Water → 2-(6-chloro-4-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

HRID 246098

反応式

HRID 246098 の反応式
Br[C:2]1[N:3]=[C:4]2[C:10]([CH:11]=[O:12])=[CH:9][N:8]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:5]2=[N:6][CH:7]=1.[Cl:21][C:22]1[CH:30]=[C:29]2[C:25]([C:26]([Sn](CCCC)(CCCC)CCCC)=[N:27][NH:28]2)=[C:24]([F:44])[CH:23]=1.O.C(=O)(O)[O-].[Na+]>CN(C=O)C.[Cu](I)I.C(OCC)(=O)C>[Cl:21][C:22]1[CH:30]=[C:29]2[C:25]([C:26]([C:2]3[N:3]=[C:4]4[C:10]([CH:11]=[O:12])=[CH:9][N:8]([CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:5]4=[N:6][CH:7]=3)=[N:27][NH:28]2)=[C:24]([F:44])[CH:23]=1

参加物

8

反応物 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 578296122-bromo-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehydeHCID 178448230HCID 178448230、化合物

生成物 1

HCID 866779472-(6-chloro-4-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde収率 47%

試薬・触媒・溶媒 3

HCID 83717Copper iodide触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

2-Bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (7.6 g, 18.6 mmol) and 6-chloro-4-fluoro-3-tributylstannanyl-1H-indazole (crude from Step 3) were dissolved in DMF (180 ml) and purged with Ar gas. Tetrakis(triphenylphosphine)pallladium (1.07 g, 0.93 mmol) and then copper iodide (707 mg, 3.71 mmol) were added and the flask was stoppered and stirred in a 90° C. oil bath for 20 h. The reaction was cooled and water, ethyl acetate and sodium bicarbonate solution were added. The layers were separated, and the aqueous layer was extracted twice more with ethyl acetate. The combined organic layers were washed with water and sodium chloride solution, then dried over sodium sulfate. After evaporation, the residue was purified by silica gel chromatography (methanol/dichloromethane) followed by trituration with diethyl ether/hexanes to give 3.9 g (47%) of 2-(6-chloro-4-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde. (M+H)+=446.

後処理

  1. custompurged with Ar gas
  2. temperatureThe reaction was cooled
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted twice more with ethyl acetate
  5. washThe combined organic layers were washed with water and sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. customAfter evaporation
  8. customthe residue was purified by silica gel chromatography (methanol/dichloromethane)

出典と根拠

ORDレコード
ord-e28515601bc4484a862ed28efbc7eb4c
出典データセット
uspto-grants-2014_02
特許番号
US08658646B2

関連ノート

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