反应详情

A solution of 4-[2-(4-amino-1-piperidinyl)ethyl]-6-(methyloxy)pyrido[2,3-b]pyrazin-3(4H)-one (150 mg, 0.494 mmoles) 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)) (82 mg, 0.496 mmoles) in anhydrous DCM (10 ml) and anhydrous MeOH (1 ml) was stirred at rt for 5 minutes. Sodium triacetoxyborohydride (316 mg, 1.49 mmoles) was added and the mixture was stirred, under argon, for 18 h, treated with sat. aq. NaHCO3 solution (5 ml) and 10:1 DCM:MeOH (10 ml). The layers were separated and the aqueous layer was washed with 10:1 DCM:MeOH (5 ml). The organic extracts were combined, washed with brine, passed through a hydrophobic frit and evaporated to an orange gum. Purification on a 20 g silica column eluted with a 0% to 30% DCM/MeOH gradient elution gave the free base of the title compound as a colourless gum (128 mg, 57%).

1. customThe layers were separated
2. washthe aqueous layer was washed with 10:1 DCM
3. washwashed with brine
4. customevaporated to an orange gum
5. customPurification on a 20 g silica column
6. washeluted with a 0% to 30% DCM/MeOH gradient elution