C(OC([N:8]1[CH2:15][CH2:14][N:13]([C:16]2[N:17]=[C:18]([C:26]3[C:27](=[O:56])[N:28]([CH2:42][O:43][P:44]([O:51]C(C)(C)C)([O:46]C(C)(C)C)=[O:45])[C:29](=[O:41])[C:30]=3[C:31]3[C:39]4[C:34](=[C:35]([CH3:40])[CH:36]=[CH:37][CH:38]=4)[NH:33][CH:32]=3)[C:19]3[C:24]([CH:25]=2)=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:12][C:9]21[CH2:11][CH2:10]2)=O)(C)(C)C.C(O)(C(F)(F)F)=O>ClCCCl.CO>[CH2:10]1[C:9]2([CH2:12][N:13]([C:16]3[N:17]=[C:18]([C:26]4[C:27](=[O:56])[N:28]([CH2:42][O:43][P:44](=[O:45])([OH:51])[OH:46])[C:29](=[O:41])[C:30]=4[C:31]4[C:39]5[C:34](=[C:35]([CH3:40])[CH:36]=[CH:37][CH:38]=5)[NH:33][CH:32]=4)[C:19]4[C:24]([CH:25]=3)=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH2:14][CH2:15][NH:8]2)[CH2:11]1To a solution of 7-{1-[1-(di-tert-butoxy-phosphoryloxymethyl)-4-(7-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-isoquinolin-3-yl}-4,7-diaza-spiro[2.5]octane-4-carboxylic acid tert-butyl ester (1.90 g, 2.42 mmol) in 1,2-dichloroethane (50 mL) was added TFA (8.27 g, 72.5 mmol) under argon at 0° C. The reaction mixture was stirred for 3.5 h under argon at 0° C. until UPLC-MS indicated that full conversion of the starting material had occurred. The reaction mixture was diluted with 1,2-dichloroethane (50 mL) and concentrated at reduced pressure to afford the crude product as a red solid. The crude reaction product was dissolved in MeOH and slowly concentrated at reduced pressure until crystallization started to occur. Pentane was added and the solids were filtered off and washed with Et2O. Further purification was achieved by suspending the crude product in DMSO, followed by sonication for 30 min. The solids were filtered off, washed with Et2O and dried at high vacuum (<1 mm Hg) to afford the title compound as a dark red solid. 1H-NMR (400 MHz, DMSO-d6): 12.10 (s, 1H), 8.08 (d, 1H), 7.65-7.61 (m, 2H), 7.44 (t, 1H), 7.20 (s, 1H), 7.06 (t, 1H), 6.74 (d, 1H), 6.43 (t, 1H), 6.00 (d, 1H), 5.29 (d, 2H), 3.87-3.01 (m, 6H), 2.37 (s, 3H), 0.97-0.62 (m, 4H). 31P-NMR (162 MHz, DMSO-d6): −6.0. LCMS: [M+1]+=574.0, Rt(1)=1.77 min., Rt(2)=0.71 min.
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