Imidazole → (1R,2R)-2-((6-((5-(1H-imidazol-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol

Participants

Reaction Conditions

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 (250 mg, 0.50 mmol) from Step 5 of Example 183, imidazole (80 mg, 1.18 mmol), potassium carbonate (82 mg, 0.59 mmol), trans-N,N-dimethylcyclohexane-1,2-diamine (9 mg, 0.063 mmol), copper (I) iodide (30 mg, 0.158 mmol) and DMF (2 mL) was heated at 120° C. for 3 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 20:1 DCM: MeOH, to afford (1R,2R)-2-((6-((5-(1H-imidazol-1-yl)-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]thiazol-2-yl)amino)cyclohexanol (78 mg, 35%) as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.52 (s, 1H), 8.18 (s, 1H), 7.91-7.96 (m, 2H), 7.72-7.86 (m, 3H), 7.47 (dd, J=8.4, 1.8 Hz, 1H), 7.30 (d, J=8.1 Hz, 1H), 7.21 (dd, J=8.1, 1.5 Hz, 1H), 7.07 (d, J=1.2 Hz, 1H), 5.52 (s, 2H), 4.71 (d, J=5.1 Hz, 1H), 3.51 (m, 1H), 3.38 (m, 1H), 2.02 (m, 1H), 1.88 (m, 1H), 1.60-1.80 (m, 2H), 1.15-1.28 (m, 4H); LCMS (ESI) m/z 445 (M+H)+.

Provenance & Evidence