1,8-Diazabicyclo(5.4.0)undec-7-ene → N-(6-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-5-fluoropyridin-2-yl)-5-chloropicolinamide

Participants

Reaction Conditions

Reaction Steps

To a suspension of 5-chloro-N-(5-fluoro-6-((4S,6S)-4-methyl-2-(4-nitrobenzamido)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)pyridin-2-yl)picolinamide (8b, 76 mg, 0.131 mmol) in MeOH (1.3 mL) was added 1,8-diazabicyclo-[5.4.0]undec-7-ene (Aldrich, 254 μl, 1.701 mmol). The reaction mixture was stirred at 70° C. for 1 h. The reaction was diluted with MeOH and 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 16 min. The product containing fractions were combined and neutralized with aqueous saturated sodium bicarbonate solution. The free-based product was extracted with DCM. The organic phase was dried over MgSO4 and the solvent was removed under reduced pressure to afford the title compound as a white solid (39 mg, 12% yield over two steps). MS m/z=432 [M+H]+. Calculated for C17H14ClF4N5O2: 431.

Provenance & Evidence