Dimethylacetamide → 6-Amino-4-fluoronicotinonitrile

HRID 1777867ノート

反応式

HRID 1777867 の反応式
[F:1][C:2]1[C:7](I)=[CH:6][N:5]=[C:4]([NH2:9])[CH:3]=1.C[C:11]([N:13](C)C)=O>C([O-])(O)=O.[Na+].[C-]#N.[Zn+2].[C-]#N.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[NH2:9][C:4]1[CH:3]=[C:2]([F:1])[C:7]([C:11]#[N:13])=[CH:6][N:5]=1

参加物

8

反応物 2

HCID 31374DimethylacetamideHCID 717211424-Fluoro-5-iodo-2-pyridinamine2 回

生成物 1

HCID 1180369016-Amino-4-fluoronicotinonitrile

試薬・触媒・溶媒 5

HCID 11186Zinc cyanide (Zn(CN)2)触媒HCID 23994Zinc触媒HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 516892Sodium Bicarbonate溶媒

反応条件

温度
100 °C

実験手順

4-fluoro-5-iodopyridin-2-amine (intermediate 22, 240 g, 1 mol), zinc cyanide (125 g, 1.05 mol), zinc (13 g, 0.2 mol), Pd2(dba)3 (25 g, 25 mmol) and dppf (55 g, 0.1 mol) in DMA (800 ml) were degassed and charged into the round bottom flask under nitrogen. The mixture was stirred at 100° C. for 3 h. The reaction mixture was diluted with 5% NaHCO3 (2 l), extracted with EtOAc (4×600 ml). The combined organic layers were washed with 5% NaOH (1 l), dried over Na2SO4, concentrated to 700 ml. The resulting organic phase was eluted through silica gel column with EtOAc (1.7 l). The combined organic filtrate was washed with 2 M HCl (3×800 ml). The pH of the aqueous phase was adjusted to 10 with saturated NaHCO3. The aqueous phase was extracted whit DCM (3×500 ml). The combined DCM was dried over Na2SO4 and concentrated. The residue was further purified by column chromatography (eluted with pentane: EtOAc 10:1 to 3:2) followed by recrystallization from pentane/EtOAc 3/1 to give the title compound as white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.40 (d, 1H), 7.40 (s, 2H), 6.34 (d, 1H).

後処理

  1. additioncharged into the round bottom flask under nitrogen
  2. extractionextracted with EtOAc (4×600 ml)
  3. washThe combined organic layers were washed with 5% NaOH (1 l)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated to 700 ml
  6. washThe resulting organic phase was eluted through silica gel column with EtOAc (1.7 l)
  7. washThe combined organic filtrate was washed with 2 M HCl (3×800 ml)
  8. extractionThe aqueous phase was extracted whit DCM (3×500 ml)
  9. dry with materialThe combined DCM was dried over Na2SO4
  10. concentrationconcentrated
  11. customThe residue was further purified by column chromatography (eluted with pentane: EtOAc 10:1 to 3:2)
  12. customfollowed by recrystallization from pentane/EtOAc 3/1

出典と根拠

ORDレコード
ord-d9913c30d3384a94969eb0b789c63bbc
出典データセット
uspto-grants-2016_02
特許番号
US09266883B2

反応ノート

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