4-Bromo-2-[4-(2-methyl-pyrrolidin-1-yl)-but-1-ynyl]-phenylamine → 5-Bromo-2-[2-(2-(R)-methyl-pyrrolidin-1-yl)-ethyl]-1H-indole

HRID 424953

Reaktionsgleichung

Reaktionsgleichung von HRID 424953
O(C(C)(C)C)[K].[Br:7][C:8]1[CH:13]=[CH:12][C:11]([NH2:14])=[C:10]([C:15]#[C:16][CH2:17][CH2:18][N:19]2[CH2:23][CH2:22][CH2:21][CH:20]2[CH3:24])[CH:9]=1>CN1C(=O)CCC1>[Br:7][C:8]1[CH:9]=[C:10]2[C:11](=[CH:12][CH:13]=1)[NH:14][C:16]([CH2:17][CH2:18][N:19]1[CH2:23][CH2:22][CH2:21][C@H:20]1[CH3:24])=[CH:15]2

Komponenten

4

Edukt 2

HCID 219800934-Bromo-2-[4-(2-methyl-pyrrolidin-1-yl)-but-1-ynyl]-phenylamineHCID 178418922HCID 178418922, Verbindung

Produkt 1

HCID 210414975-Bromo-2-[2-(2-(R)-methyl-pyrrolidin-1-yl)-ethyl]-1H-indoleAusbeute 61,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 13387N-methyl-2-pyrrolidoneLösungsmittel2×

Versuchsvorschrift

To a cooled (0° C.) suspension of KO-tBu (95%, 7.8 g, 66 mmol) in NMP (150 mL) was added a solution of 4-bromo-2-[4-(2-methyl-pyrrolidin-1-yl)-but-1-ynyl]-phenylamine (10 g, 33 mmol) in NMP (50 mL) dropwise keeping the temperature below 5° C. The resulting mixture was then stirred at room temperature for 3 hours under nitrogen. HPLC indicated that all the starting material was consumed. H2O (400 mL) was added slowly to the reaction mixture followed by addition of IPAc (500 mL). The resulting mixture was stirred for 5 min. and the organic layer was separated. The organic layer was then washed with 20% brine (3×200 mL), dried over Na2SO4 and treated with activated carbon. After filtration, the filtrate was concentrated under reduced pressure to give the title compound as a thick oil (6.2 g), which was used in the next coupling reaction without further purification. 1H NMR (400 MHz, CDCl3) δ 10.21 (s, 1H), 7.73 (s, 1H), 7.27 (s, 2H), 6.24 (s, 1H), 3.42-3.50 (m, 1H), 3.21-3.28 (m, 1H), 2.97-3.10 (m, 2H), 2.49-2.60 (m, 2H), 2.33 (q, J=8.78 Hz, 1H), 2.10-2.17 (m, 1H), 1.87-2.02 (m, 2H), 1.58-1.67 (m, 1H), 1.24 (d, J=6.2 Hz, 3H). 13C NMR (400 MHz, CDCl3) δ 140.89, 133.92, 129.91, 122.98, 121.77, 112.16, 111.75, 98.32, 60.47, 53.60, 53.34, 33.19, 26.30, 22.14, 19.56. [M+H]+ at m/z 307.

Aufarbeitung

  1. temperatureTo a cooled
  2. customthe temperature below 5° C
  3. customwas consumed
  4. additionH2O (400 mL) was added slowly to the reaction mixture
  5. additionfollowed by addition of IPAc (500 mL)
  6. stirringThe resulting mixture was stirred for 5 min.
  7. customthe organic layer was separated
  8. washThe organic layer was then washed with 20% brine (3×200 mL)
  9. dry with materialdried over Na2SO4
  10. additiontreated with activated carbon
  11. filtrationAfter filtration
  12. concentrationthe filtrate was concentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-48853fc76d1143189b398831ff2e41fb
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08106088B2

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