[CH3:1][C:2]([NH:10][C:11]([C:13]1[CH:18]=[N:17][C:16](Br)=[C:15]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=2)[N:14]=1)=[O:12])([C:4]1[N:8]=[C:7]([CH3:9])[O:6][N:5]=1)[CH3:3].Cl.[F:28][C:29]1([F:33])[CH2:32][NH:31][CH2:30]1.C1CCN2C(=NCCC2)CC1>CS(C)=O>[CH3:1][C:2]([NH:10][C:11]([C:13]1[CH:18]=[N:17][C:16]([N:31]2[CH2:32][C:29]([F:33])([F:28])[CH2:30]2)=[C:15]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=2)[N:14]=1)=[O:12])([C:4]1[N:8]=[C:7]([CH3:9])[O:6][N:5]=1)[CH3:3]5-Bromo-6-(3-chloro-phenyl)-pyrazine-2-carboxylic acid [1-methyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide (Example 1e, 0.075 g, 172 μmol) was added to a solution containing 3,3-difluoroazetidine hydrochloride (77.9 mg, 601 μmol) and DBU (91.5 mg, 89.8 μl, 601 μmol) in DMSO (1 mL). The reaction mixture was stirred at room temperature for 2 hours and extracted with ethyl acetate and 10% citric acid. The organic phase was dried with MgSO4, filtered and concentrated in vacuo. The crude material was purified by reverse phase chromatography to give the desired product (8 mg, 10%) as colorless oil; MS (ESI): 449.1 (M+H).
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