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Novel method for synthesizing cyano-substituted imidazo[1,5-a]pyridine

A cyano-substituted, 5-a technology is applied in the field of cyano-substituted imidazo[1,5-a]pyridine synthesis, and achieves the effects of simple operation and low cost

Inactive Publication Date: 2021-11-05
BEIJING UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Cyano-substituted imidazo[1,5-a]pyridines have various important biological activities, but the reported synthetic methods require multiple synthetic steps and highly toxic sodium cyanide (NaCN) or trimethylnitrile Silane (TMSCN) as a source of cyano groups
Compared with the above synthetic methods, the new method we developed uses cheap and safe NH 4 SCN as a cyano source for efficient synthesis of cyano-substituted imidazo[1,5-a]pyridines via a one-step reaction, which has not been reported in the literature

Method used

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  • Novel method for synthesizing cyano-substituted imidazo[1,5-a]pyridine
  • Novel method for synthesizing cyano-substituted imidazo[1,5-a]pyridine
  • Novel method for synthesizing cyano-substituted imidazo[1,5-a]pyridine

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Experimental program
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Effect test

Embodiment 1

[0021] Example 1: Synthesis of 1-cyano-3-phenylimidazo[1,5-a]pyridine

[0022] In a dry reactor, add NH 4 SCN (0.6 mmol, 46 mg), pyridine-2-carbaldehyde (0.3 mmol) and benzylamine (0.6 mmol) were then added to dimethylsulfoxide (2 mL). After stirring the mixture at room temperature for 5 min, add I 2 o 5 (0.3 mmol, 100 mg), and the mixture was further stirred at 100 °C for 5 h. After the reaction (TLC) was complete, the reaction mixture was cooled to room temperature and washed with saturated Na 2 S 2 o 3 The solution was quenched. The reaction mixture was then extracted with ethyl acetate. The organic phase was anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain a crude residue. Finally, the organic phase was concentrated on a rotary evaporator. The crude product was purified by column chromatography to obtain 1-cyano-3-phenylimidazo[1,5-a]pyridine. Yield: 95%.

[0023]

[0024] Structural Characterization Data: 1 H NMR (400MHz, Chlorofor...

Embodiment 2

[0025] Example 2: Synthesis of 1-cyano-3-phenylimidazo[1,5-a]pyridine

[0026] In a dry reactor, add NH 4 SCN (0.6mmol, 46mg), pyridine-2-carbaldehyde (0.3mmol) and benzylamine (0.45mmol) were added followed by dimethylsulfoxide (2mL). After stirring the mixture at room temperature for 5 min, add I 2 o 5(0.3 mmol, 100 mg), and the mixture was further stirred at 100 °C for 5 h. After the reaction (TLC) was complete, the reaction mixture was cooled to room temperature and washed with saturated Na 2 S 2 o 3 The solution was quenched. The reaction mixture was then extracted with ethyl acetate. The organic phase was anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain a crude residue. Finally, the organic phase was concentrated on a rotary evaporator. The crude product was purified by column chromatography to obtain 1-cyano-3-phenylimidazo[1,5-a]pyridine. Yield: 73%.

[0027]

[0028] Structural Characterization Data: 1 H NMR (400MHz, Chloroform...

Embodiment 3

[0029] Example 3: Synthesis of 1-cyano-3-phenylimidazo[1,5-a]pyridine

[0030] In a dry reactor, add NH 4 SCN (0.45 mmol, 35 mg), pyridine-2-carbaldehyde (0.3 mmol) and benzylamine (0.6 mmol) were then added to dimethylsulfoxide (2 mL). After stirring the mixture at room temperature for 5 min, add I 2 o 5 (0.3 mmol, 100 mg), and the mixture was further stirred at 100 °C for 5 h. After the reaction (TLC) was complete, the reaction mixture was cooled to room temperature and washed with saturated Na 2 S 2 o 3 The solution was quenched. The reaction mixture was then extracted with ethyl acetate. The organic phase was anhydrous Na 2 SO 4 Dry and concentrate under reduced pressure to obtain a crude residue. Finally, the organic phase was concentrated on a rotary evaporator. The crude product was purified by column chromatography to obtain 1-cyano-3-phenylimidazo[1,5-a]pyridine. Yield: 69%.

[0031]

[0032] Structural Characterization Data: 1 H NMR (400MHz, Chlorofo...

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Abstract

The invention discloses a novel method for synthesizing cyano-substituted imidazo[1,5-a]pyridine, and belongs to the field of chemical synthesis. The method comprises the steps: adding NH4SCN, pyridine-2-formaldehyde and amine into a dry reaction tube, and then adding a reaction solvent into the reaction tube; stirring the reaction system at room temperature for 5 minutes, adding I2O5, and further stirring and reacting under a heating condition; and after the reaction is finished, cooling a reaction mixture to room temperature, and quenching by using a saturated Na2S2O3 solution. The method provided by the invention is a synthesis method which is simple to operate, low in cost, efficient and green.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, in particular to a new synthesis method of cyano-substituted imidazo[1,5-a]pyridine. Background technique [0002] Cyano-substituted imidazo[1,5-a]pyridines have various important biological activities, and are usually used as SSTR4 agonists, FGF inhibitors, and PI3K-γ inhibitors (references: US 2014171434 A1; WO 2014184275 A1 ; US2008108648 A1). Therefore, it is of great research significance and industrial application value to develop a new method for the synthesis of highly efficient cyano-substituted imidazo[1,5-a]pyridines. At present, the reported synthetic methods need to prepare cyano-substituted imidazo[1,5-a]pyridines through multi-step reactions starting from imidazo[1,5-a]pyridines with functional groups. From the perspective of industrial application, multi-step reactions will lead to lower reaction yields, increase reaction costs, and then reduce the practicability of the reactio...

Claims

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Application Information

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IPC IPC(8): C07D471/04
CPCC07D471/04
Inventor 王会巧徐坤
Owner BEIJING UNIV OF TECH
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