反应详情

温度

100 °C

In a 25 mL sealable tube under nitrogen were combined 6-bromo-N-[(4,6-dimethyl-2-oxo-1,2-dihydro-3-pyridinyl)methyl]-1-(1-methylethyl)-1H-indazole-4-carboxamide (120 mg, 0.29 mmol) and [(2-methylphenyl)boronic acid (58.6 mg, 0.43 mmol) in dioxane/water (3 mL: 1 mL). PdCl2(dppf)-CH2Cl2 (11.74 mg, 0.014 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (72.5 mg, 0.86 mmol) was added and the insoluble mixture was heated in a microwave at 100° C. for 15 min. DCM/MeOH (1:1) was added, it was pre-absorbed on silica gel and purified by SiO2 chromatography (eluent: gradient 100% DCM to 80:20:2 DCM/MeOH/NH4OH). Fractions were evaporated. EtOAc was added along with some hexanes, it was sonicated and the solids that precipitated were filtered and dried to afford the title compound (84 mg, 66%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.51 (s, 1H) 8.55 (t, J=4.80 Hz, 1H) 8.41 (s, 1H) 7.80 (s, 1H) 7.55 (d, J=1.01 Hz, 1H) 7.27-7.35 (m, 4H) 5.87 (s, 1H) 5.09 (quin, J=6.57 Hz, 1H) 4.36 (d, J=5.05 Hz, 2H) 2.26 (s, 3H) 2.20 (s, 3H) 2.11 (s, 3H) 1.49 (s, 3H) 1.47 (s, 3H). MS(ES) [M+H]+ 429.1.

1. customIn a 25 mL sealable tube under nitrogen were combined
2. customthe resulting mixture was degassed with nitrogen for 10 min
3. customit was pre-absorbed on silica gel
4. custompurified by SiO2 chromatography (eluent: gradient 100% DCM to 80:20:2 DCM/MeOH/NH4OH)
5. customFractions were evaporated
6. additionEtOAc was added along with some hexanes, it
7. customwas sonicated
8. customthe solids that precipitated
9. filtrationwere filtered
10. customdried