1,2,4-triazolethione derivative containing (hetero)aryl group and piperazine, preparation method and application
A technology of triazolethione and its derivatives, which is applied in 1 field, and can solve the problems that the inhibitory activity of bactericidal ARI enzyme has not been disclosed, etc.
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Embodiment 1
[0030] The preparation method of compound 15
[0031] Step A: Preparation of 5-(furan-2-yl)-1,3,4-oxadiazole-2-thiol
[0032]
[0033] Add 9.00g (71.4mmol) of 2-furyl hydrazide and 300mL of absolute ethanol to a 500mL round bottom flask, and add 21.66g (285.5mmol) of CS 2 And 4.00g (71.4mmol) KOH, remove the ice bath after the addition is complete, and heat to reflux for 7h. Cool to room temperature and spin off the solvent, add an appropriate amount of water to dissolve the residue, adjust the pH to 2-3 with hydrochloric acid, stir for 2 hours, filter with suction, recrystallize with ethanol, and dry to obtain 9.36 g of white solid with a yield of 78%.
[0034] Step B: Preparation of 4-amino-5-(furan-2-yl)-4H-1,2,4-triazole-3-thiol
[0035]
[0036]In the 100mL round bottom flask, add 8.90g (52.9mmol) 5-(furan-2-yl)-1,3,4-oxadiazole-2-thiol, 17.00g (264.6mmol) hydrazine hydrate (80%) and 30mL of absolute ethanol, stirred and heated to reflux for 7h. Cool to room tem...
Embodiment 2
[0044] The preparation method of compound 23
[0045] Step A: Preparation of 5-(pyridin-3-yl)-1,3,4-oxadiazole-2-thiol
[0046]
[0047] Add 17.00g (123.9mmol) 3-pyridinecarbohydrazide and 100mL absolute ethanol to a 250mL round bottom flask, and add 37.83g (324.3mmol) CS 2 And 6.93g (123.9mmol) KOH, remove the ice bath after the addition is complete, and heat to reflux for 10h. Cool to room temperature and spin off the solvent, dissolve the residue in water and adjust the pH to 2-3 with hydrochloric acid, stir for 2 h, filter with suction, recrystallize with ethanol, and dry to obtain 9.10 g of white solid, yield 41%.
[0048] Step B: Preparation of 4-amino-5-(pyridin-3-yl)-4H-1,2,4-triazole-3-thiol
[0049]
[0050] Add 8.75g (55.8mmol) 5-(pyridin-3-yl)-1,3,4-oxadiazole-2-thiol in 250mL round bottom flask, 20.95g (334.8mmol) hydrazine hydrate (80%) and 100mL absolute ethanol, heated to reflux for 12h. Cool to room temperature and spin off the solvent, dissolve the ...
Embodiment 3
[0058] Preparation method of compound 34.
[0059] Step A: Preparation of 5-phenyl-1,3,4-oxadiazole-2-thiol
[0060]
[0061] Add 19.00g (139.6mmol) of benzohydrazide and 100mL of absolute ethanol to a 250mL round bottom flask, and add 42.43g (558.2mmol) of CS 2 And 7.81g (139.6mmol) KOH, remove the ice bath after the addition is complete, and heat to reflux for 7h. Cool to room temperature and spin off the solvent, add an appropriate amount of water to dissolve the residue, adjust the pH to 2-3 with hydrochloric acid, stir for 2 hours, filter with suction, and recrystallize from ethanol to obtain 18.16 g of white solid with a yield of 73%.
[0062] Step B: Preparation of 4-amino-5-phenyl-4H-1,2,4-triazole-3-thiol
[0063]
[0064] Add 30.00g (168.3mmol) 5-phenyl-1,3,4-oxadiazole-2-thiol, 80.00g (1.3mol) hydrazine hydrate (80%) and 100mL absolute ethanol to a 250mL round bottom flask, Stirring and heating at reflux for 6h. Cool to room temperature and spin off the so...
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