反应详情

To a mixture of 3-butyl-4-{4-cyclohexyloxy-3-[1-(2-methoxy-ethyl)-1H-pyrazol-4-yl]-phenyl}-6-(piperidin-4-yloxy)-pyridazine dihydrochloride (0.0776 mmol, 49.9 mg) in DCM (1 mL) was added formaldehyde solution in water (37%, 0.23 mmol, 0.017 mL), and 1 drop of acetic acid. Sodium triacetoxyborohydride (0.31 mmol, 69.2 mg, 95%) was added. The reaction mixture was stirred at room temperature for 1 h and partitioned between ethyl acetate (10 mL) and saturated aq. sodium bicarbonate solution (10 mL). The ethyl acetate layer was separated and dried over sodium sulfate. The crude product was purified by column chromatography on basic alumina using 0-3% MeOH in DCM, 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 (30.1 mg). LCMS: m/z 549 [M+1] 1H NMR (400 MHz, CD3OD) δ 8.24-8.27 (1H, m), 8.04-8.07 (1H, m), 7.90-7.98 (1H, m), 7.78-7.83 (1H, m), 7.37-7.43 (1H, m), 7.27-7.31 (1H, m), 5.37-5.46 (1H, m), 4.59-4.62 (1H, m), 4.38 (2H, t), 3.77 (2H, t), 3.16-3.66 (9H, m), 2.95 (3H, s), 1.25-2.59 (18H, m), 0.82 (3H, t).

1. custompartitioned between ethyl acetate (10 mL) and saturated aq. sodium bicarbonate solution (10 mL)
2. customThe ethyl acetate layer was separated
3. dry with materialdried over sodium sulfate
4. customThe crude product was purified by column chromatography on basic alumina using 0-3% MeOH in DCM
5. dissolutiondissolved in MeOH
6. additiontreated with 4 N HCl in dioxane
7. customThe organic solvents were removed in vacuo
8. customthe residue was triturated with anhydrous diethyl ether
9. customThe yellow solid was dried overnight under high vacuum