Cesium carbonate → isopropyl ((S)-7-cyano-4-(((2R,3S)-3-hydroxytetrahydrofuran-2-yl)Methyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-2-yl)carbaMate

HRID 1928581Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1928581
[CH:1]([O:4][C:5](=[O:21])[NH:6][C@@H:7]1[CH2:20][C:10]2[NH:11][C:12]3[CH:13]=[CH:14][C:15]([C:18]#[N:19])=[CH:16][C:17]=3[C:9]=2[CH2:8]1)([CH3:3])[CH3:2].CC1C=CC(S(O[CH2:33][C@@H:34]2[C@@H:38]([OH:39])[CH2:37][CH2:36][O:35]2)(=O)=O)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1CCCC1.C(OCC)(=O)C>[CH:1]([O:4][C:5](=[O:21])[NH:6][C@@H:7]1[CH2:20][C:10]2[N:11]([CH2:33][C@@H:34]3[C@@H:38]([OH:39])[CH2:37][CH2:36][O:35]3)[C:12]3[CH:13]=[CH:14][C:15]([C:18]#[N:19])=[CH:16][C:17]=3[C:9]=2[CH2:8]1)([CH3:3])[CH3:2]

Komponenten

6

Edukt 3

HCID 10796Cesium carbonateHCID 58271236[(2R,3S)-3-hydroxytetrahydrofuran-2-yl]methyl 4-methylbenzenesulfonateHCID 66933207(S)-(7-Cyano-1,2,3,4-tetrahydrocyclopenta[b]indol-2-yl)carbamic Acid Isopropyl Ester

Produkt 1

HCID 52914985isopropyl ((S)-7-cyano-4-(((2R,3S)-3-hydroxytetrahydrofuran-2-yl)Methyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-2-yl)carbaMateAusbeute 72,7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 84541-MethylpyrrolidineLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

A mixture of ((S)-7-cyano-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl)-carbamic acid isopropyl ester (2.50 g, 8.82 mmol), [(2R,3S)-3-hydroxytetrahydrofuran-2-yl]methyl 4-methylbenzenesulfonate (3.10 g, 11.38 mmol), and cesium carbonate (5.00 g, 15.35 mmol) in N-methylpyrrolidine (25 mL) is heated in a 65° C. oil bath overnight. After cooling to ambient temperature, the reaction is diluted with ethyl acetate (120 mL) and washed with water (3×100 mL) and brine. The organic portion is dried over sodium sulfate, filtered, and concentrated to dryness. The resulting residue is purified by medium pressure liquid chromatography, eluting with ethyl acetate. Fractions containing pure product are combined and concentrated to afford 2.46 g (72%) of the title compound. LC-ES/MS m/z 384.2 [M+H]+, TR=1.90 min. (Symyx Draw 3.1 (IUPAC Name) provides the following name for the compound of Example 1: Isopropyl N-[(2S)-7-cyano-4-[[(2R,3S)-3-hydroxytetrahydrofuran-2-yl]methyl]-2,3-dihydro-1H-cyclopenta[b]indol-2-yl]carbamate.)

Aufarbeitung

  1. temperatureAfter cooling to ambient temperature
  2. washwashed with water (3×100 mL) and brine
  3. dry with materialThe organic portion is dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. customThe resulting residue is purified by medium pressure liquid chromatography
  7. washeluting with ethyl acetate
  8. additionFractions containing pure product
  9. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-23a0aff16c6547539192ddf4e67fd943
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08183388B2

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