反应详情

Following the procedures described in parts A-D of example 134, 2-methoxy-4-nitrophenol was converted to 1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrazine-2,3(1H,4H)-dione. A solution of 1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)pyrazine-2,3(1H,4H)-dione prepared in Part ? (2.28 g, 7.44 mmol), EtN(iPr)2 (3.9 mL, 22.3 mmol), PyBOP (6.78 g, 13.0 mmol) in DMF (35 mL) was stirred at ambient temperature for 1.5 h. After addition of 2-pyridylethyl mercaptan (1.24 g, 8.93 mmol), the reaction was stirred at ambient temperature. After stirring overnight the reaction mixture was partially concentrated under reduced pressure, quenching by addition of aq. NaHCO3 and extracted with EtOAc. The EtOAc extracts were washed with brine, dried over MgSO4 and concentrated. Chromatography on silica employing a gradient elution with 2.5-10% methanol/methylene chloride, followed by chromatography on silica eluting with EtOAc, and trituration with EtOAc/Hexanes afforded the desired product 1-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-3-(2-(pyridin-2-yl)ethylthio)pyrazin-2(1H)-one (2.15 g, 68% yield).

1. stirringAfter stirring overnight the reaction mixture
2. concentrationwas partially concentrated under reduced pressure
3. customquenching by addition of aq. NaHCO3
4. extractionextracted with EtOAc
5. washThe EtOAc extracts were washed with brine
6. dry with materialdried over MgSO4
7. concentrationconcentrated
8. washChromatography on silica employing a gradient elution with 2.5-10% methanol/methylene chloride