Acetic Acid → 6-[(4R)-4-{[3-(6-Methoxy-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl)propyl]amino}-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

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Reaction Steps

Acetic acid (0.06 g, 1 mmol) was added dropwise to a mixture of 3-(6-methoxy-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl)propanal (synthesized with reference to WO2008/9700; 0.2 g, 0.85 mmol), 6-[(4R)-4-amino-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (synthesized using [(3R)-5-oxopyrrolidin-3-yl]carbamic acid tert-butyl ester synthesized with reference to WO2004/22536 in the same manner as in Reference Examples 20, 21 and 22; 0.25 g, 1.0 mmol) and N,N-dimethylformamide (4 ml). The mixture was cooled on ice and sodium triacetoxyborohydride (0.23 g, 1.1 mmol) was gradually added thereto. The mixture was stirred for 10 minutes under cooling on ice and subsequently stirred at room temperature for 2 hours. The reaction solution was cooled on ice again and a sodium hydrogen carbonate aqueous solution was added thereto. The obtained mixture was extracted with dichloromethane and the extract was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained crude product was purified by silica gel column chromatography (dichloromethane/methanol) to yield 90 mg (23%) of the title compound.

Provenance & Evidence