Cl.[Br:2][C:3]1[C:16]([O:17][CH3:18])=[CH:15][C:14]2[C:5](=[C:6]([O:19][C@H:20]3[CH2:24][NH:23][C@H:22]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:21]3)[N:7]=[C:8]3[C:13]=2[CH2:12][CH2:11][CH2:10][CH2:9]3)[CH:4]=1.[CH:30]1([C@H:36]([NH:40][C:41]([O:43][CH2:44][C:45]([CH3:50])([CH3:49])[CH2:46][CH:47]=[CH2:48])=[O:42])[C:37](O)=[O:38])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C.CN(C1C=CN=CC=1)C>[Br:2][C:3]1[C:16]([O:17][CH3:18])=[CH:15][C:14]2[C:5](=[C:6]([O:19][C@H:20]3[CH2:24][N:23]([C:37](=[O:38])[C@H:36]([CH:30]4[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]4)[NH:40][C:41]([O:43][CH2:44][C:45]([CH3:50])([CH3:49])[CH2:46][CH:47]=[CH2:48])=[O:42])[C@H:22]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:21]3)[N:7]=[C:8]3[C:13]=2[CH2:12][CH2:11][CH2:10][CH2:9]3)[CH:4]=1To a solution of the product from Step 2, ethyl (4R)-4-[(8-bromo-9-methoxy-1,2,3,4-tetrahydrophenanthridin-6-yl)oxy]-L-prolinate hydrochloride (466 mg, 0.96 mmol) in DMF (8 mL) was added linker intermediate B20, (2S)-cyclohexyl({[(2,2-dimethylpent-4-en-1-yl)oxy]carbonyl}amino)acetic acid (300 mg, 1.0 mmol)), DIPEA (0.50 mL, 2.88 mmol), HATU (547 mg, 1.44 mmol), and DMAP (59 mg, 0.48 mmol) were added. The mixture was stirred at r.t. for 18 h and then the mixture was poured into 120 mL of aqueous citric acid. The resulting solid was removed by filtration and washed with water. The solid was then dissolved in EtOAc, dried over Na2SO4, and the solvent was removed in vacuo. The crude material was then purified on silica (gradient elution, 20-50% EtOAc/hexanes) to yield the title compound. LRMS (M+H)+=728.0.
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