反应详情

1-[2-(4-Amino-1-piperidinyl)ethyl]-5,7-difluoro-2(1H)-quinolinone (150 mg; 0.49 mmol) and 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carboxaldehyde (for a synthesis see WO2004058144, Example 2(c) or WO03/087098, Example 19(d)) (80 mg; 0.49 mmol) were dissolved in a 5:1 mixture of chloroform and MeOH (5 ml: 1 ml) and stirred at rt for 1 h. This was then treated with NaBH(OAc)3 (310 mg; 1.47 mmol) and stirred for a further 2 h under the same conditions. The solvents were then removed from the reaction and the crude residues purified by column chromatography on silica gel using a 0-20% 2M NH3:MeOH/DCM gradient. Fractions containing the desired product were concentrated to afford the free base of the title compound (200 mg; 89%) however this was shown to be impure so was further purified by MDAP to afford the title compound (30 mg; 14%) directly as the diformate salt.

1. stirringstirred for a further 2 h under the same conditions
2. customThe solvents were then removed from the reaction
3. customthe crude residues purified by column chromatography on silica gel using a 0-20% 2M NH3
4. additionFractions containing the desired product
5. concentrationwere concentrated