A solution of methyl 4-[3-(6-cyano-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)propyl]piperidine-3-carboxylate trifluoroacetate (Intermediate 130, crude, 171, 0.48 mmol), (2E)-3-(2,5-difluorophenyl)acrylaldehyde [FR 2872164] (81 mg, 0.48 mmol), and triethylamine (0.13 mL. 0.96 mmol) in chloroform/methanol (6 mL, 10:1) was heated over 3 Å molecular sieves at 70° C. for 3 hours. The reaction mixture was cooled to 0° C., and sodium triacetoxy borohydride (200 mg, 0.94 mmol) was added. The resulting reaction mixture was allowed to warm to room temperature and stir for 18 hours. The reaction was diluted with ethyl acetate (25 mL) and water (10 mL). The aqueous phase was separated and washed twice with ethyl acetate. The organic layers were combined, dried over magnesium sulfate and evaporated at reduced pressure. Chromatography on silica gel with diethyl ether gave the title compound as a off-white foam, (79 mg, 32%).
