5-Prop-2-ynyloxypyrazine-2-carboxylic acid → N-(3-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-(prop-2-yn-1-yloxy)pyrazine-2-carboxamide

Participants

Reaction Steps

The title compound was synthesized by procedures and steps analogous to those described in Method F (Example 32) above, but using (4S,6S)-4-(5-amino-2-fluorophenyl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (intermediate 4i) and 5-(prop-2-yn-1-yloxy)pyrazine-2-carboxylic acid (J. Med. Chem. 2013, 56, 3980). The desired product was purified by reversed-phase preparative HPLC using a Phenomenex Gemini column, 10 micron, C18, 110 Å, 100×50 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 80% over 20 min. The product containing fractions were combined and neutralized with 1N NaOH solution. The free-based product was extracted with DCM. The organic phase was dried over Na2SO4 and the solvent was removed under reduced pressure to afford the title compound. MS m/z=452.1 [M+H]+. Calculated for C20H17ClF4N5O3: 451.1

Provenance & Evidence