Formaldehyde → (+/-)-trans-3-Butyl-4-(4-cyclohexyloxy-phenyl)-6-(3-fluoro-1-methyl-piperidin-4-yloxy)-pyridazine

Participants

Reaction Steps

To a stirred solution of (±)-trans-3-butyl-4-(4-cyclohexyloxy-phenyl)-6-(3-fluoro-piperidin-4-yloxy)-pyridazine (20 mg, 0.047 mmol) in DCM (4 mL) was added 37% aqueous formaldehyde (0.1 mL, 1 mmol) and sodium triacetoxyborohydride (106 mg, 0.5 mmol). After 2 hrs the mixture was diluted with saturated aqueous NaHCO3 and extracted with DCM. The organics were dried over sodium sulfate, filtered, concentrated, and purified by column chromatography using 2-5% methanolic solution of ammonia (2.0 M ammonia in methanol) in DCM to give (±)-trans-3-Butyl-4-(4-cyclohexyloxy-phenyl)-6-(3-fluoro-1-methyl-piperidin-4-yloxy)-pyridazine. The free base was dissolved in DCM, treated with 4.0 M HCl in dioxane and concentrated. The resultant salt was washed with ether and dried to provide the title compound (20 mg). LCMS: m/z 443 [M+1]. 1H NMR (400 MHz, CD3OD) δ 7.93 (1H, s), 7.51 (2H, d), 7.14 (2H, d), 5.54-5.60 (1H, m), 5.29 (1H, d), 4.41-4.50 (1H, m), 3.64-3.94 (2H, m), 3.46-3.53 (2H, m), 3.14-3.21 (2H, m), 3.00 (3H, t), 2.40-2.50 (2H, m) 1.96-2.05 (2H, m), 1.77-1.86 (2H, m), 1.23-1.66 (10H, m), 0.82 (3H, t).

Provenance & Evidence