Reacción #218688

Ecuación de reacción

1-bromo-3-fluoropropane

(S)-10-[3-(2-methoxy-ethyl)-piperazin-1-yl]-2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene

potassium carbonate

sodium iodide

sodium chloride

→

title compound

(S)-10-[4-(3-Fluoro-propyl)-3-(2-methoxy-ethyl)-piperazin-1-yl]-2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene

Disolventes

ethanol

ethyl acetate

water

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturaheat to reflux
2. 2
   Temperaturacool
3. 3
   workup.DISSOLUTIONto dissolve
4. 4
   Otroprecipitated salt
5. 5
   Otrothat formed during the extraction
6. 6
   SecadoExtract aqueous phase with ethyl acetate (2×), and dry (sodium sulfate)
7. 7
   Filtraciónfilter
8. 8
   Concentraciónconcentrate organics under reduced pressure to an oil (0.564 g)
9. 9
   OtroPurify the oil by flash chromatography
10. 10
    Lavadoeluting with a gradient of a 2% solution of 2M ammonia in methanol, in dichloromethane, (0-100%)

Procedimiento

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).

Fuente