Diisopropylethylamine → N-{5-[Acetyl(methyl)amino]-2-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}-2,2-difluoropropanamide

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Reaction Steps

HATU (1.44 g, 3.78 mmol) and N-{3-amino-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}-N-methylacetamide (1.00 g, 3.60 mmol) (for preparation, see Example 1, steps B to E) were added to a solution of 2,2-difluoropropanoic acid (0.40 g, 3.60 mmol) and DIPEA (0.75 mL, 4.32 mmol) in DMF (100 mL) at room temperature. The reaction mixture was stirred overnight. The solvent was concentrated and the crude product was recovered in EtOAc. The organic was washed with water, saturated NaHCO3 solution and brine. The organic layer was dried over anhydrous Na2SO4 and filtered. The solvent was concentrated giving the title compound that was used for the next step without further purification. Yield: 1.00 g (75%); MS (ESI) (M+H)+: 370.2.

Provenance & Evidence