Ethyl Acetate → 1-(2-aminoethyl)-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine

HRID 1731084Notes

Reaction equation

HRID 1731084 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12]([CH2:15][CH2:16][N:17]4C(=O)C5=CC=CC=C5C4=O)=[N:13][N:14]=[C:10]3[CH2:9][N:8]=[C:7]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:6]=2[CH:34]=1.C(OCC)(=O)C.O.NN>C(O)C>[NH2:17][CH2:16][CH2:15][C:12]1[N:11]2[C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:34][C:6]=3[C:7]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[N:8][CH2:9][C:10]2=[N:14][N:13]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 24654Hydrazine hydrate (1:1)HCID 126123918-chloro-6-phenyl-1-(2-phthalimidoethyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine

Product 1

HCID 126124031-(2-aminoethyl)-8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A stirred mixture of 8-chloro-6-phenyl-1-(2-phthalimidoethyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine, ethyl acetate solvate (37.6 g., 0.0675 mole) and absolute ethanol (340 ml.) is treated with hydrazine hydrate (7.43 g.) and warmed, under nitrogen, in an oil bath to 75° during 65 minutes, the bath is kept at this temperature for an additional 55 minutes. The mixture is then cooled in an ice bath, and the solid is collected by filtration and washed with absolute ethanol and methylene chloride. The combined filtrate is mixed with ice cold salt water and extracted with methylene chloride. The extract is washed with water, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue is chromatographed on silica gel (1 kg.) with methanol and the resulting product is crystallized from methylene chloride diethyl ether to give 1-(2-aminoethyl)-8-chloro-6-phenyl-4H-s-triazolo-[4,3-a][1,4]benzodiazepine in 2 crops: 5.29 g. of melting point 198°-200° C. dec., and 2.37 g., of melting point 194°-196.5° C. dec. The analytical sample is crystallized from methanol-ethyl acetate and has a melting point of 205°-207° C.

Workup

  1. temperaturewarmed, under nitrogen, in an oil bath to 75° during 65 minutes
  2. temperatureThe mixture is then cooled in an ice bath
  3. filtrationthe solid is collected by filtration
  4. washwashed with absolute ethanol and methylene chloride
  5. additionThe combined filtrate is mixed with ice cold salt water
  6. extractionextracted with methylene chloride
  7. washThe extract is washed with water
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customThe residue is chromatographed on silica gel (1 kg.) with methanol
  11. customthe resulting product is crystallized from methylene chloride diethyl ether

Sources & evidence

ORD record
ord-4a692b6968144860914d7253eed7c227
Source dataset
uspto-grants-1976_11
Patent number
US03994941

Reaction notes

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