Formaldehyde → HCID 67371250, compound

Participants

Reaction Steps

To a solution of 3-butyl-4-[4-cyclohexyloxy-3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-6-(piperidin-4-yloxy)-pyridazine dihydrochloride (0.379 mmol, 214 mg) in DCM (2 mL) was added formaldehyde solution in water (37%, 1.14 mmol, 0.085 mL) and 2 drops of acetic acid. Sodium triacetoxyborohydride (1.52 mmol, 339 mg, 95%) was added. The reaction mixture was stirred at room temperature for 1 h and partitioned between ethyl acetate (20 mL) and saturated aq. sodium bicarbonate solution (20 mL). The ethyl acetate layer was separated and dried over sodium sulfate. The crude product was purified by column chromatography on silica gel using 2 M ammonia in MeOH/DCM 1:19 to 1:14, dissolved in MeOH and treated with 4 N HCl in dioxane. The organic solvents were removed in vacuo and the residue was triturated with anhydrous diethyl ether. The yellow solid was dried overnight under high vacuum to provide the title compound (188.2 mg). LCMS: m/z 507 [M+1] 1H NMR (400 MHz, CD3OD) δ 7.85 and 7.93 (1H, s), 7.79-7.85 (1H, m), 7.69 (1H, dd), 7.49-7.53 (1H, m), 5.38-5.56 (1H, m), 4.64-4.69 (1H, m), 4.05 and 4.06 (3H, s), 3.13-3.69 (6H, m), 2.94 (3H, s), 1.97-2.54 (12H, m), 1.30-1.63 (6H, m), 0.84 (3H, dt).

Provenance & Evidence