反应详情

温度

80 °C

1-Ethyl-2-fluoro-4-(ethyloxy)-5-nitrobenzene (Example 208, step A) (0.50 g, 2.3 mmol) was dissolved in DMSO (15 mL). K2CO3 (0.97 g, 7.0 mmol) and 1-[2-(methylsulfonyl)ethyl]piperazine hydrochloride (Example 148, step B) (1.0 g, 4.7 mmol) were added and the reaction mixture was heated to 80° C. and allowed to stir over the weekend. The mixture was then heated to 120° C. for 4 h. The mixture was cooled to rt then poured into H2O and extracted with DCM. The combined organics were dried with MgSO4, filtered, and concentrated in vacuo. The crude product was purified on a 40 g ISCO column (EtOAc to 10% MeOH in EtOAc). The desired fractions were combined and the solvent removed in vacuo to give the title compound of Step A (0.63 g, 1.6 mmol, 66%) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.78 (s, 1H), 6.56 (s, 1H), 4.12 (q, J=7.0 Hz, 2H), 3.23-3.12 (m, 2H), 3.03 (s, 3H), 3.00-2.91 (m, 6H), 2.72-2.62 (m, 4H), 2.57 (q, J=7.5 Hz, 2H), 2.22 (s, 3H), 1.44 (t, J=7.0 Hz, 3H), 1.22 (t, J=7.5 Hz, 3H). MS (M+H, ES+) 386.

1. temperatureThe mixture was then heated to 120° C. for 4 h
2. temperatureThe mixture was cooled to rt
3. extractionextracted with DCM
4. dry with materialThe combined organics were dried with MgSO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe crude product was purified on a 40 g ISCO column (EtOAc to 10% MeOH in EtOAc)
8. customthe solvent removed in vacuo