Dimethylformamide → 6-Amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-nicotinonitrile

HRID 425952ノート

反応式

HRID 425952 の反応式
Br[C:2]1[CH:3]=[C:4]([O:9][CH:10]([C:12]2[C:17]([Cl:18])=[CH:16][CH:15]=[C:14]([F:19])[C:13]=2[Cl:20])[CH3:11])[C:5]([NH2:8])=[N:6][CH:7]=1.[CH3:21][N:22](C=O)C>O.[C-]#N.[C-]#N.[Zn+2].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]>[NH2:8][C:5]1[C:4]([O:9][CH:10]([C:12]2[C:17]([Cl:18])=[CH:16][CH:15]=[C:14]([F:19])[C:13]=2[Cl:20])[CH3:11])=[CH:3][C:2]([C:21]#[N:22])=[CH:7][N:6]=1

参加物

7

反応物 2

HCID 6228DimethylformamideHCID 211114785-Bromo-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine

生成物 1

HCID 211113376-Amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-nicotinonitrile収率 97%

試薬・触媒・溶媒 4

HCID 11186Zinc cyanide (Zn(CN)2)触媒HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒

反応条件

温度
100 °C

実験手順

To a solution of 5-bromo-3-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-2-ylamine (5.00 g, 13.15 mmol) in DMF (73 mL) and water (1 mL) was added Zn(CN)2 (4.50 g, 26.3 mmol), Pd2(dba)3 (0.602 g, 0.65 mmol), and DPPF (0.86 g, 1.55 mmol). The mixture was degassed and charged with nitrogen for three time, and then stirred under nitrogen at 100° C. for 3 hr. The reaction solution was partitioned between ethyl acetate and water. The organic layer was washed with a solution of sat. NH4Cl-conc. NH4OH-water (4:1:4), then dried over MgSO4. The crude product was purified on a silica gel column eluting with ethyl acetate-hexanes (1:4) to provide 6-Amino-5-[1-(2,6-dichloro-3-fluoro-phenyl)-ethoxy]-nicotinonitrile as a white solid (4.15 g, 97% yield).

後処理

  1. customThe mixture was degassed
  2. additioncharged with nitrogen for three time
  3. customThe reaction solution was partitioned between ethyl acetate and water
  4. washThe organic layer was washed with a solution of sat. NH4Cl-conc
  5. dry with materialNH4OH-water (4:1:4), then dried over MgSO4
  6. customThe crude product was purified on a silica gel column
  7. washeluting with ethyl acetate-hexanes (1:4)

出典と根拠

ORDレコード
ord-d215c3e8ca934425a94d32ac75e0590f
出典データセット
uspto-grants-2012_01
特許番号
US08106197B2

反応ノート

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