Diisopropylethylamine → N-{3-[(4s,6s)-2-Amino-4-(Fluoromethyl)-6-(Trifluoromethyl)-5,6-Dihydro-4h-1,3-Oxazin-4-Yl]-4-Fluorophenyl}-5-Cyanopyridine-2-Carboxamide

Participants

Reaction Steps

To a solution of (4S,6S)-4-(5-amino-2-fluorophenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (2a, 0.125 g, 0.404 mmol) in DCM (3 mL) was added N,N-diisopropylethylamine (0.074 mL, 0.424 mmol, Aldrich), 5-cyanopicolinic acid (0.060 g, 0.404 mmol, Aldrich) and 1-propanephosphonic acid cyclic anhydride (50% solution in ethyl acetate; 0.238 mL, 0.404 mmol, Alfa Aesar). The reaction was stirred at ambient temperature for 15 minutes. The reaction was diluted with water and DCM. The organic layer was separated and washed sequentially with aqueous saturated sodium bicarbonate solution and brine. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The crude material was purified by silica gel flash chromatography (gradient of 10-70% EtOAc in hexanes) to afford the title compound as a white solid. (0.0745 g, 0.170 mmol, 42.0% yield). MS m/z=440.0 [M+H]+. Calculated for C19H14F5N5O2: 439.34

Provenance & Evidence