反应详情

温度

110 °C

In a 25 mL sealable tube under nitrogen were combined 6-bromo-3-methyl-1-(1-methylethyl)-N-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl)methyl]-1H-indazole-4-carboxamide (85 mg, 0.19 mmol), 1-methyl-4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyridinyl]piperazine (72.9 mg, 0.24 mmol) in dioxane/water (3 mL:1 mL). PdCl2(dppf)-CH2Cl2 adduct (7.6 mg, 0.0093 mmol) was added and the resulting mixture was degassed with nitrogen for 10 min. Sodium bicarbonate (46.6 mg, 0.55 mmol) was added, the vessel was sealed, and the insoluble mixture was heated in a microwave at 110° C. for 20 min. The mixture was evaporated, DCM was added and the contents purified by SiO2 chromatography (eluent: gradient 0 to 80:20:2 DCM/MeOH/NH4OH). The collected product was suspended in EtOAc along with some hexanes. The contents were sonicated and solids that precipitated were filtered. Acetonitrile was added, the solids were triturated, and again filtered. The collected solid was then suspended in DMF along with some water and then allowed to sit at room temperature overnight. Solids that precipitated were filtered, washed with DCM, and dried to afford the title compound as a light grey solid (34 mg, 32%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.50 (s, 1H) 8.45 (t, J=4.93 Hz, 1H) 8.19 (d, J=5.31 Hz, 1H) 8.06-8.09 (m, 1H) 7.40 (s, 1H) 7.17 (s, 1H) 7.08 (d, J=5.05 Hz, 1H) 5.91 (s, 1H) 5.11 (quin, J=6.57 Hz, 1H) 4.39 (br. s., 1H) 4.38 (br. s., 1H) 3.55-3.62 (m, 4H) 2.53-2.57 (m, 2H) 2.41-2.46 (m, 7H) 2.24 (s, 3H) 2.13 (s, 3H) 1.53-1.61 (m, 2H) 1.47 (s, 3H) 1.46 (s, 3H) 0.93 (t, J=7.33 Hz, 3H); LC-MS (ES) m/z=459.2

1. customIn a 25 mL sealable tube under nitrogen were combined
2. customthe resulting mixture was degassed with nitrogen for 10 min
3. customthe vessel was sealed
4. customThe mixture was evaporated
5. additionDCM was added
6. customthe contents purified by SiO2 chromatography (eluent: gradient 0 to 80:20:2 DCM/MeOH/NH4OH)
7. customThe contents were sonicated
8. customsolids that precipitated
9. filtrationwere filtered
10. additionAcetonitrile was added
11. customthe solids were triturated
12. filtrationagain filtered
13. customSolids that precipitated
14. filtrationwere filtered
15. washwashed with DCM
16. customdried