Sodium Carbonate → (1R,2R)-2-((6-((6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol

Participants

Reaction Conditions

Reaction Steps

A stirred mixture of (1R,2R)-2-((6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol from Example 29 (80 mg, 0.175 mmol), 1-methylpyrazole-4-boronic acid pinacol ester (73 mg, 0.351 mmol), 2M aq Na2CO3 (400 μL, 0.40 mmol), and anhydrous DME (1.5 mL) was degassed under argon for 15 min. Bis(triphenylphosphine)palladium (II) dichloride (12 mg, 0.0171 mmol) was added and the reaction vessel was sealed and the mixture was heated at 100° C. for 15 h. After cooling to rt, the mixture was purified directly by reverse-phase HPLC using a mixture of water (5% CH3CN, 0.05% HOAc) and CH3CN (0.05% HOAc) as the mobile phase and Varian Pursuit XRs diphenyl column as the stationary phase to afford (1R,2R)-2-((6-((6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (33 mg, 41%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.64 (d, J=1.9 Hz, 1H), 8.56 (s, 1H), 8.26 (d, J=1.9 Hz, 1H), 8.23 (s, 1H), 7.95-8.01 (m, 2H), 7.67 (d, J=1.1 Hz, 1H), 7.20-7.32 (m, 2H), 5.47 (s, 2H), 4.76 (br s, 1H), 3.88 (s, 3H), 3.51 (m, 1H), 3.35 (m, 1H), 2.03 (m, 1H), 1.90 (m, 1H), 1.62 (d, J=4.7 Hz, 2H), 1.10-1.33 (m, 4H). LCMS (ESI) m/z 460 (M+H)+.

Provenance & Evidence