[Li]CCCC.C(NC(C)C)(C)C.[Br:13][C:14]1[CH:19]=[CH:18][C:17]([NH2:20])=[C:16]([F:21])[CH:15]=1.Cl[C:23]1[C:28]([C:29]([OH:31])=[O:30])=[CH:27][N:26]=[C:25]([Cl:32])[C:24]=1[F:33]>C1COCC1>[Br:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:23]2[C:28]([C:29]([OH:31])=[O:30])=[CH:27][N:26]=[C:25]([Cl:32])[C:24]=2[F:33])=[C:16]([F:21])[CH:15]=1nBuLi (14.7 mL, 36.7 mmol, 2.5 M solution in hexanes) was added to a stirred solution of diisopropylamine (5.15 mL, 36.7 mmol) in THF (20 mL) at 0° C. After 20 minutes, the reaction mixture was cooled to −78° C. and a solution of 4-bromo-2-fluorophenylamine (4.65 g, 24.5 mmol) in THF (10 mL) was added. After 20 minutes, a solution of 4,6-dichloro-5-fluoro-nicotinic acid (Sanchez et al J Heterocylc. Chem. 1993, 30 (4), 855-9) (2.57 g, 12.25 mmol) in THF (10 mL) was added. After 10 minutes, the reaction mixture was allowed to warm to room temperature and stirred for 1 hour. After quenching the reaction mixture with 10% HCl (20 mL), it was extracted with ethyl acetate. The combined organic extracts were dried (MgSO4) and concentrated under reduced pressure. Trituration with methylene chloride yielded 3.21 g (72%) of clean desired product.
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