1-Methylpiperazine → 4-Methyl-7-(4-methyl-1-piperazinyl)-1,2-dihydrobenzo[c]pyrrolo[1,2,3-ef][1,5]benzodiazepine

HRID 35118Notes

Reaction equation

HRID 35118 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]2[NH:10][C:9](=O)[C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[N:6]3[CH2:16][CH2:17][C:18]([CH:19]=1)=[C:5]23.[CH3:20][N:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1>[Ti](Cl)(Cl)(Cl)Cl.C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([N:24]3[CH2:25][CH2:26][N:21]([CH3:20])[CH2:22][CH2:23]3)[C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[N:6]3[CH2:16][CH2:17][C:18]([CH:19]=1)=[C:5]23

Participants

5

Reactant 2

HCID 531671-MethylpiperazineHCID 138232804-Methyl-1,2-dihydrobenzo[c]pyrrolo[1,2,3-ef][1,5]benzodiazepin-7-one

Product 1

HCID 138232734-Methyl-7-(4-methyl-1-piperazinyl)-1,2-dihydrobenzo[c]pyrrolo[1,2,3-ef][1,5]benzodiazepine

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 1140TolueneSolvent2×

Procedure

A solution of 4-methyl-1,2-dihydrobenzo[c]pyrrolo[1,2,3-ef][1,5]benzodiazepin-7-one (3.6 g, 14.3 mmoles), N-methylpiperazine (16 ml) and toluene (350 ml) was heated to 110° C. Titanium tetrachloride (4.3 ml) was added in three portions in two minute intervals. The mixture was heated under reflux for two hours and cooled to room temperature. Toluene (500 ml) and ice-water (500 ml) were added. The mixture was stirred for 30 minutes and the insoluble material was removed by filtration. The organic phase was separated. The aqueous phase was extracted with toluene (200 ml). The combined toluene solutions were washed with water (300 ml), brine (2 times, 300 ml) and dried over anhydrous sodium sulfate. The solvent was evaporated. The residue was triturated with ethanol:hexane to a solid. Recrystallization of the solid from chloroform:hexane yielded 2.4 g of product. The mother liquor was concentrated and the residue was purified on a silica gel column (60 g, 230-400 mesh) to give a second crop of 1.3 g of product (77% overall yield). Recrystallization from 2-propanol gave the analytical sample, mp 173°-174° C.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for two hours
  3. customthe insoluble material was removed by filtration
  4. customThe organic phase was separated
  5. extractionThe aqueous phase was extracted with toluene (200 ml)
  6. washThe combined toluene solutions were washed with water (300 ml), brine (2 times, 300 ml)
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent was evaporated
  9. customThe residue was triturated with ethanol
  10. customRecrystallization of the solid from chloroform

Sources & evidence

ORD record
ord-89c909ae89554910aa10d4a9318a55c3
Source dataset
uspto-grants-1988_08
Patent number
US04764616

Reaction notes

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