Hydrochloric Acid → HCID 67387597, 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 dry DCM (1.0 mL) was added 4-bromobutyryl chloride (0.4 mmol, 47 μL), DIEA (0.4 mmol, 70 μL), and DMAP (10 mg). And the mixture was stirred at room temperature for 1 hour then condensed. It was then diluted with water/EtOAc. The solvent was removed in vacuo and dried under vacuum over night. The residue was dissolved in dry THF (1.0 mL) at 0° C., NaH (60% dispersion in mineral oil, 0.8 mmol, 32 mg) was added and the mixture was heated at 50° C. for 1 hour. It was then poured into ice-water and extracted with ethyl acetate. The organic layers were combined, condensed 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 (25 mg). LCMS: m/z 508 [M+1]. 1H NMR (400 MHz, CD3OD): δ 7.56 and 7.67 (1H, s), 7.41-7.48 (1H, m), 7.33-7.37 (1H, m), 7.25-7.31 (1H, m), 5.36-5.55 (1H, m), 4.52-4.58 (1H, m), 3.20-3.70 (8H, m), 3.07-3.13 (2H, m), 2.93 (3H, s), 1.92-2.59 (8H, m), 1.27-1.82 (12H, m), 0.80 (3H, t).

Provenance & Evidence