Reaction Steps
A stirred mixture of (1R,2R)-2-((6-((5-iodo-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (300 mg, 0.59 mmol) from Step 5 of Example 183, 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (188 mg, 0.89 mmol), Na2CO3 (126 mg, 1.19 mmol), 1,4-dioxane (3 mL) and water (0.5 mL) was purged with a stream of nitrogen for 10 min. [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium (II) (44 mg, 0.59 mmol) was added and the mixture was heated at 100° C. for 2 h. The reaction mixture was cooled to rt and partitioned between EtOAc and water. The organic layer was separated, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with 30:1 DCM: MeOH and then by reverse-phase preparative HPLC to afford (1R,2R)-2-((6-((5-(3,6-dihydro-2H-pyran-4-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (54 mg, 20%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.38 (s, 1H), 7.94 (d, J=7.8 Hz, 1H), 7.67 (d, J=1.5 Hz, 1H), 7.63 (d, J=1.8 Hz, 1H), 7.50 (d, J=8.4 Hz, 1H), 7.35 (m, 1H), 7.29 (d, J=8.1 Hz, 1H), 7.18 (m, 1H), 6.19 (s, 1H), 5.46 (s, 2H), 4.71 (d, J=5.1 Hz, 1H), 4.22 (d, J=2.7 Hz, 2H), 3.81-3.84 (m, 2H), 3.51 (m, 1H), 3.38 (m, 1H), 2.02 (m, 1H), 2.00 (m, 1H), 1.61 (br s, 2H), 1.14-1.29 (m, 4H); LCMS (ESI) m/z 460 (M+H)+.
