反应详情

Add mCPBA (0.152 g, 0.616 mmol) portion wise to a solution of 1-(4-bromo-2-fluoro-5-(7-methyl-2-(methylthio)pyrido[2,3-d]pyrimidin-6-yl)phenyl)-3-(3,3-dimethylbutyl)urea (0.26 g, 0.513 mmol) in DCM (10 mL) and stir at RT for 2 h. Add methylamine in THF (2.0M, 1.027 mL, 2.054 mmol) and stir at RT overnight. Add water, extract with DCM (3×), wash the combined organics with saturated. NaHCO3, then brine, dry over MgSO4, concentrate to dryness and purify via reverse-phase chromatography (MeCN/H2O with 0.1% TFA). Combine fractions, remove the organics under reduced pressure and neutralize the resulting aqueous residue with NaHCO3. Extract the mixture with EtOAc (2×), wash the combined organics with saturated. NaHCO3, then brine, dry over Na2SO4, concentrate to dryness, treat with 1:1 MeCN/H2O, freeze and lyophilize to afford the title compound as a pale yellow solid (34 mg, 13% yield). MS (m/z): 489.1 (M+1)/491.1 (M+3).

1. extractionAdd water, extract with DCM (3×)
2. washwash the combined organics with saturated
3. dry with materialNaHCO3, then brine, dry over MgSO4
4. concentrationconcentrate to dryness
5. custompurify via reverse-phase chromatography (MeCN/H2O with 0.1% TFA)
6. customCombine fractions, remove the organics under reduced pressure
7. extractionExtract the mixture with EtOAc (2×)
8. washwash the combined organics with saturated
9. dry with materialNaHCO3, then brine, dry over Na2SO4
10. concentrationconcentrate to dryness
11. additiontreat with 1:1 MeCN/H2O, freeze