Reaction Steps
To a solution 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 (BB3) (39.0 mg, 0.0831 mmol), trifluoromethanesulfonic acid 4-fluoroisoquinolin-3-yl ester (25.1 mg, 0.0850 mmol), and PS-PPh3-Pd (0.10 mmol/g loading; 55 mg, 0.0055 mmol; Argonaut) in 1,4-dioxane (1.3 mL, 16 mmol) in a sealable microwave tube was added a solution of Cs2CO3 (53.1 mg, 0.163 mmol) in H2O (0.36 mL, 20 mmol). The tube was sealed, evacuated and refilled with nitrogen (3×), and heated in the microwave reactor to 105° C. for 30 minutes. The resin was filtered off and washed with DCM. The combined filtrate and washings were washed with water and brine, dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by preparative TLC [20×20 cm plate, 500 μm layer of silica gel, eluting with 3.5% MeOH in DCM (3×)]. Material from the main band was collected and dried in vacuo overnight giving the title compound as a yellow glassy solid. 1H NMR (400 MHz, CDCl3): δ=9.14 (s, 1H), 8.29 (d, J=2.2 Hz, 1H), 8.18 (dd, J=0.8, 8.2 Hz, 1H), 8.06 (dt, J=8.0, 0.8 Hz, 1H), 8.01 (dd, J=2.6, 2.6 Hz, 1H), 7.84 (ddd, J=1.2, 7.2, 8.2 Hz, 1H), 7.75 (d, J=0.6 Hz, 1H), 7.72 (ddd, J=1.0, 7.0, 8.2 Hz, 1H), 7.64 (d, J=0.6 Hz, 1H), 5.90 (brs, 2H), 4.40-4.15 (m, 3H), 2.91 (brt, J=10.6 Hz, 2H), 2.18 (brdd, J=2.2, 12.4 Hz, 2H), 1.97 (dq, J=4.4, 12.2 Hz, 2H), 1.48 (s, 9H). MS(ES+): m/z=489.16 (100) [MH+], 433.16 (4) [MH+-isobutene]. HPLC: tR=3.05 min (polar—5 min, ZQ3), 2.71 min (polar—5 min, ZQ2).
