[Br:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[CH:23]12[NH:31][CH:27]([CH2:28][O:29][CH2:30]1)[CH2:26][O:25][CH2:24]2.[F-].[K+]>CN(C=O)C.CCOC(C)=O>[CH:27]12[N:31]([C:3]3[C:2]([Br:1])=[CH:21][C:6]([C:7]([NH:9][C:10]4[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=4)=[O:8])=[CH:5][N:4]=3)[CH:23]([CH2:30][O:29][CH2:28]1)[CH2:24][O:25][CH2:26]25-Bromo-6-chloro-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 12.2, 55.4 mg, 0.14 mmol) and 3,7-Dioxa-9-aza-bicyclo[3.3.1]nonane (Organic Chemistry (2006), 71(1), 413-415) (24.53 mg, 0.14 mmol) were dissolved in DMF (150 μL). KF (24.4 mg, 0.42 mmol) was added and the RM mixture was stirred at 140° C. for 18 h in a pressure safe vial. After cooling at RT, the RM was dissolved in EtOAc and washed with brine. The organic phase was dried over Na2SO4 and evaporated to dryness under reduced pressure to give a residue that was purified by flash chromatography (RediSep® Silica gel column, n-hexane/EtOAc from 20% to 60% EtOAc) to afford the title compound as a white solid. HPLC (Condition 4) tR=5.84 min, UPLC-MS (Condition 3) tR=1.19 min, m/z=490.1 [M+H]+.
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