Potassium Carbonate → 3-(5-Chloro-8-fluoroisoquinolin-3-yl)-5-[1-(8-methyl-8-azabicyclo [3.2.1]-oct-3-yl)-1H-pyrazol-4-yl]-pyridin-2-ylamine

Participants

Reaction Conditions

Reaction Steps

A solution of 3-(4-iodopyrazol-1-yl)-8-methyl-8-azabicyclo[3.2.1]octane (42.7 mg, 0.135 mmol), 3-(5-chloro-8-fluoroisoquinolin-3-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyridin-2-ylamine (0.070 g, 0.18 mmol), potassium carbonate (55.9 mg, 0.404 mmol), and Pd(PPh3)4 (9 mg, 0.008 mmol) in previously degassed DME/Water (4:1) (3.0 mL) was placed in a microwave tube and evacuated and charged with N2 (2×). The reaction mixture was heated in the microwave reactor to 100° C. for 45 min. The reaction mixture was diluted with EtOAc and washed with H2O (2×), brine (2×), dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by chromatography on silica gel [eluting with 10% MeOH in CHCl3], passing through an SCX cartridge, and finally by the MDP. The fractions containing product were combined, concentrated in vacuo, and partitioned between CHCl3 and sat. NaHCO3. The organic phase was dried over Na2SO4, filtered and concentrated in vacuo resulting in the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ=1.64-1.72 (m, 2H), 1.77-1.86 (m, 2H), 1.97-2.06 (m, 2H), 2.07-2.17 (m, 2H), 2.26 (s, 3H), 3.20 (br. s., 2H), 4.47 (tt, J=11.7, 5.9 Hz, 1H), 6.89 (br. s., 2H), 7.54 (dd, J=9.9, 8.4 Hz, 1H), 7.87 (s, 1H), 8.03 (dd, J=8.4, 4.8 Hz, 1H), 8.15 (d, J=2.2 Hz, 1H), 8.25 (s, 1H), 8.35 (d, J=2.2 Hz, 1H), 8.37 (s, 1H), 9.64 (s, 1H). MS (ES+): m/z=463.13/465.15 (76/24) [MH+]. HPLC: tR=1.88 min (ZQ2, polar—5 min).

Provenance & Evidence