Hydrochloric Acid → HCID 178458667, compound

Participants

Reaction Steps

A solution of (R)-5-fluoro-2-(1-(4-fluorophenyl)-2-hydroxyethylamino)-6-(5-isopropoxy-1H-pyrazol-3-ylamino)nicotinonitrile (Example 11; 0.60 g, 1.44 mmol), conc. HCl (0.3 ml), and Pd (10 wt. %, dry basis, on activated carbon, 0.3 g) in MeOH (8 ml) was flushed with N2, evacuated, and then placed under of H2 (40 psi) for 6 hrs. The reaction was then evacuated, flushed with N2, filtered, washed with MeOH (3×30 ml), and concentrated. The resulting solid was dissolved in the mixture of DCM-MeOH (50:1, 100 ml) and treated with a saturated aqueous Na2CO3 solution (100 ml). The resulting mixture was shaken vigorously for 30 min and allowed to separate. The aqueous layer was extracted with DCM (3×100 ml). The combined organic layers were dried, filtered and concentrated. The resulting solid was purified by reverse-phase column chromatography (5-50% CH3CN in H2O over 400 ml) to give the title compound (0.40 g, 66%). 1H NMR (400 MHz, CD3OD) δ 7.47-7.44 (m, 2H), 7.37 (d, J=10.7 Hz, 1H), 7.06-7.02 (m, 2H), 5.10-5.06 (m, 1H), 4.57-4.51 (m, 1H), 4.28 (d, J=14.2 Hz, 1H), 4.07 (d, J=14.2 Hz, 1H), 3.92-3.80 (m, 2H), 1.32 (d, J=3.7 Hz, 6H). MS: Calcd.: 418. Found: [M+H]+ 419.

Provenance & Evidence