Diisopropylethylamine → N-[2-(1,1-Difluoroethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-benzimidazol-5-yl]acetamide

Participants

Reaction Conditions

Reaction Steps

HATU (1.58 g, 4.17 mmol) and N-{3-amino-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}acetamide (1.00 g, 3.79 mmol) were added to a solution of 2,2-difluoropropanoic acid (0.43 g, 3.98 mmol) and DIPEA (0.80 mL, 4.55 mmol) in DMF (100 mL) at ambient temperature. The reaction mixture was stirred overnight and the solvent was concentrated. The intermediate was heated to 80° C. for 3 h in glacial AcOH (100 mL), and the solvent was concentrated. The crude product was recovered in DCM (300 mL), washed with saturated NaHCO3 solution (3×100 mL), brine and dried over anhydrous MgSO4. The solvent was concentrated and the product was purified by normal-phase MPLC using MeOH 5% and Acetone 10% in DCM to provide the title compound as a white solid. Yield: 1.07 g (83%); MS (ESI) (M+H)+=338.2.

Provenance & Evidence