Sodium Bicarbonate → 6-[({1-[2-(6-Methoxy-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl)ethyl]piperidin-4-yl}amino)methyl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

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Reaction Steps

A solution of 4-[2-(4-amino-1-piperidinyl)ethyl]-6-(methyloxy)pyrido[2,3-b]pyrazin-3(4H)-one (50 mg, 0.1648 mmoles) and 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carboxaldehyde (for a synthesis see WO2003087098, Example 31(e)) (29.4 mg, 0.1648 mmoles) in anhydrous DCM (5 ml) and anhydrous MeOH (0.5 ml) was stirred at rt for 5 mins. Sodium triacetoxyborohydride (104.7 mg, 0.494 mmoles) was added and the mixture was stirred, under argon, for 24 h. The reaction was treated with sat. aq. NaHCO3 solution (2 ml) and 9:1 DCM:MeOH (5 ml). The layers were separated and the aqueous layer was washed with 9:1 DCM:MeOH (10 ml) and 5:1 DCM:MeOH (2×20 ml). The organic extracts were combined, passed through a hydrophobic frit and evaporated to an orange gum. Purification on a 10 g silica column eluted with an 80:20 DCM:MeOH elution gave the product as a yellow gum (39.8 mg, 52%).

Provenance & Evidence