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) (70.1 mg, 0.149 mmol), trifluoromethanesulfonic acid 8-chloroisoquinolin-3-yl ester (47.9 mg, 0.154 mmol), and Pd(PPh3)4 (11.5 mg, 0.00995 mmol) in 1,4-dioxane (2.3 mL, 29 mmol in a sealable microwave tube was added a solution of Cs2CO3 (95.5 mg, 0.293 mmol) in H2O (0.65 mL, 36 mmol). The tube was sealed, evacuated and refilled with nitrogen (3×), and heated in the microwave reactor to 105° C. for 30 minutes. The reaction mixture was diluted with DCM, washed with water, sat. NaHCO3 solution, and brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude material was chromatographed on silica gel [20 g/70 mL prepacked cartridge, eluting with DCM→1% MeOH in DCM→2% MeOH in DCM→3% MeOH in DCM]. Fractions containing the title compound were combined and dried in vacuo, yielding the title compound as a glassy, yellow solid. 1H NMR (400 MHz, CDCl3): δ=9.70 (t, J=0.8 Hz, 1H), 8.29 (d, J=2.0 Hz, 1H), 8.04 (d, J=0.4 Hz, 1H), 7.96 (d, J=2.4 Hz, 1H), 7.82 (dt, J=5.8, 3.0 Hz, 1H), 7.78 (d, J=1.2 Hz, 1H), 7.67 (d, J=0.8 Hz, 1H), 7.66-7.62 (m, 2H), 6.47 (brs, 2H), 4.40-4.19 (m, 3H), 2.92 (brt, J=11.6 Hz, 2H), 2.19 (brdd, J=12.2 Hz, 2H), 1.95 (dq, J=4.0, 12.0 Hz, 2H), 1.49 (s, 9H). MS(ES+): m/z=505.16/507.13 (100/42) [MH+], 449.05/451.07 (3/1) [MH+-isobutene]. HPLC: tR=3.15 min (polar—5 min, ZQ3).
