Cesium carbonate → (1R,2R)-2-((6-((6-(morpholinomethyl)-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 (100 mg, 0.22 mmol) from Example 29, potassium (morpholin-4-yl)methyltrifluoroborate (59 mg, 0.28 mmol), Pd(OAc)2 (1.5 mg, 0.007 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (6.2 mg, 0.013 mmol) and Cs2CO3 (213 mg, 0.66 mmol) in THF/H2O (1.5 mL, 4:1, v/v) was purged with argon for 10 min. The mixture was then heated at 85° C. in a sealed reaction vessel overnight. LCMS showed the reaction complete. After cooling to rt, the reaction mixture was filtered through a Celite plug and the filtrate was purified by reverse-phase preparative 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-((6-(morpholinomethyl)-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol as a white powder (36 mg, 35%). 1H NMR (300 MHz, DMSO-d6) δ 8.57 (s, 1H), 8.31 (d, J=1.5 Hz, 1H), 7.88-8.04 (m, 2H), 7.67 (d, J=0.9 Hz, 1H), 7.26-7.33 (m, 1H), 7.17-7.26 (m, 1H), 5.46 (s, 2H), 4.75 (br s, 1H), 3.60 (s, 2H), 3.45-3.58 (m, 5H), 2.36 (br s, 4H), 2.03 (d, J=10.4 Hz, 1H), 1.79-1.89 (m, 1H), 1.62 (d, J=5.1 Hz, 2H), 1.05-1.37 (m, 4H). LCMS (ESI) m/z 479 (M+H)+.

Provenance & Evidence