Cyanogen Bromide → 5-(5-Amino-1,3,4-oxadiazol-2-yl)-4-cyclobutyl-2-methylbenzonitrile

HRID 1487979Notes

Reaction equation

HRID 1487979 reaction equation
[C:1]([C:3]1[C:4]([CH3:17])=[CH:5][C:6]([CH:13]2[CH2:16][CH2:15][CH2:14]2)=[C:7]([CH:12]=1)[C:8]([NH:10][NH2:11])=[O:9])#[N:2].C([O-])(O)=O.[Na+].Br[C:24]#[N:25]>O.O1CCOCC1.CCOC(C)=O>[NH2:25][C:24]1[O:9][C:8]([C:7]2[C:6]([CH:13]3[CH2:16][CH2:15][CH2:14]3)=[CH:5][C:4]([CH3:17])=[C:3]([CH:12]=2)[C:1]#[N:2])=[N:10][N:11]=1

Participants

7

Reactant 3

HCID 10476Cyanogen BromideHCID 516892Sodium BicarbonateHCID 682889185-Cyano-2-cyclobutyl-4-methylbenzohydrazide2×

Product 1

HCID 682888425-(5-Amino-1,3,4-oxadiazol-2-yl)-4-cyclobutyl-2-methylbenzonitrile

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 5-cyano-2-cyclobutyl-4-methylbenzohydrazide (compound 89.5, 0.5 g, 2.18 mmol) in H2O (10 mL) and dioxane (15 mL) was added NaHCO3 (0.55 g, 6.55 mmol). After the mixture was stirred at room temperature for 5 minutes, BrCN (1.3 mL, 5 M in CH3CN, 6.55 mmol) was added drop-wise. The mixture was stirred at room temperature for 30 minutes, where upon white solids formed. The mixture was diluted with EtOAc and washed with water, then brine. The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexanes:EtOAc 1:1 to EtOAc) to yield 0.55 g (theoretical) of the title compound as a white solid. m/z (ES+) 255 (M+H)+. 1H NMR (400 MHz, Chloroform-d) δ 7.93 (s, 1H), 7.45 (s, 1H), 5.10 (br, 2H), 4.38 (m, 1H), 2.61 (s, 3H), 2.48-2.34 (m, 2H), 2.17-1.98 (m, 3H), 1.91-1.79 (m, 1H).

Workup

  1. stirringThe mixture was stirred at room temperature for 30 minutes
  2. customwhere upon white solids formed
  3. washwashed with water
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexanes:EtOAc 1:1 to EtOAc)

Sources & evidence

ORD record
ord-7c6189e666c24eaea3341b1a8e4710d1
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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