N-((1S)-1-{[((1S)-3-Hydroxy-2-oxo-1-{[(3S)-2-oxopyrrolidin-3-yl]methyl}propyl)amino]carbonyl}-3-methylbutyl)-1H-indole-2-carboxamide (49)
Following the procedure described for the preparation of N-((1S)-1-{[((1S)-3-hydroxy-2-oxo-1-{[(3S)-2-oxopyrrolidin-3-yl]methyl}propyl)amino]carbonyl}-3-methylbutyl)-4-methoxy-1H-indole-2-carboxamide but substituting N-((1S)-1-{[((1S)-3-chloro-2-oxo-1-{[(3S)-2-oxopyrrolidin-3-yl]methyl}propyl)amino]carbonyl}-3-methylbutyl)-1H-indole-2-carboxamide and making noncritical variations provided a crude black gum. This material was purified by Biotage flash chromatography, eluting with methanol/dichloromethane to afford the title compound as an off-white solid, 218 mg, 18%. 1H NMR (400 MHz, DMSO-d6) δ 11.58 (s, 1H), 8.42–8.61 (m, 2H), 7.61 (d, J = 8.6 Hz, 2H), 7.41 (d, J = 8.1 Hz, 1H), 7.26 (s, 1H), 7.17 (t, J = 7.6 Hz, 1H), 7.02 (t, J = 7.5 Hz, 1H), 5.02 (t, 1H), 4.38–4.58 (m, 2H), 4.09–4.32 (m, 2H), 3.01–3.17 (m, 2H), 2.24–2.38 (m, 1H), 2.03–2.22 (m, 2H), 1.92 (m, 1H), 1.46–1.77 (m, 4H), 0.85–0.99 (m, 6H); MS (APCI+) for C23H30N4O5m/z 443.1 (M + H)+; anal. calcd for C23H30N4O5·0.55 H2O·0.05 DCM: C, 60.62; H, 6.89; N, 12.27. Found: C, 60.83; H, 6.90; N,11.93.