Potassium Carbonate → N-(4-(Chlorodifluoromethoxy)phenyl)-5-(pyrimidin-5-yl)-6-((tetrahydro-2 h-pyran-4-yl)oxy)nicotinamide

Participants

Reaction Conditions

Reaction Steps

Tetrahydro-2H-pyran-4-ol (0.105 mL, 1.095 mmol) was added to a stirred mixture of 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(pyrimidin-5-yl)nicotinamide (Example 76, 100 mg, 0.243 mmol) and K2CO3 (201.6 mg, 1.458 mmol) in MeCN (1 mL) and the RM was stirred at 110-130° C. for 26 h. The solvent was evaporated off under reduced pressure and the crude product was purified by SFC (Column 2-EP; gradient 9% to 19% in 6 min.) and lyophilized in water/MeCN (minimum volume) to give the title compound. UPLC-MS (Condition 2) tR=1.09 min, m/z=477.0/479.1 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.62-1.76 (m, 2H) 1.98-2.11 (m, 2H) 3.48-3.60 (m, 2H) 3.70-3.82 (m, 2H) 5.37-5.49 (m, 1H) 7.38 (d, J=9.16 Hz, 2H) 7.88 (d, J=9.00 Hz, 2H) 8.50 (d, J=2.38 Hz, 1H) 8.83 (d, J=2.51 Hz, 1H) 9.16 (s, 2H) 9.23 (s, 1H) 10.45 (s, 1H).

Provenance & Evidence