N,N-diisopropylethylamine (0.166 mL, 0.953 mmol) was added to a stirred suspension of [2-(1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}piperidin-4-yl)-5-chlorophenyl]acetic acid (1-10) (40.0 mg), methylamine.HCl (42.9 mg, 0.635 mmol), O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (48.3 mg, 0.127 mmol) and 1-hydroxy-7-azabenotriazole (17.3 mg, 0.127 mmol) in N,N-dimethylformamide (0.65 mL) at ambient temperature. After approximately 18 h, the reaction mixture was poured into saturated aqueous sodium bicarbonate and extracted three times with ethyl acetate. The combined organic extracts were washed with water, brine, dried (Na2SO4) and concentrated in vacuo. Purification of the residue by preparative reversed phase high pressure liquid chromatography on YMC Pack Pro C18 phase (gradient elution; 0%-100% acetonitrile/water as eluent, 0.1% TFA modifier) gave 1-11 as a buff white solid (m/z (ES) 532 (MH+).
