[CH3:1][N:2]1[C:6]([CH3:7])=[C:5]([NH:8][C:9](=O)[CH3:10])[C:4]([CH3:12])=[N:3]1.[H-].[Na+].ClC1C=[C:20]([I:22])[C:19]([C:23]([F:26])([F:25])[F:24])=[CH:18][N:17]=1.O.[OH-].[Li+]>CCOC(C)=O.O>[I:22][C:20]1[C:19]([C:23]([F:26])([F:25])[F:24])=[CH:18][N:17]=[C:9]([NH:8][C:5]2[C:4]([CH3:12])=[N:3][N:2]([CH3:1])[C:6]=2[CH3:7])[CH:10]=1N-(1,3,5-trimethylpyrazol-4-yl)acetamide (1.142 g, 6.83 mmol) was added to sodium hydride (0.288 g, 6.83 mmol) suspended in nitrogen-degassed DMF (5 mL) under nitrogen. The resulting light suspension was stirred at 35° C. for 30 minutes then 2-chloro-4-iodo-5-(trifluoromethyl)pyridine (1 g, 3.25 mmol) was added. The reaction mixture was allowed to cool to room temperature, stirred for 1 hour and quenched with water (20 mL). Lithium hydroxide hydrate (0.409 g, 9.76 mmol) was added, the mixture was stirred at room temperature for 1.5 hour and then diluted with EtOAc and water. The phases were separated and the organic phase was washed with brine, dried over magnesium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel (40 g) eluting with 0 to 50% EtOAc in DCM to afford 4-iodo-5-(trifluoromethyl)-N-(1,3,5-trimethylpyrazol-4-yl)pyridin-2-amine (350 mg, 27.2%) as an off-white solid.
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