反应详情

温度

85 °C

Combine 1-(2,4-difluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-(3,3-dimethylbutyl)urea (3.90 g, 10.19 mmol), 6-bromo-N,7-dimethylpyrido[2,3-d]pyrimidin-2-amine (2.58 g, 10.19 mmol) and K2CO3 (4.23 g, 30.6 mmol) in dioxane (68 mL) and H2O (17 mL) and sparge with argon. Treat with tetrakis(triphenylphosphine)palladium (0.589 g, 0.510 mmol) and heat at 85° C. overnight. Cool the mixture to RT, dilute with EtOAc, filter through diatomaceous earth, and rinse well with EtOAc. Combine filtrates and wash with water (3×) and brine (1×), dry over Na2SO4, and concentrate to dryness. Treat the residue with acetonitrile and sonicate until solids precipitate. Heat the suspension at 80° C. for 2.5 h, cool to RT and collect the solids by filtration. Re-suspend solid in MeCN, heat at 80° C. for 1 h and collect by filtration. Concentrate filtrates to dryness and purify by silica gel chromatography (EtOAc/Hex, then EtOAc/MeOH/NH4OH). Treat the purified material with MeCN, sonicate, collect solids via filtration, rinsed with MeCN and dry in vacuo. Combine the crops of solids to provide title compound (2.05 g, 47%) as a pale tan solid. MS (ESI) m/z: 429.2 (M+H+).

1. temperatureCool the mixture to RT
2. filtrationfilter through diatomaceous earth
3. washrinse well with EtOAc
4. washCombine filtrates and wash with water (3×) and brine (1×)
5. dry with materialdry over Na2SO4
6. concentrationconcentrate to dryness
7. additionTreat the residue with acetonitrile
8. customsonicate until solids
9. customprecipitate
10. temperatureHeat the suspension at 80° C. for 2.5 h
11. temperaturecool to RT
12. customcollect the solids
13. filtrationby filtration
14. temperatureRe-suspend solid in MeCN, heat at 80° C. for 1 h
15. filtrationcollect by filtration
16. customConcentrate filtrates to dryness and purify by silica gel chromatography (EtOAc/Hex
17. additionTreat the purified material with MeCN
18. customsonicate
19. customcollect solids
20. filtrationvia filtration
21. washrinsed with MeCN
22. customdry in vacuo