Compounds, compositions and methods comprising 1,3,4-oxadiazole derivatives
A compound, aryl technology, applied to containing 1, can solve the problems of weak potency of CFTR inhibitors, lack of CFTR specificity, etc.
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0501] Preparation of 5-(3,5-dichloro-4-hydroxyphenyl)-N-(4-phenoxybenzyl)-1,3,4-oxadiazole-2-carboxamide (Compound 2)
[0502]
[0503] Step 1: 3,5-Dichloro-4-hydroxybenzohydrazide (compound A)
[0504] To a mixture of ethyl 3,5-dichloro-4-hydroxybenzoate (23.5 g, 100 mmol) in ethanol (250 mL) was added hydrazine monohydrate (6 mL, 130 mmol) and the mixture was heated at reflux for 18 h. More hydrazine monohydrate (18 mL, 389 mmol) was added and the mixture was reheated at reflux 9d. The mixture was cooled to room temperature and the resulting solid was collected by filtration, washed with ethanol and dried to afford 11.02 g (50%) of the title compound as a white solid. 1 H NMRδ(ppm)(DMSO-d 6 ): 7.63 (2H, s), 9.19 (1H, s).
[0505] Step 2: Ethyl 2-(2-(3,5-dichloro-4-hydroxybenzoyl)hydrazino)-2-oxoacetate (compound B)
[0506] Ethyl was added dropwise to a stirred mixture of 3,5-dichloro-4-hydroxybenzohydrazide (2.00 g, 9.05 mmol) in anhydrous dichloromethane (50 mL) un...
Embodiment 2
[0545] Preparation of N-(4-phenoxybenzyl)-5-(3-(trifluoromethylsulfonamido)phenyl)-1,3,4-oxadiazole-2-carboxamide (Compound 7)
[0546]
[0547] Step 1: Ethyl 3-(trifluoromethylsulfonamido)benzoate (compound D)
[0548] Trifluoromethanesulfonic anhydride (4.06mL, 24.1mmol) was added dropwise to a stirred solution of ethyl 3-aminobenzoate (3.32g, 20.1mmol) in anhydrous dichloromethane under nitrogen, 3°C ice bath cooling Last for 5min. After 80 min the ice bath was removed and the mixture was stirred for 26 h under nitrogen. The mixture was recooled with an ice bath and more trifluoromethanesulfonic anhydride (4.06 mL, 24.1 mmol) was added, and the mixture was stirred at room temperature for another 16 h. Then, the mixture was cooled to -70°C and triethylamine (6.72 mL, 48.2 mmol) was added dropwise for 20 min, keeping the temperature 4) and evaporate the remaining organic layer. The residue was purified by flash chromatography (silica gel, 15% EtOAc / petroleum ether) to a...
Embodiment 3
[0567] Preparation of N-(3,4-dichlorobenzyl)-N-methyl-5-(4-(trifluoromethylsulfonamido)phenyl)-1,3,4-oxadiazole-2-carboxy Amide (Compound 17)
[0568]
[0569] Step 1: Ethyl 4-(trifluoromethylsulfonamido)benzoate (Compound H)
[0570] Trifluoromethanesulfonic anhydride (4.1 mL, 24.1 mmol) was added dropwise to a stirred solution of ethyl 4-aminobenzoate (3.30 g, 20 mmol) in anhydrous dichloromethane under nitrogen, 3 °C ice bath cooling, and 5min. After 80 min the ice bath was removed and the mixture was stirred under nitrogen for 26 h. The mixture was recooled with an ice bath and more trifluoromethanesulfonic anhydride (4.06 mL, 24.1 mmol) was added and stirred at room temperature for another 16 h. The mixture was then cooled to -70°C and triethylamine (6.72 mL, 48.2 mmol) was added dropwise for 20 min, keeping the temperature 4 ) the remaining organic layer and evaporated. The residue was purified by flash chromatography (silica gel, 15% EtO Ac / petroleum ether) to af...
PUM
| Property | Measurement | Unit |
|---|---|---|
| electrical resistance | aaaaa | aaaaa |
Abstract
Description
Claims
Application Information
Login to View More