A class of heterocyclic substituted 1,3,4-oxa(thia)diazole compounds and its preparation method and use
A kind of azole compound and compound technology, applied in the field of medicinal chemistry
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Embodiment 1
[0066] Example 1: Preparation of intermediate 2-(5-bromopentyl)5-(2,4-dichlorophenyl)-1,3,4-oxadiazole to synthesize 2,4-dichlorobenzohydrazide, Reference [Wang, P.Y; Zhou, L; Zhou, J; Wu, Z.B; Xue, W; Song, B.A; Yang, S. Synthesis and antibacterial activity of pyridinium-tailored 2,5-substituted-1,3,4 -oxadiazole thioether / sulfoxide / sulfone derivatives. BioorgMed Chem Lett, 2016, 26, 1214-1217]. This (0.5 g, 2.44 mmol) was added to 8 mL POCl containing 6-bromohexanoic acid (0.48 g, 2.44 mmol) 3 In the solution, the reaction was carried out at 75°C for 10h. Removal of POCl under reduced pressure 3 , and then 70 mL of ethyl acetate was added to the residue for extraction. The organic layer was washed with water, aqueous potassium carbonate and brine, dried over anhydrous sodium sulfate, filtered, and then desolubilized. Using PE:EA=8:1 as eluent, the intermediate was obtained as a white solid in 73.2% yield, mp: 164.3-165.6°C.
Embodiment 2
[0067] Example 2: 2-(2,4-Dichlorophenyl)-5-(5-(2-methyl-5-nitro-1H-imidazol-1-yl)pentyl)-1,3,4 - Preparation of oxadiazoles
[0068] 2-(5-Bromopentyl)-5-(2,4-dichlorophenyl)-1,3,4-oxadiazole 4 (0.2 g, 0.55 mmol), 2-methyl-5-nitro -1H-imidazole (0.14 g, 1.10 mmol) and K 2 CO 3 Dissolve in DMF (7 mL) and stir at 60°C for 12 hours. The solvent was removed under reduced pressure and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over anhydrous sodium sulfate, filtered, and then desolvated. use CH 2 Cl 2 : CH 3OH=40:1 as eluent gave the desired product as a brown solid, yield: 99.9%, mp: 49.8-50.1°C.
[0069] In analogy to the synthetic procedure steps of Examples 1 and 2, other compounds were prepared using the corresponding starting materials.
[0070] The structures of the synthesized 1,3,4-oxadiazolylimidazole (partial heterocycle) compounds are shown in Table 1, and the 1,3,4-oxadiazolyl imidazole (partial heterocycle) compounds ar...
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