N-[(1S)-2-[((1S)-3-(Benzyloxy)-2-oxo-1-{[(3S)-2-oxopyrrolidin-3-yl]methyl}propyl)amino]-1-(cyclohexylmethyl)-2-oxoethyl]-4-methoxy-1H-indole-2-carboxamide
To a solution of tert-butyl [(1S)-2-[((1S)-3-(benzyloxy)-2-oxo-1-{[(3S)-2-oxopyrrolidin-3-yl]methyl}propyl)amino]-1-(cyclohexylmethyl)-2-oxoethyl]carbamate (200 mg, 0.38 mmol) in dioxane (4 mL) was added 4 M hydrochloric acid/dioxane (4 mL), and the solution was stirred at an ambient temperature for 2 h before removing the solvents in vacuo, azeotroping the residue with toluene (2 × 10 mL), and drying in vacuo for 1 h. The crude hydrochloride salt was taken into DMF (3 mL), and the solution was cooled to 0 °C before adding 4-methoxy-indole-2-carboxylic acid (73 mg, 0.38 mmol), collidine (125 μL, 0.95 mmol), and HATU (144 mg, 0.38 mmol) in order, and the resulting suspension was stirred at 0 °C for 6 h. The reaction was quenched by the addition of water (20 mL), and the mixture was extracted with diethyl ether (3 × 50 mL). The combined organics were washed with water (20 mL) and brine (20 mL), dried over MgSO4, filtered, and the solvents were removed in vacuo to yield the crude product, which was purified by Biotage flash chromatography, eluting with 1–3% methanol/dichloromethane to afford the title compound as a pale brown gum, 90 mg, 39%. The product was contaminated with ∼20% of another diastereomer from the previous step. 1H NMR (400 MHz, CDCl3) δ 9.59 (s, 1H), 8.13 (d, J = 6.6 Hz, 1H), 7.21–7.32 (m, 5H), 7.11 (t, J = 8.0 Hz, 1H), 7.02 (d, J = 1.5 Hz, 1H), 6.94 (d, J = 8.3 Hz, 1H), 6.72–6.78 (m, 1H), 6.42 (d, J = 7.8 Hz, 1H), 5.97 (s, 1H), 4.73 (m, 1H), 4.64 (m, 1H), 4.53 (d, J = 11.6 Hz, 1H), 4.46 (d, J = 11.6 Hz, 1H), 4.26 (d, J = 17.2 Hz, 1H), 4.15 (d, J = 17.4 Hz, 1H), 3.87 (s, 3H), 3.08–3.16 (m, 2H), 2.27–2.38 (m, 1H), 1.92 (m, 1H), 1.49–1.84 (m, 9H), 1.26–1.42 (m, 1H), 0.98–1.23 (m, 4H), 0.78–0.98 (m, 2H); MS (APCI+) for C34H42N4O6m/z 603.2 (M + H)+.