Potassium Carbonate → 7-bromo-3-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}isoquinoline

HRID 273224

Reaktionsgleichung

Reaktionsgleichung von HRID 273224
CC1C=CC(S(O[CH2:12][CH2:13][C:14]2[N:15]=[CH:16][C:17]3[C:22]([CH:23]=2)=[CH:21][CH:20]=[C:19]([Br:24])[CH:18]=3)(=O)=O)=CC=1.[CH3:25][C@@H:26]1[CH2:30][CH2:29][CH2:28][NH:27]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Br:24][C:19]1[CH:18]=[C:17]2[C:22]([CH:23]=[C:14]([CH2:13][CH2:12][N:27]3[CH2:28][CH2:29][CH2:30][C@H:26]3[CH3:25])[N:15]=[CH:16]2)=[CH:21][CH:20]=1

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 641544(R)-2-MethylpyrrolidineHCID 865922262-(7-Bromo-3-isoquinolinyl)ethyl 4-methylbenzenesulfonate

Produkt 1

HCID 671046927-bromo-3-{2-[(2R)-2-methyl-1-pyrrolidinyl]ethyl}isoquinoline

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
52.5 °C

Versuchsvorschrift

The product from Example 52F was dissolved in a solution of (2R)-2-methylpyrrolidine (0.26 g, 3.0 mmol) in acetonitrile (20 mL). The solution was treated with potassium carbonate (0.5 g, 3.6 mmol) and heated at 50-55° C. for 20 hours in a sealed flask. The mixture was allowed to cool to room temperature, filtered, and the filtrate was concentrated in vacuo. The residue was diluted with MTBE (20 mL) and water (20 mL) and the pH was adjusted to 3-3.5 with concentrated HCl. The aqueous layer was separated, extracted with MTBE (10 mL), adjusted to a pH of 8-8.5 with potassium carbonate, and extracted with isopropyl acetate (20 mL). The organic layer was separated and concentrated in vacuo. The residue was dissolved in heptane (20 mL), filtered, and the filtrate concentrated under vacuum to provide the title compound. 1H NMR (CDCl3) δ 1.10 (d, J=6.1 Hz, 3H); 1.35-1.49 (m, 1H); 1.62-1.85 (m, 2H); 1.85-1.98 (m, 1H); 2.23 (q, J=8.8. Hz, 1H); 2.28-2.42 (m, 1H); 2.46-2.57 (m, 1H), 3.04-3.19 (m, 2H); 3.19-3.30 (m, 2H); 7.47 (s, 1H); 7.60 (d, J=8.8 Hz, 1H), 7.647.70 (m, 1H), 8.05 (m, 1H); 9.09 (s, 1H); HRMS Calcd. for [C16H19BrN2+H+]: 319.0810. Found: 319.0795.

Aufarbeitung

  1. temperatureto cool to room temperature
  2. filtrationfiltered
  3. concentrationthe filtrate was concentrated in vacuo
  4. additionThe residue was diluted with MTBE (20 mL) and water (20 mL)
  5. customThe aqueous layer was separated
  6. extractionextracted with MTBE (10 mL)
  7. extractionextracted with isopropyl acetate (20 mL)
  8. customThe organic layer was separated
  9. concentrationconcentrated in vacuo
  10. dissolutionThe residue was dissolved in heptane (20 mL)
  11. filtrationfiltered
  12. concentrationthe filtrate concentrated under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-7d6e6e6ee70f42939f9102d4c833a78f
Quelldatensatz
uspto-grants-2008_11
Patentnummer
US07456196B2

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