Reaction Steps
tert-Butyl 2-(3-(3-(1-allyl-1H-1,2,3-triazol-4-yl)phenethoxy)-N-cyclohexylpropanamido)ethyl(2-(5-(tert-butoxycarbonyloxy)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethyl)carbamate [Example 14, Step iv)] (220 mg), 1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione (126 mg) and tetrakis(triphenylphosphine)palladium(0) (31 mg) were dissolved in DCM (2 mL) and sealed into a microwave tube. The reaction was heated to 100° C., over a period of 90 min in the microwave reactor. After cooling to room temperature, TFA (1 mL) was added and the mixture was stirred for 30 min, then concentrated. The crude product was purified by preparative HPLC on a Phenomenex Gemini column using a gradient of aqueous 0.1% trifluoroacetic acid in acetonitrile as eluent to afford the titled compound (63.5 mg) as a solid. MS [M+H]+=577.3 (calc=577.3138) (MultiMode+) 1H NMR (400 MHz, CD3OD) δ 8.12 (s, 1H), 7.71 (s, 1H), 7.63 (d, J=7.8 Hz, 1H), 7.33 (t, J=7.5 Hz, 1H), 7.21 (d, J=8.0 Hz, 1H), 6.69 (d, J=8.2 Hz, 1H), 6.47 (d, J=8.5 Hz, 1H), 4.61 (s, 2H), 3.72 (t, J=6.7 Hz, 2H), 3.72 (t, J=5.9 Hz, 2H), 3.71-3.63 (m, 1H), 3.47 (t, J=6.9 Hz, 2H), 3.11 (t, J=7.2 Hz, 2H), 3.02 (t, J=5.7 Hz, 2H), 2.89 (t, J=6.7 Hz, 2H), 2.87 (t, J=7.1 Hz, 2H), 2.62 (t, J=6.0 Hz, 2H), 1.80-1.72 (m, 2H), 1.69-1.58 (m, 3H), 1.46-1.24 (m, 4H), 1.16-1.05 (m, 1H).
