Cl.[CH3:2][S:3][C:4]1[N:5]=[N:6][C:7]([CH:10]([NH2:12])[CH3:11])=[CH:8][N:9]=1.[Br:13][C:14]1[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=1)[C:17](O)=[O:18].N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)CC)C>CN(C)C=O>[Br:13][C:14]1[CH:15]=[C:16]([CH:20]=[CH:21][CH:22]=1)[C:17]([NH:12][CH:10]([C:7]1[N:6]=[N:5][C:4]([S:3][CH3:2])=[N:9][CH:8]=1)[CH3:11])=[O:18]To a stirred solution of 1-[3-(methylthio)-1,2,4-triazin-6-yl]ethanamine hydrochloride (Intermediate 4) (10 g, 49 mmol) in N,N-dimethylformamide (100 mL) was added 3-bromobenzoic acid (11 g, 54 mmol), O-(7-azabenzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophospahte (20 g, 52 mmol) and triethylamine (24 mL, 170 mmol). After stirring for 18 hours the solution was concentrated under reduced pressure to approximately 50 mL. The solution was diluted with ethyl acetate (200 mL) and washed with 0.1N HCl (2×100 mL) and saturated sodium bicarbonate solution (100 mL). The solution was dried with magnesium sulfate and filtered, and silica gel (25 g) was added to the solution, followed by evaporation of the volatiles under reduced pressure. The pre-adsorbed solids were loaded into a solid loading cartridge and subjected to a gradient elution using ethyl acetate:hexane (0:100) to ethyl acetate:hexanes (40:60) using a RediSep silica gel cartridge (120 g; ISCO). The appropriate fractions were combined and concentrated under reduced pressure to give 3-bromo-N-{1-[3-(methylthio)-1,2,4-triazin-6-yl]ethyl}benzamide (14.5 g) as a white solid. 1H NMR (CDCl3): δ8.47(s, 1H), 7.95 (dd, J=1.8, 1.7 Hz, 1H), 7.72 (ddd, J=7.9, 1.6, 1.1 Hz, 1H), 7.64 (ddd, J=7.9, 2.0, 1.1 Hz, 1H), 7.32 (dd, J=8.0, 7.7 Hz, 1H), 7.20 (d, J=7.2 Hz, 1H), 5.47 (dq, J=7.2, 7.0 Hz, 1H), 2.68 (s, 3H), 1.70 (d, J=7.0 Hz, 3H). MS m/z 353, 355 (M+1, M+3).
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