1,2-Dichloroethane → 4-Chloro-6-(4-methyl-1-piperazinyl)-1,2,dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepine

HRID 35112

Reaction equation

HRID 35112 reaction equation
[Cl: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.ClCCCl>ClCCl>[Cl: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

4

Reactant 2

HCID 111,2-DichloroethaneHCID 13823362N-[2-(5-chloro-1-indolinyl)phenyl]-4-methyl-1-piperazinecarboxamide

Product 1

HCID 138232954-Chloro-6-(4-methyl-1-piperazinyl)-1,2,dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepineYield 29.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
75 °C

Procedure

To N-[2-(5-chloro-1-indolinyl)phenyl]-4-methyl-1-piperazinecarboxamide (13.5 g, 36.5 mmoles) was added a solution of polyphosphoric acid ethyl ester and 1,2-dichloroethane (250 ml) The solution was heated at 75° C. for 4 hours with exclusion of moisture. The solution was cooled and poured into a mixture of ice-sodium hydroxide solution (2 l) and dichloromethane (1.2 l). The mixture was stirred for 15 minutes. The layers were separated. The organic layer was washed with 2 l of 2N sodium hydroxide, then with brine (500 ml), and dried over anhydrous magnesium sulfate. Removal of the solvent at reduced pressure gave an oil. The oil was purified by flash chromatography on a silica gel column (1 kg, 230-400 mesh), packed and eluted initially with dichloromethane, then with dichloromethane containing an increasing methanol content in 1% increments to a final content of 5% (total 8 l). Concentration of the 5% methanol/dichloromethane eluent gave 3.8 g (28%) of product. Recrystallization from 2-propanol (50 ml) gave the analytical sample, mp 182°-183° C.

Workup

  1. temperatureThe solution was cooled
  2. customThe layers were separated
  3. washThe organic layer was washed with 2 l of 2N sodium hydroxide
  4. dry with materialwith brine (500 ml), and dried over anhydrous magnesium sulfate
  5. customRemoval of the solvent at reduced pressure
  6. customgave an oil
  7. customThe oil was purified by flash chromatography on a silica gel column (1 kg, 230-400 mesh)
  8. washeluted initially with dichloromethane

Sources & evidence

ORD record
ord-537b72dbff364460abb2bda845c26835
Source dataset
uspto-grants-1988_08
Patent number
US04764616

Linked notes

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