Reaction Steps
A slurry of N-{2-[(3R)-1,3′-bipyrrolidin-3-ylamino]-2-oxoethyl}-3-(trifluoromethyl)benzamide (50 mg, 0.13 mmol), methyl 4-bromobenzoate (35 mg, 0.16 mmol), Pd2(dba)3 (12 mg, 0.013 mmol), cesium carbonate (64 mg, 0.19 mmol) and R-BINAP (8 mg, 0.013 mmol) in toluene was heated at 100° C. overnight. To the mixture was added NaHCO3 (sat. aq., 10 mL) and dichloromethane (10 mL). The organic layer was separated and the aqueous layer was washed with an addition portion of dichloromethane (10 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The resulting crude product was subjected to flash chromatography (15% MeOH, 1% NH4OH in EtOAc) to afford, as a mixture of diastereomers, methyl 4-{(3R)-3-[({[3-(trifluoromethyl)benzoyl]amino}acetyl)amino]-1,3′-bipyrrolidin-1′-yl}benzoate (20 mg, 30%) as a white solid. 1H-NMR (CDCl3) δ: 1.60-1.76 (m, 1H), 1.86-2.04 (m, 1H), 2.08-2.25 (m, 1H), 2.20-2.44 (m, 2H), 2.60-2.78 (m, 2H), 2.84-3.00 (m, 2H), 3.18 (q, J=8.7 Hz, 1H), 3.32 (q, J=7.5 Hz, 1H), 3.40-3.54 (m, 2H), 3.82 (s, 3H), 4.10 (m, 2H), 4.40-4.56 (m, 1H), 6.44 (d, J=8.7 Hz, 2H), 6.54 (d, J=2.4 Hz, 1H), 7.20-7.35 (m, 1H), 7.54 (t, J=7.8 Hz, 1H), 7.74 (d, J=8.1 Hz, 1H), 7.87 (d, J=8.4 Hz, 2H), 7.97 (d, J=7.8 Hz, 1H), 8.07 (s, 1H). MS m/z: 519 (M+1)
