Potassium Iodide → ethyl (10R,15S)-3-oxo-1,4,12-triazatetracyclo[7.6.1.05,16.010,15]hexadeca-5,7,9(16)-triene-12-carboxylate

HRID 1624925Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1624925
Br[C:2]1[C:10]2[NH:9][C@H:8]3[CH2:11][CH2:12][N:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:14][C@H:7]3[C:6]=2[CH:5]=[CH:4][CH:3]=1.Cl[CH2:21][C:22]([NH2:24])=[O:23].[I-].[K+].C(N(C(C)C)CC)(C)C.CNC(=O)CCl.C(=O)([O-])[O-].[K+].[K+].CNCCNC>[Cu](I)I.O1CCOCC1>[O:23]=[C:22]1[CH2:21][N:9]2[C@H:8]3[CH2:11][CH2:12][N:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:14][C@H:7]3[C:6]3[C:10]2=[C:2]([CH:3]=[CH:4][CH:5]=3)[NH:24]1

Komponenten

10

Edukt 7

HCID 4875Potassium IodideHCID 6580ChloroacetamideHCID 8070N,N'-DimethylethylenediamineHCID 11430Potassium CarbonateHCID 667732-chloro-N-methylacetamideHCID 81531Diisopropylethylamine2×HCID 59317960ethyl (4aS,9bR)-6-bromo-1H,2H,3H,4H,4aH,5H,9bH-pyrido(4,3-b)indole-2-carboxylate

Produkt 1

HCID 20578971ethyl (10R,15S)-3-oxo-1,4,12-triazatetracyclo[7.6.1.05,16.010,15]hexadeca-5,7,9(16)-triene-12-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 83717Copper iodideKatalysatorHCID 312751,4-DioxaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
103 °C

Versuchsvorschrift

Alternative to Example 5 above, (6bR,10aS)-ethyl 3,6b,9,10,10a-hexahydro-3-methyl-2-oxo-1H-pyrido[3′,4′:4,5]-pyrrolo[1,2,3-de]quinoxaline-8-carboxylate may also be made in a one pot method starting from Compound of Formula 1D. A 2 liter 4 neck round bottom flask is equipped with a mechanical stirrer, reflux condenser, N2 inlet, teflon covered K-type temperature probe with a controller, and a heating mantle. To the flask is charged (4aS,9bR)-ethyl 6-bromo-3,4,4a,5-tetrahydro-1H-pyrido[4,3-b]indole-2(9bH)-carboxylate (250 g, 769 mmol), chloroacetamide (124 g, 1153 mmol, 1.5 equiv), potassium iodide (191.5 g, 1160 mmol, 1.5 equiv), diisopropyl ethylamine (266 mL, 1531 mmol, 2.0 equiv), and dioxane (625 mL). The reaction is heated to reflux temperature of about 103° C. until less than 3% of the starting substrate is observed by HPLC (about 48 hours). Additional charge of N-methyl chloroacetamide and diisopropyl ethylamine maybe necessary. The reaction is then cooled to ca. 80° C., and at this temperature copper iodide (29.2 g, 153.8 mmol, 0.2 equiv), potassium carbonate (232.5 g, 1682 mmol, 2.2 equiv), dimethylethylene diamine (49.6 mL, 461 mmol, 0.6 equiv), and additional dioxane (375 mL) is added. The reaction is then re-heated to reflux and is monitored by HPLC. Reflux occurs at ca. 103° C. The reaction is monitored by HPLC.

Aufarbeitung

  1. temperaturereflux condenser, N2 inlet
  2. temperatureThe reaction is heated
  3. customis observed by HPLC (about 48 hours)
  4. temperatureThe reaction is then cooled to ca. 80° C.
  5. temperatureThe reaction is then re-heated
  6. temperatureto reflux
  7. temperatureReflux
  8. customoccurs at ca. 103° C

Quellen und Nachweise

ORD-Eintrag
ord-cca6c1525efd4aecbe2a2ac167653e4f
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08779139B2

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