To a round-bottomed flask equipped with magnetic stirring was added N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-2-piperidylcarboxamide, trifluoroacetate (Step 2) (0.16 mmol), ClCH2CH2Cl (1 mL) and DIEA (Aldrich) (0.06 mL, 0.32 mmol). Formaldehyde (Aldrich, 37% aqueous soln) (0.03 mL, 0.33 mmol) was added to the reaction mixture, followed by NaBH(OAc)3 (Aldrich Chemical Company) (52 mg, 0.25 mmol), and the reaction mixture was stirred at RT 18 h. The mixture was diluted with CH2Cl2, and the organic solution was washed with satd NaHCO3 and brine. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash column chromatography (silica gel, 5:95 MeOH—CH2Cl2) to give N-[(1R)-1-[(4-chlorophenyl)methyl]-2-(4-{2-[(methylsulfonyl)amino]phenyl}piperazinyl)-2-oxoethyl]-(1-methyl(2-piperidyl))carboxamide as a white solid, (71 mg) (two diastereomers). MS (ESI, pos. ion) m/z: 562 (M+H); (ESI, neg. ion) m/z: 560 (M−H). Calc'd for C27H36ClN5O4S: 561.22.
