反应详情

A mixture of 1-[2-(4-amino-1-piperidinyl)ethyl]-7-fluoro-1,5-naphthyridin-2(1H)-one dihydrochloride (127 mg, 0.350 mmol) in chloroform (5 ml) and MeOH (0.1 ml) was treated with triethylamine (154 μl, 1.018 mmol) and stirred for 0.25 h before addition of 6,7-dihydro[1,4]dioxino[2,3-c]pyridazine-3-carbaldehyde (53 mg, 0.318 mmol). The reaction was stirred for 0.5 h before addition of NaBH(OAc)3 (202 mg, 0.954 mmol). The reaction was stirred for 0.5 h before addition of sat. aq NaHCO3 (50 ml). The reaction was then extracted with 20% MeOH in DCM (3×200 ml). The combined organic phases were dried, evaporated and the crude residue purified by chromatography on silica gel using a 0-20% MeOH/DCM gradient to provide the free base of the title compound (46 mg, 30%).

1. extractionThe reaction was then extracted with 20% MeOH in DCM (3×200 ml)
2. customThe combined organic phases were dried
3. customevaporated
4. customthe crude residue purified by chromatography on silica gel using a 0-20% MeOH/DCM gradient