Acetic Acid → 6-[(4R)-4-{[3-(3-Methoxy-6-oxopyrido[2,3-b]pyrazin-5 (6H)-yl)propyl]amino}-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

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Reaction Steps

To a solution of 3-(3-methoxy-6-oxopyrido[2,3-b]pyrazin-5 (6H)-yl)propanal (Reference Example 24, 120 mg, 0.515 mmol) in N,N-dimethylformamide (1.6 ml) were added 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, 22; 166 mg, 0.66 mmol) and acetic acid (0.04 ml, 0.66 mmol) and the mixture was stirred at room temperature for 30 minutes. The reaction solution was then cooled on ice and sodium triacetoxyborohydride (141 mg, 0.66 mmol) was added thereto. After stirring overnight, sodium triacetoxyborohydride (282 mg, 1.32 mmol) was added to the reaction solution, which was further stirred at room temperature for 2 days. A sodium hydrogen carbonate aqueous solution was added to the reaction solution, which was then extracted with ethyl acetate and the obtained organic layer was washed with water and saturated sodium chloride solution. The layer was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The obtained crude product was purified by thin layer chromatography (dichloromethane/methanol) to yield 21 mg (9%) of the title compound.

Provenance & Evidence