Cyanogen Bromide → HCID 57743019, compound

HRID 1924258Notes

Reaction equation

HRID 1924258 reaction equation
[N:1]#[C:2]Br.[CH3:4][N:5]1[C:9]([CH2:10][N:11]2[CH2:15][CH:14]([CH2:16][CH2:17][CH3:18])[CH2:13][C:12]2=[O:19])=[CH:8][N:7]=[CH:6]1>CN(C1C=CN=CC=1)C.CN(C=O)C>[CH3:4][N:5]1[C:9]([CH2:10][N:11]2[CH2:15][CH:14]([CH2:16][CH2:17][CH3:18])[CH2:13][C:12]2=[O:19])=[CH:8][N:7]=[C:6]1[C:2]#[N:1]

Participants

5

Reactant 2

HCID 10476Cyanogen BromideHCID 57743006HCID 57743006, compound

Product 1

HCID 57743019HCID 57743019, compoundYield 33.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent4×

Conditions

Temperature
0 °C

Procedure

In a 2 l, three-necked flask fitted with a magnetic stirrer and reflux condenser under inert atmosphere, DMAP (60.4 g, 0.495 mol) is dissolved in DMF (900 ml) and the solution is cooled to 0° C. Cyanogen bromide (54.4 g, 0.495 mol) is added by portions while the temperature is maintained between 0 and 10° C. The mixture is stirred for 0.5 h at this temperature and a solution of 1-[(1-methyl-1H-imidazol-5-yl)methyl]-4-propylpyrrolidin-2-one 121 (36.5 g, 0.165 mol) in DMF (500 ml) is added. The mixture is heated at 40° C. overnight. The DMAP-BrCN complex (0.165 mol) in 350 ml of DMF is added at 5° C. (after being stirred for 1 h) and the mixture is heated at 45° C. overnight. One equivalent of the DMAP-BrCN complex in DMF (150 ml) is prepared again and added to the mixture at a temperature comprised between 0° C. and 10° C. The mixture is stirred at 45° C. overnight. The solvent is evaporated, the residue is dissolved in AcOEt, then the organic phase is washed with a saturated solution of NaHCO3 and brine, dried over MgSO4 and concentrated to dryness. Purification by preparative chromatography on silicagel affords 13.5 g 1-methyl-5-[(2-oxo-4-propylpyrrolidin-1-yl)methyl]-1H-imidazole-2-carbonitrile 125.

Workup

  1. customIn a 2 l, three-necked flask fitted with a magnetic stirrer
  2. temperatureis maintained between 0 and 10° C
  3. temperatureThe mixture is heated at 40° C. overnight
  4. stirring(after being stirred for 1 h)
  5. temperaturethe mixture is heated at 45° C. overnight
  6. additionadded to the mixture at a temperature
  7. customcomprised between 0° C. and 10° C
  8. stirringThe mixture is stirred at 45° C. overnight
  9. customThe solvent is evaporated
  10. dissolutionthe residue is dissolved in AcOEt
  11. washthe organic phase is washed with a saturated solution of NaHCO3 and brine
  12. dry with materialdried over MgSO4
  13. concentrationconcentrated to dryness
  14. customPurification by preparative chromatography on silicagel

Sources & evidence

ORD record
ord-0ac4b0c0ed5042f498f6b30738fc80b3
Source dataset
uspto-grants-2012_05
Patent number
US08178533B2

Reaction notes

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