反应详情

温度

115 °C

A “Personal Chemistry” microwave vial was charged with the title compound of Example 2 (2.858 g, 8.0 mmol), 4-aminotetrahydropyran (3.236 g, 32.0 mmol), palladium (II) acetate (89.8 mg, 5 mol %), 1,1′-bis(diphenylphosphino)ferrocene (443.6 mg, 10 mol %), and sodium tert-butoxide (1.538 g, 16.0 mmol). The reagents were suspended in toluene (40 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 concentrated. After purifying the crude intermediate nitrile by flash chromatography, the nitrile was dissolved in 25% dimethylsulfoxide/ethanol, and 2 mL of 1 N sodium hydroxide and 2 mL of 30% aqueous hydrogen peroxide were added, followed by stirring at room temperature for 16 hours. The DMSO/ethanol mixture was then diluted with water and extracted with ethyl acetate (3×). The combined organics were washed with brine (2×), dried over Na2SO4, and evaporated. The residue was purified by column chromatography (EtOAc/MeOH) to yield 1.132 g (36%) of the title compound as an off-white powder. LCMS m/z: (M+H)=396.7.

1. temperatureto cool
2. filtrationthe suspension was filtered
3. concentrationthe filtrate concentrated
4. customAfter purifying the crude intermediate nitrile by flash chromatography
5. dissolutionthe nitrile was dissolved in 25% dimethylsulfoxide/ethanol
6. addition2 mL of 1 N sodium hydroxide and 2 mL of 30% aqueous hydrogen peroxide were added
7. additionThe DMSO/ethanol mixture was then diluted with water
8. extractionextracted with ethyl acetate (3×)
9. washThe combined organics were washed with brine (2×)
10. dry with materialdried over Na2SO4
11. customevaporated
12. customThe residue was purified by column chromatography (EtOAc/MeOH)