N,N'-Dimethylethylenediamine → (R)-3-(6-Ethoxy-pyridin-3-yloxy)-1-(7-fluoro-3-oxo-indan-5-yl)-pyrrolidin-2-one

HRID 533918Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 533918
[CH2:1]([O:3][C:4]1[N:9]=[CH:8][C:7]([O:10][C@@H:11]2[CH2:15][CH2:14][NH:13][C:12]2=[O:16])=[CH:6][CH:5]=1)[CH3:2].Br[C:18]1[CH:26]=[C:25]2[C:21]([CH2:22][CH2:23][C:24]2=[O:27])=[C:20]([F:28])[CH:19]=1.CNCCNC>O1CCOCC1>[CH2:1]([O:3][C:4]1[N:9]=[CH:8][C:7]([O:10][C@@H:11]2[CH2:15][CH2:14][N:13]([C:18]3[CH:26]=[C:25]4[C:21](=[C:20]([F:28])[CH:19]=3)[CH2:22][CH2:23][C:24]4=[O:27])[C:12]2=[O:16])=[CH:6][CH:5]=1)[CH3:2]

Komponenten

5

Edukt 3

HCID 8070N,N'-DimethylethylenediamineHCID 509894266-Bromo-4-fluoro-2,3-dihydro-1H-inden-1-oneHCID 86715109(R)-3-((6-ethoxypyridin-3-yl)oxy)pyrrolidin-2-one

Produkt 1

HCID 74767655(R)-3-(6-Ethoxy-pyridin-3-yloxy)-1-(7-fluoro-3-oxo-indan-5-yl)-pyrrolidin-2-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

In a further alternative preparation a mixture of (R)-3-((6-ethoxypyridin-3-yl)oxy)pyrrolidin-2-one (2.00 g), 6-bromo-4-fluoro-2,3-dihydro-1H-inden-1-one (2.30 g), N,N′-dimethyl-ethylene-diamine (10 mL) and 1,4-dioxane (20 mL) was purged with argon and cesium carbonate (3.8 g) and copper(I) iodide (100 mg) were added. The mixture was heated to 100° C. for 1.5 hours. After cooling to r.t. the mixture was diluted with EA and washed with water (5 times) and brine. The organic layer was dried (Na2SO4) and concentrated. The residue was purified by SGC (eluent: heptane with 0 to 70% EA) to provide Example 2-08. 1H-NMR (400 MHz, DMSO) δ 7.99 (1H, dd, J=11.3, 1.8 Hz), 7.97 (1H, d, J=3.1 Hz), 7.77 (1H, d, J=1.8 Hz), 7.53 (1H, dd, J=8.9, 3.1 Hz), 6.76 (1H, d, J=8.9 Hz), 5.22 (1H, dd, J=8.3, 8.3 Hz), 4.24 (2H, q, J=7.0 Hz), 3.96 (1H, m), 3.86 (1H, m), 3.11 (2H, m), 2.72 (2H, m), 2.69 (1H, m), 2.13 (1H, m), 1.30 (3H, t, J=7.0 Hz).

Aufarbeitung

  1. customIn a further alternative preparation
  2. customwas purged with argon and cesium carbonate (3.8 g) and copper(I) iodide (100 mg)
  3. additionwere added
  4. temperatureAfter cooling to r.t. the mixture
  5. additionwas diluted with EA
  6. washwashed with water (5 times) and brine
  7. dry with materialThe organic layer was dried (Na2SO4)
  8. concentrationconcentrated
  9. customThe residue was purified by SGC (eluent: heptane with 0 to 70% EA)
  10. customto provide Example 2-08

Quellen und Nachweise

ORD-Eintrag
ord-2036a86608ae4642b1b2fc0f28be29f2
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08853412B2

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