反应详情

Add 1-bromo-3-fluoropropane (0.14 mL, 1.52 mmol) to a slurry of (S)-10-[3-(2-methoxy-ethyl)-piperazin-1-yl]-2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene (0.52 g, 1.26 mmol), powdered potassium carbonate (0.87 g, 6.32 mmol), and sodium iodide (0.95 g, 6.32 mmol) in absolute ethanol (7.8 mL) and heat to reflux. After an overnight period, cool, add saturated aqueous sodium chloride and ethyl acetate, and add deionized water to dissolve precipitated salt that formed during the extraction. Extract aqueous phase with ethyl acetate (2×), and dry (sodium sulfate), filter, and concentrate organics under reduced pressure to an oil (0.564 g). Purify the oil by flash chromatography, eluting with a gradient of a 2% solution of 2M ammonia in methanol, in dichloromethane, (0-100%) to give the title compound: mass spectrum (APCI, m/e): 472 (M+1); NMR (1H, 300 MHz, DMSO-d6): δ 8.47 (s, 1H), 6.96-6.82 (m, 3H), 6.71 (m, 1H), 4.55 (td, 2H, 2J(H,F)=48 Hz, 3J(H,H)=5.7 Hz), 3.47 (br. m, 3H), 3.31-3.18 (m, 3H), 3.15 (s, 3H), 2.70 (m, 2H), 2.55 (br. m, 1H), 2.38 (m, 2H), 1.86-1.67 (in, 3H), 1.61 (m, 1H).

1. temperatureheat to reflux
2. temperaturecool
3. dissolutionto dissolve
4. customprecipitated salt
5. customthat formed during the extraction
6. dry with materialExtract aqueous phase with ethyl acetate (2×), and dry (sodium sulfate)
7. filtrationfilter
8. concentrationconcentrate organics under reduced pressure to an oil (0.564 g)
9. customPurify the oil by flash chromatography
10. washeluting with a gradient of a 2% solution of 2M ammonia in methanol, in dichloromethane, (0-100%)