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

Temperatur

0 °C

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).

1. waitat room temperature for 1 h
2. stirringThe reaction mixture was stirred for 1 h at room temperature
3. customThe organic layer was separated
4. washwashed with aqueous HCl (1N, 30 mL), saturated aqueous NaHCO3 (30 mL), brine (30 mL)
5. dry with materialdried over Na2SO4
6. concentrationconcentrated to dryness
7. dissolutionThe residue was dissolved in dichloromethane (30 mL) and excess of mercury (II) trifluoroacetate
8. additionwas added
9. stirringThe reaction mixture was stirred for 30 min at ambient temperature
10. filtrationfiltered through Celite
11. washThe organic solution was washed with saturated NaHCO3 (30 mL)
12. dry with materialdried over Na2SO4
13. concentrationconcentrated

ORD-Eintrag

ord-d4ad76e7a6364643bc41da12fd4ff3db

Quelldatensatz

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07563815B2