(3S)-3-({N-[(4-Methoxy-1H-indol-2-yl)carbonyl]-l-leucyl}amino)-2-oxo-4-[(3S)-2-oxopyrrolidin-3-yl]butyl 2,6-Difluorobenzoate (23)
Following the procedure described for the preparation of (3S)-3-({N-[(4-methoxy-1H-indol-2-yl)carbonyl]-l-leucyl}amino)-2-oxo-4-[(3S)-2-oxopyrrolidin-3-yl]butyl acetate but substituting 2,6-difluorobenzoic acid and making noncritical variations provided a crude brown oily solid. This material was triturated with chloroform/ethyl acetate to afford 180 mg (75%) of the title compound as a white solid. 1H NMR (DMSO-d6) δ 11.65 (d, J = 2 Hz, 1H), 8.68 (d, J = 8 Hz, 1H), 8.54 (d, J = 8 Hz, 1H), 7.73–7.65 (m, 2H), 7.36 (s, 1H), 7.27 (t, J = 8 Hz, 1H), 7.08 (t, J = 8 Hz, 1H), 6.99 (d, J = 8 Hz, 1H), 6.49 (d, J = 8 Hz, 1H), 5.19 (d, J = 16 Hz, 1H), 5.14 (d, J = 16 Hz, 1H), 4.48 (m, 2H), 3.87 (s, 3H), 3.11 (m, 2H), 2.32 (m, 1H), 2.11–1.91 (m, 2H), 1.81–1.56 (m, 5H), 0.94 (d, J = 4 Hz, 3H), 0.89 (d, J = 4 Hz, 3H); MS (ESI+) for C31H34F2N4O7m/z 613.2 (M + H)+; HRMS (ESI+) calcd for C31H34F2N4O7+H1 613.2469, found 613.2476.