Sodium Iodide → 5-(5-Methyl-1-{[3-(oxetan-3-yloxy)phenyl]methyl}-1H-1,2,4-triazol-3-yl)-3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazole

HRID 1475230Notes

Reaction equation

HRID 1475230 reaction equation
C([O-])([O-])=O.[K+].[K+].[CH3:7][C:8]1[N:12]([CH2:13][C:14]2[CH:15]=[C:16]([OH:20])[CH:17]=[CH:18][CH:19]=2)[N:11]=[C:10]([C:21]2[O:25][N:24]=[C:23]([C:26]3[CH:31]=[CH:30][C:29]([O:32][C:33]([F:36])([F:35])[F:34])=[CH:28][CH:27]=3)[N:22]=2)[N:9]=1.[I-].[Na+].Br[CH:40]1[CH2:43][O:42][CH2:41]1>CN(C=O)C.O>[CH3:7][C:8]1[N:12]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][CH:40]3[CH2:43][O:42][CH2:41]3)[CH:15]=2)[N:11]=[C:10]([C:21]2[O:25][N:24]=[C:23]([C:26]3[CH:31]=[CH:30][C:29]([O:32][C:33]([F:36])([F:34])[F:35])=[CH:28][CH:27]=3)[N:22]=2)[N:9]=1

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 162444933-BromooxetaneHCID 86711921HCID 86711921, compound

Product 1

HCID 867119235-(5-Methyl-1-{[3-(oxetan-3-yloxy)phenyl]methyl}-1H-1,2,4-triazol-3-yl)-3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazole

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of K2CO3 (19.8 mg, 0.144 mmol), 3-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-1,2,4-triazol-1-yl)methyl)phenol (Example 59; 30.0 mg, 0.072 mmol), sodium iodide (21.6 mg, 0.144 mmol) and 3-bromooxetane (22 uL, 0.288 mmol) in DMF (0.36 mL) was stirred at 50° C. for 48 h. The crude mixture was diluted with H2O and extracted with 4:1 CHCl3:i-PrOH. The organic layer was dried over MgSO4, concentrated under reduced pressure, and the residue was purified using Prep-HPLC to furnish the title compound; MS (ES+) C22H18F3N5O4 requires: 473. found 474 [M+H]+; 1H-NMR (600 MHz, CD3OD) δ ppm 8.28 (d, J=8.8 Hz, 2H), 7.35 (d, J=8.2 Hz, 2H), 7.28 (m, 1H), 6.86 (d, J=7.8 Hz, 1H), 6.64 (m, 2H), 5.42 (s, 2H), 5.18 (m, 1H), 4.95 (m, 2H), 4.74 (m, 2H), 2.54 (s, 3H).

Workup

  1. extractionextracted with 4:1 CHCl3
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated under reduced pressure
  4. customthe residue was purified

Sources & evidence

ORD record
ord-7b08abaa2b4b4e53b74cc35b3ef90f51
Source dataset
uspto-grants-2015_04
Patent number
US09018380B2

Reaction notes

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