Water → HCID 178521539, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of (1R,2R)-2-((6-((5-iodo-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (100 mg, 0.20 mmol) from Step 5 of Example 183 in DMF (2 mL) were added (1H-pyrazol-3-yl)boronic acid (90 mg, 0.80 mmol), NaHCO3 (100 mg 1.2 mmol), bis(triphenylphosphine) palladium(II) dichloride (28 mg, 0.04 mmol), and water (0.4 mL). The mixture was flushed with argon and heated in a sealed vessel at 90° C. for 15 h. The reaction mixture was cooled to rt and partitioned between DCM and water. The aqueous layer was extracted twice with DCM and the combined organic phases were washed three times with a 1:1 mixture of water and brine. The organic phases were then dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography eluting with 100% DCM to 10% MeOH/DCM to afford (1R,2R)-2-((6-((5-(1H-pyrazol-3-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (4 mg, 5%) as a solid. 1H NMR (500 MHz, DMSO-d6) δ 12.92 (br s, 1H), 12.53 (br s, 1H), 8.29 (br s, 1H), 8.03 (m, 1H), 7.58-7.74 (m, 3H), 7.53 (d, J=7.9 Hz, 1H), 7.31 (d, J=7.9 Hz, 1H), 7.20 (d, J=8.4 Hz, 1H), 6.63 (br s, 1H), 5.47 (s, 2H), 4.42 (d, J=4.4 Hz, 1H), 3.51 (br s, 1H), 3.41 (tt, J=4.5, 8.8 Hz, 1H), 2.06 (m, 1H), 1.90 (d, J=11.8 Hz, 1H), 1.57-1.71 (m, 2H), 1.19-1.36 (m, 4H); LCMS (ESI) m/z 445 (M+H)+.

Provenance & Evidence