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) (53.7 mg, 0.114 mmol), trifluoromethanesulfonic acid 6-methylisoquinolin-3-yl ester (35.0 mg, 0.120 mmol), and PS-PPh3-Pd (0.10 mmol/g loading; 76 mg, 0.0076 mmol; Argonaut) in 1,4-dioxane (2.0 mL, 25 mmol) in a sealable microwave tube was added a solution of Cs2CO3 (75.6 mg, 0.232 mmol) in H2O (0.60 mL, 33 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 1M NaOH, 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 to give the title compound as a yellow glassy solid. 1H NMR (400 MHz, CDCl3): δ=9.22 (s, 1H), 8.26 (d, J=2.0 Hz, 1H), 7.94 (s, 1H), 7.93 (d, J=2.0 Hz, 1H), 7.91 (d, J=8.4 Hz, 1H), 7.77 (d, J=0.4 Hz, 1H), 7.67 (brs, 1H), 7.66 (s, 1H), 7.46 (dd, J=8.4, 1.6 Hz, 1H), 6.43 (brs, 2H), 4.38-4.19 (m, 3H), 2.92 (brt, J=11.0 Hz, 2H), 2.58 (s, 3H), 2.19 (brdd, J=2.0, 12.4 Hz, 2H), 1.98 (dq, J=4.4, 12.0 Hz, 2H), 1.49 (s, 9H). MS(ES+): m/z=485.19 (100) [MH+], 429.13 (7) [MH+-isobutene]. HPLC: tR=2.71 min (polar—5 min, ZQ2).
