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 1928581Notes

Reaction equation

HRID 1928581 reaction equation
[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]

Participants

6

Reactant 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

Product 1

HCID 52914985isopropyl ((S)-7-cyano-4-(((2R,3S)-3-hydroxytetrahydrofuran-2-yl)Methyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-2-yl)carbaMateYield 72.7%

Reagents, catalysts & solvents 2

HCID 84541-MethylpyrrolidineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

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.)

Workup

  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

Sources & evidence

ORD record
ord-23a0aff16c6547539192ddf4e67fd943
Source dataset
uspto-grants-2012_05
Patent number
US08183388B2

Reaction notes

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