Acetic Acid → 6-(4-{[2-Fluoro-3-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)propyl]amino}-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-one

Participants

Reaction Steps

A crude product of 2-Fluoro-3-(7-methoxy-2-oxoquinoxalin-1(2H)-yl)propanal (196 mg) and 6-(4-amino-2-oxopyrrolidin-1-yl)-2H-1,4-benzoxazin-3(4H)-one (Reference Example 6; 147 mg, 0.595 mmol) were dissolved in a mixed solution of dichloromethane (20 ml) and N,N-dimethylformamide (2 ml). Acetic acid (0.068 ml, 1.190 mmol) and anhydrous sodium sulfate (300 mg) were added to the solution at room temperature and the mixture was stirred for 14 hours. Sodium triacetoxyborohydride (252 mg, 1.190 mmol) was added to the reaction solution, the mixture was stirred for 4 hours and then the solvent was removed under reduced pressure. A lower layer solvent of chloroform/methanol/water (7:3:1) was added to the residue and the resultant was alkalized by adding saturated sodium bicarbonate water under cooling on ice. The mixture was extracted with a lower layer solvent of chloroform/methanol/water (7:3:1), the extract was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol) and preparative thin layer chromatography (silica gel, chloroform/methanol=20:1) to yield 50 mg (18%) of the title compound in the form of a white solid.

Provenance & Evidence