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

Participants

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-(aminomethyl)-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Reference Example 54, 175 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 cooled on ice, sodium triacetoxyborohydride (141 mg, 0.66 mmol) was added thereto and stirred overnight at room temperature. Two equivalents of sodium triacetoxyborohydride (282 mg, 1.32 mmol) were further added thereto and the reaction solution was stirred 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. Subsequently, the organic 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 27 mg (11%) of the title compound.

Provenance & Evidence