Sodium Sulfate → 6-Methoxy-4-(3-{[5-oxo-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)pyrrolidin-3-yl]amino}propyl)pyrido[2,3-b]pyrazin-3(4H)-one

Participants

Reaction Steps

In N,N-dimethylformamide (3 ml) were dissolved 6-(4-Amino-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-one (Reference Example 6; 159 mg, 0.643 mmol) and 3-(6-methoxy-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl)propanal (synthesized with reference to WO2008/9700; 150 mg, 0.643 mmol). Sodium sulfate (1.0 g) was added to the solution and the mixture was stirred overnight at room temperature. Sodium triacetoxyborohydride (164 mg, 0.772 mmol) was added to the reaction solution and the mixture was stirred at room temperature for 2 hours. After completion of the reaction, the reaction solution was diluted with dichloromethane, basified by adding a saturated sodium hydrogen carbonate aqueous solution and the organic layer was then separated. The organic layer was washed sequentially with saturated sodium chloride solution, water (3×) and saturated sodium chloride solution, dried over anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform/methanol) to yield 219 mg (73%) of the title compound in the form of a colorless foamy solid.

Provenance & Evidence