反応 #218689

反応方程式

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

収率 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

収率 26.0%

溶媒

ethanol

ethyl acetate

ethyl acetate

water

water

ethanol

反応条件

後処理

1. 1
   温度heat to reflux
2. 2
   温度cool
3. 3
   workup.DISSOLUTIONto dissolve
4. 4
   その他precipitated salt
5. 5
   その他formed during the extraction
6. 6
   乾燥Extract aqueous phase with ethyl acetate (2×), and dry (sodium sulfate)
7. 7
   ろ過filter
8. 8
   濃縮concentrate organics under reduced pressure to an oil (0.564 g)
9. 9
   温度at reflux
10. 10
    workup.STIRRINGstir
11. 11
    温度at reflux
12. 12
    workup.WAITAfter 4 hours
13. 13
    抽出Extract
14. 14
    その他separated aqueous phase with ethyl acetate
15. 15
    乾燥dry (sodium sulfate)
16. 16
    ろ過filter
17. 17
    濃縮concentrate organics under reduced pressure to a residue (0.86 g)
18. 18
    その他Purify the residue by flash chromatography
19. 19
    洗浄eluting with a gradient of solutions of 2M ammonia in methanol

実験手順

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).

出典