N-((1S)-1-{[((1S)-3-Chloro-2-oxo-1-{[(3S)-2-oxopyrrolidin-3-yl]methyl}propyl)amino]carbonyl}pentyl)-4-methoxy-1H-indole-2-carboxamide
Following the procedure described for the preparation of N-((1S)-1-{[((1S)-3-chloro-2-oxo-1-{[(3S)-2-oxopyrrolidin-3-yl]methyl}propyl)amino]carbonyl}-3-methylbutyl)-4-methoxy-1H-indole-2-carboxamide but substituting N2-(tert-butoxycarbonyl)-N1-((1S)-3-chloro-2-oxo-1-{[(3S)-2-oxopyrrolidin-3-yl]methyl}propyl)-l-norleucinamide and making no other critical variations provided a crude yellow foam. This material was purified by Biotage MPLC (25 M column, 3% methanol/chloroform) to afford 254 mg (63%) of the title compound as an off-white solid. 1H NMR (DMSO-d6) δ 11.56 (s, 1H), 8.57 (d, J = 8 Hz, 1H), 8.39 (d, J = 4 Hz, 1H), 7.62 (s, 1H), 7.36 (s, 1H), 7.08 (t, J = 8 Hz, 1H), 6.99 (d, J = 8 Hz, 1H), 6.49 (d, J = 8 Hz, 1H), 4.58 (d, J = 16 Hz, 1H), 4.56 (d, J = 16 Hz, 1H), 4.43 (m, 1H), 4.35 (m, 1H), 3.87 (s, 3H), 3.09 (m, 2H), 2.27 (m, 1H), 2.08 (m, 1H), 1.97 (m, 1H), 1.74–1.54 (m, 4H), 1.30 (m, 4H), 0.86 (t, J = 8 Hz, 3H); MS (ESI+) for C24H31N4O5Cl m/z 491.1 (M + H)+; anal. calcd for C24H31ClN4O5: C, 58.71; H, 6.36; N, 11.41. Found: C, 58.66; H, 6.45; N, 11.22.