N-((1S)-1-{[((1S)-3-Hydroxy-2-oxo-1-{[(3S)-2-oxopyrrolidin-3-yl]methyl}propyl)amino]carbonyl}-3,3-dimethylbutyl)-4-methoxy-1H-indole-2-carboxamide (36)
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}-3,3-dimethylbutyl)-4-methoxy-1H-indole-2-carboxamide and making noncritical variations provided a crude brown glass. This material was purified by Biotage MPLC (40 M column, 2–10% methanol/chloroform) to afford 415 mg (53%) of the title compound as a white solid. MS (ESI+) for C25H34N4O6m/z 487.2 (M + H)+. Alternatively, following the procedure described for the preparation of N-{(1S)-1-(cyclohexylmethyl)-2-[((1S)-3-hydroxy-2-oxo-1-{[(3S)-2-oxopyrrolidin-3-yl]methyl}propyl)amino]-2-oxoethyl}-4-methoxy-1H-indole-2-carboxamide but substituting N-((1S)-1-{[((1S)-3-(benzyloxy)-2-oxo-1-{[(3S)-2-oxopyrrolidin-3-yl]methyl}propyl)amino]carbonyl}-3,3-dimethylbutyl)-4-methoxy-1H-indole-2-carboxamide and making noncritical variations provided a tan solid. This material was purified by Biotage MPLC (25 M column, 6–7% methanol/chloroform) to afford 100 mg (77%) of the title compound as a white solid. 1H NMR (DMSO-d6) δ 11.58 (s, 1H), 8.42 (d, J = 8 Hz, 1H), 8.37 (d, J = 8 Hz, 1H), 7.62 (s, 1H), 7.32 (s, 1H), 7.08 (t, J = 8 Hz, 1H), 6.99 (d, J = 8 Hz, 1H), 6.49 (d, J = 8 Hz, 1H), 5.04 (t, J = 8 Hz, 1H), 4.52 (m, 1H), 4.42 (m, 1H), 4.24 (dd, J = 8, 20 Hz, 1H), 4.12 (dd, J = 8, 20 Hz, 1H), 3.87 (s, 3H), 3.09 (m, 2H), 2.25 (m, 1H), 2.06 (m, 1H), 1.93 (m, 1H), 1.80 (dd, J = 8, 16 Hz, 1H), 0.93 (s, 9H); MS (ESI+) for C25H34N4O6m/z 487.2 (M + H)+; anal. calcd for C25H34N4O6·0.3 H2O: C, 61.03; H, 7.09; N, 11.39. Found: C, 61.07; H, 7.09; N, 11.22; HRMS (ESI+) calcd for C25H34N4O6 487.2551, found 487.2541.