反应详情

温度

90 °C

To a solution of 5-(2,6-difluorophenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indole (600 mg, 1.17 mmol), and (R)-tert-butyl 3-((4-chloro-6-methoxypyrimidin-2-yl)amino)piperidine-1-carboxylate (483 mg, 1.41 mmol) in DME (12 mL) and water (3 mL) was added Pd(PPh3)4 (270 mg, 0.234 mmol) and Na2CO3 (372 mg, 3.51 mmol) and argon gas was bubbled for 15 min. The above mixture was heated at 90° C. for 8 h. The reaction was quenched with water and extracted with EtOAc. The organic layer was separated, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified with silica gel chromatography (eluting with 30% EtOAc in petroleum ether) to give (R)-tert-butyl 3-((4-(5-(2,6-difluorophenyl)-1-tosyl-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)amino)piperidine-1-carboxylate (500 mg, 62.5%). MS (ESI, pos. ion) m/z: 690.2 (M+1); 1H-NMR (400 MHz CDCl3): δ ppm 8.16 (s, 1H), 8.09 (d, J=8 Hz, 1H), 7.84-7.90 (m, 3H), 7.26-7.46 (m, 6H), 7.02 (m, 2H), 6.41 (s, 1H), 5.07 (brs, 1H), 4.10-4.14 (m, 1H), 3.93 (s, 3H), 2.37 (s, 3H), 1.25-1.60 (m, 15H).

1. customwas bubbled for 15 min
2. customThe reaction was quenched with water
3. extractionextracted with EtOAc
4. customThe organic layer was separated
5. dry with materialdried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified with silica gel chromatography (eluting with 30% EtOAc in petroleum ether)