Potassium Carbonate → (1R,2R)-2-((6-((4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol

Participants

Reaction Conditions

Reaction Steps

To a suspension of (1R,2R)-2-((6-((4-bromo-1H-imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (50 mg, 0.12 mmol) from Step 7 of this Example and 1-methylpyrazole-4-boronic acid pinacol ester (51 mg, 0.25 mmol) in a mixture of DME (0.7 mL) and H2O (0.3 mL) was added K2CO3 (68 mg, 0.5 mmol). Argon was bubbled into the mixture for 5 min. To the mixture was added tetrakis(triphenylphosphine)palladium (0) (14 mg, 0.01 mmol). Argon was bubbled into the mixture for 5 min. The reaction vessel was sealed and the mixture was heated at 100° C. for 16 h. Additional portions of 1-methylpyrazole-4-boronic acid pinacol ester (51 mg, 0.25 mmol) and tetrakis(triphenylphosphine)palladium (0) (14 mg, 0.01 mmol) were added to the mixture and argon was bubbled into the mixture for 5 min. The reaction vessel was sealed and the mixture was heated at 110° C. for 4 h. The mixture was cooled to rt and partitioned between EtOAc (100 mL) and aq 1 N K2CO3 (50 mL). The EtOAc layer was separated and washed with water (50 mL) and brine (50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by preparative reverse-phase HPLC using a mixture of water (5% CH3CN, 0.05% HCOOH) and CH3CN (0.05% HCOOH) as the mobile phase and Varian Pursuit XRs C18 column as the stationary phase to afford (1R,2R)-2-((6-((4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (10.3 mg, 20%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 7.97 (d, J=7.5 Hz, 1H), 7.80 (s, 1H), 7.71 (s, 1H), 7.54-7.62 (m, 2H), 7.32 (d, J=8.3 Hz, 1H), 7.24 (s, 1H), 7.16 (dd, J=1.3, 8.3 Hz, 1H), 5.13 (s, 2H), 4.75 (brm, 1H), 3.80 (s, 3H), 3.52 (br s, 1H), 3.34 (br s, 1H), 2.04 (d, J=10.2 Hz, 1H), 1.88 (d, J=9.4 Hz, 1H), 1.55-1.66 (m, 2H), 1.10-1.33 (m, 4H). LCMS (ESI) m/z 409 (M+H)+.

Provenance & Evidence