Hydrochloric Acid → HCID 178437584, compound

Participants

Reaction Conditions

Reaction Steps

4-Ethyl-2-(4-iodo-2-methoxy-pyridin-3-yl)-5-phenyl-imidazol-1-ol (0.379 g, 0.90 mmol) was dissolved in acetic acid/hydrochloric acid (2 ml/2 mL) and the resulting mixture was stirred at 95° C. for 1 hour. The solvent was evaporated and the crude residue (HPLC 95% (220 nm), LCMS (+ESI, M+H+) m/z 408) was dissolved in methanol (6 mL) and treated with titanium (III) chloride (9.25 wt % in 27.4 wt % hydrochloric acid, ˜1 mL). The reaction was heated at 65° C. for ˜2.5 hours, then water was added and the solvent was evaporated to give a residue (HPLC 83% (220 nm), LCMS (+ESI, M+H+) m/z 392) which was dissolved in N,N-dimethylformamide (6 mL). The resulting solution was treated with triethylamine (0.38 mL, 2.7 mmol) and the hydrochloric acid salt of (S)-2-amino-1-[3-chlorophenyl]ethanol (0.281 g, 1.35 mmol) and this was heated at 65° C. for 4 hours. The solvent was evaporated and the residue was purified by Prep HPLC (ammonium acetate/acetonitrile/water) to give the title compound (0.132 g, 34%) as a beige solid. HPLC 97.5% (220 nm), LCMS (+ESI, M+H+) m/z 435; IR ν (cm−1): 3261, 2965, 1642; 1H NMR (400 MHz, methanol-d4) δ (ppm): 1.36 (3H, t, J=7.5 Hz), 2.97 (2H, qa, J=7.5 Hz), 3.64 (1H, dd, J=13.5 and 6.9 Hz), 3.70 (1H, dd, J=13.7 and 5.0 Hz), 4.97 (1H, br t), 6.25 (1H, d, J=7.5 Hz), 7.21-7.33 (4H, m), 7.35-7.47 (4H, m), 7.52 (1H, s), 7.69 (1H, d).

Provenance & Evidence