Reacción #218692

Ecuación de reacción

potassium carbonate

sodium iodide

water

ethyl acetate

(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

→

ammonia

title compound

Rendimiento 23.0%

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

Rendimiento 23.0%

Disolventes

ethanol

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturaheat to reflux
2. 2
   Temperaturacool
3. 3
   Lavadorinse in solids with absolute ethanol
4. 4
   Temperaturareflux
5. 5
   workup.WAITAfter 4 hours
6. 6
   Temperaturareflux
7. 7
   workup.WAITAfter 17.5 hours
8. 8
   Temperaturacool
9. 9
   OtroAfter separation of layers
10. 10
    Extracciónextract aqueous layer with ethyl acetate (2×)
11. 11
    Secadodry (sodium sulfate)
12. 12
    Filtraciónfilter
13. 13
    Concentraciónconcentrate organics under reduced pressure to a solid (1.54 g)
14. 14
    OtroPurify the solid by flash chromatography
15. 15
    Lavadoeluting with a gradient of solutions of 2M ammonia in methanol

Procedimiento

Add (S)2-(2-chloro-ethoxy)-ethanol (0.267 mL, 2.53 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 (5.2 mL), and heat to reflux. After 22 hours, cool and add powdered potassium carbonate (0.09 g, 0.65 mmol), sodium iodide (0.09 g, 0.60 mmol), and (S)-(2-2-chloro-ethoxy)-ethanol (0.100 mL, 0.938 mmol); rinse in solids with absolute ethanol, and reflux. After 4 hours, add (S)-2-(2-chloro-ethoxy)-ethanol (0.307 mL, 2.88 mmol) and reflux. After 17.5 hours, cool and add deionized water and ethyl acetate. After separation of layers, extract aqueous layer with ethyl acetate (2×), and combine, dry (sodium sulfate), filter, and concentrate organics under reduced pressure to a solid (1.54 g). Purify the solid 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 over 61 minutes), and then with a 5% solution of 2M ammonia in methanol, in ethyl acetate for 30 minutes to give the title compound (0.146 g, 23%): mass spectrum (APCI, m/e): 500 (M+1); NMR (1H, 300 MHz, DMSO-d6) δ 8.47 (s, 1H), 6.96-6.81 (m, 3H), 6.71 (m, 1H), 4.60 (t, 1H, J=5.1 Hz), 3.56-3.10 (m, 15H), 2.76 (m, 2H), 2.61-2.41 (m, 3H), 1.68 (m, 2H).

Fuente