反应详情

To a solution of 2-(4-chlorophenyl)-6-{[6-(piperidin-4-yloxy)pyridin-2-yl]methyl}thieno[2,3-d]pyridazin-7(6H)-one (0.16 g, 0.34 mmol) in DCM/MeOH (1:1, 10 mL) was added (polystyrylmethyl)trimethylammonium cyanoborohydride (0.25 g, 1.03 mmol), 36% aq. formaldehyde (0.05 mL, 0.69 mmol) and acetic acid (one drop). After 3 hours of stirring one additional amount of (polystyrylmethyl)trimethylammonium cyanoborohydride, formaldehyde and acetic acid added to the reaction mixture and stirred for two hours. The reaction mixture was filtrated, concentrated in vacuo and purified by flash chromatography using a gradient with EtOAc:MeOH:TEA (1:0.1:0.05) in n-heptane, which gave the product. Yield: 0.084 g (52%). 1H NMR (400 MHz, CDCl3) δ 8.19 (s, 1H), 7.57-7.64 (m, 2H), 7.30-7.49 (m, 4H), 6.71 (d, 1H, J=7.31 Hz), 6.52 (d, 1H, J=8.16 Hz), 5.47 (s, 2H), 4.69-4.79 (m, 1H), 2.49-2.58 (m, 2H), 2.13 (s, 3H), 1.87-1.99 (m, 2H), 1.75-1.84 (m, 2H), 1.58-1.69 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 163.0, 157.4, 153.5, 152.3, 140.3, 139.3, 136.4, 136.0, 133.1, 131.3, 129.8, 128.1, 113.8, 110.1, 70.5, 55.6, 53.3, 46.4, 31.0 MS (ESI+) 467.08 (M+1H+).

1. additionadded to the reaction mixture
2. filtrationThe reaction mixture was filtrated
3. concentrationconcentrated in vacuo
4. custompurified by flash chromatography
5. customgave the product