反应详情

温度

110 °C

A reaction vial was charged with 3-((2-chloro-5-(methylcarbamoyl)pyridin-4-yl)amino)-2-methoxybenzoic acid (600 mg, 1.787 mmol), 5-fluoro-4-methylpyridin-2-amine (316 mg, 2.502 mmol), BrettPhos (38.4 mg, 0.071 mmol) and Pd2(dba)3 (32.7 mg, 0.036 mmol) and the contents were flushed with nitrogen before adding dioxane (2 mL) and DMA (1 mL). The resulting slurry was sparged with additional nitrogen for ˜1 minutes, then LiHMDS (1 M in THF) (3.93 mL, 3.93 mmol) was added and the resulting dark amber colored solution was heated in a preheated heating block at 110° C. for 2 h, then cooled to room temperature. The reaction mixture was added to water (80 mL) and the pH was adjusted with aq. 1N HCl to ˜3 causing a solid to precipitate from solution. After stirring the slurry at room temperature for ˜4 h, the solid was collected by vacuum filtration, rinsed with water, and dried on the filter to afford 3-((2-((5-fluoro-4-methylpyridin-2-yl)amino)-5-(methylcarbamoyl)pyridin-4-yl)amino)-2-methoxybenzoic acid (736 mg, 1.730 mmol, 97% yield) as a beige solid. HPLC (Method N) RT=2.45 minutes. LCMS (m+1)=426.

1. customA reaction
2. customthe contents were flushed with nitrogen
3. additionbefore adding dioxane (2 mL) and DMA (1 mL)
4. customThe resulting slurry was sparged with additional nitrogen for ˜1 minutes
5. temperaturecooled to room temperature
6. customto precipitate from solution
7. filtrationthe solid was collected by vacuum filtration
8. washrinsed with water
9. customdried on the
10. filtrationfilter