Reaction Steps
To a solution of (R,E)-diisopropyl (3-((2-chloro-5-fluoropyrimidin-4-yl)amino)-4,4-dimethylpent-1-en-1-yl)phosphonate, 16a, (0.81 g, 1.99 mmol) and 5-fluoro-1-(p-tolylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrrolo[2,3-b]pyridine, 7a, (1.24 g, 3.00 mmol) in 2-Me-THF (16 mL) was added K3PO4 (1.27 g, 3.00 mmol) and water (4 mL). The biphasic mixture was degassed under a stream of nitrogen for 15 minutes. Then, X-Phos (0.11 g, 0.24 mmol) and Pd2(dba)3 (0.06 g, 0.06 mmol) was added to the mixture. After degassing with nitrogen for an additional 5 minutes, the vessel was sealed and heated at 100° C. for 2 hours. The mixture was cooled to room temperature and diluted with EtOAc, filtered through celite. The filtrate was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The crude residue was purified via silica gel chromatography (0-50% EtOAc/CH2Cl2 gradient) to afford 1.123 g of the desired product: 1H NMR (400 MHz, d6-DMSO) δ 8.55-8.42 (m, 3H), 8.31 (d, J=3.7 Hz, 1H), 8.06 (d, J=8.3 Hz, 2H), 7.73 (d, J=8.9 Hz, 1H), 7.44 (d, J=8.4 Hz, 2H), 6.80 (ddd, J=22.2, 17.1, 6.9 Hz, 1H), 5.99 (dd, J=20.3, 17.1 Hz, 1H), 4.95 (t, J=7.6 Hz, 1H), 4.51-4.32 (m, 2H), 2.35 (s, 3H), 1.19-1.14 (m, 6H), 1.11 (dd, J=6.0, 4.4 Hz, 6H), 1.02 (s, 9H).); LCMS Gradient 10-90%, 0.1% formic acid, 5 minutes, C18/ACN, RT=4.06 minutes (M+H) 662.35.
