Reaction Steps
A mixture of 4-{4-[6-Amino-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-3-yl]-pyrazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester (BB4) (245 mg, 0.517 mmol), 5-chloro-1,2,3,4-tetrahydroisoquinoline (175 mg, 1.03 mmol), cupric acetate (94.8 mg, 0.517 mmol), pyridine (84 μL, 1.0 mmol), 4 Å molecular sieves (139 mg, 264 mg/mmol SM), and DCM (9 mL, 100 mmol) was stirred at rt under an atmosphere of air for 3 d. The mixture was diluted with DCM (50 ml), washed with EDTA solution (2%, 3×50 ml), water (3×50 ml) and brine (50 ml), dried over MgSO4, filtered, and concentrated in vacuo to give a dark black oil that was purified by MDPS to give the title compound as a brown solid. 1H NMR (400 MHz, CDCl3): δ=1.48 (s, 9H), 1.88-1.99 (m, 2H), 2.12-2.19 (m, 2H), 2.84-2.98 (m, 2H), 3.04 (t, J=6.0 Hz, 2H), 3.36 (t, J=6.0 Hz, 2H), 4.16 (s, 2H), 4.22-4.36 (m, 3H), 7.02 (d, J=7.6 Hz, 1H), 7.19 (t, J=8.0 Hz, 1H), 7.33 (d, J=7.6 Hz, 1H), 7.50 (s, 1H), 7.62 (s, 1H), 7.66 (s, 1H), 7.69 (s, 1H). MS(ES+): m/z=508.77/511.16 (52/20) [MH+]. HPLC: tR=3.00 min (ZQ2, polar—5 min).
