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

HRID 4066

Reaktionsgleichung

Reaktionsgleichung von HRID 4066
[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

Komponenten

4

Edukt 2

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

Produkt 1

HCID 138232954-Chloro-6-(4-methyl-1-piperazinyl)-1,2,dihydrobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepineAusbeute 29,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-47b8b78671e24d5398bda6a120b7d060
Quelldatensatz
uspto-grants-1988_02
Patentnummer
US04723003

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