1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 86732148, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of N-((4S,6S)-4-(2-fluoro-5-(pyrazin-2-yloxy)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (85 mg, 0.173 mmol) in MeOH (690 μL) was added 1,8-diazabicyclo-[5.4.0]undec-7-ene (77 μL, 0.518 mmol) dropwise. The reaction mixture was stirred at 60° C. for 1 h, then at 80° C. for another hour. After cooling to room temperature, the crude material was purified 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 30 min. The fractions were combined and concentrated. It was partitioned between DCM and saturated NaHCO3. The aqueous layer was back extracted with DCM and the combined organic was dried (Na2SO4) and concentrated to provide (4S,6S)-4-(2-fluoro-5-(pyrazin-2-yloxy)phenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (38 mg, 0.098 mmol, 56.7% yield) as white solid. MS m/z=389 [M]+. Calculated for C16H13F5N4O2: 388.29.

Provenance & Evidence