N,N'-Dimethylethylenediamine → 2-(ethylamino)-4-{3-isopropyl-4-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl}benzonitrile

HRID 1625250Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1625250
[CH:1]([C:4]1[C:12]2[C:7](=[N:8][CH:9]=[CH:10][C:11]=2[N:13]2[CH:17]=[C:16]([C:18]3[CH:19]=[N:20][N:21]([CH3:23])[CH:22]=3)[N:15]=[CH:14]2)[NH:6][N:5]=1)([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:31]1[CH:38]=[CH:37][C:34]([C:35]#[N:36])=[C:33]([NH:39][CH2:40][CH3:41])[CH:32]=1.CNCCNC>O1CCOCC1.[Cu](I)I.O.C(Cl)(Cl)Cl>[CH2:40]([NH:39][C:33]1[CH:32]=[C:31]([N:6]2[C:7]3=[N:8][CH:9]=[CH:10][C:11]([N:13]4[CH:17]=[C:16]([C:18]5[CH:19]=[N:20][N:21]([CH3:23])[CH:22]=5)[N:15]=[CH:14]4)=[C:12]3[C:4]([CH:1]([CH3:3])[CH3:2])=[N:5]2)[CH:38]=[CH:37][C:34]=1[C:35]#[N:36])[CH3:41]

Komponenten

9

Edukt 4

HCID 8070N,N'-DimethylethylenediamineHCID 10796Cesium carbonateHCID 249030904-Bromo-2-(ethylamino)benzonitrileHCID 178440426HCID 178440426, Verbindung

Produkt 1

HCID 675006162-(ethylamino)-4-{3-isopropyl-4-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl}benzonitrileAusbeute 77 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 83717Copper iodideKatalysatorHCID 962WaterLösungsmittelHCID 6212ChloroformLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

Compound (100b) (1.00 g), copper iodide (0.248 g), cesium carbonate (2.12 g), and 4-bromo-2-(ethylamino)benzonitrile (0.932 g) were suspended in 1,4-dioxane (10 mL), and N,N′-dimethylethylenediamine (0.560 mL) was added to the suspension, followed by stirring at 150° C. for 20 hr. The reaction solution was distributed between chloroform and water. The organic layer was washed with a 2 N aqueous sodium hydroxide solution and dried over magnesium sulfate, and then the solvent was distilled away. The residue was purified by neutral silica gel column chromatography (chloroform/methanol) to obtain 2-(ethylamino)-4-{3-isopropyl-4-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl}benzonitrile (1.13 g, 77%) as a white solid. 2-(Ethylamino)-4-{3-isopropyl-4-(4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl}benzonitrile (0.700 g) was dissolved in DMSO (10 mL), and a 30% hydrogen peroxide solution (0.310 mL) and a 4 N aqueous sodium hydroxide solution (1.16 mL) were added to the resulting solution, followed by stirring at room temperature for 10 min. Water was added to the reaction solution, and the precipitate was collected by filtration and was dried under reduced pressure to obtain compound (109) (0.655 g, 90%) as a white solid.

Aufarbeitung

  1. washThe organic layer was washed with a 2 N aqueous sodium hydroxide solution
  2. dry with materialdried over magnesium sulfate
  3. distillationthe solvent was distilled away
  4. customThe residue was purified by neutral silica gel column chromatography (chloroform/methanol)

Quellen und Nachweise

ORD-Eintrag
ord-238255bc6220459aace1d900f06ebf92
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08779142B2

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