[Br:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1F)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([Cl:18])([F:17])[F:16])=[CH:10][CH:9]=1)=[O:6].Cl.Cl.[NH2:25][C@H:26]1[CH2:30][NH:29][CH2:28][C@@H:27]1[OH:31].C([O-])([O-])=O.[Na+].[Na+]>CS(C)=O>[NH2:25][C@@H:26]1[C@@H:27]([OH:31])[CH2:28][N:29]([C:21]2[CH:20]=[CH:19][C:4]([C:5]([NH:7][C:8]3[CH:13]=[CH:12][C:11]([O:14][C:15]([Cl:18])([F:17])[F:16])=[CH:10][CH:9]=3)=[O:6])=[CH:3][C:2]=2[Br:1])[CH2:30]13-Bromo-N-(4-(chlorodifluoromethoxy)phenyl)-4-fluorobenzamide (240 mg, 0.596 mmol) and TEA (0.332 mL, 2.384 mmol) were added to a vial containing DMSO (0.5 mL). (3S,4S)-4-aminopyrrolidin-3-ol dihydrochloride (Stage 245.2, 128 mg, 0.715 mmol) was added. The RM was stirred at 100° C. for 40 h. The RM was treated with sat. aq. Na2CO3 (50 mL) and was extracted with EtOAc. The combined extracts were washed with water (30 mL) and brine (30 mL), dried over Na2SO4, filtered and the filtrate was evaporated off under reduced pressure to give a crude product that was purified by flash chromatography (from 100% EtOAc to EtOAc/EtOH/NH3 aq. 90:9:1) to afford the title product as a beige solid. HPLC (Condition 10) tR=6.08 min, UPLC-MS (Condition 3) tR=0.82 min, m/z=476.1/478.1 [M+H]+.
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