Potassium Carbonate → isopropyl 4-(4-(4-cyano-2-fluorophenoxy)-6H-pyrimido[5,4-b][1,4]oxazin-8(7H)-yl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of isopropyl 4-(4-chloro-6H-pyrimido[5,4-b][1,4]oxazin-8(7H)-yl)piperidine-1-carboxylate from Example 20A (10.0 mg, 0.029 mmol) and 3-fluoro-4-hydroxybenzonitrile (12.07 mg, 0.088 mmol) in DMF (0.4 mL) was added K2CO3 (12.17 mg, 0.088 mmol). The reaction mixture was stirred in a sealed vial for 3 days at 120° C. The reaction mixture was cooled to RT. The reaction mixture was diluted with MeOH, filtered and purified by reverse phase HPLC (H2O/CH3CN) to give isopropyl 4-(4-(4-cyano-2-fluorophenoxy)-6H-pyrimido[5,4-b][1,4]oxazin-8(7H)-yl)piperidine-1-carboxylate (1.0 mg, 2.265 μmol, 7.72% yield) as Example 148 as an off-white solid. 1H NMR (400 MHz, CDCl3) δ ppm 1.27 (d, J=6.05 Hz, 6 H) 1.55-1.79 (m, 4 H) 2.85-2.95 (m, 2 H) 3.44-3.54 (m, 2 H) 4.05-4.15 (m, 2 H) 4.24-4.35 (m, 2 H) 4.84-4.95 (m, 2 H) 7.29-7.40 (m, 1 H) 7.45-7.52 (m, 2 H) 7.88 (s, 1 H). LRMS (ESI): 442.5 [M+H]+.

Provenance & Evidence