반응 #218689

반응 방정식

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

수율 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

수율 26.0%

용매

ethanol

ethyl acetate

ethyl acetate

water

water

ethanol

반응 조건

후처리

1. 1
   온도heat to reflux
2. 2
   온도cool
3. 3
   workup.DISSOLUTIONto dissolve
4. 4
   기타precipitated salt
5. 5
   기타formed during the extraction
6. 6
   건조Extract aqueous phase with ethyl acetate (2×), and dry (sodium sulfate)
7. 7
   여과filter
8. 8
   농축concentrate organics under reduced pressure to an oil (0.564 g)
9. 9
   온도at reflux
10. 10
    workup.STIRRINGstir
11. 11
    온도at reflux
12. 12
    workup.WAITAfter 4 hours
13. 13
    추출Extract
14. 14
    기타separated aqueous phase with ethyl acetate
15. 15
    건조dry (sodium sulfate)
16. 16
    여과filter
17. 17
    농축concentrate organics under reduced pressure to a residue (0.86 g)
18. 18
    기타Purify the residue by flash chromatography
19. 19
    세척eluting with a gradient of solutions of 2M ammonia in methanol

실험 절차

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).

출처