反应详情

温度

115 °C

A “Personal Chemistry” microwave vial was charged with the title compound of Example 2 (107.1 mg, 0.3 mmol), 2-methoxyethylamine (91.3 mg, 1.2 mmol), palladium (II) acetate (3.4 mg, 5 mol %), 1,1′-bis(diphenylphosphino)ferrocene (16.6 mg, 10 mol %), and sodium tert-butoxide (57.7 mg, 0.6 mmol). The reagents were suspended in toluene (2 mL) and were heated with microwave radiation to a temperature of 115° C. for fifteen minutes. After allowing the reaction vessel to cool, the suspension was filtered and the filtrate evaporated. After purifying the crude intermediate nitrile by flash chromatography, hydrolysis was performed by dissolving the residue in 25% dimethylsulfoxide/ethanol, adding 5 drops of 1 N sodium hydroxide and 5 drops of 30% aqueous hydrogen peroxide, followed by stirring at room temperature for 3 hours. The DMSO/ethanol mixture was then diluted with water and extracted with CH2Cl2 (3×). The combined organics were washed with brine (2×), dried over Na2SO4, and concentrated. The compound was purified by column chromatography (hexane/EtOAc) to yield the title compound (94.4 mg, 85% yield) of an off-white powder. LCMS m/z: (M+H) 370.2.

1. temperatureto cool
2. filtrationthe suspension was filtered
3. customthe filtrate evaporated
4. customAfter purifying the crude intermediate nitrile
5. customby flash chromatography, hydrolysis
6. extractionextracted with CH2Cl2 (3×)
7. washThe combined organics were washed with brine (2×)
8. dry with materialdried over Na2SO4
9. concentrationconcentrated
10. customThe compound was purified by column chromatography (hexane/EtOAc)