Dimethylformamide → 2-(6-chloro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-pyridin-3-yl-ethyl)-amide

HRID 246256ノート

反応式

HRID 246256 の反応式
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([Sn](CCCC)(CCCC)CCCC)=[N:7][NH:8]2)=[CH:4][CH:3]=1.[N:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH:30]([NH:32][C:33]([C:35]2[C:43]3[C:38](=[N:39][CH:40]=[C:41](Br)[N:42]=3)[N:37]([CH2:45][O:46][CH2:47][CH2:48][Si:49]([CH3:52])([CH3:51])[CH3:50])[CH:36]=2)=[O:34])[CH3:31])[CH:25]=1.CN(C=O)C>CCOCC.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH:30]([NH:32][C:33]([C:35]2[C:43]3[C:38](=[N:39][CH:40]=[C:41]([C:6]4[C:5]5[C:9](=[CH:10][C:2]([Cl:1])=[CH:3][CH:4]=5)[NH:8][N:7]=4)[N:42]=3)[N:37]([CH2:45][O:46][CH2:47][CH2:48][Si:49]([CH3:50])([CH3:52])[CH3:51])[CH:36]=2)=[O:34])[CH3:31])[CH:25]=1

参加物

7

反応物 3

HCID 6228DimethylformamideHCID 866779672-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-pyridin-3-yl-ethyl)-amideHCID 1784482296-chloro-3-(tributylstannyl)-1H-indazole

生成物 1

HCID 712883932-(6-chloro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-pyridin-3-yl-ethyl)-amide収率 50%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418397HCID 178418397、化合物触媒HCID 3283Diethyl Ether溶媒

反応条件

温度
90 °C

実験手順

6-Chloro-3-tributylstannyl-1H-indazole (584 mg, 1.32 mmol), copper(I) iodide (14 mg, 0.074 mmol) and 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-pyridin-3-yl-ethyl)-amide (350 mg, 0.74 mmol) were combined with DMF (6 mL) to give a yellow solution. The mixture was degassed with nitrogen for 10 min then tetrakis(triphenylphosphine)palladium (0) (42 mg, 0.037 mmol) was added and the reaction was stirred under nitrogen at 90° C. for 15 h. The reaction mixture was cooled, diluted with ether (60 mL) and washed with water and brine. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (0-3% methanol in dichloromethane with 0.5% ammonium hydroxide) to afford 203 mg (48%) of 2-(6-chloro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (1-pyridin-3-yl-ethyl)-amide as a foaming solid. MS: (M+H)+=549.

後処理

  1. customto give a yellow solution
  2. customThe mixture was degassed with nitrogen for 10 min
  3. temperatureThe reaction mixture was cooled
  4. washwashed with water and brine
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel chromatography (0-3% methanol in dichloromethane with 0.5% ammonium hydroxide)

出典と根拠

ORDレコード
ord-0a61b06efebf46f09df5a9ffa4152689
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

反応ノート

読み込み中…