ClC(Cl)(Cl)CO[C:5](=[O:50])[NH:6][C:7]1[N:8]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([O:40][CH2:41][CH2:42][O:43][CH:44]3[CH2:49][CH2:48][CH2:47][CH2:46][O:45]3)[CH:35]=2)[N:9]=[C:10]([C:12]([CH3:33])([CH3:32])[CH2:13][O:14][Si:15]([C:28]([CH3:31])([CH3:30])[CH3:29])([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:11]=1.[CH3:53][C@H:54]1[CH2:59][CH2:58][CH2:57][CH2:56][N:55]1[C:60]1[N:64]2[CH:65]=[C:66]([O:69][C@H:70]3[C:79]4[C:74](=[CH:75][CH:76]=[CH:77][CH:78]=4)[C@@H:73]([NH2:80])[CH2:72][CH2:71]3)[CH:67]=[CH:68][C:63]2=[N:62][N:61]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[Si:15]([O:14][CH2:13][C:12]([C:10]1[CH:11]=[C:7]([NH:6][C:5]([NH:80][C@@H:73]2[C:74]3[C:79](=[CH:78][CH:77]=[CH:76][CH:75]=3)[C@H:70]([O:69][C:66]3[CH:67]=[CH:68][C:63]4[N:64]([C:60]([N:55]5[CH2:56][CH2:57][CH2:58][CH2:59][C@@H:54]5[CH3:53])=[N:61][N:62]=4)[CH:65]=3)[CH2:71][CH2:72]2)=[O:50])[N:8]([C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([O:40][CH2:41][CH2:42][O:43][CH:44]3[CH2:49][CH2:48][CH2:47][CH2:46][O:45]3)[CH:35]=2)[N:9]=1)([CH3:33])[CH3:32])([C:28]([CH3:29])([CH3:31])[CH3:30])([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1A solution of Intermediate 153f (377 mg, 0.48 mmol) in 1,4-dioxane (4.8 mL) was treated with Intermediate 81d (164 mg, 0.43 mmol) and DIPEA (0.095 mL, 0.54 mmol) and the mixture was stirred at 70° C. for 30 mins then at 50° C. for 64 h then at 70° C. for 22 h. The cooled solution was concentrated in vacuo, and the residue was partitioned between DCM and water. The phases were separated and the aqueous layer was extracted with DCM (×2). The combined organic phase was washed with brine, dried (Na2SO4) and concentrated in vacuo to a brown gum. The gum was purified by FCC, using 0-7% MeOH in DCM to give the title compound as a brown glass (320 mg, 72%). LCMS (Method 3): Rt 5.66 min, m/z 1017.7 [MH+].
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