反应详情

温度

95 °C

A mixture of 1-[3-(ethyloxy)-4-nitrophenyl]-4-(4-piperidinyl)piperazine (Example 91, step A) (0.30 g, 0.90 mmol) and methyl vinyl sulfone (0.29 g, 2.7 mmol) in dioxane (9.0 mL) was stirred under N2. The reaction was heated to 95° C. and stirred for approximately 3 h, then cooled to rt. The reaction mixture was concentrated under vacuum. The residue was taken up in DCM and aqueous (saturated) NaHCO3. The aqueous layer was extracted with DCM (3×). The combined organic layers were dried over MgSO4 and concentrated under vacuum. The residue was chromatographed on silica gel to give the title compound of step A (294 mg, 0.66 mmol, 74%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 7.85 (d, 1H, J=9.35 Hz), 6.56 (dd, 1H, J=9.44 and 2.29 Hz), 6.49 (d, 1H, J=2.38 Hz), 4.17 (q, 2H, J=6.96 Hz), 3.36-3.41 (m, 4H), 3.25 (t, 2H, J=6.78 Hz), 3.01 (s, 3H), 2.92 (M, 2H), 2.66 (t, 2H, J=6.78 Hz), 2.57 (m, 4H), 2.15-2.25 (m, 1H), 1.89-1.97 (m, 2H), 1.75 (m, 2H), 1.32-1.40 (m, 5H).

1. stirringstirred for approximately 3 h
2. temperaturecooled to rt
3. concentrationThe reaction mixture was concentrated under vacuum
4. extractionThe aqueous layer was extracted with DCM (3×)
5. dry with materialThe combined organic layers were dried over MgSO4
6. concentrationconcentrated under vacuum
7. customThe residue was chromatographed on silica gel