Bromazepam → 7-Bromo-5-(pyridin-2-yl)-1,3-dihydro-2H-1,4-benzodiazepine-2-thione

HRID 1580645Notes

Reaction equation

HRID 1580645 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10](=O)[CH2:9][N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)[C:6]=2[CH:19]=1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:21]>N1C=CC=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10](=[S:21])[CH2:9][N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)[C:6]=2[CH:19]=1

Participants

4

Reactant 2

HCID 2441BromazepamHCID 14817Phosphorus sulfide (P2S5)

Product 1

HCID 126123797-Bromo-5-(pyridin-2-yl)-1,3-dihydro-2H-1,4-benzodiazepine-2-thione

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A stirred solution of 6.53 g. of 7-bromo-1,3-dihydro-5-(2-pyridyl)-2H-1,4-benzodiazepin-2-one (prepared as in J. Pharm. Sci. 53, 264) in 400 ml. of dry pyridine is heated in an oil bath, under nitrogen, with 5.05 g. of phosphorus pentasulfide at between about 110° to 120° C. for about 1 hour, cooled and concentrated under vacuum. Pyridine remaining in the residue is removed by the successive addition of xylene and toluene with vacuum concentration after each addition of solvent. The dark brown solid residue is triturated with a mixture of aqueous sodium carbonate solution and chloroform and the resulting finely divided tan solid is collected by filtration, washed with water, dissolved in a mixture of chloroform and ethanol, decolorized with activated carbon and crystallized to yield 3.39 g. of product melting at 249° C. (with decomposition) and 0.559 g. melting at 243° C. (with decomposition). The analytical sample is crystallized from ethanol to give pure 7-bromo-1,3-dihydro-5-(2-pyridyl)-2H-1,4-benzodiazepine-2-thione, with a melting point of 245° to 246° C. (with decomposition) and ultraviolet (ethanol) end absorption, μmax 219 mu (ε=24,100).

Workup

  1. temperaturecooled
  2. concentrationconcentrated under vacuum
  3. customPyridine remaining in the residue is removed by the successive addition of xylene and toluene with vacuum concentration
  4. additionafter each addition of solvent
  5. customThe dark brown solid residue is triturated with a mixture of aqueous sodium carbonate solution and chloroform
  6. filtrationthe resulting finely divided tan solid is collected by filtration
  7. washwashed with water
  8. dissolutiondissolved in a mixture of chloroform and ethanol
  9. customcrystallized
  10. customto yield 3.39 g
  11. customThe analytical sample is crystallized from ethanol

Sources & evidence

ORD record
ord-bba42334c75e43da9d37400754c3a4a8
Source dataset
uspto-grants-1976_01
Patent number
US03933794

Reaction notes

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