8-Hydroxyquinoline → N-(3-{6-[1-(4-Methoxybenzyl)-1H-pyrazol-4-yl]-1H-imidazo[1,2-b]pyrazol-1-yl}-4-methyl-phenyl)-3-(trifluoromethyl)benzamide

HRID 1055667

Reaktionsgleichung

Reaktionsgleichung von HRID 1055667
[CH3:1][O:2][C:3]1[CH:22]=[CH:21][C:6]([CH2:7][N:8]2[CH:12]=[C:11]([C:13]3[CH:14]=[C:15]4[NH:20][CH:19]=[CH:18][N:16]4[N:17]=3)[CH:10]=[N:9]2)=[CH:5][CH:4]=1.Br[C:24]1[CH:25]=[C:26]([NH:31][C:32](=[O:43])[C:33]2[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([F:42])([F:41])[F:40])[CH:34]=2)[CH:27]=[CH:28][C:29]=1[CH3:30].C(=O)([O-])[O-].C([N+](CC)(CC)CC)C.C([N+](CC)(CC)CC)C.OC1C=CC=C2C=1N=CC=C2>CN(C=O)C.O.[Cu]I>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[CH:12]=[C:11]([C:13]3[CH:14]=[C:15]4[N:20]([C:24]5[CH:25]=[C:26]([NH:31][C:32](=[O:43])[C:33]6[CH:38]=[CH:37][CH:36]=[C:35]([C:39]([F:41])([F:40])[F:42])[CH:34]=6)[CH:27]=[CH:28][C:29]=5[CH3:30])[CH:19]=[CH:18][N:16]4[N:17]=3)[CH:10]=[N:9]2)=[CH:21][CH:22]=1

Komponenten

8

Edukt 4

HCID 19238-HydroxyquinolineHCID 11045447Bis(N,N,N-triethylethanaminium) carbonateHCID 58601069N-(3-Bromo-4-Methylphenyl)-3-(Trifluoromethyl)BenzamideHCID 178490761HCID 178490761, Verbindung

Produkt 1

HCID 86690977N-(3-{6-[1-(4-Methoxybenzyl)-1H-pyrazol-4-yl]-1H-imidazo[1,2-b]pyrazol-1-yl}-4-methyl-phenyl)-3-(trifluoromethyl)benzamide

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 962WaterLösungsmittel2×HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
160 °C

Versuchsvorschrift

55 mg (0.19 mmol) of the compound of Example 5A and 74 mg (0.21 mmol) of the compound of Example 45A were dissolved in 1.24 ml of DMF and 0.12 ml of water, and 126 mg (0.39 mmol) of bis(tetraethylammonium) carbonate were added carefully. The mixture was degassed with argon, and 14.3 mg (0.08 mmol) of copper(I) iodide and 10.9 mg (0.08 mmol) of 8-hydroxyquinoline were then added. The reaction was then heated in a microwave oven (Biotage Initiator, with Dynamic Field Tuning) at 160° C. for 1 h. After cooling, the mixture was poured into 10 ml of water and extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution and concentrated under reduced pressure. The residue was purified by preparative HPLC (Method 11). The product fractions were concentrated and the residue was dried under high vacuum. This gave 26 mg (57% pure, 14% of theory) of the title compound which was reacted further in this form.

Aufarbeitung

  1. additionwere then added
  2. temperatureAfter cooling
  3. extractionextracted with ethyl acetate
  4. washThe organic phase was washed with saturated sodium chloride solution
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by preparative HPLC (Method 11)
  7. concentrationThe product fractions were concentrated
  8. customthe residue was dried under high vacuum
  9. customThis gave 26 mg (57% pure, 14% of theory) of the title compound which was reacted further in this form

Quellen und Nachweise

ORD-Eintrag
ord-2bad6955bad64bcdb91149f4b6b65e02
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09394309B2

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