Cesium carbonate → 1,1-dimethylethyl 5-cyano-2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxylate

HRID 2401172ノート

反応式

HRID 2401172 の反応式
Br[C:2]1[C:3]([NH:10][C:11](=O)[C:12]([F:15])([F:14])[F:13])=[N:4][CH:5]=[C:6]([C:8]#[N:9])[CH:7]=1.[C:17]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])(=[O:22])[CH2:18]C(C)=O.N1CCC[C@H]1C(O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.C(OCC)(=O)C.[Cu]I>[C:8]([C:6]1[CH:7]=[C:2]2[C:18]([C:17]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=[C:11]([C:12]([F:15])([F:14])[F:13])[NH:10][C:3]2=[N:4][CH:5]=1)#[N:9]

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 15538Tert-butyl acetoacetateHCID 145742L-ProlineHCID 86762581N-(3-bromo-5-cyano-2-pyridinyl)-2,2,2-trifluoroacetamide2 回

生成物 1

HCID 699286821,1-dimethylethyl 5-cyano-2-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine-3-carboxylate収率 27.5%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 679Dimethyl Sulfoxide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

N-(3-Bromo-5-cyano-2-pyridinyl)-2,2,2-trifluoroacetamide (Intermediate 1, 9.53 g, 32.4 mmol), tert-butyl acetoacetate (10.59 mL, 64.8 mmol), copper(I) iodide (0.617 g, 3.24 mmol), L-proline (0.746 g, 6.48 mmol) and cesium carbonate (42.2 g, 130 mmol) were added together in DMSO (65 mL) and the resulting mixture was heated at 80° C. for 18 hours. The reaction mixture was allowed to cool to room temperature, diluted with ethyl acetate and washed with water and saturated ammonium chloride solution. The organic layer was separated, dried under magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography (Biotage SP4) eluting with a gradient of 0-30% ethyl acetate and iso-hexane. Product containing fractions were combined and evaporated under reduced pressure to give the title compound as a brown solid (2.77 g);

後処理

  1. temperatureto cool to room temperature
  2. washwashed with water and saturated ammonium chloride solution
  3. customThe organic layer was separated
  4. customdried under magnesium sulfate
  5. customevaporated under reduced pressure
  6. customThe residue was purified by column chromatography (Biotage SP4)
  7. washeluting with a gradient of 0-30% ethyl acetate and iso-hexane
  8. additionProduct containing fractions
  9. customevaporated under reduced pressure

出典と根拠

ORDレコード
ord-8e6efdbac3514edbaa7807c40b3d5393
出典データセット
uspto-grants-2014_08
特許番号
US08796283B2

反応ノート

読み込み中…