反应详情

温度

100 °C

A mixture of 5-[4-(methylsulfonyl)phenyl]-2-pyrazinol (and tautomers thereof) (0.15 g, 0.60 mmol), {1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl methanesulfonate (prepared as in Example 100, Step 4, except that on small scale no heptane wash was performed, 0.25 g, 0.81 mmol) and K2CO3 (0.17 g, 1.20 mmol) in DMF (6 mL) was stirred at ambient temperature overnight, then heated at 100° C. for 5 h. The mixture was cooled to ambient temperature, water was added, and the mixture was extracted with EtOAc (60 mL×2). The combined organic extracts were washed with water, brine and dried over Na2SO4, filtered, and the filtrate was concentrated to a brown solid. The crude material was purified by chromatography on a silica gel column eluted with 1:20 acetone/CH2Cl2 to 1:15 acetone/CH2Cl2 to give 0.14 g (51%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.55 (d, 1H, J=0.9 Hz), 8.31 (s, 1H), 8.11 (d, 2H, J=8.6 Hz), 8.02 (d, 2H, J=8.6 Hz), 4.30-4.20 (m, 4H), 3.10-3.05 (m, 5H), 2.91 (septet, 1H, J=7.0 Hz), 2.10-2.00 (m, 1H), 2.00-1.90 (m, 2H), 1.55-1.40 (m, 2H), 1.27 (d, 6H, J=6.6 Hz); LRMS (ESI), m/z 458 (M+H).

1. washexcept that on small scale no heptane wash
2. temperatureThe mixture was cooled to ambient temperature
3. extractionthe mixture was extracted with EtOAc (60 mL×2)
4. washThe combined organic extracts were washed with water, brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationthe filtrate was concentrated to a brown solid
8. customThe crude material was purified by chromatography on a silica gel column
9. washeluted with 1:20 acetone/CH2Cl2 to 1:15 acetone/CH2Cl2