Hydrochloric Acid → HCID 178468861, Verbindung

Temperatur

0 °C

To a 0° C. solution of ethyl 4-{1-[(trans-4-tert-butylcyclohexyl)amino]ethyl}benzoate (0.55 g, 1.66 mmol) and DIEA (0.35 mL, 1.99 mmol) in dry dichloromethane (15 mL) was slowly added thiophosgene (0.13 mL, 1.66 mmol). After stirring at 0° C. for 10 min and then at room temperature for 45 min, a solution of N-methylbenzene-1,2-diamine (0.22 g, 1.83 mmol) and DIEA (0.35 mL, 1.99 mmol) in dry dichloromethane (5 mL) was added. The reaction mixture was stirred for 1 h at ambient temperature and then diluted with dichloromethane (20 mL) and poured into aqueous HCl (1N, 20 mL). The organic layer was separated and washed with aqueous HCl (1N, 20 mL), saturated aqueous NaHCO3 (20 mL), brine (20 mL), dried over Na2SO4 and then concentrated to dryness. The residue was dissolved in dichloromethane (20 mL) and mercury (II) trifluoroacetate (0.80 g, 1.86 mmol) was added. The reaction mixture was stirred for 30 min at room temperature and then filtered through Celite. The organic solution was washed with saturated NaHCO3 (20 mL), dried over Na2SO4 and concentrated. Chromatography (15% EtOAc in Hexane) afforded ethyl 4-{1-[(trans-4-tert-butylcyclohexyl)(1-methyl-1H-benzimidazol-2-yl)amino]ethyl}benzoate. HPLC/MS: m/z=462.4 (M+1), Rt=3.46 min. 1H NMR (500 MHz, CDCl3): □ 8.03 (2H, d, J=8.2 Hz), 7.78 (1H, m), 7.52 (2H, d, J=8.2 Hz), 7.28 (3H, m), 4.80 (1H, q, J=6.5 Hz), 4.39 (2H, q, J=7.5 Hz), 3.72 (3H, s), 2.86 (1H, m), 2.14 (1H, m), 1.94 (1H, m), 1.72-1.64 (2H, m), 1.48 (1H, m), 1.41 (3H, t, J=7.5 Hz), 1.17 (3H, d, J=6.5 Hz), 0.95-0.75 (4H, m), 0.73 (9H, s).

1. customTo a 0° C.
2. waitat room temperature for 45 min
3. stirringThe reaction mixture was stirred for 1 h at ambient temperature
4. customThe organic layer was separated
5. washwashed with aqueous HCl (1N, 20 mL), saturated aqueous NaHCO3 (20 mL), brine (20 mL)
6. dry with materialdried over Na2SO4
7. concentrationconcentrated to dryness
8. dissolutionThe residue was dissolved in dichloromethane (20 mL)
9. stirringThe reaction mixture was stirred for 30 min at room temperature
10. filtrationfiltered through Celite
11. washThe organic solution was washed with saturated NaHCO3 (20 mL)
12. dry with materialdried over Na2SO4
13. concentrationconcentrated

ORD-Eintrag

ord-2b877f7e8745481cafb2e8ba33458b5f

Quelldatensatz

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07563815B2