Sodium Chloride → HCID 136372576, compound

HRID 131507Notes

Reaction equation

HRID 131507 reaction equation
I[CH2:2][CH2:3][OH:4].[CH3:5][O:6][CH2:7][CH2:8][C@@H:9]1[NH:14][CH2:13][CH2:12][N:11]([C:15]2[C:24]3[N:23]=[C:22]([C:25]([F:28])([F:27])[F:26])[S:21][C:20]=3[NH:19][C:18]3[CH:29]=[CH:30][CH:31]=[CH:32][C:17]=3[N:16]=2)[CH2:10]1.C(=O)([O-])[O-].[K+].[K+].[Cl-].[Na+]>C(O)C.C(OCC)(=O)C.O>[CH3:5][O:6][CH2:7][CH2:8][CH:9]1[CH2:10][N:11]([C:15]2[C:24]3[N:23]=[C:22]([C:25]([F:27])([F:28])[F:26])[S:21][C:20]=3[NH:19][C:18]3[CH:29]=[CH:30][CH:31]=[CH:32][C:17]=3[N:16]=2)[CH2:12][CH2:13][N:14]1[CH2:2][CH2:3][OH:4]

Participants

8

Reactant 4

HCID 5234Sodium ChlorideHCID 11430Potassium Carbonate2×HCID 12225Iodoethanol3×HCID 135457486(S)-10-[3-(2-Methoxy-ethyl)-piperazin-1-yl]-2-trifluoromethyl-4H-3-thia-1,4,9-triaza-benzo[f]azulene

Product 1

HCID 136372576HCID 136372576, compoundYield 26%

Reagents, catalysts & solvents 3

HCID 702EthanolSolvent2×HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent2×

Procedure

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).

Workup

  1. temperatureheat to reflux
  2. temperaturecool
  3. dissolutionto dissolve
  4. customprecipitated salt
  5. customformed during the extraction
  6. dry with materialExtract aqueous phase with ethyl acetate (2×), and dry (sodium sulfate)
  7. filtrationfilter
  8. concentrationconcentrate organics under reduced pressure to an oil (0.564 g)
  9. temperatureat reflux
  10. stirringstir
  11. temperatureat reflux
  12. waitAfter 4 hours
  13. extractionExtract
  14. customseparated aqueous phase with ethyl acetate
  15. dry with materialdry (sodium sulfate)
  16. filtrationfilter
  17. concentrationconcentrate organics under reduced pressure to a residue (0.86 g)
  18. customPurify the residue by flash chromatography
  19. washeluting with a gradient of solutions of 2M ammonia in methanol

Sources & evidence

ORD record
ord-f97d466af76f42bb87df08a9e44a1819
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

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