[(S)-1-(3-Pyrrolidin-1-yl-propylcarbamoyl)-2-thiophen-2-yl-ethyl]-carbamic acid tert-butyl ester. To a mixture of EDC (0.53 g, 2.77 mmol), HOBT (0.37 g, 2.77 mmol) and (S)-2-tert-butoxycarbonylamino-3-thiophen-2-yl-propionic acid (0.5 g, 1.85 mmol) in DMF (10 mL), 3-pyrrolidin-1-yl-propylamine (3.85 g, 30 mmol) was added followed by N-methyl morpholine (0.37 g, 3.69 mmol) at rt. The solution was stirred for 15 h, diluted with EtOAc (150 mL), washed with saturated NaHCO3 (2×50 mL) and brine (2×50 mL), and dried (Na2SO4). The solvent was removed, and the residue was stirred in a mixture of 10% EtOAc/hexanes at 0° C. for 0.5 h to afford 0.45 g (64%) of the desired product as a white solid. MS (electrospray): mass calculated for C19H14N3O3S, 381.21; m/z found, 382.2 [M+H]+, 404.2 [M+Na]+. 1H NMR (400 MHz, CD3OD): 7.22 (d, J=4.9 Hz, 1H), 6.93–6.87 (m, 2H), 4.22 (t, J=7.2 Hz, 1H), 3.31–3.09 (m, 4H), 2.54 (br m, 4H), 2.46 (t, J=7.6 Hz, 2H), 1.8 (br m, 4H), 1.67 (m, 2H), 1.41 (s, 9H).
