2,5-difluoro-N'-hydroxybenzenecarboximidamide → 5-[1-(2-Bromophenyl)-5-methyl-1H-1,2,3-triazole-4-yl]-3-(2,5-difluorophenyl)-1,2,4-oxadiazole

HRID 219575Notes

Reaction equation

HRID 219575 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([CH3:13])=[C:11]([C:14]([OH:16])=O)[N:10]=[N:9]1.[F:17][C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=1[C:25](=[N:27]O)[NH2:26]>>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([CH3:13])=[C:11]([C:14]2[O:16][N:26]=[C:25]([C:19]3[CH:20]=[C:21]([F:24])[CH:22]=[CH:23][C:18]=3[F:17])[N:27]=2)[N:10]=[N:9]1

Participants

3

Reactant 2

HCID 43581602,5-difluoro-N'-hydroxybenzenecarboximidamideHCID 153995471-(2-Bromophenyl)-5-methyl-1H-1,2,3-triazole-4-carboxylic acid

Product 1

HCID 596040655-[1-(2-Bromophenyl)-5-methyl-1H-1,2,3-triazole-4-yl]-3-(2,5-difluorophenyl)-1,2,4-oxadiazole

Conditions

Temperature
100 °C

Procedure

The title compound was prepared following procedure described for Example 1, but starting from 1-(2-bromophenyl)-5-methyl-1H-1,2,3-triazole-4-carboxylic acid, prepared according to Zhang, Z.-Y. et al. Magn. Reson. Chem. 1998, 36, 159-460 (56.42 mg; 0.20 mmol) and 2,5-difluoro-N′-hydroxybenzenecarboximid amide (JRD-Fluoro, 37.87 mg; 0.22 mmol). The reaction mixture was filtered through an NH2 SPE column (1 g) and evaporated. The residue was taken up into pyridine and heated at 100° C. for 7 h, in order to complete oxadiazole formation. Pyridine was evaporated and the crude product was purified by flash chromatography (SiO2: 10 g; cyclohexane/EtOAc gradient from 90/10 till 50/50) and dried to afford Example 3 as a yellow solid. 1H NMR: (DMSO-d6, 300 MHz) δ 8.06 (dd, J=1.70 Hz, J=7.73 Hz, 1H), 8.02-7.97 (m, 1H), 7.86 (dd, J=1.89 Hz, J=7.53 Hz, 1H), 7.80-7.69 (m, 2H), 7.63 (dt, J=1.91 Hz, J=6.58 Hz, 2H), 2.61 (s, 3H). LC/MS: 419.93 (M+H)+. HPLC (Method A) Rt 4.92 min (Purity: 96%).

Workup

  1. customprepared
  2. filtrationThe reaction mixture was filtered through an NH2 SPE column (1 g)
  3. customevaporated
  4. customPyridine was evaporated
  5. customthe crude product was purified by flash chromatography (SiO2: 10 g; cyclohexane/EtOAc gradient from 90/10 till 50/50)
  6. customdried

Sources & evidence

ORD record
ord-fd7bcae8767b4dadb5957fe2eb68b033
Source dataset
uspto-grants-2012_06
Patent number
US08202856B2

Reaction notes

Loading…