Water → HCID 66571724, compound

Participants

Reaction Steps

To a solution of (+4-(2-chloro-2,2-difluoroethyl)-1-{[2-(methoxymethyl)-6-(trifluoro-methyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl]methyl}imidazolidin-2-one 14 (120 mg, 0.277 mmol) in CH2Cl2 (12 ml) is added, at 0° C., sodium hydroxide (3.96 ml, 1M solution), tetrabutylammonium bromide (82 mg, 0.1 eq.) and iodomethane (0.035 ml, 2 eq.). The mixture is stirred at room temperature for 120 h. Iodomethane (0.060 ml) is added and the mixture is stirred at room temperature for 24 h. Iodomethane is added (2×0.060 ml) and the mixture is stirred for 72 h. Water is added and the reaction mixture is extracted with CH2Cl2 (2 times), dried over MgSO4, filtered and condensed under reduced pressure. The residue is purified by chromatography (basic conditions; gradient; eluent: H2O/CH3CN/NH4OH 60/40/0.1 to 30/70/0.1; 10 min) to afford 54 mg of pure (+)-4-(2-chloro-2,2-difluoroethyl)-1-{[2-(methoxymethyl)-6-(trifluoromethyl) imidazo[2,1-b][1,3,4]-thiadiazol-5-yl]methyl}-3-methylimidazolidin-2-one 22.

Provenance & Evidence