Triethylamine → 6-{[(1-{2-[7-(methyloxy)-2-oxo-1,5-naphthyridin-1(2H)-yl]ethyl}-4-piperidinyl)amino]methyl}-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one Hydrochloride

Participants

Reaction Steps

A mixture of 1-[2-(4-amino-1-piperidinyl)ethyl]-7-(methyloxy)-1,5-naphthyridin-2(1H)-one dihydrochloride (164 mg, 0.440 mmol) in chloroform (5 ml) and MeOH (0.5 ml) was treated with triethylamine (194 μl, 1.40 mmol) and stirred for 0.25 h before addition of 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carboxaldehyde (for a synthesis see WO2003087098, Example 31(e)) (71 mg, 0.40 mmol). The reaction was stirred for 0.5 h before addition of NaBH(OAc)3 (254 mg, 1.20 mmol). The reaction was stirred for a further 0.5 h before addition of sat. aq NaHCO3 (20 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 (144 mg, 71%).

Provenance & Evidence