To a mixture of [4-{2-[(3S,4R)-3-(aminomethyl)-4-hydroxy-1-piperidinyl]ethyl}-6-(methyloxy)pyrido[2,3-b]pyrazin-3(4H)-one (for a preparation see Example 135(i); 0.157 g; 0.471 mmol) in anhydrous DCM (20 mL) and anhydrous MeOH (4 mL) was added 2,3-dihydro[1,4]dioxino[2,3-c]pyridine-7-carbaldehyde (for a synthesis see WO2004058144, Example 2(c) or WO03/087098, Example 19(d)) (0.042 g; 0.471 mmol) and activated 4A sieves. The reaction was stirred under N2 for 18 h. The crude intermediate was treated with sodium triacetoxyborohydride (0.942 mmol; 199 mg) and stirred for 2 h. The product was obtained as a pale yellow oil after column:chromatography (90:10:0.5:DCM:MeOH:NH4OH) to yield 24 mg (11%) of the free base of the title compound. The bis-HCl salt was made by addition of 1N HCl/ether (0.098 mL) to yield the title compound as a light brown solid.
