Acetic Acid → 3-Methoxy-5-(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-6 (5H)-one

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Reaction Steps

3-(3-Methoxy-6-oxopyrido[2,3-b]pyrazin-5(6H)-yl)propanal (292 mg, 1.25 mmol) and 6-(4-amino-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-one (Reference Example 6; 310 mg, 1.25 mmol) were dissolved in a mixed solvent (33 ml) of dichloromethane/N,N-dimethylformamide (10:1). Acetic acid (0.143 ml, 2.50 mmol) and anhydrous sodium sulfate (600 mg) were added to the solution and the mixture was stirred at room temperature for 13 hours. Sodium triacetoxyborohydride (531 mg, 2.50 mmol) was added to the reaction solution, the mixture was stirred for 4 hours and the solvent was removed under reduced pressure. A lower layer solvent of chloroform/methanol/water (7:3:1) was added to the residue, the resultant was alkalized by adding saturated sodium bicarbonate water under cooling on ice and extracted with a lower layer solvent of chloroform/methanol/water (7:3:1). After drying the extract with anhydrous sodium sulfate, the solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (chloroform/methanol) to yield 170 mg (29%) of the title compound in the form of a white solid.

Provenance & Evidence