Cyanogen Bromide → HCID 57743019, compound

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence