反应详情

A solution of 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide (0.369 g, 1.50 mmol) and 37 wt % aqueous formaldehyde (30.0 mg, 1.50 mmol) in 1 mL of HOAc:dioxane (1:4) was added to 6-chloro-1-H-indole (0.152 g, 1.00 mmol) and the reaction mixture was stirred for 12 h at room temperature. The resulting mixture was diluted with H2O (10 mL). The aqueous layer was extracted with CH2Cl2 (3×100 mL). The combined organic extracts were washed with brine (10 mL), dried over MgSO4, and concentrated in vacuo. The residue was purified by preparative TLC on silica using 5% of NH3 (2.0 M in methanol) in CH2Cl2 to give the desired product (79 mg, 42%). 1H NMR (400 MHz, CDCl3) δ 9.14 (s, 1H), 8.04 (s, 1H), 7.52 (t, 2H, J=8.1 Hz), 7.35 (d, 2H, J=13.3 Hz), 7.18 (t, 1H, J=7.9 Hz), 7.09 (dd, 1H, J=1.9, 8.5 Hz), 6.85 (d, 1H, J=7.4 Hz), 5.18 (s, 1H), 4.01 (s, 2H), 2.55 (septet, 1H, J=6.8 Hz), 2.48–2.34 (m, 3H), 2.08–1.95 (m, 4H), 1.78 (d, 2H, J=12.8 Hz), 1.22 (d, 6H, J=6.8 Hz); ESMS m/e: 410.1 (M+H)+.

1. extractionThe aqueous layer was extracted with CH2Cl2 (3×100 mL)
2. washThe combined organic extracts were washed with brine (10 mL)
3. dry with materialdried over MgSO4
4. concentrationconcentrated in vacuo
5. customThe residue was purified by preparative TLC on silica using 5% of NH3 (2.0 M in methanol) in CH2Cl2