Chloroacetyl chloride → 8-bromo-1-(chloromethyl)-6-(2-pyridyl)-4H-s triazolo[4,3-a][1,4]benzodiazepine

HRID 1731129Notes

Reaction equation

HRID 1731129 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][NH2:13])[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[C:6]=2[CH:20]=1.[Cl:21][CH2:22][C:23](Cl)=O.C([O-])(=O)C.[Na+]>C(O)(=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:23]([CH2:22][Cl:21])=[N:13][N:12]=[C:10]3[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[C:6]=2[CH:20]=1

Participants

5

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 517045Sodium AcetateHCID 12612400HCID 12612400, compound

Product 1

HCID 203612008-bromo-1-(chloromethyl)-6-(2-pyridyl)-4H-s triazolo[4,3-a][1,4]benzodiazepine

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent2×

Procedure

15 g. of 7-bromo-5-(2-pyridyl)-3H-1,4-benzodiazepin-2-yl hydrazine (obtained as in Preparation 2) is slowly added to 150 ml. of acetic acid with external cooling. A solution of 6 g. of chloroacetyl chloride in 75 ml. of acetic acid is then added during about ten minutes, the solution is stirred at room temperature for about 1.5 hours and 4 g. of sodium acetate added with additional stirring for about 30 minutes, the mixture then being refluxed for about 3.25 hours. This mixture is cooled, poured into ice water and concentrated to a small volume, then diluted with water, neutralized with sodium bicarbonate and extracted with chloroform. The extract is dried over anhydrous magnesium sulfate, concentrated and the residue chromatographed on 1 kg. column of silica gel with 1% methanol -- 99% chloroform. The product obtained from the column is crystallized from ethyl acetate to give pure 8-bromo-1-(chloromethyl)-6-(2-pyridyl)-4H-s-triazolo-[4,3-a][1,4]benzodiazepine.

Workup

  1. stirringwith additional stirring for about 30 minutes
  2. temperaturethe mixture then being refluxed for about 3.25 hours
  3. temperatureThis mixture is cooled
  4. concentrationconcentrated to a small volume
  5. additiondiluted with water
  6. extractionextracted with chloroform
  7. dry with materialThe extract is dried over anhydrous magnesium sulfate
  8. concentrationconcentrated
  9. customthe residue chromatographed on 1 kg
  10. customThe product obtained from the column
  11. customis crystallized from ethyl acetate

Sources & evidence

ORD record
ord-07d7af210e674683b84802dcb3bcf780
Source dataset
uspto-grants-1976_11
Patent number
US03995043

Reaction notes

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