N-{1-[4-((R)-2-Nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazin-7-ylmethoxy)phenyl]piperidin-4-yl}-N-[4-(4-trifluoromethoxybenzyloxy)phenyl]amine (0.30 g) was suspended in methanol (3 ml). A 37% formaldehyde aqueous solution (0.11 g), sodium cyanoborohydride (89 mg) and acetic acid (1 ml) were added to the suspension and stirred at room temperature for 1 day. A 37% formaldehyde aqueous solution (0.22 g), sodium cyanoborohydride (178 mg) and acetic acid (2 ml) were further added to the mixture and stirred at room temperature for 1 day. The reaction mixture was gradually added to a potassium carbonate aqueous solution, followed by extraction with methylene chloride. The organic layer was washed with a saturated sodium chloride aqueous solution and dried over sodium sulfate, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by medium pressure silica gel column chromatography (methylene chloride:methanol=10:0→methylene chloride:methanol=9:1) and recrystallized from methanol to afford the title compound as a pale brown powder (0.20 g).
