4-Methylmorpholine → (2R)-4-[4-(4-chloro-2,3-difluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Participants

Reaction Steps

To a suspension of (2R)-4-[4-(4-chloro-2,3-difluorophenyl)-2-oxopyridin-1(2H)-yl]-2-methyl-2-(methylsulfonyl)butanoic acid (4500 mg, 10.7 mmol) in Me-THF (450 mL) was added N-methyl morpholine (1.80 mL, 16.1 mmol) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (2520 mg, 13.9 mmol). The reaction mixture was stirred at room temperature for 1 h. To the mixture was added O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (1630 mg, 13.9 mmol) and the resulting mixture was stirred at room temperature for 1 h. The reaction mixture was washed with water and passed through pad of sodium sulfate, celite and silica gel. The pad was washed with ethyl acetate. The combined organic solution was concentrated under reduced pressure to give the title compound as a solid in quantitative yield. LCMS m/z 519.0 (M+1). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.48-1.57 (m, 3 H) 1.59 (d, J=3.90 Hz, 3 H) 1.64-1.74 (m, 3 H) 2.15-2.26 (m, 1 H) 2.39-2.49 (m, 1 H) 3.10 (d, J=6.44 Hz, 3 H) 3.46-3.58 (m, 1 H) 3.70-3.83 (m, 1 H) 4.03 (d, J=7.02 Hz, 1 H) 4.07-4.21 (m, 1 H) 4.95-5.01 (m, 1 H) 6.48-6.53 (m, 1 H) 6.61-6.64 (m, 1 H) 7.42-7.49 (m, 1 H) 7.51-7.59 (m, 1 H) 7.79 (dd, J=10.83, 7.12 Hz, 1 H), H—N wasn't observed. 19F NMR (376 MHz, DMSO-d6) δ ppm −138.09 (dd, J=22.56, 7.52 Hz) −139.10 (dd, J=22.56, 7.52 Hz)

Provenance & Evidence