Reaction Steps
A mixture of 9-bromo-1-methyl-8-(trifluoromethyl)-3-((2-(trimethylsilyl)ethoxy)methyl)-3,5-dihydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-2(1H)-one (Example #53, Step E, 0.08 g, 0.162 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (0.10 g, 0.324 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)dichloride dichloromethane complex (0.026 g, 0.032 mmol) and K2CO3 (0.045 g, 0.324 mmol) in dioxane (1.2 mL) and water (0.2 mL) was heated at reflux for 6 h. The reaction mixture was cooled to ambient temperature and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography on silica gel (eluting with 40% EtOAc in petroleum ether) to give tert-butyl 4-(1-methyl-2-oxo-8-(trifluoromethyl)-3-((2-(trimethylsilyl)ethoxy)methyl)-1,2,3,5-tetrahydrobenzo[5,6][1,4]oxazino[3,4-c][1,2,4]triazin-9-yl)-5,6-dihydropyridine-1(2H)-carboxylate (0.07 g, 73%) as a pale-white solid. 1H NMR (methanol-d4, 400 MHz): δ 7.28 (s, 1H), 7.10 (s, 1H), 5.64 (s, 1H), 5.11 (q, J=10.4 Hz, 2H), 4.97 (q, J=6.8 Hz, 1H), 4.69 (d, J=13.2 Hz, 2H), 4.04 (s, 2H), 3.70 (m, 4H), 2.39 (s, 2H), 1.51 (s, 9H), 1.47 (d, J=6.8 Hz, 3H), 0.96 (t, J=8.4 Hz, 2H), 0.00 (s, 9H).
