6-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole → 8-[4-(6-Fluoro-1H-Indol-3-Yl)-3,6-Dihydro-2H-Pyridin-1-Ylmethyl]-2-Methyl-7,8-Dihydro-1,6,9-Trioxa-3-Aza-Cyclopenta[a]Naphthalene

HRID 1060764

Reaktionsgleichung

Reaktionsgleichung von HRID 1060764
CC1C=CC(S(O[CH2:12][C@H:13]2[CH2:26][O:25][C:16]3[CH:17]=[CH:18][C:19]4[N:20]=[C:21]([CH3:24])[O:22][C:23]=4[C:15]=3[O:14]2)(=O)=O)=CC=1.[F:27][C:28]1[CH:36]=[C:35]2[C:31]([C:32]([C:37]3[CH2:38][CH2:39][NH:40][CH2:41][CH:42]=3)=[CH:33][NH:34]2)=[CH:30][CH:29]=1>CS(C)=O.C(OCC)(=O)C>[F:27][C:28]1[CH:36]=[C:35]2[C:31]([C:32]([C:37]3[CH2:38][CH2:39][N:40]([CH2:12][CH:13]4[O:14][C:15]5[C:16](=[CH:17][CH:18]=[C:19]6[N:20]=[C:21]([CH3:24])[O:22][C:23]6=5)[O:25][CH2:26]4)[CH2:41][CH:42]=3)=[CH:33][NH:34]2)=[CH:30][CH:29]=1

Komponenten

5

Edukt 2

HCID 110530726-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoleHCID 11245807(8R)-2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-ylmethyl 4-methylbenzenesulfonate

Produkt 1

HCID 102238168-[4-(6-Fluoro-1H-Indol-3-Yl)-3,6-Dihydro-2H-Pyridin-1-Ylmethyl]-2-Methyl-7,8-Dihydro-1,6,9-Trioxa-3-Aza-Cyclopenta[a]Naphthalene

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

[(8R)-2-Methyl-7,8-dihydro[1,4]dioxino[2,3-g][1,3]benzoxazol-8-yl]methyl 4-methylbenzenesulfonate (0.50 g, 1.31 mmole) and 6-fluoro-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (1.0 g, 4.6 mmole) were combined in 10 mL of DMSO under nitrogen. This solution was heated at 80° C. under nitrogen. After completion, the reaction was cooled to room temperature and diluted with 400 mL of ethyl acetate. The organic phase was washed with 400 mL portions of saturated aqueous sodium bicarbonate, water and saturated brine and concentrated in vacuum. The crude residue was column chromatographed on silica gel using 1% methanol/methylene chloride to give 0.52 g of the (S)-enantiomer of the title compound, which was a yellow solid (m.p. 188-190° C.) after evaporation of the solvent.

Aufarbeitung

  1. temperatureAfter completion, the reaction was cooled to room temperature
  2. washThe organic phase was washed with 400 mL portions of saturated aqueous sodium bicarbonate, water and saturated brine
  3. concentrationconcentrated in vacuum
  4. customchromatographed on silica gel using 1% methanol/methylene chloride

Quellen und Nachweise

ORD-Eintrag
ord-7a864842e57d40ea81ca49052ff1f370
Quelldatensatz
uspto-grants-2003_02
Patentnummer
US06525075B2

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