Br[C:2]1[C:3](=[O:20])[N:4]([C:9]2[CH:10]=[C:11]([CH:16]=[CH:17][C:18]=2[CH3:19])[C:12]([O:14][CH3:15])=[O:13])[CH:5]=[C:6]([Br:8])[N:7]=1.[CH2:21]([O:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[C:35]1([NH2:39])[CH2:38][CH2:37][CH2:36]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(N(CC)C(C)C)(C)C>O1CCOCC1.C(OCC)(=O)C.O>[CH2:21]([O:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[C:35]1([NH:39][C:2]2[C:3](=[O:20])[N:4]([C:9]3[CH:10]=[C:11]([CH:16]=[CH:17][C:18]=3[CH3:19])[C:12]([O:14][CH3:15])=[O:13])[CH:5]=[C:6]([Br:8])[N:7]=2)[CH2:38][CH2:37][CH2:36]1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1To 3-(3,5-dibromo-2-oxo-2H-pyrazin-1-yl)-4-methyl-benzoic acid, methyl ester (Example 1b, 1.083 g) in dioxane (6 mL) was added 1-(2-(benzyloxy)phenyl)cyclobutanamine (Example 268c, 1.16 g) and N,N-diisopropylethylamine (0.76 mL) and the reaction heated at 100° C. for 16 h. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and water, and the organic layer was separated, dried (MgSO4), filtered and the crude product purified (SiO2 chromatography eluting with 20-50% ethyl acetate in iso-hexane) to afford the subtitle product (1.46 g).
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