Hydrochloric Acid → 4-(2,4-Dichlorobenzyloxy)-1-(6-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indol-8-yl)pyridin-2(1H)-one

HRID 474938

Reaktionsgleichung

Reaktionsgleichung von HRID 474938
[Cl:1][C:2]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:3]=1[CH2:4][O:5][C:6]1[CH:11]=[CH:10][NH:9][C:8](=[O:12])[CH:7]=1.Br[C:19]1[CH:20]=[CH:21][C:22]2[C:23]3[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH2:29][C:24]=3[N:25]([CH3:28])[C:26]=2[CH:27]=1.OC1C=CC=C2C=1N=CC=C2.C([O-])([O-])=O.[Cs+].[Cs+].Cl>CS(C)=O.CCOCC.C(Cl)Cl.[Cu]I>[Cl:1][C:2]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:3]=1[CH2:4][O:5][C:6]1[CH:11]=[CH:10][N:9]([C:19]2[CH:20]=[CH:21][C:22]3[C:23]4[CH2:33][CH2:32][NH:31][CH2:30][CH2:29][C:24]=4[N:25]([CH3:28])[C:26]=3[CH:27]=2)[C:8](=[O:12])[CH:7]=1

Komponenten

10

Edukt 5

HCID 313Hydrochloric AcidHCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 580922344-(2,4-dichlorobenzyloxy)pyridin-2(1H)-oneHCID 58093439tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate

Produkt 1

HCID 498699134-(2,4-Dichlorobenzyloxy)-1-(6-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indol-8-yl)pyridin-2(1H)-oneAusbeute 40,6 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 679Dimethyl SulfoxideLösungsmittelHCID 3283Diethyl EtherLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
135 °C

Versuchsvorschrift

A suspension of 4-(2,4-dichlorobenzyloxy)pyridin-2(1H)-one (103 mg, 0.381 mmol), tert-butyl 8-bromo-6-methyl-1,2,4,5-tetrahydroazepino[4,5-b]indole-3(6H)-carboxylate (131 mg, 0.347 mmol), CuI (79 mg, 0.42 mmol), 8-hydroxyquinoline (10 mg, 0.069 mmol) and Cs2CO3 (124 mg, 0.381 mmol) in DMSO (10 mL) was degassed under reduced pressure for 45 min. The suspension was put under N2 and stirred at 135° C. for 48 h. The suspension was cooled, 9:0.9:0.1 CH2Cl2/MeOH/NH4OH (10 mL) was added, and the resulting suspension was stirred at 25° C. for 30 min. The suspension was passed through a plug of silica gel, and the filtrate was washed with brine. Activated carbon was added to the resulting solution, and the resulting suspension was filtered. The filtrate was dried over Na2SO4, and concentrated under reduced pressure. Flash chromatography on silica gel (Et2O/(8:1.9:0.1 Et2O/MeOH/NH4OH), 100:0 to 0:100) afforded a tan solid. 2 N HCl in Et2O (100 mL) was added to a solution of the tan solid in CH2Cl2 (5 mL) under N2, and the resulting suspension was stirred at 25° C. for 17 h. The suspension was filtered, and the solid was washed with Et2O and freeze dried to afford 66 mg (38%) of the title compound as a white powder: 1H NMR (500 MHz, DMSO-d6) δ 9.02 (br s, 2H), 7.74 (d, J=2.0 Hz, 1H), 7.66 (d, J=8.5 Hz, 1H), 7.56 (d, J=8.0 Hz, 1H), 7.54-7.50 (m, 2H), 7.45 (d, J=1.5 Hz, 1H), 6.96 (dd, J=8.5, 2.0 Hz, 1H), 6.10 (dd, J=7.5, 3.0 Hz, 1H), 6.00 (d, J=3.0 Hz, 1H), 5.19 (s, 2H), 3.69 (s, 3H), 3.42-3.31 (m, 4H), 3.26-3.22 (m, 2H), 3.13-3.09 (m, 2H); ESI MS m/z 468 [M+H]+.

Aufarbeitung

  1. customwas degassed under reduced pressure for 45 min
  2. temperatureThe suspension was cooled
  3. addition9:0.9:0.1 CH2Cl2/MeOH/NH4OH (10 mL) was added
  4. stirringthe resulting suspension was stirred at 25° C. for 30 min
  5. washthe filtrate was washed with brine
  6. additionActivated carbon was added to the resulting solution
  7. filtrationthe resulting suspension was filtered
  8. dry with materialThe filtrate was dried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. customFlash chromatography on silica gel (Et2O/(8:1.9:0.1 Et2O/MeOH/NH4OH), 100:0 to 0:100) afforded a tan solid
  11. stirringthe resulting suspension was stirred at 25° C. for 17 h
  12. filtrationThe suspension was filtered
  13. washthe solid was washed with Et2O and freeze
  14. customdried

Quellen und Nachweise

ORD-Eintrag
ord-04d62796497e40c5be3edc3f1c7e9365
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08637501B2

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