Реакция #218689

Уравнение реакции

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

Выход 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

Выход 26.0%

Растворители

ethanol

ethyl acetate

ethyl acetate

water

water

ethanol

Условия реакции

Обработка

1. 1
   Температураheat to reflux
2. 2
   Температураcool
3. 3
   workup.DISSOLUTIONto dissolve
4. 4
   Другоеprecipitated salt
5. 5
   Другоеformed 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
   Температураat reflux
10. 10
    workup.STIRRINGstir
11. 11
    Температураat reflux
12. 12
    workup.WAITAfter 4 hours
13. 13
    ЭкстракцияExtract
14. 14
    Другоеseparated aqueous phase with ethyl acetate
15. 15
    Сушкаdry (sodium sulfate)
16. 16
    Фильтрацияfilter
17. 17
    Концентрированиеconcentrate organics under reduced pressure to a residue (0.86 g)
18. 18
    ДругоеPurify the residue by flash chromatography
19. 19
    Промывкаeluting with a gradient of solutions of 2M ammonia in methanol

Методика

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).

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