reaction substrates, and tedious multi-step reactions are required to synthesize benzo[f][1,4]thiazepines derivative

Method used

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  • Synthesis method of 4-carbonyl-5-hydrobenzo [f] [1, 4] thiaza derivative
  • Synthesis method of 4-carbonyl-5-hydrobenzo [f] [1, 4] thiaza derivative
  • Synthesis method of 4-carbonyl-5-hydrobenzo [f] [1, 4] thiaza derivative

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Experimental program
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Embodiment 1

[0019] 1-(3-phenylbenzo[f][1,4]thiazepin-4(5H)-yl)ethan-1-one

[0020]

[0021] Mix 0.5 mmol E-type β-thiocyanamide derivative, 0.05 mmol palladium acetate metal catalyst, 0.1 mmol triphenylphosphine ligand, 1 mmol cesium carbonate base, and 3 mL N,N-dimethylformamide under nitrogen atmosphere React at 100°C for 12 hours; add an appropriate amount of water or sodium chloride solution to stop the reaction, and cool to room temperature. The reaction solution was washed with saturated brine, extracted three times with ethyl acetate, and the organic phase was collected. Anhydrous Mg for organic phase 2 SO 4 Drying, filtration, concentration, and purification by column chromatography yielded 50.6 mg of the target product with a yield of 36%. The NMR and high-resolution data of the target product are: 1 HNMR (400MHz, CDCl 3 )δ7.49-7.46(m,1H),7.39-7.33(m,4H),7.31-7.26(m,2H),7.20-7.15(m,2H),6.07(s,1H),4.84(s, 2H), 1.64(s, 3H). 13 C NMR (100MHz, CDCl 3 )δ170.9,141.6,139.0,138...

Embodiment 2

[0023] 1-(3-(4-chlorophenyl)benzo[f][1,4]thiazepin-4(5H)-yl)ethan-1-one

[0024]

[0025] Mix 0.3 mmol E-type β-thiocyanamide derivative, 0.05 mmol palladium acetate metal catalyst, 0.1 mmol triphenylphosphine ligand, 1 mmol cesium carbonate base, and 3 mL N,N-dimethylformamide under nitrogen atmosphere React at 100°C for 12 hours; add an appropriate amount of water or sodium chloride solution to stop the reaction, and cool to room temperature. The reaction solution was washed with saturated brine, extracted three times with ethyl acetate, and the organic phase was collected. Anhydrous Mg for organic phase 2 SO 4 Drying, filtration, concentration, and purification by column chromatography gave 52 mg of the target product with a yield of 33%. The NMR and high-resolution data of the target product are: 1 HNMR (400MHz, CDCl 3 )δ7.49-7.45(m,1H),7.36-7.31(m,2H),7.30-7.25(m,3H),7.21-7.16(m,2H),6.06(s,1H),4.82(s, 2H), 1.64(s, 3H). 13 C NMR (100MHz, CDCl 3 )δ170.7,140.3,138....

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Abstract

The invention relates to the technical field of organic synthesis, in particular to a synthesis method of a 4-carbonyl-5-hydrobenzo [f] [1, 4] thiaza derivative, which comprises the following specific reaction equations: taking an E-type beta-thiocyanate amide derivative as a raw material, adding palladium acetate, triphenylphosphine, cesium carbonate, taking N, N-dimethyl formamide as a solvent, and reacting at the temperature of 100 DEG C to obtain the 4-carbonyl-5-hydrobenzo [f] [1, 4] thiaza derivative. Compared with a traditional method, the method has the advantages of better yield, regioselectivity, stereoselectivity, mild reaction conditions, no metal participation and convenience in raw material acquisition. The benzo [f] [1, 4] thiaza compound prepared by the invention is an important skeleton structure in pharmaceutical chemistry, and has high theoretical research value and application value.

Description

technical field [0001] The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing 4-carbonyl-5-hydrobenzo[f][1,4]thiazepine derivatives. Background technique [0002] Benzo[f][1,4]thiazepine derivatives are a class of important pharmaceutical and biological intermediates. Its derivatives can inhibit glycogenase kinase-3β (GSK-3β), and can be used as non-ATP competitive small molecule inhibitors of GSK-3β for the treatment of GSK-3β-related diabetes, Alzheimer's disease and Tumor and other related diseases (Eldar-Finkelman, Hagit. Trends in Molecular Medicine. 8(3):126-132, 2002). For example: thiadiazoles (TDZD) are the first non-ATP competitive inhibitors acting on the GSK-3 signaling pathway, and have shown good selectivity (Martinez, Ana.etal.Journal of Medicinal Chemistry.45( 6): 1292–1299, 2002). Therefore, the development of synthetic methods for benzo[f][1,4]thiazepine derivatives has important application value. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D281/10
CPCC07D281/10
Inventor 曾小宝代文静王鑫谢雨杉吴桂霞
Owner NANTONG UNIVERSITY
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