Trifluoromethanesulfonic anhydride → HCID 18690686, compound

Participants

Reaction Steps

To a solution of 1-(3-Chloro-phenyl)-4-(1-trityl-1H-imidazol-4-ylmethyl)-1H-pyridin-2-one (272 mg, 0.527 mmol) from step 6 and 4-hydroxymethyl-2-methoxy-benzonitrile (90.3 mg, 0.55 mmol) in CH2Cl2 cooled to -78° C. over dry ice/acetone bath was added N,N-diisopropylethylamine (192 μl, 1.1 mmol) and trifluoromethane-sulfonic anhydride(93 μl, 0.55 mmol). The reaction was allowed to slowly warm to room temperature and stirred overnight. The reaction was diluted with methanol (10 mL), heated to reflux for 2 h, cooled and the solvent evaporated in vacuo. The residue was partitioned between sat. Na2CO3 (20 ml) and CH2Cl2 (2×50 ml). The organic extracts were dried (MgSO4) and evaporated in vacuo. The residue was chromatographed (silica gel, MeOH: CH2Cl2 3:97 to 4:96 to 10:90 gradient elution) to afford the free base which was converted to the hydrochloride salt to afford the title compound as an off white solid.

Provenance & Evidence