Hydrochloric Acid → HCID 67373322, compound

Participants

Reaction Steps

To a solution of 5-[3-butyl-6-(1-methyl-piperidin-4-yloxy)-pyridazin-4-yl]-2-cyclohexyloxy-phenylamine (Example 62, 0.2 mmol, 88 mg) in DCM (2.0 mL) was added isobutyraldehyde (0.3 mmol, 28 μL), and 1 drop of acetic acid. Then sodium triacetoxyborohydride (0.6 mmol, 127 mg) was added. The mixture was stirred at room temperature for 1 hour then condensed. The mixture was then diluted with water/EtOAc. The solvent was removed in vacuo and the residue was again dissolved in DCM (2.0 mL) at 0° C., added acetyl chloride (0.4 mmol, 29 μL), DIEA (0.6 mmol, 105 μL) and DMAP (5 mg). And the mixture was stirred at room temperature for 1 hour. It was then condensed in vacuo and the residue was purified by silica gel chromatography (DCM to DCM+10% 2N NH3 in MeOH) to give a colorless sticky solid, which was dissolved in DCM (1.0 mL), 2N HCl in ether (1.0 mL) was added, kept at room temperature for 10 min, condensed, triturated with hexanes to provide the title compound (41 mg). LCMS: m/z 537 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.40-7.43 (1H, m), 7.28-7.35 (2H, m), 7.07 (1H, s), 5.52 (1H, bs), 4.53-4.59 (1H, m), 3.65-3.71 (1H, m), 3.29-3.47 (7H, m), 2.92-2.97 (2H, m), 2.89 (3H, s), 2.18-2.37 (4H, m), 1.99-2.07 (2H, m), 1.84 (3H, s), 1.25-1.83 (9H, m), 1.18-1.26 (2H, m), 0.91-0.95 (6H, m), 0.80 (3H, t).

Provenance & Evidence