N-[2-(5-bromo-1-indolinyl)phenyl]-4-methyl-1-piperazinecarboxamide → 4-Bromo-6-(4-methyl-1-piperazinyl)-1,2dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine

HRID 4065Notes

Reaction equation

HRID 4065 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[NH:17][C:18]([N:20]1[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]1)=O)[CH2:6][CH2:5]2>P(Cl)(Cl)(Cl)=O>[Br:1][C:2]1[CH:3]=[C:4]2[CH2:5][CH2:6][N:7]3[C:8]2=[C:9]([CH:10]=1)[C:18]([N:20]1[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]1)=[N:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=13

Participants

3

Reactant 1

HCID 13823366N-[2-(5-bromo-1-indolinyl)phenyl]-4-methyl-1-piperazinecarboxamide

Product 1

HCID 138232944-Bromo-6-(4-methyl-1-piperazinyl)-1,2dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepineYield 57%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Procedure

A mixture of N-[2-(5-bromo-1-indolinyl)phenyl]-4-methyl-1-piperazinecarboxamide (11.5 g, 27.5 mmoles) and 750 ml of phosphorus oxychloride was stirred until a solution was obtained and then heated under reflux for 40 minutes. The reaction mixture was cooled. Excess phosphorus oxychloride was removed by evaporation at 50°-55° C. The residue was dried for 30 minutes under vacuum. Ice-chilled 2N sodium hydroxide solution (250 ml) and dichloromethane (350 ml) were added to the residue at 4° C. (ice-water bath). The mixture was stirred until all the solid had dissolved. The organic phase was separated and washed with brine (2 times, 200 ml), dried over anhydrous magnesium sulfate and concentrated. Crystallization from ether (100 ml) gave 5.7 g (57%) of product. Recrystallization from isopropanol yielded the analytical sample, mp 203°-204° C.

Workup

  1. customwas obtained
  2. temperatureheated
  3. temperatureunder reflux for 40 minutes
  4. temperatureThe reaction mixture was cooled
  5. customExcess phosphorus oxychloride was removed by evaporation at 50°-55° C
  6. customThe residue was dried for 30 minutes under vacuum
  7. temperatureIce-chilled 2N sodium hydroxide solution (250 ml) and dichloromethane (350 ml)
  8. additionwere added to the residue at 4° C. (ice-water bath)
  9. stirringThe mixture was stirred until all the solid
  10. dissolutionhad dissolved
  11. customThe organic phase was separated
  12. washwashed with brine (2 times, 200 ml)
  13. dry with materialdried over anhydrous magnesium sulfate
  14. concentrationconcentrated
  15. customCrystallization from ether (100 ml)

Sources & evidence

ORD record
ord-5f08fd378dbe4e63866b0a1299019a73
Source dataset
uspto-grants-1988_02
Patent number
US04723003

Reaction notes

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