N-((1S)-1-{[((1S)-3-Chloro-2-oxo-1-{[(3S)-2-oxopyrrolidin-3-yl]methyl}propyl)amino]carbonyl}-3,3-dimethylbutyl)-4-methoxy-1H-indole-2-carboxamide (35)
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)-4-methyl-l-leucinamide and making noncritical variations provided a pale yellow solid. This material was purified by Biotage MPLC (40 M column, 2–4.5% methanol/chloroform) to afford 920 g (60%) of the title compound as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 11.59 (d, J = 1.8 Hz, 1H), 8.54 (d, J = 7.8 Hz, 1H), 8.45 (d, J = 8.1 Hz, 1H), 7.64 (s, 1H), 7.32 (d, J = 1.8 Hz, 1H), 7.08 (t, J = 8.0 Hz, 1H), 7.00 (d, J = 8.3 Hz, 1H), 6.49 (d, J = 7.6 Hz, 1H), 4.52–4.62 (m, 1H), 4.40–4.51 (m, 2H), 3.87 (s, 3H), 3.01–3.16 (m, 2H), 2.19–2.31 (m, 1H), 2.03–2.12 (m, 1H), 1.91–2.01 (m, 1H), 1.81 (dd, J = 14.1, 9.9 Hz, 1H), 1.54–1.72 (m, 3H), 0.93 (s, 9H); MS (ESI+) for C25H33ClN4O5m/z 505.1 (M + H)+; HRMS (ESI+) calcd for (M + H)+ 505.2212, found 505.2204.