Cesium carbonate → 2-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

HRID 246074Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 246074
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:12]=[C:13]4[C:19]([CH:20]=[O:21])=[CH:18][N:17]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:14]4=[N:15][CH:16]=3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].I[CH:37]1[CH2:40][O:39][CH2:38]1>CN(C=O)C>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:12]=[C:13]4[C:19]([CH:20]=[O:21])=[CH:18][N:17]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:14]4=[N:15][CH:16]=3)=[N:7][N:8]2[CH:37]2[CH2:40][O:39][CH2:38]2)=[CH:4][CH:3]=1

Komponenten

5

Edukt 3

HCID 10796Cesium carbonateHCID 133566863-IodooxetaneHCID 866779442-(6-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

Produkt 1

HCID 866779432-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehydeAusbeute 86,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

In a microwave vial 2-(6-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (300 mg, 0.73 mmol) was dissolved in DMF (5 ml) and cesium carbonate (714 mg, 2.19 mmol) and 3-iodooxetane (200 mg, 1.08 mmol) were added. The vial was sealed and heated at 100° C. under microwave irradiation for 2 h. The reaction was cooled, quenched with water and extracted with EtOAc (2×). The combined organics were washed with sat LiCl and brine then dried over MgSO4 and concentrated. The crude residue was purified by silica gel chromatography with 20% to 100% EtOAc/heptane to provide 295 mg (86%) of 2-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde as a white solid. 1H NMR (CDCl3, 300 MHz): δ (ppm) 10.48 (s, 1H), 9.40 (s, 1H), 8.86 (dd, J=9.1, 5.3 Hz, 1H), 8.31 (s, 1H), 7.11-7.25 (m, 2H), 5.72-5.86 (m, 3H), 5.41 (t, J=6.6 Hz, 2H), 5.20 (t, J=7.4 Hz, 2H), 3.56-3.70 (m, 2H), 0.85-1.06 (m, 2H), −0.02 (s, 9H).

Aufarbeitung

  1. customThe vial was sealed
  2. temperatureThe reaction was cooled
  3. customquenched with water
  4. extractionextracted with EtOAc (2×)
  5. washThe combined organics were washed with sat LiCl and brine
  6. dry with materialthen dried over MgSO4
  7. concentrationconcentrated
  8. customThe crude residue was purified by silica gel chromatography with 20% to 100% EtOAc/heptane

Quellen und Nachweise

ORD-Eintrag
ord-ca819179d27f4ac4b59a1dcc0a92f6e0
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

Notizen zur Reaktion

Wird geladen…