8-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indole → (Z)-8-chloro-5-(2-(4-fluorophenyl)prop-1-enyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1400546Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1400546
Br[CH:2]=[C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)[CH3:4].P([O-])([O-])([O-])=O.[K+].[K+].[K+].N1CCC[C@H]1C(O)=O.[Cl:28][C:29]1[CH:37]=[CH:36][C:35]2[NH:34][C:33]3[CH2:38][CH2:39][N:40]([CH3:42])[CH2:41][C:32]=3[C:31]=2[CH:30]=1>CN(C=O)C.[Cu]I>[Cl:28][C:29]1[CH:37]=[CH:36][C:35]2[N:34](/[CH:2]=[C:3](\[C:5]3[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=3)/[CH3:4])[C:33]3[CH2:38][CH2:39][N:40]([CH3:42])[CH2:41][C:32]=3[C:31]=2[CH:30]=1

Komponenten

7

Edukt 4

HCID 196158-chloro-2-methyl-1H,2H,3H,4H,5H-pyrido(4,3-b)indoleHCID 62657Potassium Phosphate, TribasicHCID 145742L-ProlineHCID 86644757(1-Bromoprop-1-en-2-yl)-4-fluorobenzene

Produkt 1

HCID 46199580(Z)-8-chloro-5-(2-(4-fluorophenyl)prop-1-enyl)-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
85 °C

Versuchsvorschrift

1-(1-Bromoprop-1-en-2-yl)-4-fluorobenzene (511.2 mg, 2.4 mmol) was dissolved in DMF. Potassium phosphate (848 mg, 4 mmol) was added followed by the addition of copper (I)iodide (38 mg, 0.2 mmol) and L-proline (46 mg, 0.4 mmol). 8-chloro-2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole (440 mg, 2 mmol) was added to the reaction mixture and nitrogen gas purged for 2 min. The reaction mixture was heated at 85° C. overnight. The reaction mixture was cooled to RT and ice water was added. Solid mass was filtered under vacuum and crude purified by silica gel chromatography using 0-3% MeOH:DCM as eluent. Two isomers were further purified through reverse phase HPLC and peak 1 was submitted as the final compound. Yield: 120 mg. 1H NMR (DMSO, HCl salt) δ (ppm): 7.50 (s, 1H), 7.10-6.95 (m, 6H), 6.82 (s, 1H), 4.50 (m, 1H), 4.20 (m, 1H), 3.60 (m, 2H), 2.85 (s, 3H), 2.80 (m, 2H), 2.25 (s, 3H).

Aufarbeitung

  1. custompurged for 2 min
  2. temperatureThe reaction mixture was cooled to RT
  3. additionice water was added
  4. filtrationSolid mass was filtered under vacuum and crude
  5. custompurified by silica gel chromatography
  6. customTwo isomers were further purified through reverse phase HPLC and peak 1

Quellen und Nachweise

ORD-Eintrag
ord-003a3fcf2100469b8f055cff7ab1cb42
Quelldatensatz
uspto-grants-2014_12
Patentnummer
US08906925B2

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