Hydrochloric Acid → HCID 21448991, compound

HRID 597079Notes

Reaction equation

HRID 597079 reaction equation
[CH3:1][N:2]([CH3:26])[CH2:3][CH2:4][C:5]1[N:9]2[C:10]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:11]=3[C:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[N:13][CH2:14][C:8]2=[N:7][N:6]=1.B.Cl>O1CCCC1>[CH3:26][N:2]([CH3:1])[CH2:3][CH2:4][C:5]1[N:9]2[C:10]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:11]=3[CH:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[NH:13][CH2:14][C:8]2=[N:7][N:6]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6331BoraneHCID 134389HCID 134389, compound

Product 1

HCID 21448991HCID 21448991, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A stirred mixture of 1-[2-(dimethylamino)ethyl]-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine (3.66 g., 0.01 mole) in tetrahydrofuran (100 ml.) is cooled in an ice bath, under nitrogen, and treated with 20 ml. of a 1M solution of borane in tetrahydrofuran. The mixture is allowed to warm to ambient temperature (22°-25°) and stand for 18 hours. It is then refluxed for 1 hour, cooled in an ice bath and treated with 3 ml. of 6N hydrochloric acid. This mixture is boiled for 3 hours with distillation. During this period methanol is added so that the volume of the mixture remains about constant. The mixture is then concentrated in vacuo. The residue is mixed with water, neutralized with sodium bicarbonate and extracted with chloroform. The extract is washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue is dissolved in methanol (70 ml.) mixed with 25% aqueous ethylene diamine (42 ml.) and refluxed for 3 hours. The mixture is concentrated to remove methanol, diluted with salt water and extracted with chloroform. The extract is washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue is chromatographed over silica gel (200 g.) with methanol. The product thus obtained is crystallized from ethyl acetate-Skellysolve B (hexanes) to give 1-[2-(dimethylamino)ethyl]-8-chloro-5,6-dihydro-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine of melting point 131°-137° C.

Workup

  1. temperatureis cooled in an ice bath, under nitrogen
  2. additiontreated with 20 ml
  3. temperatureIt is then refluxed for 1 hour
  4. temperaturecooled in an ice bath
  5. additiontreated with 3 ml
  6. distillationThis mixture is boiled for 3 hours with distillation
  7. additionDuring this period methanol is added so that the volume of the mixture
  8. concentrationThe mixture is then concentrated in vacuo
  9. additionThe residue is mixed with water
  10. extractionextracted with chloroform
  11. washThe extract is washed with brine
  12. dry with materialdried over anhydrous sodium sulfate
  13. concentrationconcentrated in vacuo
  14. dissolutionThe residue is dissolved in methanol (70 ml.)
  15. additionmixed with 25% aqueous ethylene diamine (42 ml.)
  16. temperaturerefluxed for 3 hours
  17. concentrationThe mixture is concentrated
  18. customto remove methanol
  19. additiondiluted with salt water
  20. extractionextracted with chloroform
  21. washThe extract is washed with brine
  22. dry with materialdried over anhydrous sodium sulfate
  23. concentrationconcentrated in vacuo
  24. customThe residue is chromatographed over silica gel (200 g.) with methanol
  25. customThe product thus obtained
  26. customis crystallized from ethyl acetate-Skellysolve B (hexanes)

Sources & evidence

ORD record
ord-c0fde9e6d58e4fb28de310aab74a82e4
Source dataset
uspto-grants-1977_03
Patent number
US04012413

Reaction notes

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