Phosphorus pentachloride → 5-(4-methyl-1-homopiperazinyl)-11H-imidazo[1,2-c][1,3]benzodiazepine

HRID 2164809Notes

Reaction equation

HRID 2164809 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[NH:13][C:14]([N:16]1[CH2:22][CH2:21][CH2:20][N:19]([CH3:23])[CH2:18][CH2:17]1)=O.P(Cl)(Cl)(Cl)(Cl)Cl>P(Cl)(Cl)(Cl)=O>[CH3:23][N:19]1[CH2:20][CH2:21][CH2:22][N:16]([C:14]2[N:3]3[CH:4]=[CH:5][N:1]=[C:2]3[CH2:6][C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[N:13]=2)[CH2:17][CH2:18]1

Participants

4

Reactant 2

HCID 24819Phosphorus pentachlorideHCID 133449231-[2-(2-Imidazolylmethyl)phenylcarbamoyl]-4-methylhomopiperazine

Product 1

HCID 133449135-(4-methyl-1-homopiperazinyl)-11H-imidazo[1,2-c][1,3]benzodiazepine

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Procedure

To a suspension of 2.46 g of 1-[2-(2-imidazolylmethyl)phenylcarbamoyl]-4-methylhomopiperazine in 19.4 ml of phosphorus oxychloride is added at once 1.66 g of phosphorous pentachloride and the mixture is stirred at room temperature for 4 hours. The mixture is evaporated to dryness, the residue is suspended in 45.2 ml of methylene chloride, the suspension is cooled to 0° and 21.4 ml of triethylamine are added dropwise with stirring over a period of 15 minutes. The mixture is allowed to warm up to room temperature, stirred for 1.5 hours and poured into 10% aqueous potassium carbonate. The methylene chloride layer is separated, the aqueous layer is washed with methylene chloride and the combined methylene chloride extracts are dried over MgSO4, decolorized with charcoal and evaporated to dryness. The residue is purified by column chromatography with 50 g of silica gel, using methylene chloride-methanol-conc. ammonium hydroxide (300:50:1) as eluent to give 5-(4-methyl-1-homopiperazinyl)-11H-imidazo[1,2-c][1,3]benzodiazepine as an oil. This free base is dissolved in acetone and treated with maleic acid to give 5-(4-methyl-1-homopiperazinyl)-11H-imidazo[1,2-c][1,3]benzodiazepine monomaleate, m.p. 160°-163°.

Workup

  1. customThe mixture is evaporated to dryness
  2. temperaturethe suspension is cooled to 0°
  3. addition21.4 ml of triethylamine are added dropwise
  4. stirringwith stirring over a period of 15 minutes
  5. temperatureto warm up to room temperature
  6. stirringstirred for 1.5 hours
  7. additionpoured into 10% aqueous potassium carbonate
  8. customThe methylene chloride layer is separated
  9. washthe aqueous layer is washed with methylene chloride
  10. dry with materialthe combined methylene chloride extracts are dried over MgSO4
  11. customevaporated to dryness
  12. customThe residue is purified by column chromatography with 50 g of silica gel

Sources & evidence

ORD record
ord-71ad8441f9d44bd8a7b2bc818ee00c61
Source dataset
uspto-grants-1985_03
Patent number
US04507311

Reaction notes

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