Hydrochloric Acid → butyl 1-[(4-cyclohexylphenyl)(1-methyl-1H-benzimidazol-2-yl)amino]indane-5-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a 0° C. solution of butyl 1-[(4-cyclohexylphenyl)amino]indane-5-carboxylate (0.50 g, 1.27 mmol) and DIEA (0.33 mL, 1.90 mmol) in dry dichloromethane (15 mL) was added thiophosgene (0.10 mL, 1.34 mmol) slowly. After stirring at 0° C. for 10 min and then at room temperature for 1 h, a solution of N-methylbenzene-1,2-diamine (0.23 g, 1.90 mmol) and DIEA (0.33 mL, 1.90 mmol) in dry dichloromethane (5 mL) was added. The reaction mixture was stirred for 1 h at room temperature and then diluted with dichloromethane (30 mL) and poured into aqueous HCl (1N, 30 mL). The organic layer was separated and washed with aqueous HCl (1N, 30 mL), saturated aqueous NaHCO3 (30 mL), brine (30 mL), dried over Na2SO4 and then concentrated to dryness. The residue was dissolved in dichloromethane (30 mL) and excess of mercury (II) trifluoroacetate was added. The reaction mixture was stirred for 30 min at ambient temperature and then filtered through Celite. The organic solution was washed with saturated NaHCO3 (30 mL), dried over Na2SO4 and concentrated. Chromatography (8% to 15% EtOAc in Hexane) afforded butyl 1-[(4-cyclohexylphenyl)(1-methyl-1H-benzimidazol-2-yl)amino]indane-5-carboxylate. HPLC/MS: m/z=552.4 (M+1), Rt=2.58 min. 1H NMR (CDCl3): δ 7.96 (1H, d, J=7.8 Hz), 7.91 (1H, s), 7.70 (1H, d, J=7.5 Hz), 7.55 (1H, d, J=7.5 Hz), 7.27-7.20 (2H, m), 7.18 (1H, d, J=7.5 Hz), 7.01 (2H, d, J=8.5 Hz), 6.67 (2H, d, J=8.5 Hz), 6.20 (1H, t, J=7.5 Hz), 4.37 (1H, t, J=6.5 Hz), 3.21 (3H, s), 2.91-2.85 (1H, m), 2.77-2.64 (2H, m), 2.46-2.34 (2H, m), 1.86-1.75 (8H, m), 1.54 (2H, m), 1.41-1.24 (6H, m), 1.04 (3H, t, J=7.5 Hz).

Provenance & Evidence