[Cl:1][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][CH:5]=[CH:4][C:3]=1[C:12]([N:14]1[CH2:19][CH2:18][N:17]2[CH:20]=[CH:21][N:22]=[C:16]2[CH2:15]1)=[O:13].C1C(=O)N([Br:30])C(=O)C1>CN(C)C=O>[Br:30][C:20]1[N:17]2[CH2:18][CH2:19][N:14]([C:12]([C:3]3[CH:4]=[CH:5][CH:6]=[C:7]([C:8]([F:9])([F:10])[F:11])[C:2]=3[Cl:1])=[O:13])[CH2:15][C:16]2=[N:22][CH:21]=17-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine (E1) (5.68 g, 17.23 mmol) was dissolved in N,N-dimethylformamide (DMF) (100 mL) and treated with NBS (3.22 g, 18.09 mmol). The solution was stirred at 25° C. for 16 h and the bulk of the DMF was removed in vacuo. The residue was partitioned between dichloromethane (500 ml) and saturated sodium bicarbonate solution (100 ml). The aqueous phase was extracted with dichloromethane (5×100 ml) during which filtration through celite was required to remove emulsions and precipitated succinimide. The combined organic extracts were washed with brine (100 ml), dried over anhydrous sodium sulfate and concentrated to a crude oil. The crude product was purified by flash chromatography (Isolera, 340 g, 0-100% methanol:dichloromethane (1:9)/dichloromethane) to afford an oil that was triturated with hexane to afford a solid of desired product in 5.90 g.
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