Guanidine Hydrochloride → HCID 136404504, compound

HRID 2165727Notes

Reaction equation

HRID 2165727 reaction equation
[Na].Cl.[NH2:3][C:4]([NH2:6])=[NH:5].[C:7]([CH:9]([C:36](OCC)=[O:37])[CH2:10][CH2:11][CH2:12][CH2:13][N:14]([S:26]([C:29]1[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=1)(=[O:28])=[O:27])[C:15]1[CH:25]=[CH:24][C:18]([C:19]([O:21]CC)=[O:20])=[CH:17][CH:16]=1)#[N:8]>C(O)C.C(O)(=O)C.C(OCC)(=O)C>[NH2:5][C:4]1[NH:6][C:36](=[O:37])[C:9]([CH2:10][CH2:11][CH2:12][CH2:13][N:14]([S:26]([C:29]2[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=2)(=[O:28])=[O:27])[C:15]2[CH:25]=[CH:24][C:18]([C:19]([OH:21])=[O:20])=[CH:17][CH:16]=2)=[C:7]([NH2:8])[N:3]=1

Participants

7

Reactant 3

HCID 5742Guanidine HydrochlorideHCID 5360545Sodium2×HCID 15077393HCID 15077393, compound

Product 1

HCID 136404504HCID 136404504, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolvent3×HCID 702EthanolSolvent5×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 0.377 g (0.0164 mol) of sodium in 8 mL of absolute ethanol under nitrogen was added 1.04 g (0.0109 mol) of guanidine hydrochloride and 1 mL of rinse absolute ethanol. The mixture was stirred for 30 min, and to it was added a solution of 2.73 g (0.00546 mol) of ethyl 4-[(5-cyano-6-ethoxy-6-oxohexyl)tosylamino]benzoate.0.15 ethyl acetate in 6 mL of absolute ethanol and then 7 mL of rinse absolute ethanol. The mixture was refluxed for 4 h and was allowed to cool to room temperature and stand under nitrogen overnight. The reaction mixture was filtered by suction, and the filtrate was neutralized with 0.984 g (0.0164 mol) of glacial acetic acid. The solution was concentrated under vacuum at 30° C. to a solid that was washed well with 50 mL of water, collected by suction filtration, washed again with 25, 25, and 10 mL of water, and dried under vacuum at 60° C.; yield, 2.76 g. Fourier transform NMR (Me2SOd6) and chemical ionization mass spectroscopy indicated a mixture of product and uncyclized intermediates. A 2.41 g sample of solid was added to a solution of 3.16 g (0.137 mol) of sodium in 138 mL of absolute ethanol under nitrogen. The mixture was heated to reflux, and the resulting solution was refluxed for 3 h 15 min. The slightly cloudy solution was allowed to cool to room temperature, and the resulting mixture was allowed to stand under nitrogen overnight. The mixture was heated briefly back to reflux, and the resulting slightly cloudy, hot solution was neutralized with 8.30 g (0.138 mol) of glacial acetic acid. The thick mixture was concentrated under vacuum at 35° C. to a white solid to which was added 50 mL of water. Then to the stirred mixture was added approximately 5-8 mL of concentrated hydrochloric acid. The mixture with a pH of 5.5 was filtered by suction, and collected solid was washed with 15 and 20 mL of water and dried under vacuum overnight at room temperature in a desiccator; yield, 1.98 g (84%): NMR (Me2SOd6) δ 1.2-1.4 (m, 4H), 2.06 (t, 2H), 2.37 (s, 3H), 3.54 (t, 2H), 5.58 (br s, 2H), 5.89 (br s, 2H), 7.14 (d, 2H), 7.3-7.5 (AA'BB', 4H), 7.86 (d, 2H), 9.75 (br), 0.13 mol of acetic acid.

Workup

  1. temperatureThe mixture was refluxed for 4 h
  2. waitstand under nitrogen overnight
  3. filtrationThe reaction mixture was filtered by suction
  4. concentrationThe solution was concentrated under vacuum at 30° C. to a solid
  5. washthat was washed well with 50 mL of water
  6. filtrationcollected by suction filtration
  7. washwashed again with 25, 25, and 10 mL of water
  8. customdried under vacuum at 60° C.
  9. customyield
  10. additiona mixture of product and uncyclized intermediates
  11. temperatureThe mixture was heated
  12. temperatureto reflux
  13. temperaturethe resulting solution was refluxed for 3 h 15 min
  14. temperatureto cool to room temperature
  15. waitto stand under nitrogen overnight
  16. temperatureThe mixture was heated briefly back
  17. temperatureto reflux
  18. concentrationThe thick mixture was concentrated under vacuum at 35° C. to a white solid to which
  19. additionwas added 50 mL of water
  20. additionThen to the stirred mixture was added approximately 5-8 mL of concentrated hydrochloric acid
  21. filtrationThe mixture with a pH of 5.5 was filtered by suction
  22. customcollected solid
  23. washwas washed with 15 and 20 mL of water
  24. customdried under vacuum overnight at room temperature in a desiccator
  25. customyield

Sources & evidence

ORD record
ord-7986c946dd9342819576cba040f61934
Source dataset
uspto-grants-1990_07
Patent number
US04940713

Reaction notes

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