Reaktion #218689

Reaktionsgleichung

potassium carbonate

sodium chloride

2-iodo-ethanol

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

potassium carbonate

2-iodo-ethanol

2-iodo-ethanol

→

title compound

Ausbeute 26.0%

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

Ausbeute 26.0%

Lösungsmittel

ethanol

ethyl acetate

ethyl acetate

water

water

ethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturheat to reflux
2. 2
   Temperaturcool
3. 3
   workup.DISSOLUTIONto dissolve
4. 4
   Sonstigeprecipitated salt
5. 5
   Sonstigeformed during the extraction
6. 6
   TrocknenExtract aqueous phase with ethyl acetate (2×), and dry (sodium sulfate)
7. 7
   Filtrationfilter
8. 8
   Einengenconcentrate organics under reduced pressure to an oil (0.564 g)
9. 9
   Temperaturat reflux
10. 10
    workup.STIRRINGstir
11. 11
    Temperaturat reflux
12. 12
    workup.WAITAfter 4 hours
13. 13
    ExtraktionExtract
14. 14
    Sonstigeseparated aqueous phase with ethyl acetate
15. 15
    Trocknendry (sodium sulfate)
16. 16
    Filtrationfilter
17. 17
    Einengenconcentrate organics under reduced pressure to a residue (0.86 g)
18. 18
    SonstigePurify the residue by flash chromatography
19. 19
    Wascheneluting with a gradient of solutions of 2M ammonia in methanol

Vorschrift

Add 2-iodo-ethanol (0.44 mL, 2.55 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 (0.75 g, 1.82 mmol), and powdered potassium carbonate (1.26 g, 9.11 mmol) in absolute ethanol (7.5 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 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). Add absolute ethanol (8 mL), powdered potassium carbonate (0.62 g, 4.50 mmol), followed by 2-iodo-ethanol (0.098 mL, 1.26 mmol), and stir 15.5 hours at reflux. Add additional 2-iodo-ethanol (0.010 mL, 0.13 mmol), and stir at reflux. After 4 hours, cool to ambient temperature and add deionized water and ethyl acetate. Extract separated aqueous phase with ethyl acetate, and combine, dry (sodium sulfate), filter, and concentrate organics under reduced pressure to a residue (0.86 g). Purify the residue by flash chromatography, eluting with a gradient of solutions of 2M ammonia in methanol: ethyl acetate (1%-5% 2M ammonia in methanol in ethyl acetate) to give the title compound (0.213 g, 26%): mass spectrum (APCI, m/e): 456 (M+1); NMR (1H, 300 MHz, DMSO-d6) δ 8.45 (s, 1H), 6.96-6.81 (m, 3H), 6.71 (m, 1H), 4.38 (t, 1H, J=5.4 Hz), 3.54-3.06 (m, 11H), 2.71 (m, 2H), 2.55 (m, 1H), 2.41 (m, 2H), 1.68 (m, 2H).

Quelle