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 1625250Notes

Reaction equation

HRID 1625250 reaction equation
[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]

Participants

9

Reactant 4

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

Product 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}benzonitrileYield 77%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 962WaterSolventHCID 6212ChloroformSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-238255bc6220459aace1d900f06ebf92
Source dataset
uspto-grants-2014_07
Patent number
US08779142B2

Reaction notes

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