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 1625250ノート

反応式

HRID 1625250 の反応式
[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]

参加物

9

反応物 4

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

生成物 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}benzonitrile収率 77%

試薬・触媒・溶媒 4

HCID 83717Copper iodide触媒HCID 962Water溶媒HCID 6212Chloroform溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
150 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-238255bc6220459aace1d900f06ebf92
出典データセット
uspto-grants-2014_07
特許番号
US08779142B2

反応ノート

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