反应详情

温度

55 °C

Combine 1-(2-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-3-(3-methoxy-3-methylbutyl)urea (0.17 g, 0.431 mmol), 7-methyl-2-(methylamino)pyrido[2,3-d]pyrimidin-6-yl trifluoromethanesulfonate (0.139 g, 0.431 mmol) and NaHCO3 (0.109 g, 1.293 mmol) in dioxane (6 mL) and H2O (1.5 mL). Sparge the mixture with argon. Treat with tetrakis(triphenylphosphine)palladium (0.025 g, 0.022 mmol), sparge again with argon and heat at 55° C. overnight. Add an additional portion of tetrakis(triphenylphosphine)palladium (25 mg, 0.022 mmol) and heat at 65° C. overnight. Cool the mixture to RT, remove solids by filtration, and wash solids with dioxane. Combine filtrates, dilute with EtOAc, wash with saturated NaHCO3 and brine, dry over Na2SO4, concentrate to dryness and purify via silica gel chromatography (EtOAc/Hex). Dissolve in DCM, wash with saturated NaHCO3 and brine, dry over Na2SO4, concentrate to dryness. Treat with 1:1 MeCN/H2O, freeze in −78° C. bath and lyophilize to obtain the title compound (40 mg, 21% yield) as a pale yellow solid. MS (ESI) m/z: 441.2 (M+1).

1. customSparge the mixture with argon
2. customsparge again with argon
3. temperatureheat at 65° C. overnight
4. temperatureCool the mixture to RT
5. customremove solids
6. filtrationby filtration
7. washwash solids with dioxane
8. additionCombine filtrates, dilute with EtOAc
9. washwash with saturated NaHCO3 and brine
10. dry with materialdry over Na2SO4
11. concentrationconcentrate to dryness
12. custompurify via silica gel chromatography (EtOAc/Hex)
13. dissolutionDissolve in DCM
14. washwash with saturated NaHCO3 and brine
15. dry with materialdry over Na2SO4
16. concentrationconcentrate to dryness
17. additionTreat with 1:1 MeCN/H2O, freeze in −78° C. bath