反应详情

温度

100 °C

To a solution of 2-chloro-5-phenyl-N-(pyridin-2-ylmethyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine (0.500 g, 1.49 mmol) and N-(tert-butyl)-2-(difluoromethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-sulfonamide (0.697 g, 1.79 mmol) in 1,4-dioxane (5 mL) and water (1 mL) was added K2CO3 (0.412 g, 2.98 mmol). The reaction mixture was purged with nitrogen gas for 10 min. Then PdCl2(dppf)-CH2Cl2 (0.122 g, 0.149 mmol) was added and heated at 100° C. for 1 h in micro wave. The reaction mixture was allowed to cool to ambient temperature. The reaction mixture was filtered through CELITE® bed and the bed was washed with EtOAc (2×50 mL). The filtrate was diluted with water (50 mL) and extracted with EtOAc (100 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified by CombiFlash (REDISEP®, silica gel, 40 g, 40% EtOAc/hexanes) to obtain N-(tert-butyl)-2-(difluoromethyl)-5-(5-phenyl-4-((pyridin-2-ylmethyl)amino)pyrrolo[2,1-f][1,2,4]triazin-2-yl)pyridine-3-sulfonamide (0.600 g, 71.5% yield) as a pale yellow solid. LCMS Condition B-83: retention time 1.84 min, [M+1]=564.0. 1H NMR (400 MHz, CD3OD) δ ppm 1.26 (s, 9H), 4.94 (s, 2H), 6.81 (d, J=2.8 Hz, 1H), 7.27-7.31 (m, 1H), 7.44-7.55 (m, 3H), 7.59-7.63 (m, 4H), 7.77-7.82 (m, 2H), 8.43 (d, J=4.4 Hz, 1H), 9.19 (dd, J=2.0 Hz, J=1.2 Hz, 1H), 9.64 (d, J=2.0 Hz, 1H).

1. customThe reaction mixture was purged with nitrogen gas for 10 min
2. temperatureto cool to ambient temperature
3. filtrationThe reaction mixture was filtered through CELITE® bed
4. washthe bed was washed with EtOAc (2×50 mL)
5. additionThe filtrate was diluted with water (50 mL)
6. extractionextracted with EtOAc (100 mL)
7. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe resulting residue was purified by CombiFlash (REDISEP®, silica gel, 40 g, 40% EtOAc/hexanes)