Cesium carbonate → HCID 86732267, compound

Participants

Reaction Conditions

Reaction Steps

In round-bottomed flask were added N-((4S,6S)-4-(2-fluoro-5-hydroxyphenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (225 mg, 0.543 mmol), 2,6-dichloro-4-phenylpyridine (146 mg, 0.652 mmol), cesium carbonate (230 mg, 0.706 mmol) in DMSO (1358 μl). The flask was heated in 100° C. oil bath for 7 h. After cooling to RT, the reaction mixture was partitioned between EtOAc and water. The aqueous layer was back extracted with EtOAc (2×) and the combined organics was dried (Na2SO4) and concentrated. The crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 0% to 50% EtOAc in hexane, followed by reverse-phase preparative HPLC using a Phenomenex Gemini column, 10 micron, C18, 110 Å, 150×30 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 70% over 15 min, then neutralized with saturated NaHCO3 and extracted with DCM, to provide (4S,6S)-4-(5-((6-chloro-4-phenylpyridin-2-yl)oxy)-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (8 mg, 0.016 mmol, 2.96% yield) as a off-white solid.

Provenance & Evidence