Реакция #218688

Уравнение реакции

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

Растворители

ethanol

ethyl acetate

water

Условия реакции

Обработка

1. 1
   Температураheat to reflux
2. 2
   Температураcool
3. 3
   workup.DISSOLUTIONto dissolve
4. 4
   Другоеprecipitated salt
5. 5
   Другоеthat formed during the extraction
6. 6
   СушкаExtract aqueous phase with ethyl acetate (2×), and dry (sodium sulfate)
7. 7
   Фильтрацияfilter
8. 8
   Концентрированиеconcentrate organics under reduced pressure to an oil (0.564 g)
9. 9
   ДругоеPurify the oil by flash chromatography
10. 10
    Промывкаeluting with a gradient of a 2% solution of 2M ammonia in methanol, in dichloromethane, (0-100%)

Методика

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).

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