反应详情

温度

100 °C

To an RBF, under a reflux condenser, was added 6-chloro-N-methylpyrimidin-4-amine (5.0 g, 35 mmol), 2-fluoropyridin-3-ylboronic acid (7.4 g, 52 mmol), potassium acetate (10 g, 104 mmol), 1-butanol (100 mL) and DI water (20 mL). The mixture was purged with Ar (vacuum/purge three times to remove oxygen), then PdCl2(P-t-Bu2Ph)2 (0.26 g, 0.42 mmol) was added. The reaction mixture was stirred in a 100° C. oil bath for 17 h. The reaction mixture was allowed to cool to room temperature and diluted with Et2O (500 mL). The mixture was washed with water (3×200 mL), brine (200 mL), dried over Na2SO4, filtered and concentrated in vacuo to ˜100 mL bright yellow butanol solution. The solution was azeotroped with hexane (3×500 mL). Upon the third azeotrope (volume ˜90 mL) a white precipitate was observed. The suspended solid was collected by solution filtration and vacuum-dried to afford 2.48 g as a white solid. The filtrate was diluted with Et2O (300 mL) and extracted with 1 N aq HCl (2×150 mL). The aqueous extract was basified with 5 N NaOH and extracted with Et2O (2×150 mL). The organic extract was washed with saturated NaCl (100 mL), dried over Na2SO4, filtered, and concentrated in vacuo to afford 2.48 g as an off-white solid. Total yield of title compound: 6-(2-fluoropyridin-3-yl)-N-methylpyrimidin-4-amine (4.95 g, 70%). MS (M+H)+ 205.

1. customThe mixture was purged with Ar (vacuum/purge three times to remove oxygen)
2. temperatureto cool to room temperature
3. washThe mixture was washed with water (3×200 mL), brine (200 mL)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo to ˜100 mL bright yellow butanol solution
7. customThe solution was azeotroped with hexane (3×500 mL)
8. filtrationThe suspended solid was collected by solution filtration
9. customvacuum-dried
10. customto afford 2.48 g as a white solid
11. extractionextracted with 1 N aq HCl (2×150 mL)
12. extractionThe aqueous extract
13. extractionextracted with Et2O (2×150 mL)
14. extractionThe organic extract
15. washwas washed with saturated NaCl (100 mL)
16. dry with materialdried over Na2SO4
17. filtrationfiltered
18. concentrationconcentrated in vacuo
19. customto afford 2.48 g as an off-white solid