8-Hydroxyquinoline → HCID 58015559, Verbindung

HRID 422076Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 422076
[CH3:1][O:2][CH:3]([O:15][CH3:16])[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10](I)=[CH:11][CH:12]=2)[CH:7]=[N:6]1.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[O:32][C:31]3[CH:30]=[CH:29][NH:28][C:27](=[O:33])[C:26]=3[CH:25]=2)=[CH:20][CH:19]=1.C([O-])([O-])=O.[Cs+].[Cs+].OC1C=CC=C2C=1N=CC=C2>CS(C)=O.[Cu]I>[Cl:17][C:18]1[CH:19]=[CH:20][C:21]([C:24]2[O:32][C:31]3[CH:30]=[CH:29][N:28]([C:10]4[CH:9]=[C:8]5[C:13](=[CH:12][CH:11]=4)[N:5]([CH2:4][CH:3]([O:15][CH3:16])[O:2][CH3:1])[N:6]=[CH:7]5)[C:27](=[O:33])[C:26]=3[CH:25]=2)=[CH:22][CH:23]=1

Komponenten

7

Edukt 4

HCID 19238-HydroxyquinolineHCID 10796Cesium carbonateHCID 576255361-(2,2-Dimethoxyethyl)-5-iodo-1H-indazoleHCID 58015558HCID 58015558, Verbindung

Produkt 1

HCID 58015559HCID 58015559, VerbindungAusbeute 41,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 679Dimethyl SulfoxideLösungsmittel

Reaktionsbedingungen

Temperatur
128 °C

Versuchsvorschrift

To a solution of 1-(2,2-dimethoxyethyl)-5-iodo-1H-indazole (3.14 g, 9.46 mmol) in DMSO (11.2 mL) was added 2-(4-chlorophenyl)-5H-furo[3,2-c]pyridine-4-one (2.32 g, 9.46 mmol), Cs2CO3 (3.39 g, 10.4 mmol), 8-hydroxyquinoline (0.274 g, 1.89 mmol) and CuI (2.16 g, 11.4 mmol). The solution was evacuated for 15 minutes under high vacuum then backfilled with argon. The process was repeated three times. The reaction mixture was stirred at 128° C. for 5 h; then the reaction mixture was cooled to 100° C. and maintained at this temperature for 18 h. The reaction mixture was diluted with 10% NH4OH in H2O (100 mL) and the resulting solids were washed with an additional 10% NH4OH in H2O solution (300 mL). The solids were dissolved in CH2Cl2 (100 mL) and washed with H2O (2×50 mL). The organics were filtered to remove any excess solids and then concentrated. Purification by flash chromatography (silica gel, hexanes with 0.1% Et3N to hexanes/MTBE/EtOAc 35:1.25:0.25 with 0.1% Et3N, to hexanes/MTBE/EtOH 35:1.25:0.25 with 0.1% Et3N, to CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 1:1) yielded the title compound (1.78 g, 41%) as a brown solid: 1H NMR (500 MHz, CDCl3) δ 8.06 (s, 1H), 7.73-7.71 (m, 3H), 7.60 (d, J=9.0 Hz, 1H), 7.43-7.41 (m, 3H), 7.35 (d, J=7.5 Hz, 1H), 7.25 (s, 1H), 6.67 (d, J=7.5 Hz, 1H), 4.78 (t, J=5.5 Hz, 1H), 4.51 (d, J=5.0 Hz, 2H), 3.38 (s, 6H); ESI MS m/z 450 [M+H]+.

Aufarbeitung

  1. customThe solution was evacuated for 15 minutes under high vacuum
  2. temperaturethen the reaction mixture was cooled to 100° C.
  3. temperaturemaintained at this temperature for 18 h
  4. additionThe reaction mixture was diluted with 10% NH4OH in H2O (100 mL)
  5. washthe resulting solids were washed with an additional 10% NH4OH in H2O solution (300 mL)
  6. dissolutionThe solids were dissolved in CH2Cl2 (100 mL)
  7. washwashed with H2O (2×50 mL)
  8. filtrationThe organics were filtered
  9. customto remove any excess solids
  10. concentrationconcentrated
  11. customPurification by flash chromatography (silica gel, hexanes with 0.1% Et3N to hexanes/MTBE/EtOAc 35:1.25:0.25 with 0.1% Et3N, to hexanes/MTBE/EtOH 35:1.25:0.25 with 0.1% Et3N, to CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 1:1)

Quellen und Nachweise

ORD-Eintrag
ord-88da64b661f843fbaa92ae326fead87b
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08101632B2

Notizen zur Reaktion

Wird geladen…